| In photodynamic therapy (PDT) the action of light-activated drugs is controlled by targeted light irradiation. Current PDT agents are inactive in the hypoxic tissues in solid tumors and other malignant cells, and new drugs that do not require intracellular oxygen for activity are needed. Herein, the chemistry of newly synthesized dirhodium complexes, which do not require O2 for activity, is reported.;The complexes cis-H,T, and cis-H,H-[Rh 2(HNOCCH3)2(CH3CN)6] 2+ were synthesized and characterized; each bis-amidato isomer has a total of six CH3CN ligands, two along the internuclear Rh-Rh axis, CH3CNax, two in equatorial positions trans to the oxygen atoms of the bridging amidato groups, CH3CN eqO, and two in equatorial positions trans to the amidato nitrogen atoms, CH3CN eqN. Upon photolysis, both types of CH3CNeq ligands undergo efficient ligand exchange with solvent H2O molecules to form mono-aqua, followed by bis-aqua adducts, releasing two CH3CNeq ligands in the process. The quantum yields, phi400 nm, for the H,T and H,H complexes to form mono-aqua adducts are 0.43 and 0.38, respectively, which are substantially greater than the 0.13 yield observed for cis-[Rh2(O2CCH 3)2(CH3CN)6]2+. Importantly, no ligand exchange is observed when the complexes are kept in the dark. Gel electrophoresis and DNA binding studies further showed that the photoproduct cis-H,T-[Rh2(O2CCH3)2(CH 3CN)2(H2O)2]2+ binds to DNA covalently, but the complex is inactive in the dark.;The reaction of cis-H,H-[Rh2(HNOCCH 3)2(CH3CN)6]2+ with bipyridine (bpy) produced cis-H,H-[Rh2(HNOCCH 3)2(bpy)(CH3CN)4]2+ exclusively, where the bpy ligand is positioned trans to the amidato N atoms as proven by single crystal XRD. Photochemical experiments showed that one CH3CNeq ligand exchanges with H2O upon photolysis in water, forming cis-H,H-[Rh 2(HNOCCH3)2(bpy)(CH3CN)(H2O)] 2+, and the photoproduct was shown to bind to DNA covalently. Reaction of cis-H,H-[Rh2(HNOCCH3)2(CH 3CN)6]2+ with dipyridophenazine (dppz) produced cis-H,H-[Rh2(HNOCCH3)2(dppz)(CH 3CN)4]2+, and photochemical studies showed that one CH3CNeq ligand exchanges with a solvent H2O molecule to form the photoproduct cis-H,H -[Rh2(HNOCCH3)2(dppz)(CH3CN)(H 2O)]2+. Viscosity studies showed that the photo-product intercalates into DNA, but the complex does not intercalate when kept in the dark, making cis-H,H-[Rh2(HNOCCH3) 2(dppz)(CH3CN)4]2+ the first complex known to undergo light-induced intercalation.;Finally, the photochemistry and DNA binding of [Rh2(phen) 2(CH3CN)6]4+ was investigated. Photolysis of this complex in H2O results in the cleavage of the Rh-Rh single bond, with quantum yields exceeding unity, and formation of cationic radicals. DNA photocleavage gels showed that the photoproducts cleave DNA in the absence of O2. |
