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194 943-1-pb (1)


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194 943-1-pb (1)

  1. 1. J Trends Chem 2011 2(1): 9-14 Journal of Trends & Chemistry Orjinal Article Synthesis, Characterizations & Biological Activity of Transition Metal Ion Co(II) with Amino Acids & 2-substituted Benzothiazoles Premlata, Suman Verma, Gita Seth Department of Chemistry, University of Rajasthan, Jaipur (Rajasthan) Received: 15.03.2011 Accepted: 11.04.2011 Published: 29.6.2011AbstractSome new ternary complexes of Co(II) with 2-substituted benzothiazole ligands {2-(2’-aminophenyl) benzothiazole, 2-(2’-hydroxyphenyl)benzothiazole, 2-(2’-merceptophenyl) benzothiazole} as primary ligands & with some amino acids (leucine & isoleucine) were synthesized& characterized. Structure of the synthesized complexes was established on the basis of IR, 1H NMR & elemental analysis.Key words: 2-substituted Benzothiazole, Antifungal & Antibacterial Activity* Corresponding Author: G.Seth , e-mail: INTRODUCTION Benzothiazoles are found to be antimicrobial (Magdolen end groups are well known pharmaceutical substanceet al. 2000; Rajeeva et al. 2009), antifungal (Pattan et al. (Kashiyama et al. 1999).2002; Ameya et al. 2007; Bujdakova et al. 1994) & antiviral In this study, we report the synthesis, characterization &(Srinivasan et al. 2003) activity. 2-Substituted biological activity of Co(II) ternary complexes derived fromBenzothiazoles are also the heterocyclic system that have 2-substituted benzothiazole viz. 2-(2´-aminophenyl)been found to exhibit diversal biological activities such as benzothiazole (APBT), 2-(2´-hydroxyphenyl) benzothiazolecentral nervous system depressant (Paranashivappa et al. (HPBT), 2-(2´-merceptophenyl) benzothiazole (MPBT) and2003), antitumor (Geoffrg Wells et al. 2000), Antileishmanial amino acid viz. Leucine (Leu), Isoleucine (Ileu). The structure(Delmas et al. 2004), Anticancer (Kok et al. 2008; Bhuva et of ligands used, to synthesize the Co (II) ternary complexesal. 2010), Antibacterial (Pattan et al. 2002; Javed et al. 2004). are presented in Fig. 1 The survey of literature related to benzothiazolesderivatives having conjugated system with donor & acceptor A©ademy Journals 2011
  2. 2. J Trends Chem 2011 2(1): 9-14 Premleta et al. S H2N CH C OH N O R XH APBT HPBT MPBT Leucine Isoleucine X NH O S R CH2-CH(CH3)2 CH3-CH-CH2-CH3 Figure 1 Structure of the ligands APBT, HPBT, MPBT, Leucine, Isoleucine MATERIAL AND METHODS The 2-substituted benzothiazoles viz. 2-(2´-aminophenyl) benzothiazole (APBT), 2-(2´-hydroxyphenyl) benzothiazole Materials (HPBT) and 2-(2´-merceptophenyl) benzothiazole (MPBT) All the solvent were distilled perior to use, o-amino were prepared by reported method in literature (Hein et al.thiophenol, anthranilic acid, salicyclic acid thiosalicylic acid 1957).& COCl2.6H2O were purchased from Merck and use as such. Preparation of cobalt (II) ternary complex Physical Measurements A solution of COCl2.6H2O (0.059 g, 0.01 mol) in dry Microanalysis were carried out at the CDRI Lucknow, EtOH (25 ml) was added to APBT (0.056 g, 0.01 mol)/HPBTIndia, melting point were determined on a capillary melting (0.0568 g, 0.01 mol)/MPBT (0.060 g, 0.01 mol) and Leucinepoint apparatus and are uncorrected, IR spectra was recorded (0.032 g, 0.01 mole)/Isoleucine (0.0327 g, 0.01 mol) in dry(with KBr