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71st Irish Universities Chemistry Research
Colloquium
20th and 21st June 2019
Hosted by
School of Chemical & Pharmaceutical Sciences, Technological University Dublin
Department of Chemistry, Royal College of Surgeons in Ireland
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Contents Foreword .................................................................................................................................... 1
Information ................................................................................................................................ 2
Schedule ..................................................................................................................................... 5
Plenary Speakers ........................................................................................................................ 9
Abstracts .................................................................................................................................. 11
Oral Presentations ................................................................................................................ 11
Flash Presentations ............................................................................................................... 36
Poster Presentations.............................................................................................................. 60
Organising Committee ........................................................................................................... 115
Sponsors & Exhibitors ........................................................................................................... 116
List of Attendees .................................................................................................................... 117
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Foreword Welcome to the 71st Irish Universities Chemistry Colloquium Technological University Dublin and the Royal College of Surgeons in Ireland are delighted to host the 71st Annual Irish Universities Chemistry Colloquium. The colloquium is an opportunity to engage with the leading chemistry research being conducted at twelve institutions through both oral and poster presentations. Once again, the programme of presentations is indicative of the rich and varied range of Irish chemistry research in the areas of materials, sensors and analysis, biological, medicinal, inorganic and organic chemistry as well as fundamental research. The theme this year is sustainability and this is reflected in the plenary speaker presentations, and is an element that also underpins many of the other contributions. We hope that the diverse and interesting programme will be valuable to researchers, and that the networking at our social events and poster sessions will yield many fruitful discussions. One aspect that is striking from the abstracts is the level of complementary research being conducted across various institutions; we hope that this event provides a useful forum for further collaboration. An addition to the schedule this year is a roundtable discussion comprising industrial and academic mentors. The topic being addressed is ‘Opportunities available for early career researchers’. It is a particular pleasure to thank our sponsors who have generously supported the colloquium. We would also like to thank those staff and students from the School of Chemical and Pharmaceutical Sciences TU Dublin and RCSI who have committed significant time and effort to ensure the success of this event. On behalf of all of our colleagues, we welcome you to the 71st Irish Universities Chemistry Colloquium and wish you an enjoyable and productive meeting. __________________________ Professor Declan McCormack
Head, School of Chemical and Pharmaceutical Sciences Technological University Dublin
__________________________ Professor Donal O’Shea
Head, Department of Chemistry, Royal College of Surgeons in Ireland
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Information Registration Registration will be available from 2.00 to 5.00 pm on Wednesday 19th June, in the main Foyer of the TU Dublin Aungier Street Campus. Participants can also register there from 8.30 am on Thursday morning. A name badge will be provided for those registered for the colloquium, which will admit them to the BBQ at the Odeon, Harcourt St. at 6pm on Thursday 20th June. Locations and Transport The colloquium will take place in TU Dublin (Aungier St.) on Thursday the 20th June and the Royal College of Surgeons (RCSI, 123. St. Stephens Green) which is located within 5 minutes walking distance of Aungier St. on Friday the 21st June. TU Dublin Aungier St. is located at the junction of Bishop St. and Aungier St. and is served by a range of buses (9, 14, 15, 16, 83, 122, and 140) at the Redmond’s Hill bus stop. Stephen’s Green Luas stop is a 5 minute walk away and there are Dublin Bikes stations nearby at Kevin St. and St. Stephen’s Green South. Please note there will be no access to RCSI via the York Street entrance. Please use the main front door, which is opposite the Luas stop on St. Stephen’s Green. All attendees are invited to a barbeque in the Odeon, Harcourt St. at 6pm on Thursday June 20th. TU Dublin Aungier Street, the RCSI, Stephens Green and the Odeon, Harcourt Street are all shown in the map below. For attendees travelling by car, the most convenient location for parking is the St. Stephen’s Green Car Park.
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Plenary Speakers The invited plenary speakers will give talks that focus on aspects of sustainability. Prof. Luuk van der Wielen, Director, Bernal Institute and Chair of Biosystems Engineering & Design, University of Limerick, Distinguished Professor for Biobased Economy, TU Delft, The Netherlands (www.tudelft.nl) and President, BE-Basic Foundation, The Netherlands (www.be-basic.org) will give a plenary lecture on day one in TU Dublin which will focus on the area of recycling. Dr. Francesca Paradisi, Professor in Pharmaceutical and Bioorganic Chemistry, University of Bern will deliver the plenary lecture in RCSI on the second day of the colloquium, on the topic of biocatalysis and flow chemistry, both of which have roles in delivering sustainable reactions. Roundtable Discussion There will be a round table discussion at 2 pm on Thursday in Room 4068 (Aungier St.). The panel will be comprised of industrial and academic mentors namely: Brian Glennon (APC), Brenda Moore, (TE Laboratories), Bernie Capraro (Intel), and Amanda Daly (SFI). The topic for discussion is career and funding opportunities for early career researchers.
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Colloquium Theme - Sustainability The theme of the conference is sustainability and therefore: The book of abstracts will be provided online and on a complementary reusable 4 GB USB key. The teas/coffees will be provided in recyclable or porcelain cups. Attendees are encouraged to use public transport. Attendees are encouraged to refill their water bottles from the water fountains. Posters Posters can be hung up from 2.00 pm on Wednesday 19th June. The poster session will be located in room 5050 in Aungier St. and a map will be available to let you know where to locate your poster. Velcro and blue tack will be provided. You are required to attend your poster during the coffee breaks on Thursday 20th June. Posters should be removed by 4.00 pm on Friday 21st June. Disability For attendees who require mobility assistance or any other assistance, please contact [email protected] or the registration desk. Lunch Lunch will NOT be provided; however, there is a wide variety of eateries on Camden Street and Georges Street. Tea and coffee will be available during the shorter breaks. Sponsorship There will be stands from the following companies which have kindly sponsored the colloquium; abcr, GPE Scientific, Pfizer, Huber, Royal Society of Chemistry and Institute of Chemistry of Ireland. We are grateful to the Environmental Protection Agency (EPA) for funding the conference. WiFi Eduroam is accessible throughout Aungier St. and the RCSI.
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RCSI Historical Tour RCSI are offering a 10-15 minute historical chemistry tour: “History and Location of The First Chemistry Teaching and Research in Ireland” at 11.05 on Friday the 21st June. Please email Yuan Ge ([email protected]) to register your interest in attending, or sign up to attend at the colloquium registration. Prizes Prizes will be awarded by the judging panel for each of the oral categories: organic, inorganic and materials and physical/ analytical. There will also be two prizes for the flash talk and poster category, and two prizes for the poster only category. Institute of Chemistry of Ireland Attendees are invited to join the Institute, which will celebrate its centenary in 2022. Join up by signing up at the stand. The ICI will host, in collaboration with EuChemS, the EuChemS Congress in the Dublin Convention Centre during August 2022.
Schedule Wednesday 19th June Technological University Dublin, City Campus, Aungier St
14:00 – 20:00
Registration: Main Entrance Foyer
TU Dublin, Aungier Street
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Thursday 20th June Technological University Dublin, City Campus, Aungier St
8:30 Registration: Main Entrance Foyer TU Dublin, Aungier Street
9:00
Welcome Address Prof Declan McCormack - Head of School, Chemical & Pharmaceutical
Sciences, TU Dublin, City Campus Room 4027 (4th Floor) TU Dublin, Aungier Street
9:15 Plenary 1
Prof. Luuk Van der Wielden (UL) Room 4027 (4th Floor) TU Dublin Aungier Street
Room 4068 Room 4079
Session 1A:
Organic Chemistry Chair: Dr Grainne Hargaden
Session 1B: Physical & Analytical Chemistry
Chair: Dr David O’Connor
10.00
Speaker 1 Synthesis of tail Fragment Analogues of
Nisin, A bacteriocin peptide. W. Travers (TU Dublin)
Speaker 2 Quantitative resazurin assay of cell viability
for release alkaline phosphatase (ALP) T. Balbaied (UCC)
10.20
Speaker 3 Recent Advances in the Synthesis and biological Application of ferrocenyl
derivatives. K. Ontiveros (DCU)
Speaker 4 Franck-Condon Calculations of the Q-band
Absorption of Phthalocyanines K. McGuire ( NUI Maynooth)
10.40
Flash Talks Session 1 F1: C. Cioffi (RCSI) F2: G. Palop (NUIG)
F3: R Kruschel (UCC) F4: S. Kavanagh (UCD) B. Reid (GPE scientific)
Flash Talks Session 2 F5: P. McNeice (QUB) F6: M. Haskins (UL) F7: M. Craig (TCD)
F8: P. Sidambaram (TU Dublin) F9: R. de Carvalho (TU Dublin)
11.05 Coffee and Poster Session 1 Room 5050
Room 4068 Room 4079
Session 2A:
Inorganic & Materials Chemistry Chair Dr Ariane Perez-Gavilan
Session 2B: Physical & Analytical Chemistry.
Chair: Dr Eoin McGillicuddy
11.45
Speaker 5 Enhancing the bioavailability of drugs
through cocrystallization and coamorphization
M. Aljohani (NUIG)
Speaker 6 Defect modelling of LaGaO3 for solid oxide
fuel cell applications J. Savioli (TCD)
12.05
Flash Talks Session 3 F10: A.Mahon (UCD)
F11: S. O’Halloran (DCU) F12: T. Xie (QUB)
Flash Talks Session 4 F13: F. O’Maolmhuaidh (DCU)
F14: F. Muraca (UCD) F15 M. Lynch (UCC)
12.25 Lunch
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2.00
Panel discussion Where to Now?
A Roundtable Discussion With Academic Funders And Industrial Experts Room 4068
Room 4068 Room 4079
Session 3A: Organic Chemistry
Chairs: Prof. C. Marmion & Prof. John Cassidy
Session 3B: Inorganic & Materials Chemistry
Chair: Dr John Colleran & Dr Claire McDonnell
2.45
Speaker 7 Investigation of CLEC10A CRD crystal structure and interaction with MUC1
glycopeptides A. Gabba (NUIG)
Speaker 8 Multifunctional Hydrogels – A novel
approach to Interpenetrating Networks S. Bolanta (UL)
3.05
Speaker 9 Biotransformations employing nitrile
hydrolyzing enzymes towards the enantioselective synthesis of β-amino
acids T. Mareya (WIT)
Speaker 10 Manganese Coordination Complexes: From
Aesthetically Pleasing Geometries to Biological Mimics S. Tandon (TCD)
3.25
Flash Talks Session 5 F16 F. Alletto (RCSI)
F17: F. Meany (NUIG) F18: K. Tseke (WIT)
Flash Talks Session 6 F19: H. Jenkins (TU Dublin)
F20: I.F. Robayo Molina (UL) F21: D. Mulrooney (UCD)
F22: G. M Reid (UCD)
3.45 Coffee and Poster Session 2
Room 5050
4.05
Speaker 11 Development of an Asymmetric Synthesis
of Ergoline Derivatives R. Connon (UCD)
Speaker 12 Plasmon-Mediated Visible-Light-Driven
Conversion of CO2 over RuO2/TiO2 Catalysts
E. Morais (UCD)
4.25
Speaker 13 Asymmetric Copper-Catalysis used for
Efficient Desymmetrisation in Intramolecular C–H Insertion Reactions
of a-Diazo-b-oxo Sulfones T. Brouder (UCC)
Speaker 14 A Salt free method for preparing stable
Au/Ag aggregates as liquid SERS substratesfor the detection of biomolecules
under difficult conditions Z Ye (QUB)
4.45
Speaker 15 Influence of Substituants on Aggregation in a series of mono and diamideisomers
I. Osman (DCU)
Speaker 16 The Development of Metal Complexes of the Hedgehog Pathway Inhibitor GANT61-D as
Potential Anticancer Agents A. Ryan (RCSI)
5.05
Speaker 17 Carrier profiling in molecular layer doped
Si nanowires: effects of the density and width of the nanowires M. Georgieva (CIT)
6.00 Barbeque: Odeon, Harcourt St
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Friday 21st June Royal College of Surgeons of Ireland
Houston lecture Theatre
9.15 Opening & Welcome to RCSI
Prof Donal O'Shea Head of Department of Chemistry RCSI
Session 4:
Inorganic & Materials Chemistry Chair: Dr. Darren Griffith
9.30 Speaker 18
Synthesis and Design of new type 3 porous liquids J. Cahir (QUB)
9.50
Speaker 19 Investigation of Phosphine based Ligands for the Synthesis of Inorganic
CsPbX3 Nanocrystals F. McGrath (UL)
10.10 Speaker 20
An experimental and kinetic modelling study on oxidation of diisobutylene N. Locachari (NUIG)
10.30 Speaker 21
Copper ferrite (CuFe2O4) as a catalyst in CuAAC B. Wojciechowski (TU Dublin City Campus)
10.50
Coffee: 1784 Restaurant
Tour: History and Location of First Chemistry Teaching and Research in Ireland
(11.05 optional)
Session 5A: Chair: Prof. Mauro Adamo
11.20 Speaker 22
3D Printing of Spatially Patterned Magnetically Responsive Hydrogels P. Monks (RCSI)
11.40 Speaker 23
Glycocomimetics to Inhibit Candida Albicans Adhesion H. Martin (NUIM)
12.00 Plenary 2
Continuous Flow biocatalysis for highly sustainable and versatile syntheses Dr. Francesca Paradisi (The University of Bern)
12.45 Closing Session & Prize Giving
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Plenary Speakers Prof. Luuk A.M. van der Wielen
Prof.dr.ir. Luuk A.M. van der Wielen (Amsterdam) holds a MSc degree in Chemical Engineering from Twente University (Netherlands), and a PhD degree (with honours) from Delft University of Technology (TUD). Since February 2017, he is Director of the Bernal Institute at the University of Limerick, (http://www.bernalinstitute.com/) and Bernal Professor for Biosystems Engineering and Design, while continuing as Distinguished Professor for Biobased Economy of TUD. He is Full Professor at TU Delfts Dept. of Biotechnology (www.bt.tudelft.nl ),
where he headed the Bioprocess Engineering Section effectively since 1998. The activities of the section were ranked as excellent by consecutive national research evaluations and have resulted in several spin-off companies. His research interests include thermodynamics for bioprocesses, bioseparation/-conversion technologies, multifunctional bioreactors, miniaturized (‘on-chip’), high-throughput technology for rapid process development, analysis and development of (bio)renewables production systems, and their societal impacts.
He is since 2004 director of BE-BASIC (www.be-basic.org), the globally operating private-public research organisation for Biobased Sustainable Industrial Chemistry & Energy, based in The Netherlands with hubs in South East Asia and Brazil, and a cumulative budget exceeding 250 M€. BE-BASIC executes a R&D, training and innovation program in the field of industrial and environmental biotechnology, via a consortium of 50 academia and industries. He initiated the multi purpose pilot facility (www.bpf.eu, ~ M€ 80). In 2012, he coordinated the Netherlands’ Bioenergy and Biochemicals Innovation plan under the new Dutch Topsector Policy (budget exceeding 1 billion euro), and was appointed in the 1st Board of Directors of Foundation TKI- BBE. In 2007, he joined (part-time) Royal Dutch Shell as Principal Scientist Biotechnology. He was Visiting Professor at the Univ. San Carlos, the Philippines until 2008; and 2009-‘13 at Univ. of Technology Malaysia. The last Google Scholar count shows over 300 (342) publications and patents as of July 2018 (5020 citations; H-index 37 (GS), RG 43.46).
Luuk is/was member of editorial and advisory boards of several leading international scientific journals, and chaired several scientific conferences (a.o. ESBES4, BPP2005, RRB4, ECOBIO2016/-18, Braz Bioenergy S&T Conf 2017). He is/was member/chair of national and European boards: AgroPolo (agro/forestry re-industralisation board Sao Paulo, BR), coordinator Bioenergy and Biochemicals RD&I programming in NL Topsector Policy (2011- 12), Supervisory Board of Dutch Separation Technology Institute, of NL Platform Renewable Feedstocks, Sustainable Energy Cie of the Royal NL Academy of Sciences (KNAW), Steering Group of the EU Technology Platform Suschem/ Industrial Biotechnology, Steering Committee BBE (Min Economic Affairs) and BioPort of Rotterdam, Taskforce Bioenergy Systems (EU Fed. for Biotechnology), Advisory Boards of US-EU Taskforce on Biotechnology Research, KP Sinha Bioenergy Center (IIT Kharagpur, India), of CLIB2021 (Germany), of BIO4EU (EU Commission), Oversight Board Global Sustainable Bioenergy Project and advisor to several European and international industries. He is/was in Boards of Commissioners of Dutch Greentech Fund and SHIFT Invest, Bioprocess Pilot Facility BV and chairs BioPort Holland1(aviation industry group).
He is one of the initiators of the successful academic program on Life Science & Technology (www.lst.tudelft.nl ) of Leiden University and TU Delft, and director of the postgraduate program Bioprocess Design (www.bodl.bt.tudelft.nl ).
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Dr. Francesca Paradisi
I completed my MSc in Organic Chemistry from the University of Bologna in 1998 under the supervision of Prof. Cainelli. In 2002 I completed my PhD at the same institution with a thesis on the synthesis of non-natural amino acids via diketopiperazine scaffolds. During my PhD I spent a summer in Dublin as a visiting student in Trinity College working with Prof. Thorri Gunnlaugsson and it was a fantastic experience. So after my PhD I had no doubt I wanted to go abroad and I joined the group of Prof. Paul Engel at University College Dublin as Post-Doctoral Fellow where I discovered the wonders of biocatalysis. I
remained in Paul’s group until 2005 developing several projects mainly focused on amino acid dehydrogenases and their applications in the synthesis of non-natural amino acids. I owe Paul all I know about enzymes and their reaction mechanisms! I spent then a few months in Enzolve Technologies in 2005, a spin-off company of UCD where I worked on the use of mutant dehydrogeanse enzymes for neonatal screening of metabolic disorders. In 2006 I won the lotto and was appointed College Lecturer in Chemical Biology at the UCD School of Chemistry. I was promoted in 2014 to Senior Lecturer. I was fortunate to be always surrounded by a team of excellent students that made my research always interesting, certainly challenging, and thankfully rewarding. I had the great opportunity to spend the summer of 2015 in UC Davis in California as a visiting academic and I joined the group of Dr. Justin Siegel who gave me the possibility of expanding my research to a different class of enzymes (glycosyl hydrolyses) and getting my hands dirty in the lab again was awesome as they say. While I was in Davis and I thought things couldn’t get any better, I was offered the position of Associate Professor in Biocatalysis and Enzyme Engineering in the School of Chemistry at the Univeristy of Nottingham. I joined Nottingham in February 2016. In 2019 I joined the University of Bern as a Professor in Pharmaceutical and Bioorganic Chemistry. Continuous Flow biocatalysis for highly sustainable and versatile syntheses Flow chemistry has allowed many industrial processes to be carried out in continuous mode, with higher efficiency and automation. Biocatalysis has caught up with this technique and several examples have been reported in the literature in the last decade. However, the complexity of multi-enzymatic processes in the absence of cellular regulation, has limited their applications to some chemo-enzymatic synthesis, and just a few fully enzymatic processes have been implemented. Among others, the cofactor requirements of redox enzymes, the stability of the biocatalyst, and efficiency of the biotransformations, must be thoroughly optimised. Furthermore, the mobile phase is rarely recovered, minimizing the real environmental impact of enzymatic reactions. Here the steady evolution of flow biocatalysis in our laboratory will be presented, moving towards systems of increasing complexity with combinations of several enzymes, which resulted in a breakthrough in the design and implementation of an ultra-efficient zero-waste and closed-loop process with unprecedented atom efficiency and automation.
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Abstracts Oral Presentations
No. Title Presenter Affiliation Page
1 Synthesis of tail Fragment Analogues of Nisin, A bacteriocin peptide. W. Travers TU Dublin 13
2 Quantitative resazurin assay of cell
viability for release alkaline phosphatase (ALP)
Thanih Balbaied UCC 14
3 Recent Advances in the Synthesis and biological Application of ferrocenyl
derivatives.
K. Ontiveros-Castillo DCU 15
4 Franck-Condon Calculations of the Q-band Absorption of Phthalocyanines Kevin McGuire NUIM 16
5 Enhancing the bioavailability of drugs
through cocrystallization and coamorphization
M. Aljohani NUIG 17
6 Defect modelling of LaGaO3 for solid oxide fuel cell applications J. Savioli TCD 18
7
Investigation of CLEC10A CRD crystal structure and interaction with
MUC1 glycopeptides ICI postgraduate Award Winner 2018
Adele Gabba NUIG 19
8 Multifunctional Hydrogels – A novel
approach to Interpenetrating Networks
S. Bolanta UL 20
9
Biotransformations employing nitrile hydrolyzing enzymes towards the
enantioselective synthesis of β-amino acids
T. Mareya WIT 21
10 Manganese Coordination Complexes:
From Aesthetically Pleasing Geometries to Biological Mimics
S. Tandon TCD 22
11 Development of an Asymmetric Synthesis of Ergoline Derivatives R. Connon UCD 23
12 Plasmon-Mediated Visible-Light-Driven Conversion of CO2 over
RuO2/TiO2 Catalysts E. Morais UCD 24
13
Asymmetric Copper-Catalysis used for Efficient Desymmetrisation in Intramolecular C–H Insertion
Reactions of a-Diazo-b-oxo Sulfones
T. Brouder UCC 25
14
A Salt free method for preparing stable Au/Ag aggregates as liquid
SERS substratesfor the detection of biomolecules under difficult
conditions
Z Ye QUB 26
12
No. Title Presenter Affiliation Page
15 Influence of Substituants on
Aggregation in a series of mono and diamideisomers
I. Osman DCU 27
16
The Development of Metal Complexes of the Hedgehog Pathway Inhibitor GANT61-D as Potential Anticancer
Agents
A. Ryan RCSI 28
17 Carrier profiling in molecular layer doped Si nanowires: effects of the density and width of the nanowires
Margarita Georgieva CIT 29
18 Synthesis and Design of new type 3 porous liquids J. Cahir QUB 30
19 Investigation of Phosphine based
Ligands for the Synthesis of Inorganic CsPbX3 Nanocrystals
Fiona McGrath UL 31
20 An experimental and kinetic modelling study on oxidation of diisobutylene N. Locachari NUIG 32
21 Copper ferrite (CuFe2O4) as a catalyst
in CuAAC
Bartlomiej Wojciechowski TU Dublin 33
22 3D Printing of Spatially Patterned
Magnetically Responsive Hydrogels
P. Monks RCSI 34
23 Glycocomimetics to Inhibit Candida
Albicans Adhesion
H. Martin NUIM 35
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Synthesis of Tail-fragment Analogues of Nisin, a Bacteriocin Peptide
Wayne Travers, Fintan Kelleher.
Molecular Design and Synthesis Group, TU Dublin- Tallaght Campus, Dublin 24 [email protected]
Nisin, a 34 amino acid lanthipeptide, is currently used as a food preservative worldwide, and has been used for decades without significant bacterial resistance being reported [1]. It is an extremely active molecule which kills a range of different bacterial species, in the nanomolar range. However, nisin, along with some other similar peptides, suffers from low stability at physiological pH, which severely restricts its possible use as a therapeutic in human and veterinary medicine. The instability of nisin at pH 7.4 is mainly due to two unusual amino acid moieties (dehydroalanine (Dha) and dehydrobutyrine (Dhb)), which appear in three distinct regions within its structure. The current literature description of the decomposition mechanism of nisin is due to an acid-catalysed Markovnikov hydration of the Dha33 of the nisin tail [2]. Since nisin is most stable between pH 2-3, this does not support the currently accepted mechanism of decomposition. The generation of the native nisin tail (Figure 1), and a number of analogues, has been carried out, in order to fully elucidate the mechanism by which the stability of nisin is compromised at physiological pH. Our efforts to increase the stability of nisin will be presented.
SerIle
His Val X
Lys
X= Dha, AC3C
SerIle
His Val DhaX
X= Lys, His
29 29
33 33
Figure 1: Nisin Tail Region
References: [1] J. Lubelski et al., Cell. Mol. Life Sci., 2008, 65, 455-476; b) J. Dischinger et al.,“Lantibiotics”, in Handbook of Biologically Active Peptides, p119-128, Wiley, 2013. [2] W. Liu and J. N. Hansen, Appl. Environ. Microbiol. 1990, 56, 2551-2558; b) L. Lyan et al., Biocehm J. 1992, 283, 413-420; c) H. Rollema et al., Appl. Environ. Microbiol. 1995, 61, 2873-2878; d) H. Rollema et al., Eur. J. Biochem. 1996, 214, 716-722
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Quantitative resazurin assay of cell viability for release alkaline phosphatase (ALP)
Thanih A. Balbaieda, Eric Mooreb
a, b University College Cork, Sensing & Separation Group, School of Chemistry and life
Science Interface, Tyndall National Institute, Ireland.
Many studies use cell adhesion approaches in their applications. An example of this can be found in the area of cancer research where phenotype of cells enables studying the regulation of enzymes considered as biomarkers. Alkaline phosphatase (ALP) is one of these biomarkers, which is correlated with cell proliferation, differentiation and apoptosis. Simplifying the determination of cell number on those applications is significant, because the presence assays have their own limitations. Metabolic-based assays under constant experimental conditions can provide a stable rate of fluorescence intensity and quantify cell number. Resazurin which is the most sensitive assay is optimized for quantifying cell number of cancer cells during alkaline phosphatase expression using microplate formats. ALP level is investigated using optical methods and the cell number is verified using the hemocytometer device. The cancer cell lines including MCF-7, A549, and Ht-29 are used as models of the top three cancers diagnosed worldwide; lung (13 %) breast (11 %), and colon (10 %) respectively. Balb/c 3T3 cell lines is also used as it is more sensitive to contact inhibition of cell division than cancer cell lines.
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Recent advances in the synthesis and biological application of ferrocenyl derivatives
Karen G. Ontiveros-Castillo 1, Andrew Kellett 1, Mónica A. Ramírez-Cabrera 2, Eder Arredondo-Espinoza 2, Peter T. M. Kenny 1,3
1 School of Chemical Sciences, Dublin City University, Dublin 9, Ireland. 2 Universidad Autónoma de Nuevo León, Facultad de Ciencias Químicas. Av. Universidad S/N. Cd. Universitaria. San Nicolás de los Garza, Nuevo León, México. 3 National Institute for
Cellular Biotechnology, Dublin City University, Dublin 9, Ireland. [email protected]
Several series of ferrocene bioconjugates showing antineoplastic activity have been reported in recent years. Their general structure consists of three components: (1) an electroactive ferrocene core, (2) linked to an aromatic linker, (3) coupled to an amino acid or peptide chain (Figure 1). The aim of this research was to modify each of these moieties to further extend structure activity relationship (SAR) studies, with particular interest in the development of heterocyclic functionalised compounds in the segment (3), looking for more planar structure which could have a better interaction with DNA, leading to an enhancement of biological activity. This new series of ferrocenyl compounds were synthesized using conventional coupling protocols and characterised by different spectroscopic and spectrometric techniques. The biological studies involved the in vitro evaluation against both SiHa (human cervix carcinoma) and Chang (human liver) cell lines. Some ferrocenyl derivatives show a degree of selectivity between cancerous and non-cancerous cells, suggesting that ferrocenyl complexes are promising anticancer agents worthy of future therapeutic analysis. Results from DNA binding studies are also presented, showing the interaction that these novel ferrocenyl derivatives have with DNA.
Fe
O
HN
NH
O
O
O
Redox-active centre
Conjugated linker
Amino acid or dipeptide ester chain Fig. 1. General structure of the ferrocenyl bioconjugates.
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Franck-Condon calculations of the Q-band absorption of the phthalocyanines H2Pc, MgPc, AlPcCl and ZnPc compared with gas phase excitation spectra.
Kevin McGuire and John G. McCaffrey
Low Temperature Spectroscopy Laboratory, Department of Chemistry, Maynooth University,
National University of Ireland—Maynooth, County Kildare, Ireland. [email protected]
Q-band absorption spectra of the phthalocyanines (Pc) H2Pc, MgPc, ZnPc and AlPcCl have been simulated by calculating Franck-Condon (FC) factors with time-dependent density functional theory (TD-DFT) using M11, PBE0 and B3LYP functionals and the 6-31G(d) basis set. The vibronic structures in the resulting highly resolved simulated spectra were compared critically with the low temperature, jet-cooled excitation spectra which exist for these four Pc molecules. Comparisons of the gas phase electronic band origins (ν0,0) with the predicted values, indicate that the B3LYP functional provides the best results for the three metal phthalocyanines (MPc) where small mean deviations, on the order of 100 cm-1 (10 meV) was obtained. For H2Pc the M11 functional was found to be marginally better than B3LYP still but returned a larger error, on the order of 400 cm-1 (50 meV). Results obtained for H2Pc with the B3LYP functional and the larger def2-TZVP basis set yielded similar deviations. Vertical excitation energies (ΔEv
GS), obtained by simple TDDFT calculations exceed the electronic band origins (ν0,0) determined with the present adiabatic Hessian FC method by about 1000 cm-1 (120 meV). The FC simulated spectra generated by all three functionals correctly predict that absorption is dominated by an intense fundamental v’=0 ← v”=0 transition at the electronic band origin with much weaker vibronic bands. This intensity pattern is indicative of a transition coupling two electronic states with very similar geometries - behaviour entirely consistent with the optimized ground state (GS) and optimized excited state (ES) geometries found in the present study. More detailed analysis reveals that in the molecules which exhibit some structural differences between the GS and ES - as found in ZnPc and AlPcCl - low frequency out-of-plane bending modes generate significantly stronger vibronic bands. This effect, which is absent in H2Pc and MgPc can be traced back essentially to the size of the central metal cation and is most pronounced in ZnPc. In the first excited state of ZnPc, the zinc atom moves out of the molecular plane (GS ν1 mode, (a2u) at 15.6 cm-1 → ES ν2 mode, (a1) at 19.6 cm-1) reducing the ground state molecular symmetry from D4h to C4v. An out-of-plane bending motion (GS ν2 mode, (b2u) at 21.0 cm-1 → ES ν1 mode, (a1) at 11.1cm-1) of the opposite pyrrole groups reduces the symmetry further C2v. The same motion (GS ν1 mode, (b2) at 19.6 cm-1 → ES ν1 mode, (a1) mode at 17.8 cm-1) is exhibited by AlPcCl where the GS C4v symmetry is reduced to C2v in the ES. This motion generates strong overtone progressions in the ν1 and ν2 modes of AlPcCl and ZnPc respectively. The FC spectrum simulated for AlPcCl at 60 K accounts very well for the strong hot bands present in the recorded jet-cooled excitation spectrum of this molecule. The vibrational level responsible for the majority of the hot band intensity is the previously mentioned intense, low frequency normal mode, ν1.
