Interaction of Cisplatin with Adenine and Guanine: A Combined IRMPD, MS/MS, and Theoretical Study

Barbara Chiavarino (1) , Maria-Elisa Crestoni (1) , Simonetta Fornarini (1) , Debora Scuderi (2) , Jean-Yves Salpin (3)

1 Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive
2 LCPO - Laboratoire de Chimie Physique D'Orsay
3 LAMBE - Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement

Infrared multiple photon dissociation (IRMPD) spectroscopy of cis-[Pt(NH₃)₂(G)Cl]⁺ and cis-[Pt(NH₃)₂(A)Cl]⁺ ions (where A is adenine and G is guanine) has been performed in two spectral regions, 950-1900 and 2900-3700 cm^-1. Quantum chemical calculations at the B3LYP/LACV3P/6-311G** level yield the optimized geometries and IR spectra for the conceivable isomers of cis-[Pt(NH₃)₂(G)Cl]⁺ and cis-[Pt(NH₃)₂(A)Cl]⁺, whereby the cisplatin residue is attached to the N7, N3, or carbonyl oxygen atom, (O6), of guanine and to the N7, N3, or N1 position of adenine, respectively. In addition to the conventional binding sites of native adenine, complexes with N7-H tautomers have also been considered. In agreement with computational results, the IR characterization of cis-[Pt(NH₃)₂(G)Cl]⁺ points to a covalent structure where Pt is bound to the N7 atom of guanine. The characterized conformer has a hydrogen-bonding interaction between a hydrogen atom of one NH₃ ligand and the carbonyl group of guanine. The experimental C═O stretching feature of cis-[Pt(NH₃)₂(G)Cl]⁺ at 1718 cm^-1, remarkably red-shifted with respect to an unperturbed C═O stretching mode, is indicative of a lengthened CO bond in guanine, a signature that this group is involved in hydrogen bonding. The IRMPD spectra of cis-[Pt(NH₃)₂(A)Cl]⁺ are consistent with the presence of two major isomers, PtAN3 and PtAN1, where Pt is bound to the N3 and N1 positions of native adenine, respectively.

Mots clés: AdenineIons; Antineoplastic agents; Guanine; Molecular structure

Domaines: Chimie-Physique [physics.chem-ph]

Barbara Chiavarino, Maria-Elisa Crestoni, Simonetta Fornarini, Debora Scuderi, Jean-Yves Salpin. Interaction of Cisplatin with Adenine and Guanine: A Combined IRMPD, MS/MS, and Theoretical Study. Journal of the American Chemical Society, 2013, 135 (4), pp.1445-1455. ⟨10.1021/ja309857d⟩. ⟨hal-00796084⟩