In situ small-angle X-ray scattering reveals solution phase discharge of Li-O2 batteries with weakly solvating electrolytes.

Electrodepositing insulating lithium peroxide (Li2O2) is the key process during discharge of aprotic Li-O2 batteries and determines rate, capacity, and reversibility. Current understanding states that the partition between surface adsorbed and dissolved lithium superoxide governs whether Li2O2 grows as a conformal surface film or larger particles, leading to low or high capacities, respectively. However, better understanding governing factors for Li2O2 packing density and capacity requires structural sensitive in situ metrologies. Here, we establish in situ small- and wide-angle X-ray scattering (SAXS/WAXS) as a suitable method to record the Li2O2 phase evolution with atomic to submicrometer resolution during cycling a custom-built in situ Li-O2 cell. Combined with sophisticated data analysis, SAXS allows retrieving rich quantitative structural information from complex multiphase systems. Surprisingly, we find that features are absent that would point at a Li2O2 surface film formed via two consecutive electron transfers, even in poorly solvating electrolytes thought to be prototypical for surface growth. All scattering data can be modeled by stacks of thin Li2O2 platelets potentially forming large toroidal particles. Li2O2 solution growth is further justified by rotating ring-disk electrode measurements and electron microscopy. Higher discharge overpotentials lead to smaller Li2O2 particles, but there is no transition to an electronically passivating, conformal Li2O2 coating. Hence, mass transport of reactive species rather than electronic transport through a Li2O2 film limits the discharge capacity. Provided that species mobilities and carbon surface areas are high, this allows for high discharge capacities even in weakly solvating electrolytes. The currently accepted Li-O2 reaction mechanism ought to be reconsidered.

Puncturing lipid membranes: onset of pore formation and the role of hydrogen bonding in the presence of flavonoids.

Products of lipid peroxidation induce detrimental structural changes in cell membranes, such as the formation of water pores, which occur in the presence of lipids with partially oxidized chains. However, the influence of another class of products, dicarboxylic acids, is still unclear. These products have greater mobility in the lipid bilayer, which enables their aggregation and the formation of favorable sites for the appearance of pores. Therefore, dodecanedioic acid (DDA) was selected as a model product. Additionally, the influence of several structurally different flavonoids on DDA aggregation via formation of hydrogen bonds with carboxyl groups was investigated. The molecular dynamics of DDA in DOPC lipid bilayer revealed the formation of aggregates extending over the hydrophobic region of the bilayer and increasing its polarity. Consequently, water penetration and the appearance of water wires was observed, representing a new step in the mechanism of pore formation. Furthermore, DDA molecules were found to interact with lipid polar groups, causing them to be buried in the bilayer. The addition of flavonoids to the system disrupted aggregate formation, resulting in the displacement of DDA molecules from the center of the bilayer. The placement of DDA and flavonoids in the lipid bilayer was confirmed by small-angle X-ray scattering. Atomic force microscopy and electron paramagnetic resonance were used to characterize the structural properties. The presence of DDA increased bilayer roughness and decreased the ordering of lipid chains, confirming its detrimental effects on the membrane surface, while flavonoids were found to reduce or reverse these changes.

Micelle Formation in Aqueous Solutions of the Cholesterol-Based Detergent Chobimalt Studied by Small-Angle Scattering.

The structure and interaction parameters of the water-soluble cholesterol-based surfactant, Chobimalt, are investigated by small-angle neutron and X-ray scattering techniques. The obtained data are analyzed by a model-independent approach applying the inverse Fourier transformation procedure as well as considering a model fitting procedure, using a core-shell form factor and hard-sphere structure factor. The analysis reveals the formation of the polydisperse spherical or moderately elongated ellipsoidal shapes of the Chobimalt micelles with the hard sphere interaction in the studied concentration range 0.17-6.88 mM. The aggregation numbers are estimated from the micelle geometry observed by small-angle scattering and are found to be in the range of 200-300. The low pH of the solution does not have a noticeable effect on the structure of the Chobimalt micelles. The critical micelle concentrations of the synthetic surfactant Chobimalt in water and in H2O-HCl solutions were obtained according to fluorescence measurements as ~3 µM and ~2.5 µM, respectively. In-depth knowledge of the basic structural properties of the detergent micelles is necessary for further applications in bioscience and biotechnology.

