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Molecules 2014, 19(1), 980-991; doi:10.3390/molecules19010980
Article

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

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Received: 27 November 2013; in revised form: 23 December 2013 / Accepted: 26 December 2013 / Published: 15 January 2014
(This article belongs to the Section Medicinal Chemistry)
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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.
Keywords: copper-histidine complex; copper metabolism; Menkes disease; EPR spectroscopy; FT-EPR spectroscopy copper-histidine complex; copper metabolism; Menkes disease; EPR spectroscopy; FT-EPR spectroscopy
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Gala, L.; Lawson, M.; Jomova, K.; Zelenicky, L.; Congradyova, A.; Mazur, M.; Valko, M. 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, 19, 980-991.

AMA Style

Gala L, Lawson M, Jomova K, Zelenicky L, Congradyova A, Mazur M, Valko M. 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; 19(1):980-991.

Chicago/Turabian Style

Gala, Lukas; Lawson, Michael; Jomova, Klaudia; Zelenicky, Lubomir; Congradyova, Andrea; Mazur, Milan; Valko, Marian. 2014. "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 19, no. 1: 980-991.


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