| The transcription inhibition in vitro by metal complexes possessing two quinone diimine ligands was investigated. It is believed that duplex stabilization by the complexes result in the suppression of transcription. In addition, the DNA photocleavage by bimetallic complexes was investigated.; Rh(III) and Ru(II) complexes possessing two quinone diimine ligands in their coordination sphere were found to significantly increase the melting temperature (ΔTm) of a 15-mer duplex DNA and to inhibit transcription in vitro. The complexes include those containing intercalating phi (phi = 9,10-phenanthrenequinone diimine) and non-intercalating bzi (bzi = 1,2-benzoquinone diimine) ligands in their rigid octahedral coordination environment. For Ru(phi)2phen2+ and Rh(L)2phen 3+ (L = phi, bzi; phen = 1,10-phenanthroline) a distinct correlation between ΔTm and the concentration of each complex required to inhibit transcription was observed. In contrast, the parent Ru(phen) 32+ and Rh(phen)33+ complexes, as well as Ru(phen)2phi2+ and Ru(phen)2L 3+ (L = phi, bzi) result in small ΔTm and require large concentrations of each complex to effect transcription inhibition. A distinct correlation between ΔTm and the concentration of each complex required to inhibit transcription was observed, independent of the presence of an intercalative ligand and their binding constants to DNA duplex. Hydrogen bonding from the four imine protons from the quinone diimine ligands may stabilize the duplex structure, thus resulting in transcription inhibition.; Irradiation of Rh2(O2CCH3)4(H 2O)2 with visible light in the presence of electron acceptors results in the formation of the oxidized complex, Rh2(O2CCH 3)4(H2O)2+. Photogenerated Rh2(O2CCH3)4(H2O) 2+ is able to cleave plasmid DNA, whereas Rh2(O 2CCH3)4(L)2+ complexes with non-labile axial ligands, L, such as py (pyridine) and PPh3 (triphenylphosphine), do not cleave the double helix. The necessity of a labile axial ligand for the cleavage to take place may either be related to the need for an open coordination site during reactivity or for the binding of the complex to DNA.; Although the excited states of the Rh2(O2CCH 3)4(L)2 do not appear to be radical (or diradical) in nature, the oxidized complex with labile axial ligands, Rh2(O 2CCH3)4(L)2+, was reactive towards alcohols and DNA. We recently found that Rh2(O2CCH 3)4(H2O)2+ is able to produce •OH while regenerating the neutral complex, Rh2(O 2CCH3)4(H2O)2, such that under photolysis conditions in the presence of electron acceptors the production of hydroxyl radicals is photocatalytic.; The time dependence of DNA cleavage shows that increasingly smaller DNA fragments are formed with longer irradiation times. Greater DNA cleavage is observed at pH = 8, with decreasing DNA damage with decreasing pH. Furthermore, in the presence of hydroxyl radical scavengers such as azide, mannitol, and formate, the decrease in DNA cleavage was proportional to the reported rates of reaction of •OH with each scavenger. The wavelength dependence of the photoinduced DNA cleavage parallels the absorption spectrum of the dirhodium complex, indicating... |