KIT-5-Assisted Synthesis of Mesoporous SnO2 for High-Performance Humidity Sensors with a Swift Response/Recovery Speed.

Developing highly efficient semiconductor metal oxide (SMOX) sensors capable of accurate and fast responses to environmental humidity is still a challenging task. In addition to a not so pronounced sensitivity to relative humidity change, most of the SMOXs cannot meet the criteria of real-time humidity sensing due to their long response/recovery time. The way to tackle this problem is to control adsorption/desorption processes, i.e., water-vapor molecular dynamics, over the sensor's active layer through the powder and pore morphology design. With this in mind, a KIT-5-mediated synthesis was used to achieve mesoporous tin (IV) oxide replica (SnO2-R) with controlled pore size and ordering through template inversion and compared with a sol-gel synthesized powder (SnO2-SG). Unlike SnO2-SG, SnO2-R possessed a high specific surface area and quite an open pore structure, similar to the KIT-5, as observed by TEM, BET and SWAXS analyses. According to TEM, SnO2-R consisted of fine-grained globular particles and some percent of exaggerated, grown twinned crystals. The distinctive morphology of the SnO2-R-based sensor, with its specific pore structure and an increased number of oxygen-related defects associated with the powder preparation process and detected at the sensor surface by XPS analysis, contributed to excellent humidity sensing performances at room temperature, comprised of a low hysteresis error (3.7%), sensitivity of 406.8 kΩ/RH% and swift response/recovery speed (4 s/6 s).

Physicochemical Characterization and Drug Release Properties of Methyl-Substituted Silica Xerogels Made Using Sol-Gel Process.

In this work, a multi-analytical approach involving nitrogen porosimetry, small angle neutron and X-ray scattering, Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopies, X-ray diffraction, thermal analysis and electron microscopy was applied to organically modified silica-based xerogels obtained through the sol-gel process. Starting from a tetraethoxysilane (TEOS) precursor, methyltriethoxysilane (MTES) was added to the reaction mixture at two different pH values (2.0 and 4.5) producing hybrid xerogels with different TEOS/MTES molar ratios. Significant differences in the structure were revealed in terms of the chemical composition of the silica network, hydrophilic/hydrophobic profile, particle dimension, pore shape/size and surface characteristics. The combined use of structural characterization methods allowed us to reveal a relation between the cavity dimensions, the synthesis pH value and the grade of methyl substitution. The effect of the structural properties on the controlled Captopril release efficiency has also been tested. This knowledge facilitates tailoring the pore network for specific usage in biological/medical applications. Knowledge on structural aspects, as reported in this work, represents a key starting point for the production of high-performance silica-based hybrid materials showing enhanced efficacy compared to bare silica prepared using only TEOS.

Mesostructure and physical properties of aqueous mixtures of the ionic liquid 1-ethyl-3-methyl imidazolium octyl sulfate doped with divalent sulfate salts in the liquid and the mesomorphic states.

This paper extends the study of the induced temperature change in the mesostructure and in the physical properties occurring in aqueous mixtures of the ionic liquid 1-ethyl-3-methyl imidazolium octyl-sulfate [EMIm][OSO4]. For some compositions, these mixtures undergo a phase transition between the liquid (isotropic in the mesoscale) and the mesomorphic state (lyotropic liquid crystalline) at about room temperature. The behavior of mixtures doped with a divalent metal sulfate was investigated in order to observe their applicability as electrolytes. Calcium sulfate salt is almost insoluble even in the 20 wt% water mixture. The magnesium salt, in contrast, can be dissolved up to concentrations of 730 ppm in the same mixture and it has a profound impact on its properties. Six aqueous mixtures (with water content from 10 wt% to 33 wt%) of [EMIm][OSO4] were saturated with magnesium sulfate salt, producing the ternary mixture [EMIm][OSO4] + H2O + MgSO4. Viscosity, density and ionic conductivity for these samples were measured from 10 °C to 90 °C. In addition, SAXS, FTIR, diffussion NMR and Raman spectroscopy of the most interesting samples have been performed, and structural data indicate a transition between a hexagonal lyotropic liquid crystalline phase below and an isotropic solution phase above room temperature. The octyl sulfate anions of the cylindrical micelles in the hexagonal phase are coordinated with water molecules through H-bonds (about four per sulfate anion), while the [EMIm] cations seem to be poorly coordinated and so free to move. Inorganic salt addition reinforces that network, increasing the phase transition temperature.

