Cobalt(III) complexes with 2-acetylpyridine-derived Schiff bases: Studies investigating ligand release upon reduction

Abstract Cobalt(III) complexes [Co(L1) 2 ]Cl·CH 3 OH·0.5H 2 O ( 1 ), [Co(L2) 2 ]Cl·1.5H 2 O ( 2 ), [Co(L3) 2 ]Cl·2H 2 O ( 3 ) and [Co(L4) 2 ]Cl·3.5H 2 O ( 4 ) were obtained with 2-acetylpyridine- N (4)-phenylthiosemicarbazone (HL1), 2-acetylpyridine- N (4)- para -chlorophenylthiosemicarbazone (HL2), 2-acetylpyridine-phenylhydrazone (HL3) and 2-acetylpyridine- para -chlorophenylhydrazone (HL4). The complexes were characterized by means of microanalyses, molar conductivities and their infrared and 1 H and 13 C NMR spectra. Electrochemical studies showed that the Co III /Co II reduction potential of complexes ( 3 ) and ( 4 ) but not of complexes ( 1 ) and ( 2 ) are suitable for the compounds to be reduced by cellular reductants. Reactivity assays showed that complex ( 3 ) undergoes reduction by sodium dithionite with subsequent ligand release. The results suggested that coordination of 2-acetylpyridine-derived hydrazones with cytotoxic activity to cobalt(III) results in compounds which are able to release the bioactive ligand upon reduction. In addition, the cobalt(III) complexes under study interacted with human serum albumin (HSA), indicating that they could be transported by this protein.