DNA damage by copper(II) complexes: coordination-structural dependence of reactivities

Abstract

A variety of copper complexes with different structural features have been shown to bind double-helical DNA with binding constants of 10 4–10 7 M −1 and to promote double-strand DNA damage upon reductant/H 2O 2 activation. The interaction of the Cu complex with DNA results in hyperchromism and shifts to longer wavelengths of the strongest transitions in the Cu complexes, as well as striking hypochromism or hyperchromism of DNA absorption at 260 nm. In the presence of DMPO as the spin trap, the solution of each copper complex exhibits typical four-line ESR spectra of the hydroxyl radical by adding 2-mercaptoethanol and H 2O 2 to the solution. Quantitation by 2-deoxy- D-ribose shows that the competence of hydroxyl radical generation by the copper complexes upon reductant and H 2O 2 activation decreases in order, that is, Cu(HTCD) 2+∼Cu(Im) 4Cl 2∼Cu(IDB)(NO 3) 2>Cu(IDB)Cl 2>Cu(IDBt)Cl 2. The copper complex-mediated hydroxyl radical, a powerful oxidant that attacks the adjacent DNA, is responsible for the DNA oxidative damage. The λDNA damage chemistry illustrates that the competence and selectivity of double-strand λDNA damage by the copper complexes are dependent on their geometric structures and types of ligands. The decreasing order of the DNA damage capacity by the present complexes is Cu(Im) 4Cl 2∼Cu(IDB)(NO 3) 2>Cu(HTCD) 2+>Cu(IDBt)Cl 2>Cu(IDB)Cl 2.