Determination of acidity constants of pyridines, imidazoles, and oximes by capillary electrophoresis

Abstract

The acidity constant in the form of pKa is one of the most important physicochemical quantities. There are prediction tools available for calculating the pKa, but they only deliver precise calculated values for a relatively small set of chemicals. For complex structures with multiple functional groups in particular, the error in the predicted pKa is high due to the application domain of the corresponding models. Thus, we aim to enlarge the dataset of experimentally determined pKa values using capillary electrophoresis. We, therefore, selected various pyridines, imidazoles, and oximes to determine the pKa values using the internal standard approach and the classical method. Especially oximes were not investigated in the past, and predictions for them include larger errors. Thus, our experimentally determined values could contribute to an improved understanding of various functional groups impacting the pKa values and serve as additional datasets to develop improved pKa prediction tools.

Synthesis of Phenol–Pyridinium Salts Enabled by Tandem Electron Donor–Acceptor Complexation and Iridium Photocatalysis

“…Unproductive deprotonation would result in the formation of neutral phenoxyl radicals, which would likely undergo dimerization (a main reaction byproduct) . 4-Trifluoromethylpyridinium [p K a (4-CF 3 pyr-H + ) = 2.26] could serve as an acidic scavenger of O 2 •– to avoid phenoxyl deprotonation. Disproportionation with HOO • can also consume the superoxide anion. , Additionally, HFIP has been found to have a unique ability to stabilize radical cation intermediates .…”

Determination of physicochemical parameters of (bio)molecules and (bio)particles by capillary electromigration methods

“…Thus, p K a of very weak acids or very weak bases cannot be determined by this method. Concerning polyprotic acids and bases, the IS method is not suitable for cases when these compounds have small differences between their p K a values; the values should differ at least in ∼3 pH units [128]. To achieve higher precision and accuracy, several adequate ISs can be chosen, and the results have to be averaged.…”

“…Recently, IS‐CE method was utilized for the determination of p K a values of pyridines, imidazoles, and oximes [128]. A suitable p K a range for acids (3–10.5) and bases (4.0–12) was estimated for the IS‐CE method.…”

Acidity constants and protonation sites of cyclic dinucleotides determined by capillary electrophoresis, quantum chemical calculations, and NMR spectroscopy

“…CE has been utilized for pK a determination of various compounds mainly in aqueous solutions [28][29][30][31][32][33][34][35] but also in mixed hydro-organic solvents [27,36] and nonaqueous media [37][38][39]. Recently, several innovations in CE determination of pK a have been proposed.…”