Substituent effects on the ionization and partitioning of p-(aminoethyl)phenols and structurally related compounds: Electrostatic effects dependent on conformation

DRUG DISCOVERY INTERFACE: Functional Group Dependence of Solute Partitioning to Various Locations within a DOPC Bilayer: A Comparison of Molecular Dynamics Simulations with Experiment

“…These values range widely from 2.7 to 5.6 kcal/mol. 30,32,34,63,64 Values derived from permeability experiments 30 across the DOPC bilayer (3.9 kcal/ mol) and from 1,9-decadiene/water partition coefficients (4.2 kcal/mol) are in reasonable agreement. These values are lower than those obtained from the alkane/water partition coefficients.…”

“…Transfer free energy profiles (from water) generated in MD simulations as a function of depth in the bilayer are compared to previously reported experimental results. 34,35 These simulations allowed the determination of the location of the barrier domain for permeability where the transfer free energy is highest. A separate preferred binding region at the free energy minimum for each of the three solutes was studied.…”

“…determined under conditions wherein tyramine was in its predominantly protonated (positively charged) form.b Calculated from decadiene/water partition coefficients determined at 25 • C 34. c Calculated from DMPC liposome/water partition coefficients measured by Rogers and Davis.…”

Permeability of Fluid-Phase Phospholipid Bilayers: Assessment and Useful Correlations for Permeability Screening and Other Applications

“…It is shown in the companion paper 38 that the rms variability for measurements of log 10 K decadiene/w | 25 • C reported by Xiang, Anderson, and coworkers 26,[28][29][30][32][33][34][35]62,94 is ∼0.05. Given the dearth of information on this partition coefficient, which seems not to have been the subject of systematic study in any other laboratory, no data exist to gauge interlaboratory variability.…”

“…Its resolution lies in a more detailed consideration of molecular-and atomic-scale permeant-bilayer interactions. Analyses of chemical group contributions to the overall free energy of permeant-bilayer interaction by Xiang, Anderson, and coworkers 28,29,[33][34][35]50,86,94,105 represent an important step in this direction, as do numerous computer simulation studies cited above.…”