IEF-PCM Calculations of Absolute pKa for Substituted Phenols in Dimethyl Sulfoxide and Acetonitrile Solutions

Absolute (nonrelative) pK(a) calculations for substituted phenols were carried out in nonaqueous media, demonstrating the predictive power of the integral equation formalism PCM method with a mean unsigned error of 0.6 pK(a) units for DMSO and 0.7 pK(a) units for MeCN at the B3LYP/6-31+G** level of theory combined with the scaled B3LYP/6-311+G** gas-phase data. At the same time, the correlation between the calculated and experimental pK(a) values yielded the value of the linear regression slope very close to unity for both DMSO and MeCN. Computation of pK(a) of neutral acids in nonaqueous solutions with a reasonable precision obviously depends on carefully tuned cavities, optimized for nonaqueous solutions. The ability of continuum solvation model to compensate charge escape from the cavity, which is prominent in the case of anions, is also required. And finally, good quality gas-phase data is essential to achieve required pK(a) precision.