Double-strand DNA cleavage by copper complexes of 2,2'-dipyridyl with electropositive pendants

Dalton Trans. 2006 May 7:(17):2066-71. doi: 10.1039/b516132k. Epub 2006 Jan 31.

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[dot dot dot]Br atoms are 5.772 and 5.594 A, respectively, which is comparable to that of adjacent phosphodiesters in B-form DNA (ca. 6 A). 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,2'-Dipyridyl / analogs & derivatives*
  • 2,2'-Dipyridyl / chemical synthesis
  • 2,2'-Dipyridyl / chemistry
  • Copper / chemistry*
  • Crystallography, X-Ray
  • DNA / chemistry*
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Nucleic Acid Denaturation
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / chemistry
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Ultraviolet

Substances

  • Organometallic Compounds
  • 2,2'-Dipyridyl
  • Copper
  • DNA