Precious metal N-heterocyclic carbene-carbaboranyl complexes: Cytotoxic and selective compounds for the treatment of cancer

A range of precious metal complexes incorporating either benzyl or carbaboranyl functionalised tethered N-heterocyclic carbenes have been prepared and fully characterised, including single crystal X-ray crystallography for one new complex. The library has been screened for their anti-cancer potential against colorectal, ovarian, cisplatin-resistant ovarian and breast cancer cell lines and their selectivity determined by comparing the cytotoxicity towards normal cells. Overall, these complexes show significant selectivity for ovarian carcinoma, and are up to 3-fold more cytotoxic than cisplatin against cisplatin-resistant human ovarian carcinoma. Upon replacing the benzyl moiety of the NHC ligand with a carbaboranyl there is a general increase observed in the potency of the complexes, with the cytotoxicity of the ruthenium complex increasing by >16-fold against human ovarian carcinoma. Generally, the rhodium complex with the benzyl tethered NHC shows the greatest selectivity for cancer, with a selectivity index of 15, which is >2x, >9x and >6x higher than that of cisplatin, carboplatin and oxaliplatin, respectively