Complex Structures, Formation Thermodynamics and Substitution Reaction Kinetics in the Copper(ii) – Glycylglycylglycine – L/d/dl-Histidine System

Complex formation thermodynamics in the copper(II) - glycylglycylglycine (GGG center dot H) and copper(II) - glycylglycylglycine - L/D-histidine (HisH) systems (25.0 degrees C, 1.0 M KNO3) was investigated by pH-potentiometric titration and spectrophotometry methods in a wide pH range (2-13). Five hetero-ligand complexes were identified, three of which were characterized for the first time including one binuclear complex. Parameters of individual absorption spectra and ESR spectra of the heteroligand copper(II) complexes with glycylglycylglycine and histidine were obtained for the first time. Complex structures were optimized by DFT computations on the CAM-B3LYP/TZVPP and PBE/TZVPP levels with accounting solvent effect by the C-PCM model. For the complex Cu(GGG center dot H-2)(His)(2) the rapid exchange between two isomers with axial coordination of the imidazole or carboxyl group of His was first found. It was shown that the complex Cu-2(GGG center dot H-2)(His)(HisH(-1))(2) presents as two isomers where deprotonated imidazole of the HisH i ligand connects two copper ions. The kinetics of glycylglycylglycine substitution by LIDL-histidine was investigated by stopped-flow technique with spectrophotometric detection and three-step scheme of the investigated process was proposed. An unusual stereoselective effect in the tripeptide substitution by anionic form of histidine was revealed and interpreted on the basis of the formation of heteroligand complexes as intermediates in overall processes, that was confirmed by DFT calculations. It is emphasized that only combination of several informative methods (pH-metry, UV-Vis-spectroscopy, ESR, stopped-flow, and DFT calculations) made it possible to reliably describe simultaneously the thermodynamics of formation, the kinetics of substitution reactions, and the structure of complexes in the complex ternary system under study. (C) 2021 Elsevier Ltd. All rights reserved.