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.
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.
authors.affiliation: Faculty of Chemical and Food Technology, Slovak Technical University, Bratislava SK-812 37, Slovakia. lukas.gala19@gmail.com.
authors.forename: Lukas
authors.initials: L
authors.lastname: Gala
authors.affiliation: Faculty of Chemical and Food Technology, Slovak Technical University, Bratislava SK-812 37, Slovakia. alpinenewt@gmail.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Lawson
authors.affiliation: Faculty of Chemical and Food Technology, Slovak Technical University, Bratislava SK-812 37, Slovakia. kjomova@ukf.sk.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Jomova
authors.affiliation: Faculty of Chemical and Food Technology, Slovak Technical University, Bratislava SK-812 37, Slovakia. lzelenicky@ukf.sk.
authors.forename: Lubomir
authors.initials: L
authors.lastname: Zelenicky
authors.affiliation: Faculty of Chemical and Food Technology, Slovak Technical University, Bratislava SK-812 37, Slovakia. andrea.congradyova@ukf.sk.
authors.forename: Andrea
authors.initials: A
authors.lastname: Congradyova
authors.affiliation: Faculty of Chemical and Food Technology, Slovak Technical University, Bratislava SK-812 37, Slovakia. milan.mazur@stuba.sk.
authors.forename: Milan
authors.initials: M
authors.lastname: Mazur
authors.affiliation: Faculty of Chemical and Food Technology, Slovak Technical University, Bratislava SK-812 37, Slovakia. marian.valko@stuba.sk.
authors.forename: Marian
authors.initials: M
authors.lastname: Valko
mesh_terms: D056831:Coordination Complexes / Q000737:chemistry / Q000627:therapeutic use; D004578:Electron Spin Resonance Spectroscopy; D005583:Fourier Analysis; D006639:Histidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007706:Menkes Kinky Hair Syndrome / Q000188:drug therapy; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry* / Q000627:therapeutic use; D012996:Solutions
chemical_list: D056831:Coordination Complexes; D009942:Organometallic Compounds; D012996:Solutions; D006639:Histidine; C098468:copper histidine