CHEMISTRY

Reaction of methionine with bulky platinum diamine complexes. SONDRA R. MASSEY*, CARRIE ROWAN, and KEVIN M. WILLIAMS, Department of Chemistry, Western Kentucky University, Bowling Green, KY 42101.

The anticancer drug cisplatin (cis-Pt(NH₃)₂Cl₂) results in cell death due primarily to its interaction with DNA, specifically at guanine residues. The interaction of cisplatin and its analogs with proteins is a side reaction that could be responsible for toxicity and/or acquired resistance of the drug. Also, platinum complexes may be useful as agents that cleave proteins and peptides regioselectively on the C-terminal side of methionine. We are therefore characterizing the reaction of amino acids, primarily methionine, with bulky platinum complexes such as [Pt(Me₄ en)(D₂O)₂]²⁺ (Me₄en = N,N,N',N'-tetramethylethylenediamine) and [Pt(Et₂en)(D₂O)₂]²⁺ (Et₂en = N,N-diethylethylenediamine); the latter is non-C₂-symmetrical and has bulk at only one nitrogen. [Pt(Me₄en)(D₂O)₂]²⁺ reacts with methionine and N-acetylmethionine in a 1:1 molar ratio and forms chelates via the sulfur and nitrogen atoms for methionine and sulfur and oxygen atoms for N-acetylmethionine. One and two-dimensional NMR spectroscopy are being utilized to characterize these complexes.