title: Optimizing the electronic properties of photoactive anticancer oxypyridine-bridged dirhodium(II,II) complexes.
abstract: 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.
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77840, United States.
authors.forename: Zhanyong
authors.initials: Z
authors.lastname: Li
authors.forename: Amanda
authors.initials: A
authors.lastname: David
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Albani
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Pellois
authors.forename: Claudia
authors.initials: C
authors.lastname: Turro
authors.forename: Kim R
authors.initials: KR
authors.lastname: Dunbar
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004583:Electrons; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D055668:Photochemical Processes; D010778:Photochemotherapy; D011725:Pyridines / Q000737:chemistry*; D012238:Rhodium / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D011725:Pyridines; D012238:Rhodium