Synthesis of Novel Asymmetrical Single-Chain Phosphoglycol-Based Bolaamphiphiles

<div><p></p><p>The synthesis of long-chain 1,ω-diols with orthogonal cleavable protecting groups can be effectively performed with the use of the Grignard coupling reaction, successfully leading to the preparation of novel <i>asymmetrical</i> single-chain phosphoglycol-based bolaamphiphiles—a side-product that always occurred during the synthesis of <i>symmetrical</i> bolalipids.</p> <p>[Supplementary materials are available for this article. Go to the publisher's online edition of <i>Synthetic Communications</i>® for the following free supplemental resource(s): Full experimental and spectral details.]</p> </div

Probing the Role of Ceramide Headgroup Polarity in Short-Chain Model Skin Barrier Lipid Mixtures by ²H Solid-State NMR Spectroscopy

The thermoptropic phase behaviors of two <i>stratum corneum</i> model lipid mixtures composed of equimolar contributions of either Cer­[NS18] or Cer­[NP18] with stearic acid and cholesterol were compared. Each component of the mixture was specifically deuterated such that the temperature-dependent ²H NMR spectra allowed disentanglement of the complicated phase polymorphism of these lipid mixtures. While Cer­[NS] is based on the sphingosine backbone, Cer­[NP] features a phytosphingosine, which introduces an additional hydroxyl group into the headgroup of the ceramide and abolishes the double bond. From the NMR spectra, the individual contributions of all lipids to the respective phases could be determined. The comparison of the two lipid mixtures reveals that Cer­[NP] containing mixtures have a tendency to form more fluid phases. It is concluded that the additional hydroxyl group of the phytosphingosine-containing ceramide Cer­[NP18] in mixture with chain-matched stearic acid and cholesterol creates a packing defect that destabilizes the orthorhombic phase state of canonical SC mixtures. This steric clash favors the gel phase and promotes formation of fluid phases of Cer­[NP] containing lipid mixtures at lower temperature compared to those containing Cer­[NS18]

Functionalization of Bolalipid Nanofibers by Silicification and Subsequent One-Dimensional Fixation of Gold Nanoparticles

In the present work, we describe the successful stabilization of bolalipid nanofibers by sol–gel condensation (silicification) of tetraethoxysilane (TEOS) or 3-mercaptopropyltriethoxysilane (MP-TEOS), respectively, onto the nanofibers. The conditions for an effective and reproducible silicification reaction were determined, and the silicification process was pursued by transmission electron microscopy (TEM). The resulting bolalipid–silica composite nanofibers were characterized by means of differential scanning calorimetry (DSC), TEM, ¹³C, and ³¹P NMR spectroscopy. Finally, the novel silicified bolalipid nanofibers were used as templates for the fixation of 5 and 2 nm AuNPs, respectively, resulting in one of the rare examples of one-dimensional AuNP arrangements in aqueous suspension

Highly Asymmetrical Glycerol Diether Bolalipids: Synthesis and Temperature-Dependent Aggregation Behavior

In the present work, we describe the synthesis and temperature-dependent aggregation behavior of two examples of a new class of highly asymmetrical glycerol diether bolaphospholipids. The bolalipids contain a long alkyl chain (C32) bound to glycerol in the <i>sn</i>-3 position, carrying a hydroxyl group at the ω position. The C16 alkyl chain in the <i>sn</i>-2 position either possesses a racemic methyl branch at the 10 position of the short alkyl chain (lipid <b>II</b>) or does not (lipid <b>I</b>). The <i>sn</i>-1 position of the glycerol is linked to a zwitterionic phosphocholine moiety. The temperature-dependent aggregation behavior of both bolalipids was studied using differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, and X-ray scattering. Aggregate structures were visualized by transmission electron microscopy (TEM). We show that both bolalipids self-assemble into large lamellar sheetlike aggregates. Closed lipid vesicles or other aggregate structures such as tubes or nanofibers, as usually found for diglycerol tetraether lipids, were not observed. Within the lamellae the bolalipid molecules are arranged in an antiparallel (interdigitated) orientation. Lipid <b>I</b>, without an additional methyl moiety in the short alkyl chain, shows a lamellar phase with high crystallinity up to a temperature of 34 °C, which was not observed before for other phospholipids

New Micellar Transfection Agents

Two novel micelle-forming amino-functionalized lipids (OT6 and TT6) bearing two alkyl chains connected to a large positively charged hexavalent headgroup, which might be interesting polynucleotide transferring agents with the advantage of an easy and reproducible production of micelle dispersions, have been characterized. The critical micelle concentration (cmc) of both lipids has been determined by two different methods, namely, isothermal titration calorimetry (ITC) and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence experiments. In addition, the lipid dispersions were studied as a function of temperature using differential scanning calorimetry (DSC), dynamic light scattering (DLS), Fourier-transform infrared (FT-IR) spectroscopy, and cryo-transmission electron microscopy (cryo-TEM). The OT6 and TT6 micelles effectively complex DNA as determined by ITC and DSC measurements. In addition, DLS and ζ-potential measurements were performed to determine lipoplex formulations that exhibit colloidal stability. Finally, the structures of OT6/DNA complexes were investigated by means of X-ray scattering and TEM

Impact of Headgroup Asymmetry and Protonation State on the Aggregation Behavior of a New Type of Glycerol Diether Bolalipid

In the present work, we describe the synthesis and the temperature-dependent aggregation behavior of a new class of asymmetrical glycerol diether bolalipids. These bolalipids are composed of a membrane-spanning alkyl chain with 32 carbon atoms (C32) in the <i>sn</i>-3 position, a methyl-branched C16 alkyl chain in the <i>sn</i>-2 position, and a zwitterionic phosphocholine headgroup in the <i>sn</i>-1 position of a glycerol moiety. The long C32 alkyl chain is terminated either by a second phosphocholine (<b>PC-Gly­(2C16Me)­C32-PC</b>) or by a phos­pho­di­methyl­ethan­ol­amine headgroup (<b>PC-Gly­(2C16Me)­C32-Me</b>_<b>2</b><b>PE</b>). The temperature- and pH-dependent aggregation behavior of both lipids was studied using differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, small-angle X-ray scattering (SAXS), and small-angle neutron scattering (SANS) experiments. The morphology of the formed aggregates in an aqueous suspension was visualized by transmission electron microscopy (TEM). We show that <b>PC-Gly­(2C16Me)­C32-PC</b> and <b>PC-Gly­(2C16Me)­C32-Me</b>_<b>2</b><b>PE</b> at pH 5 self-assemble into large lamellar aggregates and large lipid vesicles. Within these structures, the bolalipid molecules are probably assembled in a monolayer with fully interdigitated chains. The lipid molecules seem to be tilted with respect to the layer normal to ensure a dense packing of the alkyl chains. A temperature increase leads to a transition from a lamellar gel phase to the liquid-crystalline phase at about 28–30 °C for both bolalipids. The lamellar aggregates of <b>PC-Gly­(2C16Me)­C32-Me</b>_<b>2</b><b>PE</b> started to transform into nanofibers when the pH value of the suspension was increased to above 11. At pH 12, these nanofibers were the dominant aggregates