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Predicting p K a Values in Aqueous Solution for the Guanidine Functional Group from Gas Phase Ab Initio Bond Lengths
Author(s) -
Griffiths Mark Z.,
Alkorta Ibon,
Popelier Paul L. A.
Publication year - 2013
Publication title -
molecular informatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.481
H-Index - 68
eISSN - 1868-1751
pISSN - 1868-1743
DOI - 10.1002/minf.201300008
Subject(s) - tautomer , chemistry , ab initio , substructure , bond length , molecule , computational chemistry , group (periodic table) , ab initio quantum chemistry methods , thermodynamics , stereochemistry , physics , organic chemistry , structural engineering , engineering
Here we applied a novel method1a to predict p K a values of the guanidine functional group, which is a notoriously difficult. This method, which was developed in our lab, uses only one ab initio bond length obtained at a low level of theory. The method is shown to work for drug molecules, delivers prediction errors of less than 0.5 log units, successfully treats tautomerisation in close relation with experiment, and demonstrates strong correlations with only a few data points. The high structural content of the ab initio bond length makes a given data set essentially divide itself into high correlation subsets. One then observes that molecules within a subset possess a common substructure. Each high correlation subset exists in its own region of chemical space. The high correlation subset method is explored with respect to this position in chemical space, in particular tautomerisation. The proposed method is able to distinguish between different tautomeric forms and the preferred tautomeric form emerges naturally, in agreement with experiment.