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

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/H2O2 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 com plex exhibits typical four-line ESR spectra of the hydroxyl radical by addi ng 2-mercaptoethanol and H2O2 to the solution. Quantitation by 2-deoxy-D-ri bose shows that the competence of hydroxyl radical generation by the copper complexes upon reductant and H2O2 activation decreases in order, that is, Cu(HTCD)(2+) similar to Cu(Im)(4)Cl-2 similar to Cu(IDB)(NO3)(2) > Cu(IDB)C l-2 > Cu(IDBt)Cl-2. The copper complex-mediated hydroxyl radical, a powerfu l oxidant that attacks the adjacent DNA, is responsible for the DNA oxidati ve damage. The lambda DNA damage chemistry illustrates that the competence and selectivity of double-strand lambda DNA damage by the copper complexes are dependent on their geometric structures and types of ligands. The decre asing order of the DNA damage capacity by the present complexes is Cu(Im)(4 )Cl-2 similar to Cu(IDB)(NO3)(2) > Cu(HTCD)(2+) > Cu(IDBt)Cl-2 > Cu(IDB)Cl- 2. (C) 1999 Elsevier Science Inc. All rights reserved.