Acidity of arylsulfonamides as function of quantum chemical parameters of sulfonamide nitrogen

Krylov, E. N.; Virzum, L. V.

doi:10.1007/s11172-019-2449-8

Cited by 3 publications

(3 citation statements)

References 18 publications

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“…Initially, the use of water as a solvent for the photoreaction was hampered by the very low solubility of sulfonamide 1a . By NaOMe-mediated deprotonation of the acidic N–H proton 15 of sulfonamide 1a we generated a water-soluble anion 1e . Irradiation of 1e in water, however, gave hydrolyzed biphenyl 2c .…”

Section: Resultsmentioning

confidence: 99%

Sustainable and highly controlled aryl couplings revealed by systematic assessment of photoactivatable linkers

et al. 2022

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Section: Resultsmentioning

confidence: 99%

Sustainable and highly controlled aryl couplings revealed by systematic assessment of photoactivatable linkers

et al. 2022

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“…Remko and Lieth employed the p K a predictor module in the Jaguar program to compute the dissociation constants of 20 primary sulfonamides and observed good agreement for six of the compounds with experimental data . Krylov and Virzum have also developed quantitative p K a relationships using density functional theory (DFT) molecular electrostatic potential of a series of para-substituted arylsulfonamides to develop quantitative relationships for predicting the p K a values of related compounds . Quite recently, Popelier and co-workers have also demonstrated the use of computed equilibrium bond lengths using DFT calculations to predict the p K a values of sulfonamides and derivatives with very good accuracies .…”

Section: Introductionmentioning

confidence: 99%

“…12 Krylov and Virzum have also developed quantitative pK a relationships using density functional theory (DFT) molecular electrostatic potential of a series of parasubstituted arylsulfonamides to develop quantitative relationships for predicting the pK a values of related compounds. 13 Quite recently, Popelier and co-workers have also demonstrated the use of computed equilibrium bond lengths using DFT calculations to predict the pK a values of sulfonamides and derivatives with very good accuracies. 14 An alternative approach to predicting pK a values is to directly estimate the deprotonation free energy, as shown in eq 2.…”

Section: ■ Introductionmentioning

confidence: 99%

Quantum Chemical Prediction of the Acidities of Sulfonamide Inhibitors of Carbonic Anhydrase

Jiang

Supuran

2022

J. Phys. Chem. A

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This study examined two pK a calculation approaches (direct and proton exchange schemes) that employ high-level quantum chemical methods and implicit solvent models to predict aqueous Brønsted acidities of a large set of sulfonamides. For gas-phase deprotonation energies, the DSD-PBEP86-D3(BJ) double-hybrid functional provided the best agreement with the LNO-CCSD(T)/CBS benchmark with a mean absolute deviation less than 2 kJ mol −1 when the aug-cc-pVTZ or larger basis sets are used. For a large test set of 54 primary and secondary sulfonamides, the use of the DSD-PBEP86-D3(BJ)/aug-cc-pVTZ level of theory in conjunction with SM12 solvation free energies predict their pK a values with a mean accuracy of 0.9 units. In comparison, the SMD and ADF-COSMO-RS models have slightly higher mean errors of 1.4 and 1.1 pK a units provided that the proton exchange scheme was employed to cancel the systematic errors in these models. The performance of these protocols was less ideal when applied to sulfonic acids, sulfamates, and N-substituted sulfonamides, indicating that the degree of error cancellation is sensitive to the chemical environment around the −NH 2 head group. The validated protocols were then used to estimate the pK a values of arylsulfonamide carbonic anhydrase inhibitors, which are used to correct their experimentally measured binding free energies to account for deprotonation of the sulfonamide group upon binding to the enzyme. These corrected values did not have a significant impact on the correlation with MMGBSA binding free energies obtained from classical MD simulations where the ligand is usually considered in the deprotonated form.

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Atomic Electrostatic Potential as a Descriptor of Aminolysis of Phenyl and Thiophenyl Acetates and Hydrolysis of Acetanilides

Krylov,

Virzum,

Gruzdev

et al. 2024

LOC

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Hydrolysis of acetanilides and aminolysis of phenyl and thiophenyl acetates are related reactions since these are processes of nucleophilic substitution on the carbonyl carbon. Current views of chemical reactivity based on the DFT theory rely upon reactivity indices that are descriptors of both the reaction center and the molecule as a whole, and have not been applied to the given processes before. One of such descriptors is an atomic electrostatic potential. The given parameter was calculated by the DFT theory M06/6-311+G (non-specific solvation, MeCN, SMD, and full optimization) for the structures of substituted phenyl acetates XPhO-C(O)Me, acetanilides XPhNHC(O)Me, thiophenyl acetates ZPhSC(=O)Me, and benzyl amines XPhСH2NH2 (X, Z substituents). It has been found that all relationships between the atomic electrostatic potential, the charge on the reaction center in the Hirshfeld scheme, and logK are symbatic. Consequently, in all of the cases, the rate is determined by the nucleophilic attack on the reaction center, with the activity/selectivity relationship being observed. The fact that the reaction rate is limited by the nucleophilic attack of the reagent is not inconsistent with the views of the reaction being concerted, since it is known that such reactions may be quite concerted though not quite synchronous.

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Acidity of arylsulfonamides as function of quantum chemical parameters of sulfonamide nitrogen

Cited by 3 publications

References 18 publications

Sustainable and highly controlled aryl couplings revealed by systematic assessment of photoactivatable linkers

Sustainable and highly controlled aryl couplings revealed by systematic assessment of photoactivatable linkers

Quantum Chemical Prediction of the Acidities of Sulfonamide Inhibitors of Carbonic Anhydrase

Atomic Electrostatic Potential as a Descriptor of Aminolysis of Phenyl and Thiophenyl Acetates and Hydrolysis of Acetanilides

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