What do we know about the reduction of Pt(IV) pro-drugs?

Platinum(IV) pro-drugs are an important class of molecules that might improve the pharmacological properties of the platinum(II) anticancer agents that are currently used in the clinic. Their axial ligands that are detached during cellular activation by reductive elimination can be used to confer favorable pharmacological properties to the complexes allowing for potentially lower toxicity and improved efficacy. This manuscript describes the various approaches taken to design and prepare Pt(IV) complexes that will be effective anticancer agents. We review the working hypotheses guiding the researchers in the field while pointing out some more recent results that contradict some of the accepted paradigms in the hope of triggering some rethinking of the existing working hypotheses.