Indi an 10urnal of Chemi stry Vol. 40A, September 200 1. pp. 989-993

Template synthesis, spectroscopic studies and biological screening of macrocycIic

complexes of lead(II)

Anil Bansal & R V Singh*

Department of Chemi stry, University of Rajasthan Jaipu r 302 004, India

Received 29 August 2000; revised 2 Jall uary 2001

A new series of macrocyc li c lead( II ) complexes of the type [Pb(macn)X2) (X = CI. NO) or OAc) has been prepared by the condensati on reactions of maloni c acid. succi nic acid or adipic acid with diethylenetriamine in the presence of lead ions as tem­plates in methanol medium. The complexes have been character­ized on the basis of elemental analyses. molecular weight deter­minati ons. IR and IH NMR spectral studies. as well as conduct iv­ity data. All the complexes have octahedral structure. The bi olog i­cal activi ties of all the lead salts and their metal complexes have been tested ill vitro agai nst a number of pathogenic fungi and bacteria to assess their growth inhibiting potential.

The design and study of well arranged metal contai ning macrocycles is one of the major current research areas in supramolecular chemistr/ . Apart from their particular structural features, supramolecul ar speci es formed by self-assembly of transition metal s introduce many special functional properties such as luminescence2

, redox activi ty3, and magnet ism4 into the structure. More recently , transition metal based molecuiar squares have been synthesized by utiJizing self- assembly of preorganized metal centers and pyridine based bridging ligands2

.5

. However, there are only a few reported examples of self-assembly molecular squares based on an octahedral geometry at the metal centre2

.6

.

Macrocyc les with delocalized structures have 'also attracted attention as components of molecular electronic devi ces, as building blocks of electroactive networks, and for their molecular recogn ition

. 7 properties.

Supramolecular chemistry, se lf-assembly , inclusion phenomena, molecul ar recognition and non-cova lent interactions are at the forefront of modern chemi st ry. These phenomena are commonly accessed by various macrocyclic and related assemblies. Diverse macrocycles and hosts such as crown ether, cyclophanes. cryptands, molecular clefts , and like species are well known8

. The great majority of these

macrocycles are orgal11c molecules that are conformationally reasonably flexible and preferentially interact with cationic guests8

. Much less is known , however, about inorganic or organometallic macrocycles.

Macrocyclic ligands have been shown to form very stable complexes with alkali and alkaline earth metal cations. These complexes can be used as model s for investigations of ion transport through membranes in biological systems. Saturated macrocycles wi th different number of rings have been synthesized and interesting information concerning both the stabilities and structure of their metal complexes has been reported9

. Macrocyclic ionophores can also bind anions and small neutral organic molecules 10 . The initial design of macrocycles focused on the simple ether and amine donors that were essential for efficient substrate binding. From thi s point of view, metal ion complexes of ionophores can be considered as host-guest complexes in which the guest entity is of spherical shape and entrapped in a cavity-like structure formed by the cyclic host molecul es.

The synthesis of some of new lead(lI) complexes of twenty to twenty six membered macrocycles by the reactions of diethylenetriamine with dicarboxyl ic acids, their structure el uc idation and biologi cal screening are reported in thi s communication.

Experimental Diethyl enetriamine, malonic acid, succ ini c acid

and ad ipic acid (Fluka) were used as received without further purifi cation. The lead salts , PbC I2, Pb( 0 3h and Pb(OAch3 H20 , were used as such . All the solvents used were of high purity and distill ed in the laboratory before use. Moisture was excluded from the g lass apparatus using CaCh guard tubes.

I H NMR spectra were obtained in DMSO-d6 usi ng a l eOL FX 90Q spectrometer w ith Me4Si as an internal standard. Chemical sh ifts are reported in ppm units . Molecul ar weights were determined by the Rast Camphor M ethod II. IR spectra were recorded as KBr discs, using a Nicolet Megna FTlR-550 spectropho tometer and conductivity measurements were calTied out in 1O·3M dimethylformamide

solutions at 25°C using a Systronic Type 305 Conductivity Bridge. Lead was estimated as lead

990 INDIAN 1. CHEM. , SEC A, SEPTEMBER 200 1

sulphate. Nitrogen and chlorine were determined by Kjeldahl 's and Volhard's methods, respectivel/ 2.

