Comparison of PredictedpKaValues for Some Amino-Acids, Dipeptides and Tripeptides, Using COSMO-RS, ChemAxon and ACD/Labs Methods

Toure, Oumar; Dussap, Claude-Gilles; Lebert, André

doi:10.2516/ogst/2012094

Cited by 17 publications

(4 citation statements)

References 16 publications

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“…However, the results obtained using ACDLabs showed a slight sensitivity to the tautomeric species, as the p K a values determined for tautomers A and B differed by less than 1 p K a unit (Table ). These differences are surprising, as several studies have reported that these methods exhibit a close agreement in the p K a prediction of ionizable sites for a variety of compounds, leading to p K a estimates that accurately reproduce the experimental values (generally with mean average deviations <0.7 log units). − However, these studies have often found discrepancies in the predicted p K a values that appear to be related to the presence of specific chemical features, which likely originate from the different natures of the formalisms used by these tools in the p K a prediction and the chemical diversity and structural complexity of the compounds included in the data sets. Overall, these data pose the question about the origin of the chemical factors that determine the experimental p K a of the two sets of tetrahydroazocino enamino ester derivatives.…”

Section: Resultsmentioning

confidence: 99%

Interplay between Ionization and Tautomerism in Bioactive β-Enamino Ester-Containing Cyclic Compounds: Study of Annulated 1,2,3,6-Tetrahydroazocine Derivatives

et al. 2019

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Depending on the chemical scaffold, the bioactive species could reflect the interplay between ionization and tautomerism, often complicated by the possibility to populate different conformational states in the case of flexible ligands. In this context, theoretical methods can be valuable to discern the role of these factors, as shown here for βenamino esters of 1,2,3,6-tetrahydroazocino fused ring systems, some of which had proven to be suitable scaffolds for designing novel acetylcholinesterase inhibitors. The compounds investigated herein form two clusters with distinctive experimental pK a values (i.e., α,β-diesters and β-esters ranging within 6.1-7.3 and 8.2-9.0 pK a intervals, respectively), which implies a drastic difference in the most populated species at physiological conditions. While chemoinformatic tools did not provide a consistent description of the actual pK a values, the theoretical analysis performed for the protonated and neutral species of these compounds revealed a marked change in the tautomeric preference of the tetrahydroazocine moiety upon (de)protonation. Excellent agreement between calculated and experimental pK a values was found when the tautomeric preference of protonated and neutral species was considered. Overall, this study highlights the potential use of high-level computational methods to disclose the mutual influence between ionization, tautomerism and conformational preferences in multifunctional (bio)organic compounds.

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Section: Resultsmentioning

confidence: 99%

Interplay between Ionization and Tautomerism in Bioactive β-Enamino Ester-Containing Cyclic Compounds: Study of Annulated 1,2,3,6-Tetrahydroazocine Derivatives

et al. 2019

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“…1 . According to the ChemAxon method [ 25 – 27 ], the calculated p K a of three hydroxy groups are 7.4 (O6), 7.8 (O3), and 8.2 (O5). For that reason, the α-mangostin was considered as neutral molecule in the MD simulation (pH 7).…”

Section: Methodsmentioning

confidence: 99%

Co-solvation effect on the binding mode of the α-mangostin/β-cyclodextrin inclusion complex

Rungnim¹,

Phunpee²,

Kunaseth³

et al. 2015

Beilstein J. Org. Chem.

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SummaryCyclodextrins (CDs) have been extensively utilized as host molecules to enhance the solubility, stability and bioavailability of hydrophobic drug molecules through the formation of inclusion complexes. It was previously reported that the use of co-solvents in such studies may result in ternary (host:guest:co-solvent) complex formation. The objective of this work was to investigate the effect of ethanol as a co-solvent on the inclusion complex formation between α-mangostin (α-MGS) and β-CD, using both experimental and theoretical studies. Experimental phase-solubility studies were carried out in order to assess complex formation, with the mechanism of association being probed using a mathematical model. It was found that α-MGS was poorly soluble at low ethanol concentrations (0–10% v/v), but higher concentrations (10–40% v/v) resulted in better α-MGS solubility at all β-CD concentrations studied (0–10 mM). From the equilibrium constant calculation, the inclusion complex is still a binary complex (1:1), even in the presence of ethanol. The results from our theoretical study confirm that the binding mode is binary complex and the presence of ethanol as co-solvent enhances the solubility of α-MGS with some effects on the binding affinity with β-CD, depending on the concentration employed.

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“…The COSMO‐RS algorithm allows the calculation of the chemical potential

μ_{i}^{*}

of each compound i in a given solvent. The knowledge of

μ_{i}^{*}

allows the calculation of a wide variety of thermodynamic properties, including the pK a of acids and bases, the Gibbs free energy of solvation and the activity coefficients . For a given compound i , the latter (

γ_{i}^{(x)}

) is generally computed in molar scale and is calculated using Equation :

γ_{i}^{(x)} = \exp (\frac{μ_{i}^{*} - μ_{i}^{*, 0}}{R T}) .

…”

Section: Methodsmentioning

confidence: 99%

Development of a thermodynamic model of aqueous solution suited for foods and biological media. Part A: Prediction of activity coefficients in aqueous mixtures containing electrolytes

et al. 2014

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In food and biological processes, aqueous complexes cover a wide diversity of species and the presence of several phases. The modelling of such processes must take into account these specificities, which require a generalization of the existing thermodynamic models of aqueous solutions. The chemical potential (the molar Gibbs free energy) of a given compound is an important variable to characterize the physical‐chemical properties at equilibrium. Its value depends on two parameters: the Gibbs free energy of formation and the activity coefficient. Both are linked to a chosen reference state. Then, the main thermodynamic modelling task consists in the prediction and/or the collection of formation properties data and in the development of a predictive model of activity coefficients. This work introduces a new prediction tool of activity coefficients of electrolytes in {water‐salt} systems. This tool is based on an extension of the COSMO‐RS method towards the representation of the thermodynamic equilibrium properties of charged species. For this purpose, the long‐range interactions between ions are taken in account by a Pitzer‐Debye‐Hückel term. The resulting model called “COSMO‐RS‐PDHS” is then fully predictive.

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Comparison of PredictedpK_aValues for Some Amino-Acids, Dipeptides and Tripeptides, Using COSMO-RS, ChemAxon and ACD/Labs Methods

Cited by 17 publications

References 16 publications

Interplay between Ionization and Tautomerism in Bioactive β-Enamino Ester-Containing Cyclic Compounds: Study of Annulated 1,2,3,6-Tetrahydroazocine Derivatives

Interplay between Ionization and Tautomerism in Bioactive β-Enamino Ester-Containing Cyclic Compounds: Study of Annulated 1,2,3,6-Tetrahydroazocine Derivatives

Co-solvation effect on the binding mode of the α-mangostin/β-cyclodextrin inclusion complex

Development of a thermodynamic model of aqueous solution suited for foods and biological media. Part A: Prediction of activity coefficients in aqueous mixtures containing electrolytes

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