Investigation of cobalt(iii)-TPA complexes as potential bioreductively activated carriers for naphthoquinone-based drugsElectronic supplementary information (ESI) available. CCDC 1567378-1567380. see DOI: 10.1039/c7nj03072j

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 Co 3+ /Co 2+ potential. The expected [Co(TPA)(NQ-X)] 2+ species was obtained for the NQ-CH 3 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 Co 3+ /Co 2+ 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. Differently from CH 3 , halogens as substituents foster incorporation of methoxide into NQs upon complexation.