Buffer biological membranes

Several factors affect the selection of the buffer solution, such as the optimum pH the buffer anionic or cationic species (which can interfere in the subsequent purification steps) the pH variation with ionic strength or temperature the buffer reactivity with the proteins in solution the biological activity (e.g. phosphates can inhibit or activate a protein in biological reactions) the interaction of the buffer with other components the buffer permeation in biological membranes the toxicity the light absorption at 280 nm the cost (especially if used in large-scale processes) and the protein solubility. 

Also, it is not the overall lipophilicity of a drug molecule determined in octanol-buffer that is important, but the 3-D distribution pattern of lipophilicity on the surface of the molecule, which may generate a hydrophobic-hydrophilic dipole. Such a dipole can determine the specific interaction and orientation of an amphiphilic drug in a highly structured biological membrane. This includes domain formation and accumulation, change in drug conformation, and so forth. All this is... 

Tab. 4.29 1,4-Dihydropyridine partition coefficients into biological membranes and octanol-buffer. (Reprinted from Tab. 1 of ref. 95 with permission from the American Chemical Society)...

Drug Biological membranes (sarcoplasmic reticulum) Octanol-buffer... 

The lipophilicity of a drug is the most-used single physicochemical property to predict permeability across biologic membranes (12). The most common distribution model is octanol/ water (log P) or octanol/buffer (log D, at fixed pH). 

Ernster. L. and Schatz, G. (1981) Mitochondria A historical review. J. Cell Biol. 91, 227s-255s. Skulachev, V.P. (1981) The proton cycle History and problems of the membrane-linked energy transduction, transmission, and buffering. In Chemiosmotic Proton Circuits in Biological Membranes. (Skulachev, V.P. and Hinkle, P.C., eds.) pp. 3-46. Addison-Wesley, Reading. MA. 

Ideally, a well-balanced drug molecule (position 1) as represented by, for example, antipyrine or caffeine, is hydrophilic enough to be soluble in the aqueous body fluids as well as in the pharmaceutically preferred aqueous buffers, but is also sufficiently lipophilic for permeating the biological membranes, thus having no absorption problems. A polar substance is soluble but lacks the lipophilicity for membrane permeation (position 2 examples sorbitol and... 

Both the above factors promote unequal distribution of dlfiusible ions on either side of biological membranes which in turn would result in establishment of a pH difference and an oanotlc difference between the compartments. Minor pH changes are tolerable for most of the tissues but drastic pH changes may pose problems. Ihe body saves Itself finm the harmful influence of the latter with the help of its buffer tems. But sometimes maintenance of a drastic pH difference is a necessity, as is in the case of stomach. Gastric dilation cannot proceed if the pH is not maintained at a very low level. In this case, the gastric mucosal membrane i up to permit the hydrolysis reaction... 

---