A log 7-Hydrogen Bonding and Ionic Equilibrium Effects

Most drug-like molecules dissolved in water form hydrogen bonds with the solvent. When such a molecule transfers from water into a phospholipid bilayer, the solute-water hydrogen bonds are broken (desolvation), as new solute-lipid H bonds form in the lipid phase. The free-energy difference between the two states of solvation has direct impact on the ability of the molecules to cross biological barriers. 

DOUBLE-SINK (Soy Lecithin 20% wt/vol in Dodecane, SINK in Acceptor) 

Seiler [250] proposed a way of estimating the extent of hydrogen bonding in solute partitioning between water and a lipid phase by measuring the so-called A log P parameter. The latter parameter is usually defined as the difference between the partition coefficient of a solute measured in the octanol-water system and that measured in an inert alkane-water suspension AlogP = log Kp oet — log Kp aik. 

Avdeef et al. [556] measured the PAMPA permeabilities of a series of drug molecules and natural products using both dodecane- and (dodecane + 2%DOPC)-coated filters. It was proposed that a new H-bonding scale could be explored, based not on partition coefficients but on permeabilities. 

---