Determination of pK_a values of some novel benzimidazole salts by using a new approach with ¹H NMR spectroscopy

Abstract

Benzimidazoles and their derivatives including imidazole are studied widely because they exist in the structure of natural products and different drugs. pKa values are extremely important for drug discovery and improvement in order to determine pharmacokinetic and pharmacodynamic features such as permeation through biological barriers, interactions with the target area or side effects. Acid-base features (pKa ) have great importance not only for physiological characteristics but also for being used as a ligand or changing physico-chemical features by turning benzimidazoles into salts. Within the scope of this study, a variety of new benzimidazole salts were synthesized, and their characterizations were made by NMR spectroscopy, FTIR spectroscopy and element analysis techniques. The pKa values of synthesized benzimidazole salts were determined by inflection point approach using integration values obtained with (1) H NMR spectroscopy and Henderson-Hasselbalch analysis. pKa values of some benzimidazole salts were also determined by potentiometric methods in order to compare those of NMR spectroscopy results.

A robust and tunable halogen bond organocatalyzed 2-deoxyglycosylation involving quantum tunneling

“…While the non-iodinated control catalyst E gave good yields of 3a (Fig. 2, entry 8), the benzimidazolium hydrogen is known to be acidic and could function as either a nonclassical HB or a Brønsted acid catalyst (Supplementary Note 15) 70,71 , and does not constitute exclusionary proof of XB catalysis by A. To better investigate the criticality of XB catalyst influences on our system, TBAB and TBAI are added into the reaction to inhibit the XB activation mechanism by competition for the σ-hole site, due to the extremely high affinity of halide ions to the XB catalyst ( Fig.…”

NMR spectroscopy in drug discovery and development: Evaluation of physico-chemical properties

“…NMR spectroscopy is also based on analysis of protonation degree of a molecule with changing pH. The protonation degree is monitored either by the chemical shift changes close to the acidic or basic regions of molecule [ 47 ] or via changes of the integration values of peaks that arise from ionizable groups ( Figure 4 ) [ 48 ].…”

“… Different pH value 1 H NMR spectrums obtained by the 10 mM tetrabutylammonium hydroxide solution (TBAH) titration of 1-[2-(4-methoxyphenyl)ethyl]-3-methylbenzimidazolium iodide (2) compound in 10 mM solution and the sigmoidal curve that was acquired with the passing of integral values obtained from these spectrums to the against pH values. Taken with permission from [ 48 ]. Copyright (2019) with permission from Wiley.…”

Determination of acid dissociation constants of Alizarin Red S, Methyl Orange, Bromothymol Blue and Bromophenol Blue using a digital camera

“…They play a basic role in different analytical procedures such as acid-base titrations, complex formations, and solvent extraction. Various methods were used to determine the pK a values including spectrophotometry, 1-9 spectro-uorimetry, 10 potentiometry, 1,10-13 conductometry, 14,15 cyclic voltammetry, 16 chromatography, 1,17-20 electrophoresis, 21,22 NMR, 23,24 mass spectrometry, 25 and Raman spectroscopy; 26 however the majority of these methods require expensive and sophisticated instruments. Therefore, solution scanometric methods were used, [27][28][29][30] but the lack of uniformity of the captured images greatly affected the precision of the analysis posing a serious disadvantage of these methods.…”