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Effect of precursor chemical composition on the formation and stability ofG-quadruplex core supramolecular star polymers†

Ikhlas Gadwal,a Swati De,a Mihaiela C. Stuparub and Anzar Khan*a

Received 27th May 2012, Accepted 6th July 2012

DOI: 10.1039/c2py20371e

A homologous series of guanosine end-functional poly(butadiene)s has been prepared. The potassium

cation-templated assembly of these guanosine functionalised precursors then furnished supramolecular

star polymers with a G-quadruplex core. Comparison with the previously reported poly(ethylene

glycol)-based supramolecular star polymers revealed that in designing supramolecular star polymers,

chemically non-polar assembly precursors – that do not interfere with the supramolecular interactions

of the core – are essential for the preparation of high stability and high molecular weight

supramolecular branched architectures. In addition, in comparison to star polymers composed of

chemically polar polymer chains, the non-polar supramolecular ensembles show chain-length

independent properties.

Introduction

Supramolecular star polymers are branched polymer architec-

tures in which the branches radiate from a core that is formed via

non-covalent bonding. Various non-covalent interactions

including hydrogen bonding, inclusion complex formation,

metal–ligand coordination, pseudorotaxane complexation, and

G-quadruplex formation have been employed to prepare

supramolecular star polymers consisting of 3–8 polymer

chains.1–9 The G-quadruplex formation10,11 from guanosine end-

functional polymeric precursors is an attractive motif for

supramolecular star polymer synthesis due to its capacity to

assemble a large number of polymer chains. In this context,

chemically homogeneous8,9 and heterogeneous7 star polymers

have been prepared. Interestingly, in the case of poly(ethylene

glycol)-based stars,8 we suggested that the chemical nature of the

repeat unit influences the supramolecular interactions of the

core,12 and chain-length dependent properties are observed.8

This motivated us to prepare star polymers composed of chem-

ically non-polar chains that do not interfere with the supramo-

lecular interactions of the polymer core. We envisaged that such

a system would provide a comparison with the poly(ethylene

glycol)-based star polymers and shed light on the effect of the

chemical composition of the precursor on the formation and

stability of the star polymers. For this purpose, we prepared a

aDepartment of Materials, ETH-Z€urich, CH-8093 Z€urich, Switzerland.E-mail: anzar.khan@mat.ethz.ch; Fax: +41446331390; Tel:+414463366474bInstitute of Organic Chemistry, University of Z€urich, CH-8057 Z€urich,Switzerland

† Electronic supplementary information (ESI) available: Synthesisdetails, characterization, and the properties data (Fig. S1–S10) areprovided. See DOI: 10.1039/c2py20371e

This journal is ª The Royal Society of Chemistry 2012

homologous series of guanosine end-functional butadiene poly-

mers (n ¼ 18, 37, 81, 185) and carried out a systematic study on

their potassium cation-templated assembling properties (Fig. 1).

The results reveal that star polymers prepared via assembly of

chemically non-polar polymer chains show much higher stabili-

ties and chain-length independent properties when compared to

star polymers formed from assembly precursors capable of

destabilizing the supramolecular core.

Fig. 1 Chemical and cartoon representation of a free polymeric

precursor end-functionalized with a guanosine molecule (left) and a

potassium-templated assembly of this precursor into a star polymer

composed of 8 polymer chains (right). The anion remains at the complex

periphery and is not shown.

Polym. Chem., 2012, 3, 2615–2618 | 2615

Scheme 1 Synthesis of the guanosine chain-end functional polymer precursors 1, 2, 3, and 4.

Fig. 3 Variable-temperature 1H NMR (500 MHz) spectra of 18.K+

in CDCl3.

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Results and discussion

The synthesis of polymeric precursors 1, 2, 3, and 4 was

accomplished via an esterification reaction between hydroxy-

terminated polybutadienes (PBD) (n ¼ 18, 37, 81, 185) and

guanosine acid (Scheme 1).13

Building blocks 1 (n ¼ 18), 2 (n ¼ 37), 3 (n ¼ 81), and 4 (n ¼185) show well-defined proton signals in CDCl3 (Fig. 2 and S1–

S3†). Noteworthy are the sharp signals from the amide (;NH)

and the amine (-NH2) protons at 12.07 and 6.14 ppm,

respectively. Addition of 0.125 equivalents of KI (8 : 1 ratio of

the polymer precursor to the potassium ion) to the chloroform

solution of 1, 2, 3, and 4 results in a downfield shift of the amide

proton (;NH) to 12.33 ppm (Fig. 2). As expected for a hydrogen

bonded cyclic quartet, the amine protons split into two signals;

one is hydrogen bonded and hence shifts downfield to 9.43 ppm

(,NH, Fig. 3) while the other is free and shifts upfield to 6.1

ppm (-NH, Fig. 3). These signals are very weak at room

temperature due to the fast rotation of the amine protons around

the C–N bond, however, at low temperatures (0 �C to �20 �C,Fig. 3 and Fig. S4–S5†), the amine protons exchange slowly on

the NMR time scale and hence signals of a relatively high

intensity can be observed. Furthermore, the CH proton (BCH,

Fig. 2 and 3) of the heterocyclic ring shows a pronounced upfield

shift to 7.17 ppm in a templated-assembly process, presumably

due to the aromatic stacking interactions. The singlet from the

amide proton suggests formation of an octameric assembly in all

cases. Even the highest molecular weight assembly precursor 4

(n ¼ 185, Mw ¼ �10 kDa) completely converted into 48.K+ star

Fig. 2 1HNMR (500MHz) spectra of precursor polymers 1 (A) and star poly

an internal standard. Solvent signals are shown with a cross sign.

