Amphiphilic compound ionization

Balaz and Lukacova (1999) attempted to model the partitioning of 36 non-ionizable compounds in 7 tissues. Amphiphilic compounds, or those possessing extreme log Kow values, tended to show complex distribution kinetics because of their slow membrane transport. However for the non-amphiphilic, non-ionizable compounds with non-extreme log Kow values studied it should be possible to characterize their distribution characteristics based on tissue blood PCs. Distribution is dependent on membrane accumulation, protein binding, and distribution in the aqueous phase. As these features are global rather than dependent on specific 3D structure, distribution is not expected to be structure-specific. In this study, tissue compositions in terms of their protein, lipid, and water content were taken from published data. This information was used to generate models indicating that partitioning was a non-linear function of the compound s lipophilicity and the specific tissue composition. 

The results revealed the importance of directed interaction of water molecules with the polar groups of the amphiphilic compounds. Even extremely strong hydrogen bonds such as those between ionized carboxylate and nonionized carboxylic groups could be intercalated by water molecules with energy conservation. 

At least two of the recognized mechanisms for the formation of electrical double layers (Hunter, elal. 1981 Russel etal., 1989) are relevant to LB film depositions (1) ionization of carboxylic acid group and amphoteric acid groups on solid surfaces, and (2) differences between the affinities of two phases for ions or ionizable species. The latter mechanism includes the uneven distribution of anions and cations between two immiscible phases, the differential adsorption of ions from an electrolyte solution to a solid surface, and the differential solution of one ion over the other from a crystal lattice. Since the solid-liquid and the film-liquid interfaces are flat, large surfaces and since both have a large, solid-like concentration, the analysis that follows applies to both interfaces. For an interface conformed by a thin film of an amphiphilic compound with the hydrophilic end of the molecule in contact with the water subphase, the equilibrium of charges is based on pH and subphase concentration. The effect of pH is highlighted by the definition of the of the carboxylic acid ... 

The use of amphiphilic ions, such as alkylsulfonate or alkylquaternary ammonium compounds, as hetaerons to augment retention of ionized sample components having charges opposite is quite popular in RPC. By... 

The cross-sectional area, AD, of a compound oriented in an amphiphilic gradient such as the air-water or lipid-water interface has been shown to be even more reliable for permeability predictions than the molecular weight [52]. For BBB permeation, the limiting cross-sectional area, AD, was determined as AD 73 A2, and the limiting ionization constants, p Cas, for bases and acids were determined as 9 and 4, respectively [52]. For intestinal barrier permeation, the limiting cross-sectional area was assessed as A D 100 A2, and the limiting ionization constants (pICas) for bases as 9 and for acids as 2 [53]. In this approach, the role of P-gp is again implicit [49]. 

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