1. J Trends Chem 2011 2(1): 9-14
Journal of Trends & Chemistry
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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: 29.6.2011
Abstract
Some 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: gita_seth@yahoo.co.in
INTRODUCTION
Benzothiazoles are found to be antimicrobial (Magdolen end groups are well known pharmaceutical substance
et 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 from
Benzothiazoles 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) benzothiazole
central nervous system depressant (Paranashivappa et al. (HPBT), 2-(2´-merceptophenyl) benzothiazole (MPBT) and
2003), 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 complexes
al. 2010), Antibacterial (Pattan et al. 2002; Javed et al. 2004). are presented in Fig. 1
The survey of literature related to benzothiazoles
derivatives having conjugated system with donor & acceptor
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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)/HPBT
India, melting point were determined on a capillary melting (0.0568 g, 0.01 mol)/MPBT (0.060 g, 0.01 mol) and Leucine
point 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 the
Spectrophotometer. 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. These
NMR spectrometer in CDCl3 using TMS as an internal were filtered, recrystallized from EtOH and dried in vacuo.
reference. Molecular weight was determined by the Rast
campher method. Nitrogen was determined by the Kjeldhal
method, and sulfur was estimated by the messenger’s method. RESULTS AND DISCUSSION
Chlorine was estimated volumetrically by using Volhard
method. 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 molar
HPBT, 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
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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. studies
Table 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
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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 CDCl3
indicating deprotonation of phenolic oxygen and coordination (Table-3). The 1H NMR spectrum of ligand APBT exhibit
to the Co atom with the formation of Co-O bond. This gets –NH2 proton, is shifted
further supports by the appearance of band in the region 445- slightly down field in the metal complexes, suggesting the
440 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 ppm
vibrations, which appears in the Co(II) ternary complexes, due to OH proton. The absence of this signal in the spectra of
suggesting the deprotonations of –SH group and coordination metal complexes indicates the deprotonation of the OH group
through thiophenolic sulfur with the Co atom. It is further and coordination of the phenolic oxygen with the metal. The
supported by the appearance of new band in the region 330- singlet at -SH proton of the free ligand
320 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 on
ligands (APBT, HPBT, MPBT). This band is shifted to lower complexation with the metal ion. The aromatic protons of the
frequency by 15-20 cm-1 in Co(II) ternary complex indicate ligands. (APBT, HPBT, MPBT) were observed as multiplet at
the 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 on
the region 430-410 cm-1 -N) vibration. coordination of ligands with metal.
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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
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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, and
Chemistry, University of Rajasthan, Jaipur, India for Biological Properties of the C-and N-Oxidation products of
providing necessary facilities to carry out this research work. Antitumor 2-(4-Aminophenyl)benzothiazoles. Journal of
Medicinal Chemistry 42: 4172-4184
Premlata is grateful to University Grant Commissions, New
Delhi, 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
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