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Conformational analysis of the bis(D, L -isoleucinato)copper(II) complex in aqueous solution

Copper is as an essential element indispensable for optimal catalytic activity of numerous enzymes such as Cu, Zn-superoxide dismutase, cytochrome c oxidase and tyrosinase [1]. Bis(amino acidato)copper(II) complexes are known since the second half of 19th century, but their structure and properties started to be systematically investigated a century later. They are interesting for studying because they can be used as model compounds for determination of the copper binding sites in metalloproteins, and owing to their stereochemical diversity. The crystal and molecular structure of the bis(L-isoleucinato)copper(II) monohydrate complex was solved in 1969 (orthorhombic space group P212121) [2], while the monoclinic polymorph (space group C2) was characterized 40 years afterwards [3]. Both polymorphs have cis-configuration. It is assumed that both cis- and trans-isomers are stable in aqueous solution [3], even though the trans-one has never been isolated. On the contrary, the bis(D, L-isoleucinato)copper(II) complex was reported only in polycrystalline form ; its IR [4] and ESR [5] spectra showed that it could exist as a trans-isomer, but its crystal structure has not yet been reported. Each chelate ring in bis(D, L-isoleucinato)copper(II) can have 18 conformations, when considering two conformations of the five-membered ring (with C in an axial or equatorial position) and nine conformations of the isoleucine residue (defined by the Nam-C-C-C1 and C-C-C-C torsional angles which can take values of  60°, –60° and 180°). To calculate the conformational analysis for bis(D, L-isoleucinato)copper(II) in aqueous solution we used two methods: the molecular dynamics (MD) and the density functional theory (DFT) with the polarizable continuum model (PCM). The MD simulations are done using the FFWa-SPCE force field, developed to study the properties of the bis(amino acidato)copper(II) complexes in aqueous solution, solid state and in vacuo [6]. The goal of this work is to investigate the relative energies of the cis- and trans-conformers of bis(D, L-isoleucinato)copper(II) and to compare two methods` predictions of the most stable groups of conformers in aqueous solution. References [1] M. DiDonato, B. Sarkar, Biochem. Biophys. Acta, 1360 (1997) 3-16. [2] C. M. Weeks, A. Cooper, D. A. Norton, Acta Cryst., 25 (1969) 443-450. [3] M. Marković, D. Milić, J. Sabolović, Cryst. Growth Des., 12 (2012) 4116-4129. [4] A. W. Herlinger, S. L. Wenhold, T. Veach Long, J. Am. Chem. Soc., 92 (1970) 6474-6481. [5] S. Misumi, T. Isobe, S. Kimoto, Bull. Chem. Soc. Japan, 45 (1972) 2695-2697. [6] J. Sabolović, V. Gomzi, J. Chem. Theory Comput., 5 (2009) 1940-1954. This work has been supported by Croatian Science Foundation under the project IP–2014–09–3500.

DL-isoleucine ; copper ; molecular dynamics ; density functional theory ; conformers

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