N. Idayu Zahid

Thermotropic and lyotropic liquid crystalline phases of Guerbet branched-chain -D-glucosides

The effect of chain branching on glycolipid thermotropic and lyotropic phases was investigated for a series of synthetic β-D-glucosides derived from Guerbet alcohols, whose total hydrocarbon chain length ranged from C8 to C24. The compounds, which can be viewed as isosteric mimics for glycoglycerolipids, were synthesised in high purity and their liquid crystalline phases were studied using optical polarising microscopy (OPM), and small-angle X-ray diffraction. When dry, the shortest compound (total C8) exhibits a monotropic Lα phase while longer ones (C16 and C20) adopt inverse hexagonal HII phases. The C24 compound forms an ordered lamellar phase at room temperature, but exhibits a metastable HII phase upon cooling. Curiously the intermediate chain length homologue (C12) adopts an isotropic inverse micellar (L2) phase in the dry state over the range of temperatures studied. Upon hydration, the C8 compound dissolves, and the C12 compound forms a fluid lamellar Lα phase. The C16 Guerbet glucoside (i.e. β-Glc-C10C6) exhibits an inverse bicontinuous cubic phase of space group Ia3d in excess water, never previously observed in branched-chain lipids, and very seldom observed in excess water. The C20 compound remains in the HII phase upon hydrating, with the lattice parameter swelling substantially.

Fluorescence Probing of the Temperature-Induced Phase Transition in a Glycolipid Self-Assembly: Hexagonal ↔ Micellar and Cubic ↔ Lamellar

Water-driven self-assembly of lipids displays a variety of liquid crystalline phases that are crucial for membrane functions. Herein, we characterize the temperature-induced phase transitions in two compositions of an aqueous self-assembly system of the octyl β-D-glucoside (βGlcOC(8)) system, using steady-state and time-resolved fluorescence measurements. The phase transitions hexagonal ↔ micellar and cubic ↔ lamellar were investigated using tryptophan (Trp) and two of its ester derivatives (Trp-C(4) and Trp-C(8)) to probe the polar headgroup region and pyrene to probe the hydrophobic tail region. The polarity of the headgroup region was estimated to be close to that of simple alcohols (methanol and ethanol) for all phases. The pyrene fluorescence indicates that the pyrene molecules are dispersed among the tails of the hydrophobic region, yet remain in close proximity to the polar head groups. Comparing the present results with our previously reported one for βMaltoOC(12), increasing the tail length of the hexagonal phase from C(8) to C(12) leads to less interaction with pyrene, which is attributed to the more random and wobbling motion of the longer alkyl tail. We measured a reduction (more hydrophobic) in the ratio of the vibronic peak intensities of pyrene (I(1)/I(3)) for the lamellar phase compared to that of the cubic phase. The higher polarity in the cubic phase can be correlated to the nature of its interface, which curves toward the bulk water. This geometry also explains the slight reduction in polarity of the headgroup region compared to the other phases. Upon the addition of Trp-C(8), the fluorescence lifetime of pyrene is reduced by 28% in the lamellar and cubic phases, whereas the I(1)/I(3) value is only slightly reduced. The results reflect the dominant role of dynamic interaction mechanism between the C(8) chain of Trp-C(8) and pyrene. This mechanism may be important for these two phases since they participate in the process of membrane fusion. Both lipid compositions show completely reversible temperature-induced phase transitions, reflecting the thermodynamic equilibrium structures of their mesophases. Probing both regions of the different lipid phases reveals a large degree of heterogeneity and flexibility of the lipid self-assembly. These properties are crucial for carrying out different biological functions such as the ability to accommodate various molecular sizes.

Cubosome particles of a novel Guerbet branched chain glycolipid

ABSTRACT Cubic liquid crystalline nanoparticles (cubosomes) of bicontinuous nature with internal networks of water channels have received great interests in nanomedicine applications, particularly as potential vehicle for loading and release of therapeutic agents. These nanoparticles have been most commonly produced using monoolein and phytantriol. In this study, we explore the use of a Guerbet branched chain glycolipid, namely 2-hexyl-decyl-β-D glucopyranoside (β-Glc−OC10C6), as a new and alternative material for cubosomes production. The fully hydrated glycolipid assumes a reverse bicontinuous cubic liquid crystal phase of an Ia3d space group with lattice parameter of ca. 74 Å, as confirmed using a small-angle X-ray scattering. Dynamic light scattering and a conventional transmission electron microscopy were used to investigate the average size and morphology of the cubosomes. The effectiveness of Poloxamer 407 (stabiliser typically used in other cubosome systems against aggregations and particle coalescence) in providing steric stabilisation of the glycolipid cubosomes was assessed through visual assessment. GRAPHICAL ABSTRACT

Biomass derived xylose Guerbet surfactants: thermotropic and lyotropic properties from small-angle X-ray scattering

