Understanding the photothermal heating effect in non-lamellar liquid crystalline systems, and the design of new mixed lipid systems for photothermal on-demand drug delivery.

Lipid-based liquid crystalline systems are showing potential as stimuli-responsive nanomaterials, and NIR-responsive gold nanoparticles have been demonstrated to provide control of transitions in non-lamellar phases. In this study, we focus on a deeper understanding of the photothermal response of both lamellar and non-lamellar phases, and new systems formed by alternative lipid systems not previously reported, by linking the photothermal heating to the bulk thermal properties of the materials. Dynamic photothermal studies were performed using NIR laser irradiation and monitoring the structural response using time resolved small angle X-ray scattering for the bulk phases and hexosomes. In addition, cryoFESEM and cryoTEM were used to visualise and assess the effect of GNR incorporation into hexagonal phase nanostructures. The ability of the systems to respond to photothermal heating was correlated with the thermal phase behaviour and heat capacities of the different structures. Access to alternative phase transitions in these systems and understanding the likely photothermal response will facilitate different modes of application of these hybrid nanomaterials for on-demand drug delivery applications.

Sodium uptake in cell construction and subsequent in operando electrode behaviour of Prussian blue analogues, Fe[Fe(CN)6](1-x)·yH2O and FeCo(CN)6.

The development of electrodes for ambient temperature sodium-ion batteries requires the study of new materials and the understanding of how crystal structure influences properties. In this study, we investigate where sodium locates in two Prussian blue analogues, Fe[Fe(CN)6]1-x·yH2O and FeCo(CN)6. The evolution of the sodium site occupancies, lattice and volume is shown during charge-discharge using in situ synchrotron X-ray powder diffraction data. Sodium insertion is found to occur in these electrodes during cell construction and therefore Fe[Fe(CN)6]1-x·yH2O and FeCo(CN)6 can be used as positive electrodes. NazFeFe(CN)6 electrodes feature higher reversible capacities relative to NazFeCo(CN)6 electrodes which can be associated with a combination of structural factors, for example, a major sodium-containing phase, ∼Na0.5FeFe(CN)6 with sodium locating either at the x = y = z = 0.25 or x = y = 0.25 and z = 0.227(11) sites and an electrochemically inactive sodium-free Fe[Fe(CN)6]1-x·yH2O phase. This study demonstrates that key questions about electrode performance and attributes in sodium-ion batteries can be addressed using time-resolved in situ synchrotron X-ray diffraction studies.

Sensitivity of nanostructure in charged cubosomes to phase changes triggered by ionic species in solution.

The phase behavior of dispersions comprising mixed ionic surfactant and phytantriol was precisely controlled by varying the ionic surfactant content in the mixed lipid and the ionic strength in the system. Two important trends in the phase transition of the mixed lipid systems were identified: (1) An increase in the ionic surfactant content increased the curvature of the self-assembled system toward the hydrophobic region, resulting in the phase transition from cubic phase to lamellar phase. (2) An increase in ionic strength decreased repulsion between the headgroups of the ionic surfactant, resulting in a phase transition from lamellar phase to cubic phase. The phase transitions were confirmed using small-angle X-ray scattering and cryo-TEM and were strongly correlated with the visual turbidity of the dispersions. The lipid mixture with anionic surfactant showed high sensitivity to multivalent cations for triggering the phase transition, which may be a potential strategy to develop a detection/treatment system for toxic multivalent metallic cations such as chromium.

Nanofibrillar micelles and entrapped vesicles from biodegradable block copolymer/polyelectrolyte complexes in aqueous media.

Here we report a viable route to fibrillar micelles and entrapped vesicles in aqueous solutions. Nanofibrillar micelles and entrapped vesicles were prepared from complexes of a biodegradable block copolymer poly(ethylene oxide)-block-poly(lactide) (PEO-b-PLA) and a polyelectrolyte poly(acrylic acid) (PAA) in aqueous media and directly visualized using cryogenic transmission electron microscopy (cryo-TEM). The self-assembly and the morphological changes in the complexes were induced by the addition of PAA/water solution into the PEO-b-PLA in tetrahydrofuran followed by dialysis against water. A variety of morphologies including spherical wormlike and fibrillar micelles, and both unilamellar and entrapped vesicles, were observed, depending on the composition, complementary binding sites of PAA and PEO, and the change in the interfacial energy. Increasing the water content in each [AA]/[EO] ratio led to a morphological transition from spheres to vesicles, displaying both the composition- and dilution-dependent micellar-to-vesicular morphological transitions.