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Enhancing the bioavailability of drugs through cocrystallization and coamorphization
Marwah Aljohani 1, Patrick McArdle 1, and Andrea Erxleben 1
1 School of Chemistry, National University of Ireland, Galway, Ireland
During drug research and development, improving the solubility of poorly water soluble drugs without chemically modifying the drug molecule is one of the biggest challenges for the pharmaceutical industry. Most medicines are formulated as solid dosage forms like tablets and capsules. Cocrystallization and coamorphization are attractive strategies to enhance their dissolution rates and to reduce the number of medications a patient must take. Chlorothiazide (CTZ) is a short-acting thiadiazine diuretic. It is a Biopharmaceutics Classification System (BCS) class IV drug, indicating low solubility and permeability. In this study, cocrystals and a CTZ salt were obtained by ball milling followed by crystallization from solution. X-ray diffraction techniques indicated 13 coformers produced cocrystals upon milling, eight cocrystals were produced, and enhanced dissolution properties were observed in three cases. There is a correlation between the crystal packing index, lattice energy and dissolution rate. In pharmaceutical production, cocrystals are usually formulated with excipients, which may compete with the coformer for hydrogen bonding; therefore, it is important to study the stability of cocrystals in the presence of excipients. In this study, isolated cocrystals were mixed with PVP and MCC, the two most common excipients, and then milled and kept at 56% relative humidity (RH). The results suggested it is possible to form cocrystals in the presence of excipients, which would simplify the pharmaceutical process. Gliclazide (GLZ) has been shown to be effective in the long-term treatment of diabetes mellitus. It is a class II API, exhibiting low solubility. Patients being treated for diabetes mellitus often exhibit high blood pressure. Drug-drug cocrystals and coamorphous systems containing antidiabetic drugs and hypertension drugs such as triamterene (TRI) and hydrochlorothiazide (HTZ) offer interesting opportunities for combination therapy. In this study, coamorphization of GLZ-TRI with 15 % sodium taurocholate (NaTc) gave a viable coamorphous formulation with an enhanced dissolution rate.
Fig. 1. Dissolution profiles of coamorphous GLZ-TRI. (a) without surfactants (b) with 15% NaTc.
18
Defect modelling of LaGaO3 for solid oxide fuel cell applications
Julia Savioli 1, Graeme W. Watson1
1 School of Chemistry, Trinity College Dublin [email protected]
Solid oxide fuel cells (SOFCs) can directly convert chemical energy into electrical power and have been widely studied as an alternative to fossil fuel-based technologies. These devices are composed of two electrodes separated by a solid electrolyte. Energy can be generated from a variety of fuels (hydrogen, natural gas and biogas, carbon monoxide, hydrocarbons among others) and the device environmental impact due to its gas emissions depends only on the fuel choice. The high temperatures (1073-1273 K) required for SOFC operation decrease its life-time due to mechanical and chemical compatibility issues among device components. Therefore, extensive research has been made to develop electrolyte materials with high ionic conductivities in the intermediate temperature (IT) range (873-1073 K)1. Doping LaGaO3 with divalent cations generates oxygen vacancies and enhance the perovskite oxide-ion conductivity, enabling its application as solid electrolyte in IT-SOFCs. This process can be favoured by changes in the concentration and “identity” of dopants, which introduce distortions to the perovskite structure due to their distinct ionic radii when compared to the host cations, or interact with oxygen vacancies affecting the mobility of these charge compensating defects, affecting the ionic transport properties of the material. In this study, DFT calculations using the meta-GGA SCAN2 functional were performed to investigate the effects of a series of divalent metals as dopants in LaGaO3 and their influence in the defect chemistry and ionic conductivity of the perovskite. The oxygen vacancy position was varied with respect to the dopants to determine where it would preferentially lie. The lowest energy structure for each doped perovskite was determined to investigate key features that impact the ionic conductivity – the doping energy, the preferable doping site (La or Ga site) and the association energy between vacancies and dopants – as a function of dopant identity and chemical environment. We determined that the behaviour of the oxygen vacancies can be associated with the ionic radii and electronic structure of the considered dopants.
[1] A. J. Jacobson, Chem. Matter, 22, (2010), 660-674 [2] J. Sun et al. Nat. Chem., 8, (2016), 831-836
19
Investigation of CLEC10A CRD crystal structure and interaction with MUC1 glycopeptides
Adele Gabba1, Ulrika Westerlind2,3, Sandra J. van Vliet4, Gabriel Birrane5, Paul V. Murphy1.
1 School of Chemistry, 2 National University of Ireland Galway; Leibniz-Institut für Analytische Wissenschaften – ISAS, Dortmund; 3 Department of Chemistry, Umeå
University, Umeå; 4 Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam; 5Beth Israel Deaconess Medical Center, Division of
Experimental Medicine, Harvard Medical School. [email protected]
Lectins are the main class of protein which recognize glycans. A member of the C-type lectin family is CLEC10A (h-MGL, CD301), an endocytic receptor located on the surface of some immune system cells, mainly dendritic cells (DCs) and macrophages. This protein displays exceptional selectivity for GalNAc derivatives. The binding event is believed to trigger the antigen internalization/presentation, such as in the case of aberrant MUC1 overexpressed in several tumours histotype, but there are also strong evidence suggesting CLEC10A involvement in Ebola virus entry into DCs. The role of h-MGL in DCs function is not fully understood and therefore the development of potent inhibitors of h-MGL could be significant in gaining understanding of the purpose of this receptor in DCs biology and in improving DC-based vaccine development and immunotherapy. A compressive library with CLEC10A nM inhibitors and more than fifty MUC1 glycopeptides decorated with h-MGL ligands were synthesized. Their ability to be recognized and internalized by h-MGL and their ability to create immunological memory in a rabbit model is currently under evaluation. We were able to obtain the first crystal structure of CLEC10A and elucidate the GalNAc binding mode with this protein, providing structural data long awaited in the glycobiology and immunology community.
Fig.1. Crystal structure of CLEC10A CRD and protein crystal packing.
20
Multifunctional Hydrogels for Biomedical Applications: A Novel Approach to Interpenetrating Networks.
Sharon Bolanta1,2, Javed Iqbal1 and Emmet O’Reilly1
1Department of Chemical Sciences and Biomaterials Cluster Bernal Institute, University of Limerick
2Irish Research Council [email protected]
The development of smart, responsive materials with the capacity to bridge the gap between soft biological tissue and artificial implants represents a massive leap forward in the fields of regenerative medicine and biomedical engineering. Electroactive hydrogels are a class of polymers, which show significant potential towards achieving this goal. Electroactive hydrogels are polymeric blends comprised of hydrated hydrogels, which are similar in structure to mammalian tissue, and electroactive polymers. The ability to combine the unique properties of each of these materials offers enormous potential to reduce inflammation and promote cell growth at material/soft tissue interfaces, representing a significant leap forward in biomedical device design. (Goding et al. 2017) This work focuses on the fabrication of smart electroactive hydrogels via novel fabrication routes. The approach involves the incorporation of electroactive polymer monomers within hydrogels via inkjet printing technology. A series of other techniques including photocrosslinking and electropolymerisation are used to form a pH responsive hydrogel with electroactive architecture. Results show that with this approach, the electroactivity of the electroactive polymer is maintained within the hydrogel and an interpenetrating network formed within the hydrogel matrix. Cell culture studies show that the hydrogel formed exhibits excellent biocompatibility and provides a suitable environment for cell growth. Figure 1. Schematic of the electroactive hydrogels. References Goding, J., Gilmour, A., Martens, P., Poole-Warren, L. and Green, R. (2017) 'Interpenetrating Conducting Hydrogel Materials for Neural Interfacing Electrodes', Advanced Healthcare Materials, 1601177-n/a.
Electroactive polymer within
Hydrogel matrix
Biological Tissue
Electropolymerised Polymer
Hydrogel matrix
Cells penetrating hydrogel matrix
Electrode
21
Biotransformations employing nitrile hydrolyzing enzymes towards the enantioselective synthesis of β-amino acids
Tatenda M Mareya,1 Lee V Coffey1, Michael Kinsella1, Caio R S Bragança1, Tríona-Marie
Dooley Cullinane1, and Claire M Lennon1
1Department of Science, Waterford Institute of Technology, Cork Road, Waterford X91
K0EK, Ireland [email protected]
Nitrile hydrolysing enzymes continue to be of great interest particularly for their pharmaceutical applications1,2. This work set out to utilise novel bacterial isolates containing nitrile-metabolising enzyme systems in the synthesis of a series of chiral β-amino acids with key goals to achieve high enantioselectivity and reaction efficiency. Initial work focussed on further assessing the functional group tolerance and mechanistic action of bacterial strain Rhodococcus erythropolis SET-1 which had been previously studied with β-hydroxynitriles by Coady et al in our research group3,4. In studies with the aliphatic substrate 3-hydroxybutyronitrile in particular, acid product was obtained with high yield and excellent ee. Ten model β-aminonitriles, structurally related to the β-hydroxynitriles previously studied were synthesised and evaluated in biocatalytic studies with SET-1 varying conditions such as pH and solvent additive. In each case chiral HPLC methods were developed for substrates and reaction products. Studies on the N-protected variants of the aliphatic 3-aminobutyronitrile gave the most promising results, with the N-Tosyl protected nitrile yielding acid product in 10% yield and >99% ee. A second stage of the project has involved screening the substrates with other novel bacterial isolates (Rhodococcus sp.) and a purified enzyme exhibiting nitrilase activity to try to identify further biocatalytic systems capable of generating enantiopure β-amino acids. References 1 K. Ni, H. Wang, L. Zhao, M. Zhang, S. Zhang, Y. Ren and D. Wei, J. Biotechnol., 2013,
167, 433–440. 2 H. Fan, L. Chen, H. Sun, H. Wang, Y. Ren and D. Wei, Bioprocess Biosyst. Eng., 2017,
40, 1271–1281. 3 T. M. Coady, L. V. Coffey, C. O’Reilly, E. B. Owens and C. M. Lennon, J. Mol. Catal. B
Enzym., 2013, 97, 150–155. 4 T. M. Coady, L. V. Coffey, C. O’Reilly and C. M. Lennon, European J. Org. Chem.,
2015, 2015, 1108–1116.
22
Manganese Coordination Complexes: From Aesthetically Pleasing Geometries to Biological Mimics
Swetanshu Tandon 1, Graeme W. Watson 1, Wolfgang Schmitt 1.
1 School of Chemistry and CRANN, Trinity College Dublin, University of Dublin,
Dublin, Ireland. [email protected]
Due to the ever increasing energy demands, the development of renewable energy resources has become one of the most important scientific challenges today.1 Solar energy is very promising but due to its irregular nature, the energy needs to be stored. Water is a potential candidate for energy storage as water can be split into H2 and O2, and H2 can be then be used as a fuel with no pollutants.2 The oxidation-half reaction of water splitting, however, is a challenging step for moving towards the use of H2 as an alternative fuel. In nature, this reaction is facilitated in plants by the oxygen evolving complex (OEC) in photosystem-II2,3 which has driven the scientific efforts towards developing OEC mimics for splitting water. A few complexes that are structurally similar to the OEC have been synthesized but water oxidation by these has not been reported.4,5 We have synthesised [Mn8K2O4(OH)2((CH3)3CCOO)16], {Mn8K2} where the core is structurally very similar to the OEC and can catalyse the oxidation half-reaction of water splitting electrochemically. Here we discuss our synthetic approach for the synthesis of novel Mn complexes aim towards mimicking the OEC and describe the electronic and electrochemical properties of {Mn8K2}.
Fig.1. Crystal structure of [Mn8K2O4(OH)2((CH3)3CCOO)16]. 1. N. S. Lewis, D. G. Nocera, Proc. Nat. Acad. Sci. USA, 103, (2006), 5729. 2. A. J. Bard, M. A. Fox, Acc. Chem. Res., 28, (1995), 141. 3. M. Perez-Navarro, F. Neese, W. Lubitz, D. A. Pantazis, N. Cox, Curr. Opin. Chem.
Biol., 31, (2016), 113. 4. C. X. Zhang, C. H. Chen, H. X. Dong, J. R. Shen, H. Dau, J. Q. Zhao, Science,
348, (2015), 690. 5. E. Y. Tsui, T. Agapie, Proc. Nat. Acad. Sci. USA, 110, (2013), 10084.
23
Development of an Asymmetric Synthesis of Ergoline Derivatives
Robert Connon1, 2, Christina Despotopoulou1, Sean McKeon1, Vincent Coeffard1, Patrick J. Guiry1, 2
1 Centre for Synthesis and Chemical Biology, School of Chemistry, University College
Dublin, Belfield, Dublin 4. 2 Synthesis and Solid State Pharmaceutical Centre (SSPC), School of Chemistry, University College Dublin, Belfield, Dublin 4.
Ergot alkaloids, isolated from fungi of the claviceps genus, exhibit a wide spectrum of structural diversity, biological activity and therapeutic uses. Ergot alkaloids with dopaminomimetic properties have attracted significant interest because of their potential to treat neurological and endocrine disorders. The industrial synthesis of the most important commercial ergot alkaloids starts from naturally occurring lysergic acid obtainable by fermentation. Lysergic acid already contains the full ergoline skeleton and therefore does not allow the introduction of substituents at the C4-position in the ergoline scaffold. Presented here is our work on the asymmetric synthesis of the tricyclic core of the ergoline skeleton (3) with, for the first time, substitution in the C4-position. By using bis(oxazoline) ligands (4) in the Zn(II)-catalysed asymmetric Friedel-Crafts (FC) alkylation of 4-substituted indole derivatives (1) with nitrostyrene derivatives (2), a tandem FC-alkylation/Michael addition sequence was developed, installing three contiguous chiral centres with high levels of enantioselectivity (up to >99% ee, 20 examples). The resulting products of this reaction have been used to synthesise novel C4-substituted tetracyclic ergoline derivatives (5), in a total of 5-6 steps from commercially available starting materials.
NO2R3
N
Zn(OTf)2 (10 mol%)
Ligand (11 mol%)
R1
+
1 2
NH
O N N O
R RR R4
N
**
*R3
R1
N
**
*R3
R1
NO2
R2 OR2 O
5
3
NHR4R2
*up to 94% ee
20 examples
24
Plasmon-Mediated Visible-Light-Driven Conversion of CO2 over RuO2/TiO2 Catalysts
Eduardo Morais 1, Colin O’Modhrain 1, K. Ravindranathan Thampi 2, James Sullivan 1.
1 UCD School of Chemistry, 2 UCD School of Chemical & Bioprocess Engineering, Belfield, Dublin 4, Ireland
Worldwide, geat effort has been made to mimic the natural photosynthesis reaction (i.e. CO2 + H2O + hν → C6H12O6 + O2) producing fuels (or chemicals), via Artificial Photosynthesis (AP). Following a significant amount of research (over 40 years), the scientific community is still a long way from producing efficient and viable devices for promoting AP. The use of semiconductor photocatalysts is desirable, as these materials can absorb sunlight to promote the catalytic conversion of a variety of substrates, including CO2 and H2O.1,2 This work aims to prepare and characterise a range of visible-light-responsive RuO2/TiO2 catalysts, then test these in the photoreduction of CO2 using H2O(g) as co-reactant, i.e. AP. The materials investigated are catalytically active under artificial photosynthesis conditions. The products obtained – CH4 and CO – are potential fuels and chemical feedstocks that could be availed of within the current energy and petrochemical infrastructures. The findings also highlight the plasmonic nature of RuO2 nanoparticles under visible light irradiation and the use of the ensuing hot charge carriers in the CO2 photoconversion (Figure 1a). Furthermore, they demonstrate the synergistic effect between metal nanoparticles and semiconductors (enhancing the reactivity) and the impact of TiO2 incorporation on the selectivity and catalytic performance of these composite catalysts.
Figure 1 (a) plasmon-aided photocatalysis mechanism, (b) absorption spectra of Ru3+ in H2O, (c) variation in the concentration of Ru3+ vs time, (d) TEM image of RuO2, (e) XRD profiles of the prepared catalysts, (f) plasmon absorption of RuO2 in isopropanol and (g) profile of catalytic O2 evolution with time. References (1) Morais, E.; O’Modhrain, C.; Thampi, R.; Sullivan, J. A. Int. J. Photoenergy 2019,
2019, 1–10. (2) Over, H. Chem. Rev. 2012, 112 (6), 3356–3426.
250 300 350 400 450 500 550 600 650 700 750 8000.00
0.03
0.06
0.09
0.12
0.15
Abso
rban
ce /
au
Wavelength / nm
stabilised RuO2 NPs
424
20 25 30 35 40 45 50 55 60 65 70 75 80 85 90
RuO2
10% RuO2 / TiO2
10% TiO2 / RuO2
rutile TiO2
anatase TiO2
RuO2
2θ / °
Inte
nsity
/ au
200 300 400 500 600 700 800
Nor
mal
ised
Abs
orba
nce
/ au
Wavelength / nm
RT 0 h 80 °C 1 h 130 °C 2.5 h 150 °C 3.5 h 160 °C 4 h 160 °C 4.5 h 160 °C 6 h
λ = 304 nm
0 2000 4000 6000 8000 10000 12000
0.0E+00
2.0E-04
4.0E-04
6.0E-04
8.0E-04
1.0E-03
1.2E-03
T = 160 °C
[Ru3+
] mol
L-1
Time / s
0 2 4 6 8 24
0
20
40
60
80
100
120
Con
cent
ratio
n / µ
mol
g-1
Time / h
P25 10%TiO2/RuO2
O2 O2
100%RuO2 10%RuO2/TiO2
O2 O2
(b)
(a)
(c) (d)
(e)
(f) (g)
25
Asymmetric Copper-Catalysis used for Efficient Desymmetrisation in Intramolecular C–H Insertion Reactions of α-Diazo-β-oxo Sulfones
Thomas A. Brouder,a Catherine N. Slattery,a Alan Forda and Anita R. Maguireb
a School of Chemistry; b School of Chemistry and School of Pharmacy, Analytical and
Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland.
The formation of a new C–C bond by insertion into an unactivated C(sp3)–H bond is a powerful transformation enabling access to useful synthetic intermediates. α-Diazocarbonyl compounds are efficient and effective precursors to metal carbenoids, in particular acceptor/acceptor substituted carbenoids, leading to transition metal catalysed C–H insertion, since Taber’s pioneering work in this area.[1,2,3] Over the past two decades, examples of good enantiocontrol in C–H insertion processes have been reported using rhodium carboxylate / carboxamidate catalysts.[4,5,6] Our team has developed an effective copper catalyst system for C–H insertions in α-diazo-β-oxo sulfones, consisting of copper chloride–bis(oxazoline)–NaBARF, that has led to the synthesis of cis-thiopyran dioxides, cyclopentanones and γ-lactams with excellent enantioselectivities of up to 98% ee,[7] 91% ee,[8] and 82% ee,[9] respectively.
S
O O O
R1
Up to 98% ee
R2
O
R2
SR1
O O
NR1
O
SR2
O O
R3
Up to 91% ee Up to 82% ee
M
EWG
EWG
acceptor/acceptor substituted carbenoid
To probe the versatility of the chemistry, we describe herein copper mediated C–H insertion in α-diazo-β-oxo sulfones designed to enable exploration of desymmetrisation.[10] Thus, C–H insertion into a cyclohexane ring, forming a fused bicyclic thiopyran dioxide 1 with control of three stereocentres in a highly diastereo- and enantioselective (dr 98:2, and up to 98% ee) manner, has been achieved for the first time. The impact of substrate variation was explored including the use of a phenyl ketone substrate, in place of the methyl ester, the impact of variation of ring size and C−H insertion into an acyclic C−H bond compared to insertion into a cyclic C−H bond. Similarly, desymmetrisation in the formation of a fused cyclopentanone 2 proceeds with up to 64% ee, which is the highest enantioselectivity reported to date in a copper mediated desymmetrisation to form a cyclopentanone through C−H insertion.
SOMe
O
N2
O O
S
O O O
OMe
CuCl2Bis(oxazoline)
NaBARF
CH2Cl2, ∆
1dr 98:2
Up to 98% ee
H
H
O
S
N2
Ph
O O CuCl2Bis(oxazoline)
NaBARF
CH2Cl2, ∆
O
S
HH
Ph
O O
2dr 12:2
Up to 64% ee 1. Taber, D. F.; Ruckle, R. E. J. Am. Chem. Soc., 1986, 108, 7686. 2. Taber, D. F.; Raman, K. J. Am. Chem. Soc., 1983, 105, 5935. 3. Taber, D. F.; Petty, E. H. J. Org. Chem., 1982, 47, 4808. 4. Ford, A.; Miel, H.; Ring, A.; Slattery, C. N.; Maguire, A. R.; McKervey, M. A. Chem. Rev., 2015, 115, 9981. 5. Doyle, M. P.; Duffy, R.; Ratnikov, M.; Zhow, L. Chem. Rev., 2010, 110, 704. 6. Davies, H. M. L.; Beckwith, R. E. J. Chem. Rev., 2003, 103, 2861. 7. Flynn, C. J.; Elcoate, C. J.; Lawrence, S. E.; Maguire, A. R. J. Am. Chem. Soc., 2010, 132, 1184. 8. Shiely, A. E.; Slattery, C. N.; Ford, A.; Eccles, K. S.; Lawrence, S. E.; Maguire, A. R. Org. Biomol. Chem., 2017, 15, 2609. 9. Clarke, L. A.; Ring, A.; Ford, A.; Sinha, A. S.; Lawrence, S. E.; Maguire, A. R. Org. Biomol. Chem., 2014, 12, 7612. 10. Brouder, T. A.; Slattery, C. N.; Ford, A.; Khandavilli, U. B. R.; Skořepová, E.; Eccles, K. S.; Lusi, M.; Lawrence, S. E.;
Maguire, A. R. J. Org. Chem., 2019, in press.
26
A salt-free method for preparing stable Au/Ag aggregates as liquid SERS substrates for the detection of biomolecules under difficult conditions
Ziwei Ye, Yikai Xu, Steven. E. J. Bell
Queen’s University Belfast
Plasmonic metal nanoparticles have found widespread use in a variety of applications due to the optical properties arising from their localized surface plasmon resonance (LSPR). Assembly of nanoparticles into secondary nanostructures causes the surface plasmons to couple, giving new collective properties that are distinct from those of individual particles. One of the major fields where plasmonic coupling is exploited is in surface enhanced Raman spectroscopy (SERS) where the intense electromagnetic fields in hot spots created between neighboring Au/Ag nanoparticles result in large increase in the Raman scattering intensity. Au/Ag colloids aggregated by added salt are the most widely used substrates for SERS. However, such aggregates are well-known to be unstable and are inherently irreproducible due to the randomness of the process by which they form. Typically, SERS measurements using these aggregates need to be performed within a short time window, which significantly limits their use in time-dependent SERS studies. Here, we demonstrate that evaporation-induced aggregation of emulsified colloids leads to the formation of stable Au/Ag colloidal aggregates without the need for conventional aggregating agents (normally high concentration salt). Critically, the product aggregates display excellent stability and SERS enhancement over days. The Figure below illustrates an example of using Ag aggregates for the detection of adenine down to 0.01 µM in 3.3% albumin solution, under normal conditions using simple colloid adenine cannot be detected at even 1000x higher concentration.
Fig .1. SEM image of Ag aggregates (left). Inset shows the optical image of Ag aggregate colloid. Schematic illustration of SERS measurement perform on Ag aggregates.
27
Influence of substituents on aggregation in series of mono- and di-amide isomers
Islam A. Osman, John F. Gallagher
School of Chemical sciences, Dublin City University. [email protected]
Structural systematics presents a systematic approach in structural science by the
comprehensive multidisciplinary survey of structurally related compounds. The main concept of structural systematics is comparison of chemical structure data, usually derived from
single crystal or powder X-ray diffraction, with physical properties of structurally similar compounds (salts, complexes and small organic molecules).
2 × 6 isomer grid of six N-(difluorophenyl) benzamides (F2-xx) and six N-(phenyl)difluorobenzamides (xx- F2) (xx = 23/24/25/26/34/35) integrating crystal structure analyses (at 294 K), gas phase calculations and conformational analyses is reported. All 12 isomers (C13H9N1O1F2) aggregate via N–H⋯O=C intermolecular interactions and usually in combination with intermolecular C–H⋯O/F/π interactions and often F⋯F contacts. An understanding of the relationships between F/H atom permutations in substituted difluorobenzenes is realised with the influence of fluorine substitution patterns on molecular aggregation rationalised in a series of twelve isomers. Expanding the amide group to di-amide increased the possibility of pharmacological activities. 5 compounds of halogenated N1,N3-di(pyridin-2-yl)isophthalamide in the para- position were synthesised and characterized by spectroscopy and X-ray diffraction. Halogens X influence aggregation in the crystal structures by varying interactions and halogen bonding from F to Cl to Br to I. The third system is a series of di-amide 2x3 isomers substituted with ethyl ester group at ortho-, meta-, and para- positions of isophthalamide and pyridine-2,6-(dicarbonyl)bis-(azanediyl). The addition of the ester group increases interactions and enforcing a change on the molecular geometry. Pyridine (2/3/4-E-PYR) derivatives bind to water molecules by hydrogen bonding as seen in their crystal structures which can be replaced by metals in the future.
28
The Development of Metal Complexes of the Hedgehog Pathway Inhibitor GANT61-D as Potential Anticancer Agents
Aisling Ryan 1, Brendan Twamley 2, Claire Fitzgerald 3, Brona Murphy 3, Darren Griffth 1
1 RCSI Dept of Chemistry, 2 TCD School of Chemistry, 3 RCSI Dept of Physiology & Medical Physics.
Cancer is a major cause of death and disease in Ireland and worldwide. There is an urgent need to develop novel strategies for the treatment of colorectal cancer as many existing therapies do not elicit the required response. Chemotherapeutic treatment failure and cancer relapse are primarily due to drug resistance and the self-renewal properties associated with a subpopulation of tumour cells called cancer stem cells (CSCs). The Hedgehog (Hh) pathway regulates cell differentiation, cell proliferation and stem cell maintenance during embryonic development. Although usually silent in adult tissues, abnormal Hh signalling does occur and is strongly associated with tumour growth, tumour resistance to drug treatment, and metastasis. This pathway is also thought to play a role in maintenance and differentiation of CSCs, which are responsible for resistance, disease progression and metastasis.1
GANT61 inhibits the Hh pathway by reducing the transcriptional activity of proteins Gli 1 and Gli 2. It exhibits antiproliferative/antitumour activity in vitro and in vivo.2 GANT61 hydrolyses under physiological conditions to give 4-pyridine carboxaldehyde (GANT61-A) and the bioactive diamine derivative (GANT61-D), which is responsible for the inhibition of Gli-mediated transcription.2 Furthermore GANT61-D has the structural potential to act as a multidentate ligand forming a diverse range of metal complexes. A series of metal (Ni, Pd and Pt) complexes of GANT61-D were synthesised and fully characterised, including by X-ray crystallography. These complexes were used to investigate (i) the reactivity of GANT61-D as a bioligand and (ii) their anticancer activity. Results to date in relation to the development, pH stability, and in vitro cytotoxicity of the drug candidates will be presented. References:
1. Jia, Y. et al., J. Arch. Toxicol. 2015, 89 (2), 179–191. 2. Calcaterra, A. et al., J. Enzyme Inhib. Med. Chem., 2018, 33 (1), 349-358.
29
Carrier profiling in molecular layer doped Si nanowires: effects of the density and width of the nanowires
Margarita Georgieva1, Noel Kennedy2, Luke Eaton2, Fintan Meaney3, John MacHale3,
Christopher Hatem4, Brenda Long2, Ray Duffy3, Nikolay Petkov1.
1 Physical Sciences Department, Cork Institute of Technology, Bishopstown, Cork, Ireland; 2School of Chemistry, University College Cork, Cork, Ireland,
3 Tyndall National Institute; University College Cork, Lee Maltings, Cork, Ireland; 4Applied Materials, Gloucester, Massachusetts, USA.
With the transition from a planar to 3D device architecture and the continued increase in the density of the functional units, an alternative method for doping that is conformal and non-destructive will be required. Others and we, have shown that molecular layer doping (MLD) is a promising non-destructive alternative to conventional ion-implantation, specifically when carrier concentrations at the order of 1 x 1019 atoms/cm3 or higher are required. However, a uniform dopant profile in the radial (across the width) and axial (along the length) direction of the structures has been flagged as a potential issue with the MLD process. Moreover, extreme density of the structures e.g. sub-20 nm pitch at 10 nm width may present an additional challenge due to reduced access of the dopant-carrying molecules to the nanowire surface. Herein we present our first results on carrier dopant profiling of MLD doped Si nanowires fabricated with varying pitch and size using SOI wafers. To determine the radial uniformity of the carriers a room temperature chemical oxidation/etch is performed, consuming about 1 nm of Si per cycle, and the same device is tested electrically, while the Si removal is calibrated by x-TEM. The axial carriers profiling is obtained by developing on-wire TLM-type structures with minimum spacing between the contacts of about 40 nm.
30
Synthesis and design of new Type 3 Porous Liquids
J. CahirA, M. TsangA, S.L. JamesA, D. RooneyA, J. JacqueminA, B
A) School of Chemistry and Chemical Engineering, Queens University Belfast, Belfast.
