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, eventually leading to cell death, which provides opportunities to develop cytotoxic drugs. With the aim of developing compounds capable of specifically inducing fatal redox reactions upon light 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 showed that the compounds are oligomeric clusters. The clusters display high photooxidation capacity towards cysteine - an essential amino acid - upon light irradiation in the visible range (450 nm), while remaining completely inactive in the dark. This photoredox activity against a biological thiol is very encouraging for the development of anticancer photoredox drugs.The in vitro assay on murine colorectal cancer cells (CT26) 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.