SYNTHESIS, CHARACTERIZATION AND CHELATING PROPERTIES OF METAL COMPLEXES WITH TRANSITION METALS. Purvesh J. Shah

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1 HL ISSN: (print) ISSN: (Online) Coden HLEEAI Vol. 4: (2), 2014, SYNTHESIS, CHARACTERIZATION AND CHELATING PROPERTIES OF METAL COMPLEXES WITH TRANSITION METALS Purvesh J. Shah Department of Chemistry, Shree P.M.Patel Institute of P.G.Studies and research in science, Anand , Affilited to Sardar Patel University, Vallabh Vidyanagar , India - Abstract: The novel ligand ethyl-6-methyl-2-thioxo-4-phenyl-1,2-dihydropyrimidone-5- carboxylate with 5-amino-8-hydroxyquinoline afford a N-(4-hydroxyquinolin-5-yl)-6-methyl-2- thioxo-4-phenyl-1,2-dihydro pyrimidine-5-carboxamide(tpdhq) was synthesized by reaction of ethyl-6-methyl-2-thioxo-4-phenyl-1,2-dihydropyrimidone-5-carboxylate with 5-amino-8- hydroxy quinoline and their various metal complexes were synthesized using Cu 2+,Co 2+, Ni 2+, Mn 2+ and Zn 2+ metal salts. All the novel synthesized complexes were characterized by elemental analysis, molar conductance and spectral studies. The antibacterial and antifungal activities of the ligand and their metal complexes have also been screened. Keywords: Ethyl-6-methyl-2-thioxo-4-phenyl-1,2dihydro pyrimidone-5-carboxylate,5-amino - 8-hydroxy quinoline, metal chelates, spectral studies, antibacterial and antifungal activity. INTRODUCTION Pyrimidone belonging to the heterocyclic system prepared by multiple-component chemical reaction from ethylacetoacetate, an aryl aldehyde and urea are associated with diverse pharmaceutical activities such as antibacterial, insecticidal, fungicidal, antimicrobial, antagonist, anthelmintic, anti-inflamonatary, antiviral, antitumor and antimicrobial agents i-xi etc. The reaction between pyrimidine derivatives with 8-hydroxy quinoline has not been reported so far. Though 8-hydroxy quinoline has excellent antimicrobial effect xii-xvi. Thus this may afford good chelating ligand with better microbicidal activity. Hence it was thought interesting to prepare the ligand having thiopyrimidine-quinoline moieties. Thus the present communication comprises the studies on thiopyrimidine-quinoline combined molecule and its metal chelates. (Figure-1). 215

2 EXPERIMENTAL All the chemicals used were of analytical grade and purified by standard methods prior to use. Ethyl-6-methyl-2-thioxo-4-phenyl-1,2-dihydro pyrimidone-5-carboxylate was prepared by method reported in literature xvii. 5-Amino-8-hydroxy quinoline was prepared by method reported in literature xviii. SYNTHESIS OF N-(4-HYDROXYQUINOLIN-5-YL)-6-METHYL-2-THIOXO-4- PHENYL-1,2-DI HYDRO PYRIMIDINE -5-CARBOXAMIDE (TPDHQ): A mixture of ethyl-6-methyl-2-thioxo-4-phenyl-1,2-dihydropyrimidone-5-carboxylate (PD) (0.015 mole) and 5-Amino-8-hydroxy quinoline (AHQ) (0.015 mole) in ethanol (70 ml) was heated under reflux for 4.5 hrs. Subsequently ethanol was distilled off and the lump mass obtained. It was triturated with petroleum ether (40-60 C). The solid designated as PDHQ was isolated and dried in air. Yield was 84%. It s m.p. was C(uncorrected).Elemental Analysis for C 21 H 16 N 4 O 2 S (388): Calc.(Found): C%,64.93(64.9); H%,4.15(4.1); N%,14.42(14.4), S%, 8.25(8.2).Acid Value (mg KOH/ 1gm sample):calc.(found):196.8(196).ir(kbr,cm -1 ): (OH),3410(Sec.NH),3030,1520,1650 (Aromatic C-H),1638,1575,1560,1475(8-Hydroxy quinoline moiety),1685(co of COOH),1180 (C=S). 1 HNMR(DMSO,ppm): (m,5H,Ar- H), (m,5H,Quinoline),2.1(s,3H,CH 3 );4.1(s,1H, OH); 9.7,2.8(s,1H,NH). SYNTHESIS OF METAL CHELATES OF TPDHQ The Cu 2+,Co 2+, Ni 2+, Mn 2+ and Zn 2+ metal ion chelates of TPDHQ have been prepared in a similar manner. To a solution of TPDHQ (38.8g, 0.1 mole) in ethanol-acetone (1:1v/v) mixture (150 ml), 0.1N KOH solution was added dropwise with stirring. The pasty precipitates were obtained at neutral ph. These were dissolved by addition of water up to clear solution. It was diluted to 250 ml. by water and was known as stock solution. 25 ml of the stock solution (which contains 0.01 mole TPDHQ) was added drop wise to the solution of metal salt in water at room temperature. Sodium acetate or ammonia was added up to complete precipitation. The precipitates were digested on water bath at 80 C for 2 hrs. The digested precipitates of chelates were filtered washed with water and air dried. It was amorphous powder. Yield was almost quantitative. The details are given in Table