B) Chemistry Department, Université de Tours, Tours. [email protected]
c.uk
Porous liquids, recently proposed by James et al.1, are a class of material which combine fluidity with permanent porosity and therefore may have some advantages over solid sorbents, for example, in being able to be implemented into continuous flow processes. Three types were first hypothesized where Type 1 consists of neat porous liquids, Type 2 being porous molecular hosts dissolved in hindered solvents and finally Type 3, porous solids suspended in hindered solvents (Figure 1). Until recently, porous liquids have been a challenge to synthesize. However, Type 3 porous liquids which incorporate the use of porous solids, such as MOFs, and size excluded solvents can be synthesized and characterized with relative ease.
Figure 1. Three types of porous liquids2
The solubilities of gases in each of these porous liquids can be theoretically calculated and the experimental gas uptake measurements suggest that the adsorption behavior of these Type 3 porous liquids can be determined with some porous liquids showing as much as an eight-fold increase in solubility of gases such as carbon dioxide, compared to the pure liquid component. [1] Liquids with permanent porosity, N. Giri et al., Nature, 2015, 527, 216–220 [2] Porous Liquids, N O’Reilly et al., Chem. Eur. J., 2007, 13, 3020 – 3025
31
Investigation of Phosphine based Ligands for the Synthesis of Inorganic CsPbX3 Nanocrystals
Fiona McGrath 1, 2, Kevin M. Ryan 1, 2
1 Department of Chemical Sciences, University of Limerick.
2 Nanotechnology Group, Bernal Institute, University of Limerick. [email protected]
Inorganic metal halide perovskites have received considerable attention recently for their potential use in optoelectronics. These materials demonstrate negligible electron/hole trapping and undergo ultrafast charge transfer to acceptor/donor species; photoluminescent yield close to unity; variable morphology; and tunable bandgaps. However, there are some disadvantages, such as stability in moisture and polar solvents. The aim of this work is to use phosphonic ligands in place of the traditionally used carboxylic acid and amine ligands, in order to control growth and optical properties. Here, we present a simple, effective strategy to synthesise CsPbX3 (X = Br, I, Cl) quantum dots using Trioctylphosphine Oxide (TOPO) and Dodecylphosphine Acid (DDPA). They are characterised using electron microscopy, XRD and FTIR as well as UV-Vis and PL, to provide insights into the morphology and passivation of the material.
32
An experimental and kinetic modelling study on oxidation of diisobutylene
Nitin Lokachari1, Kuiwen Zhang2, William J. Pitz2, Henry J. Curran1
1 Combustion chemistry centre, NUI Galway, University road, H91 TK 33 Galway, Ireland.
2 Lawrence Livermore National Laboratory, Livermore, USA. [email protected]
Alkenes are an important constituent of practical fuels and are also key intermediates during the decomposition of higher hydrocarbons, however alkene kinetics is not well understood. The development of surrogate fuels to represent the combustion characteristics of commercial fuels is important to enable multi-dimensional simulations of IC engine combustion. 2,4,4 trimethyl-1-pentene (iso-octene) is one of the isomers of di-isobutylene (DIB), which gained significant attention in the recent past as a representative of branched alkenes in commercial gasoline [1-5]. In addition, studying DIB also offers kinetic insights into the effect of a double bond presence in the primary reference fuel. However, there is very limited experimental ignition delay data available in the literature for neat DIB at engine-like conditions, and hence most existing DIB models have not been extensively validated. Most of the gasoline surrogate models include DIB sub-mechanism from Metcalfe et al. [6] with little or no modification. In this study, we provide extensive and reliable experimental database for a DIB oxidation study conducted in both high-pressure shock tube (HPST) and rapid compression machine (RCM) facilities at NUI Galway. The ignition delay time (IDT) experiments are performed at pressures (15 and 30 bar) and equivalence ratios (φ = 0.5, 1.0, 2.0) in the temperature range (650–1350 K). Moreover, all available DIB and multi-component gasoline surrogate kinetic models are tested to compare their predictions against the experimental data recorded in this study. Work is under progress at NUIG to develop a detailed chemical kinetic model to represent DIB oxidation. Sensitivity and flux analyses were performed using available models to understand the controlling chemistry at high temperatures.
References: [1] J.C.G. Andrae, R.A. Head, Combustion and Flame, 156 (2009) 842-851. [2] L.R. Cancino, M. Fikri, A.A.M. Oliveira, C. Schulz, Fuel, 90 (2011) 1238-1244. [3] H. Li, Y. Qiu, Z. Wu, S. Wang, X. Lu, Z. Huang, Fuel, 235 (2019) 1387-1399. [4] B.-J. Zhong, D. Zheng, Fuel, 128 (2014) 458-466. [5] E. Hu, G. Yin, Z. Gao, Y. Liu, J. Ku, Z. Huang, Fuel, 195 (2017) 97-104.
[6] W.K. Metcalfe, W.J. Pitz, H.J. Curran, J.M. Simmie, C.K. Westbrook, Proceedings of the Combustion Institute, 31 (2007) 377-384.
33
Copper ferrite (CuFe2O4) as a catalyst in CuAAC
Bartlomiej Wojciechowski and Dr. Grainne Hargaden
School of Chemical and Pharmaceutical Science, Kevin St. lower, D8 [email protected] , [email protected]
Copper catalysed Azide-Alkyne Cycloadditon (CuAAC) is the only synthetic way leading to exclusive formation of 1,4-disubstituted-1H-1,2,3-triazoles in scientifically significant quantities.1 Initially, the 1,4-regioisomers were synthesized via homogeneous types of catalytic systems, but this approach suffers from drawbacks associated with the handling of organic azides and the use of organic solvents as well as post-reaction removal of the catalyst, which often results in contamination of the triazole product with copper2. Nanosized Magnetic Heterogeneous Catalysts offer an attractive change to the catalytic process as due to nano-size, these particles collectively have a very large area of catalytically active surface, that is believed to promote the formation of 1,4-disubstituted-regioisomer in a one-pot three-component reaction performed in aqueous medium with ease of removal from the reaction mixture by application of an external magnetic field.3 One of such catalysts, commercially available nano-CuFe2O4 was first used by Nageswar et al. in CuAAC4a,b and the method presented in this study finds its origin in their findings.
Scheme 1 – model reaction for triazole preparation in presence of CuFe2O4 The presented here work focuses on the preparation and application of nano-Copper ferrite powders (CuFe2O4), with tetragonal and cubic crystalline lattice structure, in the three component CuAAC reaction performed in Scott’s tap water substitute (scheme 1) with the intention of accessing a library of antibacterial and antimicrobial 1,4-disubstituted-1H-1,2,3-triazoles as potential candidates for the composition of protective coatings. We performed 57 reactions according to the model presented in scheme 1, and we report formation of 25 desired triazole products, with 10 that have not been reported before, in average yields. We also determined if the catalyst is in fact heterogeneous and whether contamination of the final product with copper occurs, which lead to very interesting results regarding the mechanism of the catalytic process. References:
1. Hein J. E., Fokin V. V. Chem. Soc. Rev. 39, 1302–1315 (2010). 2. Meldal, M.; Tornoe, CW. Chem. Rev. Vol. 108. Washington, DC, U. S.: 2008. p. 2952-
3015 3. Albadi, J.; Keshavarz, M.; Shirini, F.; Vafaie-nezhad, M. Catal. Commun. 2012, 27, 17. 4. Kumar, B. S. P. A.; Reddy K. H. V.; Madhav, B.; Ramesh, K.; Nageswar, Y. V.
D.Tetrahedron Lett. 2012, 53, 4595. b) Anil Kumar, B.S.P.; Harsha Vardhan Reddy, K.; Satish, G.; Uday Kumar, R.; Nageswar, Y.V.D RSC Adv. 2014, 4, 60652–60657.
34
3D Printing of Spatially Patterned Magnetically Responsive Hydrogels
Patricia Monks1,2, Jacek Wychowanieac, Dermot F. Brougham2 and Andreas Heise1
1Department of Chemistry, Royal College of Surgeons in Ireland, 2School of Chemistry, University College Dublin, Ireland.
Hydrogels, baring similarities to the extracellular matrix and having excellent water retention capabilities, have emerged as a biocompatible material for applications in tissue engineering and as drug delivery devices. Next generation gel applications include as “bio-inks” for 3D printed bio-materials for cell scaffolding and ultimately organ printing. To realise this potential, it is critical to finely control the deposition of the hydrogel in the printing process to produce high fidelity structures. Due to their small size, superparamagnetic iron oxide nanoparticles offer distinguishable advantages from bulk arising from rapid reorientation of their moments. This results in rapid heating, in AC magnetic fields, and in attractive forces in permanent magnetic fields irrespective of initial moment orientation. The integration of magnetic nanoparticles into hydrogels has the potential to alter the properties of the original material and create a hydrogel matrix that can be manipulated in situ using magnetic fields. We are working towards the incorporation of magnetic nanoparticles in the fabrication of novel 3D printable architectures which allows for unique applications as stimulus responsive materials. Here we demonstrate; (i) reproducible and robust extrusion of a hydrogel network; (ii) spatial patterning of thermally active components and drug loading, and; (iii) in situ manipulation using applied magnetic fields with high resolution thermal mapping. The technical development of the responsive nanocomposite gels and preliminary results will also be described.
Fig.1. Schematic Assembly and Application of Magnetically addressable hydrogels
35
Glycocomimetics to Inhibit Candida Albicans Adhesion
Harlei Martin1, Trinidad Velasco-Torrijos 1, Kevin Kavanagh2.
1 Chemistry Department, Maynooth University, 2 Biology Department, Maynooth University. [email protected]
The yeast C albicans. is an opportunistic fungal pathogen which induces superficial and systemic infections in immunocompromised patients. Adherence to host tissue is critical to its ability to colonise and infect the host. In this study, anti-adhesion compounds were evaluated as inhibitors of C. albicans adherence to exfoliated buccal epithelial cells (BECs). A small library of aromatic glycoconjugates were synthesised using synthetic carbohydrate chemistry and Copper-Catalyzed Azide-Alkyne Cycloaddtion (CuAAC) chemistry. These were evaluated as anti-adhesion ligands and it was found that a divalent galactoside showed the best anti-adhesive properties, capable of displacing over 50% of yeast cells already attached to the BECs. 1 To increase the potency of this lead compound, two approaches were tried. The first was using alternative scaffolds which would display the two galactoses in a different orientation. These compounds have shown some promising results, with increased biological activity in some cases. The second approach exploited the multivalency effect, where the lead compound was graphed numerous times onto a common scaffold. This creates a greater interaction with the target and therefore increases the biological effect. Fluorescence studies indicates that this lead compound may bind to structural components of the fungal cell wall. Current work involves synthesising molecular tags that will allow for the identification of this component in the C. albicans. This technique can then be used in the identification of therapeutic targets for the design of new, more efficient anti-adhesion drugs.
NH
NH
O
NNN
NH
O
NN N
OOH
HOOH
OH
O
O
OH
HO
HOHO
Fig.1. Graphical representation of the anti-adhesion approach and chemical structure of divalent galactoside.
1. Martin H, Mc Govern M, Abbey L, Gilroy A, Mullins S, Howell S, Kavanagh K and Velasco-Torrijos T. Eur. J. Med. Chem. 2018, 160: 82-93.
36
Flash Presentations
No. Title Presenter Affiliation Page
F1 Sulfide as Leaving Group: Stereospecific Bromination of Benzylic Phenyl Sulfides C. Cioffi RCSI 38
F2 Macrocyclic N-carboxyanhydrides to achieve homogeneous monodisperse
Collagen-type materials Guillermo Palop NUIG 39
F3 Synthesis of Isoquinolinequinone N-oxides as Anticancer Agents organic pharma Ryan Kruschel UCC 40
F4 Development for the Asymmetric Grignard
Synthesis of Tertiary Alcohols Saranna
Kavanagh UCD 41
F5 Binary Alkoxide Ionic Liquids:
Homogeneous and Heterogeneous Catalysts
Peter McNeice QUB 42
F6 Crystal Engineering of Dihydrogen Phosphate-Phosphoric Acid Cocrystals Molly Haskins UL 43
F7 High-Throughput Screening of Molecular Water Splitting Catalysts Michael Craig TCD 44
F8 Electrochemistry Investigation of Uptake of Bioinorganic Silver-based Drug P. Sidambaram TU Dublin 45
F9 A Simple Nanoparticle-Based TiO2
Memristor Device and the Role of Defect Chemistry in its Operation
Rafaela C de Carvalho TU Dublin 46
F10 Design, Synthesis and Biological
Evaluation of Aromatic Lipoxin A4 Analogues
Aine Mahon UCD 47
F11
Development of Superoxide Dismutase (SOD) Mimetic Microstructures using Two-
Photon Polymerization (2PP) and Click Chemistry
Sean O’Halloran DCU 48
F12 UV-Light Triggering Bioactive Nitric
Oxide Release from Amine-Functionalised Polymers
Tianchao Xie QUB 49
F13 Biocompatible Screen-Printed Electrodes: Cell Viability Investigations
Fionn Ó’Maolmhuaidh DCU 50
F14 A novel tissue culture platform for the long term assessment of nanomaterial fate
Francesco Muraca UCD 51
F15 Computational Investigation of the
Clustering Behaviour of Isonicotinamide in Common Solvents
Mark Lynch UCC 52
F16 Desulfurative fluorination of benzylic
phenyl sulfides: a mean to late-stage 18F-labeling
Francesco Alletto RCSI 53
F17
Study of substituents on the influence of a 2-O-benzoate group on the Lewis acid
promoted anomerisation of a glucopyranoside
Fiach Meany NUIG 54
37
No. Title Presenter Affiliation Page
F18
Development and Optimisation of a Continuous-flow Process for the
Enantioselective Synthesis of 3-Substituted Oxindoles
Kavnen Tseke WIT 55
F19
Investigating the Cytotoxicity under Hypoxic and Normoxic Conditions of
Copper-Based Complexes in both Cancer-derived and Normalised cell lines
Hollie Jenkins TU Dublin 56
F20
Organisation and Photoreactivity of Self-Assembled Metalloporphyrin Aggregates at
the Interface between Two Immiscible Electrolyte Solutions
Iván F. Robayo Molina
UL 57
F21 multifunctional layered magnetic
materials: 2-D magnetic coordination polymers
David Mulrooney UCD 58
F22 Production of Antibacterial Polymeric Materials Graham M Reid UCD 59
38
Sulfide as Leaving Group: Stereospecific Bromination of Benzylic Phenyl Sulfides
D. Canestrari,1 C. Cioffi,1 I. Biancofiore,1,2 S. Lancianesi,1 L. Ghisu,1 M. Ruether,3 J. O’Brien,3 M. F. A. Adamo1 and H. Ibrahim1
1 Department of Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephen's Green,
Dublin 2, Ireland 2 IRBM Science Park S.p.A., Department of Medicinal Chemistry, Via Pontina,
30.600, 00071 Pomezia RM, Italy 3 Trinity Biomedical Sciences Institute, School of Chemistry, The University of Dublin, Trinity
College, Dublin 2, Ireland [email protected], [email protected], [email protected]
Benzylic bromides are versatile synthetic intermediates with wide ranging applications. Common access to this class of compounds is via the nucleophilic bromination of alcohol precursors. This can usually be accomplished with P(V) or P(III) based brominating agents such as PPh3Br2 or PBr3, respectively.[1] Herein, we disclose the adaptation for oxidative nucleophilic chlorination to the analogous brominations using molecular bromine as a widely available and cheap oxidative brominating agent, using phenyl sulfides as leaving groups.[2] This exceedingly simple and mild desulfurative bromination delivers elimination sensitive sulfa-Michael derived benzylic bromides in excellent yields. Moreover, the protocol is stereospecific and provides access to highly enantiomerically enriched β-bromo esters from optically active β-sulfido ester precursors.
Ar
SPhEWG
Ar
BrEWG
excellent yields,high stereospecificity
easily accessiblein high ee's
Br2
This transformation displays remarkable functional group tolerance. For instance, the reaction can be carried out in the presence of a carboxylic acid, a transformation incompatible with P(V) or P(III) based brominating agents. The scope of this reaction, stereospecific bromination of optically active sulfa-Michael derived phenyl sulfides, as well as studies on the configurational stability of optically active bromide products will be presented. NMR studies reveals an initial formation of a sulfide-bromine molecular complex, which in turn is in an equilibrium with a postulated dibromosulfurane intermediate that undergoes C-Br bond formation. References: [1] (a) R. O. Hutchins, D. Masilamani, C. A. Maryanoff, J. Org. Chem. 1976, 41, 1071. (b) R.
Stein, R. D. Dawe, J. R. Sweet, Can. J. Chem. 1985, 63, 3442. [2] D. Canestrari, S. Lancianesi, E. Badiola, C. Strinna, H. Ibrahim, M. F. A. Adamo, Org.
Lett. 2017, 19, 918.
39
Macrocyclic N-carboxyanhydrides to achieve homogeneous monodisperse Collagen-type materials.
Guillermo Palop 1, Eddie Myers 1.
1 NUIG School of Chemistry [email protected]
Collagen, which is main structural protein in the extracellular matrix, is composed of repeating X–Y–Glycine units. Naturally-sourced collagen is heterogeneous, is difficult to modify and can produce an unexpected immunologic response, thus adversely affecting its application in regenerative medicine. Synthetic collagen may provide a solution. Living polymerisation of N-carboxyanhydrides provides well-defined single-residue-repeat polypeptides. A similar reagent that would provide large amounts of multi-residue-repeat polypeptides is currently not available. We will test whether macrocyclic N-carboxyanhydrides, or a similar construct, composed of three or more amino acid residues can be triggered by a nucleophile to undergo ring-opening polymerization to give collagen polypeptides of controlled length with functional handles for further modification to improve physiochemical properties or interact with biochemical triggers. Macrocyclic monomers containing traceless linkers will be designed using a combination of molecular mechanics and DFT calculations (Irish Centre for High-End Computing). Designed monomers will be synthesized and characterised by standard synthetic organic chemistry methods (including Schlenk-line techniques) and analytical tools (NMR spectroscopy, mass spectrometry). Polymeric material will be produced, characterised, and purified (gel permeation chromatography). Polymeric material will be processed for incorporation into a medical device in collaboration with CÚRAM.
NH
OHN
OZNH
Y OHN
XNH
NHO
HN
OO
OO
X
Y
Z NH2
CO2
Post-functionalisation
NH
OHN
OZNH
Y OHN
X Fig.1. Synthetic scheme for the polymerisation and further modification of our Macrocycles.
40
Synthesis of Isoquinolinequinone N-oxides as Anticancer Agents
Ryan D. Kruschel,1 and Florence O. McCarthya
1 School of Chemistry, Analytical Biological Chemistry Research Facility, University College
Cork, Cork, Ireland
The isoquinolinequinone (IQQ) pharmacophore is a privileged framework in known cytotoxic natural product metabolites, caulibugulones and mansouramycins both isolated from marine sponges.1 Both series exhibit cytotoxicity in the sub-micromolar range across multiple cancer cell lines including renal, breast and ovarian. A multitargeted approach is often adopted to explain the IQQ’s potent cytotoxicity. This includes mitochondrial destruction through redox cycling and enzyme inhibition through electrophilic addition to critical amino acids in vivo for example in Cdc25 isoforms, whose function is crucial in normal cell cycle regulation.2,3 We report on the discovery of a potent novel anticancer N-oxide derived framework (Fig. 1). A library of novel IQQ’s were synthesised exhibiting nM cytotoxic activity against breast, melanoma and ovarian cancer cell lines. A lead compound has been identified to conduct further mechanistic studies in view of progression towards clinical development.
Fig.1. Novel IQQ N-oxide framework derived from marine metabolites families, mansouramycin and caulibugulone.
References 1. Milanowski, J.D. et al., Journal of Natural Products, 2004, 67, 70-73 Hawas W.U. et al, Journal of Natural Products, 2009, 72, 2120-2124 2. Kuang S. et al, Oncotarget, 2017, 61, 104057-104071 3. Brisson M. et al., Molecular Pharmacology, 2007, 71, 184-192
• Mitochondrial Destruction • CDC25 Inhibition • Redox Toxicity
Multitargeted
Cancer Cell Death
N
O
O
HN
R
X
O O
O
Novel IQQ Framework
41
Ligand Development for the Asymmetric Grignard Synthesis of Tertiary Alcohols
Saranna E. Kavanagh, Bartosz Bieszczad and Declan G. Gilheany
Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland
[email protected], [email protected]
Chiral tertiary alcohols and their derivatives are a common motif in natural products and pharmaceuticals.[1] Their asymmetric synthesis remains a challenge, and a general highly enantioselective methodology is sought-after.[2] The enantioselective 1,2-addition of Grignard reagents to ketones is an efficient and desirable route to chiral tertiary alcohols. Of the methodologies reported to date, there have been just two cases in which high enantioselectivities were achieved without the need for an additional metal to magnesium to induce asymmetry.[3,4] Through semi-rational design based on a mechanistic hypothesis, an asymmetric system for the 1,2-addition of organomagnesium reagents to ketones has been developed. A tridentate, diamine/phenol ligand (1) has induced enantioselectivities for a range of ketones and Grignard reagents and has been applied in the formal synthesis of vitamin E.[5,6]
N
N
OHR1 R2
OR3-MgBr+
R1 R2
(i) ligand 1, PhMe (dry), -82 °C
(ii) aqueous work-up
HO R3
>70% ee for addition of alkyl Grignard reagents to alkyl-aryl ketones
>90% ee for addition of alkyl Grignard reagents to cyclic alkyl-aryl ketonesN
NR1
R2
OH
Newly developed ligands:
1
The development of derivatives of this ligand with alternative nitrogen-substitution has led to an improvement on some of the previous best enantioselectivities obtained with this methodology. For the addition of alkyl Grignard reagents to alkyl-aryl ketones >90% ee has been achieved. With no alteration in the chirality of the ligand backbone, an inversion of enantioselectivity was observed in the presence of certain moieties. Acknowledgements: This work has been supported by the Irish Research Council (Grant number: GOIPG/2017/1179). References: [1] M. Shibasaki, M. Kanai, Chem. Rev. 2008, 108, 2853–2873. [2] T. Rovis, J. Am. Chem. Soc. 2006, 128, 8095–8096. [3] B. Weber, D. Seebach, Angew. Chem. Int. Ed. 1992, 31, 84–86. [4] K. Osakama, M. Nakajima, Org. Lett. 2016, 18, 236–239. [5] B. Bieszczad, D. G. Gilheany, Angew. Chem. Int. Ed. 2017, 56, 4272–4276. [6] B. Bieszczad, D. G. Gilheany, Org. Biomol. Chem. 2017, 15, 6483–6492.
42
Binary Alkoxide Ionic Liquids: Homogeneous and Heterogeneous Catalysts
Peter McNeice, A. C. Marr and P. C. Marr.
School of Chemistry and Chemical Engineering, and QUILL, Queen’s University Belfast, Belfast, Northern Ireland. [email protected]
We address here the dual problems of ionic liquid instability under basic conditions, and the lack of versatile basic ionic liquids. Ionic liquids are materials which are composed entirely of ions, and are often hailed as “Green Solvents”.[1] Exchanging one ion for another allows the properties of ionic liquids to be tuned, which has led to the concept of “functionalised ionic liquids” (previously known as task-specific ionic liquids).[2] However, there are relatively few examples of base-catalysed reactions being performed in ionic liquids, probably because of the lacuna of basic ionic liquids, resulting from the instability of many ionic liquids under basic conditions. We have previously prepared binary mixtures of ionic liquids containing alkoxide anions to produce highly basic ionic liquids (Figure 1).[3] These novel materials have been proven to be homogeneous basic catalysts for Knoevenagel condensations and Aldol reactions. Catalyst reuse has been unsuccessful with the homogeneous system. We have obtained promising initial results working towards heterogenised systems based on sol-gel materials and immobilisation of ionic liquids upon clay supports.
[1] M. Freemantle, An Introduction to Ionic Liquids, RSC Publications, Cambridge, UK, 2010. [2] E.D. Bates, R.D. Mayton, I. Ntai and J.H. Davis Jr., J. Am. Chem. Soc., 2002, 124, 926-927. [3] P. McNeice, A. C. Marr, P. C. Marr, M. J. Earle, K. R. Seddon, Binary Alkoxide Ionic Liquids, ACS Sustainable Chem. Eng, 2018, 6, 13676-13680
43
Crystal Engineering of Dihydrogen Phosphate-Phosphoric Acid Cocrystals
Molly Haskins, Krishna Peraka and Michael J. Zaworotko
Department of Chemical Sciences and the Bernal Institute, University of Limerick, Ireland
“Cocrystals are solids that are crystalline single phase materials composed of two or more different molecular and/or ionic compounds generally in a stoichiometric ratio which are neither solvates nor simple salts.”1 They are advantageous to the pharmaceutical industry in their ability to alter the physicochemical properties of drug molecules without affecting their biological efficacy. Ionic cocrystals have generated widespread interest as they exhibit strong hydrogen bonding. They have multiple components leading to greater diversity compared to a single component crystal. One pharmaceutical cocrystal, Odomzo® used in the treatment of skin cancer, is an ionic multi-component cocrystal.3 It has attracted interest in the field of crystal engineering as it features an understudied dihydrogen phosphate-phosphoric acid synthon3 (Fig.1), with 38 cocrystal structures found on the CSD (CSD, v.59, 2019).
PO
OHHO
-O
P O
OHHO
HOBH+
Fig. 1. Proposed dihydrogen phosphate-phosphoric acid synthon New dihydrogen phosphate-phosphoric acid cocrystals with bipyridine, 4,4’-(2,5-methyl-1,4-phenylene)dipyridine, and azopyridine have been harvested and analysed by single crystals x-ray diffraction. Aromatic nitrogen groups are very commonly found in API molecules, thus the development of this synthon could open new avenues in the pharmaceutical industry and contribute to the development of crystal engineering principles for ionic cocrystal. References 1. Duggirala, N., Perry M., Almarsson O. and Zaworotko M. J., Chem Comm, 2016, 52, 640. 2. Kish L. and Corry L., P T, 2016, 41, 322. 3. Chen A., Ellison M., Peresypkin A., Wenslow R., Variankaval N., Savarin C., Natishan T., Mathre D., Dormer P., Euler D., Ball R., Ye Z., Wang Z. and Santos I., Chem Comm, 2007, 0, 419.
Cation Anion Neutral
44
High-Throughput Screening of Molecular Water Splitting Catalysts
Michael Craig, Max García-Melchor
School of Chemistry, Trinity College Dublin
Large scale production of hydrogen could be powered by electrochemical water splitting; a major roadblock in realizing this is that current water oxidation catalysts are either costly or inefficient. The oxygen evolution reaction (OER) reaction is the bottleneck reaction for the electrolysis of water. Computational research has driven important developments in the understanding of certain classes of OER catalysts, the bottleneck reaction for the electrolysis of water. A prime example of this is the elucidation of linear relationships in the binding energies of OER intermediates on oxide surfaces.1 Scaling relationships are of paramount importance in catalysis research since they reduce the amount of time required to traverse the vast chemical search space of potential materials. We have recently confirmed the existence of these scaling relations in experimentally-investigated, well-established molecular OER catalysts and have set out design principles for their optimisation, outlining the possibility of a 0 mV overpotential catalyst.2 In this presentation I will present this data, along with data for automatically generated hypothetical catalysts, as seen in Fig. 1.' Furthermore, the results of applying Gaussian processes and statistical learning algorithms to the prediction of the ΔGHO* intermediate which has been identified as an effective initial filter in the computational screening of oxygen-evolving molecular catalysts.
Figure 1: Data for a number of catalysts. Shapes denote the geometry of the catalyst. Manuscript catalysts appear in [2]. The blue line represents the line of best fit through
the data, the equation for which is also displayed in the bottom right, along with the Pearson R correlation coefficient.
(1) Nørskov, J. K.; Rossmeisl, J.; Logadottir, A.; Lindqvist, L.; Kitchin, J. R.;
Bligaard, T.; Jónsson, H. J. Phys. Chem. B 2004, 108 (46), 17886–17892. (2) Craig, M.; Coulter, G.; Dolan, E.; Soriano-López, J.; Schmitt, W.; Garcia-Melchor, M.
2019. https://doi.org/10.26434/chemrxiv.7963592.v2.
45
Electrochemistry Investigation of Uptake of Bioinorganic Silver-based Drug
Prabhakar Sidambaram1, John Colleran2
1Applied Electrochemistry Group, FOCAS Research Institute, Technological University
Dublin, Ireland 2School of Chemical and Pharmaceutical Sciences, Technological University Dublin, Ireland
[email protected]; [email protected]
Heterogeneity in a cell population is a universal phenomenon in all biological systems including whole tissues, and cell cultures.1 Intra-tumour heterogeneity has been widely reported for decades from morphological perspectives, whereas phenotypic and genotypic heterogeneity has also been detected.2 DNA platination is widely assumed as the central mode of action for most platinum anti-cancer drugs. This generalisation on the mode of action for conventional chemotherapy might be a hindrance for effective drug development. Clinical approval for most novel anti-cancer drugs were denied, due to uncertainty in optimal usage, and the mode of action is unclear.3 For a better understanding of the variations, from cell to cell, in response to metal-based drugs, single cell analysis is the key. Single cell experiments should provide critical information about the pathway and disease state, which will guide personalised medicine and therapeutic strategies. The efficacy of tumour-specific metal-based drugs depends primarily on its redox nature. Therefore, electrochemistry is the foremost approach for studying the uptake of metal-based drugs on single cell analysis. This strategy involves positioning a micro or nanoelectrode inside or near the surface of a single cell for the electrochemical monitoring of individual cellular events.4 In this work, the aim is to exploit electrochemical analysis, to study the uptake of silver-based bioinorganic drugs and to elucidate the mode of action. Single cell electrochemistry experiments will be carried out using the platinum, gold and platinum-platinum black nanoelectrodes on human lung carcinoma (A549) cell lines. The speciation of the silver-phenanthroline bioinorganic drugs will be examined using stripping voltammetry for metal detection, and the redox behaviour analysis will be determined by cyclic voltammetry for in vitro and in vivo single cell analysis. References
1. Andrew G. Ewing. et al., Anal. Chem. 2019, 91, 1, 588-621 2. Glenn Deng. et al., Front Cell Dev Biol. 2016, 4: 116. 3. Walter Berger. et al., ESMO Open. 2017, 2(3): e000239. 4. Dechen Jiang. et al., ACS Sens. 2018, 3 (2), 242–250
46
A SIMPLE NANOPARTICLE-BASED TIO2 MEMRISTOR DEVICE AND THE ROLE OF DEFECT CHEMISTRY IN ITS OPERATION
Rafaela C de Carvalhoa, Anthony J. Bettsa. John F. Cassidy a, b
aApplied Electrochemistry Group, FOCAS Research Institute Technological University Dublin, City Campus, Kevin Street, Dublin DO8 NF82, Ireland bSchool of Chemical and Pharmaceutical Sciences Technological University Dublin, City Campus, Kevin Street, Dublin D08 NF82 Ireland
rafaela.decarvalho.mydit.ie, [email protected], [email protected]
A simple metal-semiconductor-metal device comprising TiO2 cast from a suspension of Degussa P25 and placed between two metal plates (Al/Al lap shears) demonstrated memristive-like resistive switching behaviour (Fig. 1). A mechanism is proposed which relies upon the formation of p and n-type regions within the P25 semiconductor material ultimately leading to the formation of a p-n junction. This device also exhibited enhanced steady-state currents upon the imposition of potential steps, most notably at higher potential magnitudes (both anodic and cathodic). Indicating a lack of ionic conduction. Sustaining the notion that electrons and holes were charge carriers rather than ions in this simple device.
