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Title: Quantum Chemical Calculation of p K as of Environmentally Relevant Functional Groups: Carboxylic Acids, Amines, and Thiols in Aqueous Solution

Developing accurate quantum chemical approaches for calculating p K as is of broad interest. Useful accuracy can be obtained by using density functional theory (DFT) in combination with a polarizable continuum solvent model. However, some classes of molecules present problems for this approach, yielding errors greater than 5 p K units. Various methods have been developed to improve the accuracy of the combined strategy. These methods perform well but either do not generalize or introduce additional degrees of freedom, increasing the computational cost. The Solvation Model based on Density (SMD) has emerged as one of the most commonly used continuum solvent models. Nevertheless, for some classes of organic compounds, e.g., thiols, the p K as calculated with the original SMD model show errors of 6–10 p K units, and we traced these errors to inaccuracies in the solvation free energies of the anions. To improve the accuracy of p K as calculated with DFT and the SMD model, we developed a scaled solvent-accessible surface approach for constructing the solute–solvent boundary. By using a “direct” approach, in which all quantities are computed in the presence of the continuum solvent, the use of thermodynamic cycles is avoided. Furthermore, no explicit water moleculesmore » are required. Three benchmark data sets of experimentally measured p K a values, including 28 carboxylic acids, 10 aliphatic amines, and 45 thiols, were used to assess the optimized SMD model, which we call SMD with a scaled solvent-accessible surface (SMD sSAS). Of the methods tested, the M06-2X density functional approximation, 6-31+G(d,p) basis set, and SMD sSAS solvent model provided the most accurate p K as for each set, yielding mean unsigned errors of 0.9, 0.4, and 0.5 p K units, respectively, for carboxylic acids, aliphatic amines, and thiols. As a result, this approach is therefore useful for efficiently calculating the p K as of environmentally relevant functional groups.« less
Authors:
ORCiD logo [1] ; ORCiD logo [1] ; ORCiD logo [1] ; ORCiD logo [1]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Publication Date:
Grant/Contract Number:
AC05-00OR22725
Type:
Accepted Manuscript
Journal Name:
Journal of Physical Chemistry. A, Molecules, Spectroscopy, Kinetics, Environment, and General Theory
Additional Journal Information:
Journal Volume: 122; Journal Issue: 17; Journal ID: ISSN 1089-5639
Publisher:
American Chemical Society
Research Org:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
OSTI Identifier:
1459306

Lian, Peng, Johnston, Ryne C., Parks, Jerry M., and Smith, Jeremy C.. Quantum Chemical Calculation of pKas of Environmentally Relevant Functional Groups: Carboxylic Acids, Amines, and Thiols in Aqueous Solution. United States: N. p., Web. doi:10.1021/acs.jpca.8b01751.
Lian, Peng, Johnston, Ryne C., Parks, Jerry M., & Smith, Jeremy C.. Quantum Chemical Calculation of pKas of Environmentally Relevant Functional Groups: Carboxylic Acids, Amines, and Thiols in Aqueous Solution. United States. doi:10.1021/acs.jpca.8b01751.
Lian, Peng, Johnston, Ryne C., Parks, Jerry M., and Smith, Jeremy C.. 2018. "Quantum Chemical Calculation of pKas of Environmentally Relevant Functional Groups: Carboxylic Acids, Amines, and Thiols in Aqueous Solution". United States. doi:10.1021/acs.jpca.8b01751. https://www.osti.gov/servlets/purl/1459306.
@article{osti_1459306,
title = {Quantum Chemical Calculation of pKas of Environmentally Relevant Functional Groups: Carboxylic Acids, Amines, and Thiols in Aqueous Solution},
author = {Lian, Peng and Johnston, Ryne C. and Parks, Jerry M. and Smith, Jeremy C.},
abstractNote = {Developing accurate quantum chemical approaches for calculating pKas is of broad interest. Useful accuracy can be obtained by using density functional theory (DFT) in combination with a polarizable continuum solvent model. However, some classes of molecules present problems for this approach, yielding errors greater than 5 pK units. Various methods have been developed to improve the accuracy of the combined strategy. These methods perform well but either do not generalize or introduce additional degrees of freedom, increasing the computational cost. The Solvation Model based on Density (SMD) has emerged as one of the most commonly used continuum solvent models. Nevertheless, for some classes of organic compounds, e.g., thiols, the pKas calculated with the original SMD model show errors of 6–10 pK units, and we traced these errors to inaccuracies in the solvation free energies of the anions. To improve the accuracy of pKas calculated with DFT and the SMD model, we developed a scaled solvent-accessible surface approach for constructing the solute–solvent boundary. By using a “direct” approach, in which all quantities are computed in the presence of the continuum solvent, the use of thermodynamic cycles is avoided. Furthermore, no explicit water molecules are required. Three benchmark data sets of experimentally measured pKa values, including 28 carboxylic acids, 10 aliphatic amines, and 45 thiols, were used to assess the optimized SMD model, which we call SMD with a scaled solvent-accessible surface (SMDsSAS). Of the methods tested, the M06-2X density functional approximation, 6-31+G(d,p) basis set, and SMDsSAS solvent model provided the most accurate pKas for each set, yielding mean unsigned errors of 0.9, 0.4, and 0.5 pK units, respectively, for carboxylic acids, aliphatic amines, and thiols. As a result, this approach is therefore useful for efficiently calculating the pKas of environmentally relevant functional groups.},
doi = {10.1021/acs.jpca.8b01751},
journal = {Journal of Physical Chemistry. A, Molecules, Spectroscopy, Kinetics, Environment, and General Theory},
number = 17,
volume = 122,
place = {United States},
year = {2018},
month = {4}
}