Protonation of Pt(IV) Anticancer Complexes Assayed by Vibrational Ion Spectroscopy
Year: 2025
Type: article
Abstract: Platinum(IV) complexes are being studied as potential alternatives to traditional platinum(II)-based chemotherapy drugs. They promise reduced side effects and potential for oral administration. In fact, a preliminary reduction in the cellular medium is recognized as a crucial step for activation. However, a deeper understanding of the protonation sites and substitution behavior of Pt(IV) complexes is needed, considering that ligand hydrolysis may compete with reduction-mediated activation, particularly in acidic environments such as the stomach. In this study, we investigated protonated Pt(IV) complexes with equatorial ligands common to widely used Pt(II) drugs containing square planar geometry, such as cisplatin and carboplatin. The additional axial substituents in the octahedral coordination sphere of Pt(IV) include different combinations of hydroxido and acetato ligands. Mass spectrometry-based methods, including collision-induced dissociation (CID) and infrared multiple photon dissociation (IRMPD) spectroscopy, supported by density functional theory (DFT) calculations, were employed. Structural characterization revealed that protonation preferences are influenced by the type and position of the ligands. Notably, protonation is generally favored on the carboxylato ligands; however, the carboplatin-derived complex exhibited a mixed population of protomers, highlighting the significance of both axial and equatorial ligand configurations in shaping the prototropic equilibria happening in solution.
Source: ChemPlusChem
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,030
Funder: Sapienza Università di Roma
Award: G3631972369
OpenAlex ID: W4408549759