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- Title
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.
- Authors
Gala, Lukas; Lawson, Michael; Jomova, Klaudia; Zelenicky, Lubomir; Congradyova, Andrea; Mazur, Milan; Valko, Marian
- 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 physiologicalpH 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.
- Subjects
TRANSITION metal ions; HISTIDINE; RADICALS (Chemistry); NEURODEGENERATION; ELECTRON paramagnetic resonance spectroscopy; INTERMEDIATES (Chemistry); OXIDATIVE stress
- Publication
Molecules, 2014, Vol 19, Issue 1, p980
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules19010980