Exploring the interactions of irbesartan and irbesartan-2-hydroxypropyl-ß-cyclodextrin complex with model membranes.

The interactions of irbesartan (IRB) and irbesartan-2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) complex with dipalmitoyl phosphatidylcholine (DPPC) bilayers have been explored utilizing an array of biophysical techniques ranging from differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS), ESI mass spectrometry (ESI-MS) and solid state nuclear magnetic resonance (ssNMR). Molecular dynamics (MD) calculations have been also conducted to complement the experimental results. Irbesartan was found to be embedded in the lipid membrane core and to affect the phase transition properties of the DPPC bilayers. SAXS studies revealed that irbesartan alone does not display perfect solvation since some coexisting irbesartan crystallites are present. In its complexed form IRB gets fully solvated in the membranes showing that encapsulation of IRB in HP-ß-CD may have beneficial effects in the ADME properties of this drug. MD experiments revealed the topological and orientational integration of irbesartan into the phospholipid bilayer being placed at about 1nm from the membrane centre.

Self-emulsification of Lipidic Drug Delivery System in Pure Water and in Concentrated Glycerol Solution.

Self-emulsifying drug delivery systems (SEDDS), often intended for oral delivery, are normally explored in biorelevant aqueous media. The high complexity of these multi-component systems leaves the understanding of self-emulsification poor, hindering formulation rationalization. In this work, we aimed to fill this gap by studying the effects of glycerol on the self-emulsification of a ternary component formulation made of 20% w/w Tween 80, 15% w/w Span 80, and 65% w/w Captex 300 Low C6. The behavior of SEDDS in pure water and a binary mixture of water and glycerol (58.8% w/w) were investigated by optical microscopy, SAXS (small angle X-ray scattering), dynamic light scattering, and surface tension measurements. The presence of glycerol, at 58.8% w/w, altered the self-emulsification behavior by suppressing the formation of lamellar structures observed in the presence of water, reducing the droplet mean diameter from 0.2 to 0.1 µm and changing the mechanism of self-emulsification. As co-surfactant, glycerol may intercalate within the polyoxyethylene chains of the surfactant at the palisade layer, increasing the interface flexibility and expanding it. Since no free water is available at the investigated glycerol concentration, glycerol, which is also a co-solvent, may additionally modify long-range interactions by reducing Van-der-Waals attractions or giving rise to repulsive surface-solvent mediated forces of entropic origin. These effects could be exploited to rationalize SEDDS formulations, widening their use within the pharmaceutical industry.

Phospholipid-driven differences determine the action of the synthetic antimicrobial peptide OP-145 on Gram-positive bacterial and mammalian membrane model systems.

