Cyclometalated Rhodium(III) Polypyridyl Complexes with Anti-Cancer Stem Cell Activity

Investigations into the anticancer stem cell (CSC) properties of rhodium complexes are extremely rare. Here we report the synthesis, characterization, photophysical properties, and <i>in vitro</i> anti-CSC activity of a series of cyclometalated rhodium-(III)-polypyridyl complexes <b>1</b>-<b>4</b>. The 4,7-diphenyl-1,10-phenanthroline-bearing complex <b>4</b> exhibits activity against monolayer- and three-dimensionally cultured breast CSCs and osteosarcoma stem cells in the sub-micromolar to low micromolar range, outperforming the metallodrug cisplatin and the established anti-CSC agent salinomycin. Our results suggest that the reported rhodium-(III) scaffold, containing cyclometalated 2,2'-(phenylmethylene)-dipyridine, could be a useful synthon for the future development of anti-CSC rhodium complexes.