Biophysical Factors in Drug Action 19 



found that cephalin forms a salt-like lipo-protein with salniine, 

 which is a basic protein, over a pH range of 2-11 ; lecithin forms 

 an analogous complex only at />H 10-11. The complex formed 

 between cephalin and salmine has rubberlike physical proper- 

 ties. The dried precipitates swell in water and organic solvents, 

 and they may be recrystallized from ethyl alcohol. Other basic 

 proteins, such as histone, also form complexes. 



X-ray Diffraction Analysis 



From X-ray diffraction analysis of such complexes, Schmitt 

 and Palmer,^^ in collaboration with Chargaff, assumed the 

 existence of a single layer of protein between each bimolecular 

 double layer of cephalin. According to Schmitt and Palmer, 

 the positive polar groups of the extended protein molecules are 

 attached to the negative polar groups of the cephalin molecules 

 on both sides of the protein, and this association results in a 

 decrease in the solvation or hydration of the system. Analogous 

 bimolecular lipid leaflets were detected in emulsions prepared 

 from mixed brain lipids, but the diffraction spacings between 

 the leaflets were much larger than those which occur in the 

 dried lipoprotein complexes. This shows that even in highly 

 solvated systems, the lipid molecules retain their relative orienta- 

 tion to the interlayer aqueous phase. The spacing between the 

 lipid layers in the mixed lipid emulsions is greatly reduced 

 by the presence of divalent cations such as calcium, and this 

 may be related to the conduction of the nerve impulse, for 

 Scott ^^ has reported that the bulk of the calcium in a nerve 

 fiber is located in the myelin sheath. 



Boehm ^ and Handovsky ^^ have described the results of 

 X-ray diffraction analysis on surviving nerves. The association 

 of narcotics with the lipids results in a dispersant action on the 

 packing or orientation of the layers, which become wider and 

 more diffuse. Using similar methods, supplemented by bire- 

 fringence studies in polarized light, Reynolds, Corrigan, and 

 Hayden ^^ were led to believe that orientated lipid associations 

 occur in the human brain, but the degree of orientation varies 



