Browsing by Subject "Dirhodium"
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Item A new class of dirhodium compounds with an electron acceptor ligand: enhancing chemotherapeutic properties with light(2009-05-15) Angeles Boza, Alfredo MiltonThe syntheses and characterization of new dirhodium complexes based on the electron acceptor ligand dipyrido[3,2-a:2?,3?-c]phenazine (dppz) and its derivatives are reported. These complexes have been shown to photocleave pUC18 plasmid in vitro under irradiation with visible light which results in the nicked, circular form of DNA. Unlike typical DNA photocleavage agents, the new compounds are capable of photocleaving DNA in the absence of oxygen as well as in the presence of oxygen. The toxicity of the complexes which contain the electron acceptor dppz ligand toward human skin cells increases when the cell cultures are irradiated with visible light. In contrast, the photocytotoxicity of those complexes that do not contain the dppz do not differ from cytotoxicity in the dark. The chemistry of the newly synthesized dirhodium-dppz complexes with glutathione, which is considered to be an important molecule in the deactivation of metal-based drugs, has also been investigated. The results show that glutathione reversibly reduces [Rh2(?-O2CCH3)2(dppz)2]2+ (6) and [Rh2(?-O2CCH3)2(dppz)(bpy)]2+ (7), and that they are easily reoxidized to the original form in air. EPR measurements and DFT calculations indicate that the additional electron is delocalized in the ligand orbitals. The molecular characteristics that affect the in vitro activity of dirhodium complexes is discussed. The lability of the groups coordinated to the dirhodium complexes is a significant factor that influences the toxicity of the complexes. In addition, the presence of labile solvent molecules and monodentate acetate groups provide potential ?open sites? accessible for nucleophilic substitution, as opposed to these sites being occupied by non-labile groups that reduce the reactivity of the complexes. Finally, the results also demonstrate that the carbonato-bridged complexes of the type [Rh2(?-O2CO)2(diimine)2(H2O)2]2+ are useful precursors to access new dirhodium-diimine compounds that are not accessible from the acetate precursors. These compounds react with trifluoroacetamide, 2-pyrrolidinone, and trifluoroacetic acid to form products in which the carbonato ligands are substituted in favor of the new bridging group. This work provides a foundation for the preparation of new series of dirhodium complexes that contain the dppz ligand and bridging ligands other than acetate.Item Synthesis, Characterization, and Toxicity Studies of Dirhodium and Diiridium Metal-Metal Bonded Compounds(2012-10-19) Lane, Sarah MargaretThe anticancer properties of dirhodium tetraacetate were discovered in the 1970's, and subsequently motivated the research of several dirhodium paddlewheel derivatives. The promising results of this research led the Dunbar group to investigate the biological properties of dirhodium partial paddlewheel compounds. Previous work in our group has focused on dirhodium carboxylate derivatives with a series of diimine ligands, namely 1,10-phenanthroline (phen), dipyrido[3,2-f:2',3'-h]quinoxaline (dpq), dipyrido[3,2a:2',3'c] phenazine (dppz), and benzo[i]dipyrido[3,2-a:2',3'-c]phenazine) (dppn). Current research has expanded this diimine series by substituting the carobxylate bridging group with p-methoxyphenylphosphine (PMP). This new series of compounds was characterized by several techniques, including: X-Ray crystallography, 1H NMR spectroscopy, and electronic absorption spectroscopy. The cytotoxicity of these compounds towards HeLa cells was investigated in presence and absence of light in an effort to investigate the ability to use these compounds as photodynamic therapy (PDT) agents. Cytotoxicity measurements were carried out using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. It was found that in the dark [Rh2(PMP)2(dppz)2][BF4]2 (the dppz derivative of the dirhodium PMP compound) had no cytotoxicity towards HeLa cells, but experienced a 7 fold increase in cytotoxicity upon irradiation (with lambdai_rr equal to 350 nm). This dramatic increase in cytotoxicity upon irradiation makes this compound a potential PDT agent. Diiridium (II,II) compounds were prepared in a dual attempt to determine how the properties of the dirhodium core effect the biological activities of these compounds, as well as investigate the biological activity of a set of compounds that has yet to be explored. The compound [Ir2(DTolF)2(CH3CN)6][BF4]2 was chosen because it has a well understood dirhodium analogue, and it is a known compound. However, it was discovered that there was a potential silver contamination in the final product, stemming from the silver trifluoroacetate oxidant used during synthesis. Consequently, a new method of preparing this compound was required. The new synthetic pathway for the diiridium compound [Ir2(DTolF)2(CH3CN)6][BF4]2 was devised, and the cytotoxicity and photocytotoxicity studies were performed for the first time (to our knowledge) on a diiridium (II,II) compound. Despite the stability of the compound, it was determined to be highly toxic, both in the dark and upon irradiation.