Systematic Assessment on Aqueous pKa and pKb of an Amino Acid Base on RISM-SCF-SEDD Method: Toward First Principles Calculations

Toward accurate computations of pK(a) and pK(b) 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 pK(a) and pK(b). 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 pK(a) and pK(b). (C) 2011 Wiley Periodicals, Inc. Int J Quantum Chem 112: 103-112, 2012