Raman and Infrared Studies of Platinum-Based Drugs: Cisplatin, Carboplatin, Oxaliplatin, Nedaplatin, and Heptaplatin

This study reports the optimized structures and lowest-energy conformations/stereochemistry of five currently used platinum-based drugs: cisplatin, carboplatin, nedaplatin, oxaliplatin, and heptaplatin. Normal Raman and IR spectra of each drug are experimentally obtained and have been compared to various levels of density functional theory (DFT). Although some combination of structure, reactivity, or spectroscopy for these drugs has been studied by various groups, there are no known experimental normal Raman and IR spectra for nedaplatin, oxaliplatin, and heptaplatin in the literature. The detailed structural and vibration findings of these drugs are very important to understanding platinum behavior and drug dynamics. The following work explores the vibrational frequencies of these drugs particularly by focusing on the low-energy modes between 200 and 600 cm^-1, where anharmonicity effects will have less influence on the accuracy of computed frequencies. Ideally, the Pt-N stretching modes provide vibrational diagnostics for each drug. Interestingly, a vibrational energy decomposition analysis (VEDA) suggests that oxaliplatin and heptaplatin Pt-N stretching modes are not Raman or IR active. Instead, C-C and Pt-O stretching frequencies in the various bidentate dioxo ligands might be more useful in characterizing new cisplatin derivatives. Analysis of anharmonicity effects was compared against (and in tandem with) dimer computations of four of the five drugs. Harmonic vibrational computations of the dimeric cisplatin derivatives provided greater qualitative improvement than that of the monomeric derivatives. Satisfying agreement with experimental Raman spectra was obtained, even without resorting to linear scale factors for the harmonic dimer frequencies.