Resolution of a Challenge
for Solvation Modeling:
Calculation of Dicarboxylic Acid Dissociation Constants Using Mixed
Discrete–Continuum Solvation Models
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Abstract
First and second dissociation constants (p<i>K</i><sub>a</sub> values) of oxalic acid, malonic acid, and adipic acid
were
computed by using a number of theoretical protocols based on density
functional theory and using both continuum solvation models and mixed
discrete–continuum solvation models. We show that fully implicit
solvation models (in which the entire solvent is represented by a
dielectric continuum) fail badly for dicarboxylic acids with mean
unsigned errors (averaged over six p<i>K</i><sub>a</sub> values) of 2.4–9.0 log units, depending on the particular
implicit model used. The use of water–solute clusters and accounting
for multiple conformations in solution significantly improve the performance
of both generalized Born solvation models and models that solve the
nonhomogeneous dielectric Poisson equation for bulk electrostatics.
The four most successful models have mean unsigned errors of only
0.6–0.8 log units