Synthesis and three-dimensional structure of 5,5-disubstituted 2-alkoxy-1,3-dioxanes

It was established by PMR spectroscopy that a chair conformation with an axial orientation of the alkoxy substituent is the primary conformation for 5,5-disubstituted (and unsubstituted) 2-alkoxy-1,3-dioxanes. As compared with alkyl-1,3-dioxanes, 2-alkoxy-1,3-dioxanes are characterized by reversal of the chemical shifts of the axial and equatorial protons attached to C₄, and C₆.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1182–1185, September, 1981.     

Emulsions and microemulsions with a fluorocarbon phase

A phase III clinical study of a perfluorooctyl bromide emulsion demonstrated reduction and avoidance of donor blood transfusion in surgery. Novel fluorocarbon-in-water emulsions are being investigated, including emulsions highly stabilized by fluorocarbon–hydrocarbon diblocks and targeted emulsions for molecular imaging, diagnosis and drug delivery. Reverse water-in-fluorocarbon emulsions and microemulsions that have potential for pulmonary drug delivery are also being studied. Microemulsions with highly fluorinated components are being actively investigated, with applications in polymerization technology and as research tools.     

Development of 1,3-acetonedicarboxylate-derived glucoside amphiphiles (ACAs) for membrane protein study

Detergents are extensively used for membrane protein manipulation. Membrane proteins solubilized in conventional detergents are prone to denaturation and aggregation, rendering downstream characterization of these bio-macromolecules difficult. Although many amphiphiles have been developed to overcome the limited efficacy of conventional detergents for protein stabilization, only a handful of novel detergents have so far proved useful for membrane protein structural studies. Here, we introduce 1,3-acetonedicarboxylate-derived amphiphiles (ACAs) containing three glucose units and two alkyl chains as head and tail groups, respectively. The ACAs incorporate two different patterns of alkyl chain attachment to the core detergent unit, generating two sets of amphiphiles: ACA-As (asymmetrically alkylated) and ACA-Ss (symmetrically alkylated). The difference in the attachment pattern of the detergent alkyl chains resulted in minor variation in detergent properties such as micelle size, critical micelle concentration, and detergent behaviors toward membrane protein extraction and stabilization. In contrast, the impact of the detergent alkyl chain length on protein stability was marked. The two C11 variants (ACA-AC11 and ACA-SC11) were most effective at stabilizing the tested membrane proteins. The current study not only introduces new glucosides as tools for membrane protein study, but also provides detergent structure–property relationships important for future design of novel amphiphiles.

Newly developed amphiphiles, designated ACAs, are not only efficient at extracting G protein-coupled receptors from the membranes, but also conferred enhanced stability to the receptors compared to the gold standards (DDM and LMNG).     

Characterization of CdSe nanocrystals coated with amphiphiles. A capillary electrophoresis study

We have synthesized CdSe nanocrystals (NCs) possessing a trioctylphosphine surface passivation layer and modified with amphiphilic molecules to form a surface bilayer. The NCs covered with single amphiphiles are not stable in aqueous solution, but a mixed amphiphilic system is shown to provide stability in solution over several months. The solutions of the modified NCs were characterized by UV-Vis absorbance, photoluminescence, and transmission electron microscopy. An electrophoretic study revealed two operational modes. The first relies on the enrichment of NCs using a micellar plug as a tool. The accumulation of NCs at the plug-electrolyte buffer interface results in a sharp peak. By controlling the electrophoretic conditions, nanocrystals were forced to exit a micellar plug into an electrolyte buffer. We conclude that a system consisting of modified nanocrystals and a micellar plug can act as a mixed pseudomicellar system, where modified nanocrystals play the role of pseudomicelles.FigureElectrophoretic focusing of amphiphile coated CdSe nanocrystals using a micellar plug. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00604-011-0727-8) contains supplementary material, which is available to authorized users.     

Reaction of 2,4-disubstituted 1,3-dioxolanes with dihalocarbenes

The insertion of dihalocarbenes into the C₍₂₎-H bond of cis- and trans-2-alkyl-4-propyl-1,3-dioxolanes leads to mixtures of stereoisomers.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1030–1031, August, 1991.     