3 Compound Table 1. Analytical Data of the Metal Chelates of HL (i.e. TPDHQ) Yield (%) Elemental Analysis C% H% N% S% M% Cald Found Cald Found Cald Found Cald Found Cald Found HL(TPDHQ) (L) 2 Cu (L) 2 Co (L) 2 Ni (L) 2 Mn (L) 2 Zn MEASUREMENTS The elemental analysis for C, H and N were carried out on elemental analyzer TF-EA.1101 (Italy). IR spectra of TPDHQ and its metal complexes were scanned on a Nicolet 760 FTIR spectrophotometer in KBr. The NMR spectrum of TPDHQ was scanned on Brucker NMR spectrophotometer using DMSO solvent. The metal content of the metal chelate were performed by decomposing a weighed amount of each metal complexes followed by EDTA titration as reported in literature xix. Magnetic susceptibility measurement of the entire metal complex was carried out at room temperature by the Gouy method. Mercury tetrathio cynatocobalate (II) Hg[Co(NCS) 4 ] was used as a calibrant. The diffused reflectance spectra of solid metal complex were recorded on a Backman DK Spectrophotometer with a solid reflectance attachment, go was employed as the reflectance compound. The electrical conductivity of all the complexes was measure in acetonitrile at10-3 M concentration. Table 2. Magnetic Moment and Reflectance Spectral data of Metal Chelates Metal chelate Magnetic Moment µ eff (B.M.) Cu-HL Ni-HL Co-HL Mn-HL Zn 2+ Diamagnetic in Nature. Molar Conductivity Ωm ohm -1 cm 2 mol -1 Absorption band (cm -1 ) Transitions C.T 2 T 2 T 2 g 3 A 2 g 3 T 1 g(p) 3 A 1 g 3 T 1 g(f) 4 T 1 g(f) 4 T 2 g(f) 4 T 1 g(f) 3 A 2 g 6 A 1 g 4 T 1 g(4eg) 6 A 1 g 4 T 2 g(4g) 6 A 1 g 4 T 1 g(4g) ANTIBACTERIAL ACTIVITIES Antibacterial activity of TPDHQ ligand and its metal complexes were studied against grampositive bacteria (Bacillus subtilis and Staphylococcus aureus) and gram-negative bacteria (E.coli and Salmonella typhi) at a concentration of 50µg/ml by agar cup plate method. Methanol system was used as control in this method. The area of inhibition of zone measured in mm. The 217