A series of novel branched-chain glycosides were synthesised from xylose, an aldopentose and Guerbet alcohols whose total number of carbon atoms ranges from C8–C24. The thermotropic and lyotropic phases of the highly pure Guerbet xylosides were investigated, using differential scanning calorimetry, optical polarising microscopy and small-angle X-ray scattering. In dry conditions, the shortest compound (total C8) exhibits a monotropic lamellar (Lα) phase while the C12 compound forms a rectangular columnar (Colr) phase at room temperature, a rarely reported phase in lipidic systems. The longer ones (C16, C20 and C24) adopt inverse hexagonal (HII) phases. Upon hydration, the Lα phase of the C8 compound remains, and while that of the C12 compound exhibits an inverse bicontinuous cubic phase of space group Ia3d in excess water. The C16 and C20 compounds remain in the HII phase upon hydrating, but the lattice parameters for the hydrated forms increase considerably. An inverse micellar Fd3m cubic phase is observed in the fully hydrated C24 compound. The amphiphilic nature of these compounds coupled with the ability to form inverse non-lamellar phases at room temperature makes them ideal candidates for a variety of applications such as controlled release drug-carriers.

Detecting local heterogeneity and ionization ability in the head group region of different lipidic phases using modified fluorescent probes

Local heterogeneity in lipid self-assembly is important for executing the cellular membrane functions. In this work, we chemically modified 2-(2′-hydroxyphenyl)benzoxazole (HBO) and attached a C8 alkyl chain in two different locations to probe the microscopic environment of four lipidic phases of dodecyl β-maltoside. The fluorescence change in HBO and the new probes (HBO-1 and HBO-2) shows that in all phases (micellar, hexagonal, cubic and lamellar) three HBO tautomeric species (solvated syn-enol, anionic, and closed syn-keto) are stable. The formation of multi tautomers reflects the heterogeneity of the lipidic phases. The results indicate that HBO and HBO-1 reside in a similar location within the head group region, whereas HBO-2 is slightly pushed away from the sugar-dominated area. The stability of the solvated syn-enol tautomer is due to the formation of a hydrogen bond between the OH group of the HBO moiety and an adjacent oxygen atom of a sugar unit. The detected HBO anions was proposed to be a consequence of this solvation effect where a hydrogen ion abstraction by the sugar units is enhanced. Our results point to a degree of local heterogeneity and ionization ability in the head group region as a consequence of the sugar amphoterism.

Swelling of Bicontinuous Cubic Phases in Guerbet Glycolipid: Effects of Additives

Inverse bicontinuous cubic phases of lyotropic liquid crystal self-assembly have received much attention in biomedical, biosensing, and nanotechnology applications. An Ia3d bicontinuous cubic based on the gyroid G-surface can be formed by the Guerbet synthetic glucolipid 2-hexyl-decyl-β-d-glucopyranoside (β-Glc-OC6C10) in excess water. The small water channel diameter of this cubic phase could provide nanoscale constraints in encapsulation of large molecules and crystallization of membrane proteins, hence stresses the importance of water channel tuning ability. This work investigates the swelling behavior of lyotropic self-assembly of β-Glc-OC6C10 which could be controlled and modulated by different surfactants as a hydration-modulating agent. Our results demonstrate that addition of nonionic glycolipid octyl-β-d-glucopyranoside (β-Glc-OC8) at 20 and 25 mol % gives the largest attainable cubic water channel diameter of ca. 62 Å, and formation of coacervates which may be attributed to a sponge phase were seen at 20 mol % octyl-β-d-maltopyranoside (β-Mal-OC8). Swelling of the cubic water channel can also be attained in charged surfactant-doped systems dioctyl sodium sulfosuccinate (AOT) and hexadecyltrimethylammonium bromide (CTAB), of which phase transition occurred from cubic to a lamellar phase. Destabilization of the cubic phase to an inverse hexagonal phase was observed when a high amount of charged lecithin (LEC) and stearylamine (SA) was added to the lipid self-assembly.

Guerbet glycolipids from mannose: liquid crystals properties

ABSTRACT Using mannose as the sugar head, five Guerbet glycolipids with chain ranges from C8 to C24 were synthesised and studied for their liquid crystal behaviour. Differential scanning calorimetry, optical polarising microscopy and small-angle X-ray scattering were employed to determine the thermal, phase and structure properties. Unlike monoalkylated glycolipids, these Guerbet mannosides showed a glass transition below 0°C, except for α-Man-OC14C10. In the dry state, lamellar was observed for α-Man-OC6C2 and α-Man-OC8C4, while α-Man-OC12C8 and α-Man-OC14C10 formed non-lamellar phases, including inverse bicontinuous cubic phase of space group Ia3d and inverse hexagonal phase, respectively. The phase for middle-chain mannoside (α-Man-OC10C6) could not be assigned conclusively at room temperature, but this metastable phase forms lamellar above 37°C. The partial binary phase diagrams in water were also determined. Under excess water conditions at room and physiological temperatures, these materials form normal micellar solution, lamellar, inverse bicontinuous cubic of space group Pn3m and inverse hexagonal phases. The results were compared with those from other monosaccharide glycolipids from the same sugar Guerbet family. Although these compounds are obvious candidate material for lyotropic applications such as drug carrier and protein crystallisation medium, possible thermotropic application is now being explored. GRAPHICAL ABSTRACT

