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) has been studied spectrophotometrically in aqueous medium as a function of complex and thiol concentrations, pH, and temperature at constant ionic strength. The observed pseudo-first-order rate constants k_obs (s⁻¹) obeyed the equation k_obs = 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. The rate constants for the process are of the order: k₁ ≈ 10⁻³ M⁻¹ s⁻¹ and k₂ ≈ 10⁻⁵ s⁻¹. The association equilibrium constant (K_E) 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 steps were evaluated using Eyring's equation. The low ΔH^‡₁ = (34.91 ± 0.97 kJ mol⁻¹) and ΔH^‡₂ = (29.10 ± 0.72 kJ mol⁻¹) values and large negative values of ΔS^‡₁ = (−174.68 ± 2.18 J K⁻¹ mol⁻¹) and ΔS^‡₂ = (−233.74 ± 2.4 J K⁻¹ mol⁻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 processes. Antibacterial properties on both gram positive and gram negative bacteria and anticancer properties of complex 1 and its substituted complexes 2 and 3 on HeLa cells have been investigated. Complexes 1 to 3 show remarkable growth inhibition of bacteria. They also show anticancer activity of about 70% when compared to cis-platin. The complexes bind to DNA and change its electrophoretic mobilization pattern in agarose gel.