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Insights from Computations on the Mechanism of Reduction by Ascorbic Acid of Pt IV Prodrugs with Asplatin and Its Chlorido and Bromido Analogues as Model Systems
Author(s) -
Ponte Fortuna,
Russo Nino,
Sicilia Emilia
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201800488
Subject(s) - ascorbic acid , chemistry , prodrug , ligand (biochemistry) , combinatorial chemistry , electron transfer , redox , platinum , reduction (mathematics) , stereochemistry , computational chemistry , catalysis , organic chemistry , mathematics , biochemistry , food science , geometry , receptor
The elucidation of the mechanism by which the reduction of coordinatively saturated Pt IV prodrugs occurs, leading to the release of the two axial ligands, is of foremost importance, being the key step for the activation of these anticancer compounds, and addressing their synthetic strategies. A systematic DFT computational analysis of the reduction process by small biomolecules, which is supposed to occur by inner‐ or outer‐sphere electron‐transfer mechanisms, has been undertaken using the recently synthesised Asplatin Pt IV complex, c , c , t ‐[PtCl 2 (NH 3 ) 2 (OH)(aspirin)], as model system and l ‐ascorbic acid as reducing agent. Further calculations have been carried out on Asplatin analogues that should be obtained replacing the OH − ligand with Cl − and Br − . The most accredited inner‐sphere mechanistic suggestions have been explored and a recently proposed computational methodology has been applied to estimate the corresponding standard redox potentials, which cannot be directly obtained from voltammetric experiments due to the irreversibility of the platinum(IV)‐to‐platinum(II) reduction process.