EPR spectroscopy of a clinically active (1:2) copper(II)-histidine complex used in the treatment of Menkes disease: a Fourier transform analysis of a fluid CW-EPR spectrum

Molecules. 2014 Jan 15;19(1):980-91. doi: 10.3390/molecules19010980.

Abstract

Redox active transition metal ions (e.g., iron and copper) have been implicated in the etiology of many oxidative stress-related diseases including also neurodegenerative disorders. Unbound copper can catalyze formation of reactive oxygen species (hydroxyl radicals) via Fenton reaction/Haber-Weiss chemistry and therefore, under physiological conditions, free copper is potentially toxic and very rarely exists inside cells. Copper(II) bound to the aminoacid L-histidine represents a species discovered in blood in the mid 60s and since then extensive research on this complex was carried out. Copper bound to L-histidine represents an exchangeable pool of copper(II) in equilibrium with the most abundant blood plasma protein, human serum albumin. The structure of this complex, in aqueous solution, has been a subject of many studies and reviews, however without convincing success. The significance of the (1:2) copper(II)-L-histidine complex at physiological pH documents its therapeutic applications in the treatment of Menkes disease and more recently in the treatment of infantile hypertrophic cardioencephalomyopathy. While recently the (1:2) Cu(II)-L-His complex has been successfully crystallized and the crystal structure was solved by X-ray diffraction, the structure of the complex in fluid solution at physiological pH is not satisfactorily known. The aim of this paper is to study the (1:2) Cu(II)-L-histidine complex at low temperatures by X-band and S-band EPR spectroscopy and at physiological pH at room temperature by Fourier transform CW-EPR spectroscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coordination Complexes / chemistry
  • Coordination Complexes / therapeutic use
  • Electron Spin Resonance Spectroscopy
  • Fourier Analysis
  • Histidine / analogs & derivatives*
  • Histidine / chemistry
  • Histidine / therapeutic use
  • Humans
  • Hydrogen-Ion Concentration
  • Menkes Kinky Hair Syndrome / drug therapy
  • Molecular Conformation
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / therapeutic use
  • Solutions

Substances

  • Coordination Complexes
  • Organometallic Compounds
  • Solutions
  • Histidine
  • copper histidine