NMR studies of the reaction of platinum complexes with a peptide

Donald J. Chapman and Kevin M. Williams

A bulky platinum diamine complex has been reacted with the tetrapeptide Phe-Met-Arg-Phe. This peptide is small enough to have an easily interpreted ¹H NMR spectrum and has only one primary site (Met) where the platinum could react. The goal of the study was to examine whether the platinum complex would form sulfur-oxygen chelates as it did with N-acetylmethionine. A downfield shift of the ¹H NMR signal of the S-methyl group indicated coordination to the methionine sulfur atom. However, a downfield shift of the corresponding alpha hydrogen peak did not occur; such a shift would have been expected for a sulfur-oxygen chelate. Thus, the presence of a carbonyl rather than a carboxyl oxygen appears to prevent chelation. A sulfur-nitrogen chelate was also not observed because steric clashes prevent chelation of the amide nitrogen; thus, the peptide is coordinated via only the sulfur atom. Experiments with a nonbulky platinum complex used 90% ¹H₂O/10% ²H₂O to make the amide hydrogen peaks visible. These experiments show that the platinum coordinated to both the sulfur and the amide nitrogen on the N-terminus of methionine. This interaction is expected since coordination of nitrogen is thermodynamically favored over oxygen.