Structure-Reactivity Correlations for Reactions of Palladium(II) and Platinum(IV) Complexes

Abstract: The kinetics and mechanism for substitution reactions on tetraaquapalladium(II) by an extended series of thioethers, a great number of carboxylic acids, and olefins have been studied by use of UV-VIS, stopped-flow, and high-pressure stopped-flow spectrophotometry and NMR spectroscopy. Second-order rate constants k and activation parameters (activation enthalpies, entropies, and volumes) for formation of monodentate 1:1 complexes have been determined. The reactivity of thioethers toward the metal center can be described by a 3-term equation, in while the electronic effects and steric requirements are expressed by the sum of Taft constants and the ligand cone angle, respectively. The reactivity trends of thioethers toward other square-planar complexes reported in literature can be given a general interpretation. Neither basicity nor steric factors of carboxylic acids influence their reactivities toward the Pd(II) complex in a significant extent due to an excellent isokinetic relation between activation enthalpies and and entropies. Analysis of volume profiles for the carboxylic acid reactions and a linear relation between logk and logK observed for all experimental data so far for tetraaquapalladium(II) complex formation reactions support an Ia mechanism. Reaction between maleic acid and the metal complex results in a chelate with one carboxylate group and the carbon-carbon double bond coordinated to the metal center. The complicated kinetics has been analyzed in terms of a reaction mechanism involving several consecutive and parallel pathways. The kinetics and mechanism for reduction of trans-dichlorotetracyanoplatinate(IV) (as a model compound for Pt(IV) antitumor prodrugs) by l-methionine and thiols (thioglycolic acid, l-cysteine, dl-penicillamine, and glutathione) have been studied in a wide pH range by use of stopped-flow spectrophotometry. Reduction proceeds via parallel pathways involving various protolytic species and via transition states where electron transfer is mediated by coordinated halide. Two types of Brønsted correlations have been found for the thiol reactions, suggesting that the basicity is the predominant factor in determining the reactivity of thiols toward the Pt(IV) complex. This has been interpreted in terms of different transition states. The present work demonstrates that Pt(IV) complexes are reduced rapidly at physiological pH, implying that Pt(IV) antitumor prodrugs are very likely being reduced to their Pt(II) analogues before interaction with DNA. Several structure-reactivity correlations have been derived and a number of experimental relations have been examined, enabling rationalization and systematization of reactivity in a broad sense and also improving the understanding of the reaction mechansims.