In vitro and in vivo activity of a new unsymmetrical dinuclear copper complex containing a derivative ligand of 1,4,7-triazacyclononane: catalytic promiscuity of [Cu2(L)Cl3]

Dalton Trans. 2013 May 21;42(19):7059-73. doi: 10.1039/c3dt33046j.

Abstract

Here we present the synthesis of the dinuclear complex [Cu(II)2(L)Cl3] (1), where L is the deprotonated form of the 3-[(4,7-diisopropyl-1,4,7-triazacyclononan-1-yl)methyl]-2-hydroxy-5-methylbenzaldehyde ligand. The complex was characterized by single crystal X-ray diffraction, potentiometric titration, mass spectrometry, electrochemical and magnetic measurements, EPR, UV-Vis and IR. Complex 1 is able to increase the hydrolysis rate of the diester bis-(2,4-dinitrophenyl)phosphate (2,4-BDNPP) by a factor of 2700, and also to promote the plasmidial DNA cleavage at pH 6 and to inhibit the formazan chromophore formation in redox processes at pH 7. Using Saccharomyces cerevisiae (BY4741) as a eukaryotic cellular model, we observed that 1 presents reduced cytotoxicity. In addition, treatment of wild-type and mutant cells lacking Cu/Zn-superoxide dismutase (Sod1) and cytoplasmic catalase (Ctt1) with 1 promotes increased survival after H2O2 or menadione (O2˙(-) generator) stress, indicating that 1 might act as a Sod1 and Ctt1 mimetic. Considered together, these results support considerations regarding the dynamic behaviour of an unsymmetrical dinuclear copper(II) complex in solid state and in aqueous pH-dependent solution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemistry
  • Antioxidants / metabolism
  • Biomimetic Materials / chemical synthesis
  • Biomimetic Materials / metabolism
  • Biomimetic Materials / pharmacology
  • Catalysis
  • Coordination Complexes / chemistry*
  • Coordination Complexes / metabolism
  • Coordination Complexes / pharmacology
  • Copper / chemistry*
  • Crystallography, X-Ray
  • DNA / chemistry
  • DNA / metabolism
  • DNA Cleavage
  • Heterocyclic Compounds / chemistry*
  • Hydrogen-Ion Concentration
  • Kinetics
  • Ligands
  • Magnetics
  • Molecular Conformation
  • Saccharomyces cerevisiae / drug effects
  • Superoxide Dismutase / metabolism
  • Temperature

Substances

  • Antioxidants
  • Coordination Complexes
  • Heterocyclic Compounds
  • Ligands
  • 1,4,7-triazacyclononane
  • Copper
  • DNA
  • Superoxide Dismutase