Structural aspects of the anti-cancer drug oxaliplatin: A combined theoretical and experimental study

The conformational behavior of the third generation antitumor drug, oxaliplatin, has been explored by GGA-PW91 density functional calculations and FT-IR spectra. The difference in the biological activities of cisplatin and oxaliplatin are attributed to the presence of the DACH ligand in the latter. The trans forms of the ligand are found to be more stable than the cis form, but, of the two equally stable enantiomers, the trans-1 (1R,2R) one is found to be more potent biologically. Since very minor differences are observed in the electronic structures of the two enantiomers, their difference in activity is attributed to the chiral recognition of the ligand by DNA. The calculated vibrational frequencies are in good agreement with our experimental FT-IR spectrum. Calculations have also been performed on the cis isomer and its monohydrate. Comparison between the theoretically predicted geometries and the experimental ones yielded good correspondence, validating our methodology. (C) 2008 Elsevier Ltd. All rights reserved.