Reduction of the anti-cancer drug analogue cis, trans, cis-[PtCl_2(OCOCH_3)_2 (NH_3)_2] by L-cysteine and L-methionine and its crystal structure

摘要

The complex cis, trans, cis-[PtCl_2(OCOCH_3)_2 (NH_3)_2] 1 has been synthesized as a simplified and more soluble model of the anticancer drug cis, trans, cis-[PtCl_2(OCOCH_3)_2 (NH_3)(C_6H_(11)NH_2)] (JM216). The crystal structure of 1 shows an octahedral co-ordination sphere around the Pt~(IV) with strong intramolecular and weak intermolecular hydrogen bonding. The kinetics of reduction of 1 by the divalent sulfur amino acids L-cysteine and L-methionine has been determined over a range of pH values by multinuclear NMR. The reduction is strongly pH dependent, being related to the protonation state of the amino acid and the basicity of the sulfur. Reduction rates are dramatically slower than for previous models of platinum (IV) drug systems.