Individual dispersion of carbon nanotubes in epoxy via a novel dispersion-curing approach using ionic liquids.

The effective dispersion of carbon nanotubes (CNTs) in a thermoset was achieved using ionic liquid as the dispersion-curing agent. We preferentially dispersed multiwalled carbon nanotubes (MWCNTs) down to individual tube levels in epoxy resin. Here the dispersion is ruled by the depletion of physical bundles within the MWCNT networks, for which molecular ordering of ionic liquids is considered responsible. The quantitative analyses using ultra small angle X-ray scattering (USAXS) confirmed the dispersion of individual MWCNTs in the matrix. The distance between the dispersed nanotubes was calculated at different nanotube loadings using the power law fitting of the USAXS data. The fine dispersion and subsequent curing, both controlled by ionic liquid, lead to composites with substantially enhanced fracture mechanical and thermomechanical properties with no reduction in thermal properties. Merging processing techniques of nanocomposites with ionic liquid for efficient dispersion of nanotubes and preferential curing of thermosets facilitates the development of new, high performance materials.

Characterizing the photoinduced switching process of a nitrospiropyran self-assembled monolayer using in situ sum frequency generation spectroscopy.

Sum frequency generation (SFG) vibrational spectroscopy is employed to investigate the reversible, photoinduced spiro→merocyanine isomerization of a self-assembled monolayer, the result of attachment of nitrospiropyran to a gold surface using a dithiolane anchoring group. The attachment of these molecular "alligator clips" to spiropyran molecules provide an easily accessible method to self-assemble a robust monolayer of spiropyran on a gold surface, which allows photoswitching of the spiropyran units. Probing the symmetric and antisymmetric stretching modes of the nitro group allows the determination of the structural orientation of the charged moiety with respect to the surface normal as well as the isomerization rates under photoinduced switching conditions. The photoisomerization of the spiropyran SAM on the gold surface is much faster than the rates of switching spiropyrans in a solid crystalline form, and the rate of thermal relaxation of the opened to closed form in this study is found to be on the same time scale as the relaxation of spiropyran when present in solutions with polar solvents.

Controlling the nanostructure of gold nanorod-lyotropic liquid-crystalline hybrid materials using near-infrared laser irradiation.

Lipid-based liquid-crystalline matrixes provide a unique prospect for stimuli-responsive nanomaterials, attributed to the ability to effect self-assembly of the lipids at the molecular level. Differences in liquid crystal nanostructure have previously been shown to change drug diffusion and hence release, with research progressing toward the use of in situ changes to nanostructure to control drug release. Toward this goal, we have previously communicated the ability to switch between nonlamellar structures using gold nanorod (GNR)-phytantriol-based liquid-crystalline hybrid nanomaterials as near-infrared light responsive systems (Fong et al. Langmuir 2010, 26, 6136-6139). In this study, the effect of laser activation on matrix nanostructure with changes in a number of system variables including lipid composition, GNR aspect ratio, GNR concentration, and laser pulse time were investigated. The nanostructure of the matrix was followed using small-angle X-ray scattering, while both cryoFESEM and cryoTEM were used to visualize the effect of GNR incorporation into the liquid crystal nanostructure. The system response was found to be dependent on all variables, thus demonstrating the potential of these nanocomposite materials as reversible "on-demand" drug delivery applications.

Uranyl-sorption properties of amorphous and crystalline TiO2/ZrO2 millimeter-sized hierarchically porous beads.

Hierarchically porous TiO(2)/ZrO(2) millimeter-sized beads were synthesized using a sol-gel templating technique, and investigated for suitability as radionuclide sorbents using uranyl as a radionuclide-representative probe. The bead properties were varied by altering either composition (22, 36, and 82 wt % Zr in the Ti/Zr composite) or calcination temperature (500 or 700 °C). Uranyl adsorption was higher for the crystalline beads (surface area: 52-59 m(2) g(-1)) than the amorphous beads (surface area: 95-247 m(2) g(-1)), reaching a maximum of 0.170 mmol g(-1) for the 22 wt % Zr sample. This was attributed to the higher surface hydroxyl density (OH nm(-2)), presence of limited microporosity, and larger mesopores in the crystalline beads. Mass transport properties of the crystalline beads were not compromised by the large bead diameter: sorption rates comparable to those reported for powders were achieved and rates were higher than exclusively mesoporous reported systems, thereby highlighting the importance of pore hierarchy in designing materials with improved kinetics. Chemical stability of the sorbent, an important property for processes involving corrosive effluents (e.g., radioactive waste), was also assessed. Crystalline beads displayed superior resistance against matrix leaching in HNO(3). Stability varied with composition: the 22 wt % Zr sample demonstrated the highest stability.

