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Multi‐pH QSAR: II. Regression Analysis Sensitive Enough to Determine the Transition‐State p K a of Human Buccal Absorption
Author(s) -
Scherrer Robert A.
Publication year - 2011
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.201100024
Subject(s) - quantitative structure–activity relationship , chemistry , penetration (warfare) , aqueous solution , absorption (acoustics) , limiting , stereochemistry , computational chemistry , materials science , mathematics , engineering , operations research , composite material , mechanical engineering
An analysis of published human buccal absorption data of an acid and a base at six pH values extends multi‐pH QSAR to an extreme: QSAR on a single compound. The compounds analyzed are 4‐ n ‐hexylphenylacetic acid and propranolol. This analysis might be considered as much an analysis of the model as the compound, itself. Ionizable compounds undergo a p K a change in the process of absorption. Multi‐pH QSAR allows determination of the p K a of the presumed rate‐limiting step for absorption, which we label the transition‐state p K a (p K a TS ). Comparison of the p K a TS with the corresponding aqueous and membrane p K a values provides the extent of molecular penetration at the transition state. It is 49 % of the path length for the arylacetic acid and 73 % for propranolol.