pellets) on a Shimadzu 8400 FTIR EtOH (25 ml). The reaction mixture was then refluxed in theSpectrophotometer. presence of a drop of pyridine with constant stirring for 4h, 1 H NMR data were recorded on JEOL AL 300 MHz FT and allowed to stand at room temperature overnight. TheseNMR spectrometer in CDCl3 using TMS as an internal were filtered, recrystallized from EtOH and dried in vacuo.reference. Molecular weight was determined by the Rastcampher method. Nitrogen was determined by the Kjeldhalmethod, and sulfur was estimated by the messenger’s method. RESULTS AND DISCUSSIONChlorine was estimated volumetrically by using Volhardmethod. Cobalt was estimated by gravimetrically. The Co(II) ternary complexes was synthesized by CoCl2.6H2O with 2-substituted benzothiazoles (APBT, Synthesis of 2-substituted benzothiazoles (APBT, MPBT, MPBT) or amino acids (Leu & Ileu) in 1:1:1 molarHPBT, MPBT) ratio according to the following equations. COCl2.6H2O + (L-L) + (A-A) Ethanol [ CoCl(L-L)(A-A)(H2O)] Reflux CoCl2.6H2O + (L-L´) + (A-A) Ethanol [CoCl(L-L´)(A-A)(H2O)2] Reflux L-L APBT L-L´ HPBT, MPBT and A-A Leu, Ileu 10 A©ademy Journals 2011
  3. 3. J Trends Chem 2011 2(1): 9-14 Premleta et al. These reactions processed easily and lead to the The analytical data & physical properties of the ligands formation of coloured solids, which are stable to air & and their Co(II) ternary complexes are given in Table-1. The moisture. The resulting Co(II) ternary complexes are soluble compounds have been characterized on the basis of following in methenol & ethanol, DMSO & DMF. studiesTable 1 Analytical data & physical properties of 2-substituted benzothiazoles and their Co(II) complexes with Leucine &Isoleucine Compd. & empirical Colour Yield M.P. Elemental analysis found Molecular formula (%) (°C) (Calcd.) weight Found (Calcd.) C H N S Cl Co 1. APBT C13H10N2S Light 68 128 69.01 4.45 12.37 14.6 - - 226.30 Yellow 2. HPBT C13H9NOS Cremish 66 131 68.72 3.96 6.61 14.11 - - 227.28 3. MPBT C13H9NS2 Ash 65 130 64.18 3.69 5.75 28.36 - 243.25 Green 4. [CoCl(APBT)(Leu)(H2O)] Light 54 228 48.67 5.15 8.95 6.84 7.57 12.57 468.81 CoC19H24O3N3SCl Blue 5. [CoCl(APBT)(Ileu)(H2O)] Light 52 232 48.67 5.15 8.95 6.84 7.57 12.57 468.81 CoC19H24O3N3SCl Blue 6. [Co(HPBT)(Leu)(H2O)2] Pinkish 58 235 50.56 5.35 6.20 7.10 - 13.05 451.29 CoC19H24O5N2S Blue 7. [Co(HPBT)(Ileu)(H2O)2] Pinkish 56 240 50.56 5.35 6.20 7.10 - 13.05 451.29 CoC19H24O5N2S Blue 8. [Co(MPBT)(Leu)(H2O)2] Purple 59 245 48.82 5.16 6.00 13.71 - 12.60 467.36 CoC19H24O4N2S2 Blue 9. [CoCl(MPBT)(Ileu)(H2O)2] Violet 60 251 48.82 5.16 6.00 13.71 - 12.60 467.36 CoC19H24O4N2S2 Blue complexes, suggesting the coordination through nitrogen lone Infrared Spectra pair of the NH2 group to the Co atom without any The important IR spectral bands and their tentative deprotonation(Maurya et al 1999).It is further supported by assignments are summarized in Table 2. The ligands APBT, appearance of the new bands in the region 410-430 cm-1 due HPBT, MPBT, Leu, Ileu act as bidentate ligands in these -N) vibrations. The apperance of absorption bands in Co(II) ternary complexes using nitrogen oxygen & sulfur as the regions 445-440 cm-1 donor atoms. The IR spectra of APBT, Leu/Ileu shows two vibrations. The occurance of no-ligand absorptions band in strong bands in the region 3400-3350 cm-1 and 3300-3200 the regions 302-290 cm-1 may be attributed to (Co-Cl) cm-1 as (N- s(N-H) vibrations of NH2 of these vibrations(Hosny et al. 2002). ligands, respectively. These bands are shifted to lower frequency by 30-70 cm-1 in the respective Co(II) ternary A©ademy Journals 2011