-0.6 -0.4 -0.2 0.0 0.2 0.4 0.6-0.3
-0.2
-0.1
0.0
0.1
0.2
Curre
nt (A
)
Voltage (V)
Fig.1. Typical behaviour of a bipolar resistive random-access memory (or memristor) of a structure of Al/TiO2/Al assembly
47
Design, Synthesis and Biological Evaluation of Aromatic Lipoxin A4 Analogues
Áine Mahon1, Prof. Pat Guiry1.
1 Centre for Synthesis & Chemical Biology, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland.
[email protected] Lipoxins, a group of bioactive compounds enzymatically derived from arachidonic acid by a family of lipoxygenase enzymes, were first isolated from human leukocytes by Serhan and Samuelsson in 1984.(1) The two naturally occurring Lipoxins, Lipoxin A4 (LXA4) (1) and Lipoxin B4 (LXB4) (2) are trihydroxytetraene-containing eicosanoids. Lipoxins regulate components of both the innate and adaptive immune systems to initiate the resolution of inflammation by activating the FPR2/ALX receptor.(2,3) Although a healthy bodily response, the effective resolution of inflammation is essential for maintaining normal tissue homeostasis and the prevention of chronic inflammatory diseases.
The major obstacle associated with using Lipoxins to treat diseases caused by chronic inflammation is the rapid metabolism observed in vivo, which is characteristic of all autacoids. These LX metabolites exhibit dramatically decreased biological activity and are considered inactive metabolites, rendering them poor potential pharmacological agents.(4) Within our research group the rapid metabolic inactivation has been overcome by synthesizing aromatic and heteroaromatic analogues of LXA4.(5) The aim of this project is to synthesise a range of aromatic LXA4 analogues with various upper chain modifications to probe the stability in vivo, in particular the -oxidation of the upper chain of which is known to be another source of metabolic instability in LXA4. Bibliographic references : (1) Serhan, C. N.; Hamberg, M.; Samuelsson, B.; Biochem. Biophys. Res. Commun. 1984, 118, 943. (2) Ye, R. D.; Boulay, F.; Wang, J.; Dahlgren, C. Pharmacol. Rev. 2009, 61, 119. (3) Brink, C.; Dahlén, S.-E.; Drazen, J.; Evans, J. F.; Hay, D. W. P.; Nicosia, S.; Serhan, C. N.; Shimizu, T.; Yokomizo, T. Pharmacol. Rev. 2003, 55, 195. (4) Clish, C. B.; Levy, B. D.; Chiang, N.; Tai, H. H.; Serhan, C. N. J. Biol. Chem. 2000, 275, 25372. (5) Duffy, C. D.; Maderna, P.; McCarthy, C.; Loscher, C. E.; Godson, C.; Guiry, P. J. ChemMedChem 2010, 5, 517.
48
Development of Superoxide Dismutase (SOD) Mimetic Microstructures using Two Photon Polymerisation (2PP) and Click Chemistry
Seán O’Halloran 1,2, Andrew Kellett 1,2
. 1 School of Chemical Sciences and Nano Research Facility, Dublin City University, Dublin 9,
Ireland, 2 CÚRAM, School of Chemical Sciences and Nano Research Facility, Dublin City
University, Dublin 9, Ireland. [email protected]
Reactive oxygen species (ROS) have been implicated in a wide variety of pathological conditions including cancer, inflammation, cardiovascular disease, ageing and neurological conditions such as Alzheimer’s and Parkinson’s disease.[1–4] Naturally occurring Cu/Zn superoxide dismutase (SOD) enzymes –such as SOD1 and SOD3– detoxify the superoxide anion (O2
•−) through a dismutation reaction (Fig. 1) resulting in the formation of hydrogen peroxide (H2O2) and molecular oxygen (O2). The aim of this project is to develop next generation implantable medical devices with innate anti-inflammatory activity. This will be achieved utilising two photon polymerisation (2PP) printed microscale structures functionalised with small molecule SOD mimetics. Functionalisation will be achieved via incorporation of reactive handles into the polymeric microstructures for “click” reactions with alkyne/azide functionalised chelating ligands. These microstructures will be imaged using scanning electron microscopy (SEM) and analysed using SOD mimetic xanthine/xanthine oxidase assays.
Fig. 1: Dismutation of superoxide radical ion by superoxide dismutase.
[1] D. Salvemini, D. P. Riley, S. Cuzzocrea, Nat. Rev. Drug Discov. 2002, 1, 367–374. [2] J. C. Dabrowiak, in Metals in Medicine, John Wiley & Sons, Ltd., 2009, pp. 219–249. [3] S. Reuter, S. C. Gupta, M. M. Chaturvedi, B. B. Aggarwal, Free Radic. Biol. Med. 2010, 49, 1603–1616. [4] A. Kellett, Z. Molphy, C. Slator, V. McKee, N. P. Farrell, Chem. Soc. Rev. 2019, 48, 971–988.
49
UV-Light Triggering Bioactive Nitric Oxide Release from Amine-Functionalised Polymers
Yusheng Qiu, Tianchao Xie and Bo Xiao
School of Chemistry & Chemical Engineering, Queen’s University of Belfast, Belfast BT9
Nitric oxide (NO) has well known acting as a signaling molecule to mediate numerous processes in the nervous, immune, and cardiovascular systems in the human body. It also plays antimicrobial roles and accelerates chronic wound healing. A variety of methods have been developed aiming to deliver nitric oxide effectively, among which porous organic polymeric materials (POPs) have been investigated recently. POPs have a wide range of porosity and diverse functionalities that are readily tailored to suit nitric oxide storage and release required for therapeutic applications. Secondary amine groups are incorporated in the POPs that react with nitric oxide molecules to form N-Nitroso (>N-NO). In this manner, nitric oxide is stored in POPs, which converts POPs into a new type of NO donors. Experiments have demonstrated that nitric oxide release from POPs can be triggered by UVA or natural light irradiation (see Fig. 1), which is fully controlled by turning on and off the light.
Fig.1. POPs delivering nitric oxide mechanism. (A and B) Nitric oxide release under UVA light irradiation (~365 nm).
50
Biocompatible Screen-Printed Electrodes: Cell Viability Investigations
Fionn Ó Maolmhuaidh 1, Loanda Cumba 1, Robert Forster 1
1 School of Chemical Sciences, National Centre for Sensor Research, Dublin City University,
Collins Avenue, Dublin 9 [email protected]
Screen-Printed Electrodes (SPE) are established platforms for developing novel (bio)sensors.1 the electrodes performance can be tuned based on the conductive material chosen for the ink and the solvent, binder, and dielectric paste used in formulating the ink. The biocompatibility of these inks is very important as bioassays move toward smart wearable and even implantable assay platforms, as such ensuring the biocompatibility of new ink formulations is essential as they come into prolonged contact with human tissues.2 In this study we aim to improve the biocompatibility of inks by utilising non-toxic and biocompatible binders and solvents in novel ink formulations. There is a trade-off in binder choice as specific binders can affect the characteristics of the electrode with regards to functionalisation following printing, however they are a significant ingredient in the ink and using a known biocompatible binder can vastly reduce cell toxicity. In addition to this we will examine the effect of adding metal-based nanoparticles to the ink formulation. These nanoparticles improve the conductivity of the ink and increase the possibility of down-stream functionalisation. Printed disks of commercially available silver ink, lab formulated biocompatibly optimised silver ink, commercially available carbon ink, lab formulated biocompatibly optimised carbon ink, and l lab formulated biocompatibly optimised carbon ink with gold nanoparticles were used for this study. Following initial culture to confluency in a T75 flask 3, HL-1 cardiomyocytes were then seeded into 6 well plates at a cell density of 2.5 x105 /ml and cultured for a further 12 hours to allow cell adherence. The media was then replaced with fresh media to begin the experiment. The printed electrode disks were then added to the wells facedown, to ensure maximum exposure of the ink to the cell culture media. Over the time course of 1-5 days the cells were cultured without exchanging fresh media. For each ink type a control well was seeded at the same cell density and cultured under the same conditions with the exception to the presence of any ink disk. Cell viability was assessed by haemocytometer using Trypan blue dye to establish the number of living cells per ml, and thus the relative biocompatibility of the ink compared to the control population of cells. Following prolonged culture, the disk surfaces of the electrodes were also visually inspected through SEM imaging. Initial results indicate that there is a significant cytotoxicity associated with the commercially available silver ink. Additionally, these initial results also show that a standard carbon-based electrode ink shows low toxicity levels. This is encouraging towards the formulation of a novel, truly biocompatible biosensor which can be readily functionalised and tailored to a wide range of applications. References (1) Arduini, F.; Micheli, L.; Moscone, D.; Palleschi, G.; Piermarini, S.; Ricci, F.; Volpe, G. TrAC
- Trends in Analytical Chemistry. 2016. https://doi.org/10.1016/j.trac.2016.01.032. (2) Fletcher, S. Advances in Electrochemical Science and Engineering; Wiley-VCH, 2016; Vol.
16, pp 425–443. https://doi.org/10.1002/9783527697489.ch12. (3) Claycomb, W. C.; Lanson, N. A.; Stallworth, B. S.; Egeland, D. B.; Delcarpio, J. B.; Bahinski,
A.; Izzo, N. J. Proc. Natl. Acad. Sci. 1998, 95 (6), 2979–2984. https://doi.org/10.1073/pnas.95.6.2979.
51
A novel tissue culture platform for the long term assessment of nanomaterial fate
Francesco Muraca, Amirah Alahmari, Mura McCafferty and Kenneth A. Dawson
Centre for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland
[email protected], [email protected]
Nanoscience and nanotechnology are research fields in rapid growth, hence nanomaterials are becoming ubiquitous in our everyday life. This has triggered an effort to understand the interactions of nanoparticles with living organisms, and any potential hazardous or beneficial effects that these could cause. While much research is undergoing to understand the short term effects of nanomaterials in our biological systems,1 there is still a significant lack of knowledge regarding the long term fate of nanoparticles that accumulate within the organelles of our cells if they are not efficiently degraded and cleared. This is mainly due to the fact that currently available in vitro platforms designed to study nanomaterials are based on the monolayer culture of cancer cell lines which presents several drawbacks including loss of phenotype and cell-to-cell interactions, and a fast doubling time which results in the exponential dilution of the nanoparticles within the cell population,2 preventing experimental observation times longer than 96 hours. In this study we present the development of a novel in vitro 3D tissue culture model that is able to overcome the main drawbacks of standard monolayer culture systems for the purposes of studying long term nanoparticle-cell interactions. By inducing a healthy quiescent state in the cells suspended in this platform, we were able to not only stop nanoparticle dilution over time, but also observe the formation of complex cell-to-cell interactions typical of biological tissues. In this scenario it is therefore possible to study the fate of nanoparticles and their degradation products in cells over longer periods of time (up to one month) than previously possible, and in a more biologically significant environment; thus uncovering the long-term effects of nanoparticle accumulation, or other important events related to nanomaterial formulation.
Figure 1: A549 cell clusters stained for cadherin and LAMP1 lysosomal marker (RED),
containing nanoparticles (GREEN) at 2 weeks from exposure. 1. Yildirimer, L., Thanh, N. T. K., Loizidou, M. & Seifalian, A. M. Toxicological
considerations of clinically applicable nanoparticles. Nano Today 6, 585–607 (2011). 2. Kim, J. A., Åberg, C., Salvati, A. & Dawson, K. A. Role of cell cycle on the cellular
uptake and dilution of nanoparticles in a cell population. Nat. Nanotechnol. 7, 62 (2011).
52
Computational Investigation of the Clustering Behaviour of Isonicotinamide in Common Solvents
M. B. Lynch,1,2 S. E. Lawrence,
1 M. Nolan 2
1 Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid-State Pharmaceutical Centre, University College Cork, Ireland.
2 Tyndall National Institute, Lee Maltings, UCC, Cork, Ireland Crystallisation is the crucial final process in pharmaceutical manufacturing to separate and isolate the purified material. At present, the exact role of the solvent on nucleation remains elusive.1 Thus, there has been a growing trend in using computational methods to help elucidate the role of solvent. One approach to predict the ease of nucleation is based on atomic models of solute and solvent interaction energies,2-6 correlated with experimental data. Recently, we predicted that isonicotinamide will nucleate easiest from chloroform and hardest from acetic acid based on computed solute – solvent interaction energies.6 To advance the understanding of the role of solvent at a molecular level, we have employed molecular dynamics to probe the influence on different solvents on the initial clustering behaviour of isonicotinamide. Depending on the solvent, several patterns of clustering were observed. As the number of isonicotinamide molecules in the simulations was increased, larger clusters of isonicotinamide form. Clustering in solvents with strong isonicotinamide – solvent interactions is inhibited, while solvents possessing the weakest interactions give rise to larger clusters.
Figure 2: Example of the solvation of an Isonicotinamide trimer (left) and a heptamer cluster formed in the MD simulation in dichloromethane (right). References: [1] Davey, R. J.; Schroeder, S. L. M.; ter Horst, J.H. Angew. Chem. Ind. Ed., 2013, 52, 2166 [2] Yang, H.; Svärd, M.; J. Zeglinski, Å. C. Rasmuson, Cryst. Growth Des. 2014, 14, 3890. [3] D. Khamar, J. Zeglinski, D. Mealey, Å. C. Rasmuson, J. Am. Chem. Soc. 2014, 136, 11664. [4] D. Mealey, J. Zeglinski, D. Khamar, Å. C. Rasmuson, Faraday Discuss. 2015, 179, 309. [5] Zeglinski, J. et al. Chem. Eur. J. 2018, 24, 4916. [6] Lynch, M. B.; Lawrence, S. E.; Nolan, M. J. Phys. Chem. A, 2018, 122, 3301-3312
53
Desulfurative fluorination of benzylic phenyl sulfides: a mean to late-stage 18F-labeling
Francesco Alletto1, Robert Williams2 and Mauro F. A. Adamo1
1Centre for Synthesis and Chemical Biology (CSCB), Department of Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland
2Lifescientific Ltd, Nova UCD, Belfield Innovation Park, Belfield, Dublin 4 [email protected]
18F-labelling – known since the 1960s[1] – has grown importance thanks to its peculiar decay by positron emission which is used in the well-established positron emission tomography (PET). PET has become standard medical care in oncology, permitting both early-stage and metastatic diagnosis[12]. Development of new reactions capable of including 18F radionuclide presents unique challenges due to the peculiar characteristics of this isotope. This is why the state-of-the-art [66, 67, 53, 68, 69] suffers from various drawbacks – such as long reaction times, substrate restrictions and poor enantioselectivity – that refrain the true potential of the field. Following our recently developed chlorination method through oxidation of phenyl sulphides[5], we adapted the concept to analogous fluorinations using N-F reagents. After optimization of the reaction, this simple and mild desulfurative fluorination delivers benzylic fluorides in reasonable timings and with good conversions. We are now studying the stereoselevtivity of the reaction and aim to increase its scope.
Ar
SPhR
Ar
FR
74%easily accessible
F+
The proposed mechanism for this reaction, along with its optimization and kinetic studies will be presented. References: [1] M. Blau, R. Ganatra, M. A. Bender, Semin. Nucl. Med. 1972, 2, 31–37. [2] E. Miele, G. P. Spinelli, F. Tomao, A. Zullo, F. De Marinis, G. Pasciuti, L. Rossi, F.
Zoratto, S. Tomao, J. Exp. Clin. Cancer Res. 2008, 27, 52. [3] J. A. Kalow, A. G. Doyle, J. Am. Chem. Soc. 2010, 132, 3268–3269 [4] R. Neelamegam, W. Liu, J. T. Groves, J. M. Hooker, X. Huang, H. Ren, J. Am. Chem.
Soc. 2014, 136, 6842–6845. [5] T. D. Beeson, D. W. C. MacMillan, J. Am. Chem. Soc. 2005, 127, 8826–8828. [6] D. O’Hagan, H. Deng, Chem. Rev. 2015, 115, 634–649. [7] S. Bloom, C. R. Pitts, R. Woltornist, A. Griswold, M. G. Holl, T. Lectka, G. Holl, T.
Lectka, 2013. [8] D. Canestrari, S. Lancianesi, E. Badiola, C. Strinna, H. Ibrahim, M. F. A. Adamo, Org.
Lett. 2017, 19, 918–921.
54
Study of substituents on the influence of a 2-O-benzoate group on the Lewis acid promoted anomerisation of a glucopyranoside
Fiach B. Meany, Paul V. Murphy.
School of Chemistry, National University of Ireland, Galway, University Road, Galway.
The stereoselective synthesis of glycosidic bonds remains a challenge to the modern day carbohydrate chemist. One method of achieving stereoselective glycoside synthesis is via the Lewis acid promoted anomerisation of a glycoside, which often means converting 1,2-trans glycosidic linkage to the 1,2-cis anomer. This reaction has been shown to be successful in some cases, but applications are somewhat limited due to lack of a full understanding of factors which influence the reactivity of glycosides in this reaction. In order to gain greater insight to the mechanism of anomerisation, a series of benzoylated butyl glycosides 1 have been prepared, where X (H, F, Me, Cl, Me, CF3, F, OMe) has been varied at C-2 as shown in Fig. 1 and the rates of anomerisation have been determined by 1H NMR spectroscopy. The data has been used to obtain both Hammett and Swain-Lupton plots, which can be interpreted as the 2-OBz group influencing reactivity through a combination of resonance and inductive effects. A resonance contribution indicates the carbonyl group at C-2 can contribute to cation stabilisation in the rate influencing step.
OOBz
BzOBzO
OOBu
O
X
SnCl4 (0.34 M in CDCl
3,
1 equiv)
CDCl3, 25 oC
OOBz
BzOBzO
O
O
X
OBu
Fig.1. Anomerisation of Glucopyranoside
55
Development and Optimisation of a Continuous-flow Process for the Enantioselective Synthesis of 3-Substituted Oxindoles
Kavnen Tseke , Claire Lennon, Joe O’Mahony, Mike Kinsella
Pharmaceutical and Molecular Biotechnology Research Centre (PMBRC), Department of
Science, Waterford Institute of Technology, Waterford, Ireland [email protected]
Continuous-flow processes are progressively gaining ground in organic synthesis and API manufacturing as they are well adapted toward process intensification providing faster, safer, more efficient, greener and sustainable alternatives to traditional batch synthesis. Enantiopure 3-substituted oxindoles form key core structures in several biologically relevant molecules with antiviral, anticonvulsant and anticancer activities. They can be accessed via organocatalysed aldol reactions of isatin with desirable aldehyde or ketone. Organocatalysis is a fast advancing, eco-friendly, non-toxic and cost-effective approach to asymmetric synthesis with significant benefits over transition metal catalysis. This work therefore aims at merging the advantages of organocatalysis and flow chemistry to develop a neat, process intensified and faster route for accessing 3-substituted oxindoles using leucinol catalysed aldol reaction of isatin and acetone as a model. Solvent screening to achieve reagent/ product homogeneity under conditions which do not compromise yield and selectivity revealed neat conditions with 10 equivalents of water additive at room temperature as ideal reaction conditions in batch. A coiled tubing flow reactor of tailored dimensions was fabricated, and the reaction conditions transferred from batch to flow. Flow rates were optimised to give improved yields in reaction times twice as fast as the batch process at room temperature. Furthermore, reactions above the boiling point of acetone proceeded in a safe and seamless fashion, giving increased yields and accelerated reaction speed (8 times faster than the batch process) with just a marginal loss of 3% in enantioselectivity.
O
Temperature,Residence time
acetone
NH
O
O
NH
O
HOO
+
Isatin in acetone and 10eq water
3-substituted-3-hydroxy-2-oxindole
OHNH2
20 mol% L-Leucinol Back PressureRegulator
Batch at 20oC, 48hrs: 92% yield, 93% ee
Flow at 20oC, 24hrs: 99% yield, 94% eeFlow at 60oC, 6hrs: 98% yield, 91% ee
Scheme 1.: Flow synthesis of 3-substituted-3hydroxy-2-oxindoles References: (a) Malkov, A.V., et al, 2007, Org. Lett., 9(26), 5473-5476. (b) Gérardy, R., et al, 2018, Eur. J. Org. Chem., 2301-2351
56
Investigating the Cytotoxicity under Hypoxic and Normoxic Conditions of Copper-Based Complexes in both Cancer-derived and Normal cell lines
Hollie Jenkins 1, Bernie Creaven 1, Orla Howe 2.
1 Technological University Dublin, Tallaght Campus, Blessington Rd, Tallaght, Dublin 24,
2Technological University Dublin, City Campus, Focas Institute, Camden Row, Saint Kevin’s, Dublin 8.
Generation of reactive oxygen species (ROS) is a normal process within a cell, with such species having a role in normal metabolic pathways as well as in programmed cell death and proliferation. However, the generation of excess ROS and subsequent oxidative stress is believed to be a contributory factor to both cancer development and progression[1] via damage caused to cell organelles including DNA. It is a conundrum that ROS production is the mechanism of action shared by most non-surgical treatments for cancer, and hypothesized to be the mechanism of action for many copper-based chemotherapeutics, and yet generation of ROS is thought to be both initiative and cause metastasis of some cancers. This project attempts to understand the role of copper-based chemotherapeutics in treating cancer and whether they increase or decrease oxidative stress in cancer cells under different oxygen conditions. Complexes synthesised by our group which have significant anti-cancer activity did not appear to generate ROS or act as chemical nucleases but are thought to damage other organelles of the cell, as cell morphology studies using confocal microscopy have shown that the DNA is intact. The cytotoxicity of a selection of these complexes have been determined in the breast cancer cell line MCF7 and non-cancerous HaCaT cell line. Treatment of these cell lines with selected complexes and their cytotoxicity under varying oxygen conditions will be discussed in this poster.
References:
1. Miyata, Y.; Matsuo, T.; Sagara, Y.; Ohba, K.; Ohyama, K.; Sakai, H. Int. J. Mol. Sci. 2017, 18, 2214.
57
Organisation and Photoreactivity of Self-Assembled Metalloporphyrin Aggregates at the Interface between Two Immiscible Electrolyte Solutions
Iván F. Robayo Molinaa, Andrés F. Molina Osorioa, Micheál D. Scanlona
aDepartment of Chemical Sciences and the Bernal Institute, University of Limerick (UL),
Limerick V94 T9PX, Ireland [email protected]
Porphyrin aggregates and their metallo-derivatives are good candidates as components of photoelectronic materials, photosensitized solar cells, and organic light-emitting devices, due to their unique structure and excellent photochemical and photophysical properties [1]. The Interface between Two Immiscible Electrolyte Solutions (ITIES) provides a surface that is free from defects, an ideal framework for bottom-up fabrication of these supramolecular assemblies [2]. Under potentiostatic conditions, a photoinduced heterogeneous electron transfer across the ITIES may arise from hydrophobic redox species in the oil phase to hydrophilic redox species in the aqueous phase through the light excitation of the interfacial porphyrin assembly [3]. The hydrophobicity gradient that the ITIES provides helps to separate the subsequent photoproducts, minimising recombination. On the other hand, the efficiency of harvesting light from these porphyrin aggregates is intrinsically determined by their specific adsorption and molecular organization [4]. Thus, new methodologies for controlling the aggregation process and determining the type of structure under potentiostatic conditions can help us maximise the photocurrents from this process. Ultraviolet and Visible Total Internal Reflection spectroscopy (UV-Vis-TIR), coupled with cyclic voltammetry (CV), is a low cost technique which can provide in situ information about the type of porphyrin aggregates adsorbed at ITIES. Thus, in this presentation, the relation between the structure of a porphyrin aggregate and the dynamic of a charge transfer reaction was studied by correlation between spectro-electrochemical signals obtained with UV-Vis-TIR and CV, and later corroborated with photocurrent transient data. Our aim is to understand the influence of different fundamental steps on the rate and efficiency of photo-induced interfacial electron transfer reactions and to improve the efficiency of the charge separation at electrochemically active soft interfaces. References: [1] M.D. Scanlon, et al., Chem. Rev., 2018, 118, 3722. [2] C.M. Drain, et al., Chem. Rev., 2009, 109, 1630. [3] D.J. Fermín, et al., Chem. Commun., 1998, 0, 1125. [4] D.J. Fermín, N. Eugester, Organization and Photoelectrochemical Reactivity of Water-Soluble Metalloporphyrins at the Liquid/Liquid Interfaces, in N4-Macrocyclic Metal Complexes (Ed.: J.H. Zagal, F. Bedioui, J.P. Dodelet), Springer Science+Business Media, New York, 2006.
58
MULTIFUNCTIONAL LAYERED MAGNETIC MATERIALS: 2-D MAGNETIC COORDINATION POLYMERS
David Z.T. Mulrooney 1,Tony D. Keene.
School of Chemistry, University College Dublin, Belfield, Dublin 4.
The field of coordination polymers (CPs) and metal–organic frameworks (MOFs) has impacted many areas of science including commercial applications from gas storage agents to new investigations as drug-delivery vehicles.1 CPs and MOFs are prepared from the combination of metal cations, commonly d- or f-block metals, and ligands capable of bridging metal centres to create polymeric structures which extend in one, two or three dimensions.2 Careful consideration of the properties of these components permits rational and systematic synthesis of compounds with known and expected properties.3 Molecular magnetism is a field acquiring significant interest as single molecule magnet (SMM) materials are on the cusp of becoming industrially viable; these materials stand to revolutionise data storage. This project focuses on the synthesis, structural and magnetic characterisation of three different groups of 2-D CPs; a ferromagnetic copper compound prepared via a modified Solvay process,4 a series of multifunctional lanthanide CPs illustrating the effect of solvent, and a series of hexagonal oxalate layered compounds.
Fig.1. Various layered compounds left-right – (a/b) copper kagome CP, (c) layered europium
compound, (d) hexagonal oxalate compound.
References: 1 R. Ricco, C. Pfeiffer, K. Sumida, C. J. Sumby, P. Falcaro, S. Furukawa, N. R.
Champness and C. J. Doonan, CrystEngComm, 2016, 18, 6532–6542. 2 S. R. Batten and N. R. Champness, Philos. Trans. R. Soc. A Math. Phys. Eng. Sci.,
2017, 375, 20160032. 3 N. W. Ockwig, O. Delgado-Friedrichs, M. O’Keeffe and O. M. Yaghi, Acc. Chem.
Res., 2005, 38, 176–182. 4 D. Z. T. Mulrooney, J. E. Clements, D. J. Ericsson, J. R. Price, I. A. Kühne, S. J. Coles, C. J. Kepert and T. D. Keene, Eur. J. Inorg. Chem., 2018, 5223–5228.
59
Production of Antibacterial Polymeric Materials
Graham M Reid1, Shauna P Flynn1,2, James Mc Cormack1, Lucia Podhorska1, Colm Delaney1, Laura Quinn2, Eoin Casey2 and Susan M Kelleher1
1 UCD School of Chemistry, 2 UCD School of Chemical & Bioprocess Engineering
The nanostructured topography of cicada wings has been shown to possess antibacterial properties. Although the bactericidal action is not fully understood, it has been suggested to be based on the physical surface structure, making it an attractive route for controlling bacterial contamination of surfaces without the use of chemical agents. There is an opportunity to fabricate nanostructured polymeric materials that could maintain the bactericidal action found in nature. Our group is interested in producing nanostructured polymeric materials which could have applications in the coating of surfaces in a medical or food packaging setting. We have used block copolymer (BCP) lithography to transfer nanopatterns to a Si substrate. Our cylinder forming poly (styrene - block - methyl methacrylate) polymer is thermally annealed over a neutral brush layer to microphase separate into perpendicular cylinder domains of 20 nm in diameter, with a spacing of 40 nm, while another BCP system, poly (styrene – block – 4 - vinylpyridine) has been solvo-thermal annealed using our custom designed chamber to produce a similar nanopattern on Si substrates. Activation of the BCP surfaces allows the incorporation of an Fe(NO3)3 hard mask with similar dimensions of the minor block. An oxidation step of the Fe(NO3)3 produces a final iron oxide hard mask that allows plasma etching of the underlying Si, producing a master template of a nanostructured surface. A two-step soft-lithography procedure has been utilised to transfer the pattern from Si templates to UV-curable polymers, producing nanostructured polymer surfaces. Si and polymer surfaces have been characterised using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The bactericidal activity of both the moulds and Si masters will be studied using static cultivation tests against Pseudomonas fluorescens.
