Elusive Intermediates in the Breakdown Reactivity Patterns of Prodrug Platinum(IV) Complexes

  • Davide Corinti
  • Maria Elisa Crestoni
  • Simonetta FornariniEmail author
  • Fortuna Ponte
  • Nino Russo
  • Emilia SiciliaEmail author
  • Elisabetta Gabano
  • Domenico OsellaEmail author
Focus: Honoring Helmut Schwarz’s Election to the National Academy of Sciences: Research Article


Kinetically inert platinum(IV) complexes are receiving growing attention as promising candidates in the effort to develop safe and valid alternatives to classical square-planar Pt(II) complexes currently used in antineoplastic therapy. Their antiproliferative activity requires intracellular Pt(IV)–Pt(II) reduction (activation by reduction). In the present work, a set of five Pt(IV) complexes has been assayed using mass spectrometry–based techniques, i.e., collision-induced dissociation (CID), and IR multiple photon dissociation (IRMPD) spectroscopy, together with ab initio theoretical investigations. Breakdown and reduction mechanisms are observed that lead to Pt(II) species. Evidence is found for typically transient Pt(III) intermediates along the dissociation paths of isolated, negatively charged (electron-rich) Pt(IV) prodrug complexes.


Collision-induced dissociation IRMPD spectroscopy FT-ICR mass spectrometry Reduction processes Cisplatin 



This work has been supported by Università della Calabria, Università del Piemonte Orientale, and Università di Roma “La Sapienza” (DR n. 3210/16), by the European Union’s Horizon 2020 research and innovation program under grant agreement no. 731077, and by the French FT-ICR network (FR3624CNRS). We are indebted to Inter-University Consortium for Research on the Chemistry of Metals in Biological Systems (CIRCMSB, Bari, Italy) for providing opportunities of stimulating discussion during the annual meetings.

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© American Society for Mass Spectrometry 2019

Authors and Affiliations

  1. 1.Dipartimento di Chimica e Tecnologie del FarmacoUniversità di Roma “La Sapienza”RomeItaly
  2. 2.Department of Chemistry and Chemical TechnologiesUniversità della CalabriaArcavacata di RendeItaly
  3. 3.Dipartimento di Scienze e Innovazione TecnologicaUniversità del Piemonte OrientaleAlessandriaItaly

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