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Linear Free‐Energy Relationships between a Single Gas‐Phase Ab Initio Equilibrium Bond Length and Experimental p K a Values in Aqueous Solution
Author(s) -
Alkorta Ibon,
Popelier Paul L. A.
Publication year - 2015
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.201402711
Subject(s) - ab initio , chemistry , ab initio quantum chemistry methods , molecule , tautomer , bond length , computational chemistry , aqueous solution , phase (matter) , thermodynamics , crystallography , stereochemistry , organic chemistry , physics
Remarkably simple yet effective linear free energy relationships were discovered between a single ab initio computed bond length in the gas phase and experimental p K a values in aqueous solution. The formation of these relationships is driven by chemical features such as functional groups, meta / para substitution and tautomerism. The high structural content of the ab initio bond length makes a given data set essentially divide itself into high correlation subsets (HCSs). Surprisingly, all molecules in a given high correlation subset share the same conformation in the gas phase. Here we show that accurate p K a values can be predicted from such HCSs. This is achieved within an accuracy of 0.2 p K a units for 5 drug molecules.