Hydrogenated Diglucose Detergents for Membrane-Protein Extraction and Stabilization.

We report herein the design and synthesis of a novel series of alkyl glycoside detergents consisting of a nonionic polar headgroup that comprises two glucose moieties in a branched arrangement (DG), onto which octane-, decane-, and dodecanethiols were grafted leading to ODG, DDG, and DDDG detergents, respectively. Micellization in aqueous solution was studied by isothermal titration calorimetry, 1H NMR spectroscopy, and surface tensiometry. Critical micellar concentration values were found to decrease by a factor of ∼10 for each pair of methylene groups added to the alkyl chain, ranging from ∼0.05 to 9 mM for DDDG and ODG, respectively. Dynamic light scattering and analytical ultracentrifugation sedimentation velocity experiments were used to investigate the size and composition of the micellar aggregates, showing that the aggregation number significantly increased from ∼40 for ODG to ∼80 for DDDG. All new compounds were able to solubilize membrane proteins (MPs) from bacterial membranes, insect cells, as well as the Madin-Darby canine kidney cells. In particular, native human adenosine receptor (A2AR) and bacterial transporter (BmrA) were solubilized efficiently. Striking thermostability improvements of +13 and +8 °C were observed when ODG and DDG were, respectively, applied to wild-type and full-length A2AR. Taken together, this novel detergent series shows promising detergent potency for solubilization and stabilization of membrane proteins (MPs) and thus makes a valuable addition to the chemical toolbox available for extracting and handling these important but challenging MP targets.

Tren-Capped Hexaphyrin Zinc Complexes: Interplaying Molecular Recognition, Möbius Aromaticity, and Chirality.

Over the past decade, the hexaphyrin skeleton has emerged as a multifaceted frame exhibiting strong interplay between topology, aromaticity, and metal coordination, opening new research areas beyond porphyrins. However, molecular recognition with hexaphyrins has been underexplored, mainly because of the lack of general synthetic strategies leading to sophisticated molecular hosts. Here we have developed a straightforward approach for capping the heteroannulene frame with tripodal units (e.g., tris(2-aminoethyl)amine [tren]) through postsynthetic modification of a readily accessible meso-(2-aminophenyl) tris-substituted platform. The resulting tren-capped hexaphyrins, obtained in three steps from a 5-(aryl)dipyrromethane precursor, display remarkable features: (i) Considering the 28π-conjugated system, instantaneous and site-selective Zn(II) metalation at the level of a dipyrrin versus tren unit triggers a planar-to-singly twisted conformational change and hence a Hückel antiaromatic-to-Möbius aromatic transformation. In spite of the tripodal linkage, a smooth twist and efficient π overlap are preserved. (ii) Selective and cooperative binding of both an acetato ligand and an amino ligand to zinc occurs in distinct confined environments, reminiscent of substrate discrimination at the buried metal centers of metalloenzymes. The ligand binding pockets are allosterically tuned by monoprotonation of the tren unit. (iii) Substantial chiral induction of the molecular twist is achieved using chiral amino ligands (diastereomeric excess up to 77%, the highest reported to date for a Möbius compound), to which is associated a strong chiroptical signature in circular dichroism. These results provide unprecedented insights into molecular recognition with hexaphyrins, paving the way to innovative Möbius-type molecular hosts for sensing and catalysis.

Self-Assembling Behavior of Glycerol Monoundecenoate in Water.

The self-assembling properties of glycerol esters in water are well known. Still, few data on glycerol monoesters of undecylenic acid are available. The aim of this study was to highlight the behavior of glycerol monoundecenoate (GM-C11:1) in different diluted and concentrated states. Its self-assembling properties in water and upon solid inorganic surfaces were investigated in the diluted state using surface tension experiments, atomic force microscopy, and cryogenic transmission electron microscopy studies. In the concentrated state, the gelling properties in the presence of water were investigated using polarized light microscopy, differential scanning calorimetry (DSC), and small-angle X-ray scattering (SAXS) experiments. GM-C11:1 at 100 mg/L self-assembles at the liquid/air interfaces as aggregates of approximately 20 nm in diameter, organized into concentric forms. These aggregates are spherical globules composed of several molecules of GM-C11:1. At higher concentrations (1000 and 104 mg/L), GM-C11:1 is able to uniformly coat liquid/air and liquid/solid interfaces. In bulk, GM-C11:1 forms spontaneously aggregates and vesicles. In a more concentrated state, GM-C11:1 assembles into lamellar Lß and Lα forms in water. By cross-referencing SAXS and DSC findings, we were able to distinguish between interlamellar water molecules strongly bound to GM-C11:1 and other molecules remaining unbound and considered to be "mobile" water. The percentage of water strongly bound was proportional to the percentage of GM-C11:1 in the system. In this case, GM-C11:1 appears to be an effective molecule for surface treatments for which water retention is important.