Synthesis of camp/exes Weighed amollnt of PbCh ( 1.0 ISS-1.1709g),

Pb(NO})2 (1.2142-1.2778g) or Pb(OAch3H20 (1.2 I 82-1.2S03g) was added to the calculated amounts of malonic acid (0.680S-0.8762g),succinic acid (0.778S-0.9112g) or adipic acid (0.9385-1.2062g) and diethylenetriamine (0.662S-0.8687g) in 1 :2:2 molar ratio using dry MeOH(50 ml) as the reaction medium. The resulting mixture was stirred for 7-9 hr. The contents were kept at room temperature for 12 hr, resulting in the formation of crystalline compounds. The products were repeatedly washed with methanol so as to assure their purity and dried. These compounds were recrystallized from benzene and dried again ill vacuo. Their important properties and analytical data are given in Table I.

Results and discussion The elemental analysis and spectral data suggested

the formation of macrocyclic complexes [Pb(Macn)X2]. A proposed scheme of synthetic route for macrocyclic complexes is g iven in Scheme 1.

The resulting complexes are coloured solids, having high melting points. These complexes are only slightly solubl e in common organic solvents, but soluble in DMF and DMSO without change in colour. The low molar conductance value of all the

compounds indicate that they are non-electrolytes in DMF. The monomeric nature of these complexes is confirmed by molecular weight determinations (Table l) .

In the infrared spectra of all the complexes a single peak is observed in the region 3209-3240 cm-' which

may be assigned to v(NH) of amide group or secondary amino group of the diethylenetri amine moiety, which is found to be negatively shifted in comparison to that of the metal-free ligand 13. This information along with the absence of primary amino and hydroxyl groups reveals that cyclization has taken place. In the spectra of all the complexes the appearance of new bands in the 1666-1705 , 1496-

~ MeOH

x = CI, NO.) or Oac [Pb(mac,)X2]; n = I [Pb(mac2)X2J ; n =2

[Pb(mac, )X21; n =4

Scheme 1

Tab le I - Phy s ica l properties a nd a na ly tical data of th e lead(ll) complexes

C o mp o un d and P hys ic a l C ha ra c te ri s ti cs Ana lysi s Found (Calcd) % Mol.wt.

E mpirical Fo rmula Colo ur M.p . (OC) Yield ( % ) N Pb CI Fo und (Ca lcd)

[Pb(mac, )C I21 White 160 62 13.14 32 .89 11.01 597.89

C , ~ H 26N 60~ C1 2 Pb ( 13 .54) (33.39) ( 11. 43) (620 .50)

[Pb( mac 2)C l2J Light 177 56 12 .57 3 1.44 10.55 636 .22

C' 6 H ,oN 60~CI 2 Pb Yellow ( 12 .96) (3 1. 95) (10.9 3 ) (648.56)

[Pb(mac ) C I2J Light 189 49 11.5 3 28 .91 9.62 680.73

C 2o H '8 N 60~C1 2 Pb Browh (11.93) (29.40) (10 .06) (704.66)

[Pb(mac, )(NO.Jh l Cream 228 53 16 . 17 30.28 652 .96

C '4 HU, NgO, oPb (16.64) (30. 7 6) (673.60)

[Pb( mac 2)(NO.1h l Yell o w 210d 65 15.56 29 .05 684.96

C' 6HJo NgO, oPb ( 15 .97) (29.53) (70 1.66)

IPb(mac,)( NO .\ )2] C ream 241 46 14 .36 26 .8 7 738.47

C 2o H.Js NgO, oPb (14. 79) (2 7 .34) (757 .7 6)

[Pb ( mac, )(OAc h ] Li gh t 205 58 12.16 30.52 642 .8 1

C !R HJ2 N r, O gPb Brown (12.59) (3 1.03 ) (667.69)

I Pb( ma c 2)( OAc h l Light 215 SO 11. 64 29 .3 1 674.25

C 2o H .J6N r, O gPb Yellow ( 12.08) (29 .78) (695.74)

[ Pb (mac , )(OAc h l Dark 208d 61 10 .78 27 . 10 734.10 C 24 H44N60gPb Brow n (11.18) (2 7 .56) (751.84 )

NOTES 99 1

1524, 1237-1269 and 648-680 cm-I regions assignable to amide I, amide II , amide III and amide IV in-plane deformation vibrations, respectively 14, further suggested the formation of macrocyclic complexes. The presence of bands around 413-450 cm-I is due to v(Pb-N) vibration which unequivocally supports the coordination of the amide nitrogen to the metal ion . rn the spectra of lead nitrate complexes bands around 1240, 982 and 870 cm-I are in agreement with the monodentate nature of the nitrato group.

