Biological Studies of Dirhodium(II,II) Compounds and Their Applications as Photochemothreapeutic Agents

The work contained in this dissertation focuses on the synthesis and characterization of dirhodium (II,II) compounds and studies of their anticancer activities against cervical and ovarian cancer cell lines. It has been demonstrated that tailoring the coordination environment of the dirhodium core and irradiation using low energy light (λ > 400 nm) dramatically affects the anticancer properties of the compounds. In order to improve the anticancer activity of dirhodium compounds, a series of compounds containing two different bridging ligands was prepared and characterized. A new precursor was prepared from the reactions of dirhodium tetraacetate with N,N’-2,6-o-difluoroformamidinate to afford, [Rh2(F2form)(μ-O2CCH3)3] (1). Compound 1 was reacted with diimine ligands phen (2) (1,10-phenathroline), dpq (3) (dipyrido[3,2-f:2',3'-h]-quinoxaline), dppz (4) (dipyrido[3,2-a:2’,3’-c]phenazine) and (5) dppn (benzo[i]dipyrido[3,2-a:2’,3’-h]quinoxaline) to obtain compounds of general formula [Rh2(F2form)(μ-O2CCH3)(NN)2]^2+. Compounds 2-5 exhibit significant photocytotoxic activities against HeLa, COLO-316, OVCAR-8 and NCI-ADR/RES. This new family of compounds is capable of depleting mitochondrial potential and inducing cell death on a short time scale (~ 10 min) after irradiation with compounds 4 and 5 being the most active of the series. The ease of tuning dirhodium compounds prompted the study of another series of the mixed-bridging ligand compounds [Rh2(F2form)(μ-O2CCH3)(CH3CN)6]^2+ (6) and [Rh2(Ph2P(C6H4))(μ-O2CCH3)(CH3CN)6]^2+ (7). The presence of strong σ-donating ligands renders the trans CH3CN ligands labile in the dark, whereas the ones trans to the acetate are stable. These compounds were found not to exhibit significant anticancer activity against HeLa cells but they may be used as scaffolds for further functionalization with biologically or photocatalytically active ligands. The antioxidant, antineoplastic molecule 2-pyrrolidinone was used as a bridging ligand in the partially solvated dirhodium complexes [Rh2(μ-NOC4H6)2(NOC4H7)ax(CH3CN)5]^2+ (8) and [Rh2(μ-NOC4H6)2(NOHC4H6)eq(CH3CN)5]^2+ (9). The aim of this chapter was to design a multifunctional drug that, upon irradiation, releases the anticancer drug 2-pyrrolidione and has open coordination sites that are available to bind to other biological molecules. Compound 8 does not exhibit anticancer properties upon irradiation, but 9 induces a 22-fold increase in cytotoxicity as compared to the dark control. These results are highly promising indicators that designer heteroleptic dirhodium compounds hold considerable potential as prodrugs for photochemotherapy