Conformational Analyses of Physiological Binary and Ternary Copper(II) Complexes with l-Asparagine and l-Histidine;...

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.