B. Chiavarino ; M. E.Crestoni ; S. Fornarini ; D. Scuderi ; J-Y. Salpin
Inorg. Chem. 56(15) 8793-8801 (2017). DOI

Travail réalisé sur le site de l’Université Paris Sud.

Abstract

The complex obtained by the reaction of cisplatin and 2′-deoxyadenosine-5′-monophosphate (5′-dAMP) in water has been isolated and detected by electrospray ionization mass spectrometry. The so-formed cis-[PtCl(NH3)2(5′-dAMP)]+ complex has been studied in detail by infrared multiple photon dissociation (IRMPD) spectroscopy in two spectral ranges, namely, 700–1900 and 2800–3800 cm–1, backed by quantum-chemical calculations at the B3LYP/LACV3P/6-311G** level of theory. In agreement with the computational results, the vibrational spectroscopic characterization of cis-[PtCl(NH3)2(5′-dAMP)]+ shows that the sampled ionic population comprises two major isomers, differentiated in the X–H stretching region by their distinct fragmentation patterns. One of these species presents coordination of the platinum moiety at the N3 position of adenine, whereas in the second one, platinum is bound at the N1 position of adenine. IRMPD kinetics have allowed an estimation of their relative proportions. Surprisingly, the most abundant component of cis-[PtCl(NH3)2(5′-dAMP)]+ is the N3 isomer, although it is slightly less stable than the other potential isomers in the gas phase. In contrast, the lowest-energy species, namely, the one showing cisplatin binding to the N7 position of adenine, seems to be the one less represented in the sampled ionic population. These findings suggest that the reaction of cisplatin with 5′-dAMP is governed by the kinetics of the process occurring in solution rather than by the thermodynamic factors.