ABSTRACT
Van der Waals complexes formed between chiral molecules in the isolated gas phase were studied by combining supersonic expansion techniques with laser spectroscopy. The weakly bound diastereoisomers formed between a chiral secondary alcohol, butan-2-ol, and a chiral aromatic derivative such as 2-naphthyl-1-ethanol or 1-phenylethanol used as a resolving agent were discriminated on the basis of the spectral shifts of the UV S(0)-S(1) transition of the chromophore. Ground-state depletion spectroscopy (hole burning) has shown that, while only one structure was detected for the 1-phenylethanol/butan-2-ol homochiral complex, the heterochiral complex is trapped in the jet under two different conformations. Two isomers have also been shown for each diastereoisomeric pair of the 2-naphthyl-1-ethanol/butan-2-ol complexes. Using a semiempirical potential model, these isomeric forms were related to calculated structures which exhibit a folded or extended geometry depending on the solvent conformation (anti or gauche). The relative binding energy of the complexes involving R-1-phenylethanol and R- or S-butan-2-ol were obtained from fragmentation threshold measurements following two-color photoionization. Comparison of the diastereoisomers exhibiting a similar spectral signature shows that the homochiral pair is more stable than the heterochiral one by about 0.7 kcal/mol. The fragmentation threshold has been shown to depend on the jet-cooled isomer and this result addresses the role of conformational control in enantioselective interactions.
ABSTRACT
Endothelial cells that make up brain capillaries and constitute the blood-brain barrier become different from peripheral endothelial cells in response to inductive factors found in the nervous system. We have established a cell culture model of the blood-brain barrier by treating brain endothelial cells with a combination of astrocyte-conditioned medium and agents that elevate intracellular cAMP. These cells form high resistance tight junctions and exhibit low rates of paracellular leakage and fluid-phase endocytosis. They also undergo a dramatic structural reorganization as they form tight junctions. Results from these studies suggest modes of manipulating the permeability of the blood-brain barrier, potentially providing the basis for increasing the penetration of drugs into the central nervous system.