Vesicular catalysis of an S(N)2 reaction: toward understanding the influence of glycolipids on reactions proceeding at the interface of biological membranes.

The kinetics of the S(N)2 reaction of a series of aromatic alkylsulfonates with water and bromide ions in membrane mimetic media have been investigated. These media include vesicles formed from only synthetic amphiphiles, vesicles composed only of phospholipids and mixtures of these components. Special focus is placed on the influence of the addition of n-dodecyl-beta-glucoside as a mimic for glycolipids. The kinetic data have been analyzed by using the pseudophase model for bimolecular reactions. Contrary to previous results on a base-catalyzed E2 reaction (Org. Biomol. Chem. 2004, 2, 1789-1799), the presence of n-dodecyl-beta-glucoside at the vesicular surface does not lead to large rate accelerations for the S(N)2 reaction. In fact, when present at 50 mol % (i.e., the additive covers 34% of the vesicular surface) these glycolipid mimics appear not to affect the bimolecular rate constants, but they only decrease the local water concentration by about 40%. The reactivity of water at the surface of vesicles that are formed from cationic amphiphiles appears to be increased about 10-fold relative to the reactivity of water in the bulk liquid, whereas in zwitterionic vesicles the reactivity is comparable to that in bulk water. The obtained rate constants are also compared to micellar rate constants.