Ligand substitution reaction on a platinum(II) complex with bio-relevant thiols: kinetics, mechanism and bioactivity in aqueous medium

Abstract

The kinetics of the interaction between [Pt(pic)(H2O)2](ClO4)2, cis-diaqua(2- Aminomethylpyridine)platinum(II) perchlorate 1 and selected thiols (L-cysteine and N-acetyl-L-cysteine) 10 has been studied spectrophotometrically in aqueous medium as a function of complex concentration as well as thiol, pH, and temperature at constant ionic strength. The observed pseudo-first-order rate constants kobs (s-1) obeyed the equation kobs = k1[thiol]. At pH = 4.0, complex 1 interacts with the thiols via two distinct consecutive steps. The first step is dependent while the second step is independent of ligand concentration in each case. The rate constants for the process are of the order: k1 ≈ 10-3 M−1s−1 and k2 ≈ 10-5 s-1. The association equilibrium constant (KE15 ) for the outer sphere complex formation has been evaluated together with the rate constants for the two subsequent steps. Both the steps are ligand-assisted anation and the final step is the ring closure process. The activation parameters for both the steps were evaluated using Eyring's equation. The low ΔH # 1 = (34.91 Å} 0.97 kJmole-1) and ΔH # 2 = (29.10 Å} 0.72 kJmole-1) values and large negative values of ΔS # 1 = (-174.68 Å} 2.18 JK-1mole-1) and ΔS # 2 = (-233.74 Å} 20 2.4 JK-1mole-1) for both the anation steps were evaluated. On the basis of the kinetic observations, evaluated activation parameters and spectroscopic data, a plausible associative mechanism is proposed for both the processes. Antibacterial property on both gram positive and gram negative bacteria and anticancer property of complex 1 and its substituted complexes 2 and 3 on HeLa cells have been investigated. Complexes 1 to 3 show growth inhibition remarkably on bacteria. The same of them show 25 anticancer activity near about 70% when compared to cisplatin. The complexes bind to DNA and change its electrophoretic mobilization pattern in Agarose gel.