Investigation of Cobalt(III)‐Tetrachlorocatechol Complexes as Models for Catechol‐Based Anticancer Prodrugs

Two novel cobalt(III) complexes, [Co(TPA)(TCC)]ClO4·H2O (1) and [Co(py2en)(TCC)]ClO4·2H2O (2), were synthesized and fully characterized by IR, UV/Vis and 1H NMR spectroscopy, ESI mass spectrometry, and X‐ray diffraction. Cyclic voltammetry experiments revealed an irreversible reduction of the Co3+ center for both complexes. The Co3+/Co2+ redox potential, –0.91 V for 1 and –1.15 V for 2 (vs. Fc/Fc+), was obtained by square wave voltammetry in DMSO. Reactions of 1 and 2 with ascorbic acid and sodium dithionite at pH 7.4 and 6.2 were carried out in argon and open‐air atmospheres, to simulate biological redox activation under hypoxia and normoxia. Neither the Co3+/Co2+ reduction nor the dissociation of TCC2– was observed. Thermodynamic parameters calculated for the Co3+/Co2+ reduction and substitution of the TCC2– ligand by water indicate an endothermic non‐spontaneous reaction. The two CoII‐TCC complexes are unreactive regarding ligand exchange in DMSO, aqueous solutions, or in the presence of reducing agents. The Co3+/Co2+ potential (–0.91 and –1.15 V vs. Fc/Fc+) denotes the stability of the +3 oxidation state. The calculated Gibbs free energy for the Co3+/Co2+ reduction followed by the substitution of TCC2– by water points to non‐spontaneous endothermic reactions.