  4. 4. J Trends Chem 2011 2(1): 9-14 Premleta et al. Table 2 IR spectral data (cm-1) of ternary complexes of Co(II) Compound (NH2) (C=C) (C=N) (C=O) (Co-N) (Co-N) (Co-O) (Co-Cl) Asym. Sym. [CoCl(APBT)(Leu)H2O] 1570 1604 1620 3320 3220 430 - 445 302 [CoCl(APBT)(Ileu)H2O] 1568 1602 1678 3318 3225 426 - 440 290 [Co(HPBT)(Leu)H2O]2 1572 1608 1630 3335 3215 425 - 450 - [Co(HPBT)(Ileu)(H2O)2] 1566 1606 1628 3334 3231 422 - 448 - [Co(MPBT)(Leu)(H2O)2] 1577 1601 1640 3333 3225 415 330 435 - [Co(MPBT)(ILeu)(H2O)2] 1566 1600 1621 3330 3225 410 320 432 - 1 H NMR spectra -1 The broad band at 3330 cm due to The 1H NMR spectra of the ligands (APBT, HPBT,mode of HPBT, disappears in the Co(II) ternary complexes MPBT) & their Co(II) complexes were recorded in CDCl3indicating deprotonation of phenolic oxygen and coordination (Table-3). The 1H NMR spectrum of ligand APBT exhibitto the Co atom with the formation of Co-O bond. This gets –NH2 proton, is shiftedfurther supports by the appearance of band in the region 445- slightly down field in the metal complexes, suggesting the440 cm-1 -O) vibrations. The IR spectrum of coordinations of nitrogen of the NH 2 group with the metal.MPBT shows a band at 2560 cm-1 due to (S-H) (thiopronotic) The free ligands HPBT show a broad singlet at 10.00 ppmvibrations, which appears in the Co(II) ternary complexes, due to OH proton. The absence of this signal in the spectra ofsuggesting the deprotonations of –SH group and coordination metal complexes indicates the deprotonation of the OH groupthrough thiophenolic sulfur with the Co atom. It is further and coordination of the phenolic oxygen with the metal. Thesupported by the appearance of new band in the region 330- singlet at -SH proton of the free ligand320 cm-1 -S) vibrations. A medium weak band in MPBT, disappears in the spectra of the metal complexes,the 1600-1620 cm-1 region in the IR spectra of the free there by suggesting the deprotonation of the –SH group onligands (APBT, HPBT, MPBT). This band is shifted to lower complexation with the metal ion. The aromatic protons of thefrequency by 15-20 cm-1 in Co(II) ternary complex indicate ligands. (APBT, HPBT, MPBT) were observed as multiplet atthe bonding of the benzothiazole ternary nitrogen with Co -8.4 ppm shifted downfield in their respective Co(II)atoms. It is further confirmed by the appearance of band in complex, which may be possibly due to deshielding onthe region 430-410 cm-1 -N) vibration. coordination of ligands with metal. 12 A©ademy Journals 2011
  5. 5. J Trends Chem 2011 2(1): 9-14 Premleta et al. Table 3 1H NMR spectral data (ppm) of the ligands (APBT, HPBT, MPBT) and their Co(II) complexes 1 Compound H NMR (CDCl3) ppm -NH2 -OH -SH Aromatic proton APBT 2.18 - - 7.26-8.42 HPBT - 10.00 - 7.15-8.30 MPBT - - 3.56 7.04-8.20 [CoCl(APBT)(H2O)] 2.41 - - 7.22-8.40 [CoCl(HPBT)(H2O)2] - 9.81 - 7.10-8.20 [CoCl[MPBT](H2O)2] - - 3.26 7.02-8.01 BIOLOGICAL ACTIVITY radial growth method was used to check an activity against fungi by taking Bavistin as a standard. The toxicity of all Antifungal Activity these 2-substituted benzothiazole ligands & their Co(II) The results of antifungal activity of 2-substituted ternary complexes have been compared with the conventional benzothiazole ligands & their Co(II) ternary complexes were fungicide bavistin taken as standards in Table-4. summarized in Table-4. 