Encounter complex of adenine with Carboplatin and Oxaliplatin anticancer drugs elucidated by IRMPD spectroscopy and theoretical study

Ionic complexes containing the nucleobase adenine and either carboplatin (CarboPt) or oxaliplatin (OxaliPt) were generated in solution and subsequently studied in the gas phase by combining tandem mass spectrometry, infrared multiple photon dissociation (IRMPD) spectroscopy, and density functional theory (DFT) calculations. The protonated complexes of the general formula [Pt drug+H+adenine]+ were first analyzed by collision-induced dissociation (CID). Their CID mass spectra show only one fragment, corresponding to the loss of neutral adenine. The structure of these complexes was elucidated by comparing their IRMPD spectra recorded in the fingerprint and H-X stretching ranges with DFT-calculated IR spectra. Unexpectedly, the IRMPD spectra of both complexes were not consistent with the calculated vibrational spectra of structures characterized by direct platinum-adenine coordination. All spectroscopic evidence suggest that each sampled [Pt drug+H+adenine]+ ion population comprises multiple proton-bound complexes stabilized by hydrogen bonds between the drug carboxylate groups and protonated adenine. Interestingly, while calculations support an external binding scheme in protonated adenine-oxaliplatin complexes, in the case of carboplatin, a direct monodentate interaction of Pt with N1, N3, or N7 positions of adenine turns out to be energetically favored. This study adds further evidence of the intrinsic lower affinity of platinum for adenine relative to guanine.