Stereochemistry of platinum complexes of the neutral amino acids allylglycine, S-methylcysteine, methionine, and corresponding sulfoxides

The stereochemistry-both configuration and conformation-of platinum complexes of the neutral amino acids allylglycine, methionine, S-methylcysteine and their sulfoxides, which all contain a potential metal binding site, X, has been investigated by 1-D and 2-D proton NMR spectroscopy, molecular mechanics calculations, and X-ray crystallography. The configuration of each diastereomer of square-planar complexes of general formula N, X-Pt(amino acidH)Cl-2 has been assigned for all five of the amino acids. Relative equilibrium concentrations in solution of isomers of allylglycine (2S,4S/2S,4R = 2R,4R/2R,4S = 5), S-methylcysteine (2S,SR/2S,SS = 2), and methionine (2S,SR/2S,SS = 1.1) have been determined. The vicinal proton-proton coupling constants and NOESY spectra employed to assign configurations to the isomers also permitted an assessment of chelate ring conformations for the coordinated ligands. X-ray structures of kinetically stable sulfoxide complexes were employed to assign their configurations, and subsequent decomposition of isolated methionine and S-methylcysteine sulfoxide chelate isomers isomers was used to assign the very similar proton spectra of the two diastereomers of the corresponding free sulfoxides amino acids. With the significant exception of the methionine sulfoxide complexes, molecular mechanics calculations generally yield low energy conformations and isomer ratios in qualitative agreement with the NMR and X-ray structure data for these platinum complexes. (C) 2002 Elsevier Science B.V. All rights reserved.