DNA cleavage studies of mononuclear and dinuclear copper(II) complexes with benzothiazolesulfonamide ligands.
Copper-based transition metal complexes performing single- and double-strand scission of DNA have been studied. The dinuclear complexes [Cu(2)(L)(2)(OCH(3))(2)(NH(3))(2)] and [Cu(2)(L)(2)(OCH(3))(2)(DMSO)(2)] are more active than the corresponding mononuclear [Cu(L)(2)(py)(2)] (where HL= N-(4-methylbenzothiazol-2-yl)benzenesulfonamide), suggesting that the dinuclearity is an important factor in the oxidative cleavage of DNA. The cleavage efficiency of the complexes depends on the reducing agent used in the process, the tandem ascorbate/H(2)O(2) being the most efficient. PAGE analyses have shown that these complexes cleave DNA without sequence selectivity. The DNA degradation process takes place mainly by C1' oxidation, but C4' and C5' oxidations cannot be ruled out as minor pathways. These copper complexes preferably oxidize guanine under mild conditions, but under more drastic conditions the oxidation reactivity appears to be T>G>C>A, suggesting the intervention of hydroxyl radicals as active species.
Departamento de Química Inorgánica, Facultad de Farmacia, Universidad de Valencia, Avda Vicent Estellés s/n, 46100, Burjassot, Spain.
Marta
M
González-Alvarez
Gloria
G
Alzuet
Joaquín
J
Borrás
Marguerite
M
Pitié
Bernard
B
Meunier
D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003855:Deoxyribose / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D016166:Free Radical Scavengers / Q000494:pharmacology; D008024:Ligands; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D019163:Reducing Agents / Q000494:pharmacology; D013449:Sulfonamides / Q000737:chemistry / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism*
D016166:Free Radical Scavengers; D008024:Ligands; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D019163:Reducing Agents; D013449:Sulfonamides; D013844:Thiazoles; D003855:Deoxyribose; D003300:Copper; D004247:DNA; D003851:Deoxyribonucleases