A new class of dirhodium compounds with an electron acceptor ligand: enhancing chemotherapeutic properties with light

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Title: A new class of dirhodium compounds with an electron acceptor ligand: enhancing chemotherapeutic properties with light
Author: Angeles Boza, Alfredo Milton
Abstract: The 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 .
URI: http : / /hdl .handle .net /1969 .1 /ETD -TAMU -1251
Date: 2009-05-15

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A new class of dirhodium compounds with an electron acceptor ligand: enhancing chemotherapeutic properties with light. Available electronically from http : / /hdl .handle .net /1969 .1 /ETD -TAMU -1251 .

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