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(NH3)(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(NH3)(2)(ROH)Cl](+)) show unexpected reactions when fragmented in a tin-ear 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(NH3)(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(NH3)(2)(CH3OH)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 the Pt-II center such as the chloro ligand con directly catalyze the reaction by intermediate binding of H atoms. Upon collision activation, adducts without an a-H atom such as [Pt(NH3)(2){(CH3)(3)COH}Cl](+) show loss of water or the corresponding alkene.