OP-145, a synthetic antimicrobial peptide developed from a screen of the human cathelicidin LL-37, displays strong antibacterial activities and is--at considerably higher concentrations--lytic to human cells. To obtain more insight into its actions, we investigated the interactions between OP-145 and liposomes composed of phosphatidylglycerol (PG) and phosphatidylcholine (PC), resembling bacterial and mammalian membranes, respectively. Circular dichroism analyses of OP-145 demonstrated a predominant α-helical conformation in the presence of both membrane mimics, indicating that the different membrane-perturbation mechanisms are not due to different secondary structures. Membrane thinning and formation of quasi-interdigitated lipid-peptide structures was observed in PG bilayers, while OP-145 led to disintegration of PC liposomes into disk-like micelles and bilayer sheets. Although OP-145 was capable of binding lipoteichoic acid and peptidoglycan, the presence of these bacterial cell wall components did not retain OP-145 and hence did not interfere with the activity of the peptide toward PG membranes. Furthermore, physiological Ca++ concentrations did neither influence the membrane activity of OP-145 in model systems nor the killing of Staphylococcus aureus. However, addition of OP-145 at physiological Ca++-concentrations to PG membranes, but not PC membranes, resulted in the formation of elongated enrolled structures similar to cochleate-like structures. In summary, phospholipid-driven differences in incorporation of OP-145 into the lipid bilayers govern the membrane activity of the peptide on bacterial and mammalian membrane mimics.

Effects of High Pressure on Internally Self-Assembled Lipid Nanoparticles: A Synchrotron Small-Angle X-ray Scattering (SAXS) Study.

We present the first report on the effects of hydrostatic pressure on colloidally stabilized lipid nanoparticles enveloping inverse nonlamellar self-assemblies in their interiors. These internal self-assemblies were systematically tuned into bicontinuous cubic (Pn3m and Im3m), micellar cubic (Fd3m), hexagonal (H2), and inverse micellar (L2) phases by regulating the lipid/oil ratio as the hydrostatic pressure was varied from atmospheric pressure to 1200 bar and back to atmospheric pressure. The effects of pressure on these lipid nanoparticles were compared with those on their equilibrium bulk, nondispersed counterparts, namely, inverse nonlamellar liquid-crystalline phases and micellar solutions under excess-water conditions, using the synchrotron small-angle X-ray scattering (SAXS) technique. In the applied pressure range, induced phase transitions were observed solely in fully hydrated bulk samples, whereas the internal self-assemblies of the corresponding lipid nanoparticles displayed only pressure-modulated single phases. Interestingly, both the lattice parameters and the linear pressure expansion coefficients were larger for the self-assemblies enveloped inside the lipid nanoparticles as compared to the bulk states. This behavior can, in part, be attributed to enhanced lipid layer undulations in the lipid particles in addition to induced swelling effects in the presence of the triblock copolymer F127. The bicontinuous cubic phases both in the bulk state and inside lipid cubosome nanoparticles swell on compression, even as both keep swelling further upon decompression at relatively high pressures before shrinking again at ambient pressures. The pressure dependence of the phases is also modulated by the concentration of the solubilized oil (tetradecane). These studies demonstrate the tolerance of lipid nanoparticles [cubosomes, hexosomes, micellar cubosomes, and emulsified microemulsions (EMEs)] for high pressures, confirming their robustness for various technological applications.

Structural and functional implications of the interaction between macrolide antibiotics and bile acids.

Macrolide antibiotics, such as azithromycin and erythromycin, are in widespread use for the treatment of bacterial infections. Macrolides are taken up and excreted mainly by bile. Additionally, they have been implicated in biliary system diseases and to modify the excretion of other drugs through bile. Despite mounting evidence for the interplay between macrolide antibiotics and bile acids, the molecular details of this interaction remain unknown. Herein, we show by NMR measurements that macrolides directly bind to bile acid micelles. The topology of this interaction has been determined by solvent paramagnetic relaxation enhancements (solvent PREs). The macrolides were found to be bound close to the surface of the micelle. Increasing hydrophobicity of both the macrolide and the bile acid strengthen this interaction. Both bile acid and macrolide molecules show similar solvent PREs across their whole structures, indicating that there are no preferred orientations of them in the bile micelle aggregates. The binding to bile aggregates does not impede macrolide antibiotics from targeting bacteria. In fact, the toxicity of azithromycin towards enterotoxic E. coli (ETEC) is even slightly increased in the presence of bile, as was shown by effective concentration (EC50 ) values.

Synthesis and Characterization of Citric Acid-Modified Iron Oxide Nanoparticles Prepared with Electrohydraulic Discharge Treatment.