A simple and effective approach to vesicles and large compound vesicles via complexation of amphiphilic block copolymer with polyelectrolyte in water.

This work reports for the first time a simple and effective approach to trigger a spheres-to- vesicles morphological transition from amphiphilic block copolymer/polyelectrolyte complexes in aqueous solution. Vesicles and large compound vesicles (LCVs) were prepared via complexation of polystyrene-block-poly(ethylene oxide) (PS-b-PEO) with poly(acrylic acid) (PAA) in water and directly visualized using cryo-TEM. The complexation and morphological transitions were driven by the hydrogen bonding between the complementary binding sites on the PAA and PEO blocks of the block copolymer. The findings in this work suggest that complexation between amphiphilic block copolymer and polyelectrolyte is a viable approach to vesicles and LCVs in aqueous media.

Nanoscale water condensation on click-functionalized self-assembled monolayers.

We have examined the nanoscale adsorption of molecular water under ambient conditions onto a series of well-characterized functionalized surfaces produced by Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC or "click") reactions on alkyne-terminated self-assembled monolayers on silicon. Water contact angle (CA) measurements reveal a range of macroscopic hydrophilicity that does not correlate with the tendency of these surfaces to adsorb water at the molecular level. X-ray reflectometry has been used to follow the kinetics of water adsorption on these "click"-functionalized surfaces, and also shows that dense continuous molecular water layers are formed over 30 h. For example, a highly hydrophilic surface, functionalized by an oligo(ethylene glycol) moiety (with a CA = 34°) showed 2.9 Å of adsorbed water after 30 h, while the almost hydrophobic underlying alkyne-terminated monolayer (CA = 84°) showed 5.6 Å of adsorbed water over the same period. While this study highlights the capacity of X-ray reflectometry to study the structure of adsorbed water on these surfaces, it should also serve as a warning for those intending to characterize self-assembled monolayers and functionalized surfaces to avoid contamination by even trace amounts of water vapor. Moreover, contact angle measurements alone cannot be relied upon to predict the likely degree of moisture uptake on such surfaces.

CO2 triggering and controlling orthogonally multiresponsive photochromic systems.

We report a new generic method of reversibly controlling the photochromism of spiropyrans. It was found that the photochromic effect of spiropyrans can be reversibly switched on and off by addition and removal of carbon dioxide (CO(2)) to spiropyran in alcohol solutions containing an amidine (i.e., DBU) that acts as a CO(2) sensitizer. Spiropyrans are not photochromic in the presence of DBU but photochromic when CO(2) is subsequently added to the solution. The CO(2) is readily removed by inert gas bubbling, thus allowing facile activation and deactivation of the photochromic effect. Carbon dioxide, without the presence of the sensitizing amidine, had no effect on photochromism of the spiropyrans. Other photochromic dyes classes such as spirooxazines and chromenes are not affected by this CO(2)/DBU stimulus. As a result, orthogonal activation of mixtures of spirooxazines and spiropyrans was achieved to provide four color states (clear, yellow, green, and blue) by varying the combinations of the stimuli of UV, visible light, CO(2), and CO(2) depleted. This finding now permits the many applications using spiropyrans to be CO(2) responsive.

Plasmonic nanorods provide reversible control over nanostructure of self-assembled drug delivery materials.

The nanostructure of mesophase liquid crystals prepared from amphiphilic lipids controls the rate of release of incorporated agents from the material, such as drug molecules, and reversible transition between different nanostructures essentially provides an "on-off" switch for release (Fong, W.-K.; Hanley, T.; Boyd, B. J. J. Controlled Release 2009, 135, 218-226). In this study, the incorporation of plasmonic hydrophobized gold nanorods (GNRs) permits reversible manipulation of nanostructure on-demand, by irradiation of the matrix using a near-infrared laser. Synchrotron small-angle X-ray scattering was used to probe the kinetics of the response of nanostructure to laser irradiation, and the specificity of the approach is shown by the lack of response in the absence of nanorods, or for GNR whose dimensions are not matched to the specific wavelength of the incident light.

