Synthesis, crystal structures and DNA-cleaving activities of [Cemp]2[MCl4] (Cemp = N-carbethoxymethyl-1,10-phenanthrolinium, M = Cu(II), Zn(II), Co(II), Ni(II) and Mn(II))

Chem Pharm Bull (Tokyo). 2013;61(7):714-21. doi: 10.1248/cpb.c13-00198.

Abstract

N-Carbethoxymethyl-1,10-phenanthrolinium bromide (CempBr) and its five ionic metal complexes, [Cemp]2[MCl4] where M = Cu(II) (1), Zn(II) (2), Co(II) (3), Ni(II) (4) and Mn(II) (5) were synthesized and fully characterized. Complexes 1-5 have similar structures, and consist of isolated [Cemp](+) cations and [MCl4](2-) anions in which there are no obvious interactions between the oxygen or nitrogen donor atoms in [Cemp](+) and the metal center in [MCl4](2-). Agarose gel electrophoresis studies on the cleavage of plasmid pBR322 DNA by complexes 1-5 indicated that complex 1 was capable of efficiently cleaving DNA under physiological conditions, most probably via an oxidative mechanism. Kinetic assay of complex 1 afforded the maximal catalytic rate constant kmax of 0.55 h(-1) and Michaelis constant KM of 47.6 µM, respectively, which gives about 1.5×10(7)-fold rate acceleration over uncatalyzed cleavage of supercoiled DNA. Ethidium bromide displacement experiments indicated that complex 1 had a binding affinity of (1.58±1.12)×10(6) M(-1) toward calf-thymus DNA, 20-100-fold higher than those shown by CempBr and complexes 2-5. The high cleaving efficacy of complex 1 is thought to be due to the efficient catalysis of the copper(II)-coordinated center and the efficient binding of the quaternized 1,10-phenanthroline cation to DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cobalt / chemistry
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Copper / chemistry
  • Crystallography, X-Ray
  • DNA / chemistry*
  • DNA / metabolism
  • DNA Cleavage / drug effects
  • Kinetics
  • Manganese / chemistry
  • Metals / chemistry*
  • Molecular Conformation
  • Nickel / chemistry
  • Phenanthrolines / chemistry*
  • Zinc / chemistry

Substances

  • Coordination Complexes
  • Metals
  • Phenanthrolines
  • Cobalt
  • Manganese
  • Copper
  • Nickel
  • DNA
  • Zinc
  • 1,10-phenanthroline