Possible interactions between fused pyrazole derivative and magnesium ions - NMR experiments and theoretical calculations

Abstract

The paper verifies our recently described NMR approach for the determination of interaction sites between a heterocyclic ligand and magnesium ions. The method is based on the comparison of chemical shifts of condensed pyrazole derivative before and after the complexation with magnesium salt and is supported by DFT (B3LYP/6-31G(d,p) level of theory, CPCM solvation model, GIAO method) and classical molecular dynamics theoretical calculations.

On the Interactions of Fused Pyrazole Derivative with Selected Amino Acids: DFT Calculations

“…The analysis of azole 7 coordination with magnesium ions proved that the pyrrolic nitrogen NH with a labile Table 1: Interaction energies between compound 7 andalanine (7Ala), lysine (7Lys), glutamic acid (7Glu), and methionine (7Met). Suffixes added to the names of adducts mean that the structure was optimized at functional: B, B-C, B-N, B-N exchangeable proton is the principal position in this interaction [8]. Moreover, the pH alterations are unimportant for small molecules that, like compound 7, contain practically one protonation site.…”

“…Moreover, the pH alterations are unimportant for small molecules that, like compound 7, contain practically one protonation site. Additionally, we prove that such compounds do not tautomerize (tautomerism involving protonation of the nitrogen atoms can be neglected) [7][8][9]. Based on this information, we decided to examine the interaction of the pyrrolic nitrogen with the following amino acids: alanine, lysine, glutamic acid, and methionine.…”

“…The abovementioned method was also used for calculation of TMS (reference compound) and the investigated 7-amino acid adducts. Then the values obtained for TMS allowed calculating the chemical shifts of 7 and 7-amino acid adducts, in accordance with the following equation: = ref − , with being chemical shift of -nuclei of 7-amino acid adducts and ref and being the calculated isotropic magnetic shielding tensors of TMS and 7-amino acid adducts, respectively [8,[20][21][22]. An average of the estimated chemical shifts was calculated for the methyl groups protons A or E and also these of C or D (Scheme 1).…”

“…Various analytical methods can be applied to investigate them, including 1 H NMR spectroscopy. Noteworthy is the fact that NMR spectroscopy has found its use for the determination of interactions of some ligands with proteins and allows assessing quantitatively these interactions if the equilibrium constants and changes in chemical shifts are taken into account [8,20,21,26,[28][29][30][31]. As a result, we decided to focus only on 1 H NMR spectroscopy in our study.…”

“…In our subsequent papers, we hypothesized that they could disrupt the intracellular Mg 2+ ions balance through the action of pyridinic nitrogen within the pyrazole moiety [8,9]. An NMR experiment elucidating the interaction of chosen amino acids and the condensed pyrazole derivative showed that this interaction primarily happens between the pyrrolic nitrogen atom (NH) and carbon fragment B (Scheme 1) [7][8][9].…”