Binding Motifs of Carboplatin and Oxaliplatin with Guanine: A Combined MS/MS, IRMPD, and Theoretical Study.

Complexes generated in the gas phase involving the purine nucleobase guanine bound to second and third generation platinum drugs, namely, carboplatin (CarboPt) and oxaliplatin (OxaliPt), were investigated by combining tandem mass spectrometry, collision-induced dissociation (CID), infrared multiple photon dissociation spectroscopy (IRMPD), and density functional theory (DFT) calculations. As the first step, a spectroscopic characterization of the protonated platinum drugs was accomplished. Protonation of both CarboPt and OxaliPt in the gas phase occurs on one of the two carbonyl groups of the cyclobutanedicarboxylate and oxalate ligand, respectively. Such protonation has been postulated by several theoretical studies as a key preliminary step in the hydrolysis of Pt drugs under acidic conditions. Subsequently, the protonated drugs react with guanine in solution to generate a complex of general formula [Pt drug + H + guanine]