Towards Copper(I) Clusters for Photo-Induced Oxidation of Biological Thiols in Living Cells

The cell redox balance can be disrupted by the oxidation of biological peptides and lead to the cell death, which paves the way for a new class of cytotoxic drugs. With the aim of developing compounds capable of specifically inducing fatal redox reactions upon irradiation, we have developed a library of copper compounds. This metal is abundant and considered essential for human health, making it particularly attractive for the development of new anticancer drugs. Copper(I) clusters with thiol ligands (including 5 novel ones) have been synthesized and characterized. Structures were elucidated by X-ray diffraction and show that the compounds are oligomeric clusters. The clusters display high photooxidation capacity towards cysteine – an essential amino acid – upon irradiation in the visible range (450 nm), while remaining completely inactive in the dark. This photoredox activity against a biological thiol was very encouraging for the development of an anticancer photoredox drug. However, the in vitro assay on murine cancer cells did not show any toxicity – whether in the dark or when exposed to 450 nm light, likely because of the poor solubility of the complexes in biological medium.