HEADGROUP ORIENTATIONS OF ALKYL GLYCOSIDES AT A LIPID BILAYER INTERFACE

A series of functionally related alkyl monoglycosides was prepared, and their headgroup orientations were examined using dipolar coupling data from C-13 NMR spectra in oriented liquid crystalline phases. The following C-13-labeled compounds were synthesized: beta-dodecyl galactopyranoside, beta-tetradecyl 2-deoxyglucopyranoside, beta-dodecyl 6-deoxyglucopyranoside, alpha-dodecyl glucopyranoside, alpha-tetradecyl 2-deoxyglucopyranoside, alpha-dodecyl 2,3-dideoxyglucopyranoside, and alpha-dodecyl 2,3-dideoxy-erythro-hex-2-enopyranoside. These glycolipid analogs were solubilized in oriented bilayers composed of 1,2-dimyristoyl-sn-3-glycerophosphocholine (DMPC) and 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate (CHAPSO). The alpha-2,3-dideoxyglycosides induced an oriented to isotropic transition in the bilayers which precluded the measurement of dipolar coupling constants and further structural characterization. However, each of the other molecules examined yielded at least five C-13-C-13/H-1-C-13 coupling constants. In some cases, the anisotropy of the chemical shifts was also measured. The dipolar data sets were analyzed in structural terms using a general order matrix approach. Both unrestricted order matrices and matrices in which it was assumed that the headgroups execute axially symmetric motions were used. Both approaches led to nearly the same averaged headgroup orientation for each glycoside. Where the data were sufficient in quality and/or quantity, the unrestricted approach allowed the anisotropy of motion to be defined. The orientations observed for each glycoside were found to be consistent with a model previously suggested to account for the observed structure of beta-dodecyl glucopyranoside at a bilayer interface (Sanders, C. R.; Prestegard, J. H. J. Am. Chem. Soc. 1991, 113, 1987-1996). These results suggest that, despite the energetic complexity of membrane interfaces, it may be possible to make reasonable predictions about the interfacial structures of amphiphiles based on consideration of the topological placement of hydrophobic/hydrophilic moieties within the molecule.