Fig.1. 2 µm2 AFM height image of Fe(NO3)3 hard mask on Si surface, and an SEM image of
Si surface following plasma etch (scale bar 200 nm)
60
Poster Presentations
No. Title Presenter Affiliation Page
P1 Synthesis of Nisin Derivatives to Investigate their Antibiotic Properties Dean Winder TU Dublin 63
P2
The First Enantioselective Synthesis of Gingesulfonic Acids and Unequivocal
Determination of their Absolute Stereochemistry
Grazia Bencivenni RCSI 64
P3 Deep-Sea Drug Discovery; The Isolation And
Characterisation Of Potent Novel Anti-Inflammatory Glycolipopeptides
Sam Afoullouss NUIG 65
P4 Metal-Based Glycoconjugates for the Targeted Anticancer Chemotherapy Ioannis Titilas NUIG 66
P5
NIR Osmium (II) polypyridyl probe with a therapeutic twist: disrupting the
mitochondrial membrane potential for targeted therapy
Karmel Gkika DCU 67
P6 Investigation of Hosts for Type 2 Porous Liquids
Francesca M. Alexander QUB 68
P7 Optimisation and Scale-up of the β-
Chloroacrylamide Process using Batch and Continuous Flow Methods
Olga Dennehy UCC 69
P8 Photo-induced Electron Transfer at Liquid-
Liquid Interfaces for Solar Energy Conversion
Kamil A. Cywinski
UL 70
P9 Coordination chemistry of 2-picolyl
naphthalene diimide and bis- phthalimide ligands
June Lovitt TCD 71
P10 Stability Studies on the Hydrolysis of
Antimicrobial Inorganic Tellurium(IV) complexes
Kenneth D’Arcy NUIM 72
P11 Conjugated Polymer Nanoparticles as A New
Class of Fluorescent Probes based on Emission Anisotropy
Zixu Zhao UCD 73
P12 New Tetrazole-Based Compounds for Coating
Medical Implants: Synthesis and Corrosion Studies
Rónan McAteer TU Dublin 74
P13 Pyridine 5-hydroxytriazoles: a new class of
potential ligands for drug discovery and catalysis
Roberta Pacifico RCSI 75
P14 Synthesis Towards Constrained Anti-Adhesive Sia(α2-3)Gal Glycomimetics Sylvester Byrne NUIG 76
P15 Next Generation Antisense Therapeutics Brionna Mc Gorman DCU 77
P16
CTAB as a Non-Adsorbing “Promoter” for the Self-Assembly of Charged Colloidal
Nanoparticles at Liquid-Liquid Interfaces into Multi-Dimensional Arrays
Li, Xinyuan QUB 78
61
No. Title Presenter Affiliation Page
P17 Source apportionment of ambient
carbonaceous aerosol in Ireland using a variety of analytical techniques
Eimear Heffernan UCC 79
P18 Supramolecular Isomers of [Zn(glycolate)(bipy)1.5]n Chenghua Deng UL 80
P19 Synthesis, spectroscopic properties and aggregation behaviour of terpyridine
functionalized building blocks Jason Delente TCD 81
P20 Estrogen-Copper(II) complexes as targeted anticancer metal-based drugs Stephen Barrett NUIM 82
P21 Continuous Flow Photorearrangement of Isoxazoles Cormac Bracken UCD 83
P22 Polypeptide-based hydrogels for tissue engineering Shona O’Brien RCSI 84
P23 Novel Zn and Mg MOFs based on azo-
dicarboxylate ligands and their potential for drug delivery
Ahmed Ahmed NUIG 85
P24 Plasmonic fluorescent assay for molecular lipid membrane binding, permeation and
dynamics of permeation. Agata Steplewska DCU 86
P25 Porous Polymeric Materials for Active Pharmaceutical Ingredient (API) Delivery Hung-Jui Chen QUB 87
P26 Ambident Reactivity of Enolates: The Last Stand for HSAB Theory? Kevin Sheehy UCC 88
P27 Electrochemiluminescence of Heavy Metal
Free Nanomaterials for Applications in Biosensing
Siobhán O’Connor UL 89
P28 Smart Anionophores: Stimuli-Responsive Anion Transport Luke Marchetti NUIM 90
P29 Synthesis and Applications of Cyclic Sulfonamides Aisha Khalifa UCD 91
P30
Effects of nanoparticle-corona’s glycoproteins and their glycan component on
the macrophage uptakes of silica nanoparticles
Duong N. Trinh RCSI 92
P31 Ion-Responsive Self-Immolative Linkers for Drug Delivery Liam Fitzgerald NUIG 93
P32 An investigation of mycotoxin induced DNA damage in IPEC-J2 Porcine Intestinal Cells Asmita Thapa DCU 94
P33 Star polymers and cross-linked star polymer model networks prepared by aqueous RAFT
polymerization for drug/DNA delivery Gavin Irvine QUB 95
P34 On-line Analysis of Organic Aerosols in Air Niall O'Sullivan UCC 96
P35 C2H2/CO2 Separation Studies of Pyrazole Ligand Derived Hybrid Ultramicroporous
Materials Naveen Kumar UL 97
62
No. Title Presenter Affiliation Page
P36 Directed Self Assembly of Near Infrared
Fluorescence Responsive Nanoparticles and their use for Cellular Imaging
Niamh Curtin RCSI 98
P37 Intrinsic Properties of Nitric Oxide Binding to Hemin and Hemin Conjugates: A Theoretical
Study Amir Abdo NUIG 99
P38 Gas Chromatography-Mass Spectrometry Analysis of Bacterial Volatiles Shane Fitzgerald DCU 100
P39 Ionic Liquid-Assisted Synthesis of
Nanocatalysts for the Direct Conversion of CO2 to Hydrocarbons
Zara Shiels QUB 101
P40 Pressing solids directly into sheets of
plasmonic nanojunctions enables solvent-free surface-enhanced Raman spectroscopy
Li, Chunchun QUB 102
P41 Filling in the gaps: A comprehensive analysis
of light transmission through void-filled inverse opal photonic crystal materials
Alex Lonergan UCC 103
P42
Rapid Profiling of Enteric Coated Drug Forulations via Broadband Acoustic Resonance Dissolution Spectroscopy
(BARDS)
Niamh O' Mahony UCC 104
P43 Electrochemical sensing of Lactose in Fermentation Process Monitoring Grace Halpin NUIM 105
P44 Bio-conjugations In Flow for Drug Conjugates and Theranostic Imaging Agents Sheila Fitzgerald RCSI 106
P45 Cyclometalated Ir(III) Complexes as Triplet
Photosensitisers for Efficient Visible-Light Absorption
Nidhi Arora TCD 107
P46 Developing tools for pesticide detection and toxicity testing in agricultural soils
Mathavan Vickneswaran DCU 108
P47 The Control of Single Nanowire Device’s Electrical Performance via Seed Mediated
Doping and Contact Design Adrian Hannon UL 109
P48 In Search of Highly Emissive Donor-Acceptor Structures for Thermally Activated Delayed
Fluorescence Organic Light Emitting Diodes Martha Gulman TCD 110
P49 Design of Coordination Networks using Rod Building Blocks Daniel J.O’Hearne UL 111
P50 Switching Adsorbent Layered Materials Shi-Qiang Wang UL 112
P51 Investigation of Steel Serving Utensils on the Irish Market for Migration of Metals using
ICPMS Xinyi Wu TU Dublin 113
P52 Development of Novel Anticancer Agents Targeting Glioblastoma Multiforme Kate Byrne TU Dublin 114
63
Synthesis of Nisin Analogues to Investigate Their Antibiotic Properties
Dean Winder, Fintan Kelleher
Molecular Design and Synthesis Group, TU Dublin – Tallaght Campus, Dublin 24 [email protected]
Worldwide, there has been an increase in antibiotic resistance. According to the World Health Organisation “Antibiotic resistance is one of the biggest threats to global health, food security, and development today”. As such, the discovery of new antimicrobial agents, with the potential to be used as antibiotics, is now more important than ever. One such antimicrobial peptide that is currently used is Nisin (Figure 1), produced by L. lactis. Nisin has a wide range of uses in dairy products, however, its optimum solubility and stability is in the acidic pH range, which presents a number of issues with its use in many food products, as well as a veterinary or human therapeutic. It is known that small modifications to the tail of antimicrobial peptides can lead to improvements in their stability, solubility and antimicrobial activity profiles. In an attempt to improve the stability and solubility of both Nisin A and Z at physiological pH, the preparation of a number of Nisin A and Z derivatives has been investigated. To date a number of these derivatives including Nisin A and Z allylamides, and Nisin A allylmethylamide, have been synthesised, characterised by LC-MS and NMR spectroscopy, and are awaiting biological testing. Details of these synthetic studies will be presented.
Figure 1: Amino acid structure of both Nisin A and Z
64
The First Enantioselective Synthesis of Gingesulfonic Acids and Unequivocal Determination of their Absolute Stereochemistry
G. Bencivenni,a M. Moccia,b M. W. Gillick-Healy,a and M. F. A. Adamoa
aCentre for Synthesis and Chemical Biology (CSCB), Department of Pharmaceutical and Medicinal Chemistry, The Royal College of Surgeons in Ireland, 123 St. Stephen’s Green,
Dublin 2, Dublin, Ireland bInstitute of Crystallography, Consiglio Nazionale delle Ricerche (CNR)-Bari,
Via G. Amendola 122/O, 70126 Bari, Italy [email protected], [email protected]
Gingesulfonic acids are a family of natural compounds found in ginger-based remedies. They have been proved to be very effective in the treatment of ulcers1, however their limited availability in nature (0.0013% to mass of Ginger2) and the difficulty in their purification has prevented them from being used as active principles. In this work, we report the first organocatalysed enantioselective synthesis of natural and unnatural gingesulfonic acids and shogasulfonic acids via a mild and convenient aminothiourea-catalysed addition of bisulfite to the olefin moiety of α,β-unsaturated carbonyls—a technology previously reported by us.3 A series of optically active sulfonic acids are prepared in their natural and unnatural configurations with moderate to high ee, and their absolute configurations are unequivically confirmed by single crystal X-ray diffractometry. Fig.1. Sinthesys of 2a-g involving catalysts 3a-b. Fig.2. X-ray structure of compound 4b. References: [1] Y. Johji, M. Michihiko, H. Q. Rong, M. Hisashi, F. Hajime, Journal of ethnopharmacology. 1988; 23(2), 299-304. [2] Y. Hori, T. Miura, Y. Hirai, M. Fukumura, Y. Nemoto, K. Toriizuka, Phytochemistry, 2003, 62(4), 613-7. [3] Moccia, M. , Fini, F. , Scagnetti, M. and Adamo, M. F, Angew. Chem. Int. Ed., 2011, 50: 6893-6895
O
HO
O
RO
HO
O SO3H
RNaHSO3
(0.48 M),
catalyst (10 mol %)
MeOH/toluene (3:1), 0 °C
*
N HN
MeO S
HN
CF3
CF3
NHN
MeO S
HN
CF3
CF3
1a-g 2a-g
3a 3b
65
Deep-Sea Drug Discovery; The Isolation And Characterisation Of Potent Novel Anti-Inflammatory Glycolipopeptides
Sam Afoullouss1,2, Kevin Calabro1, Christine Morrow2, Louise Allcock2, Olivier P. Thomas1
1 Marine Biodiscovery. School of Chemistry and Ryan Institute, National University of Ireland Galway University Road, H91TK33 Galway, Ireland.
2 Zoology, School of Natural Sciences and Ryan Institute, NUI Galway, University Road, Galway, Ireland.
As part of a deep sea drug discovery program aimed at characterizing hotspots of biological and chemical diversity in Celtic continental margin, samples of marine sponges and corals were collected from cold water reefs (CWR) from a depth between 750 – 3000 m. The extreme physical conditions of the deep sea force these organisms to develop unique specialized metabolites with original chemical structures and characteristics.
Using a rigorous chemical screening approach, we decided to focus on the Tetractinellida sponge Characella pachastrelloides (Carter, 1876). We report herein the isolation and structure elucidation of four novel glycolipopeptides named characellides. These compounds (867 Da) consist of three separate moieties: a tripeptide (O-Me-Tyr, Asp, Thr), a nine/ten-member alkyl chain capped with a dimethyl substituted tetrahydropyran ring bound to the threonine and a 2-α-aminopyranuronamide sugar connected to the tripeptide via a O-glycosidic linkage with the threonine also. Characellides A and B are epimers which only differ with the sugar moieties, where the 2-α-glucuronamide replaces a 2-α-galacturonamide and they have a ten member alkyl chain while characellides C and D are epimers with a nine member alkyl chain. Additionally, 6 methylhercynine, two new poecillastroside saponins and cyanocobalamin were also isolated from this sponge.
O NH
O NH2
O
HN ONH
OOH
O
O
OO
H2N
HOOH
NH2
OHO
Figure 3: Structure of Characellide A
66
Metal-Based Glycoconjugates for the Targeted Anticancer Chemotherapy
Ioannis Titilas1, Luca Ronconi1
1National University of Ireland Galway, School of Chemistry, University Road, H91 TK33
Galway. [email protected]
Rapidly dividing tumor cells require higher amounts of nutrients and energy for their fast proliferation, and glucose is no exception (the so-called “Warburg effect”).[1] Consequently, such increased demand of glucose by cancer cells makes it very attractive to selectively target tumor sites. In particular, tailored glucose-like substrates can be conjugated to chemotherapeutics (including metal-containing anticancer agents) to attain the site-specific delivery of drugs into the affected tissues.[2]
We here report on the design of gold(I/III)-dithiocarbamato glycoconjugates[3] (Fig. 1) which can combine the antitumor properties and the favorable toxicological profile of the metal-dithiocarbamato scaffold,[4] along with an improved selectivity and cellular uptake provided by the glucose-containing ligands coordinated to the metal center, through the exploitation of the glucose-mediated cellular internalization facilitated by glucose transporters (GLUTs).
R
NC
S
S
C
O
O
Au
SUGAR
PF6
NC
S
S
C
O
O
Au
SUGAR
Br
Br
N
NC
S
S
C
O
O
SUGAR
AuPh3P Figure 1. General structure of the target gold(I/III)-dithiocarbamato glycoconjugates.
Acknowledgements: Financial support by NUI Galway (Millennium Fund Minor Project 2013 to LR) and the Irish Research Council (Postgraduate Scholarship GOIPG/2018/38 to IT) is gratefully acknowledged. References [1] M.G. Van der Heiden, L.C. Cantley, C.B. Thompson, Science2009, 324, 1029. [2] Y. Zhao, E.B. Butler, M. Tan, Cell Death Dis.2013, 4, e532. [3] A. Pettenuzzo, D. Montagner, P. McArdle, L. Ronconi, Dalton Trans.2018, 47, 10721. [4] M. Celegato, D. Fregona, M. Mongiat, L. Ronconi, C. Borghese, V. Canzonieri, N.
Casagrande, C. Nardon, A. Colombatti, D. Aldinucci, Fut. Med. Chem.2014, 6, 1249.
67
NIR Osmium (II) polypyridyl probe with a therapeutic twist: disrupting the mitochondrial membrane potential for targeted therapy
Karmel Sofia Gkika, Aisling Byrne, Tia E. Keyes
School of Chemical Sciences, National Centre for Sensor Research, Dublin City University, Glasnevin, Dublin 9, Ireland. [email protected]
Mitochondria play a significant role in key biochemical processes of eukaryotic cells and mitochondrial dysfunctions are associated with several conditions and diseases such as inflammatory diseases.1 Cancer cells exhibit various mitochondrial dysfunctions including change in energy metabolism and increased transmembrane potential. These metabolic changes are often associated with upregulation of NADP(H) oxidase and pro-apoptotic proteins thus mitochondrial targeting has attracted significant attention, not only in the field of imaging but also in the field of medicinal chemistry as a cancer therapeutic strategy.2,3 Our group has focused extensively on the development of peptide conjugated metal complexes with targeting capability utilised for cellular imaging and intracellular studies.4 Recently we developed a ruthenium (II) mitochondrial nucleoid-driven complex which stimulated cell death upon intense photoirradiation emphasizing the potential use of such probes in photodynamic therapy.5 Here, we present a novel Osmium (II)-mitochondrial targeting complex which induces cell death via targeting the mitochondrial membrane potential. This to our knowledge is the first metal complex baring two mitochondrial penetrating peptides (MPP) to be studied in cells and first MPP-driven Os(II) complex. Co-localisation studies with MitoTracker Red confirmed localization of the Os-probe within the mitochondria structures. Confocal imaging revealed a concentration dependent cytotoxic behaviour related to the probe. The effect of the OsII MPP probe on the mitochondrial. Results indicate the activation of a caspase dependent apoptosis due to membrane depolarization and leakage of apoptotic factors. References 1. Duchen, M. R.; Szabadkai, G. Essays Biochem 2010, 47, 115–137. 2. Martin, A.; Byrne, A.; Burke, C. S.; Forster, R. J.; Keyes, T. E. J. Am. Chem. Soc. 2014, 136, 15300–15309. 3. Sanchez-Cano, C. et al. Chem. - Eur. J. 2017, 23, 2512–2516. 4. Byrne, A.; Burke, C. S.; Keyes, T. E. Chem. Sci. 2016, 7, 6551–6562. 5. Burke, C. S.; Byrne, A.; Keyes, T. E. Angew. Chem. Int. Ed. 2018, 57, 12420–12424.
68
Investigation of Hosts for Type 2 Porous Liquids
Francesca M. Alexander, Stuart L. James
School of Chemistry and Chemical Engineering, Queen’s University Belfast, David Keir Building, Stranmillis Road, Belfast BT9 5AG, UK
[email protected] Porous solids, such as metal organic frameworks (MOFs) and zeolites are widely recognised for their application in catalysis and molecular separation1, whilst the area of porous liquids2 is still a relatively new concept.3 Porous liquids, like porous solids, exhibit permanent microporosity; however, porous liquids have the added advantage of being able to flow giving them the potential to be favourable in continuous flow separations.1,2 Here we report a range of new Type 2 porous liquids based on organic host molecules which have a well-defined pore cavity (approx. 5 Å).4 Synthesis of the porous liquids was achieved by dissolving the organic host molecules in a size excluded solvent (i.e. too large to enter the pore). Although much research has been conducted into the gas adsorption properties of the new Type 2 porous liquids, few detailed studies of kinetics and thermodynamics have been carried out. Unlike simple solutions of host species where the pores of the host are occupied by solvent molecules, porous liquids sterically exclude solvent molecules from their cavities.2 Therefore, the thermodynamics of guest inclusion may differ significantly from systems where the host cavity is already solvated. Here we will describe concentration-dependent and temperature-dependent guest binding studies using 19F NMR spectroscopy toward understanding fundamental differences between guest binding in conventional liquids and in porous liquids (Figure 1).
Figure 1 – Guest Binding in Liquids.
References 1. N. Giri, M. Del Pópolo, G. Melaugh, R. Greenaway, K. Rätzke, T. Koschine, L. Pison, M. Gomes, A. Cooper and S. James, Nature, 2015, 527, 216-220. 2. N. O'Reilly, N. Giri and S. James, Chem. Eur. J. 2007, 13, 3020-3025. 3. R. Greenaway, D. Holden, E. Eden, A. Stephenson, C. Yong, M. Bennison, T. Hasell, M. Briggs, S. James and A. Cooper, Chem. Sci. 2017, 8, 2640-2651. 4. J. Holst, A. Trewin and A. Cooper, Nat. Chem. 2010, 2, 915-920.
69
Optimisation and Scale-up of the β-Chloroacrylamide Process using Batch and Continuous Flow Methods
Olga C. Dennehya, Denis Lyncha, Stuart G. Collinsa, Anita R. Maguirea,b & Humphrey A.
Moynihana
aSchool of Chemistry & bSchool of Pharmacy Analytical and Biological Chemistry Research
Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland
This project aims to develop control strategies to deliver tuneable processes for API manufacturing, which are capable of producing specific API characteristics across a range of manufacturing scales, facilitating more robust and predictable design and optimisation. To achieve this, we are investigating a model system which poses realistic scale up challenges. This process consists of a complex cascade that has been previously studied and is mechanistically well understood.1 This model system is a three step synthesis (Scheme 1) to produce the α-thio-β-chloroacrylamide Z-3.2
SPhNHTol
O
SPhNHTol
O
Cl
ClNHTol
O
ClCl
O
NH2Tol, Et3N HSPh, NaOEt 1.95 eq. NCS
CH2Cl2, RT, 4 h EtOH, RT, 20 h Toluene, 90 °C, 3 h
2-chloropropionyl chloride
α-chloroamide
1
α-thioamide
2
α-thio-β-chloroacrylamide
Z-3 Scheme 1
This process presented a number of challenges that needed to be overcome before scale-up. These included a significant exotherm in the first step, problems with product purity and challenging reaction conditions in the second step, and the use of the ‘hot plunge’ method in the third step. Utilising a combination of continuous flow and batch methods gave access to higher levels of process control through expanding choice of available reaction conditions. This allowed for efficient optimisation and led to significant improvements in the safety profile, product purity and feasibility on a large scale.3
SPhNHTol
O
SPhNHTol
O
Cl
8 bar
2
Z-3
PhSNHTol
OPhS
NHTol
O
Cl
Cl
4 5
SPhNHTol
OClE-3
PhSNHTol
O
Cl
Cl
6Cl
NCS
Scheme 2
This research is supported by the SFI 12/RC/2275 (Synthesis and Solid State Pharmaceutical Centre). (1) Foley, D. A.; Doecke, C. W.; Buser, J. Y.; Merritt, J. M.; Murphy, L.; Kissane, M.; Collins, S. G.; Maguire, A. R.; Kaerner, A. J. Org. Chem. 2011, 76, 9630. (2) Kissane, M.; Maguire, A. R. Synlett 2011, 11, 1212. (3) Dennehy, O. C.; Cacheux, V. M. Y.; Deadman, B. J.; Lynch, D.; Collins, S. G.; Moynihan, H. A.; Maguire, A. R. Beilstein J. Org. Chem. 2016, 12, 2511.
70
Photo-induced Electron Transfer at Liquid-Liquid Interfaces for Solar Energy Conversion
Kamil A. Cywinski1, Andrés F. Molina Osorio1, Iván F. Robayo Molina1, Micheál D.Scanlon
1.
1 The Bernal Institute and Department of Chemical Sciences, University of Limerick (UL), Ireland
A novel approach to solar energy conversion involves dye-sensitizing of electrified liquid-liquid or “soft” interfaces. Photocurrent transient data can provide a lot of information about the kinetic processes of photo-induced interfacial electron transfer (PIET) across these junctions, such as rates of photoproduct separation or recombination. By assembling a film of semiconductor nanoparticles or organic dyes at this liquid-liquid interface, in the presence of an electron donor, it is possible to use light in order to generate an electric current.[1,2]
In this study focus was placed on optimizing the experimental conditions, such as pH or concentration of donor, to control the formation of interfacial assemblies of nanoparticles and porphyrin dyes and maximize their photoresponses. Using electrochemical methods, interfacial films were formed at a water/trifluorotoluene interface that can facilitate charge transfer and thus generate photocurrent responses under visible light illumination. These findings represent a novel approach to solar energy conversion at electrochemically active soft interfaces, without the use of solid electrodes for the charge separation step.
Fig.1. Schematic representation of the pathway of electron transfer event through the
interface, facilitated by (i) semiconductor nanoparticle; (ii) dye sensitizer. References: [1] F. Plana & D. J. Fermín. J. Electroanal. Chem. 780 (2016) 373–378. [2] Y. Yuan et al. Chem. Eng. J. 275 (2015) 8–16.
71
Coordination chemistry of 2-picolyl naphthalene diimide and bis- phthalimide ligands
June I. Lovitt, Chris S. Hawes and Thorfinnur Gunnlaugsson
School of Chemistry and Trinity Biomedical Sciences Institute, Trinity College
Dublin, Ireland. [email protected]
The naphthalenediimide (NDI) motif has been utilised as a structural building block in supramolecular coordination chemistry for many years.1 Recently, we reported a family of coordination compounds of late 3d metal ions in which an unusual (N,O) chelating coordination mode is observed from several 2-picolyl substituted 1,8-naphthalimide ligands.2 In this work, to probe the generality of this interaction, two further N-(2-picolyl) substituted bis-imide ligands, N,N’-di(2-picolyl)-1,4,5,8-naphthalenetetracarboxylic diimide (L1) and N,N’-di(2-picolyl)-4,4’- oxybisphthalimide (L2), were synthesised and characterised. Their coordination chemistry with late d-block metal ions in the crystalline and solution states was subsequently explored. In the crystalline phase there was the formation of four new crystalline coordination compounds incorporating the NDI ligand. These included two structurally-related Zn one- dimensional coordination polymers containing significant solvent-accessible channels and whose crystal packing behaviour is strongly connected to the steric and electronic properties of the guest solvent. An Ag complex provided evidence of the desired chelating interaction but indicates that these interactions are subtly disfavoured in these bis-imide systems despite their similarities to the previous system. Further supporting this, upon reaction with transition metals the bis-phthalimide only crystallised as the free ligand itself which indicates an underlaying barrier to coordination of these species compared to 1,8-napthalimides.3
Fig.1. (a) Structures of compounds L1 and L2 and comparison to previously reported N-(-2- picolyl)-1,8-naphthalimide chelators (b) Interactions between
lattice acetonitrile molecules and the π-surface of L1 within the structure of poly-[ZnCl2(L1)]·MeCN.
[1] X. Ao, S. A. Bright, N. C. Taylor and R. B. P. Elmes., Org. Biomol. Chem., 15, (2017), 6104- 6108. [2] J. I. Lovitt, C. S. Hawes, A. D. Lynes, B. Haffner, M. Mobius and T. Gunnlaugsson., Inorg. Chem.
Front., 4, (2017), 296-308.
[3] J. I. Lovitt, C. S. Hawes and T. Gunnlaugsson., CrystEngComm, 21, (2019), 207-217.
72
Stability Studies on the hydrolysis of antibacterial inorganic Tellurium (IV) complexes
Kenneth Patrick D’Arcy,a Barbara Freschb, Kevin Kavanagh,c Diego Montagnera
aDepartment of Chemistry, Maynooth University, Ireland bDepartment of Chemistry,
University of Padua, Italy aDepartment of Biology, Maynooth University, Ireland
Ammonium[trichloro(dioxoethylene)tellurate], also called AS-101, (Figure 1) is a Tellurium (IV) complex with several interesting biological properties.[1] AS-101 showed anticancer activity in phase I and II clinical trials with advance cancer patients and the mechanism of action is attributed to its ability to inhibit integrins and the ensuing secretion of the cytokine IL-10. AS-101 also showed antibacterial activity against Enterobacter cloacae.[2]
In a recent paper it was found that AS-101 is not stable in physiological conditions and once dissolved in water the “diol” ligand is released.[3,4] The hydrolysis reaction forms ammonium trichloro Te(IV) oxide and it was concluded that this latter compound is effectively responsible for the biological activities described before. The aim of this work is to synthetize analogues of AS-101 with different substituents (Figure 1) in order to increase the stability of the Te(IV) based compounds. The complexes were synthesised, characterized with different spectroscopic techniques (multi-NMR, El. Anal, IR, Mass) and the stability was studied via 1H, 13C and 125Te-NMR. This analysis showed that, increasing the alkyl chain of the “diol”, the stability increases. The decomposition reaction of AS-101 and its analogues was studied computationally at the DFT level. The results support the experimental trend on the stability of different compounds and points out the important contribution of the micro-solvation shell of water in determining the energetics of the reaction. Antimicrobial studies on E. Coli show high activity of the compounds that act as prodrugs releasing the active bio species [TeOCl3]+.[5]
Figure 1. Left. Structure of AS-101. Right. Hydrolysis reaction of AS-101 analogues.
[1] B. Sredni, R.R. Caspi, A. Klein, Y. Kalechman, Y. Danziger, M. Banyakov, T. Tamari, F. Shalit, M. Albeck, Nature, 1987, 330, 173. [2] M.D. Hoffmann, B. Sredni, Y. Nitzan, J. Antimicrobial. Chemoth. 2012, 67, 2165. [3] A. Silberman, M. Albeck, B. Sredni, A. Albeck, Inorg. Chem. 2016, 55, 10847. [4] C.R. Princival, M.V.L.R. Archilha, A.A. Dos Santos, M.P. Franco, A.A.C. Braga, A.F. Rodrigues-Oliveira, T.C. Correra, R.L.O.R.Cunha, J.V. Comasseto, ACS Omega, 2017, 2, 4431. [5] K. D’Arcy, K. Kavanagh, B. Fresch, D. Montagner, J. Inorg. Biochem. 2019, JINORGBIO_2019_103_R2
73
Conjugated Polymer Nanoparticles as A New Class of Fluorescent Probes based on Emission Anisotropy
Zixu Zhao1, Clara Zehe1, Jason Beirne1, Ruba Hendi2, Alex Robinson2, Gareth Redmond1.
