Inverse hexagonal and cubic micellar lyotropic liquid crystalline phase behaviour of novel double chain sugar-based amphiphiles.

The lyotropic phase behaviour of a library of sugar-based amphiphiles was investigated using high-throughput small-angle X-ray scattering (SAXS). Double unsaturated-chain monosaccharide amphiphiles formed inverse hexagonal and cubic micellar (Fd3m) lyotropic phases under excess water conditions. A galactose-oleyl amphiphile from the library was subsequently formulated into hexosome nanoparticles, which have potential uses as drug delivery vehicles. The nanoparticles were shown to be stable at elevated temperatures and non-cytotoxic up to at least 200µgmL-1.

Using SANS with Contrast-Matched Lipid Bicontinuous Cubic Phases To Determine the Location of Encapsulated Peptides, Proteins, and Other Biomolecules.

An understanding of the location of peptides, proteins, and other biomolecules within the bicontinuous cubic phase is crucial for understanding and evolving biological and biomedical applications of these hybrid biomolecule-lipid materials, including during in meso crystallization and drug delivery. While theoretical modeling has indicated that proteins and additive lipids might phase separate locally and adopt a preferred location in the cubic phase, this has never been experimentally confirmed. We have demonstrated that perfectly contrast-matched cubic phases in D2O can be studied using small-angle neutron scattering by mixing fully deuterated and hydrogenated lipid at an appropriate ratio. The model transmembrane peptide WALP21 showed no preferential location in the membrane of the diamond cubic phase of phytanoyl monoethanolamide and was not incorporated in the gyroid cubic phase. While deuteration had a small effect on the phase behavior of the cubic phase forming lipids, the changes did not significantly affect our results.

The search for new amphiphiles: synthesis of a modular, high-throughput library.

Amphiphilic compounds are used in a variety of applications due to their lyotropic liquid-crystalline phase formation, however only a limited number of compounds, in a potentially limitless field, are currently in use. A library of organic amphiphilic compounds was synthesised consisting of glucose, galactose, lactose, xylose and mannose head groups and double and triple-chain hydrophobic tails. A modular, high-throughput approach was developed, whereby head and tail components were conjugated using the copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction. The tails were synthesised from two core alkyne-tethered intermediates, which were subsequently functionalised with hydrocarbon chains varying in length and degree of unsaturation and branching, while the five sugar head groups were selected with ranging substitution patterns and anomeric linkages. A library of 80 amphiphiles was subsequently produced, using a 24-vial array, with the majority formed in very good to excellent yields. A preliminary assessment of the liquid-crystalline phase behaviour is also presented.

The high-throughput synthesis and phase characterisation of amphiphiles: a sweet case study.

A new method for the discovery of amphiphiles by using high-throughput (HT) methods to synthesise and characterise a library of galactose- and glucose-containing amphiphilic compounds is presented. The copper-catalysed azide­alkyne cycloaddition (CuAAC) "click" reaction between azide-tethered simple sugars and alkyne-substituted hydrophobic tails was employed to synthesise a library of compounds with systematic variations in chain length and unsaturation in a 24-vial array format. The liquid­crystalline phase behaviour was characterised in a HT manner by using synchrotron small-angle X-ray scattering (SSAXS). The observed structural variation with respect to chain parameters, including chain length and degree of unsaturation, is discussed, as well as hydration effects and degree of hydrogen bonding between head groups. The validity of our HT screening approach was verified by resynthesising a short-chain glucose amphiphile. A separate phase analysis of this compound confirmed the presence of numerous lyotropic liquid­crystalline phases.

Synthesis of stereoisomers of Artemisia and Chrysanthemum bis(acetylenic) enol ether spiroacetals.

An 11-step synthesis is described of two diastereomeric candidates for a bis(acetylenic) enol ether spiroacetal isolated from Chrysanthemum boreale. Key steps in the synthetic route include spiroacetal lactone alkylidenation and subseqent modified Cadiot-Chodkiewicz cross-coupling to install the bis(acetylenic) enol ether functionality. From NMR comparisons, neither of the candidates, whose structures were confirmed by single-crystal X-ray diffraction, correspond to the natural product, and a proposal for the correct structure is put forward.

Structure and reactivity of bicyclic methylene aziridines prepared by intramolecular aziridination of allenes.

Unprecedented bicyclic methylene aziridines are prepared by rhodium(II)-catalyzed allene aziridination of buta-2,3-dienyl carbamates. Aspects of their NMR and X-ray data are described and a preliminary reactivity profile is given, including overall S(N)V-mode ring-opening with organometallic reagents.

The intramolecular amination of allenes.

Rhodium-bound nitrenoids are trapped by tethered allenes generating acyloxy-enamines, aminocyclopropanes, and methylene aziridines. The aminocyclopropanes undergo substitution of the acetoxy group by a variety of nucleophiles.

An unusual methylene aziridine refined in P2(1)/c and the nonstandard setting P2(1)/n.

The unusual methylene aziridine 6-tert-butyl-3-oxa-2-thia-1-azabicyclo[5.1.0]oct-6-ene 2,2-dioxide, C(9)H(15)NO(3)S, was found to crystallize with two molecules in the asymmetric unit. The structure was solved in both the approximately orthogonal and the oblique settings of space group No. 14, viz. P2(1)/n and P2(1)/c, respectively. A comparison of these results clearly displayed an increase in the correlation between coordinates in the ac plane for the oblique cell. The increase in the corresponding covariances makes a significant contribution to the standard uncertainties of derived parameters, e.g. bond lengths. Since there is yet no CIF definition for the full variance-covariance matrix, there are clear advantages to reporting the structure in the nonstandard space-group setting.

(1RS,4SR)-3-Dichloro-methyl-ene-1,4-dimethyl-2-oxabicyclo-[2.2.2]oct-5-ene.

X-ray crystallography was used to confirm the structure of the enantio-enriched title compound, C(10)H(12)Cl(2)O, a bicylic enol ether. A bridged boat-like structure is adopted and the dichloro-methyl-ene C atom is positioned significantly removed from the core bicyclic unit. In the crystal structure, mol-ecules pack to form sheets approximately perpendicular to the a and c axes.