4 antibacterial activity results revealed that the ligand TPDHQ and its metal complexes shows moderate to good activity are presented in Table Table 3. Antibacterial Activities of Ligand TPDHQ (HL) and its metal chelates Zone of Inhibition Gram +Ve Gram Ve Compounds Bacillus Salmonella Staphylococcus aureus subtilis typhi E.coli HL (TPDHQ) (L) 2 Cu (L) 2 Co (L) 2 Ni (L) 2 Mn (L) 2 Zn ANTIFUNGAL ACTIVITY The fungicidal activity of all the compounds was studied at 1000 ppm concentration in vitro plant pathogenic organisms listed in Table 3. The antifungal activities of all the samples were measured by cup plate method xx. Each of the plant pathogenic strains on potato dextrose agar (PDA) medium. Such a PDA medium contained potato 200 gms, dextrose 20gms, agar 20gms and water 1 litre 5 days old cultures were employed. The compounds to be tested were suspended (1000ppm) in a PDA medium and autoclaved at 120 C for 15 min. at 15 atm pressure. These medium were poured into sterile Petri plate and the organisms were inoculated after cooling the Petri plate. The percentage inhabitation for fungi was calculated after 5 days using the formula given below. The fungicidal activity all compounds are shown in Table 4. Percentage of inhibition =100 (1-Y/X) Where, X: Area of colony in control plate Y: Area of colony in test plate. Table 4. Antifungal Activities of Ligand TPDHQ (HL) and its metal chelates Zone of inhibition of fungus at 1000ppm (%) Compounds Aspergillus niger. Nigrospra sp. Penicillium expansum Rhizopus nigricans Trichothesium sp. HL (TPDHQ) (L) 2 Cu (L) 2 Co (L) 2 Ni (L) 2 Mn (L) 2 Zn RESULTS AND DISCUSSION The parent ligand TPDHQ was an amorphous brownish red powder, soluble in various organic solvents like dioxane, DMSO and DMF. The results of elemental analysis of the ligand are reported in experimental part. They are consistent with the predicted structure as shown in Figure-1.

5 Examination of IR spectrum (not shown) of TPDHQ reveals that broad band of phenolic hydroxyl stretching is observed at cm -1 as well as additional absorption bands at 1638,1575,1560,1475 cm -1 are characteristics of the 8-Hydroxy quinoline moiety xxi,xxii. The strong bands at 1685 cm -1 for C=O and band at 3410 cm -1 for sec. NH. The NMR data (shown in experimental part) also confirm the structure of TPDHQ.. The metal chelates of TPDHQ with ions Cu 2+, Co 2+, Ni 2+, Mn 2+ and Zn 2+ vary in colors. On the basis of the proposed structure as shown in Figure-1, the molecular formula of the TPDSA ligand is C 21 H 16 N 4 O 2 S, which upon complexion coordinates with one central metal atom at four coordination sites and with two water molecules. Therefore the general molecular formula of the resulting metal chelate is [C 21 H 15 N 4 O 2 S] 2 M.2H 2 O for divalent metal ions. This has been confirmed by results of elemental analysis reported in Table 1. The data are in agreement with the calculated values. Inspection of the IR Spectra (not shown) of metal chelates reveals that all the spectra are identical in all respects. The comparison of IR spectrum of the parent ligand TPDHQ with that of its each metal chelates has revealed certain characteristics differences. One of the significant differences to be expected between the IR spectrum of the parent ligand and its metal chelates is the presence of more broadened bands in the region of cm -1 for the metal chelates as the oxygen of the O-H group of the ligands forms a coordination bond with the metal ions xxiii,xxiv. This is explained by the fact that water molecule might have strongly absorbed to the metal chelates samples during their formation. Another noticeable difference is that the bands due to the CO at 1730 cm -1 in the IR spectrum of the each metal chelates. The band at 1400 cm -1 in the IR Spectrum of HL assigned to inplane OH determination is shifted towards higher frequency in the spectra of confirmed by a week bands at 1095 cm -1 corresponding to C-O-M xxv. Thus all of these characteristics features of the IR studies suggested the structure of the metal chelates. Examination of data of the metal content in each compound revealed a 1:2 metal:ligand (M:L) stoichiometry in all of the chelate of divalent metal ions. Magnetic moment (µ eff ) of each of the metal chelates is given in Table 2. Examination of these data reveals that all chelates other than that of Zn 2+ are paramagnetic while those of Zn 2+ are diamagnetic. The diffuse electronic spectrum of the [CuHL(H 2 O) 2 ] metal complex shows broad bands at and cm -1 due to the 2 T 2 T 2 g transition and charge transfer, respectively suggesting a distorted octahedral structure xxvi for the [CuHL(H 2 O) 2 ] complex. Which is further confirmed by the higher value of µ eff of the [CuHL(H 2 O) 2 ] complex. The [NiHL(H 2 O) 2 ] and [CoHL(H 2 O) 2 ] complex gave two absorption bands respectively at 15697,22991 and 15378,22723 cm -1 corresponding to 4 T 1 g 2 T 1 g and 4 T 1 g (p) transitions. Thus absorption bands at the diffuse, reflectance spectra and the value of the magnetic moments µ eff indicate and octahedral configuration for the [NiHL(H 2 O) 2 ] and [CuHL(H 2 O) 2 ] complex. The spectra of [MnHL(H 2 O) 2 ] shows weak bands at 15378,17652 and cm -1 assigned to the transitions 6 A 1g 4 T 1g (4G), 6 A 1g 4 T 2g (4G) and 6 A 1g (F) 4 T 1 g, respectively suggesting an octahedral structure for the [MnHL(H 2 O) 2 ] chelate. The high intensities of the bands suggests that they might be charge transfer in origin µ eff is found to be lower than normal range. In the absence of low temperature moments it is difficult to give any significance. As the spectrum of the [ZnHL(H 2 O) 2 ] polymer is not well resolved, it is not interpreted but it is µ eff value shows that it is diamagnetic as expected. 219