1 School of Chemistry, UCD, 2 School of Chemical Engineering, University of Birmingham. [email protected]
Fluorescence correlation spectroscopy (FCS) is a widely used single-molecule technique that can quantitatively monitor fluctuations in fluorescence intensities due to mechanisms like diffusion, blinking, changes in conformation, etc. In my work, FCS, in combination with fluorescence spectroscopy and electron microscopy (TEM), was employed to characterise the properties of novel, emissive conjugated polymer nanoparticles (CP NPs). Specifically, I investigated the influence of polymer side-chain type and the degree of co-polymerisation on the resulting polymer chain arrangement and photophysics in nanoparticles formed by a reprecipitation process by studying poly(9,9-dioctylfluorene) (PF8 – a fluorene homopolymer with linear (octyl) side chains) and other fluorene polymers: PF2/6 – a homopolymer with branched side (ethyl-hexyl) chains; PFBT10 – a F8 random copolymer with 10% thiadiazole in the polymer backbone, and PFBT50 – an alternating copolymer composed of F8 and thiadiazole units. Absorption and emission spectroscopy of aqueous nanoparticle dispersions indicated that polymer chains underwent collapse and aggregation during the reprecipitation process. In addition, intramolecular polymer chaining ordering via β-phase formation – a mesomorphic phase with a more planar, extended conformation and longer conjugation length compared with the amorphous phase – was observed in PF8 NPs (ca. 22% β-phase) and PFBT10 NPs (ca. 10% β-phase) while PF2/6 NPs and PFBT50 NPs contained no β-phase. These observations were consistent with the known role of side-chain geometry and co-monomer ratio, respectively, in polymer backbone planarisation. Further, steady-state excitation and emission anisotropy measurements suggested the existence of intermolecular chain ordering (net transition dipole alignment) in all NPs with PF8 NPs exhibiting the highest anisotropy followed by PFBT10, PF2/6 and, lastly, PFBT50. In FCS measurements, the auto-correlation functions (ACFs) acquired for all four types of NPs in aqueous media exhibited a slow process in the millisecond time scale, characteristic of translational diffusion of the NPs through the effective detection volume, and a fast process in the microsecond time scale that was assigned to rotational diffusion upon polarisation-resolved (pol.) FCS via two-channel acquisition. The amplitude of the fast process varied with the polarisation condition indicating that the particles were emission anisotropic and that the fast decay was due to depolarisation of fluorescence by rotational diffusion of the particles. The amplitude of the fast process, which corresponded with the degree of polarisation of NP emission, followed a trend identical to that observed in the steady-state fluorescence anisotropy data cited above. Finally, following drying in air, all four NP types displayed lattice fringes in TEM images indicating that the semi-crystalline phase (α- or α’-phase) of polyfluorene formed by further polymer chain ordering during the drying process. The strong emission anisotropy makes the PF8 NPs a potentially attractive fluorescent probe for biological studies. To this end, I used pol. FCS to study the rotational dynamics of PEGylated PF8 NPs (formed using a PF8:PS-PEG-COOH blend) while interacting with human serum albumin (HSA) at various NP:protein ratios. The tracking of protein-NP interactions by monitoring the change in the rotational diffusion coefficient of the protein-NP ensemble was shown to be feasible, and, using this approach, the adsorption of HSA on these NPs was found to be anti-cooperative and the dissociation constant of the complex was estimated (with the assumption of spherical diffusors).
74
New Tetrazole-Based Compounds for Coating Medical Implants: Synthesis and Corrosion Studies.
Ronan McAteer1, Adrienne Fleming1 and Mary Deasy1.
1 Centre of Applied Science for Health, TU Dublin – Tallaght Campus, Blessington Road,
Tallaght, Dublin 24, D24 FKT9. [email protected]
Biomaterials are either natural or man-made materials which are used to aid or replace the functions of living tissues. They must possess special properties, such as non-toxic, corrosion resistance, fatigue durability and biocompatibility. Metal and metal alloy biomaterials are frequently used in orthopaedic and cardiac stents. In most cases, metal-based implants are coated with an oxide layer to protect against corrosion.[1] However, when these coated systems are planted into a complex physiological environment, even the oxide stability can be affected, thereby causing release of metal ions into the local surrounding tissue and bone. There is well documented evidence in the literature outlining the risk of in vivo release of trace metals from medical implants into the human body.[2] One approach, is to devise an implant with an improved protective layer. This would serve the dual function of protection against wear and preventing release of harmful small molecules into the bloodstream. The aim of the project is to design new azole macromolecule compounds that can be polymerised into a coating, protecting the metal implant from metal leaching into the local biological fluids and tissue. The results to date are positive. A total of twenty-four compounds have been synthesised and coatings have been prepared. Preliminary corrosion studies indicate a reduction in metal leaching.
Figure 1: Metal ion release from medical implant.[1]
References:
1. Bijukumar, Divya Rani et al. "Systemic And Local Toxicity Of Metal Debris Released From Hip Prostheses: A Review Of Experimental Approaches". Nanomedicine: Nanotechnology, Biology And Medicine, vol 14, no. 3, 2018, pp. 951-963. Elsevier BV, doi:10.1016/j.nano.2018.01.001.
2. Chen, Qizhi, and George A. Thouas. "Metallic Implant Biomaterials". Materials Science And Engineering: R: Reports, vol 87, 2015, pp. 1-57. Elsevier BV, doi:10.1016/j.mser.2014.10.001. Accessed 23 Apr 2019.
75
Pyridine 5-hydroxytriazoles: a new class of potential ligands for drug discovery and catalysis
Roberta Pacifico 1,, Mauro Adamo 1
1 Centre for Synthesis and Chemical Biology (CSCB), Department of Chemistry, Royal
College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland. [email protected]
1,2,3-triazoles are a promising chemical framework due to their extensive biological activities as antiviral, anti-cancer, anti-inflammatory and antibacterial compounds. This scaffold can be easily obtained in good to excellent yields through Huisgen 1,3-Dipolar Cycloaddition reaction of aryl/alkyl halides, alkynes and sodium azide under ambient conditions.1 Herein we present an innovative synthesis of a more interesting class of triazoles, named 5-hydroxytriazoles, attached to various substituted pyridine scaffolds.(Figure 1)
N NN
R' OH
N
R''
R'''O O
OR
+N N3
DBU (1.2eq), Cu(OTf)2*toluene complex
(0.2 eq)
DMSO,120°C, overnight,under pressure
R=H,CH3R'=H, CH3, COOEt, COOH, (CH2)4COOH, (CH2)4COOEt R'',R'''= H, EDG, EDW
R'''
R''
R
O
NH
OH
Fig.1. Mechanism for the synthesis of 5-hydroxytriazoles pyridine substituted.
Indeed our final compound has the great chance to be substituted with both ED and EW groups on the pyridine aromatic ring. As it is commonly accredited that 5-hydroxytriazoles are, potentially, hydroxamic acids bioisosters,2 the challenge will focus on accurate docking studies on this new set of molecules. This will allow us to identify the best biological system to realize our tests and to expand the versatility of these compounds to the promising world of organocatalysis. 1 D. Dheer et al.; Bioorganic Chemistry, 71, 2017, 30–54 2 D.Destro, M F.A Adamo,; Org. Biomol. Chem., 15, 2017, 5227–5235
76
Synthesis Towards Constrained Anti-Adhesive Sia(α2-3)Gal Glycomimetics
Sylvester Byrne1, Paul V. Murphy1
1 National University of Ireland, Galway [email protected]
Carbohydrates are found on cell surfaces and within cells of every organism and play an essential role in infection, cellular adhesion and migration, organism development, disease progression, and the modulation of immunological responses. Sialic acid containing oligosaccharides are often found to cap these glycan chains and are thus an attractive, but rather unexplored structures on which to base anti-adhesive therapeutic discovery. Bacteria exhibit a significantly higher resistance to clearance via cleaning and killing (immune factors, bacteriolytic enzymes and antibiotics) when adherent to surface, therefore targeting the adhesion event can prevent the onset of infection. The normal glycosidic linkage is freely rotatable for sialic acid glycosides, however, when bound the bond becomes rigid and locked into the favoured binding position. This encounters an unfavourable entropic penalty. If a compound was designed whereby the linkage was permanently locked into the favoured binding orientation, it should bind without incurring the entopic penalty and thus have greater affinity compared to the native ligand. Efforts to synthesise constrained glycomimetics have been carried out previously in the Murphy group. The pre-organization of the Sia(α2-3)Gal linkage by use of the cyclic constraint in FB127 avoids an entropic penalty of ~1.5 kcal/mol, and this gave rise to an observed affinity enhancement of ~20 fold relative to the native disaccharide for influenza hemagglutinin. This work aims to synthesise other constrained mimics of Sia(α2-3)Gal while investigating these compounds with other sialic acid binding proteins involved in bacterial and viral infection.
O
COO-
OHAcHN O
OMeOO
OHOH
HO OH
HO O
COO-
OHAcHN O
OMeHO
OOH
OH
HO OH
HO
FB127 Natural sialoside
Figure 4: Constrained mimic FB127 and the natural Sia(α2-3)Gal disaccharide.
77
Next Generation Antisense Therapeutics
Bríonna McGorman 1, Nicolò Zuin Fantoni 1, Andrew Kellett 1.
1 School of Chemical Sciences, Dublin City University. [email protected]
Antisense gene therapy is a gene silencing technique which employs short strands of nucleotides (oligonucleotides) that bind to specific sequences of DNA and thereby inhibit protein production. Traditionally, antisense therapeutics sequestered mRNA and inhibited translation in the ribosome, but more recently the focus has shifted to triplex forming oligonucleotides (TFOs) which bind directly to specific sequences on the DNA duplex1. This triplex formation prevents the RNA polymerase accessing a specific gene and inhibits mRNA transcription. Triplexes can form at sequences which are poly-purine/poly-pyrimidine as purine bases in Watson-Crick dsDNA have two additional sites which are capable of forming Hoogsteen hydrogen bonds with a TFO. Antisense therapeutics have also been functionalised through click chemistry2,3. ‘Clicking’ a DNA damaging agent, such as an artificial metallo-nuclease4, to a TFO combines the sequence selectivity of antisense therapeutics with the DNA damaging capabilities of inorganic metal complexes. This sequence specific DNA damage has been observed by polyacrylamide gel electrophoresis and quantified by real-time PCR. These next generation antisense therapeutics have the ability to overcome many of the issues currently associated with metallo-drugs and represent a new class of gene targeting agents.
Fig.1. Inhibition of transcription and translation by antisense therapeutics.
1. K. R. Fox, T. Brown and D. A. Rusling, in DNA-Targeting Molecules as Therapeutic Agents, 2018, pp. 1–32.
2. A. H. El-Sagheer and T. Brown, Chem. Soc. Rev., 2010, 39, 1388. 3. J. Gierlich, G. a. Burley, P. M. E. Gramlich, D. M. Hammond and T. Carell, Org. Lett.,
2006, 8, 3639–3642. 4. A. Kellett, Z. Molphy, C. Slator, V. McKee and N. P. Farrell, Chem. Soc. Rev., 2019,
48, 971–988.
78
CTAB as a Non-Adsorbing “Promoter” for the Self-Assembly of Charged Colloidal Nanoparticles at Liquid-Liquid Interfaces into Multi-Dimensional Arrays
Chunchun Li‡, Xinyuan Li‡, Ziwei Ye, Qinglu Cheng, Yikai Xu, Steven E. J. Bell
Queen’s University Belfast
Previously, we reported a cost-effective one-pot method to prepare surface-clean multi-dimentional assemblies at the LLI, which allows assembly of all kinds of NPs includes metallic and non-metallic NPs by using non-adsorbing promoter. For instance, tetrabutylammonium nitrate (TBA+NO3
−) is a kind of molecules that can be used as such promoters. the TBA+ side, which acts as a cation, can supply opposite charge to the initially negatively charged capping agents on NPs and achieve charge screening without removing any initially capping agents thus decrease the electrostatic repulsion between NPs. In general, the promoters are chemically diverse, ranging from all kinds of transition metal complexes and crown ethers, as well as organic salts. It has been proved that despite from the structure-diversity, all the promoters which can successfully induce NPs self-assembly at the LLI possess a common essential quality: they are all hydrophobic salts which is ionic and thus can provide opposite charge to NPs from the water-immiscible oil side. In other words, the key interaction in this promoter induced NPs self-assembly process is between the NPs at the LLI and oppositely charged ions dissolve in the oil phase. This character can also match well with surfactants that are frequently used in particles synthesis process such as cetyl trimethylammonium bromide (CTAB). A CTAB molecule owns a hydrophobic cation side and a hydrophilic anion side. Normally speaking, the hydrophobic cation side of such molecules should act well in NPs self-assembly process as functional charge-screening promoters. Since CTAB is almost the most common surfactant used in various different NPs synthesis, it is worth studying as a representative structure for guiding significance. Candidates for promoters among surfactants are not limited for CTAB, theoretically, all the surfactants possess the same feature with it can be used as promoters, which may potentially simplify the NPs self-assembly process since promoters has well-capped on NPs surfaces. Furthermore, various techniques such as UV/vis, scanning electron microscope (SEM) and SERS were applied to explore more properties of CTAB induced self-assembled NPs arrays.
79
Source apportionment of ambient carbonaceous aerosol in Ireland using a variety of analytical techniques.
Eimear Heffernan1, Paul Buckley1, Darius Ceburnis2, Jurgita Ovadnevaite2, Damien Martin2,
John Wenger1, Stig Hellebust1
1 School of Chemistry and Environmental Research Institute, University College Cork, Ireland
2 School of Physics, National University of Ireland, Galway, Ireland
As part of the EMEP/ACTRIS/COLOSSAL Winter Campaign (2017 – 2018), 150 PM2.5 filter samples were collected at four sites across Ireland; Carnsore Point, Co. Wexford, Mace Head, Co. Galway, Malin Head, Co. Donegal and on the campus of University College Dublin, all either rural or urban background sites, covering the four corners of the country. An AE33 multi-wavelength aethalometer was deployed at each site. Filter collections of PM for further offline analysis were made with a DIGITEL DHA-80 High Volume Sampler or a Partisol 2025i Sequential Air Sampler. The aethalometer model was employed for apportioning biomass burning and fossil fuel combustion black carbon. Using source specific Ångström exponent values of 0.9 and 1.68 for αTR and αWB, respectively [Zotter et al., 2017], initial results from the AE33 aethalometer show a strong diurnal trend. A traffic-related peak in black carbon levels is observed during morning rush hour in Dublin, while the evening peaks are dominated by domestic solid fuel burning emissions at all sites, with the exception of Mace Head which is extremely remote. Previous studies have noted the strong correlation between black carbon originating from wood burning (BCWB) and levoglucosan concentrations, which is a wood burning marker compound [Fuller et al., 2014, Martinsson et al., 2017]. The results from this campaign will be used to investigate this relationship further. A portion of each filter was reserved for thermal-optical organic carbon/elemental carbon (OC/EC) analysis using the EUSAAR_2 protocol and the Sunset Laboratories OC-EC aerosol analyzer. The data processing employed the Attenuation Versus Evolved Carbon (AVEC) plot approach developed by Nicolosi et al., 2018. The AVEC plots show the OC and EC content on each filter, and also enable quantification of pyrolysed carbon. The elemental carbon (EC) fraction derived from these measurements was subsequently compared to the BC measurements from the aethalometer at 880 nm and the levoglucosan content determined by GC-MS.
80
Supramolecular Isomers of [Zn(glycolate)(bipy)1.5]n
Chenghua Deng1, Michael J. Zaworotko1
1Department of Chemical Sciences and Bernal Institute, University of Limerick, Limerick, Republic of Ireland
Supramolecular isomerism in coordination polymers (CPs) is observed when compounds with the same chemical composition exist in different network topologies.1,2 While supramolecular isomerism in CPs is well established for those conforming to the “node and linker” design principle, the ones described by rod building blocks (RBBs) (also called rod secondary building units)3 remain underexplored. Template-directed synthesis4 has led us to prepare four supramolecular isomers of the CP [Zn(glycolate)(bipy)1.5]n (bipy = 4,4’-bipyridine). In each isomer, the RBB was constructed with Zn(II) and glycolate with each Zn ion being hexacoordinate. Network topology for all these structures consisted of 5-connected nets that could be described as 2D hexagonal nets (hcb) pillared by bipy, thus affording 3D networks. Four different network topologies (nov, bnn, skb and vmb) were obtained, and selectivity for a particular net could be achieved by varying the reaction conditions and utilising the template effect. Powder X-ray diffraction profiles could confirm the phase purity for each of these four compounds.
References: 1. B. Moulton and M. J. Zaworotko, Chem. Rev., 2001, 101, 1629-1658. 2. J.-P. Zhang, X.-C. Huang and X.-M. Chen, Chem. Soc. Rev., 2009, 38, 2385-2396. 3. A. Schoedel, M. Li, D. Li, M. O. Keeffe, and O. M. Yaghi, Chem. Rev., 2016, 116, 12466-12535. 4. X.-X Guo, S.-B Geng, M.-J Zhuo, Y. Chen, M. J. Zaworotko, P. Cheng, and Z.-J Zhang, Coord. Chem. Rev., 2019, 391, 44-68.
Fig.1. Topology Images of [Zn(glycolate)(bipy)1.5]n supramolecular isomers
81
Synthesis, spectroscopic properties and aggregation behaviour of terpyridine functionalized building blocks
Jason Delente,1 Sankarasekaran Shanmugaraju,2 Thorfinnur Gunnlaugsson.1
1 TBSI, Trinity College Dublin, 152-160 Pearse Street, Dublin 2, Ireland.
2 Indian Institute of Technology Palakkad, Kerala, India. [email protected]
Currently metallo-supramolecular architectures are the focus of significant attention in the field of chemistry; their coordination-driven architecture using various linkers and coordination sites is an extremely useful tool to obtain assemblies of increased complexity and functionality such as metallo-supramolecular gels,[1] emissive materials using lanthanides,[2] to name a few. The interest in terpyridine (terpy) motif has continuously grown through the years which can be explained by the fact that it acts as a key structural unit in the design of metallo-organic structures. Its ability to bind strongly to metal ions makes terpy a great building block for use in supramolecular chemistry to achieve complex architectures through self-assembly approach. This projects focus on the synthesis and uses of building blocks functionalised with terpy to achieve supramolecular architectures that can be further modified using metal ions or to be used as a sensor in the case of naphthalimide based Tröger’s base (TB).[3] Presented here is a summary of our work to date: the synthesis, spectroscopic properties and aggregation behaviour of a terpyridine functionalized TB that can be further used for the detection of nitroaromatic (Figure 1).
Fig.1.Spectroscopic properties and aggregation behaviour of a terpyridine functionalized
TB [1] L. E. Buerkle, S. J. Rowan, Chem. Soc. Rev. 41, (2012), 6089-6102. [2] O. Kotova, R. Daly, C. M. G. dos Santos, P. E. Kruger, M. Boese, J. J. Boland, T.
Gunnlaugsson, Angew. Chem. Int Ed. 51, (2012), 7208-7212 [3] S. Shanmugaraju, C. Dabadie, K. Byrne, A. J. Savyasachi, D. Umadevi, W. Schmitt,
J. A. Kitchen, T. Gunnlaugsson, Chem. Sci. 8, (2017), 1535-1546.
82
Estrogen-Copper(II) complexes as targeted anticancer metal-based drugs
Stephen Barrett,a Valentina Gandin,b Andrew Kellett,c Eithne Dempsey,a Andrea Erxleben,d Diego Montagnera
aDepartment of Chemistry, Maynooth University, Ireland, bDepartment of Pharmaceutical Science, University of Padua, Italy , cDepartment of Chemistry,Dublin City University,
Ireland and dSchool of Chemistry, NUIG Galway, Ireland [email protected]
A pioneer series of copper(II) complexes bearing planar phenanthroline-modified aromatic ligands and the steroid estrogen estradiol, with generic formula [Cu(N∩N)(phen-estradiol)](NO3)2 where N∩N is phenanthroline, DPQ, DPPZ and DPPN (Figure 1), were synthetized, characterized and screened in vitro against a series of 2D and 3D human cancer cell line.[1] Estrogens are overexpressed in several cancer cell lines and they can act as a carrier agents to selectively deliver the drugs to the tumour tissues.[2] Together with the cytotoxicity data, DNA binding studies have been performed using CT-DNA. These studies showed that these complexes are able to intercalate between the DNA nucleobases and the intercalation properties correlates with the increasing planarity of the N∩N ligand.[3] Electrochemistry studies allowed to determine the redox potential of the Cu(II)/Cu(I) couple that is related to the production of ROS (Reactive Oxygen Species) responsible of the cleavage of the phospho-diester bonds of the DNA. Drug uptake and production of ROS have also been evaluated and the results correlated with the cytotoxicity data.
N
NHOCu
N
N N
N
N
N
2+
HO
N
N
=
N
N N
N
N
N N
N
DPQ
DPPZ
DPPN
N
N
PHEN
Figure 1. Generic Structure of the estradiol-Cu(II) complexes
[1] S. Barrett, S. Delaney, K. Kavanagh, D. Montagner, Inorg. Chim. Acta 2018, 479, 261-265 [2] A Hurtado, K.A. Holmes, C.S. Ross-Innes, D. Schmidt, J.S. Carroll, Nat. Gen. 2011, 43, 27-33 [3] Z. Molphy, A. Prisecaru, C. Slator, M. McCann, A. Kellett, Inorg. Chem. 2014, 53, 5392-5404
83
Continuous Flow Photorearrangement of Isoxazoles
Cormac Bracken, Marcus Baumann.
UCD School of Chemistry, Belfield, Dublin 4, Ireland. [email protected]
Oxazoles are classical 5-membered heteroaromatic structures that can be found in many bioactive entities such as aleglitazar (antidiabetic), ditazole (platelet aggregation inhibitor), mubritinib (tyrosine kinase inhibitor) and oxaprozin (COX-2 inhibitor). Although several methods for their preparation from acyclic precursors exist, these involve unfavourable features like lengthy linear sequences, oxidation state adjustments or the use of toxic and expensive catalysts. An alternative access to these important oxazole structures is the direct photochemical rearrangement of isoxazoles yielding the desired products, an attractive transposition for which no practical and general process exists to date. In this poster we will discuss our results in developing a continuous flow approach that converts isoxazole precursors into trisubstituted oxazole products. This involves the use of state-of-the-art flow equipment to ascertain precise control over the photochemical process via a tuneable medium pressure Hg-lamp that can be used with filters and external temperature control modules to bring about the effective and practical synthesis of various oxazole target structures. Importantly, this flow approach overcomes obstacles commonly associated with photochemical reactions performed in batch mode such as scalability, process control and excessive by-product formation.
Figure 5. Photo-rearrangement of isoxazoles within Vapourtec UV150 reactor.
84
Polypeptide-based hydrogels for tissue engineering
Shona O’Brien 1, Ruairí P Brannigan1, Joanne O’Dwyer1, Sally-Ann Cryan1, Andreas Heise 1
Department of Chemistry, Royal College of Surgeons in Ireland , 123 St. Stephens Green, Dublin 2, Ireland
[email protected] This research focuses on design, synthesis, and development of functional polymers as scaffolds for tissue engineering. Specifically, this involves the formation of strong double network hydrogels (DN) i.e. tough hydrogels with good mechanical properties. Therefore present efforts are on the development of complex polypeptide networks that have desirable properties including the ability to be readily functionalised and the ability to either self-assemble into physical hydrogel and/or permit chemical cross-linking. Currently, functionalised copolypeptides are being developed to investigate their ability to form DN hydrogels with contrasting network structure – where the first network is tightly cross-linked while the second network is loosely cross-linked – and their mechanical properties: tensile and compression strengths.1 These networks will be achieved through well-known chemical methodologies; they are synthesised by N-carboxyanhydride (NCA) ring opening polymerisation (ROP) from amino acid backbones – that have been modified to include cross-linkable functionalities.2 This method is used as it facilitates click chemistry reactions e.g. CuAAC reaction between alkyne and polyethylene glycol (PEG) - azide, yielding networks that are ideally suited to biomedical applications as, being derived from amino acids; they do display secondary structures (i.e. α-helixes and β-sheets), self-assembly properties, biocompatibility, and biodegradability.
Scheme 3. Fabrication of DN gel; polypeptide gel is swollen in an acrylate solution
followed by UV curing.
References 1 H. Chen, F. Yang, R. Hu, M. Zhang, B. Ren, X. Gong, J. Ma, B. Jiang, Q. Chen and J.
Zheng, J. Mater. Chem. B, 2016, 4, 5814–5824. 2 T. Borase, T. Ninjbadgar, A. Kapetanakis, S. Roche, R. O’Connor, C. Kerskens, A.
Heise and D. F. Brougham, Angew. Chemie - Int. Ed., 2013, 52, 3164–3167.
Polypeptide Gel
3 Days Dialysis
Freeze Dry
Swollen in Acrylate Solution
Swollen Polypeptide Gel
Double Network Gel
85
Novel Zn and Mg MOFs based on azo-dicarboxylate ligands and their potential for drug delivery
Ahmed Ahmed 1, Constantina Papatriantafyllopoulou 1, Constantinos G. Efthymiou, Patrick
McArdle 1
1 Synthesis and Solid-State Pharmaceutical Centre (SSPC), School Of Chemistry, College of
Science, National University of Ireland Galway, University Road, H91 TK33, Galway, Ireland
Metal-organic frameworks (MOFs) find a large variety of applications (gas storage, purification, sensors etc.) that stem from their high porosity and host guest chemistry potential. Of particular interest is their application as drug delivery vectors. Many common and important drugs show difficulties in their administration and behaviour within the body. These range from poor bioavailability, degradation in the body and the ‘burst’ effect. MOFs may provide an advantage over conventional methods due to their large loading capacities, stability, tuneable size and greater biocompatibility.1 Thus, this is an area of ongoing research with a focus on metals and linkers that have a low toxicity.2 Two novel ZnII and MgII based MOFs have been synthesised from the use of novel elongated dicarboxylate ligands, and characterised using single crystal and powder XRD, thermogravimetric analysis and FTIR spectroscopy. The ibuprofen absorption and release properties of the two MOFs have been analysed and discussed in detail. Ibuprofen is used for preliminary results as it is a small and affordable drug.
Fig.1. Crystal structure of MgII MOF
[1] Wu, M. X. & Yang, Y. W. Metal–Organic Framework (MOF)-Based Drug/Cargo Delivery and Cancer Therapy. Adv. Mater. 29, 1606134 (2017). [2] Horcajada, P. et al. Metal-organic frameworks in biomedicine. Chem. Rev. 112, 1232–68 (2012). Acknowledgments We are grateful to the Science Foundation Ireland for funding this project.
86
Plasmonic Fluorescent assay for molecular lipid membrane binding, permeation and dynamics of permeation.
Agata Steplewska 1 , Kiang Wei Kho 1, Aurelian Gimenez 1, Tia Keyes 1.
1 School of chemical sciences, DCU, Dublin, Ireland
Membrane permeability is a key property of any prospective drug and the interaction of a drug with the cellular membrane influences its pharmokinetics as many drug targets are intracellular, Herein we describe a new concept based on plasmonics for gaining new insights into the determination as to whether a molecule is membrane permeable, mechanic insights into membrane interactions and the kinetics of permeability. This is achieved using metal cavity supported lipid bilayers. In this approach lipid bilayers spanned over gold microcavities are exploited as surface enhanced fluorescence (SEF) substrates. Through the use of Raman and Fluorescence spectroscopy, we can detect if and how a drug interacts with the lipid membrane, while also obtaining an insight of the dynamics of the interaction and the rate of permeation through the bilayer and arrival into the plasmonic field of the gold cavity. It was found that gold microcavity substrates gave a significant increase in fluorescence intensity over planar gold substrates, regardless of modifications or bilayer presence. Through Electrochemical Impedance spectroscopy (EIS), DOPC symmetric bilayers are shown to be stable for an average of 7 hours, which increases with membrane complexity, where our ternary bilayer composition (DOPC/SM/CH) (40/40/20%) shown an average stability for 8 hours. Through SEF measurements, the bilayer residential time and diffusion time were found for the drugs Doxorubicin and Daunorubicin over a range of concentrations and membrane compositions. Interestingly, the method could easily distinguish aggregation of drug above certain concentrations that lead to a reduction in permeation rate. Through Raman spectroscopy we can clearly identify that drug-membrane interactions occur. This work demonstrates a new versatile and useful paradigm for drug- membrane permeability assay.
Fig.1. Schematic diagram showing the introduction of a fluorescent drug to our membrane platform. As the drug reaches the bilayer, fluorescence is observed, which is then drastically increased once the drug diffuses into the cavity region of plasmonic enhancement.
Lipid Bilayer
Gold microcavities
Drug
Site of plasmonic enhancement.
87
Porous Polymeric Materials for Active Pharmaceutical Ingredient (API) Delivery
Hung-Jui Chen and Bo Xiao
School of Chemistry & Chemical Engineering, Queen’s University of Belfast, Belfast BT9 5AG
Metal-organic frameworks (MOFs) emerged as a new type of hybrid coordination polymeric materials have shown great potential for gas adsorption, catalysis, and drug delivery.1 In drug delivery, MOF properties e.g. pore geometry, ligand functionalities, metal unsaturated sites, framework flexibility, and phase transformation can be utilized for storing API molecules and controlling their release. These factors influencing API storage capacity and release profiles have been experimentally observed. In addition, the API loading condition such as solubility in solvents affects the API storage and release. As shown in Fig. 1, discharging Ibuprofen from MOF HKUST-1 takes ~ 3 days in phosphate buffered saline solution (PBS, pH 7.4). In n-hexane, MOF HKUST-1 can store more ibuprofen than in ethanol. This is related to complicated mutual interactions among the MOF framework, solvent and API molecules, which is now under investigation.
Fig. 1. The profiles of Ibuprofen releasing from MOF HKUST-1. References
1. Chui, S. S. et al Science 1999, 283 (5405), 1148–1151. 2. Xiao, B. et al J. Am. Chem. Soc. 2007, 1295, 1203-1209. 3. Horcajada, P. et al J. Am. Chem. Soc. 2008, 130, 21, 6774-6780. 4. Seo, P. W. et al Scientific Reports 2016, 6, 34462.
88
Ambident Reactivity of Enolates: The Last Stand for HSAB Theory?
Kevin Sheehy,1 Martin Breugst,2 Peter A. Byrne.1 1 School of Chemistry, University College Cork
2 Department für Chemie, Universität zu Köln [email protected]
The regioselectivity in reactions of ambident nucleophiles is typically rationalised using the related principles of Hard and Soft Acids and Bases (HSAB theory) and charge vs. orbital control.[1a-e] Although numerous deficiencies in these principles have been highlighted previously,[2] they remain the “go-to” means of rationalising the outcomes of enolates – ambident nucleophiles with C and O nucleophilic sites. Herein we report our observations on reactions of enolates derived from cyclic 1,3-diones with various alkyl halides that are representative “soft” electrophiles. The ratio of O-alkylation to C-alkylation in these reactions was established through quantitative NMR spectroscopic monitoring of the reactions mixtures. O-alkylation was found to be significantly preferred for reactions of all enolates investigated in THF, even for reactions involving methyl iodide, the archetypal “soft” electrophile. Similar outcomes were observed in other solvents, although the preference for O-alkylation was diminished. The effect of variation of the enolate counter-ion was investigated (amidinium, ammonium, Li+), and the effect was observed to operate regardless of which counter-ion was employed. That “soft” electrophiles become attached at the “hard” site of these enolate nucleophiles shows that the outcomes of these reactions are not adequately accounted for by HSAB theory. If this rationale does not apply for these enolates, then it must not apply generally in reactions of other enolates. Crossover experiments involving enolates derived from cyclic 1,3-diones and their alkylation products indicate that in instances in which high C-alkylation is observed, O-alkylation occurs reversibly, meaning that the final product ratios observed in reactions of these enolates underestimate the kinetic favourability of O-alkylation. By reference to our experimental results and high level quantum chemical calculations, we propose an alternative rationale to explain the regioselectivity in reactions of enolates as ambident nucleophiles.
