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
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 c...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2014-01-01
|
Series: | Molecules |
Subjects: | |
Online Access: | http://www.mdpi.com/1420-3049/19/1/980 |
id |
doaj-efc3dbc14a354b508321def6155cbfb1 |
---|---|
record_format |
Article |
spelling |
doaj-efc3dbc14a354b508321def6155cbfb12020-11-24T23:15:34ZengMDPI AGMolecules1420-30492014-01-0119198099110.3390/molecules19010980molecules19010980EPR 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 SpectrumLukas Gala0Michael Lawson1Klaudia Jomova2Lubomir Zelenicky3Andrea Congradyova4Milan Mazur5Marian Valko6Faculty of Chemical and Food Technology, Slovak Technical University, Bratislava SK-812 37, SlovakiaFaculty of Chemical and Food Technology, Slovak Technical University, Bratislava SK-812 37, SlovakiaFaculty of Natural Sciences, Constantine The Philosopher University, Nitra SK-949 74, SlovakiaFaculty of Natural Sciences, Constantine The Philosopher University, Nitra SK-949 74, SlovakiaFaculty of Natural Sciences, Constantine The Philosopher University, Nitra SK-949 74, SlovakiaFaculty of Chemical and Food Technology, Slovak Technical University, Bratislava SK-812 37, SlovakiaFaculty of Chemical and Food Technology, Slovak Technical University, Bratislava SK-812 37, SlovakiaRedox 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.http://www.mdpi.com/1420-3049/19/1/980copper-histidine complexcopper metabolismMenkes diseaseEPR spectroscopyFT-EPR spectroscopy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lukas Gala Michael Lawson Klaudia Jomova Lubomir Zelenicky Andrea Congradyova Milan Mazur Marian Valko |
spellingShingle |
Lukas Gala Michael Lawson Klaudia Jomova Lubomir Zelenicky Andrea Congradyova Milan Mazur Marian Valko 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 copper-histidine complex copper metabolism Menkes disease EPR spectroscopy FT-EPR spectroscopy |
author_facet |
Lukas Gala Michael Lawson Klaudia Jomova Lubomir Zelenicky Andrea Congradyova Milan Mazur Marian Valko |
author_sort |
Lukas Gala |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2014-01-01 |
description |
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. |
topic |
copper-histidine complex copper metabolism Menkes disease EPR spectroscopy FT-EPR spectroscopy |
url |
http://www.mdpi.com/1420-3049/19/1/980 |
work_keys_str_mv |
AT lukasgala eprspectroscopyofaclinicallyactive12copperiihistidinecomplexusedinthetreatmentofmenkesdiseaseafouriertransformanalysisofafluidcweprspectrum AT michaellawson eprspectroscopyofaclinicallyactive12copperiihistidinecomplexusedinthetreatmentofmenkesdiseaseafouriertransformanalysisofafluidcweprspectrum AT klaudiajomova eprspectroscopyofaclinicallyactive12copperiihistidinecomplexusedinthetreatmentofmenkesdiseaseafouriertransformanalysisofafluidcweprspectrum AT lubomirzelenicky eprspectroscopyofaclinicallyactive12copperiihistidinecomplexusedinthetreatmentofmenkesdiseaseafouriertransformanalysisofafluidcweprspectrum AT andreacongradyova eprspectroscopyofaclinicallyactive12copperiihistidinecomplexusedinthetreatmentofmenkesdiseaseafouriertransformanalysisofafluidcweprspectrum AT milanmazur eprspectroscopyofaclinicallyactive12copperiihistidinecomplexusedinthetreatmentofmenkesdiseaseafouriertransformanalysisofafluidcweprspectrum AT marianvalko eprspectroscopyofaclinicallyactive12copperiihistidinecomplexusedinthetreatmentofmenkesdiseaseafouriertransformanalysisofafluidcweprspectrum |
_version_ |
1725590486913122304 |