Investigation in monolayers of double-chain fluorocarbon amphiphiles Effect of headgroups on molecular packing and interaction between hydrocarbon and fluorocarbon monolayers

The surface pressure-area diagrams of double-chain fluorocarbon amphiphiles with different headgroup compositions show that the amphiphiles arrange almost perpendicularly to the water subphase and the structure of headgroups exerts significant influence on the amphiphile packing. Strong hydrogen bonding and weak electrostatic interaction favor the formation of stable monolayers. Perfluorooctanoic acid (FOA) cannot form monolayer at water/air interface and can only form liquid monolayer in subphase of calcium nitrate solution. Complete phase separation of palmitic acid and a fluorocarbon amphiphile with shorter hydrocarbon spacer group, 1, could be demonstrated in monolayers by using the phase rule of Crisp. The creation of phase-separated monolayers is possible when the monolayer is composed of a mixture of palmitic acid and a fluorocarbon amphiphile with longer hydrocarbon spacer group, 2. It can be suggested that the miscibility of hydrocarbon amphiphiles with fluorocarbon amphiphiles is determined by the hydrocarbon fraction of fluorocarbon amphiphiles.     

Synthesis and structure of 2-aryl-2,4-dimethyl-1,2,3,4-tetrahydroquinolines and 1,3-disubstituted indenes

It has been shown that the intramolecular cyclization of N-(1-arylbutenyl)arylamines under acid catalysis conditions may proceed in two directions with the formation of 2-aryl-2,4-dimethyl-1,2,3,4-tetrahydroquinolines and 1,3 disubstituted indenes.     

Characterization of giant vesicles formed by phase transfer processes

Vesicles are of great interest as drug delivery system or models for cell membranes. For many applications, it is necessary to produce vesicles which are unilamellar, monodisperse, easy to adjust in size, and which can be filled with various types of active compounds. In a series of experiments, we produced giant vesicles with dimension of several millimeters by phase transfer processes. This new technique allowed synthesizing defined vesicles with lipid and surfactant membranes. The preparation of these aggregates occurred in two steps. First, we filled some amount of water into a cuvette and covered this liquid with an oil phase. Surfactants or lipids were solved either in the water or the oil phase. In the second step, a water droplet filled with methyl blue and saccharose was formed with a syringe in the oil phase. Due to density difference, the water droplet passed the plane oil/water interface and during this process it was transformed into a vesicle. The giant liposomes, thus formed, showed a high sensitivity against variations of the osmotic pressure, and their stability reached from seconds to hours. Due to the phase transfer process, the vesicle membranes often contained incorporated lenses of oil. If this hydrophobic liquid was released from the membrane, the vesicles decayed into smaller liposomes with a broad particle size distribution.     

Stabilized vesicles consisting of small amphiphiles for stepwise photorelease via UV light

A small amphiphile consisting of hydrophilic tetraethylene glycol monoacrylate and hydrophobic alkyl chain which were connected by an o-nitrobenzyl unit, a photolabile group, was designed and synthesized. The critical aggregate concentration of the synthesized amphiphile was determined to be about 3 × 10(-5) M by the fluorescence probe technique. Nanosized vesicles were prepared and stabilized by in-situ radical polymerization without altering the morphology. The polymeric vesicle was highly stable which retained vesicular shape under dilution or UV irradiation. Hydrophobic guests can be encapsulated within the vesicle membrane and released out of the vesicle by UV stimulus through splitting the amphiphilic structure of the amphiphile. Distinguished dose-controlled photorelease of the polymeric vesicle is achieved due to the maintenance of the vesicular shape integrity which makes the guest release depend on the cleavage amount of amphiphilic structure during UV irradiation. This study provides a promising strategy to develop stable drug delivery systems for sustained and phototriggered release.     

Temperature-responsive phase transition of polymer vesicles: real-time morphology observation and molecular mechanism

Novel thermosensitive polymer vesicles with controlled temperature-responsive phase transition at the lower critical solution temperature (LCST) varying from 8 to 81 degrees C were prepared via self-assembly of amphiphilic hyperbranched star copolymers having a hydrophobic hyperbranched poly[3-ethyl-3-(hydroxymethyl)oxetane] (HBPO) core and many hydrophilic polyethylene oxide (PEO) arms. Real-time optical microscopic observation revealed that the polymer vesicles have undergone sequential morphology changes including enrichment, aggregation, fusion, and vesicle-to-membrane transformation near the LCST. Molecular-level investigation indicates that the LCST transition results from the decreasing water solubility of the polymer vesicles with increasing temperature based on the partial dehydration of the PEO vesicle corona. On the basis of these results, a LCST transition mechanism, in view of the molecular configuration, balance of hydrophilic and hydrophobic moieties, and the vesicle morphology transformations, was proposed. As far as we know, the work presented here is the first demonstration of thermosensitive vesicles based on PEO, and the finding may be useful to design the thermosensitive core-shell structures by introducing the PEO segments.     