O
O
MeO
O
Me
O
OTHFn nn
n = 1, 2
MeTHF
I
Preferred Product
Should be favoured (HSAB theory)
Soft electrophile attaches to Hard site
Soft electrophile attaches to Soft site
+
Hard site Soft
site
Figure 6: Alkylation of enolates using “soft” electrophiles produces results inconsistent with those predicted by HSAB Theory.
[1] (a) Pearson, R. G. J. Am. Chem. Soc. 1963, 85, 3533 (b) Pearson, R. G. Science, 1966, 151, 172 (c) Pearson, R. G.; Songstad, J. J. Am. Chem. Soc. 1967, 89, 1827 (d) Klopman, G. J. Am. Chem. Soc. 1968, 90, 223 (e) Salem, L. J. Am. Chem. Soc. 1968, 90, 543 [2] Mayr, H.; Breugst, M.; Ofial, A. R., Angew. Chem. Int. Ed. 2011, 50, 6470-6505.
89
Electrochemiluminescence of Heavy Metal Free Nanomaterials for Applications in Biosensing
Siobhán O’Connor 1,2, Fiona McGrath1,2, Kevin Ryan1,2, Emmet O’Reilly 1,2
1Department of Chemical Sciences, University of Limerick
2Bernal Institute, University of Limerick [email protected]
Electrochemiluminescence (ECL) is a chemical process in which light is emitted during chemical reactions. It can be used to detect and quantify analytes in solutions due to its low background noise and selectivity. Coreactant ECL, a type of ECL, involves a lumiphore, which is a chemical that emits light, and a coreactant, which is involved in the chemical reaction. Organometallic complexes such as ruthenium have been used as lumiphores but have limitations such as complicated structures and fixed emission wavelengths. In 2002 Bard1 first used CdSe nanocrystals for ECL. Advantages associated with nanomaterials include size-tuneable emission and opportunities for multiplexing. ECL has been used in biosensing with ruthenium and cadmium quantum dot (QD) lumiphores to detect various molecules such as heavy metal ions and dopamine. In spite of the success of ECL as an analytical technique, a number of issues such as the high toxicity of cadmium and the remaining work to be done on multiplexing have to be addressed. The aim of this project is to compile a library of lower toxicity nanomaterials suitable for ECL and apply them in the detection and quantification of multiple analytes in biological samples. Low toxicity nanomaterials based on copper, silver, and carbon will be produced by various synthetic methods including microwave synthesis and “heat up” or “hot injection” synthesis. Their shapes and sizes, and thus their emission wavelengths, will be varied by altering their composition, reaction time, and reaction temperature. Multiplexing will be investigated by utilizing oxidative and reductive pathways (by changing the input voltage) and labelling the lumiphores with antibodies or DNA strands. The nanomaterials produced will be compatible with inkjet printing methods, thereby facilitating use as “lab-on-chip” devices for point-of-care measurements, involving whole blood samples. References
1. Myung et al, Nano Lett., 2002, 2, 11, 1315-1319
90
Smart Anionophores: Stimuli-Responsive Anion Transport
Luke A. Marchetti,1 Christopher S. Hawes2 and Robert B. P. Elmes.1 1Department of Chemistry, Maynooth University, Co. Kildare, Ireland.
2School of Chemical and Physical Sciences, Keele University, Newcastle, England.
Recent research has put squaramides at the forefront of supramolecular chemistry due to their many advantageous properties, but in particular due to their ability to form strong hydrogen bonds, which allows for a number of applications such as asymmetric catalysis1, anion sensing2 and anion transport.3 Squaramide-based anion transporters have previously been shown to have superior anionophoric activity compared to their urea/thiourea analogues,4 while also exhibiting potent anti-cancer properties.5 However, due to the prevalence and diversity of anionic species in a biological context, the likelihood of unwanted side effects caused by non-discriminate anion transport is a cause for concern. There is therefore an urgent need to develop new and improved anionophores that display spatiotemporal control of anion transport activity. In this poster, we describe the synthesis of a series of stimuli responsive squaramide-based anion transporters and our initial analysis where we show the ability to control receptor release in response to both enzymatic and chemical stimuli.
Fig.1. Schematic representation of stimuli-responsive anion transporters
References: [1] Malerich, J. P.; Hagihara, K.; Rawal, V. H. J. Am. Chem. Soc. 2008, 130, 14416-14417. [2] Gale, P. A.; Caltagirone, C. Coord. Chem. Rev. 2018, 354, 2-27. [3] Bao, X.; Wu, X.; Berry, S. N.; Howe, E. N. W.; Chang, Y.-T.; Gale, P. Chem. Commun.
2018, 54, 1363-1366. [4] Busschaert, N.; Kirby, I. L.; Young, S.; Coles, S. J.; Horton, P. N.; Light, M. E.; Gale, P. A. Angew. Chem. Int. Ed. 2012, 51, 4426-4430. [5] Busschaert, N.; Park, S.-H.; Baek, K.-H.; Choi, Y. P.; Park, J.; Howe, E. N. W.;
Hiscock, J. R.; Karagiannidis, L. E.; Marques, I.; Félix, V.; Namkung, W.; Sessler, J. L.; Gale, P. A.; Shin, I. Nat Chem 2017, 9, 667–675.
91
SYNTHESIS AND APPLICTIONS OF CYCLIC SULFONAMIDES
Aisha Khalifa and Paul Evans
UCD Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland
The sulfonamide functional group has a long history in the field of organic chemistry. It is widely used in medicinal chemistry, forming a large family of antibacterial agents as well as being found in numerous other drugs and in pharmaceutical products. Also, it is widely used as a protecting group for nitrogen. In this work we describe the straight-forward synthesis of a range of saturated benzo-fused cyclic sulfonamides. The aim of this work as shown in the Scheme below this was achieved using a new reductive intramolecular Heck reaction sequence which employs ammonium formate as the hydrogen source and utilises the palladium catalyst for two distinct chemical processes (the Heck reaction and the subsequent alkene reduction) instead of H2 gas previously used by Evans group. The range of compounds thus prepared were then subjected to a low-valent titanium species formed in situ from Ti(Oi-Pr)4 and Mg. Typically, this method excised the sulfonyl functionality and produced the corresponding aryl substituted cyclic amines in reasonable to excellent yield. As shown in the Scheme below following this process both the C-S and N-S bonds undergo reductive cleavage.
SO2
N
R
R'
R
R' SO2
N
Br
1) Pd(OAc)2 (10 mol%),
PPh3 (20 mol%),
K2CO3,DMF, 110 °C, 15 h
2) NH4CHO2 (55 equiv.),
80 °C, 18 h;
R'' R
''
16 examples
R
R'
NTs
R''
R, R' = H, OMe, OCH
2O, Cl, NO2R
''= Me, i-C3H5
, i-Pr yield % (65- 93)yield % (65- 93)
4) TsCl, Et3N, DCM, 0 °C, 15 h;
16 examples
3) Mg (powder) Ti(Oi-Pr)4
,Me3SiCl.
THF, 80-10015 h, Argon;
°C
Notably, using the new low-valent titanium method the loss of substituents on the aromatic ring does not occur. This contrasts with the same type of reaction process performed under dissolved usually conditions (Li-NH3). And the usefulness of this method was demonstrated with the synthesis of mesembrane. A second method for the for double reduction of cyclic sulfonamides uses the reducing reagent Mg/MeOH. The results indicate that this system is compatible with unsubstituted cyclic benzo-fused sulfonamides and, in the limited cases examined, with other functional groups.
92
Effects of nanoparticle-corona’s glycoproteins and their glycan component on the macrophage uptakes of silica nanoparticles
Duong N. Trinh 1, Marco P. Monopoli 1.
1 Department of Chemistry, RCSI, 123 St. Stephen's Green, Dublin 2, Ireland
Cell-nanoparticle (NP) interaction is being extensively investigated for the underlying cellular mechanisms and safety, as well as successful clinical translation of NPs as drug delivery systems. It is well known that the NP size, shape and surface chemistry affect the degree of uptake and can trigger different pathways [1]. However, NPs after exposure to the biological fluid are covered by biomolecules with high affinity towards the NP surface forming biocorona. This layer determines the cell-NP interactions, while the pristine surface is no longer available [2, 3]. Recent findings suggested that the corona is naturally glycosylated and the glycoprotein component plays a fundamental role in the cellular responses [4]. In this study, we used 200-nm fluorescent silica NPs carrying different protein corona to valuate their uptake into THP-1 macrophages. While most studies have been focussed on the protein component of the corona, we show that the glycans component of the corona is both biologically available and important for the macrophage recognition of the NPs.
[1] Hasanzadeh Kafshgari et al. (2015); Current drug delivery, 12(1), 63-77. [2] Nel, A. E. et al. (2009); Nature materials, 8(7), 543. [3] Monopoli, M. P. et al. (2012); Nature nanotechnology, 7(12), 779. [4] Wan, S. et al. (2015); ACS nano, 9(2), 2157-2166.
93
Ion-Responsive Self-Immolative Linkers for Drug Delivery
Liam Fitzgerald1, 2, Miriam O’Duill1, 2
1School of Chemistry NUI Galway,
2 CÚRAM Centre for Research in Medical devices. Targeted drug delivery is a powerful therapeutic strategy that selectively delivers small molecules or biomolecular drugs to their target in the body to improve efficacy. An interesting conjugate system for targeted drug delivery that is becoming increasingly popular are prodrugs containing so-called self-immolative linkers between the carrier molecule and the drug. [1] A general structure of these linkers is shown in Fig. 1: they are are capped by protecting groups that become labile upon activation, resulting in a rapid, irreversible cascade reaction which liberates the drug molecule. Enzymatic, pH and temperature triggers have been successfully used for targeted drug release in these systems. Due to the important role of ion channels in disease, we are currently developing ion-responsive self-immolative linkers for targeted drug delivery to ion channels.
Figure 7: Concept of Self-Immolative Linkers.
[1] Blencowe, C. A.; Russell, A. T.; Greco, F.; Hayes. W.; Thornthwaite, D. W. Polym. Chem. 2011, 2, 773–790.
94
An investigation of mycotoxin induced DNA damage in porcine intestinal cells
Asmita Thapa1, Blánaid White1, Dermot Walls2, Karina Horgan3.
1School of Chemical Sciences, Dublin City University, Dublin 9, 2 School of Biotechnology, Dublin City University, Dublin 9,
3 Alltech Ltd., Summerhill, Dunboyne, Co. Meath [email protected]
Mycotoxins are naturally occurring secondary metabolites produced by fungal species and mostly found in wheat, barley and corn. Deoxynivalenol (DON) is one of the most frequently occurring mycotoxins. Pigs are particularly susceptible to DON and consumption of contaminated wheat, barley and corn based feed can result in vomiting, diarrhoea and reduced growth. Alltech’s selenium-enriched yeast (Sel-Plex) is an organic selenium product that is used as an animal feed supplement as it has a positive impact on animal health. Mycosorb A+ is a mycotoxin binder produced by Alltech that reduces the amount of mycotoxin absorbed by animals and is therefore, also used as supplement to animal feeds. The aim of the project is to investigate the effects of DON on cultured pig intestinal cells at a cellular level and to investigate the mode of action of protective effects of Sel-Plex and Mycosorb A+ on these cells after exposure to DON.
95
Star polymers and cross-linked star polymer model networks prepared by aqueous RAFT polymerization for drug/DNA delivery
Gavin Irvine, Efrosyni Themistou
School of Chemistry and Chemical Engineering, Queen’s University Belfast, BT9 5AG, UK. Star polymers synthesized in organic solvents are commonly used for biomedical applications.1,2 However, synthesis of biocompatible star polymers under aqueous conditions has yet to be fully explored and could be of high importance in medical research, especially in the field of DNA delivery. Herein, the synthesis of ‘arm-first’ and ‘in-out’ star polymer structures via reversible addition-fragmentation chain transfer (RAFT) polymerization3 methodologies under aqueous conditions is examined. Three different monomers are used for the preparation of “arm-first” and “in-out” star polymers, the neutral oligo(ethylene glycol)methacrylate (OEGMA), the positively charged 2-(dimethylamino)ethyl methacrylate (DMAEMA) and the zwitterionic 2-methacryloyloxyethyl phophorylcholine (MPC), together with the degradable bis[(2-methacryloyloxy)ethoxymethyl] ether (MOEME4) and the non-degradable ethylene glycol dimethacrylate (EGDMA) cross-linkers. Upon addition of further cross-linker to the “in-out” star polymers, cross-linked star polymer model networks (CSPMNs5) are also synthesised. These well-defined gel structures can be used for drug encapsulation and release. The linear polymers, the “arm-first” and the “in-out” star polymers were characterized by proton nuclear magnetic resonance (1H NMR) spectroscopy and gel permeation chromatography (GPC). Dynamic light scattering (DLS) was used for determination of the star polymer size. “In-out” star polymer formation was followed by GPC in two kinetic studies. Future studies will involve the optimization of the star polymers and CSPMNs syntheses, the encapsulation and release of DNA and drug molecules. 1 D. J. A. Cameron and M. P. Shaver, Chem. Soc. Rev., 2011, 40, 1761–1776. 2 J. M. Ren, T. G. McKenzie, Q. Fu, E. H. H. Wong, J. Xu, Z. An, S. Shanmugam, T. P.
Davis, C. Boyer and G. G. Qiao, Chem. Rev., 2016, 116, 6743–6836. 3 G. Moad, E. Rizzardo and S. H. Thang, Acc. Chem. Res., 2008, 41, 1133–1142. 4 E. Themistou and C. S. Patrickios, Macromolecules, 2007, 40, 5231–5234. 5 S. N. Georgiades, M. Vamvakaki and C. S. Patrickios, Macromolecules, 2002, 35, 4903–
4911.
96
On-line Analysis of Organic Aerosols in Air
Niall O’Sullivan, Elena Gomez-Alvarez, Stig Hellebust, John Wenger
School of Chemistry and Environmental Research Institute, University College Cork
Organic aerosols play a key role in the global atmosphere by affecting both climate and health. The organic compounds can exist in both particle and gas phases and undergo many different reactions in the atmosphere. Organic aerosols are thus highly complex mixtures and chemical analysis, particularly at the molecular level, has proven to be very challenging. However, the recent development of the Filter Inlet for Gases and Aerosols (FIGAERO) coupled with a time-of-flight Chemical Ionization Mass Spectrometer (ToF-CIMS) now enables detailed molecular characterization of both gas and particle phase species to be analysed on-line and in near real-time (Lopez-Hilfiker et al. 2014). The ToF-CIMS is a high-resolution mass spectrometer utilising a soft ionisation technique via the addition of an iodide adduct generated by passing methyl iodide in nitrogen over a Corona discharge. This analytical technique has sub pptv limits of detection, thus allowing the ToF-CIMS to be effectively utilised in the field to determine organic species present in the ambient atmosphere. In this work, the FIGAERO ToF-CIMS has been used for the first time in Ireland to analyse the composition of ambient organic aerosols at an urban background location in Cork City. Measurement campaigns were performed in late August/September 2018 and January/February 2019 in order to examine seasonal differences in aerosol composition. The data from the summer indicated that naturally occurring compounds and their atmospheric oxidation products were the dominant species. Oxalic acid and glycolic acid were among the species detected at higher concentrations. These compounds are known products from the oxidation of isoprene, a naturally occurring compound which is the second most abundant hydrocarbon in the Earth’s atmosphere (Guenther et al. 1995). Their time profiles show strong diurnal patterns influenced by the weather conditions. The data collected in the winter campaign suggested a high prevalence of species known to be produced by solid fuel burning. Strong night-time peaks were observed for a range of wood-burning marker compounds (nitrophenol, guaiacol and vanillic acid) (Lauraguais et al. 2014), as well as other known combustion by-products, such as polycyclic aromatic hydrocarbons which are known to be toxic. Work is ongoing to determine how the various species vary with differing conditions including ambient concentrations of nitrogen oxides and ozone as well as meteorological factors.
This work was funded by the Environmental Protection Agency of Ireland through a Government of Ireland Postgraduate Scholarship (GOIPG/2017/1364). Guenther, A., and Coauthors, 1995: A global model of natural volatile organic compound emissions. Vol. 100, 8873-8892 pp. Lauraguais, A., C. Coeur-Tourneur, A. Cassez, K. Deboudt, M. Fourmentin, and M. Choël, 2014: Atmospheric reactivity of hydroxyl radicals with guaiacol (2-methoxyphenol), a biomass burning emitted compound: Secondary organic aerosol formation and gas-phase oxidation products. Atmospheric Environment, 86, 155-163. Lopez-Hilfiker, F. D., and Coauthors, 2014: A novel method for online analysis of gas and particle composition: description and evaluation of a Filter Inlet for Gases and AEROsols (FIGAERO). Atmos. Meas. Tech., 7, 983-1001.
97
C2H2/CO2 Separation Studies of Pyrazole Ligand Derived Hybrid Ultramicroporous Materials
Naveen Kumar, Soumya Mukherjee, Michael J. Zaworotko
Department of Chemical Sciences and Bernal Institute, University of Limerick, Limerick V94 T9PX, Republic of Ireland.
Acetylene (C2H2), an important fuel, also serves as a building block for a range of industrially relevant polymer syntheses. C2H2 production processes generate CO2 as a major impurity. Therefore, selective separation of C2H2 from C2H2/CO2 mixture is industrially relevant, but remains challenging because of closeness in their size and other physical properties. State-of-the-art C2H2 purification technologies include chemical extraction of C2H2, an energy intensive process, which affords a large amount of organic solvent as waste. To address the energy economy and avoid solvent wastage, physisorbents offer a promising route to separate the highly combustible gas C2H2 via selective sorption. Of late, crystal engineering approaches have enabled a new-generation hybrid ultramicroporous physisorbents (HUMs) with facile regenerability and recyclability to emerge as the current benchmarks in trace and bulk C2H2/CO2 separation.1 In this context, there is a need to develop simpler, cost-effective design principles of crystal engineering, touted to offer task-specific sorbents. Herein, we report a series of isostructural HUMs, incorporating pyrazole ligands, with the ability to selectively adsorb C2H2 over CO2 with high selectivity (> 10). Dynamic breakthrough separation studies conducted on these hydrolytically stable sorbents reveal high separation factors (> 35) for 1:1 and 2:1 C2H2/CO2 binary gas mixtures.
References 1. a) Chen, K.-J.; Scott, H. S.; Madden, D. G.; Pham, T.; Kumar, A.; Lusi, M.; Forrest,
K.; Space, B.; Perry, J. J., IV; Zaworotko, M. J. Chem 2016, 1, 753−765. b) Peng, Y.-L.; Pham, T.; Li, P.; Wang, T. Y.; Chen, K.-J.; Forrest, K. A.; Space, B.; Cheng, P.; Zaworotko, M. J.; Zhang, Z. Angew. Chem. Int. Ed. 2018, 57, 10971.
Fig.1. Schematic illustration of a pyrazole ligand derived HUM exhibiting C2H2
separation from C2H2/CO2 binary gas mixture
98
Directed Self Assembly of Near Infrared Fluorescence Responsive Nanoparticles and their use for Cellular Imaging
Niamh Curtin, Donal O’Shea.
Dept. of Chemistry, RCSI, 123 St Stephen's Green, Dublin 2.
Directed self-assemblies in water are the most efficient means of forming higher ordered structures in nature. The aim of this work is to form a nanoparticle by directed self-assembly (DSA) with a measurable fluorescence response that is dependent upon the micro-environment. The formation of fluorescence responsive nanoparticles is achieved by the thermodynamically favourable directed self-assembly of an amphiphilic tri-block co-polymer (P188) in the presence of a hydrophobic fluorophore in water. The directing template of this self-assembly comes from hydrophobic fluorophore / poloxamer interactions between the fluorophore and PPO segment of the poloxamer leading to nanoparticles of ~100 nm in size. Small lipophilicity changes in fluorophore microenvironment result in off to on fluorescence switching which has been investigated for cell imaging applications. This feature of the fluorophore can be utilised to convey real time information about the environment that it is in. The fluorescence of the DSA particles in water has been shown to be quenched but can be turned on by cellular uptake into lipid droplets. Other poloxamers such as PS20 and P105 with the fluorophore were used to compare how the fluorophore interacts and assembles in water. DLS and fluorescence measurements were used to show how the response of the fluorophore alters depending on the environment it is in. Fluorescence microscopy was used to show how the fluorophore-P188 can elicit a response when it is taken up into a cell.
Ph Ph
N
N
NB
F F
O O
1O
(OCH2CH2)XOHHOW(CH2CH2O)
(OCH2CH2)YOH
O(CH2CH2O)ZCH2CH2OC(O)CH2(CH2)9CH3
OOO
OHH
79 28 79
w+x+y+z = 20
P188
PS20 Fig. 1. Directed self-assembly of fluorophore with poloxamers
template1
water, rt
NP1-P188
~100 nm
~6.5 nm
PPO
PEO
non-fluorescent
P188
99
Intrinsic Properties of Nitric Oxide Binding to Hemin and Hemin Conjugates: A Theoretical Study
Amir Abdo1, Pau Farràs2, Abhay Pandit1
1Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), NUI Galway, Ireland and 2School of Chemistry, NUI Galway, Ireland
The real-time NO sensing and/or scavenging, specifically at the low physiological concentrations, is of paramount importance for studying its roles in various physiological and pathological processes and for fabricating special therapeutics targeting NO. Due to its high binding capacity and selectivity to NO, the Fe(III)-porphyrin complex, hemin, was conjugated to the biocompatible aromatic molecules tyrosine and tyramine for the further manufacturing of a biocompatible NO-scavenger/sensor. Herein, density functional theory (DFT) methodologies were used to assess the stability of these conjugates and their affinity to bind NO. The geometries of the molecules were optimized, and the thermochemical properties were obtained by frequency calculations with computing the NBO charges. The calculated NO-binding energies were -218.86704, -216.25, -214.63186 and -216.3706 kcal/mol, for hemin, hemin/styrene, hemin/tyramine and hemin/tyrosine conjugates, respectively, with different ionization potential within the range 79-84 kcal/mol, and binding affinity to OH- ion within the range -27 to -22 kcal/mol. The d-orbital occupancy before and after NO-binding was investigated; where NO once binds with hemin/tyrosine showed the least energy (-0.00707 eV), referring to a greater reduction of the Fe(III) ion than the other molecules, while the total NO energies were -0.0214, -0.02496 and -0.01412 eV in case of hemin, hemin/tyramine and hemin/tyrosine conjugates, respectively. Moreover, the HOMO and LUMO orbitals were investigated and their energies were compared between the different analysed structures. It was found that the hemin conjugation could control the binding affinity to NO, which was optimum in the case of tyramine, followed by tyrosine, and styrene.
Figure 1. The binding of hemin to NO
Acknowledgements The authors thank Science Foundation Ireland (SFI) and the European Regional Development Fund (Grant Number 13/RC/2073), the college of engineering and informatics, NUIG and the DJEI/ DES/ SFI/HEA Irish Centre for High-End Computing (ICHEC) for the provision of computational facilities and support.
100
Gas Chromatography-Mass Spectrometry Analysis of Bacterial Volatiles
Shane Fitzgerald 1, Emer Duffy 1, Linda Holland 2, Aoife Morrin 1.
1 The Insight Centre for Data Analytics, School of Chemical Sciences, Faculty of Science
and Health, Dublin City University, 2 School of Biotechnology, Faculty of Science and Health, Dublin City University
An open wound can be thought of as its own mini microbiome, providing a readily available nutrient source for a variety of opportunistic microbes. As some of these microbes can be pathogenic, efficient monitoring of open wounds is critically important to prevent severe infections. The detection of volatile organic compounds (VOCs) emitted from pathogenic microbes on the wound bed may potentially provide an early diagnostic tool for wound infections in the future. However, before testing of real wound samples can commence, it is necessary to build up a library of VOCs emitted from prominent pathogenic bacteria commonly found in wounds. To begin this study, we investigated the emission of VOCs from planktonic liquid cultures of Staphylococcus aureus (S.aureus) and Pseudomonas aeruginosa (P.aeruginosa); both of which are responsible for many wound infections. In vitro studies of bacterial VOC profiles rely on headspace analysis of planktonic cultures. Single strain cultures were set to a particular optical density (OD) corresponding to a specific cell count and inoculated into a small volume of media in a headspace vial. Solid phase microextraction (SPME) fibers were used to sample the headspace of the samples. The primary aim of this study is to obtain a profile of volatile organic compounds (VOCs) emitted from each pathogen using Gas Chromatography-Mass spectrometry (GC/MS); that can be referenced and used to identify/classify these organisms in more complex studies. Secondary aims of this study were: to investigate the variation in VOC emission over time, and to assess the contribution of the growth media to the VOCs emitted from each sample.
101
Ionic Liquid-Assisted Synthesis of Nanocatalysts for the Direct Conversion of CO2 to Hydrocarbons
Zara Shiels1,2, Nancy Artioli1, Peter Nockemann1, John Harrison2
1Queen’s University Belfast 2South West College, Cookstown [email protected]
This project involves the development of new nanocatalysts for the direct conversion of biogenic carbon dioxide (CO2) to “Drop-In” fuels in the gasoline range (C8-C12) resulting in a sustainable production route. Thereby, using hydrogen from renewable energies and directly converting CO2, which offers an attractive route for the efficient utilisation of CO2 as a renewable feedstock. Generally, the direct CO2 hydrogenation to hydrocarbons proceeds via a modified Fischer−Tropsch synthesis (FTS) process. Fe-based catalysts have been widely investigated recently because of their low cost, high activity, and they operate with different syngas ratios in a temperature range of 220−270 °C to produce gasoline components in FTS. Controlling the metal particle size and their dispersion is the major challenge when investigating structure–activity relationships. Novel synthetic catalytic approaches will result in a pathway for the controlled growth and dispersion of the nanocatalyst.
102
Pressing solids directly into sheets of plasmonic nanojunctions enables solvent-free surface-enhanced Raman spectroscopy
Li, Chunchun; Xu, Yikai; Bell, Steven E. J.
School of Chemistry and Chemical Engineering, Queen’s University of Belfast [email protected]
Often chemical analysis of solid materials begins with dissolving the sample in a solvent but this is undesirable, particularly if the physical form is important. In principle surface-enhanced Raman spectroscopy (SERS) should allow detection of solid analytes and offers attomolar sensitivity combined with molecular specificity. However, in SERS experiment solid samples typically need to be dissolved in a solvent so they can diffuse into the enhancing region. Here, we show how SERS spectra of picograms of solid analytes can be directly obtained by pressing the solid analytes into a flexible SERS substrate with a dense field of exposed nanojunction hot-spots anchored on its surface. The key component is a flexible SERS substrates, surface exposed nanoparticle sheets (SENS), in which the plasmonic nanojunctions are partly submerged into the polymer but still exposed and accessible. We demonstrate that this can be a powerful tool for straightforward and non-destructive forensic analysis of layered materials (crossing ink lines), solid explosives and illicit drugs as well as for studying previously intractable samples such as pharmaceutical co-crystals, whose important solid state structure is lost when they are dissolved.
Figure 1. (A) Schematic representation of a surface-exposed nanoparticle sheet enhanced Raman spectroscopy (SENSERS) measurement. (B) SENSERS spectra of crystal violet (CV) obtained with different probed sample masses. Inset shows the calibration plot of the intensity of the 1180 cm-1 CV (peak) against log concentration over the range 5×10 7- 5×10-5 M, corresponding to ca. 2-200 pg of probed analyte.
103
Filling in the gaps: A comprehensive analysis of light transmission through void-filled inverse opal photonic crystal materials
Alex Lonergan1 and Colm O’Dwyer1,2,3,4
1School of Chemistry, University College Cork, Cork, T12 YN60, Ireland
2Micro-Nano Systems Centre, Tyndall National Institute, Lee Maltings, Cork, T12 R5CP, Ireland 3AMBER@CRANN, Trinity College Dublin, Dublin 2, Ireland
4Environmental Research Institute, University College Cork, Lee Road, Cork T23 XE10, Ireland
Photonic crystal structures possess the ability to mold the flow of light in accordance with their structural composition[1,2]. Photonic crystals can be naturally occurring, creating the vibrant array of colours seen in peacock feathers and butterfly wings or the iridescence observed in opal gemstones. These colourful effects are a result of a microscopic arrangement of material interacting with incident light. Designing a material with an induced periodicity gives rise to a photonic crystal effect, whereby light propagation can be controlled by the presence of a repeating structure. Using artificial opals as templates, fabricated from stacks of polystyrene or PMMA spheres, it is possible to form an inverse photonic crystal structure (inverse opal) composed of a wide variety of metal oxides. Inverse opal photonic crystals are currently of great interest in many research disciplines. Optical waveguides, solar cells, colourimetric sensors, nonlinear optics materials and battery electrodes are just some of the many applications of photonic crystal materials[3]. A photonic bandgap describes the prevention of light transmission through a material as a result of structural interference with the incident light. Certain wavelengths of light can be partially or completely restricted in transmission. The wavelength position of the photonic bandgap can be tuned by controlling certain parameters in the photonic crystal. The size of the spheres in the artificial opal template dictate the size of the pores observed in the inverse opal. Larger sphere and pore sizes prevent transmission of longer wavelengths of light and vice-versa. The refractive index of the material comprising the photonic crystal also controls the position of the photonic bandgap, larger indices of refraction act to red shift the wavelengths prohibited by the structure. Larger indices of refraction also have the advantage of creating a more complete photonic bandgap, with a full photonic bandgap acting to prevent any light propagation across specific wavelengths[4]. One of the most appealing aspects of photonic crystals, lies in their ability as sensors. Post-fabrication, the position of the photonic bandgap can be tuned by filling the voids in the structure with various liquids of varying refractive index. The main focus of this work is to characterise the optical response of inverse opal structures in the presence of various solvents. The position of the photonic bandgap is known to vary with changes to the angle of incidence between the light and normal to the sample surface. Here, we combine the effects of solvents filling the voids of TiO2 and SnO2 inverse opals with controlled variation of the angle of incidence. The optical response of inverse opals under these conditions has only been speculated upon to date. Analysis of the resultant optical spectra shows a small deviation from the anticipated response, but nevertheless presents a readily predictable optical response of inverse opals to a wide variety of experimental conditions. This complete understanding of the photonic bandgap in inverse opal structures is hoped to form the basis of an all-optical photonic probe, mapping changes in energy storage devices in real time[5]. [1] E. Yablonovitch, Inhibited spontaneous emission in solid-state physics and electronics, Phys. Rev. Lett. 58, 2059 (1987). [2] S. John, Strong localization of photons in certain disordered dielectric superlattices, Phys. Rev. Lett. 58, 2486 (1987). [3] K. R. Phillips, G. T. England, S. Sunny, E. Shirman, T. Shirman, N. Vogel, and J. Aizenberg, A colloidoscope of colloid-based porous materials and their uses, Chem. Soc. Rev. 45, 281 (2016). [4] K. Busch and S. John, Photonic band gap formation in certain self-organizing systems, Phys. Rev. E 58, 3896 (1998). [5] C. O'Dwyer, Color-coded batteries – Electro-photonic inverse opal materials for enhanced electrochemical energy storage and optically encoded diagnostics, Adv. Mater. 28, 5681 (2016).
