Biotransformation of ruthenium(III) anticancer complexes as hypothesized in the activation-by-redn. theory is the central topic of the present paper. The redox behavior of tetrachlorobis(azole)ruthenate(III)-type complexes was studied by NMR spectroscopy and square wave voltammetry. The influence of reducing agents on the binding behavior toward the DNA-modeling nucleotide GMP was detd. by capillary electrophoresis, accompanied by identification of arising peaks by online coupling to electrospray ionization mass spectrometry. The detn. of redox potentials revealed that the biol. relevant reductants ascorbic acid and glutathione are capable of reducing the studied Ru(III) complexes under physiol. conditions. Characteristic differences in redn. kinetics dependent on the pH value can be explained by higher redn. strength of ascorbic acid and glutathione at higher pH compared to the pH-independent redox response of ruthenium(III) complexes. Binding behavior of (H2ind)[trans-RuCl4(Hind)2] (Hind = 1H-indazole) toward GMP was found to be increased upon addn. of two equiv. of glutathione but not of ascorbic acid. In contrast, only a minor influence on the GMP-binding under reductive conditions was found for (H2i.m.)[trans-RuCl4(Him)2] (KP418, Him = 1H-imidazole). [on SciFinder (R)] ; CAN 144:480387 1-3 Pharmacology Institute of Inorganic Chemistry-Bioinorganic, Environmental and Radiochemistry, Faculty of Chemistry,University of Vienna,Vienna,Austria. Journal 50-81-7 (Ascorbic acid); 70-18-8 (Glutathione); 5550-12-9 Role: BSU (Biological study, unclassified), BIOL (Biological study) (redox behavior of tumor-inhibiting ruthenium complexes and effects of physiol. reductants on their binding to GMP); 103875-27-0 (KP418); 124875-20-3 (KP1019); 197723-00-5 (KP1339) Role: PAC (Pharmacological activity), THU (Therapeutic use), BIOL (Biological study), USES (Uses) (redox behavior of tumor-inhibiting ruthenium complexes and effects of physiol. reductants on their binding to GMP)