2-Substituted benzothiazole The antifungal screening data (Table-4) reveals that the derivatives & their Co(II) ternary complexes have screened Co(II) ternary complexes are more fungitoxic than the parent for fungicidal properties against Aspergillus niger and ligands (APBT, HPBT and MPBT). The enhanced activity of Fusarium oxysporium at concentration 50, 100, 200 ppm. The the Co(II) ternary complexes may be ascribed to the increased lipophilic nature of these complexes arising due to the chelations (Tunde Bamgboye and Omolara 1987). The toxicity increased with increasing concentrations.Table 4 Fungicidal screening data for the ligands (APBT, HPBT, MPBT) and their Co(II) ternary complexes Complex Average % inhibition (concentration in ppm) Aspergillus niger Fusarium oxysporium (ppm) 50 100 200 50 10 200 APBT 30 40 60 34 43 61 HPBT 28 39 55 30 40 57 MPBT 38 47 60 40 48 64 [CoCl(APBT)(Leu)(H2O)] 50 61 71 54 66 73 [CoCl(APBT)(Ileu)(H2O)] 51 62 72 55 68 74 [Co(HPBT)(Leu)(H2O)2] 40 55 65 44 63 68 [Co(HPBT)(Ileu)(H2O)2] 41 56 66 45 64 70 [Co(MPBT)(Leu)(H2O)] 58 78 80 60 79 88 [Co(MPBT)(Ileu)(H2O)2] 59 79 82 62 80 92 Bavistin (standard) 85 95 100 86 96 100 Antibacterial Activity activity was evaluated by Inhibition zone technique. The The results of Antibacterial activity of 2-substituted results of antibacterial screening of (APBT, HPBT, MPBT) & benzothiazole ligands (APBT, HPBT, MPBT) their Co(II) Co(II) ternary complexes shows that the highest bacterial ternary complexes were summarized in Table-5. activity among all the derivatives but they show less activity The organism selected for the studies are Staphylococcus than standard streptomycin. aureus (+ve) and Escherichia coli (-ve). The antibacterial 13 A©ademy Journals 2011
  6. 6. J Trends Chem 2011 2(1): 9-14 Premleta et al. Table 5 Antibacterial screening data for the ligands (APBT, HPBT, MPBT) & their Co(II) ternary complexes Compd. Staphylococcus aureus (+ve) Escherichia coli (-ve) Diameter of inhibition zone (mm) Diameter of Inhibition zone (mm) 500 1000 500 1000 APBT 6 8 6 9 HPBT 4 7 5 8 MPBT 7 10 8 10 [CoCl(APBT)(Leu)(H2O)] 11 13 12 14 [CoCl(APBT)(Ileu)(H2O)] 12 15 14 16 [Co(HPBT)(Leu)(H2O)2] 8 11 13 17 [Co(HPBT)(Ileu)(H2O)2] 9 12 10 18 [Co(MPBT)(Leu)(H2O)2] 10 14 11 15 [Co(MPBT)(Ileu)(H2O)2] 14 18 15 19 Streptomycin (standard) 16 20 17 21 ACKNOWLEDGEMENT Kashiyama E, Hutchnson I, Chau MS, Stinson SF, Philips LR, Kaw G, Sansville EA, Bradshaw TD, Westwell AD, Stevens MFG , 1999. The authors are thankful to the Head, Department of Antitumor Benzothiazoles 8, Synthesis, Metabolic Formation, andChemistry, University of Rajasthan, Jaipur, India for Biological Properties of the C-and N-Oxidation products ofproviding necessary facilities to carry out this research work. Antitumor 2-(4-Aminophenyl)benzothiazoles. Journal of Medicinal Chemistry 42: 4172-4184Premlata is grateful to University Grant Commissions, NewDelhi, India for the financial support in the form of Rajiv Kok SHL, Gambari R, Chui CH, Yuen MCW, Lin E, Wong RSM, Lau FY, Cheng GYM, Lam WS, Chan SH, Lam KH, Cheng CH, Lai PBS,Gandhi National fellowship wide grant No. F(14)-2(SC)/2009 Yu MWY, Cheung F, Tang JCO, Chan ASC, 2008. Synthesis and(SA-III). Anticaner