Optimizing the Electronic Properties of Photoactive Anticancer Oxypyridine-Bridged Dirhodium(II,II) Complexes

A series of partial paddlewheel dirhodium compounds of general formula cis-[Rh2­(xhp)2­(CH3CN) n ]­[BF4]2 (n = 5 or 6) were synthesized {xhp = 6-R-2-oxy­pyridine ligands, R = −CH3 (mhp), −F (fhp), −Cl (chp)}. X-ray crystallographic studies indicate the aforementioned compounds contain two cis-oriented bridging xhp ligands, with the remaining sites being coordinated by CH3CN ligands. The lability of the equatorial (eq) CH3CN groups in these complexes in solution is in the order −CH3 > −Cl > −F, in accord with the more electron rich bridging ligands exerting a stronger trans effect. In the case of cis-[Rh2­(chp)2­(CH3CN)6]­[BF4]2 (5), light irradiation enhances the production of the aqua adducts in which eq CH3CN is replaced by H2O molecules, whereas the formation of the aqua species for cis-[Rh2­(fhp)2­(CH3CN)6]­[BF4]2 (7) is only slightly increased by irradiation. The potential of both compounds to act as photo­chemo­therapy agents was evaluated. A 16.4-fold increase in cytotoxicity against the HeLa cell line was observed for 5 upon 30 min irradiation (λ > 400 nm), in contrast to the nontoxic compound 7, which is in accord with the results from the photochemistry. Furthermore, the cell death mechanism induced by 5 was determined to be apoptosis. These results clearly demonstrate the importance of tuning the ligand field around the dimetal center to maximize the photoreactivity and achieve the best photodynamic action.