| Autor: |
Chiavarino B; Dipartimento di Chimica e Tecnologie del Farmaco, Università di Roma 'La Sapienza', P.le A. Moro 5, Roma I-00185, Italy., Rotari L; Dipartimento di Chimica e Tecnologie del Farmaco, Università di Roma 'La Sapienza', P.le A. Moro 5, Roma I-00185, Italy., Crestoni ME; Dipartimento di Chimica e Tecnologie del Farmaco, Università di Roma 'La Sapienza', P.le A. Moro 5, Roma I-00185, Italy., Corinti D; Dipartimento di Chimica e Tecnologie del Farmaco, Università di Roma 'La Sapienza', P.le A. Moro 5, Roma I-00185, Italy., Fornarini S; Dipartimento di Chimica e Tecnologie del Farmaco, Università di Roma 'La Sapienza', P.le A. Moro 5, Roma I-00185, Italy., Scuderi D; CNRS, Institut de Chimie Physique, Université Paris-Saclay, Orsay 91405, France., Salpin JY; Université Paris-Saclay, Univ Evry, CY Cergy Paris Université, CNRS, LAMBE, Evry-Courcouronnes 91025, France. |
| Abstrakt: |
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] + , which was then mass-selected. CID experiments provided evidence of the presence of strong binding between guanine and platinum-based drugs within the complexes. The structures of the two complexes have also been examined by comparing the experimental IRMPD spectra recorded in two spectral regions with DFT-computed IR spectra. For each system, the IRMPD spectra agree with the vibrational spectra calculated for the global minimum structures, which present a monodentate complexation of Pt at the N7 position of canonical guanine. This binding scheme is therefore akin to that observed for cisplatin, while other coordination sites yield substantially less stable species. Interestingly, in the case of oxaliplatin, the IRMPD spectra are consistent with the presence of two isomeric forms very close in energy. |
