Aqueous acidities of primary benzenesulfonamides: Quantum chemical predictions based on density functional theory and SMD

Abstract

Aqueous pK(a) of selected primary benzenesulfonamides are predicted in a systematic manner using density functional theory methods and the SMD solvent model together with direct and proton exchange thermodynamic cycles. Some test calculations were also performed using high-level composite CBS-QB3 approach. The direct scheme generally does not yield a satisfactory agreement between calculated and measured acidities due to a severe overestimation of the Gibbs free energy changes of the gas-phase deprotonation reaction by the used exchange-correlation functionals. The relative pK(a) values calculated using proton exchange method compare to experimental data very well in both qualitative and quantitative terms, with a mean absolute error of about 0.4 pK(a) units. To achieve this accuracy, we find it mandatory to perform geometry optimization of the neutral and anionic species in the gas and solution phases separately, because different conformations are stabilized in these two cases. We have attempted to evaluate the effect of the conformer-averaged free energies in the pK(a) predictions, and the general conclusion is that this procedure is highly too costly as compared with the very small improvement we have gained.

Antitubulin sulfonamides: The successful combination of an established drug class and a multifaceted target

“…Primary and secondary sulfonamides are weak acids with varying pK a values depending on the substitutions . Different therapeutic applications of sulfonamides possess distinct optimal acidity ranges, for instance carbonic anhydrase antiglaucoma sulfonamides present higher acidity than anticancer ones, whereas for bacteriostatic activity reduced acidity is usually preferred .…”

Computational study on the Rh‐catalyzed chemodivergent oxidative annulation of benzamides and enynes

“…Intrinsic coordinate reaction [ 40‐42 ] calculations were carried out to examine the connectivity of a transition state with its backward and forward minima when necessary. The energetic results were then further refined by single‐point calculations at the M06 [ 43,44 ] /BSII level with solvation effects accounted for by the solvation model based on density [ 45‐49 ] solvent model using ethanol or 1,4‐dioxane as a solvent according to the experimental conditions, where BSII denotes the basis set combination of SDD [ 50‐52 ] for Rh atom and 6‐311++G(d,p) for main group elements. Natural bond orbital (NBO) analyses were performed at the B3LYP/BSII level on selected systems with the NBO code included in Gaussian 09.…”

Theoretical study on the Rh-catalyzed C−C activation of cyclopropanol to construct diketone or monoketone

“…Intrinsic coordinate reaction (IRC) [19][20][21] calculations were carried out to examine the connectivity of a transition state with its backward and forward minima when necessary. The energetic results were then further refined by single-point calculations at the M06 [22,23] /BSII level with solvation effects accounted for by the SMD [24][25][26][27][28] solvent model using TFE as solvent according to the experimental conditions, where BSII denotes the basis set combination of SDD [29][30][31] for Rh atom, and 6-311++G(d,p) for main group elements. Natural bond orbital (NBO) analyses were performed at the B3LYP/BSII level on selected systems with the NBO code included in Gaussian 09.…”