Chemical co-precipitation from ferrous and ferric salts at a 1:1.9 stoichiometric ratio in NH4OH base with ultrasonication (sonolysis) in a low vacuum environment has been used for obtaining colloidal suspensions of Fe3O4 nanoparticles coated with citric acid. Before coating, the nanoparticles were processed by electrohydraulic discharges with a high discharge current (several tens of amperes) in a water medium using a pulsed direct current. Magnetite nanoparticles were obtained with an average crystallite diameter D = 25-28 nm as obtained by XRD and particle sizes of 25 nm as measured by small-angle X-ray scattering. Magnetometry showed that all samples were superparamagnetic. The saturation magnetization for the citric acid covered samples after electrohydraulic processing showed higher value (58 emu/g) than for the directly coated samples (50 emu/g). Ultraviolet-visible spectroscopy and Fourier transform infrared spectroscopy showed the presence and binding of citric acid to the magnetite surface by chemisorption of carboxylate ions. Hydrodynamic sizes obtained from DLS and zeta potentials were 93 and 115 nm, -26 and -32 mV for the citric acid covered nanoparticles and 226 nm and 21 mV for the bare nanoparticles, respectively. The hydraulic discharge treatment resulted in a higher citric acid coverage and better particle dispersion. The developed method can be used in nanoparticle synthesis for biomedical applications.

The Nanostructured Self-Assembly and Thermoresponsiveness in Water of Amphiphilic Copolymers Carrying Oligoethylene Glycol and Polysiloxane Side Chains.

Amphiphilic copolymer self-assembly is a straightforward approach to obtain responsive micelles, nanoparticles, and vesicles that are particularly attractive for biomedicine, i.e., for the delivery of functional molecules. Here, amphiphilic copolymers of hydrophobic polysiloxane methacrylate and hydrophilic oligo (ethylene glycol) methyl ether methacrylate with different lengths of oxyethylenic side chains were synthesized via controlled RAFT radical polymerization and characterized both thermally and in solution. In particular, the thermoresponsive and self-assembling behavior of the water-soluble copolymers in water was investigated via complementary techniques such as light transmittance, dynamic light scattering (DLS), and small-angle X-ray scattering (SAXS) measurements. All the copolymers synthesized were thermoresponsive, displaying a cloud point temperature (Tcp) strongly dependent on macromolecular parameters such as the length of the oligo(ethylene glycol) side chains and the content of the SiMA counits, as well as the concentration of the copolymer in water, which is consistent with a lower critical solution temperature (LCST)-type behavior. SAXS analysis revealed that the copolymers formed nanostructures in water below Tcp, whose dimension and shape depended on the content of the hydrophobic components in the copolymer. The hydrodynamic diameter (Dh) determined by DLS increased with the amount of SiMA and the associated morphology at higher SiMA contents was found to be pearl-necklace-micelle-like, composed of connected hydrophobic cores. These novel amphiphilic copolymers were able to modulate thermoresponsiveness in water in a wide range of temperatures, including the physiological temperature, as well as the dimension and shape of their nanostructured assemblies, simply by varying their chemical composition and the length of the hydrophilic side chains.

Lignin-Derived Mesoporous Carbon for Sodium-Ion Batteries: Block Copolymer Soft Templating and Carbon Microstructure Analysis.

The demand for versatile and sustainable energy materials is on the rise, given the importance of developing novel clean technologies for transition to a net zero economy. Here, we present the synthesis, characterization, and application of lignin-derived ordered mesoporous carbons with various pore sizes (from 5 to approximately 50 nm) as anodes in sodium-ion batteries. We have varied the pore size using self-synthesized PEOn-b-PHAm block copolymers with different PEO and PHA chain lengths, applying the "soft templating" approach to introduce isolated spherical pores of 20 to 50 nm in diameters. The pore structure was evaluated by transmission electron microscopy (TEM), nitrogen physisorption, and small-angle X-ray scattering (SAXS). We report the microstructure analysis of such mesoporous lignin-based carbons using Raman spectroscopy and wide-angle X-ray scattering (WAXS). In comparison with nontemplated carbon and carbons templated employing commercial Pluronic F-127 and PIB50-b-PEO45, which created accessible channels and spherical pores up to approximately 10 nm in diameter, the carbon microstructure analysis revealed that templating with all applied polymers significantly impedes graphitization upon thermal treatment. Furthermore, the gained knowledge of similar carbon microstructures regardless of the type of template allowed the investigation of the influence of different pore morphologies in carbon applied as an anode material in sodium-ion batteries, supporting the previous theories in the literature that closed pores are beneficial for sodium storage while providing insights into the importance of pore size.

