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

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

“…The thermodynamic parameters (stepwise enthalpies and entropies of formation) measured for the l ‐hystidyl‐copper(II)‐proton system in aqueous solution (3.0 m NaClO 4 , 25 °C) suggested that the complexes existing in aqueous solution were of only one tautomer, the N τ ‐protonated one with N π as the potential chelating atom . In line with that, the study of Cu( l ‐His)( l ‐Thr) showed that generally, the glycinato‐mode conformers with protonated N τ have a lower energy, but several conformers with protonated N π are in a comparable energy range . Hence, the glycinato‐mode initial structures were prepared in both variants, and the N π ‐protonated ones are labelled as “Gp” (Scheme ).…”

“…For both title complexes, the much larger number of aqueous conformers compared to the gaseous ones (Tables and ) with a distorted‐planar Cu II coordination geometry suggests that intermolecular interactions stabilize the conformers which are unstable in the gas phase. Similar results were obtained by the conformational analyses of Cu( l ‐His)( l ‐Thr) . Additionally, we evaluate the population of conformers in aqueous solution (Tables and ), analyze apical Cu–donor distances (Table ), list the means of in‐plane Cu–donor bond lengths and valence angles around Cu II (Tables S90–S92), as well as the number of intra‐ and inter‐ligand hydrogen bonds (Tables S93–S95) in the title complexes.…”

“…Such an axial coordination was achieved in only one NONo conformer in the gas phase (Table ), for cNONo1 (Figure S1), in which an inter‐ligand C β −H⋅⋅⋅O interaction is formed. A similar result was obtained by the B3LYP calculations of isolated and aqueous Cu( l ‐His) 2 , and Cu( l ‐His)( l ‐Thr) conformers, that the axial coordination of carboxylato O atom(s) can be stabilized only by intramolecular and/or intermolecular noncovalent interactions.…”

“…During the last years we have performed quantum‐chemical conformational analyses of Cu( l ‐His) 2 , bis( l ‐threoninato)copper(II) [Cu( l ‐Thr) 2 ], and ( l ‐histidinato)( l ‐threoninato)copper(II) [Cu( l ‐His)( l ‐Thr)] aimed at elucidating the structural properties of physiological Cu(aa) 2 species in solutions. As a continuation of these analyses, this paper investigates the structural properties, energy landscapes, and structure–magnetic property relation of physiological bis( l ‐asparaginato)copper(II) [Cu( l ‐Asn) 2 ] and ( l ‐histidinato)( l ‐asparaginato)copper(II) [Cu( l ‐His)( l ‐Asn)] in different surroundings using the density functional theory (DFT) method with the B3LYP functional.…”

“…The suitability of theoretically modeled aqueous environment to encounter the noncovalent interactions was examined by comparing the experimental X‐ray molecular structures with the ones calculated in the gas phase and aqueous solution. The computational outcomes were compared for the title complexes with previously obtained ones for physiological Cu( l ‐His) 2 , Cu( l ‐Thr) 2 , and Cu( l ‐His)( l ‐Thr) …”