Studies of drug hydrophobicity, dissociation constants, and protein unfolding using capillary electrophoresis

Capillary electrophoresis (CE) was used to evaluate drug hydrophobicity, di ssociation constants (pK(a)), and protein unfolding. in one study, the hydr ophobicity of solutes was measured by microemulsion electrokinetic chromato graphy (MEEKC). The logarithm of the capacity factors was highly correlated with the logarithm of the octanol/water partition coefficients (log P-ow). The reproducibility was drastically improved by using the migration index (MI). MI provided a better correlation with some bioactivites than did othe r hydrophobicity parameters, such as log P-ow. In a second study, a general equation for use in calculating pK(a)s from solute mobilities observed at different pHs was derived to be suitable for multivalent compounds with clo se pK(a)s. This method was useful for slightly soluble compounds and compou nds containing some impurities or that decompose easily. In a third study, the thermodynamic parameters of the thermally-induced unfolding of proteins were determined by CE using an in-column incubation method. Although the a pparent transition temperatures by CE were generally consistent with those obtained by far-UV CD, these two methods had different detection selectivit ies for changes in the protein structures. These nanoscale methods have som e advantages, such as high speed and high reproducibility, and should be ap plicable in various fields.