Nonequilibrium effects in self-assembled mesophase materials: unexpected supercooling effects for cubosomes and hexosomes.

Polar lipids often exhibit equilibrium liquid crystalline structures in excess water, such as the bicontinuous cubic phases (Q(II)) at low temperatures and inverse hexagonal phase (H(II)) at higher temperatures. In this study, the equilibrium and nonequilibrium phase behavior of glyceryl monooleate (GMO) and phytantriol (PHYT) systems in excess water were investigated using both continuous heating and cooling cycles, and rapid temperature changes. Evolution of the phase structure was followed using small-angle X-ray scattering (SAXS). During cooling, not only was supercooling of the liquid crystalline systems by up to 25 degrees C observed, but evidence for nonequilibrium phase structures (not present on heating; such as the gyroid cubic phase only present at low water content in equilibrium) was also apparent. The nonequilibrium phases were surprisingly stable, with return to equilibrium structure for dispersed submicrometer sized particle systems taking more than 13 h in some cases. Inhibition of phase nucleation was the key to greater supercooling effects observed for the dispersed particles compared to the bulk systems. These findings highlight the need for continued study into the nonequilibrium phase structures for these types of systems, as this may influence performance in applications such as drug delivery.

Analysis of monoPEGylated human galectin-2 by small-angle X-ray and neutron scattering: concentration dependence of PEG conformation in the conjugate.

Protein conjugation with polyethylene glycol (PEG) is a valuable means for improving stability, solubility, and bioavailability of pharmaceutical proteins. Using human galectin-2 (hGal-2) and 5 kDa PEG as a model system we first produced a PEG-hGal-2 conjugate exclusively at the Cys75 residue, resulting in two monosubstituted subunits per hGal-2 homodimer. Small angle X-ray and neutron scattering (SAXS and SANS) were combined to provide complementary structural information about the PEG-hGal-2 conjugate, wherein signal generation in SAXS depends mainly on the protein while SANS data presents signals from both the protein and PEG moieties. SAXS data gave a constant radius of gyration (R(g) = 21.5 Å) for the conjugate at different concentrations and provided no evidence for an alteration of homodimeric structure or hGal-2 ellipsoidal shape upon PEGylation. In contrast, SANS data revealed a concentration dependence of R(g) for the conjugate, with the value decreasing from 31.5 Å at 2 mg/mL to 26 Å at 14 mg/mL (based on hGal-2 concentration). Scattering data have been successfully described by the model of the ellipsoidal homogeneous core (hGal-2) attached with polymer chains (PEG) at the surface. Evidently, the PEG conformation of the conjugate strongly depends on conjugate concentration and PEG's radius of gyration decreases from 24.5 to 15 Å. An excluded volume effect, arising from steric clashes between PEG molecules at high concentration, was quantified by estimating the second virial coefficient, A(2), of PEGylated hGal-2 from the SANS data. A positive value of A(2) (6.0 ± 0.4 × 10(-4) cm(3) mol g(-2)) indicates repulsive interactions between molecules, which are expected to protect the PEGylated protein against aggregation.

Photochromic spirooxazines functionalized with oligomers: investigation of core-oligomer interactions and photomerocyanine isomer interconversion using NMR spectroscopy and DFT.

Photochromic spirooxazines functionalized with poly(ethylene glycol) (PEG) and poly(dimethylsiloxane) (PDMS) oligomers were monitored using NMR spectroscopy at temperatures between 193 and 233 K before and after in situ exposure to UV irradiation. NOESY and ROESY experiments reveal the TTC (trans-s-trans-cis) isomer to be the dominant merocyanine isomer formed on photolysis, with some CTC (cis-s-trans-cis) isomer also present. Significant ROE cross peaks were observed between the "bulk" of the oligomeric units and protons across the entire photochromic core of the molecule, the intensity of these cross peaks suggesting that the interaction of the oligomer side chain and core of the molecule is significantly enhanced by the permanent attachment, especially with the PDMS side chain. The 2D NMR spectra indicate that there is exchange between the TTC and CTC isomers even at 193 K. This isomerization of the parent spirooxazine compounds, lacking the oligomeric side chains, was found to be acid-catalyzed, and DFT calculations support the strong possibility that it is the protonated merocyanine form that undergoes the facile isomerization process. Interconversion of the different merocyanine isomers is suggested to be fast on the NMR time scale under many experimental conditions, precluding the observation of different isomers using NMR spectroscopy at room temperature.

