Measurement of drug lipophilicity and pK(a) using acoustics

Li, Xin and Cooper, Matthew A. (2012) Measurement of drug lipophilicity and pK(a) using acoustics. Analytical Chemistry, 84 6: 2609-2613. doi:10.1021/ac300087z

Author Li, Xin
Cooper, Matthew A.
Title Measurement of drug lipophilicity and pK(a) using acoustics
Formatted title
Measurement of drug lipophilicity and pKa using acoustics
Journal name Analytical Chemistry   Check publisher's open access policy
ISSN 0003-2700
Publication date 2012-03
Sub-type Article (original research)
DOI 10.1021/ac300087z
Volume 84
Issue 6
Start page 2609
End page 2613
Total pages 5
Place of publication Washington, DC, United States
Publisher American Chemical Society
Collection year 2013
Language eng
Formatted abstract
Lipophilicity of chemicals and drug candidates is normally described in terms of  octanol/water partitioning and log P. We investigated an alternate approach to lipophilicity determination using a mimic of an alkyl alcohol with compound partitioning quantified using acoustic sensing. A self-assembled monolayer composed of HSC10(CH2CH2O)6C18 was formed on planar gold electrodes of a piezoelectric acoustic sensor. The system was challenged with compounds covering a 4-log range of log D values. As compounds partitioned in the interfacial layer, changes in sensor resonant frequency were found to correlate with compound partition coefficients (log P) and with distribution coefficients (log D). Linear concordance (R2 = 0.933) was established between log(−dF/Mwt) and log P and with log D in both water and biological buffers at variant pH (pH 5.2 to 7.8). In turn, drug pKa could be determined by profiling log D changes during pH titration. The lipophilicity/pH profile of a weakly basic drug (quinine; pKa = 7.95) was sigmoidal with respect to −dF/Mw values, with a profile inverse to that of a weakly acidic drug (naproxen; pKa = 4.15).
Keyword Performance Liquid Chromatography
Water Partition Coefficients
Quartz Crystal Microbalance
Bioactive Compounds
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
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