Langmuir 2005, 21, 9809-9817
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Vesicular Catalysis of an SN2 Reaction: Toward Understanding the Influence of Glycolipids on Reactions Proceeding at the Interface of Biological Membranes† Jaap E. Klijn and Jan B. F. N. Engberts* Contribution from the Physical Organic Chemistry Unit, Stratingh Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands Received February 22, 2005. In Final Form: May 19, 2005 The kinetics of the SN2 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-β-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-βglucoside at the vesicular surface does not lead to large rate accelerations for the SN2 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.
Part of the Bob Rowell Festschrift special issue. * To whom correspondence should be addressed. E-mail:
[email protected].
examined the reaction of 5-nitrobenzisoxazole with hydroxide ions in (synthetic) cationic vesicles in the presence of anionic amphiphiles, and the biologically relevant additives cholesterol, long linear alcohols, and sugar-based surfactants. In general, large rate accelerations (about 103) are observed when the maximum observed rate constant is compared to the observed aqueous rate constant. This is due to two effects. The first effect comes from a reduced reaction volume as a result of the binding of both reactants to the vesicular pseudophase. The second effect arises from a change in the properties of the reaction environment upon going from the aqueous pseudophase to the vesicular pseudophase. Particularly large rate accelerations (about 104) were observed upon addition of sugar-based surfactants (e.g., n-dodecyl-β-glucoside (C12Glu)). On the basis of the observation that the unimolecular decarboxylation reaction of 6-nitrobenzisoxazole-3-carboxylate anion in cationic vesicles is slightly slower in the presence of C12Glu than in its absence,8 it was anticipated that the presence of C12Glu leads to disturbance of the interface (less packing, more water at the interface). However, since the reaction of 5-nitrobenzisoxazole with hydroxide ions is more efficient in the presence of C12Glu, it is has been concluded that, despite the disturbance of the interface, hydroxide ions are dehydrated to a further extent in the presence of C12Glu. This might result from the replacement of hydration water by the sugar moieties.9-11 However, the applied kinetic model did not allow a detailed analysis due to the number
(1) Fendler, J. H. Membrane Mimetic Chemistry; Wiley: New York, 1982. (2) Duynstee, E. F. J.; Grunwald, E. J. Am. Chem. Soc. 1959, 81, 4540-4542. (3) Duynstee, E. F. J.; Grunwald, E. J. Am. Chem. Soc. 1959, 81, 4542-4548. (4) Bunton, C. A.; Nome, F.; Quina, F. H.; Romsted, L. S. Acc. Chem. Res. 1991, 24, 357-364. (5) Pe´rez-Juste, J.; Hollfelder, F.; Kirby, A. J.; Engberts, J. B. F. N. Org. Lett. 2000, 2, 127-130. (6) Klijn, J. E.; Engberts, J. B. F. N. J. Am. Chem. Soc. 2003, 125, 1825-1833.
(7) Klijn, J. E.; Engberts, J. B. F. N. Org. Biomol. Chem. 2004, 2, 1789-1799. (8) Jongejan, M. G. M.; Klijn, J. E.; Engberts, J. B. F. N. Manuscript in preparation. (9) Bales, B. L.; Howe, A. M.; Pitt, A. R.; Roe, J. A.; Griffiths, P. C. J. Phys. Chem. B 2000, 104, 264-270. (10) Griffiths, P. C.; Pettersson, E.; Stilbs, P.; Cheung, A. Y. F.; Howe, A. M.; Pitt, A. R. Langmuir 2001, 17, 7178-7181. (11) Bales, B. L.; Ranganathan, R.; Griffiths, P. C. J. Phys. Chem. B 2001, 105, 7465-7473.
Introduction Micelles have been extensively used in a wide variety of (kinetic) studies as mimics for biological membranes.1 The similarities between micelles and biological membranes are significant. For example, both types of aggregates consist of a hydrophobic interior, which is small relative to the total volume of the solution, and a polar (often charged) interface. However, there are also marked differences between the two types of aggregates. Micelles are in thermodynamic equilibrium involving the breaking up and formation of micelles on the millisecond time-scale. Phospholipid vesicles (liposomes) on the other hand are metastable, and irreversible precipitation or fusion can occur after some time (hours, days, or months). Vesicles, which are formed from synthetic amphiphiles or (synthetic or natural) phospholipids, are more closely related to biological membranes as far as their general properties and aggregate structure are concerned. Therefore, they are better mimics of biological membranes than micelles, despite the fact that biological membranes have many different components and these components are present in a wide variety of compositions. Contrary to micellar catalysis,2-4 studies of vesicular catalysis are more rare. Consequently, fewer details of vesicular catalysis are known. In previous studies,5-7 we †
10.1021/la0504715 CCC: $30.25 © 2005 American Chemical Society Published on Web 07/14/2005
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of unknown variables and significant parameter compensation. In the present paper, the influence of sugar moieties on the SN2 reaction of bromide ions and water with 2-alkylnaphthtalenesulfonate and 2-methyl-4-nitrobenzenesulfonate has been studied in the presence of vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), di-n-hexadecyldimethylammonium bromide (C16C16+), and C12Glu. This system allows a more detailed analysis of the kinetic data due to fewer unknown parameters and only slight parameter compensation.
Klijn and Engberts Scheme 1. SN2 Reaction of MNBS and AlkONS with Nucleophiles.
Experimental Section Materials. 2-Methyl-4-nitrobenzenesulfonate (Acros, 99+%), sodium bromide (Acros, 99+%), 1-palmitoyl-2-oleoyl-sn-glycero3-phosphocholine (Avanti, 99%), di-n-hexadecyldimethylammonium bromide (Fluka, 97+%), and n-dodecyl-β-glucoside (Fluka, 99+%) were used as received. 2-Alkylnaphthtalenesulfonates were synthesized starting from 2-naphthalenesulfonyl chloride (Arcros, 99+%) and the alcohol according to a literature reference.12 The purity of the products was checked by 1H NMR, 13C NMR and elemental analysis. Vesicle Preparation. Vesicles were prepared by weighing the appropriate amounts of the amphiphiles and dissolving them in a small amount of chloroform, followed by removal of the organic solvent under a stream of nitrogen and subsequent removal of residual organic solvent under vacuum for several hours. Then the resulting film was hydrated with slightly acidified water (pH ca. 5, HCl) and briefly sonicated (