The intriguing dose-dependent effect of selected amphiphilic compounds on insulin amyloid aggregation: Focus on a cholesterol-based detergent, Chobimalt.

The amyloidogenic self-assembly of many peptides and proteins largely depends on external conditions. Among amyloid-prone proteins, insulin attracts attention because of its physiological and therapeutic importance. In the present work, the amyloid aggregation of insulin is studied in the presence of cholesterol-based detergent, Chobimalt. The strategy to elucidate the Chobimalt-induced effect on insulin fibrillogenesis is based on performing the concentration- and time-dependent analysis using a combination of different experimental techniques, such as ThT fluorescence assay, CD, AFM, SANS, and SAXS. While at the lowest Chobimalt concentration (0.1 µM; insulin to Chobimalt molar ratio of 1:0.004) the formation of insulin fibrils was not affected, the gradual increase of Chobimalt concentration (up to 100 µM; molar ratio of 1:4) led to a significant increase in ThT fluorescence, and the maximal ThT fluorescence was 3-4-fold higher than the control insulin fibril's ThT fluorescence intensity. Kinetic studies confirm the dose-dependent experimental results. Depending on the concentration of Chobimalt, either (i) no effect is observed, or (ii) significantly, ∼10-times prolonged lag-phases accompanied by the substantial, ∼ 3-fold higher relative ThT fluorescence intensities at the steady-state phase are recorded. In addition, at certain concentrations of Chobimalt, changes in the elongation-phase are noticed. An increase in the Chobimalt concentrations also triggers the formation of insulin fibrils with sharply altered morphological appearance. The fibrils appear to be more flexible and wavy-like with a tendency to form circles. SANS and SAXS data also revealed the morphology changes of amyloid fibrils in the presence of Chobimalt. Amyloid aggregation requires the formation of unfolded intermediates, which subsequently generate amyloidogenic nuclei. We hypothesize that the different morphology of the formed insulin fibrils is the result of the gradual binding of Chobimalt to different binding sites on unfolded insulin. A similar explanation and the existence of such binding sites with different binding energies was shown previously for the nonionic detergent. Thus, the data also emphasize the importance of a protein partially-unfolded state which undergoes the process of fibrils formation; i.e., certain experimental conditions or the presence of additives may dramatically change not only kinetics but also the morphology of fibrillar aggregates.

Effects of pressure and temperature on the self-assembled fully hydrated nanostructures of monoolein-oil systems.

Synchrotron small-angle X-ray scattering (SAXS) was applied for studying the effects of hydrostatic pressure and temperature on the structural behavior of fully hydrated tetradecane (TC)-loaded monoolein (MO) systems. Our main attention focused on investigating the impact of isobaric and isothermal changes on the stability of the inverted type discontinuous Fd3m cubic phase as compared to the inverted type hexagonal (H(2)) liquid crystalline phase. The present results show that compressing the TC-loaded Fd3m phase under isothermal conditions induces a significant increase of its lattice parameter: it approximately increases by 1 A per 75 bar. Further, the Fd3m phase is more pressure-sensitive as compared to the Pn3m and the H(2) phases. At ambient temperatures, we observed the following structural transitions as pressure increases: Fd3m --> H(2) --> Pn3m. Our findings under isobaric conditions reveal more complicated structural transitions. At high pressures, we recorded the interesting temperature-induced structural transition of (Pn3m + L(alpha)) --> (Pn3m + L(alpha) + H(2)) --> (L(alpha) + H(2)) --> H(2) --> Fd3m --> traces of Fd3m coexisting with L(2). At high pressures and low temperatures, the TC molecules partially crystallize as indicated by the appearance of an additional diffraction peak at q = 3.46 nm(-1). This crystallite disappears at high temperatures and also as the system gets decompressed. The appearance of the Pn3m and the L(alpha) phases during compressing the fully hydrated MO/TC samples at high pressures and low temperatures is generally related to a growing hydrocarbon chain condensation, which leads to membrane leaflets with less negative interfacial curvatures (decreasing the spontaneous curvatures |H(0)|). Both the effects of pressure and temperature are discussed in detail for all nonlamellar phases on the basis of molecular shape and packing concepts.

