SYNTHESIS, CHARACTERISATION AND ANTIFUNGAL STUDIES OF Cu (II) HALIDE COMPLEXES OF SOME STERYL DERIVATIVES OF SUBSTITUTED BENZIMIDAZOLES

SYNTHESIS, CHARACTERISATION AND ANTIFUNGAL STUDIES OF Cu (II) HALIDE COMPLEXES OF SOME STERYL DERIVATIVES OF SUBSTITUTED BENZIMIDAZOLES

L.K. Mishra*¹ and Madhu Bala ²

Department of Chemistry, Patna University ¹, Patna-800005 Bihar, India

Department of Chemistry, National Institute of Technology ², Patna-800005, Bihar, India

ABSTRACT: Complexes of Copper (II) halides with steryl derivative of 2- methylbenzimidazole (stmbz), 2-ethylbenzimidazole (stebz) and 2-benzylbenzimidazole (stbbz) of composition CuL₂X₂ (L = stmbz, stebz and stbbz and X = Cl, Br) have been prepared and characterised. The magnetic susceptibility e.p.r. data, electronic absorption pattern and i.r. spectral studies of complexes indicated distorted octahedral environment of ligand around copper (II) atom. Steryl derivatives and their copper (II) complexes were screened for their antifungal activity in dilute aqueous ethanolic media where bromide complexes show higher antifungal activity than free ligands.

Copper (II) halide, Benzimidazole steryl derivatives complexes, Synthesis, Antifungal studies

INTRODUCTION:  Benzimidazole substituent of a molecule is an important pharmacophore and a previleged structure in medicinal chemistry ^1-3. One of the prominent benzimidazole compound in nature is α-ribosyl-dimethyl benzimidazole which is an axial ligand for Cobalt in Vitamin- B₁₂ whose imidazole part provide an important binding sites in biological systems, displaying a vital role in metal - protein interaction ³.

The wide spectrum of pharmacological and medicinal properties of benzimidazole derivatives and their metal complexes aroused huge interest to study the preparation and characterisation of complexes of benzimidazole derivatives ^4-12.

In pursuance of interest of one of us ^{8, 9},we here report antifungal activity of the complexes of copper (II) halide with steryl derivatives of 2- alkyl/aryl of benzimidazole (L).

(R= H, CH₃, C₆H₅)

MATERIAL AND METHODS: Metal salts and solvents used were extra pure reagent of E. Merck or Anal-R grade chemical of B.D.H. The ligands were prepared by known procedure ⁹. The metal content of complexes was determined by standard procedure. The elemental analyses were performed as reported earlier ^8-9. The results of IR and U-V were obtained from I.I.T, Patna and C.D.R.I. Lucknow.

Preparation of CuL2X2 (L= Steryl derivatives of benzimidazole derivatives, X=Cl or Br): About 0.01 mole of copper (II) halides were dissolved in 20-25 ml dry methanol and treated with hot solution of steryl benzimidazole derivative (0.02 mole) in 30-35 ml methanol. The mixed solutions were heated for 15-20 minutes with constant stirring and resulting solution cooled at room temperature, when light ash or brown coloured dihalo-copper (II) complexes separated gradually. The products were collected on a filter, washed with cold methanol and dried in air oven CaCl₂. The complexes were analysed for Cu^II, halogens nitrogen contents, and results of analysis are given in Table 1. The e.p.r. spectra of complexes were recorded on Varian EPR (E-112) Spectrophoto- meter in micro crystalline form at LNT. The magnetic susceptibility was determined by Gouy method making diamagnetic correction using Pascal’s constants.

RESULTS AND DISCUSSION: The elemental analysis of Cu (II) halides complexes correspond to composition CuL₂X₂ (L= steryl derivatives of 2- methyl, 2- ethyl and 2- benzylbenzimidazole and X = Cl or Br). The dichloro complexes CuL₂Cl₂   has less solubility in methanol or ethanol than dibromo product CuL₂Br₂. The complexes dissolve appreciably in DMF yielding greenish yellow or brownish yellow solutions. The freshly prepared DMF solution of dihalo complexes show negligible electrical conductance value (6-8 ohm^-1 mol^-1 cm²) suggesting coordinated nature of halide ions in complexes ¹¹. The magnetic susceptibility of complexes occurs in the range 1.79-1.86 BM at 304K (Table 1). The magnetic moment values do not indicate antiferomagnetism in complexes at room temperature ¹². The E.P.R. Spectra of Cu(stebz)₂ Cl₂ and Cu(stebz)₂ Br₂ have been interpreted according to Kneubuhl's method¹³. The calculated g_^ and g_çç value of Cu(stebz)₂ Cl₂ was found to be 2.062 and 2.151 and g_av equal to 2.091 which gives G value 2.43. The g_^ and g_çç value of Cu (stebz)₂ Br₂ was found as 2.032 and 2.121 and calculated g_av was found 2.062, which gave G value 3.78. The G value of bromo complexes [Cu(stebz)₂ Br₂] are greater than that of dichloro complexes indicated lower exchange coupling in dibromo product¹⁴.

