Double-strand DNA cleavage by copper complexes of 2,2 '-dipyridyl with guanidinium/ammonium pendants

Two ligands with guanidinium/ ammonium groups were synthesized and their copper complexes, [Cu( L-1)Cl-2](ClO4)(2) center dot H2O ( 1) and [Cu(L-2)Cl-2](ClO4)(2) ( 2) ( L-1 = 5,5'- di[1-( guanidyl) methyl]- 2,2' - bipyridyl cation and L-2 = 5,5'- di[1-(amino)methyl]-2,2' - bipyridyl cation), were prepared to serve as nuclease mimics. X-Ray analysis revealed that Cu( II) ion in 1 has a planar square CuN2Cl2- configuration. The shortest distance between the nitrogen of guanidinium and copper atoms is 6.5408( 5) angstrom, which is coincident with that of adjacent phosphodiesters in DNA (ca. 6 angstrom). In the absence of reducing agent, supercoiled plasmid DNA cleavage by the complexes were performed and their hydrolytic mechanisms were demonstrated with radical scavengers and T4 ligase. The pseudo-Michaelis-Menten kinetic parameters (k(cat), K-M) were calculated to be 4.42 h(-1), 7.46 x 10(-5) M for 1, and 4.21 h(-1), 1.07 x 10(-4) M for 2, respectively. The result shows that their cleavage efficiency is about 10-fold higher than the simple analogue [Cu(bipy)Cl-2] (3) (0.50 h(-1), 3.5 x 10(-4) M). The pH dependence of DNA cleavage by 1 and its hydroxide species in solution indicates that mononuclear [Cu(L-1)(OH)(H2O)] (3+) ion is the active species. Highly effective DNA cleavage ability of 1 is attributed to the effective cooperation of the metal moiety and two guanidinium pendants with the phosphodiester backbone of nucleic acid.