Geometric structure of molecule of 1,3-dinitro-1,3-diazacyclopentane in the gas phase

M. V. Lomonosov Moscow State University. Translated from Zhurnal Strukturnoi Khimii, Vol. 33, No. 1, pp. 35–40, January–February, 1992.     

Small angle x-ray scattering study of local structure and collapse transition of (1,3)-beta-D-glucan-chitosan gels

Scleroglucan is a (1,3)-beta-D-glucan polysaccharide produced by the fungus Sclerotium. Dissolved in water at room temperature it adopts a linear, rigid, triple helical structure. Gelation of scleroglucan can be obtained by Schiff-base formation between partly periodate oxidized scleroglucan and the primary amine groups of chitosan. The scleraldehyde-chitosan gels exhibit a collapse transition when exposed to volume fractions of isopropanol, Wp, larger than 65%. The aim of the present study is to provide structural information concerning the local polymer distribution and the collapse transition in (1,3)-beta-D-glucan-chitosan gels. Small angle x-ray scattering was used to investigate solutions and gels of scleroglucan in water, as well as in an aqueous mixture containing 65% isopropanol. The results reveal that in aqueous solution, the polysaccharide scleroglucan chains have an approximately cylindrical cross section of external diameter close to 17 A. The gels display the same local structure, but form clusters on a longer distance scale. For the collapsed gels in the water-isopropanol mixture, partial phase separation occurs in which ordered domains of approximate size of 110 A develop. This study indicates that local ordering in liquid-crystalline-type domains is a possible molecular mechanism contributing to the collapse of gels composed of semiflexible polymers. The triple helical structure of the molecule appears not to be conserved in the majority phase in this solvent, but it is conserved in the liquid crystalline domains.     

Controlled synthesis of cis or trans isomers of 1,3-disubstituted tetrahydroisoquinolines and 2,5-disubstituted pyrrolidines

[reactions: see text] The stereoselective outcome of Pd(II)- or Ag(I)-catalyzed intramolecular N-alkylation to afford 1,3-disubstituted 1,2,3,4-tetrahydroisoquinolines was examined. In the absence of additional substituents, Pd(II) allows a facile access to the cis isomers, while Ag(I) favors formation of the trans isomers. The same observation was made for the synthesis of 2,5-disubstituted pyrrolidines. Possible reasons for the observed stereoselectivities are discussed.     

Synthesis of 3-substituted and 1,3-disubstituted 4,7-diazaindoles

On the basis of a study of electrophilic substitution reactions (the Mannich reaction and bromination) it was shown that 4,7-diazaindoles react with greater difficulty with soft electrophilic agents than indoles or 4- and 7-monoazaindoles. 3-Substituted and 1,3-disubstituted 4,7-diazaindoles containing amino(dialkylamino)alkyl substituents in the 1 or 3 positions were synthesized.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 848–852, June, 1976.     

Stable vesicles composed of monocarboxylic or dicarboxylic fatty acids and trimethylammonium amphiphiles

The self-assembly of cationic and anionic amphiphile mixtures into vesicles in aqueous media was studied using two different systems: (i) decanoic acid and trimethyldecylammonium bromide and (ii) hexadecanedioic acid (a simple bola-amphiphile) and trimethyldecylammonium bromide. The resulting vesicles with varying amphiphile ratios were characterized using parameters such as the critical vesicle concentration, pH sensitivity, and encapsulation efficiency. We also produced and observed giant vesicles from these mixtures using the electroformation method and confocal microscopy. The mixed catanionic vesicles were shown to be more stable than those formed by pure fatty acids. Those containing bola-amphiphile even showed the encapsulation of a small hydrophilic solute (8-hydroxypyrene-1,3,6-trisulfonic-acid), suggesting a denser packing of the amphiphiles. Compression and kinetics analysis of monolayers composed of these amphiphiles mixtures at the air/water interface suggests that the stabilization of the structures can be attributed to two main interactions between headgroups, predominantly the formation of hydrogen bonds between protonated and deprotonated acids and the additional electrostatic interactions between ammonium and acid headgroups.     

1,3-Dipolar cycloadditions. Reactions of nitrile imines with 1,2-disubstituted alkenes

Nitrile imines react with 1-phenylsulphonyl-2-benzoyl (or methoxycarbonyl)alkenes to give 4-phenylsulphonyl-5-benzoyl (or methoxycarbonyl) substituted pyrazolines. The cycloaddition regioselectivity is discussed in terms of Frontier Orbital energies and coefficients.