Microwave assisted synthesis, spectral, bio-potential and antituberculosis activities of Co(II) complex with Isoniazid and benzoate ion

P. Manikandan¹*, K. Rajasekar¹, T. Gomadurai¹, B. Sathiyamoorthy¹, P. Sudhakar

Department of Chemistry, Government Arts College, Ariyalur-621 713,Tamil Nadu, India

*Corresponding Author E-mail: manijayakavin@gmail.com, yokkesh111@gmail.com, gomadurait@gmail.com,sathia78@yahoo.com, sudhakar9715@gmail.com

ABSTRACT:

Microwave assisted synthesis was the new strategies in Green Chemistry. The first row transition metal of Co(II) complex was synthesized with neutral bidentate Isoniazid(INH) and benzoate anionic ligands using microwave techniques. The complex was characterized by various analytical, spectral and biological studies. The structural aspects and 1:2:2 (metal : INH : Benzoate ion) composition of the complex were determined from elemental analysis and metal estimation. Neutral nature of the complex from molar conductance and redox properties from cyclic voltammetry studies were also find out. The magnetic moment (VSM) and electronic spectral data value of the complex confirming by its octahedral geometry. From the IR and Far-IR spectral data the complexation and coordination mode of the complex was measured. The antibacterial and antifungal activities of the pure ligand(INH) and its Co(II) complex were carried out by Agar well diffusion method using gram negative E.coli, Salmonella and gram positive Actinobacter and C.albicance (pathogenic fungal strain). The bio-potential activities indicate the complex has much more activity than the INH. The in-vitro antituberculosis activity of INH and its complex were performed using M.tuberculosis.

KEYWORDS:INH, Benzoate ion, Co(II) complex, Antibacterial, Antifungal, antituberculosis.

INTRODUCTION:

Microwave assisted reactions are very interesting Eco-friendly techniques due to their enhanced reaction rate, safety, low-cost and higher yield.^[1]Green chemistry synthetic method is the eco-friendly process that avoid the uses of higher volume of solvents and also minimize the formation of unwanted byproduct.^[2]M.tuberculosis is a human pathogen which cause tuberculosis. The INH is the first line antituberculosis agent against M.tuberculosis^[3-4].

Transition metal complexes with bio-active ligands have immense interest in the field of Bio-inorganic chemistry ^[5-6]. Variety of Bio-active ligands used in coordination chemistry, apart from that the Isoniazid is well known nicotinic acid derivatives which is used as the primary ligand and benzoate anion as the mixed ligands. The complex formation ability and more positive charge of transition metal ions, Co(II) used as the central metal ion in the present work. We have synthesized one new complex of Co(II) with Isoniazid and benzoate ion using microwave energy.

MATERIALS AND METHODS:

All the chemicals were purchased and used as it is without further purification. Isoniazid: Alfa Aesar, cobalt nitrate, sodium benzoate, DMSO, methanol, ethanol and CH₃CN were used of AnalaR grade.

Instruments

The elemental analysis of the complex was carried out using (Thermo Finnegan make, Flash EA1112 series) CHNS(O) analyzer instrument. The metal ion estimated by volumetrically using standard procedure. The molar conductance of 10^-3 M complex in acetonitrile was conducted using Systronic Conductivity Bridge at 30⁰C. Cyclic voltammogram of a complex were recorded in DMSO solution at room temperature on Versa Stat (Princeton Applied Research-Make) electrochemical analyzer. The three electrode cell comprised of reference calomel, auxiliary (or) counters Ag/AgCl and the working glassy carbon (part number-CHI 101) electrodes. The diffused reflectance spectra of the complex in the solid state were measured using Varian carry-5000 model UV-Visible spectrophotometer. IR spectra of the free INH (ligand) and its complex were carried out using Schimadzu FT-IR8400s spectroscopy at 4000-400 cm^-1 wave number with KBr pellet technique. The Far IR spectrum of the complex was recorded in a Bruker make, 3000 Hyperion Microscope with Vertex 80 FTIR system model instruments. The antibacterial and antifungal activities of INH and its complex were done by in-vitro Agar well diffusion method using Amikacin and ketoconazole as a standard for bacterial and fungal strain respectively. The Antimycobacterial activity of the new complex will be studied by adopting luciferase reporter phage (LRP) assay with M. tuberculosis.

Preparation of complex

The Co(II) complex were synthesized by mixing Isoniazid 0.94 g (6.87 mmol) in 5ml methanol with 1g (3.36 mmol) Co(NO₃)₂.6H₂O in 5ml methanol irradiated on a microwave oven for 10 sec, then sodium benzoate 0.99g (6.87 mmol) in ethanol was mixed and whole mixture was irradiated on a microwave oven for another 10 sec. The precipitated pink complex were filtered, washed with 1:1 water and ethanol and dried.

