Determination of Acid Dissociation Constants (pKa) of Bicyclic Thiohydantoin-Pyrrolidine Compounds in 20% Ethanol-Water Hydroorganic Solvent

Abstract

The acid dissociation constants of potential bioactive fused ring thiohydantoin-pyrrolidine compounds were determined by potentiometric titration in 20% (v/v) ethanol-water mixed at 25 ± 0.1°C, at an ionic background of 0.1 mol/L of NaCl using the HYPERQUAD computer program. Proton affinities of potential donor atoms of the ligands were calculated by AM1 and PM3 semiempiric methods. We found, potentiometrically, three different acid dissociation constants for 1a–f. We suggest that these acid dissociation constants are related to the carboxyl, enol, and amino groups.

Acid Dissociation Constants of 5,5-Diphenylpyrrolidine N-Aroylthioureas and Stability Constants of their Pt(II) and Ni(II) Complexes in Acetonitrile-Water Hydroorganic Solvent

“…pKa values for each C(O)NHC(S)N type of ligands in a dioxane-water (50% (v/v)) mixture have been reported [61]. In the previous study [59], we reported that three acid dissociation constants exist for each fused ring thiohydantoin-pyrrolidine derivative having a C(O)NHC(S)N cyclic moiety and suggested that the pKa values were related to their carboxyl, enol andamide NH groups. Herein, we have reported that three pKa values for each 5,5-diphenylpyrrolidine N-aroylthioureas were determined in acetonitrile-water hydroorganic solvent by using the HYPERQUAD computer programme.…”

“…2.2 Procedure. As described in our previous study [59], the potentiometric titrations were performed in the double-wall glass titration vessel, kept at 25.0  0.1 C, the titration solution was magnetically stirred. Before and after each titration process, the double-wall glass titration vessel was rinsed and dried.…”

Synthesis and Determination of Acid Dissociation Constants in Dimethyl Sulfoxide–Water Hydroorganic Solvent of 5,5-Diphenylpyrrolidine N-Aroylthiourea Derivatives

“…Acid dissociation constant is one of resorted data for the studies on molecular modeling and drug design and those determining the optimal conditions of analysis methods (35)(36)(37). Many studies in the literature focused on determining the acidity of the constants of the compounds (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40).…”

Determination of pKa values of alendronate sodium in aqueous solution by piecewise linear regression based on acid-base potentiometric titration

“…As a kind of bisphosphonates containing four hydroxyl groups that can all be dissociated, alendronate sodium has four dissociation constants, which leads to its different electrochemical states existing in aqueous solution with different pH values [7] . Dissociation constants are considered as vital physicochemical parameters from which we could get important information about drug properties such as solubility [8] , acidity [9] , [10] , biological uptake [11] , and metabolism [12] . Moreover, pKa values are important for estimating the charged state of analytes and the retention order in the development of chromatographic and electrophoretic methods.…”