Cisplatin, carboplatin, and oxaliplatin are anticancer drugs that react with deoxyribonucleic acid, ribonucleic acid and proteins both in vitro and in vivo.  Cellular reactions involving these compounds have become a major field of study in order to determine the extent to which these drugs' antineoplastic activities exist.  Our research focuses on synthesizing analogs of oxaliplatin and understanding how bulky ligand groups affect reaction with amino acids.  (R,R)�N,N'�dimethyl�1,2�diaminocyclohexane platinum (II) oxalate or Pt(Me2dach)(ox) varies from oxaliplatin (Pt(dach)(ox)) in that it has one methyl group attached to each platinum coordinated nitrogen.  Theoretically Pt(Me2dach)(ox) has two stereoisomers � RRRR and SRRS � based on the chirality centers of the two platinum coordinated nitrogens and the molecule's C2-symmetry.  However, upon synthesis and spectroscopic interpretation, it has been determined that the SRRS conformation is predominant.  Nuclear Magnetic Resonance (NMR) spectroscopy has shown that the reactions of N-Acetylmethionine (N-AcMet) with Pt(Me2dach)(ox) and Pt(dach)(ox) react at similar rates suggesting that the methyl groups of Pt(Me2dach)(ox) have little effect on the initial reaction.  Whereas reaction of Pt(dach)(ox) and N-AcMet can form 1:1 or 1:2 complexes, Pt(Me2dach)(ox) with N-AcMet can form only 1:1 products.  Depending on Pt:N-AcMet ratios, Pt(dach)(ox) has the potential to form either a [Pt(dach)(N-AcMet-S)2]or [Pt(dach)(N-AcMet-S,N)] complex.  The bis product is not found in Pt(Me2dach)(ox) reactions because the formation of a [Pt(Me2dach)(N-AcMet-S,O)]+ product retards the coordination of  a second N-AcMet.  It has therefore been deduced that the additional methyl groups of Pt(Me2dach)(ox) limit reaction with N-AcMet to a 1:1 molar product.  In addition, experimentation involving the enantiomer (S,S)�N,N'�dimethyl�1,2�diaminocyclohexane platinum (II) oxalate is currently being studied.

Characterization and reaction of an analog anticancer drug oxaliplatin

246th National Meeting (2013)

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