Partition coefficients desolvation

In this model, one can argue that a peptide must have both an affinity for the interface (favorable n-octanol partition coefficient) and small desolvation energy (favorable A log PC) in order to efficiently cross a cell membrane. On the other hand, this model also predicts that a peptide with a large n-octanol/water partition coefficient and large desolvation energy, due to a significant number of polar groups, should adsorb and remain at the membrane interface. Both of these predicted events have been observed in the laboratory. 

Fig. 37), suggesting that desolvation of the polar bonds in the molecule is a major determinant of permeability. Consistent with this, good correlations were found between the permeabilities of these peptides and their partition coefficients between heptane-ethylene glycol (r2 = 0.87) or the differences in partition coefficients between n-octanol-buffer and isooctane-buffer (r2 = 0.82) both these buffer systems provide experimental estimates of hydrogen-bonding potential. These results are qualitatively identical with those described earlier for the permeability of these peptides across Caco-2 cell monolayers. 

Pearlman, R. S. (1986) Molecular surface area and volume Their calculation and use in predicting solubilities and free energies of desolvation. In Partition coefficient, Determination and Estimation. Dunn, III, W. J., Block, J. H., Pearlman R. S., Eds., pp. 3-20, Pergamon Press, New York. 

The choice of a solvent model for the hydrophobic interaction. Obviously the selectivity of the biological system cannot be modeled by a solvent. However, solvents can be chosen to model the partial desolvation observed in protein-protein interactions (see above) because there is a qualitative analogy between water and non-polar solvents and the interaction of small molecules with biological systems. This can be expressed as a quantitative relation between partition coefficients and the binding to biological systems (receptors, proteins, membranes, etc.) It... 

A drug is absorbed through diffusion across a series of separate barriers where the single layer of epithelial cells is the most significant barrier to absorption. Many in vitro methods have been developed for the study of this phenomenon. These methods include small animal gut studies, cell culture (i.e., Caco-2 cell culture model), octanol-water partition coefficients, measures of hydrogen bonding and desolvation energies, immobilized artificial membranes, and retention time on reversed-phase HPLC columns. 

R. S. Pearlman, in Partition Coefficient Determination and Estimation, W. J. Dunn, J. H. Block, and R. S. Pearlman, Eds., Pergamon Press, New York, 1986. Molecular Surface Area and Volume Their Calculation and Use in Predicting Solubilities and Free Energies of Desolvation. J. S. Murray, P. Lane, T. Brinck, K. Paulsen, M. E. Grice, and P. Politzer, J. Phys. Chem., 97, 9369 (1993). Relationships of Critical Constants and Boiling Points to Computed Molecular Surface Properties. 

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