2616 | Polym. Chem., 2012, 3, 2615–2618

with a calculated molecular weight of 80 kDa. Preparation of

such high molecular weight supramolecular structures remains a

challenge and points towards the broad scope of the present

strategy in the synthesis of supramolecular star polymers.

UV-Vis spectroscopy of all systems exhibited absorption

maxima around 255 nm (Fig. 4 and S6†). A marked difference in

the UV-Vis spectra of the free polymer precursors and their

mer 18.K+ (B) in CDCl3 (1.25 mM). Tetramethylsilane (TMS) was used as

This journal is ª The Royal Society of Chemistry 2012

Fig. 4 UV-Vis spectra of 1 as a solid line and 18.K+ as a dashed line in

chloroform (0.07 mM).

Fig. 5 CD spectra of 18.K+ (dash), 28.K

+ (dot), 38.K+ (dash–dot), and

48.K+ (dash–dot–dot) in chloroform (0.07 mM).

Fig. 6 1H NMR (500 MHz) spectra of 18.K+ upon addition of DMSO-

d6 in CDCl3. TMS was used as an internal standard.

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respective star polymers can be observed at 270–280 nm at which

the assemblies show significant reduction in the absorption

intensity, and at 295 nm at which the assemblies show a new

absorption band, presumably due to a specific stacked arrange-

ment of the aromatic units in the G-quadruplex core.14

To investigate the stereochemical nature of the star polymers

formed, circular dichroism (CD) spectroscopy was employed

(Fig. 5). All of the branched systems (18.K+, 28.K

+, 38.K+, 48.K

+)

exhibit typical exciton couplets with two bands of opposite signs

at 265 and 290 nm, where lmax in absorption (250 nm) corre-

sponds to zero CD intensity.15 This feature is diagnostic of a

heteropolar (D4-symmetric) stacked chiral arrangement of the

heterocyclic guanine chromophores of the supramolecular

octamer.16 As expected, the precursor polymer chains 1, 2, 3, and

4 do not exhibit any CD signal in the range 250–320 nm (region

of guanine absorption) due to the absence of any supramolecular

chiral structure.

Temperature-dependent NMR spectroscopy was then used to

study the thermal stability of the supramolecular polymers

This journal is ª The Royal Society of Chemistry 2012

(Fig. 3 and S4–S5†). The 18.K+, 28.K

+, and 38.K+ star polymers

behaved in a similar fashion and showed no sign of disintegration

even at 70 �C as judged by their heterocyclic CH (BCH) and the

amide proton (;NH) signals.17 In comparison, PEG-based star

polymers showed a chain-length dependent disintegration

behavior at a lower temperature range of 40–60 �C.8

Previous studies have shown the sensitivity of the supramo-

lecular star polymer to dilution.7,8 For example, PEG-based stars

were found to be stable at a concentration range of 0.6–0.1 mM

depending upon the chain length of the assembly precursor.8 In

contrast, the PBD-stars did not show any sensitivity to dilution

and were stable at the investigated range of 0.6–0.017 mM

(Fig. S7–S10†). Moreover, both of the systems behaved in a

similar fashion.

To examine the relative stabilities of the supramolecular stars

towards polar solvents, mixed solvent studies were carried out.

This was accomplished by gradual addition of DMSO to the

chloroform solution of 18.K+ and 28.K

+ (Fig. 6 and S11–S12†).

From these experiments, it became clear that 20% DMSO

addition is required to completely break 18.K+, 28.K

+, and 38.K+

star polymers into their precursors. This was in contrast to the

PEG-based stars that showed chain-length dependent sensitivity

to polar solvents in a range of 5–15% DMSO addition.8

Conclusions

In designing star polymers with a G-quadruplex core, chemically

non-polar assembly precursors – that do not interfere with the

supramolecular interactions of the core – are essential for the

preparation of high stability and high molecular weight supra-

molecular branched architectures. In comparison to PEG-based

star polymers, the non-polar supramolecular stars show higher

stabilities and chain-length independent properties.

AK would like to thank A. D. Schl€uter (ETH) for his financial

and moral support. Financial support from the Swiss National

Science Foundation (SNSF) is gratefully acknowledged.

Notes and references

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13 Please see the ESI† for the characterization and MALDI-TOF massanalysis.

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17 Sample 48.K+ was found to become insoluble within a period of few

days after synthesis. This is most likely due to the chemicalcrosslinking between the pendent olefins.

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