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A Density Functional Method Study of Physiological bis(L-asparaginato)copper(II)

Of all 23 amino acids known to exist in human blood plasma, a substantial number were shown to compete effectively with albumin for the binding of copper. [1] Besides the albumin- bound copper, approximately 5-10% of copper in serum exists in the form of mixed amino acid copper(II) complexes. One of the amino acids present in the exchangeable pool of copper(II) is L-asparagine, which can form different complexes with copper(II). Therefore, the copper(II) complexes with amino acids, small peptides and other low-molecular-weight ligands are used as valuable model systems that mimic the actual copper-binding sites existing in biological systems. [2] During the past 40 years various experimental studies on bis(L- asparaginato)copper(II), Cu(L-Asn)2, were conducted, like ultraviolet absorption and reflectance spectroscopy, potentiometric titration in aqueous solution, magnetic and electron spin resonance measurements, X-ray absorption edge spectroscopy, as well as infrared and Raman vibrational spectra in the solid state. [3-5] The overall stability constants were determined for Cu(L-Asn)2 in water-dioxane mixtures but their precise molecular geometries and relative stabilities in solution are still unknown. [5] Cu(L-Asn)2 crystallises in the solid state as an anhydrous complex, with copper(II) coordinated via the amino nitrogen and carboxylato oxygen atoms (namely, the glycinato-like coordination mode) in a trans square-planar configuration. Two axially placed amide group oxygen atoms of adjacent molecules extend this geometry to a tetragonal distorted octahedron. [6] As a step to determine the precise molecular geometries of Cu(L-Asn)2, firstly in vacuum, we undertook a full conformational analysis of this complex with cis and trans configurations and glycinato-like coordinations. The density functional theory (DFT) method and the unrestricted B3LYP functional with the LanL2DZ double-ζ basis set were used and augmented by polarisation and diffuse functions. The investigation included the computation of 171 cis- and 171 trans-conformers, resulting in 42 different minima of Cu(L-Asn)2. Among the most stable conformers in vacuum we noticed strong intramolecular hydrogen bonds between the amide group and the free carboxyl oxygen and/or amino nitrogen atom. The experimental X-ray conformer of Cu(L-Asn)2 is not stable in vacuum. Due to stereochemical reasons, the trans-Cu(L-Asn)2 conformers have a higher tendency of forming hydrogen bonds than the cis-complexes. The intramolecular interactions are discussed as a function of sterical and energetic parameters in this poster presentation. [1] P.Z. Neumann, A. Sass-Kortsak, J. Clin. Invest. 46 (1967) 646–658. [2] H. C. Freeman Adv. Protein Chem. 22 (1967) 257–424. [3] M. N. Srivastava et al. J. inorg. nucl. Chem., 38 (1976) 1897–1900. [4] E. J. Baran et al. Spectrochimica Acta Part A 66 (2007) 114–117. [5] A. Doğan et al. Analytical Biochem. 295 (2001) 237–239. [6] I. Vencato et al. Acta Cryst. E60 (2004) m1428– m1430.

copper; asparagine; physiological complex; isolated molecules; conformational analysis; DFT; B3LYP

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