01 December 2022

Séminaire ICP Davide Corinti – jeudi 1er décembre à 14h

Davide Corinti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza- Università di Roma, Roma, Italy, will give a seminar on Thursday, December 1st 2022 at 2 pm in salle Magat



The periodic table for a medicinal chemist or a biochemist is usually restricted to very few elements. More than 95% of the mass of living systems is indeed composed by carbon, hydrogen, nitrogen and oxygen. Besides, elements present only in trace amount can have irreplaceable roles in the chemistry of life. Even more surprisingly, transition metals completely unrelated to living systems have found their way in therapy and, nowadays, antineoplastic drugs containing for example platinum are widespread. The use of electrospray ionization (ESI) mass spectrometry (MS) allows to capture from solution elusive metal-containing species whose characterization may shed light on reaction mechanisms of biological relevance and about coordination sites of biomolecules in binding metals. As an example, a novel way of exploring the interaction of platinum complexes with biomolecules will be presented, based on the study of non-covalent encounter complexes delivered from solution as isolated gaseous species.  Formally penta-coordinated cisplatin-derived complexes presenting an aminoacid together with a water ligand (cis-[PtCl(NH3)2(AA)(H2O)]+) were characterized by IR ion spectroscopy. Those species represent the first step of the substitution reaction between the aqua complex of cisplatin and the incoming aminoacid, namely the encounter complex along the reaction coordinate of the bimolecular reaction in solution. ESI-MS was also able to reveal the encounter complex of platinum(IV) prodrugs with ascorbic acid. This complex was subsequently assayed using IR ion spectroscopy, allowing to obtain significant structural information. The resulting photofragmentation pattern showed the presence of Pt(II) containing fragments, thus proving the reduction process to happen when the encounter complex is activated. Finally, DFT calculations of the energy surface for the reduction reaction revealed crucial interactions between the axial ligands and ascorbic acid.

- D. Corinti, G. Frison, B. Chiavarino, E. Gabano, D. Osella, M.E. Crestoni, S. Fornarini, Can an Elusive Platinum(III) Oxidation State be Exposed in an Isolated Complex?, Angew. Chemie Int. Ed. 59 (2020) 15595–15598. doi:10.1002/anie.202007597.

- D. Corinti, M.E. Crestoni, B. Chiavarino, S. Fornarini, D. Scuderi, J.-Y. Salpin, Insights into Cisplatin Binding to Uracil and Thiouracils from IRMPD Spectroscopy and Tandem Mass Spectrometry, J. Am. Soc. Mass Spectrom. 31 (2020) 946–960. doi:10.1021/jasms.0c00006.

- D. Corinti, M.E. Crestoni, S. Fornarini, E. Dabbish, E. Sicilia, E. Gabano, E. Perin, D. Osella, A multi-methodological inquiry of the behavior of cisplatin-based Pt(IV) derivatives in the presence of bioreductants with a focus on the isolated encounter complexes, JBIC J. Biol. Inorg. Chem. 25 (2020) 655–670. doi:10.1007/s00775-020-01789-w.

- R. Paciotti, D. Corinti, P. Maitre, C. Coletti, N. Re, B. Chiavarino, M.E. Crestoni, S. Fornarini, From Preassociation to Chelation: A Survey of Cisplatin Interaction with Methionine at Molecular Level by IR Ion Spectroscopy and Computations, J. Am. Soc. Mass Spectrom. 32 (2021) 2206–2217. doi:10.1021/jasms.1c00152.

- D. Corinti, R. Paciotti, C. Coletti, N. Re, B. Chiavarino, M.E. Crestoni, S. Fornarini, Elusive intermediates in cisplatin reaction with target amino acids: Platinum(II)-cysteine complexes assayed by IR ion spectroscopy and DFT calculations, J. Inorg. Biochem. 237 (2022) 112017. doi:10.1016/j.jinorgbio.2022.112017.

01 December 2022, 14h0015h00
Salle Magat, ICP