Comparison of N-acetylmethionine reactivity between oxaliplatin and an oxaliplatin derivative with chiral (S,S) amine nitrogen atoms

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• 作者：Kevin M. Williams ; ^{kevin.williams@wku.edu} ; Amy D. Poynter ; Jonathan D. Hendrie ; Daniel C. Jackson ; Virginia K. Martin
• 关键词：dach ; 1 ; 2-diaminocyclohexane ; Me2dach ; N ; N&prime ; -dimethyl-1 ; 2-diaminocyclohexane ; N-AcMet ; N-acetylmethionine ; ox ; oxalate ; Me4en ; N ; N ; N&prime ; N&prime ; -tetramethylethylenediamine ; Et2en ; N ; N-diethylethylenediamine ; Me5dien ; N ; N ; N&prime ; N&prime ; N&Prime
• 刊名：Inorganica Chimica Acta
• 出版年：2013
• 出版时间：24 May, 2013
• 年：2013
• 卷：401
• 期：Complete
• 页码：64-69
• 全文大小：843 K

文摘

We have synthesized an oxaliplatin derivative using N,N¡ä-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 by ¹H 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.