The gas-phase chemistry of cis-diammineplatinum(II) complexes: a joint experimental and theoretical study.

Prior to reactions with DNA, the anticancer drug cisplatin [Pt(II)(NH(3))(2)Cl(2)] forms a series of solvolysis intermediates by successive replacement of the chloro ligands by water or hydroxyl groups. The bonding of water to Pt(II) is weak, and it is easily substituted by donor ligands present in the solution, for example, amines or alcohols. We studied such compounds using high-resolution electrospray mass spectrometry with a linear ion trap and DFT computations. This combination allows for the first time a detailed description of the reactions initiated by the central atom of the complexes. Positively charged cisplatin adducts with primary and secondary alcohols ([Pt(II)(NH(3))(2)(ROH)Cl](+)) show unexpected reactions when fragmented in a linear ion trap. Either water loss is accompanied by formation of the corresponding carbene complex, or loss of the corresponding aldehyde/ketone leads to the formation of the complex [Pt(NH(3))(2)(H(2))Cl](+). Complete loss of the alcohol ligand is not observed for kinetic reasons. A detailed investigation by DFT and molecular dynamics for the cisplatin/methanol complex [Pt(II)(NH(3))(2)(CH(3)OH)Cl](+) allowed identification of the reaction mechanisms leading to the observed fragmentation patterns. The initial step for both fragmentation pathways is activation of the alpha-CH bond and subsequent H transfer within the complex. Direct activation of the OH or CO bond is less favorable. Ligands bound to the Pt(II) center such as the chloro ligand can directly catalyze the reaction by intermediate binding of H atoms. Upon collision activation, adducts without an alpha-H atom such as [Pt(NH(3))(2){(CH(3))(3)COH}Cl](+) show loss of water or the corresponding alkene.