Density Functional Theory Calculation of pK_a’s of Thiols in Aqueous Solution Using Explicit Water Molecules and the Polarizable Continuum Model

Abstract

The pKa's of substituted thiols are important for understanding their properties and reactivities in applications in chemistry, biochemistry, and material chemistry. For a collection of 175 different density functionals and the SMD implicit solvation model, the average errors in the calculated pKa's of methanethiol and ethanethiol are almost 10 pKa units higher than for imidazole. A test set of 45 substituted thiols with pKa's ranging from 4 to 12 has been used to assess the performance of 8 functionals with 3 different basis sets. As expected, the basis set needs to include polarization functions on the hydrogens and diffuse functions on the heavy atoms. Solvent cavity scaling was ineffective in correcting the errors in the calculated pKa's. Inclusion of an explicit water molecule that is hydrogen bonded with the H of the thiol group (in neutral) or S(-) (in thiolates) lowers error by an average of 3.5 pKa units. With one explicit water and the SMD solvation model, pKa's calculated with the M06-2X, PBEPBE, BP86, and LC-BLYP functionals are found to deviate from the experimental values by about 1.5-2.0 pKa units whereas pKa's with the B3LYP, ωB97XD and PBEVWN5 functionals are still in error by more than 3 pKa units. The inclusion of three explicit water molecules lowers the calculated pKa further by about 4.5 pKa units. With the B3LYP and ωB97XD functionals, the calculated pKa's are within one unit of the experimental values whereas most other functionals used in this study underestimate the pKa's. This study shows that the ωB97XD functional with the 6-31+G(d,p) and 6-311++G(d,p) basis sets, and the SMD solvation model with three explicit water molecules hydrogen bonded to the sulfur produces the best result for the test set (average error -0.11 ± 0.50 and +0.15 ± 0.58, respectively). The B3LYP functional also performs well (average error -1.11 ± 0.82 and -0.78 ± 0.79, respectively).

A second life for low‐grade wool through formation of all‐keratin composites in cystine reducing calcium chloride–water–ethanol solution

“…Thus in the solvent used for the experiments TGC will be present in dissociated form as thioglycolate. Under these experimental conditions the thiol group will be present in un‐dissociated form as the p K a of this group has been reported with p K a = 10.40 for TGC …”

Thiophenols, Promising Scavengers of Peroxyl Radicals: Mechanisms and kinetics

“…However, the CH 3 OO − anion formed in the SET reaction has a pK a of 11.5. Thus, at pH = 7.4, it will be immediately protonated in a process that is exergonic by 5.59 kcal/mol, and therefore this process is able to drive the SET reaction. Hence, the correct reaction Gibbs free energies for the SET mechanism are actually 5.59 kcal/mol lower and, except for the reaction with specie F, all the reactions are thermodynamically feasible. On the other hand, for the HAT mechanism, the energetics of the reaction does not change with pH, so endergonic pathways are clearly not relevant in the CH 3 OO • scavenging activity of thiophenols.…”

“…As in the previous case, SET reactions with species A, D, F and L are endergonic. However if the working pH is taken into account, the HOO − anion will be immediately protonated (pK a = 11.6), and the calculated free energies must be corrected by a factor of 5.73 kcal/mol. That is because the corresponding Gibbs energy of reaction would explicitly depend on the pH. Thus, this effect has been considered here, and the reported data correspond to pH = 7.4.…”

Chemiresistors for the Real‐Time Wireless Detection of Anions

“…Experimental p K a values were determined by UV‐vis titration with TBA benzoate in DMSO (Figures S19–S21, Supporting Information) . Theoretical p K a values of the selectors were calculated by DFT using the SMD implicit solvation model, wherein the solution phase Gibbs free energies were calculated by combining free energies of solvation in DMSO with the gas phase free energies (Supporting Information). The experimental and computational p K a values are within 1 p K a unit and a consistent order of the selectors with 2 < 3 < 1 ( Table 3 ).…”