Small-angle Neutron and X-ray Diffraction

6-dimethyl-4-(2-nitrophenyl)-3,5-pyri-dine dicarboxylic acid dimethyl ester NIM, ni- 

It is interesting to note that the concentrations of verapamil that exert the perturbing effect are in the same range as concentrations that have been reported to have in vitro biological membrane effects. It is also remarkable that for this series of drags no correlation has been found between the degree of perturbation and their log P [68], 

X-ray diffraction [72], often in combination with DSC or NMR, is another useful tool for the study of drug-membrane interactions. It is especially useful to obtain information on the localization of drag molecules and on the conformational (phase) changes of membranes. The method is based on comparing the electron density profile of membranes to which drug has or has not been added. If partially hydrated probes are used, coherent Bragg-like scattering is obtained at reasonable resolution. 

The observed differences provide information on the localization of the drug within the bilayer as well as on the perturbation of the membrane induced by the drug. 

Several other examples of drug-membrane interactions have been reported. Using X-ray diffraction techniques, interactions with tetracyclines [75], pindolol [76], and chlorpromazine [77, 78] have been described. In these studies, it was shown that in the presence of chlorpromazine the bilayer thickness or lipid head group separation in DPPC liposomes is only 30 A, which is about 20 A smaller than two fully extended DPPC molecules. Chlorpromazine produced an interdigitated phase, which is in agreement with the observed effect of chlorpromazine on the shape of erythrocytes. 

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