Steric control over the complex-formation and chelation kinetics of cis-bis(amine)palladium(II) complexes with methionine and S-methylcysteine in weakly acidic aqueous solution

Abstract

A detailed kinetic study was undertaken of the complex-formation reactions of cis-[Pd(R₂NCH₂CH₂NR₂)Cl₂](R = H, Me or Et) with L-methionine (Hmet) and S-methyl-L-cysteine (mcys) as a function of nucleophile and chloride concentrations. Two consecutive reaction steps were observed for nearly all cases studied. All complex-formation reactions proceed via the formation of a reactive intermediate of the type [Pd(R₂NCH₂CH₂NR₂)Cl(H₂O)]⁺. The kinetic data for the reaction with Hmet for R = H at low concentration are equally in accord with pre-equilibrium and steady-state rate laws, which is also the case for R = Et. In addition, a direct methionine path with [Pd(en)Cl₂](en = H₂NCH₂CH₂NH₂) was observed at higher methionine concentrations. This is followed by a slower ring-closure reaction. The kinetic data for the first reaction steps for R = H and with mcys are only consistent with the preequilibrium model. This is followed by slower nucleophilic attack by a second mcys molecule to give the 1:2 complex for R = H in competition with either a solvolysis or a ring-closure reaction. The results are compared to available data for the complex-formation reactions with inosine and inosine 5′-monophosphate and allow a detailed discussion of the steric control over the kinetics and the nucleophilicity of such reactions.