The proton magnetic resonance spectra of the ligands as well as the corresponding metal complexes have been recorded in DMSO-d6 using TMS as the internal standard . In the spectra of free di amines and dicarboxyli c ac ids, proton resonance signals due to -NH2 and - OH groups were observed, which di sappeared completely in the spectra of lead complexes indicating condensation and formation of macrocyclic complexes. All the complexes show a broad signal in the 88.07-8.25 ppm region , which may be ass igned to the four equi valent amide protons (CO­NH ). Similar data have been reported by several authors l5

.16 showing the presence of NH group in the

macrocyclic ring. A multiplet observed in the 82.90-3.05 ppm region is ass ignable to the methylene protons (C-CH2-N-) nearer to the secondary amino protons of the diethylenetriamine port ion. Another

multiplet at 86. 15-6.30 ppm corresponds to the secondary amino protons (C-NH-C) of the amine moiety . However, singlets in the regions 83 .24-3.38 and 83. 18-3.26 ppm and a multiplet in the region 83.07-3.15 ppm were observed for the respective complexes [Pb(mac ,)X2], [Pb(mac2) X2] and [Pb(mac3)X2], which can be assigned to CO-CHrCO, CO-(CH2h-CO and CO-(CH2)4-CO protons, respectively. According to the above interpretation we can say that the ligands act as tetradentate chelati ng agents having four coordinating sites. Secondly, since the anions CI, NO) and OAc remained bonded with the metal atom, a hexacoordinated environment around the lead atom seems to be reasonable.

Biological screening The food poison technique was used to check the

acti vity against fungi. The antifungal acti vities were evaluated against Fusarium oxysporu/ll and Alternaria altemata by the agar plate technique l7

. The compounds were directly mixed with the mediu m in di fferent concentrations. The fungus was placed on the medium with the help of an inoculum needl e. The Petri dishes were wrapped in polythene bags, contai ning some drops of alcohol and were placed in an incubator at 30±1 °C. The control s were also run and three replicates were used in each case. The linear

Table 2 - Ant ifunga l ac t ivit y of lead ( II ) macrocyc li c co mp lexes

Average pe rce nt age of inh ib it ion afte r 96h (c o nc . in ppm )

Co mpo und F usa r i ulII oxyspo rulII A /l ema r ia a /l em ala

125 200 250 125 200 250

Standard (Bavist in) 90 100 100 82 100 100

PbC I2 71 75 77 68 66 74

Pb(NO) h 80 88 92 74 70 76

Pb(OAc )2· 3 H20 63 63 69 63 65 68

HOOC-CH 2-COO H 48 54 58 46 50 54

HOOC -(C H2h- COOH 43 47 50 45 48 51

HOOC-(C H2kCOOH 40 44 47 42 45 49

NH 2-CH r C Hr H-C Hr C H1-NH l 46 49 5 1 43 47 50

[Pb( mac l)C I11 56 59 64 59 61 65

[Pb( mac l )CI 21 53 57 63 56 59 63

[Pb( lllac »)C I21 55 60 6 1 53 57 62

[Pb( mac Il( N0 3 h l 58 62 65 49 55 60

[Pb( mac 2)( NO )h l 54 56 59 60 64 67

[Pb( ma c J )( N 0 3 )2] 50 58 60 55 57 61

[Pb( mac I )(OAc)21 60 62 65 58 60 65

IPb( mac 2)( OA chl 52 59 63 6 1 65 66

[Pb(mac .ll(OAch l 50 56 62 52 58 60

992 INDIAN 1. CHEM ., SEC A, SEPTEMBER 200 1

Table 3 - Antibacterial activity of lead (II) macrocycl ic complexes

Di a me te r ( mm ) of inhibiti o n zo ne after 24h (co nc. i n ppm)

Co m po und Staphy lococcus a I/reus (+ ) Es cheri chia coli (-)

S ta nda rd (St rep tomyc in )

Pb C l1

Pb(N03h Pb(OAc) ~ . 3 H ~O

HOOC-C H]-COOH

HOOC-(C Hlh-COO H

HOOC-(CH])4-COO H

N H2-C H 1-CH 2-N H- C HrCH rN H 2

[Pb ( mac l)C I21

[P b( m ac~)C l l 1

[Pb( ll1 ac 3)C I11 [Pb ( ll1ac l )(N03)21

I Pb( mac ])( N03h l

[Pb( mac 3)(N03h l

[Pb(ll1acd (OAc )] l

[Pb ( ma c])(OAch l

I Pb ( ll1a c 1)(OAchJ

500

15

8

9

6

3

5

4

3

6

7

5

6

8

7

4

6

5

growth of the fungus was obtained by measuring the fungal colony diameter after 96 hr. The amount of growth inhibition was calculated by the equation, % inhibition = (C-T) x 100/C, where, C = di ameter of funga l colony in control plate and T = diameter of fungal colony in tes t pl ate.

