Double-strand DNA cleavage by copper complexes of 2,2′-dipyridyl with electropositive pendants†
Abstract
Two highly charged cationic copper(II) complexes have been synthesized and characterized structurally and spectroscopically: [Cu(L1)2(Br)](ClO4)5 (1) and [Cu(L2)2(Br)](ClO4)5 (2) (L1 = 5,5′-di(1-(triethylammonio)methyl)-2,2′-dipyridyl cation and L2 = 5,5′-di(1-(tributylammonio)methyl)-2,2′-dipyridyl cation bidentate ligands). X-Ray structures show that Cu(II) ions in both complexes have a trigonal-bipyramidal CuN4Br-configuration. Two nitrogen atoms of the electropositive pendants and coordinated bromine atom basically array in a straight line. Their close distances of N⋯Br atoms are 5.772 and 5.594 Å, respectively, which is comparable to that of adjacent phosphodiesters in B-form DNA (ca. 6 Å). In the absence of reducing agent, supercoiled plasmid DNA cleavage by the complexes has been performed and their hydrolytic mechanisms have been investigated. The pseudo-Michaelis–Menten kinetic parameters (kcat), 4.15 h−1 for 1, 0.43 h−1 for 2 and 0.61 h−1 for [Cu(bipy)(NO3)2], were obtained. This result indicates that 1 exhibits markedly higher nuclease activity than its corresponding analogues. The high ability of DNA cleavage for 1 is attributed to the effective cooperation of the metal moiety and two positive pendants since the array of linear tri-binding sites matches with one of three phosphodiester backbones of nucleic acid.