Activity of Benzothiazole Containing Phthalimide on Human Carcinomia Cell lines. Bioorganic & Medicinal Chemistry REFERENCES 16: 3626-3631 Magdolen P, Zahradnik P, Foltinova P, 2000. Synthesis, antimicrobial testingAmeya AC, Nandini RP, 2007. Synthesis and Bidogical Activity of N- and QSAR Study of New 2-Phenylethenylbenzothiazolium Salts Substituted-3-chloro-2-Azetidinoms. Molecules 12: 2467-2477 Substituted by Cyclic Amines. Pharmazie 55: 803-810Bamgboye TT, Bomgboye OA, 1987. Synthesis, Characterization and Maurya RC, Sharma P, 1999. Synthesis, Magnetic and Spectral Studies of Fungitoxity of Complexes of P-Anisaldehye Thiosemicarbazone Co(ED Picrate Complexes with heterocyclic Nitrogen donors). with Mn(II), Fe(II), Co(II) and Ni(II). Inorganica Chemica Acta Indian Journal of Chemistry 38: 509-513 133: 247-249 Nagarajan SR, De Crescenzo GA, Getman DP, Lu HF, Sikorski JA, WalkerBhuva HA, Kini SG, 2010. Synthesis, Anticancer Activity and Docking of JL, McDonald JJ, Houseman KA, Kocan GP, Kishore N, Mehta Some Substituted Benzothiazoles as Tyrosine Kinase Inhibitors. PP, Funkes-Shippy CL, Blystone L, 2003. Discovery of Novel Journal of Molicular Graphics Modelling 29: 32-37 Benzothiazolesulfonamides as potent inhibitors of HIV-I protease.Bujdakova H, Muckova M, 1994. Antigunfal Activity of a new Bioorganic & Medicinal Chemistry 11: 4769-4777 Benzothiazole Derivatives Against Candida in vitro and in vivo. Paranashivappa R, kumar PP, Rao PVS, Rao AS, 2003. Design, Synthesis International Journal of Antimicrobial Agents 4: 303-308 and Biological evaluation of Benzimidazole/benzothiazole andDelmas F, Avellaneda A, Giorgies CD, Robin M, Cleareq ED, Timon-David Benzoxazole Derivatives as Cycloxygenase Inhibitors. Bioorganic P, Galy JP, 2004. Synthesis & Antileishmanial activity of (1,3- & Medicinal Chemistry Letters 13: 657-660 Benzothiazole-2-yl)amino-9-(10H)-acridinone derivatives. Pattan SR, Manikarao AM, Maste MH, Talath S, 2002. Synthesis of Some European Journal of Medicinal Chemistry 39: 685-690 (Merceptothiazole) Carboxylic Acid Compounds and TheirEl-Tabl HM, El-Saied FA, Ayad MI, 2002. Manganese(II) Iron(II), Nickel(II) Derivatives of Biological Interest. Indian Drugs 39: 265-269 Copper(II), Zn(II) and Uranyl(VI) complexes of N-(4- Pattan SR, Narendra SNB, Angadi JS, 2002. Synthesis & Biological Activity Formylantipyrine)Benzothiazole-2-Ylacetohydrazide. Synthesis of a-[(6-chloro-5-fluoro-2-benzothiazolyl) amino] Acetanilides. and Reactivity in Inorganic and Metal–Organic Chemistry 32: Indian Drugs 139: 515-517 1245-1262 Rajeeva B, Srinivasulu N, Shantakumar SM, 2009. Synthesis andHein DW, Alheim RJ, Leavitt JJ, 1957. The use of Polyphosphoric Acid in Antimicrobial Activity of Some New 2-Substituted Benzothiazole the Synthesis of 2-Aryl- and 2-Alkyl-substituted Benzimidazoles, Derivatives. E-Journal of Chemistry 6: 775-779 Benzoxazoles and Benzothiazole. Journal of American Chemical Society 79: 427-429 Wells G, Bradshaw TD, Diana P, Seaton A, Shi D-F, Westwell AD, Stevens MFG, 2000. The Synthesis and Antitumour Activity ofJaved SA, Siddiqui N, Drabu S, 2004. Synthesis and Antibacterial Activity of Benzothiazole substituted quinol derivatives. Bioorganic & Some 2-[(4-halophenyl)thioureido]-6-substituted Benzothiazoles. Medicinal Chemistry Letters 10: 513-515 Indian Journal of Heterocyclic Chemistry 13: 287-288 A©ademy Journals 2011