Investigation of cobalt(iii)–TPA complexes as potential bioreductively activated carriers for naphthoquinone-based drugs

Abstract

Four cobalt(III)–TPA complexes with 2-hydroxy-3-X-1,4-naphthoquinones (HNQ-X), X = methyl (1), chlorine (2), bromine (3) and iodine (4), were designed and investigated as potential bioreductively activated carriers for naphthoquinone-based drugs. The substituents X were used in order to avoid dimerization of the naphthoquinone ligands and evaluate their effect on the Co³⁺/Co²⁺ potential. The expected [Co(TPA)(NQ-X)]²⁺ species was obtained for the NQ-CH₃ ligand in 1, while the chlorine, bromine and iodine derivatives fostered the attachment of a methoxide to the C(1)_carbonyl atom to produce complexes 2, 3 and 4, respectively. The structure and electronic properties of the complexes were investigated by single crystal X-ray diffraction analysis and DFT calculations. Cyclic voltammetry analysis showed that the Co³⁺/Co²⁺ potential is 0.21 V for complex 1 and 0.32 V vs. SHE for complexes 2–4. Redox activation with dissociation of the naphthoquinones was successfully achieved by reduction of the complexes with the biologically relevant reducing agent ascorbic acid.