Complex structures, formation thermodynamics and substitution reaction kinetics in the copper(II) – glycylglycyl-l-tyrosine – l/d-histidine systems

Complex formation thermodynamics, spectral parameters, structures and kinetics of glycylglycyl-l-tyrosine substitution by l/d-histidine in the Cu(II) – GGY∙H – l/d-HisH systems were investigated by pH-potentiometry, spectrophotometry, ESR, DFT and stopped-flow methods. Six hetero-ligand complexes were characterized. Stereoselective effects in the Cu(GGY)(His) formation and tripeptide substitution by His- were first revealed and interpreted. [Display omitted] Complex formation thermodynamics in the copper(II) – glycylglycyl-l-tyrosine (GGY∙H) and copper(II) – glycylglycyl-l-tyrosine – l/d-histidine (HisH) systems (25.0 °C, 1.0 M KNO3) was investigated by pH-potentiometric titration and spectrophotometry methods in a wide pH range (2–11). As a result five homoligand and six heteroligand complexes were discovered for the first time. Parameters of individual absorption spectra and ESR spectra of the heteroligand copper(II) complexes were first evaluated. Structures of complexes were optimized by DFT computations on the B3LYP/TZVPP level with accounting solvent effect by the C-PCM model and with dispersion correction (D3BJ). Based on the experimental data and the results of quantum chemical computations, it was suggested that there is a d-π interaction between the aromatic system of tyrosine and copper(II) in homoligand complexes with a metal/ligand ratio of 1:1. The stereoselective effect in the formation of Cu(GGY)(His) form having higher stability of complex with l-histidine relative to d-histidine was revealed and explained in terms of trans-influence and π-π-stacking interactions, that was confirmed by quantum-chemical calculations. Using stopped-flow technique with spectrophotometric detection, the kinetics of glycylglycyl-l-tyrosine substitution by l/d-histidine was investigated and three-step scheme of the ligand replacement was proposed. The stereoselective effect in substitution of the glycylglycyl-l-tyrosine by histidine with faster process for d-His− than to l-His− form was detected and explained on the basis of the formation of heteroligand intermediates.