Self-Assembly, Thermotropic and Lyotropic Phase Behavior of Guerbet Branched-Chain Maltosides

Five synthetic β-d-maltosides derived from Guerbet branched alcohols, whose total hydrocarbon chain length ranged from C8 to C24, were synthesized to a high anomeric purity, and their thermal properties, liquid-crystalline phases, and structures were characterized using differential scanning calorimetry, optical polarizing microscopy, and small-angle X-ray scattering. Thermal investigations of all anhydrous Guerbet maltosides showed that they do not form solid crystals but undergo a glass transition upon temperature change in the range of 35-53 °C. The glassy crystalline structure turns into the liquid-crystalline structure upon heating or addition of water. In thermotropic studies, the lamellar phase formation is prominent in shorter-chain-length analogues, whereas the longer-chain compounds exhibit a more frustrated form of self-assembly in the formation of a metastable state, polymorphism, and inverse bicontinuous cubic structure ( Ia3 d). The excess water conditions show that the phase formation is dominated by the lamellar phase for the longer-chain compounds. Normal micellar solution was observed in the shortest-chain-length maltosides because of the enlargement of hydrated maltose headgroups. The self-assembly of both dry and fully hydrated Guerbet maltosides, which exhibited glass-forming abilities and showed surface activity and also the ability to act as membrane-stabilizing compounds, makes them ideal candidates for practical use in industry as well as biomedical research.

Comparative study of the inverse versus normal bicontinuous cubic phases of the β-D-glucopyranoside water-driven self-assemblies using fluorescent probes

Lipid/water systems displaying cubic symmetry are pervasive in biomembranes and important in technological applications such as nanoparticle templating and drug-delivery systems. Herein, we characterized the inverse bicontinuous cubic phase of the 2-hexyl-decyl-β-D-glucopyranoside/water system and the normal bicontinuous cubic phase of the octyl-β-D-glucopyranoside/water system. We investigated the head group region using 2-(2′-hydroxyphenyl)benzoxazole (HBO) and two of its derivatives as fluorescent probes. In the inverse phase, the syn-enol tautomer of HBO dominates the signal. This is attributed to the very narrow water channels (diameter of 2.3 nm) which support the formation of a hydrogen bond between the OH group of HBO and oxygen from the sugar units. A small contribution from the HBO anion species was also detected and is proposed to be the result of a hydrogen ion abstraction by the sugar units. In contrast, fluorescence of HBO in the normal phase is dominated by the keto tautomer with some contribution from the anionic form. Fluorescence lifetimes indicate that efficient excited-state intermolecular proton transfer, facilitated by the confined water molecules, yields the keto tautomer. This confined water contributes also toward the stability of the anion species in both cubic phases. Attaching a C4 (HBO-C4) or a C8 (HBO-C8) alkyl chain to the phenyl ring of HBO yielded similar results which indicates that the HBO moiety occupies the same position in the hydrophilic region, regardless of the attached hydrophobic chain. The two detected forms of HBO in each lipid suggest a degree of local heterogeneity that was also observed in the measured two fluorescence lifetime components. The current study is anticipated to contribute toward a better understanding of drug–lipid interaction which is important for drug absorption by the cell membrane.

Fluorescence characterization of water-driven self-assembled lipids and their temperature-induced phase transitions

Water-driven self-assembly of lipids displays a variety of liquid crystalline phases that are crucial for membrane functions. In this work, we characterized the temperature-induced phase transitions in aqueous self-assembly systems using steady-state and time-resolved fluorescence measurements. The polar head group region was investigated using tryptophan (Trp) and two of its ester derivatives, and the hydrophobic tail region was probed using pyrene. The spectral changes in tryptophan and pyrene were used as a benchmark to estimate the polarity of the head group region and the tail region, respectively. A basic medium was detected and estimated for the polar region in the inverse cubic phase of a Guerbet glycolipid and was attributed to the structural effect of the narrow nanochannels. All the studied lipid compositions show completely reversible temperature-induced phase transitions, reflecting the thermodynamic equilibrium structures of their mesophases. The results reveal a large degree of heterogeneity and flexibility of the lipid self-assembly which may be crucial for carrying out different biological functions.