The activity against bacteria was evaluated by paper di sc plate method t8

• For thi s purpose nutrient agar medium [peptone, beef extract, NaCI and agar­agar and 5 mm diameter paper di scs (Whatman No.1)] were used. All the compounds di ssolved in DMSO and diluted with distilled water in 500 and 1000 ppm concentrations. Paper di scs of Whatman No.1 with a diameter of 5 mm were soaked in these solutions. These discs were dried and then placed in the medium previously seeded with test organism in Petri dishes at suitable di stances . The Petri di shes were stored in an incubator at 30±2°C for 24-30 hr. The zone of inhibition thus formed around each disc containing the test compound was measured accurately. The results of these studi es have been given in Tables 2 and 3.

The degradative enzy mes produced by microorganism are important in host infection , food deterioration and break down of organic matter19

• The metal chelates inhibit the growth of microorganism. It is assumed that production of the ·enzymes is affected as the microorgani sms is unable to utilize food for

1000 500 1000

17 17 18

10 10 12

II II 13

9 7 10

5 4 6

6 6 7

5 5 7

5 4 6

9 8 [0

10 9 I I

7 6 9

8 8 10

9 7 8

10 6 I I

7 5 8

8 6 8

6 6 9

itself, or intake of nutrient decreases and consequently growth ceases. Further, the results of biocidal activity have been compared with the conventional fungicide, bavistin and the conventional bactericide streptomycin as standards. The results of the antifungal activity indicated that the metal chelates are more active than their parent diamine and dicarboxylic ac ids but less active than the respective metal salts. In case of antibacterial activity the metal chelates, diamine, dicarboxylic acids and respective metal salts showed similar type of behaviour as indicated in case of antifungal activity .

Acknowledgement The authors are thankful to h1e Council of

Scientific and Industrial Research, New Delhi for the financ ial assistance.

References Fujita M & Ogura K, 8ul/ cllelll Soc Japan, 69 ( 1996) 147 1 and references there in .

2 Belanger S, Hupp 1 T, Stern C L. Slo ne R V, Watsen D F. Carrell T G, J Alii chelll Soc, 121 ( 1999) 557 .

3 Mc Quillan F S, Berridge T E, Chen H. Hamor T A & Jones C J. Illorg Chelll . 37 (1998) 4959.

4 Solari E. Lesueur W, Klose A. Schenk K. Flos iani C. Ch ies i­Villa A & Kizzoli C, Chelll COIIIIIIUII , ( 1996). 807.

5 Stang PJ , Fan J & Oleyuk B, Ace chelll Res. 30 ( 1997) 502. 6 Fujita M, Knon Y J. Washi zu S & Og ura K J. J Alii chem Soc.

I 16 (1994) I I 5 I.

NOTES 993

7 (a) Bi sse ll R A. Cordova E, Ka ifer A E. Stoddart J F, Natl/re, 133 ( 1994) 369. (b) Bunz UH F. AI/ gew Chem II/t, Ed Engl , 33 ( 1994) 1073.

8 Vogtle F, Cyc/ophane chemistry (John Wiley & Sons, Chich­es ter), 1993.

9 Fuji wara M, Watika H, Matsushita T & Shono T, BI/ll chem Soc Japal/ , 63 (1990) 3443.

10 Black D St C. Horsham M A & Rose M, Tetrahedrol/ , 51 ( 1995),48 19.

II Vogel A I, A text-book of practical orgal/ic chemistry, 4th Edition (Longmans. ELBS London), 1978,232.

12 Vogel A I, A text-book of inorganic analysis (Longmans, Green and Co , London), 1968.

13 Cook D H & Fenton D E. lnorg chim Acta. 25 ( 1977 ) L95. 14 Pandey U K, Pandey 0 P. Sengupta S K & T ripathi S C,

Polyhedron, 6 ( 1987) 1611 . 15 Woon T C & Fa irlie D P, Inorg Chem, 3 1 ( 1992) 4069. 16 Tabushi I, Taniguchi Y & Kato H, Tetrahedron Leu, 12

(1977) 1049. 17 Horsfall J G, Bot Rev. 419 (1945). 18 Thornberry H H, Phytopathology, 40 (1 950) 4 19. 19 Hamkin L & Anagnostaki s S L, Mycologia, 67 ( 1975 ) 597.