title: Comparison of N-acetylmethionine reactivity between oxaliplatin and an oxaliplatin derivative with chiral (S,S) amine nitrogen atoms.
abstract: We have synthesized an oxaliplatin derivative using N,N'-dimethyl-1,2-diaminocyclohexane (Me2dach) as the diamine ligand. The complex (S,R,R,S)-Pt(Me2dach)(oxalate), where S,R,R,S represents the chiralities at N,C,C,N, respectively, was prepared and characterized by1H NMR spectroscopy, COSY, NOESY, and HMQC. Oxaliplatin reacts with N-acetylmethionine (N-AcMet) to form [Pt(dach)(N-AcMet-S)2] and [Pt(dach)(N-AcMet-S,N)], with the former favored at higher molar ratios of N-AcMet. In contrast, Pt(Me2dach)(oxalate) reacts to form [Pt(Me2dach)(N-AcMet-S,O)]+even in the presence of excess N-AcMet. Molecular mechanics calculations are consistent with significant steric clashes in models of [Pt(Me2dach)(N-AcMet-S)2]. When N-AcMet was reacted with an excess of each platinum complex, the rate of N-AcMet decrease was very similar for both complexes. Thus, the methyl groups at the nitrogen atoms had little to no effect on the addition of the sulfur atom of a single N-acetylmethionine, but they prevented chelation of the amide nitrogen or coordination of a second N-acetylmethionine residue.
authors.affiliation: Department of Chemistry, Western Kentucky University, 1906 College Heights Blvd #11079, Bowling Green, KY 42101-1079.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Williams
authors.forename: Amy D
authors.initials: AD
authors.lastname: Poynter
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Hendrie
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Jackson
authors.forename: Virginia K
authors.initials: VK
authors.lastname: Martin
keywords: Nuclear magnetic resonance; amino acids; methionine; oxaliplatin; platinum