Pronounced conformational flexibility of physiological (L-histidinato)(L-threoninato)copper(II) in aqueous solution disclosed by a quantum chemical study

Conformational analyses are performed for the physiological ternary (L-histidinato)(L-threoninato)copper(II) complex in the gas phase and in an implicitly modeled aqueous medium using the density functional theory (DFT) functional B3LYP to study the effects of intermolecular interactions on the complex properties. Different energy landscapes in the gas phase and aqueous solution are obtained with much more possible aqueous than vacuum conformers in three copper(II) coordination modes with trans- and cis-configuration. While the trans conformers in glycine-like coordination are the most stable in vacuum, conformers in all coordination modes are predicted within 15 kJ mol−1 in aqueous solution. The DFT simulations suggest that the interactions between the title complex and surrounding water molecules can alleviate intramolecular strain and stabilize many conformers that are unfavorable in the gas phase. The diversity of lowest-energy aqueous geometries with or without intra- and inter-residual hydrogen bonds, and comparisons with the previously studied parent binary complexes bis(L-histidinato)copper(II) and bis(L-threoninato)copper(II) reveal a so far unidentified conformational flexibility of (L-histidinato)(L-threoninato)copper(II) in aqueous solution. The flexibility explains previous experimental findings on the lack of inter-residual strain and the abundance of the ternary over the parent complexes determined in aqueous solutions at physiological pH values.