Abstract
The kinetics and mechanism of the complex-formation reactions of [Pd(AEP)(H2O)](2+), where AEP stands for 1-(2-aminoethyl)piperazine, with biologically relevant ligands were studied as a function of selected nucleophiles and pH. The reactivity of the ligands follows the sequence L-methionine > guanosine-5'-monophosphate > glycine > mosine >> glutathione. The substitution reactions with glutathione showed two reaction steps in which the first step involves coordination through nitrogen and depends on the nucleophile concentration, whereas the second step involves intramolecular isomerization from N- to S-bonded glutathione and does not depend on the nucleophile concentration. The stoichiometry and stability constants of the formed complexes are also reported, and the concentration distribution of the various complex species was evaluated as a function of pH. The results are discussed in terms of the mechanism of antitumor activity of related platinum complexes. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)