Paper Info
Title
A Reliable And Efficient First Principles-Based Method For Predicting Pka Values. 4. Organic Bases
Abstract
The ionization (dissociation) constant (pKa) is one of the most important properties of a drug molecule. It is reported that almost 68% of ionized drugs are weak bases. To be able to predict accurately the pKa value(s) for a drug candidate is very important, especially in the early stages of drug discovery, as calculations are much cheaper than determining pKa values experimentally. In this study, we derive two linear fitting equations (pKa = a x ?E + b; where a and b are constants and ?E is the energy difference between the cationic and neutral forms, i.e., ?E = Eneutral-Ecationic) for predicting pKas for organic bases in aqueous solution based on a training/test set of almost 500 compounds using our previously developed protocol (OLYP/6-311+G**//3-21G(d) with the the conductor-like screening model solvation model, water as solvent; see Zhang, Baker, Pulay, J. Phys. Chem. A 2010, 114, 432). One equation is for saturated bases such as aliphatic and cyclic amines, anilines, guanidines, imines, and amidines; the other is for unsaturated bases such as heterocyclic aromatic bases and their derivatives. The mean absolute deviations for saturated and unsaturated bases were 0.45 and 0.52 pKa units, respectively. Over 60% and 86% of the computed pKa values lie within +/- 0.5 and +/- 1.0 pKa units, respectively, of the corresponding experimental values. The results further demonstrate that our protocol is reliable and can accurately predict pKa values for organic bases. (c) 2012 Wiley Periodicals, Inc.
Year
DOI
Venue
2012
10.1002/jcc.23068
JOURNAL OF COMPUTATIONAL CHEMISTRY
Keywords
Field
DocType
pKa prediction, organic bases, COSMO solvation model, ab initio, density functional theory
Organic base,Acid dissociation constant,Computational chemistry,COSMO solvation model,Chemistry,Density functional theory,Solvation,Ab initio,Protein pKa calculations,Aqueous solution
Journal
Volume
Issue
ISSN
33
31
0192-8651
Citations 
PageRank 
References 
0
0.34
8
Authors
1
Name
Order
Citations
PageRank
Shuming Zhang102.37