6 Conductivities of all the complexes were measured in acetonitrile solvent and all the complexes were found to be electrolytic in nature of 1:2 type and molar conductivity values are in the range of ohm -1 cm 2 mol -1. The antibacterial activity of ligand and its metal complexes shows moderate to good activity against gram positive as well as gram nagetive bacteria. The antifungal activity of all the compounds measured for various plant pathogens. Inspection of the result shown in Table 3 indicates that all compounds are good toxic for fungi. Out of all the compounds copper chelates is more toxic than other. These compounds almost inhibit the fungi approximate 75%. Hence produced metal chelates can be employed as garden fungicides. Further work in the direction is in progress. CONCLUSION In conclusion, a novel N-(4-hydroxyquinolin-5-yl)-6-methyl-2-thioxo-4-phenyl-1,2-dihydro pyrimidine-5-carboxamide (TPDHQ) and its octahedral metal(ii) oxinates (1:2 metal to ligand ratio) were synthesized and characterized. This ligand form metal complexes with 3d Series transition metals. The novel ligand and their metal complexes show moderate to good antibacterial and antifungal activities.this might be due to the additive biological effect of parent molecules and/or due to the metal chelating properties. Reference i. Wistreich, G.A. and Lechtman M.D., Mechanism of Drug Resistance in Microbiology, Macmallan Publishing Company, 5 th Ed.,2004, 299. ii. Al-Thebeiti, M. S., Boll Chim Farm, 2001,140,221. iii. iv. Tozkoparan, B.; Ertan, P.; Kelicen, M. and Demirdamar, R., Farmaco,1999,54,588. Satyavathi, K.; Naga, T.; Kiran, R.; Bhoja Raju, P. and Sharmila, M.,Asian journal of chemistry, 2010, 22(7),5182. v. Rashad, A. E. and Ali, M. A., Nucleosides Nucletides,2006,13,67. vi. Shah, P. J., Oct. Jour. Env. Res.,2013,1(3),205. vii. Dave, C. G.; Shah, D. R.; Shah, G. K.; Pandya, P. S.; Dave, K. C. and Patel, V. J.,Indian J. Pharm Sci., 1986,48,75. viii. Bos, M.; Godel, T.; Reimer, C. and Sleight, A., Eur Pat Appl.,1998,Ep ;Chem Abstr,1998, 128,145382x. ix. Shigeta,S.; Mori,S.; Watanabe,F.; Takahashi, K.; Nagata, T.; Koike, N.; Wakayama, T. and Saneyoshi, M., antivir Chem Chemother.,1997,13, x. El-Gaby, M. S. A.; Abdel-Hamide, S. G.; Ghorab M. M. and El-Sayed, S. M., Acta pharm.,2009, 49, xi. Shah, P.J., International Journal of Chemtech Applications,2013,2(2),103. xii. Greenberg, J.; Turesky, S.S. and Warner, V.D., J. Periodontol,1976,47(11),664. xiii. Philips, J. P., The Reactions of 8-Quinolinol, Chem. Review,1956,56(2),271. xiv. Patel D.K. and Singh, A., E-Journal of Chemistry,2009,6(4),1017. xv. Block,S. S., Fungitoxicity of 8-Quinolinols,1955,3,229. xvi. Mohsen A. and Shawkat, A., J. of Chinese Chem. Soc,2003,50(5),1085. xvii. Biginelli, P., Ber,1891,24,1317 & xviii. Belov A.V. and Nichvoloda, V.M., Russian Journal of Organic Chemistry,2004,40(1),93. xix. Jeffery, G. H.; Bassett, J.; Mentham, J. and Denney, R. C., Vogel s Text Book of Quantitative Inorganic Analysis, Longman, Harlow,6 th Ed.,1989,

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