Download Conformational analysis of the bis(D,L-isoleucinato

25th Croatian meeting of chemists and chemical engineers, Poreč, 2017.
Conformational analysis of the bis(D,L-isoleucinato)copper(II) complex in
aqueous solution
Konformacijska analiza kompleksa bis(D,L-izoleucinato)bakra(II) u vodenoj
otopini
Jelena Budimčić1, Jasmina Sabolović1
Institute for Medical Research and Occupational Health, Ksaverska cesta 2, Zagreb, Croatia
E-mail: [email protected]
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 [2].
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) [3], while the monoclinic
polymorph (space group C2) was characterized 40 years afterwards [4]. Both polymorphs
have cis-configuration. It is assumed that both cis- and trans-isomers are stable in aqueous
solution [4], even though the trans-one has never been isolated. On the contrary, the bis(D,Lisoleucinato)copper(II) complex was reported only in polycrystalline form; its IR [5] and ESR
[6] 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  60ᵒ, -60ᵒ and 180ᵒ). Hence, the overall
number of possible conformers could be 171 for cis-isomer, and 171 for trans-isomer.
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 [7]. The goal of
this work is to investigate the relative energies of the cis- and trans-conformers of bis(D,Lisoleucinato)copper(II) and to compare two methods` predictions of the most stable groups
of conformers in aqueous solution.
This work has been supported by Croatian Science Foundation under the project IP-2014-093500.
References
[1] M. DiDonato, B. Sarkar, Biochem. Biophys. Acta, 1360 (1997) 3-16.
[2] H. C. Freeman, Adv. Protein Chem., 22 (1967) 254-424.
[3] C. M. Weeks, A. Cooper, D. A. Norton, Acta Cryst., 25 (1969) 443-450.
[4] M. Marković, D. Milić, J. Sabolović, Cryst. Growth Des., 12 (2012) 4116-4129.
[5] A. W. Herlinger, S. L. Wenhold, T. Veach Long, J. Am. Chem. Soc., 92 (1970) 6474-6481.
[6] S. Misumi, T. Isobe, S. Kimoto, Bull. Chem. Soc. Japan, 45 (1972) 2695-2697.
[7] J. Sabolović, V. Gomzi, J. Chem. Theory Comput., 5 (2009) 1940-1954.