version date: 1 December 2006 and air-dry at 37C for 30 min. Gold-coat the Al stubs for 3 min at 13.3 pascal in a sputter device and examine the samples in an SEm DESCRIPTION OF RESULTS n order to understand the possible results to be obtained, a description of the experimental results observed with the local anesthetic bupivacaine is presented X-ray diffraction studies Figure lA shows a comparison of the diffraction patterns of DMPC alone immersed in excess water and those of dMPC incubated with bupivacaine in the range of 0.1 mM up to 15 mM. The reflections labeled(a) correspond to the 64 a distance between DMPC polar groups(see Fig. 2a), whereas the strong reflection of 4.2 A labeled(b) corresponds to the average distance between DMPc fully extended acyl chains organized with rotational disorder in hexagonal packing. It is noticeable that addition of 0. 1 mM bupivacaine caused only a very slight decrease in the phospholipid reflection intensities, but 1 mM induced a marked decrease of the (a) intensities, whereas the intensity of 4.2 A reflection was essentially unchanged. However, 8 mM bupivacaine induced a marked decrease of the 4.2 A reflection intensity and the complete disappearance of the(a)reflections, which were replaced by a diffuse halo. This pattern remained practically unchanged after exposure to 15 mM bupivacaine. These results imply that bupivacaine induced serious molecular disorder in the dmPc bilayer, especially in the region of the polar head groups Figure 1B shows the results of the interaction of bupivacaine with DMPE. The perturbing effect of this compound upon the structure of dmpe bilayers was practically negligible even at a 23 mM concentration. As a matter of fact, these two phospholipids differ only in their terminal amino groups, these being N(CH3 )3 in DMPC and NH3 in DMPE. Moreover, both molecular conformations are very similar with the hydrocarbon chains mostly parallel and extended, and the polar groups lying perpendicular to them (Fig. 2b ). However, the hydration of DMPC results in water filling the highly polar interbilayer spaces, a phenomenon that allows the incorporation of bupivacaine into DMPC bilayers, producing its structural perturbation and almost complete destruction at a 8 mM concentration. On the other hand. dmPe molecules pack tighter than those of dmpc due to their smaller polar group and higher effective charge, resulting in a <www.iupac.org/publ ns/cd/medicinal chemistry/>3 and air-dry at 37 ºC for 30 min. Gold-coat the Al stubs for 3 min at 13.3 pascal in a sputter device and examine the samples in an SEM. DESCRIPTION OF RESULTS In order to understand the possible results to be obtained, a description of the experimental results observed with the local anesthetic bupivacaine is presented. X-ray diffraction studies Figure 1A shows a comparison of the diffraction patterns of DMPC alone immersed in excess water and those of DMPC incubated with bupivacaine in the range of 0.1 mM up to 15 mM. The reflections labeled (a) correspond to the 64 Å distance between DMPC polar groups (see Fig. 2a), whereas the strong reflection of 4.2 Å labeled (b) corresponds to the average distance between DMPC fully extended acyl chains organized with rotational disorder in hexagonal packing. It is noticeable that addition of 0.1 mM bupivacaine caused only a very slight decrease in the phospholipid reflection intensities, but 1 mM induced a marked decrease of the (a) intensities, whereas the intensity of 4.2 Å reflection was essentially unchanged. However, 8 mM bupivacaine induced a marked decrease of the 4.2 Å reflection intensity and the complete disappearance of the (a) reflections, which were replaced by a diffuse halo. This pattern remained practically unchanged after exposure to 15 mM bupivacaine. These results imply that bupivacaine induced serious molecular disorder in the DMPC bilayer, especially in the region of the polar head groups. Figure 1B shows the results of the interaction of bupivacaine with DMPE. The perturbing effect of this compound upon the structure of DMPE bilayers was practically negligible even at a 23 mM concentration. As a matter of fact, these two phospholipids differ only in their terminal amino groups, these being + N(CH3)3 in DMPC and + NH3 in DMPE. Moreover, both molecular conformations are very similar with the hydrocarbon chains mostly parallel and extended, and the polar groups lying perpendicular to them (Fig. 2b). However, the hydration of DMPC results in water filling the highly polar interbilayer spaces, a phenomenon that allows the incorporation of bupivacaine into DMPC bilayers, producing its structural perturbation and almost complete destruction at a 8 mM concentration. On the other hand, DMPE molecules pack tighter than those of DMPC due to their smaller polar group and higher effective charge, resulting in a <www.iupac.org/publications/cd/medicinal_chemistry/> version date: 1 December 2006