MOLECULAR MODELLING OF COPPER(II) COMPLEXES WITH
HISTIDINE
Marijana Marković,a Vjeran Gomzi,b Jasmina Sabolovića
a
Institute for Medical Research and Occupational Health, Ksaverska cesta 2,
P. O. Box 291, HR-10001 Zagreb, Croatia
b
Ruđer Bošković Institute, Bijenička cesta 54, HR-10000 Zagreb, Croatia
Copper is an essential transition metal usually complexed in metalloproteins and
low-molecular-weight complexes with peptides and amino acids in biological fluids. LHistidine was identified as the predominant amino acid bound to copper(II) in the bis(Lhistidinato)copper(II) complex (with imidazole nitrogen, amino nitrogen, and
carboxylato oxygen donor atoms) and in mixed copper(II) complexes with other Lamino acids in human blood serum [1]. Their prevailing species and stability constants
in aqueous solution were derived by spectroscopic and electrochemical methods.
However, these methods are unable to provide details on the geometry in solution.
We have developed a set of force field empirical parameters equally applicable
for predicting and simulating the structural properties of the copper(II) complexes with
aliphatic –amino acids (the donor atoms are amino nitrogen and carboxylato oxygen
atoms) in vacuo and in the crystal by molecular mechanics (MM) calculations, as well
as in aqueous solution by molecular dynamics (MD) simulations [2]. To be able to
model also copper(II)-histidinato complexes, we included new atom types for imidazole
ring atoms and their interactions to a force field parametrisation. The parametrisation
was based on the experimental crystal and molecular structures of the bis copper(II)
complexes with L-histidine and D,L-histidine and quantum chemically gas-phase
optimised geometries of their anhydrous and aqua complexes. The ability of the new
force field to reproduce and predict the structural properties of the copper(II) histidinato
complexes in the gas phase, in simulated crystalline surroundings, and solvated in water
is examined.
1. P. Deschamps, P.P. Kulkarni, M. Gautam-Basak, B. Sarkar, Coord. Chem. Rev. 249
(2005) 895-909.
2. J. Sabolović, V. Gomzi, J. Chem. Theory Comput. 2009 (accepted for publication)