Multi-pH QSAR: II. Regression Analysis Sensitive Enough to Determine the Transition-State pKa of Human Buccal Absorption
✍ Scribed by Robert A. Scherrer
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 2011
- Tongue
- English
- Weight
- 290 KB
- Volume
- 30
- Category
- Article
- ISSN
- 1868-1743
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✦ Synopsis
Abstract
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.