Di-imine copper(II) complexes as redox mediator and modulator in 2-deoxy-D-ribose oxidative damage.
Redox properties of copper complexes are important for their catalytic functions in vitro and in biological systems, and can contribute to their reactivity toward selected targets. In order to evaluate the influence of different ligands on the reactivity of copper ions, comparative studies were carried out with some copper(II) complexes containing a tridentate imine, or a tetradentate di-Schiff base ligand with a mixed pyridine, pyrazine, or imidazole donor set, acting as catalysts in the oxidation of 2-deoxy-D-ribose. Addition of the reducing agent glutathione (gamma-glutamylcysteinylglycine; GSH), which can also act as a good ligand for copper(I), mediated the oxidation of the substrate. For some of these compounds, a reductive activation followed by competition for the metal ion was verified, with formation of copper(I)-glutathione complex monitored by fluorescence measurements. For others, however, the reduction of the metal by the glutathione seems to not occur. In the presence of hydrogen peroxide, the oxidative damage is significantly enhanced for all the complexes tested. Redox potential measurements by cyclic voltammetry corroborated partially these results, indicating that the most reactive complexes are those with more positive redox potential. Evidence for site-specific attack to 2-deoxy-D-ribose was also observed, consistent with the intermediary formation of a copper-hydroxyl species, [LCu(II)(*OH)], rather than 'free' hydroxyl radical.
Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
Maria Amélia de Almeida
MA
Azzellini
Izilda Aparecida
IA
Bagatin
Ana Maria da Costa
AM
Ferreira
D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D005978:Glutathione / Q000737:chemistry / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000494:pharmacology; D007098:Imino Acids / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D012266:Ribose / Q000737:chemistry*; D012545:Schiff Bases / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000737:chemistry / Q000378:metabolism
D007098:Imino Acids; D009942:Organometallic Compounds; D012545:Schiff Bases; D017392:Thiobarbituric Acid Reactive Substances; D012266:Ribose; D003300:Copper; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D005978:Glutathione