Abstract

Mechanism of interaction of metronidazole with bovine serum albumin has been reported. Association constant for drug -protein binding showed that the interactions are non-covalent in nature and there are two independent binding sites. The reaction was found to be first order with rate constant 1.832 S-1 and activation energy 13.194 KJ mol-1. The drug does not compete with hydrophobic probe, 8-anilino-1-naphthalene sulphonic acid sodium salt (ANS) for hydrophobic sites on the surface. The decrease in critical micellar concentration (CMC) of cationic surfactant, cetyltrimethylammonium bromide (CTAB) in the presence of metronidazole showed that the drug does not have predominantly hydrophobic character and is not solubilized inside the micelle. Reduction in surface tension of the solvent suggested that the drug has a weakly hydrophobic character. Stern-Volmer analysis of fluorescence quenching data showed that both tryptophan residues of BSA are involved in the drug-protein interaction. The high magnitude of the rate constant for quenching, kq, (1013M-1S-1) could be attributed to increase in the encounter radii of tryptophan-metronidazole due to hydrogen bonding interaction between BSA and drug. Thermodynamic parameters, obtained from data at different temperatures, showed that the binding of metronidazole to BSA involves the formation of both hydrogen and hydrophobic bonds. However, much smaller magnitude of ΔS° value showed that the hydrogen bond formation interaction predominates.