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

A series of partial paddlewheel dirhodium compounds of general formula <i>cis</i>-[Rh₂­(xhp)₂­(CH₃CN)<i>_n</i>]­[BF₄]₂ (<i>n</i> = 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 <i>cis</i>-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 <i>trans</i> effect. In the case of <i>cis</i>-[Rh₂­(chp)₂­(CH₃CN)₆]­[BF₄]₂ (<b>5</b>), 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 <i>cis</i>-[Rh₂­(fhp)₂­(CH₃CN)₆]­[BF₄]₂ (<b>7</b>) 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 <b>5</b> upon 30 min irradiation (λ > 400 nm), in contrast to the nontoxic compound <b>7</b>, which is in accord with the results from the photochemistry. Furthermore, the cell death mechanism induced by <b>5</b> 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