Influence of the chloride concentration on ligand substitution reactions of [Pt(SMC)Cl2] with biologically relevant nucleophiles

Abstract

The kinetics and mechanism of ligand substitution reactions of [Pt(SMC)Cl₂] (SMC = S-methyl-L-cysteine) with biologically relevant ligands were studied as a function of chloride and nucleophile concentrations at pH 2.5 and 7.2. It was observed that the slope and intercept obtained from the linear dependence of the observed rate constant on the nucleophile concentration strongly depend on the [Cl⁻] for all the studied substitution reactions. At high [Cl⁻], the rate constant for the forward reaction is almost zero and that for the back reaction follows the order: L-met > GSH ∼ INO > 5′-GMP. Ion-pair formation between the positively charged Pt(II) complex and the chloride ion is suggested to account for the saturation kinetics observed for the back reaction. The results are discussed in terms of the mechanism of the anti-tumour activity of related platinum complexes.