TABLE 1: ANALYTICAL RESULTS AND PHYSICAL DATA OF COMPLEXES

The electronic absorption spectrum of complexes in ethanol display strong absorption band   below 400nm attributed to charge transfer transition. A broad shoulder near 440-460nm and weak broad band near 680-700nm was observed in spectrum of [Cu(stebz)₂ Cl₂] and [Cu(stmbz)₂ Cl₂] attributed to ²B_1g→ ²E_g and ²B_1g →²A_1g, ²B_1g →²B_2g transitions in distorted octahedral field¹⁵.

In case of dibromo complexes [CuL₂Br₂], (L=stmbz, stebz and stbbz), the spectra display much stronger absorption below 420nm and a broad bands shoulder near 630-680nm attributed to combination of ²B_1g →²A_1g, ²B_1g →²B_2g transition in tetragonally distorted field¹⁵.

The i.r. spectrum of stebz and other steryl derivatives display broad band between 3030-3250 cm^-1 attributed from ν(C-H) phenyl ring and νN-H) of benzimidazole ν(N-H) group. A medium band at 2928-2875 cm^-1 is assigned to CH₃ group ν(C=H) vibrations. These i.r. bands are retained in Cu(II) complexes with slight change in positions and intensities.

The benzimidazole ring ν(C=N) and steryl group (C=C) stretching bands were observed at 1605±5 cm^-1 and 1635-1640 cm^-1. The ν(C=N) band near 1605±5 of ligand shifted to lower frequency by 10-15 cm^-1 in their complexes suggesting the bonding of imidazole ring (C=N) nitrogen to metal atom.

In finger print regions the steryl derivatives show a large number of prominent and medium to strong i.r. bands originated from phenyl ring skeletal, ν(C-N), ν(C-C), δ(C-H), out of plane and in plane bending band and these bands are retained in complexes. The δ(NH) of benzimidazole part located near 1535±5 in steryl derivatives are not affected appreciably indicating that (N-H) nitrogen is not involved in bonding with Copper (II) halide ^16-18.

Antifungal activity of the ligands and their copper(II) halide complexes were evaluated by Radial growth method ¹⁹ using Czapek's agar medium having composition 20g starch, 20 agar agar, 20g glucose dissolved in 1000ml. To this solution 50, 100 and 200 ppm concentration of ligands and complexes were made with ethanolic solution of products.

The medium was then poured in petri plate and then spores of fungi (F. oxysporum, A. flavus, A. niger and R. phaseoli) were placed on the medium with the help of an inoculum needle. These petri plates were wrapped in polythene bags containing a few drops of ethanol and placed in an incubator at 30±1⁰c. The linear growth of fungi was obtained by measuring the fungal colony diameter after five days. The percentage (%) inhibition was calculated as 100 (C-T)/C where C and T are the diameter of the fungus colony in the control and test plates respectively. The antifungal activities of metal complexes were much larger than free ligand and shown in Table 2. The bromo derivatives have larger activity than chloro complexes.

TABLE 2: ANTIFUNGAL ACTIVITY OF LIGAND AND COMPLEXES AFTER 120 HOUR INCUBATION AT 30±1⁰C

The reference Antifungal material is Mycostatin; L=stmbz,   L^׀=stebz  and L^׀׀=stbbz

CONCLUSION: The ligand coordinates as unidentate nitrogen donor forming distorted octahedral structure with halogen bridging atom. The bromo complexes show higher microbial activity than the free ligand.

ACKNOWLEDGEMENT: The author is grateful to Director of National Institute of Technology, Patna for providing the necessary laboratory facilities.

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How to cite this article:

Mishra LK and Bala M: Synthesis, characterisation and antifungal studies of Cu (II) halide complexes of some steryl derivatives of substituted benzimidazoles. Int J Pharm Sci Res 2013: 4(9); 3620-3624. doi: 10.13040/IJPSR. 0975-8232.4(9).3620-24

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