Multinuclear NMR and potentiometric study on tautomerism during protonation and zinc(II) complex formation of some imidazole-containing peptide derivatives

Abstract

The acid-base properties and zinc( ti) complexes of glycylhistamine, sarcosyl histamine, carcinine and carnosine have been studied by potentiometric, 13C and 14N N M R methods. Macroscopic species for the three states of protonation (LH;', LH +, L) and the corresponding microspecies involving three protonation sites (terminal amino, N -I and -3 imidazole nitrogens) are quantitatively estimated for the metal-free ligands. Zinc(ii) complexation is shown to reverse the tautomeric preference between 1 -and 3-H tautomeric forms of the imidazole ring (in LH' and L), as compared to the free ligands where the 1 -H tautomer is predominant.

Determination of microscopic acid?base parameters from NMR?pH titrations

“…Due to the low sensitivity, there are only a few examples of its application. Gajda and co-workers observed an upfield shift of 10-60 ppm upon 14 N-protonation of imidazole derivatives [99].…”

“…First, the low occurrence of the minor microspecies holding proton at the imidazole nitrogen precludes the determination of reliable microconstants by conventional NMR-pH titrations [99,120]. Instead, microconstants have been derived from the kinetics of deuteron exchange of the imidazole C 2 -H proton in D 2 O [120].…”

“…By using N-alkylated model compounds, tautomeric ratios have been determined for imidazole, histidine, and histamine derivatives including peptides and proteins by 1 H NMR titrations [122,123,124], 15 N NMR titrations [125,126,127], and 13 C NMR titrations in aqueous [122,128,129,130,131,132] and solid phases [132,133]. Microconstants of individual N 1 -H and N 3 -H tautomers of histidine derivatives have been estimated using model com- pounds [122] and directly from the 14 N NMR-pH titration of glycylhistamine and sarcosylhistamine [99].…”

“…In favorable cases, the overlapping protonating groups are separated by more than four covalent bonds, allowing the use of the adjacent carbon-bound protons as selective, "reporter" nuclei. Based on this principle, microconstants have been determined by 1 H NMR titration for lysine [105], L-3,4-dihydroxyphenylalanine (DOPA, structure 1 in Table 2) [116], histidine or histamine-containing dipeptides [99,117], glycylglycylhistamine [118], reduced glutathione (γ-GluCysGly) [21], oxidized glutathione [18], and the γ-methylphosphino analogue of glutamic acid (phosphinothricin, 2) [56].…”

Molecular Tailored Histidine‐Based Complexing Surfactants: From Micelles to Hydrogels

“…Gly-Gly-His-aEO 2 e-C10 (4d) 7.79 6.14 Gly-Gly-His [19] 7.94 6.82 Gly-Gly-Ha [20] 7.85 6.81 β-Ala-His-aEO 2 e-C10 (3d) 9.13 5.95 β-Ala-His-aEOe-C10 (3b) 9.24 6.20 β-Ala-His [22] 9.35 6.74 β-Ala-Ha [21] 9.21 6.84 Table 2. Cu 2+ and Ni 2+ formation constants of complexes of hydrophilic Gly-Gly-His-aEO 2 e-C4 compared to Ala-Gly-Ha and Gly-GlyHa (T = 25°C, I = 0.1 ).…”