Search

Pyrazine‑2‑amidoxime (PAOX) is a prototypical sp2-hybridized amidoxime. Although, we described first time in details PAOX structure in solid state, the profile of PAOX behavior in aqueous solution still needs to be improved. While, acid-base properties of PAOX have been tried to define just once, the presented description was not complete and based only on the results of potentiometry during complexometric studies. The selection of method gives rise problems to observation the protonation or deprotonation processes of compound studied. Due to above, the presented studies show first time the complete description of PAOX acid-base properties by obtaining its pKa, solubility, partition (P) and distribution (D) coefficients using various methods. Among them, experiments: potentiometry; UV spectrophotometry by using Hammett's function and pH-metric titrations; cyclic voltammetry (CV) with glassy carbon electrode (GCE) and with GCE electropolymerized by poly‑ l ‑glycine (PGGCE); 1H NMR and theoretical calculations (DFT). Generally, combined four types of experimental and theoretical methods were used to estimate PAOX macro acidic-dissociation constants values. Moreover, log P and log D were determined spectrophotometrically and calculated also by DFT methods. No previous reports were found in the presented form regarding the complete drug-like properties, including negative together with positive values of pKa. Additionally, we proved by our electrochemical results that the quantitative analysis of PAOX do not need the special conditions of the electrode used in research. Hence, the comparison of our results to those described in the literature about analysis made for others, amidoxime derivatives.

The results of the first structural studies (with the use of both experimental and theoretical methods) on pyrazine-2-amidoxime (PAOX) were shown and discussed. FT-IR spectra were recorded in different concentrations of the PAOX in apolar solvent to check the possibility of the inter- or intramolecular hydrogen-bond formation. All possible tautomers–rotamers of PAOX were then theoretically considered at the DFT(B3LYP)/6-311+G** level in vacuo. For selected isomers, calculations were also performed at higher levels of theory {B3LYP/6-311+G(3df,2p) and G3B3}. Based on the results of DFT calculations, the most stable isomers were found, and their total free energies and infrared spectra were calculated. The energy variation plots for the N8C7N9O10 and N1C2C7N9 dihedral angles were also computed to find two energy barriers, one for E/Z isomerization around the C7N9 double bond and the other one for rotation of the pyrazinyl ring around the C2C7 single bond. The results show that the stability of the PAOX isomers strongly depend on their configuration and orientation of the substituents. The possibilities of inter- and intramolecular hydrogen bonds were also experimentally and theoretically checked. Finally, a potential of mean force was determined in CHCl3 for a dimer of PAOX with hexamethylphosphoramide. Both, experimental and theoretical results are in agreement. Copyright © 2016 John Wiley & Sons, Ltd.