Anticancer half-sandwich Ir(III) complex and its interaction with various biomolecules and their mixtures - a case study with ascorbic acid

The extent of interactions with various biomolecules is a crucial feature of newly developed metallodrugs, worthy of thorough investigation, as its understanding helps uncover the fate of these xenobiotics in the physiological environment. In this work, promisingly cytotoxic half-sandwich complexes [Ru(eta(6)-pcym)Cl(L-1)]PF6 (1), [Ir(eta(5)-Cp*)Cl(L-1)]PF6 (2) and [Ir(eta(5)-Cp*)Cl(L-2)]PF6 (3), with 2-{n-[(E)-phenyldiazenyl]pyridin-2-yl)-1H-benzimidazole as a bidentate N-donor azo ligand (n = 5 for L-1 and 6 for L-2; pcym = p-cymene, Cp* = pentamethylcyclopentadienyl), were subjected to an extensive and detailed study of interactions with a plethora of extra- and intracellular biologically relevant molecules. For the first time in the field of anticancer half-sandwich complexes, mixtures of 3 with ascorbic acid (ASA) and its combinations with reduced glutathione (GSH) and/or reduced nicotinamide adenine dinucleotide (NADH) were studied. Complex 3 undergoes azo bond reduction when mixed with NADH or ASA, which oxidizes to NAD(+) or dehydroascorbate (DHA), respectively. Intriguingly, the presence of the natural antioxidant ASA has a relevant prooxidative impact on GSH, which is connected with ASA recovery from DHA. Although the azo bond of L-2 involved in 3 seems to be the reaction centre for the dehydrogenation reactions of the biomolecules, L-2 by itself is a negligible oxidant and thus complexation in 3 represents a necessary prerequisite for the redox reactions.

Automated summary

The study investigated the interactions of newly developed metallodrugs with various biomolecules, revealing the reduction and oxidation reactions of azo bonds in the presence of certain biologically relevant molecules. The complexation of the metallodrugs played a crucial role in facilitating these redox reactions, shedding light on the mechanisms of action in extracellular and intracellular environments.