Thermodynamic analysis of nonelectrolyte permeation across the toad urinary bladder

Permeability coefficients (P's) and apparent activation energies (Ealpha's) for nonelectrolyte permeation across the toad urinary bladder have been analyzed in terms of the thermodynamics of partition between membrane lipids and water. Particular attention has been paid to the contributions made by -CH2- and -OH groups: on the average, the addition of one -CH2- group to a molecule increases P fourfold, while the addition of one -OH group reduces P 500-fold. Using these changes in P, we have calculated the incremental free energies (delta delta F), enthalpies (delta delta H), and entropies (delta delta S) for partition, hydration, and solution in membrane lipids. The results for toad bladder have been compared and contrasted with those extracted from the literature for red blood cells, lecithin liposomes, and bulk phase lipid solvents. The partition of -CH2- groups into toad bladder and red cell membranes is dominated by entropy effects, i.e., a decrease in entropy of the aqueous phase that "pushes" the group out of water, and an increase in entropy of the membrane lipid that "pulls" the group into the membrane. This process resembles that in "frozen" liposome membranes. In "melted" liposomes and bulk lipid solvents the free energy of solution in the lipid is controlled by enthalpy of solution. PArtition of -OH groups in all systems is governed by hydrogen bonding between the -OH group and water. However, the solution of the -OH group in the toad bladder membranes is complex, and processes such as dimer and tetramer formation in the lipid phase may be involved. The results presented in this and the previous paper are discussed in terms of the structure of phospholipid bilayer membranes. Attention is drawn to the possible role of structural defects in the quasi-crystalline structure of the lipid (so-called 2 gl klinks) in the permeation of small molecules such as water, urea, methanol and acetamide.