A detailed computational exploration of the most relevant steps of iodido Pt(IV) complexes reduction and Pt(II) drugs mechanism of action and eventual deactivation is presented here inspired by the recent findings on iodido Pt(II) complexes and surprising re-evaluation of their cytotoxic activity. Pt(II) and Pt(IV) model systems are investigated and compared with cisplatin and its Pt(IV) derivative. Both monodeprotonated ascorbic acid and l-cysteine are used as reducing agents in the inner-sphere reduction mechanism of Pt(IV) complexes. Aquation mechanism of iodido Pt(II) complexes, interaction with guanine and sulfur containing compounds and reaction with the model protein hen egg white lysozyme are explored, due to a detected different behavior with respect to classical platinum drugs. The outcomes of such exploration allow to shed light on the role that the increased soft character together with bridging and leaving abilities of iodide over chloride could play in determining the cytotoxic profile of iodido Pt drugs.
Keywords: DFT; Pt iodido complexes; Pt(II) mechanism of action; Pt(IV) reduction.
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