Conformational Analyses of Physiological Binary and Ternary Copper(II) Complexes with l-Asparagine and l-Histidine; Study of Tridentate Binding of Copper(II) in Aqueous Solution.

This study explores the structural properties and energy landscapes of the physiologically important bis(L-asparaginato)copper(II) [Cu(L-Asn)(2)] and (L-histidinato)(L-asparaginato)copper(II) [Cu(L-His)(L-Asn)]. The conformational analyses in the gas phase and implicitly modeled water medium, and magnetic parameters of electron paramagnetic resonance spectra were attained using density functional theory calculations. The apical Cu-II coordination and hydrogen bonding were analyzed. Predicted lower-energy structures enabled the confirmation and, for apical bonding, also the refinement of structural proposals from literature. Available experimental results were indecisive regarding the amido-group binding in the Cu-II equatorial plane in solutions, but the examination of the relative stability of Cu(L-Asn)(2) conformers in 30 binding modes confirms the glycine-like mode as the most stable one. Previously reported experimental results for Cu(L-His)(L-Asn) were interpreted for L-His to have a tridentate histamine-like mode. However, the aqueous conformers with L-His in the glycinato mode are also predicted to have low energies, which does not contradict the tridentate L-His binding. The predicted magnetic parameters of conformers with an apical oxygen atom (intramolecular or from a water molecule) can reproduce the experimental data. An extent of conformational flexibility and abundance of L-His-containing ternary copper(II) amino acid complexes under physiological conditions may be related.