• pKa;
  • pKb;
  • a hybrid method of QM and MM


Toward accurate computations of pKa and pKb from the first principles, a systematic assessment based on accurate evaluation of free energy is presented. Because the process is essentially bond formation and dissociation in aqueous solution, both of highly sophisticated quantum chemistry and an accurate evaluation of solvation-free energy are necessary to appropriately compute pKa and pKb. In this study, the proton dissociation of carboxyl and amino groups in glycine molecule in aqueous solution was examined. A hybrid approach called reference interaction site model self consistent field with spatial electron density distribution (RISM-SCF-SEDD) was used, in which HF, DFT, and CCSD(T) were combined with statistical mechanical theory for molecular liquid. We found that a spatial extension of electronic distribution of the carboxyl group was essential to correctly evaluate pKa and pKb. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012