104
Rapid Profiling of Functional Polymer Drug Formulations via Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS).
Niamh O’Mahoney,a Anas Alfarsia, Marcel Arndtb, Theresia, Kuntzb, Jacob Krüsec, Brigitte
Skalskyb, Dara Fitzpatrick a,
a Department of Chemistry, Analytical and Biological Chemistry Research Facility
(ABCRF), University College Cork, Ireland b Evonik, Nutrition & Care GmbH, Darmstadt, Germany
c Kinetox, Beilen, The Netherlands [email protected]
Rapid dissolution test that measures the coating thickness and integrity during or after manufacturing of controlled pellets are non-existent. The production of the controlled release pellets takes several process steps before being ready to release to the market. BARDS is a novel technique that has the potential to economise the production process of these kinds of pellet and tablet formulation. The manufacture of these medications requires several coating steps, depending on the formulation. The sub and enteric coating steps typically take up to six hours, each followed by additional drying steps. Post-production regulatory dissolution testing also takes up to six hours to determine if the batch can be released for commercial sale. The thickness of the enteric coating is a key factor that determines the release rate of the drug in the gastro-intestinal tract. Correspondingly, the amount of drug per unit mass of pellets decreases with increasing thickness of the enteric coating. In this study, the thickness of the coating process is investigated by testing pellets and tablets using BARDS (Broadband Acoustic Resonance Dissolution Spectroscopy). BARDS offers a rapid approach to characterising enteric coatings during their manufacture. BARDS measurements are based on reproducible changes in the compressibility of a solvent during dissolution which is monitored acoustically via associated changes in the frequency of induced acoustic resonances. A steady state acoustic lag time is associated with the disintegration of the enteric coatings in low pH solution. This lag time is pH dependent and is indicative of the rate at which the coating layer dissolves. BARDS represents a possible future surrogate test for conventional USP dissolution testing as its data correlates directly with the thickness of the enteric coating, its integrity and also with the drug loading as validated by UV-Vis spectroscopy.
105
Mediated Lactose and Lactate Biosensing in Fermentation Media
Grace Halpin, Eithne Dempsey
Chemistry Department, Maynooth University, Maynooth, Co. Kildare. [email protected]
Rapid and selective monitoring of small molecules is of significance in relation to fermentation process control where optimisation and scale up relies on accurate measurement of species such as lactose and lactic acid. Here, a lactose biosensing methodology is presented based on co-immobilisation of Glucose Oxidase (GOx) and β-Galactosidase (β-Gal) on carbon transducers. Quantitative chronocoulometric signals were achieved within 5 sec via a mediated (ferricyanide) approach at carbon screen-printed electrodes realising linearity 2.91 x 10
-3 – 9.09
x 10-3
M (R2 = 0.98), sensitivity 8 Acm-2M-1 and LOD 140 µm. Lactate sensing involved use of the heterocyclic quinoid species 1,10-phenanthroline-5,6-dione which acts as proton and electron acceptor in relation to FADH2 cofactor regeneration. The use of scanning electron microscopy and scanning electrochemical microscopy (SECM redox competition mode) provided surface topographical and imaging/enzyme reactivity information respectively (Fig. 1). On-site analytical performance was examined in diluted fermentation media, comparing well to the established HPLC-RI lactose separation approach, with 100-106 % correlation over the range of sampling time points investigated.
Figure 1. Cyclic voltammogram response to 0 – 7 mM Lactate concentrations in 5 mM K3Fe(CN)6 at LOx modified glassy carbon electrode, potential range -0.5 V – 0.7 V vs Ag/ AgCl at 20 mV/s. (B) Area scan SECM experiment at ET = -0.4 V vs. Ag/AgCl Esub = OFF, 25 mm Pt (RG = 15) 5000 x 8000 mm2 100 mm per point at LOx modified GCE substrate in 10 mM lactate and 5 mM potassium ferricyanide.
-0.5 0 0.5-0.0025
0
0.0025
E (Volts)
J (A
mps
/cm
2 )
(A) (B)
106
Bio-conjugations In Flow for Drug Conjugates and Theranostic Imaging Agents
Sheila Fitzgerald, Donal O’Shea
Department of Chemistry, RCSI, 123 St Stephen’s Green, Dublin 2
The aim of this work is to develop universal bio-conjugation protocols for biomolecules in flow by employing coupling partners such as azide/alkyne, amine/activated ester, and malemide/thiol. Where applicable, naturally occurring lysine and cysteine residues will be exploited for conjugation, and in their absence appropriate functional groups will be engineered into the biomolecule. To date, through the use of solid phase peptide synthesis, a 24-mer peptide has been synthesised and subsequently modified to include the strained alkyne bicyclo[6.1.0]non-4yn-9ylmethanol (BCN). In addition to the peptide, a water soluble, azide functionalised, near-infrared BF2–azadipyrromethene fluorochrome has also been synthesised. Optimal conditions for the two molecules to undergo an in flow strain promoted alkyne-azide cycloaddition (SPAAC) will be identified. This first prototype reaction will lay the foundations for the development of a comprehensive in flow bio-conjugation tool kit.
O
N
N NBF FR1 R2
Ph Ph
O
HN
O
NN
N
Ph
Ph
O
O
BF F
NNN
3
O3S
O
Fig.1. Schematic of water soluble azide NIR BF2 fluorochrome and BCN conjugation in flow
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Cyclometalated Ir(III) Complexes as Triplet Photosensitisers for Efficient Visible-Light Absorption
Nidhi Arora,a Xiaoneng Cui,a,b and Sylvia M. Drapera
a School of Chemistry, University of Dublin, Trinity College, Dublin 2, Ireland
b State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, E-208 West Campus, 2 Ling-Gong Road, Dalian 116024, P. R.
Chi [email protected], [email protected]
Luminescent transition metal (TM) complexes as triplet photosensitisers are attractive for their efficacy in diverse applications. The effectiveness of a complex in a specific role is determined by its excited state properties which can be manipulated through synthetic modifications.1 Heavy atom TM photosensitisers can be efficiently excited to their triplet excited states which is required for a number of photochemical reactions.2 A range of cyclometalated Ir(III) complexes have been synthesised via Sonogashira cross coupling reactions of the 3,8-disubsituted 1,10-phenanthroline participating ligand, and show strong absorption in the visible region. Addition of chromophoric boron dipyrromethene (BODIPY) and triphenylamine (TPA) light harvesting groups was achieved via acetylenic linkers. This was also found to broaden the absorption wavelength of the complexes. One complex with two BODIPY units, showed very strong absorption (Ɛ= 1.8×105M-1cm-1) at λ=538 nm. The emission properties of the complexes were studied under different atmospheres (RT, N2, 77K). The emission spectra of a further compound, bearing one BODIPY and one TPA, was different to that of previous bis-BODIPY complex. Two close emissive bands at λ=501 and λ=555 nm were perceived under both air and N2 for the second complex. The complexes are highly phosphorescent at low temperature (77K), but no room temperature phosphorescence was observed. The low temperature emission was assigned to the phosphorescence-type emission band of the BODIPY triplet excited state.3 The quantum yields and luminescence lifetimes were studied for the complexes. The measured luminescence lifetimes at room temperature were observed to be quite short which usually is a typical excited state value for fluorescence. DFT calculations were performed to corroborate the findings of the photo-physical studies. 1. M. S. Lowry and S. Bernhard, Chem. Eur. J., 2006, 12, 7970-7977. 2. J. Zhao, W. Wu, J. Sun and S. Guo, Chemical Society Reviews, 2013, 42, 5323-5351. 3. J. Zhao, K. Xu, W. Yang, Z. Wang and F. Zhong, Chemical Society Reviews, 2015, 44,
8904-8939.
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Developing Tools for Pesticide Detection and Toxicity Testing in Agricultural Soils
Mathavan Vickneswaran1, Michael Kitching1, James Carolan2, Blánaid White1
1DCU Water Institute, School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland,
2 Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland. [email protected]
Agriculture practices are crucial in securing global food security and reducing the hunger of an ever-increasing global population. However, crop cultivation faces a consistent battle against insects, weeds, and diseases, that can negatively impact yield. In this circumstance, the introduction of synthetic pesticides has significantly contributed to overcoming the pest attack and helped farmers ensure better agricultural yield. Usage of pesticides had presented a conundrum to the global community, as ideally, a pesticide should only affect the targeted pests, but in reality, chemical pesticides residues have been shown to persist in soil or have a longer half-life than was intended. In the global context, we still have a poor understanding of how the pesticides behave in the soil under numerous physico-chemical factors and microbiological communities. Hence, for this project a number of widely used pesticides including glyphosate (half-life: 1.85-47 days) and neonicotinoids (half-life: 200-1000 days) were chosen to develop analytical methods to quantify pesticides in soil and to screen soil samples using biosensor tools developed through this project for genotoxicity. Subsequently, the quantified pesticide residues from the soil samples will be used to evaluate their impact on pollinators. Findings from this project will help us fill in the knowledge gap on the behaviour of pesticides in the soil and enable us to assist in developing soil protection framework ensuring continuous soil resource conservation and sustainable pesticide usage. Keywords: pesticide, soil, half-life, biosensor tool, conservation, sustainable Acknowledgement - The authors thank the Department of Agriculture, Food and the Marine in Ireland for funding this research.
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The Control of Single Nanowire Device's Electrical Performance via Seed Mediated Doping and Contact Design
Adrian Hannon1, Dylan Storan1, Kevin M. Ryan1
1Bernal Institute, Department of Chemical Sciences, University of Limerick [email protected]
With the current rate of growth for electronic applications generating significant demand for smaller and smaller devices, the need for nanodevice research has never been greater. One area of such research is semiconductor nanowire doping and contacting. Nanowires offer promising potential in a vast array of applications, such as sensors, photovoltaics, field-effect transistors, and energy storage. This potential is due to the intrinsic properties of nanowires, namely their advantageous thermal, optical, mechanical, and electrical properties. Controlling their physical properties, such as dimensionality, growth direction, composition, and, especially, their doping, during the growth processes offer noticeable advantages for stable structures that can optimise the electrical properties for nanoscale devices (Figure 1.). To date, while there have been many studies conducted to develop simple, reliable techniques for a precise understanding of the electrical properties, consistent analysis of electrical characteristics remains a challenge. The challenges of nanowires arise through their susceptibility to surface contamination, control of crystallographic orientation during growth, the nanowire diameter, computation of carrier concentrations, mobility, and determination of transport mechanisms. Furthermore, to probe these electrical properties, the fabrication of metal nanowire semiconductor contacts is central to the characterisation techniques (Figure 1.), while simultaneously playing a vital role in the operation of nanodevices. However, more challenges emerge in contacting the nanowires through attempts to realise good Ohmic contacts, achieving low resistance, and efficient, stable carrier transport. Controlling the behaviour between contacts and nanowires relies heavily on understanding the design principles of their intermetallic reactions, defect formations, temperature relations, and in particular the behaviour of their metal-nanowire interface layer. The aim of this work is to design a reliable process for contacting nanowires through the development and optimisation of in-situ seed mediated doping of the nanowires, as well as intermetallic compound formation at the metal nanowire interface. By understanding the doping effects that occur via the fabrication stages due to these mechanisms, optimisation and control of the electrical characteristics for ‘next generation’ nanodevices will be possible
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In Search of Highly Emissive Donor-Acceptor Structures for Thermally Activated Delayed Fluorescence Organic Light Emitting Diodes
Martha Gulman 1, Dr. Xiaoneng Cui 2, and Prof. Sylvia Draper
Trinity College Dublin
Electroluminescence is the emission of light from a material when subjected to an electric field. This phenomenon was first observed from single crystals of anthracene in 1964.1 Organic light emitting diodes (OLEDs) are diodes containing light, flexible sheets of highly electroluminescent organic materials for use in visual displays. Upon electrical excitation, 25% of excitons populate the singlet-excited state, and 75% populate the triplet-excited state. A monumental breakthrough came in 2012, when Adachi et al.2,3 pioneered the thermally activated delayed fluorescence (TADF) OLED materials. By careful design of fully organic small molecule electroluminescent materials, the whole span of the solar light could be accessed, with near-infrared (NIR) materials emitting up to 900 nm. Utilising the photophysical phenomenon of TADF, internal quantum efficiencies of up to 100% could be achieved within an OLED device. The TADF photophysical processes were studied in depth in an acceptor-donor-acceptor type system. Utilising phenothiazine (PTZ) as the central core, two triazine appendages linked via an acetylene bridge are proposed as di-acceptor systems. PTZ is substituted with a long aliphatic chain, which serves to reduce π-π stacking and protect the amine from any further undesired reactions both during synthesis and in an OLED device. The acetylene linker has been incorporated to spatially separate the HOMO and LUMO orbitals in order to induce charge transfer (CT), as well as retain planarity to limit non-radiative decay pathways.4 All triazines are asymmetric appendages to the donor PTZ core, to ensure a small ΔES-T gap and efficient krISC.5 The cyano functionality has been incorporated to enhance the accepting capabilities of the triazine. Exploration into the most effective positioning of the electron-withdrawing cyano moiety proved that the para- positioning has the largest effect on the emissive properties of the materials. The compounds all have high molar absorptivity coefficients, efficient photoluminescent quantum yields (PLQY) and excited state lifetimes in the nanosecond region. The emission profiles of the compounds exhibit CT character and are orange to green emitters. 1 Helfrich W and Schneider, Phys. Rev. Lett., 1965, 14, 229. 2 G. Méhes, H. Nomura, Q. Zhang, T. Nakagawa and C. Adachi, Angew. Chemie - Int.
Ed., 2012, 51, 11311–11315. 3 H. Tanaka, K. Shizu, H. Nakanotani and C. Adachi, Chem. Mater., 2013, 25, 3766–
3771. 4 L. Xue, B. Cui, S. Xie and S. Yin, J. Phys. Chem. Lett, 2019, 10, 308. 5 T. Chen, L. Zheng, J. Yuan, Z. An, R. Chen, Y. Tao, H. Li, X. Xie and W. Huang, Sci.
Rep., 2015, 5, 1–11.
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Design of Coordination Networks using Rod Building Blocks
Daniel J. O’Hearn,1 Suman Bhattacharya,1 and Michael J. Zaworotko1
1 Bernal Institute, Department of Chemical Sciences, University of Limerick, Limerick, Ireland
The design of metal-organic frameworks (MOFs) and other coordination networks (CNs) has developed rapidly over the past three decades. By applying the “node and linker” strategy developed in the early 1990s by Robson et al,1 Fujita et al,2 and later, the concept of molecular building blocks (MBBs)3 and supermolecular building blocks (SBBs),4 chemists have been able to exercise control over the seemingly unpredictable self-assembly of CNs. Despite these successes, the custom-built design of MOFs and CNs based upon infinite 1D building blocks, called rod building blocks (RBBs), or rod secondary building units, has remained elusive.5 To address this, we have identified RBBs based upon inexpensive hydroxy functionalised carboxylic acids and divalent transition metal ions. We have been able to construct RBBs that can be cross-linked by bipyridyl linkers to afford 2D and 3D CNs. Unlike most RBBs, the linker in these examples is independent of the RBB structure itself, allowing it to be used as a crystal engineering tool similar to MBBs and SBBs. When terminal pyridyl ligands are used, the RBBs can also be isolated as 1D coordination polymers and used as starting materials for higher dimensional CNs.
Figure 1. An example of a rod building block being used to construct 2D and 3D coordination networks. References 1 Gable, R. W.; Hoskins, B. F.; Robson, R. J. Chem. Soc., Chem. Commun. 1990, 23, 1677-1678. 2 Fujita, M.; Kwon, Y. J.; Washizu, S.; Ogura, K. J. Am. Chem. Soc. 1994, 116 (3), 1151-1152. 3 Gardner, G. B.; Venkataraman, D.; Moore, J. S.; Lee, S. Nature 1995, 374 (6525), 792-795. 4 Perry IV, J. J.; Perman, J. A.; Zaworotko, M. J. Chem. Soc. Rev. 2009, 38 (5), 1400-1417. 5 Catarineu, N. R.; Schoedel, A.; Urban, P.; Morla, M. B.; Trickett, C. A.; Yaghi, O. M. J. Am. Chem. Soc. 2016, 138 (34), 10826-10829.
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Switching Adsorbent Layered Materials
Shi-Qiang Wang and Michael Zaworotko
Bernal Institute, Department of Chemical Sciences, University of Limerick, Limerick, Ireland. [email protected]; [email protected]
We introduce here Switching Adsorbent Layered Materials (SALMAs), which belong to a broad but understudied family of metal-organic materials1. The main features of SALMAs can be summarised as follows: 1) “switching” behaviour, meaning they can switch between nonporous (closed) and porous (open) phases when induced by appropriate stimuli such as gases or vapours; 2) “layered” structure, indicating they are typically 2D layered materials wherein the adjacent layers pack via non-covalent interactions; 3) “modular” ability, implying they can be amenably prepared by changing the metal node and ligand linker via crystal engineering2. It is our hypothesis that SALMAs have the potential to solve the scientific and technical hurdles yet to be overcome by existing porous 3D materials: low working capacity (caused by inappropriate type-I isotherms and/or low uptake capacity); and poor recyclability (caused by poor mechanical, thermal and/or hydrolytic stability). A representative compound, sql-1-Co-NCS, will be detailed in the poster regarding the applications of CO2 storage3 and C8 aromatics separation4.
Fig.1. Schematic representation of SALMAs which switch between nonporous (closed) and porous (open) phases induced by appropriate stimuli. References 1. J. J. Perry IV, J. A. Perman, M. J. Zaworotko, Chem. Soc. Rev. 2009, 38, 1400-1417. 2. B. Moulton, M. J. Zaworotko, Chem. Rev. 2001, 101, 1629-1658. 3. Shi-Qiang Wang, et al., Chem. Commun. 2018, 54, 7042-7045. 4. Shi-Qiang Wang, et al., Angew. Chem. Int. Ed., 2019, 58, 6630-6634.
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Investigation of Steel Serving Utensils on the Irish Market for Migration of Metals using ICPMS
Xinyi Wu1,2, Dr John Keegan1, Dr Patrice Behan2
1Public Analyst's Laboratory Dublin, 2School of Chemical and Pharmaceutical Sciences, TU Dublin
Food Contact Materials (FCMs) are anything that intends to come into contact with food and are posing a threat to the public health if the level of contaminants present within exceeds the legal limit set by the European Commissioner. Nowadays stainless-steel serving utensils are generally seen as a popular presentative tool to deliver meals in restaurants, considering the frequent high demands of the general public in dining in restaurants as such, the level of contaminants being released from the steels need to be monitored for health and safety purposes. 120 samples were collected from both kitchen appliances stores in Ireland and online in the EU market varying in type, size and intended use. Release tests were carried out under two different condition being extraction of articles from immersion of pre-heated 3% acetic acid solution at 1) 22ͦC after 24 hours, 2) 70ͦC every 30 minutes with third extract being sampled. Extracted solutions were analysed by the Elan DRC II model of the Inductively Couple Plasma – Mass Spectrometer (ICP-MS) for the metal contents of Cr, Ni, Al, Fe, Mn, Cu, Zn and Mo. Ammonia gas was used as the reaction gas to precondition the cell in order to avoid polyatomic spectral interferences, plasma gas -Argon. Accuracy of the method was confirmed by the series of calibration standards yielding a linearity coefficient of >0.999 for each element, 90-120% recoveries achieved for the spiking test. QC standards with known concentration were analysed in between batches of samples. LOD for Cr, Ni, Al, Fe, Mn, Cu, Zn and Mo are 0.12ng/L, 0.1ng/L, 0.05ng/L, 0.12ng/L, 0.17ng/L, 0.05ng/L, 0.45ng/L and 0.11ng/L respectively. Migration (mg/kg) was calculated based on sample total surface area of immersion. Results have shown a significant greater amount of metal release from the EU method (24 hours at 22ͦC) than from the in-house method (70ͦC extraction at 30 min interval). Problematic samples containing high metal content exceeding the legal limit are as follows: Cr for bucket (2) exceeds by 409.6%; Ni for basket (8) by 148.6%; Al for bucket (7) by 129.3%; Fe for bucket (5) and (7) by 348.8% and 167% respectively; Mn for bucket (2) by 227.2% and Cu for basket (4) by 162.5%. Contamination of FCMs through the process of metal leaching can results in serious health damage over time. Although the migration represents the worst-case scenario under testing conditions, the level of toxic chemicals would require to be monitored carefully for human health and safety.
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“DEVELOPMENT OF NOVEL ANTICANCER AGENTS TARGETING GLIOBLASTOMA MULTIFORME”
Kate Byrne
School of Food Science and Environmental Health, TU Dublin
Glioblastoma Multiforme (GBM) are among the most aggressive and challenging cancers to treat with an average survival time of only 12-15 months after diagnosis. Notably, there has been no improvement in the 3-5 year survival rate in the last decade. This project aims to build on exciting preliminary results and develop new compounds to improve current GBM treatment strategies. Recently, the anti-cancer properties of Metformin used for type 2 diabetes treatment has been studied. Metformin treatment in combination with Temozolomide (TMZ, the standard GBM chemotherapy) and/or irradiation induced a synergistic anti-tumoral response in glioma cell lines. In proof of concept studies, an in-house compound series with a similar mechanism of action to Metformin, exhibited activity in cancer-cell viability assays. This work shall encompass: 1) Computational techniques to rationally design and optimise these (and other) novel compounds with potential to pass the blood brain barrier. 2) Synthetic chemistry to explore structure activity relationships of this novel compound family in functionally relevant in vitro and ex vivo GBM cancer cell assays. 3) Co-treatment options with TMZ shall also be explored enabling current therapies to be more effective and hence improve patient survival for this aggressive cancer. If successful animal models will be pursued.
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Organising Committee Chairperson: Professor John Cassidy (TU Dublin) Committee: Professor Declan McCormack (TU Dublin) Dr Claire McDonnell (TU Dublin) Dr Eric Moore (UCC/RSC) Dr Darren Griffith (RCSI) Dr David O’Connor (TU Dublin) Dr Eoin McGillicuddy (TU Dublin)
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Sponsors & Exhibitors
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List of Attendees
Surname First Name Affiliation Georgieva Margarita CIT
Cullen Aoibhin DCU Dreschers Alina DCU Fitzgerald Shane DCU
Gkika Karmel DCU McGornan Brionna DCU
Ó’Maolmhuaidh Fionn DCU O'Halloran Sean DCU Ontiveros Karen DCU O'Reilly Stephen DCU Osman Islam DCU Stalcup Apryll DCU
Steplewska Agata DCU Thapa Asmita DCU
Vasquez Mercedes DCU Vickneswaran Mathavan DCU
Zwane Reabetswe DCU Monolakis Ionnas IT Sligo
Barrett Stephen NUI Maynooth D’Arcy Ken NUI Maynooth
Dempsey Eithne NUI Maynooth Elmes Rob NUI Maynooth Halpin Grace NUI Maynooth
Kraemer Tobias NUI Maynooth Marchetti Luke NUI Maynooth
Martin Harlei NUI Maynooth McCaffrey John NUI Maynooth McGuire Kevin NUI Maynooth
Montagner Diego NUI Maynooth Torrijos Trini NUI Maynooth Abdo Amir NUIG
Afoullouss Sam NUIG Ahmed Ahmed NUIG
Aljohani Marwah NUIG Byrne Sylvester NUIG Curran Henry NUIG
Erxleben Andrea NUIG Farras Pau NUIG
Fitzgerald Liam NUIG Lokachari Nitin NUIG
Meany Fiach NUIG
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Surname First Name Affiliation Murphy Paul NUIG Myers Eddie NUIG O'Duill Miriam NUIG Palop Guillermo NUIG
Papatriantafyllopoulou Constantina NUIG Ronconi Luca NUIG Thomas Olivier NUIG Titilas Ioannis NUIG
Alexander Francesca M QUB Cahir John QUB Chen Hungjui QUB Irvine Gavin QUB
Li Chunchun QUB Li Xinyuan QUB
McNeice Peter QUB Qiu Yusheng QUB
Shiels Zara QUB Xie Tianchao QUB Ye Ziwei QUB
Adamo Mauro RCSI Aletto Francesco RCSI Barlow James RCSI
Bencivenni Grazia RCSI Carr James RCSI
Caulfied Cathal RCSI Cioffi Caterina RCSI
Clemente Eva RCSI Curtin Niamh RCSI
Dobricic Marko RCSI Fitzgerald Sheila RCSI Griffith Darren RCSI Heise Andreas RCSI Kelly Graeme RCSI
Marmion Celine RCSI Monks Patricia RCSI
Monopoli Marco RCSI O’Brien Shona RCSI O’Shea Donal RCSI
O'Flaherty Siobhan RCSI Pacifico Roberta RCSI
Ryan Aisling RCSI Stefanovic Smiljana RCSI
Trinh Duong RCSI
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Surname First Name Affiliation Ude Ziga RCSI Wu Dan RCSI
Arora Nidhi TCD Craig Michael TCD
Delente Jason TCD Gulman Martha TCD Lovitt June TCD Lyons Mike TCD Savioli Julia TCD Tandon Swetanshu TCD Byrne Kate TU Dublin, City Campus
Cassidy John TU Dublin, City Campus Colleran John TU Dublin, City Campus
de Carvalho Rafaela TU Dublin, City Campus Hargaden Grainne TU Dublin, City Campus McCarron, Pauraic TU Dublin, City Campus
McCormack Declan TU Dublin, City Campus McDermott Sean TU Dublin, City Campus McDonnell Claire TU Dublin, City Campus
McGillicuddy Eoin TU Dublin, City Campus O'Connor Christine TU Dublin, City Campus O'Connor David TU Dublin, City Campus O'Connor David TU Dublin, City Campus
Perez-Gavilan Ariane TU Dublin, City Campus Sewell Gavin TU Dublin, City Campus Sewell Gavin TU Dublin, City Campus
Sidambaram Prabhakar TU Dublin, City Campus Wojciechowski Bartlomiej TU Dublin, City Campus
Wu Xinyi TU Dublin, City Campus Creaven Bernie TU Dublin, Tallaght Deasy Mary TU Dublin, Tallaght
Fleming Adrienne TU Dublin, Tallaght Hembrecht Adam TU Dublin, Tallaght
Jenkins Hollie TU Dublin, Tallaght Joshi Reeta TU Dublin, Tallaght
Kelleher Fintan TU Dublin, Tallaght McAteer Ronan TU Dublin, Tallaght Mooney Erica TU Dublin, Tallaght Travers Wayne TU Dublin, Tallaght Walsh Maureen TU Dublin, Tallaght Winder Dean TU Dublin, Tallaght
Balbaied Thanih UCC Brouder Thomas UCC
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Surname First Name Affiliation Colman Emma UCC Dennehy Olga UCC Heffernan Eimear UCC Kearney Aoife UCC Kruschel Ryan UCC Lonergan Alex UCC
Lynch Mark UCC Ni Thuama Eilis UCC
O Donoghue Amy UCC O'Mahony Niamh UCC O'Sullivan Niall UCC
Sheehy Kevin UCC Bracken Cormac UCD Bulawa Sandra UCD Connon Robert UCD
Cunningham Laura UCD di Filippo Mara UCD
Doran Alexander UCD Howe Kristy UCD Judge Eric UCD
Kavanagh Saranna UCD Khalifa Aisha UCD Mahon Aine UCD Morais Eduardo UCD Morris Morgan UCD
Mulrooney David UCD Muraca Francesco UCD
O’Loughlin Jennie UCD Owen Benjamin UCD Reid Cian UCD Reid Graham UCD Risse Wilhelm UCD Roche Brendan UCD Sharma Kirti UCD Sullivan James UCD
Zhao Zixu UCD Barrett Stephen UL Bolanta Sharon UL
Cheng Hua Den UL Cywinski Kamil UL D’Arcy Kenneth UL Deng Chenghua UL
Halpin Grace UL
121
Surname First Name Affiliation Hanly Noreen UL
Hannon Adrian UL Haskins Molly UL Kumar Naveen UL Martin Harlei UL
McGrath Fiona UL McGuire Kevin UL O’Connor Siobhan UL O’Hearn Daniel J. UL
Robayo Molina Ivan UL Ryan Kevin M. UL
Soulimane Tewfik UL Wang Shi-Qiang UL
Mareya Tatenda M WIT Tseke Kavnen WIT
