Pt(iv) analogs of oxaliplatin that do not follow the expected correlation between electrochemical reduction potential and rate of reduction by ascorbate

Abstract

In contrast to the Pt(IV) derivatives of cisplatin, Pt(IV) derivatives of oxaliplatin do not show the expected correlation between the electrochemical reduction potentials and rates of reduction by ascorbate. This is probably due to the lower ability of the amine and carboxylato ligands to form a bridge with the reducing agents to facilitate electron transfer.

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

“…They did not however suggest that GSH was the reducing agent [76][77][78]. Similarly, Nakai reported that when the cis-diamminetetrachlorido-platinum(II) complex was reduced by GSH, cisplatin-GSH adducts were formed that sequestered the cisplatin away from the DNA [79]. Dabrowiak noted that when oxoplatin and its carboxylate analog were reduced with GSH, cisplatin is not produced in the reaction medium.…”

De Novo Generation of Singlet Oxygen and Ammine Ligands by Photoactivation of a Platinum Anticancer Complex

“…There are a number of reports of the chemical reduction of Pt IV to Pt II , and it is widely accepted that a concerted twoelectron transfer from, for example, ascorbate, GSH, or guanine, to Pt IV is involved. [12,15] However, the photoreduction of 1 may not follow the above pathway. Pt IV is more likely to gain one electron from each of the two N 3 or two OH ligands and give rise to N 3 C or OHC radicals, respectively.…”

Unsymmetric Mono- and Dinuclear Platinum(IV) Complexes Featuring an Ethylene Glycol Moiety: Synthesis, Characterization, and Biological Activity

“…Therefore, these compounds are prodrugs that have to undergo extracellular or preferably intracellular reduction by agents like ascorbic acid, glutathione, or high molecular weight biomolecules, thereby resulting in the antitumor active square-planar platinum(II) metabolites. [24][25][26][27][28] Thus, the activity of these complexes depends on a range of bioinorganic and pharmacological attributes like the reduction potential, lipophilicity and solubility, binding behavior to biomolecules, and inertness with regard to ligand exchange reactions. [29][30][31] Several studies show that the type of axial ligands has an exceptionally high influence on the reduction potential and consequently on the cytotoxicity (chlorido ligands, high reduction potential and high cytotoxicity; hydroxido ligands, low reduction potential and low cytotoxicity).…”