Experimental validation of proton transverse relaxivity models for superparamagnetic nanoparticle MRI contrast agents.

Analytical models of proton transverse relaxation rate enhancement by magnetic nanoparticles were tested by making measurements on model experimental systems in a field of 1.4 T. Proton relaxivities were measured for five aqueous suspensions of iron oxide (maghemite) nanoparticles with nominal mean particle sizes of 6, 8, 10, 11, and 13 nm. Proton relaxivity increased with mean particle size ranging from 13 s(-1) mM Fe(-1) for the 6 nm sample, up to 254 s(-1) mM Fe(-1) for the 13 nm sample. A strong correlation between the measured and predicted values of the relaxivity was observed, with the predicted values being consistently higher than the measured values. The results indicate that the models give a reasonable agreement with experimental results and hence can be used as the basis for the design of new magnetic resonance imaging contrast and labelling agents.

Nanostructure of liquid crystalline matrix determines in vitro sustained release and in vivo oral absorption kinetics for hydrophilic model drugs.

Nanostructured lipid-based liquid crystalline systems have been proposed as sustained oral drug delivery systems, but the interplay between their intrinsic release rates, susceptibility to digestive processes, and the manner in which these effects impact on their application in vivo, are not well understood. In this study, two different bicontinuous cubic phases, prepared from glyceryl monooleate and phytantriol, and a reversed hexagonal phase formed by addition of a small amount of vitamin E to phytantriol (Q(II GMO), Q(II PHYT) and H(II PHYT+VitEA), respectively) were prepared. The release kinetics for a number of model hydrophilic drugs with increasing molecular weights (glucose, Allura Red and FITC-dextrans) was determined in in vitro release experiments. Diffusion-controlled release was observed in all cases as anticipated from previous studies with liquid crystalline systems, and it was discovered that the release rates of each drug decreased as the matrix was changed from Q(II GMO) to Q(II PHYT) to H(II PHYT+VitEA). Formulations containing (14)C-glucose, utilized as a rapidly absorbed marker of drug release, were then orally administered to rats to determine the relative in vivo absorption rates from the different formulations. The results showed a trend by which the rate of absorption of (14)C-glucose followed that observed in the corresponding in vitro release studies, providing the first indication that the nanostructure of these materials may provide the ability to tailor the absorption kinetics of hydrophilic drugs in vivo, and hence form the basis of a new drug delivery system.

The structure of the KinA-Sda complex suggests an allosteric mechanism of histidine kinase inhibition.

The Bacillus subtilis histidine kinase KinA controls activation of the transcription factor governing sporulation, Spo0A. The decision to sporulate involves KinA phosphorylating itself on a conserved histidine residue, after which the phosphate moiety is relayed via two other proteins to Spo0A. The DNA-damage checkpoint inhibitor Sda halts this pathway by binding KinA and blocking the autokinase reaction. We have performed small-angle X-ray scattering and neutron contrast variation studies on the complex formed by KinA and Sda. The data show that two Sda molecules bind to the base of the DHp dimerization domain of the KinA dimer. In this position Sda does not appear to be able to sterically block the catalytic domain from accessing its target histidine, as previously proposed, but rather may effect an allosteric mode of inhibition involving transmission of the inhibitory signal via the four-helix bundle that forms the DHp domain.

The Topobiology of Chemical Elements in Seabird Feathers.

The highly organized morphogenesis of bird feathers holds important phylo- and ontogenetic information on the evolution of birds, organogenesis, tissue regeneration, and the health status of individual animals. Altered topobiological patterns are regularly used as retrospective evidence for disturbed developmental trajectories due to the past exposure to environmental stressors. Using the most advanced high-resolution (5-70 µm) X-ray fluorescence microscopy (XFM), we describe in the feathers from three species of Procellariiformes hitherto unknown, depositions of elements (Zn, Ca, Br, Cu, Fe) that are independent of pigmentation or any underlying variation in density or polymer structure. In the case of Zn, the pattern across several species of Procellariiformes, but not other species, consisted of highly regular bands of Zn numbering 30-32, which may reflect the estimated number of days of active feather growth or the duration of the moult period. Thus, speculatively, the highly consistent Zn pattern might be the result of a so far unknown diurnal systemic regulation rather than local heterogeneity amongst the follicular stem cells.