Figure- 1: Structure of Isoniazid

RESULTS AND DISCUSSION:

The synthesized complex is pink in colour and the yield is 65%. The complex is stable under ordinary conditions. The metal ion in complex was estimated by volumetrically after decomposing a known weight of complex in H₂SO₄. From the results of metal estimation and elemental analysis, the complex has the formula of [Co(INH)₂(Benz)₂]. The molar conductance was measured using 10^-3 Molar concentration of complex solution in acetonitrile and the conductance value lie in 44.5 Ohm^-1cm²mol^-1, according to Geary the complex is neutral and non-electrolytic nature(1:0 type).^[7-8]

Redox properties of Co(II) complex

The redox properties of Co(II) complex explained by cyclic voltammetry study. It is very important tool to give the nutshell information about the redox reaction in coordination complexes. In Co(II) complex the anodic peak potential Epa at 0.900 mV and the cathodic peak potential Epc at -1.00V with 100 mV/s scan rate. The peak to peak separation ΔEp is at -1.900 which is confirmed by the quasi reversible one electron transfer reaction.^[9]

Figure-2: Cyclic voltammogram of Co(II) complex

UV-Visible spectrum

The UV-Visible spectrum of INH shows the two well resolved peak ν1 at 305 nm and ν2 at 261 nm indicating the Π-Π^* transition and charge transfer transition respectively. In Co(II) complex three well resolved peak at 16,393cm^-1(ν₁), 27,777 cm^-1(ν₂) and 40, 000cm^-1(ν₃) respectively which are corresponding to three transitions ⁴T_1g← ⁴A_2g, ⁴T_1g(F) ← ⁴A_2g and⁴T_1g(P) ← ⁴A_2g indicating the octahedral geometry of the complex which is further confirmed by effective magnetic moment of 3.50-3.70 BM.^[10]The ν₂/ν₁value is 1.69 cm^-1 and the electronic repulsion parameters B (971cm^-1) and C (4366cm^-1) are lower than the free ion (d⁷electronic state) indicating that the delocalization of the metal electrons over the molecular orbitals

IR and Far-IR spectra of INH and Co(II) complex

The IR spectral techniques are useful and important techniques in the metal-organic frame work studies. It is easily find out the functional groups and complexation ability in metal complexes. The ligand INH shows the stretching frequencies of ν(NH₂) at 3200cm^-1and ν(C=O) at 1650-1660 cm^-1 in complex the ν(NH₂) shifted at higher value of 3231 cm^-1 where as ν(C=O) shifted to slightly higher frequency at 1663cm^-1the ν(C-O) at 1020 cm^-1 in complex indicating the INH forming complex with Co(II) through nitrogen and oxygen atom of ligand. The additional anionic ligand shows the stretching frequency of ν(C=O) at 1680-1750 cm^-1 and ν(C-O) at 1210-1320 cm^-1these frequencies are shifted to 1695 cm^-1 and 1226 cm^-1 in complex, this fact also confirming the anionic ligand can coordinate through oxygen atom.^[11]

In this region of IR spectrum the metal-chelating atom were predicted (M-N, M-Oand M-X). In Co(II) complex the strong frequencies at 523cm^-1 and at 458 cm^-1 respectively indicating the metal-nitrogen and metal-oxygen coordination of INH. The frequency at 418 cm^-1 corresponding to the metal-oxygen coordination of benzoate ion.^[12]

Figure-3: IR spectrum of Co(II) complex

Table-1: IR spectral data for ligand and its Co(II) complex

Complex	ν(NH₂) cm^-1	ν (N-H) cm^-1	ν(C=O) cm^-1	ν(C-N) cm^-1	ν (N-N) cm^-1	ν (C-O) cm^-1	ν(C=C) cm^-1	ν (C=O) cm^-1	ν (C-H) cm^-1	ν (C-O) cm^-1
INH	3200	3100	1650-1660	1490	1140	1020-1100	-	-	-	-
Benzoate ion	-	-	-	-	-	-	1400-1600	1680-1750	3000-3050	1210-1320
Co(II) complex	3231	3090	1663	1405	1176	1021	1545	1595	3062	1226

CONCLUSION:

In this work, the Co(II) complex of INH and benzoate ion was synthesized using microwave heating an eco-friendly techniques and characterized on the basis of analytical, spectral and Biological methods. The formulae of the complex is [Co(INH)₂(Benz)₂] it is non-ionic, neutral and non-electrolyte and octahedral structure. The Cyclic Voltammetry studies reveal that the complex is a well defined redox process corresponding to the formation of one electron transfer quasi reversible Co(II)/Co(I) couple. Based on the Bio-potential activities, the complex is biologically active against the tested microorganisms. The complex is moderate antituberculosis agent compared with those for pure INH.

ACKNOWLEDGEMENT:

The Authors are grateful to the Principal and Head, Department of Chemistry, Government Arts College, Ariyalur for giving the opportunity to carry out research work and also thanks to the Director and Head of the STIC(Cochin), SAIF(Chennai), CIF(St.Joseph College), Boss Clinical Lab(Madurai), Harman research lab, Thanjavur, and SAIF (Mumbai) for providing analytical, Spectral and Biological facilities. Special thanks to Dr. V. N. Azger Dusthakeer, National institute for Research in Tuberculosis

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