Probing chemical reduction in a cobalt(III) complex as a viable route for the inhibition of the 20S proteasome

Abstract In this paper we evaluate the viability of ligand dissociation in the cobalt complex [Co III (L 1 ) 2 ]ClO 4 ( 1 ) following biological reduction. We performed detailed electrochemical characterization of 1 in several solvents, along with spectroelectrochemical and chemical reduction to monitor the phenolate-to-cobalt(III) LMCT band observed at 440 nm in the UV–Vis region in presence and absence of a sacrificial reductant. DFT calculations were performed to confirm the nature of this band. Species 1 displays no signs of ligand protonation at pH 3 over a period of 24 h while probing its stability in solution. Spectrophotometric monitoring at pH 3 in presence of ascorbic acid shows clearly a decrease of the LMCT band, implying that reduction of the metal center has taken place. The products of chemical reduction were analyzed by high resolution ESI + mass spectrometry and support a mechanism in which biological reduction leads to ligand dissociation.