The Structural Integrity of the Model Lipid Membrane during Induced Lipid Peroxidation: The Role of Flavonols in the Inhibition of Lipid Peroxidation.

The structural integrity, elasticity, and fluidity of lipid membranes are critical for cellular activities such as communication between cells, exocytosis, and endocytosis. Unsaturated lipids, the main components of biological membranes, are particularly susceptible to the oxidative attack of reactive oxygen species. The peroxidation of unsaturated lipids, in our case 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), induces the structural reorganization of the membrane. We have employed a multi-technique approach to analyze typical properties of lipid bilayers, i.e., roughness, thickness, elasticity, and fluidity. We compared the alteration of the membrane properties upon initiated lipid peroxidation and examined the ability of flavonols, namely quercetin (QUE), myricetin (MCE), and myricitrin (MCI) at different molar fractions, to inhibit this change. Using Mass Spectrometry (MS) and Fourier Transform Infrared Spectroscopy (FTIR), we identified various carbonyl products and examined the extent of the reaction. From Atomic Force Microscopy (AFM), Force Spectroscopy (FS), Small Angle X-Ray Scattering (SAXS), and Electron Paramagnetic Resonance (EPR) experiments, we concluded that the membranes with inserted flavonols exhibit resistance against the structural changes induced by the oxidative attack, which is a finding with multiple biological implications. Our approach reveals the interplay between the flavonol molecular structure and the crucial membrane properties under oxidative attack and provides insight into the pathophysiology of cellular oxidative injury.

Comprehensive characterization of nanostructured lipid carriers using laboratory and synchrotron X-ray scattering and diffraction.

The development of lipid nanoparticles requires knowledge on the crystalline structure, polymorphic transitions and lipid-drug interactions. This study aimed at introducing advanced techniques to characterize nanostructured lipid carriers (NLC) comprising palmitic acid, oleic acid, stabilizer and Domperidone. Crystallinity of single components and mixtures was investigated by laboratory Small Angle X-ray Scattering (SAXS). NLC were studied with laboratory Small and Wide Angle X-ray Scattering (SWAXS). Photon Correlation Spectroscopy and Freeze Fracture Transmission Electron Microscopy were used to monitor particle size, zeta potential and shape. Stability of NLC was investigated using synchrotron X-ray Diffraction (XRD) and SAXS and laboratory SAXS. Palmitic acid showed a lamellar structure (polymorph C), which was still present after particle preparation. Spherical 300 nm-sized particles with zeta potential values above -30 mV were obtained and Domperidone was incorporated in its amorphous form. During storage, no differences in synchrotron XRD spectra were seen. However, laboratory SAXS measurements showed a second lamellar structure, identified as polymorph B. Synchrotron SAXS temperature scans confirmed that polymorph B did not affect the morphology of the encapsulated drug or the shape of NLC. These results highlight the unique capabilities of laboratory and synchrotron X-ray Scattering and Diffraction for improved structural characterization of lipid nanoparticles.

High Hydrostatic Pressure Induces a Lipid Phase Transition and Molecular Rearrangements in Low-Density Lipoprotein Nanoparticles.

Low-density lipoproteins (LDL) are natural lipid transporter in human plasma whose chemically modified forms contribute to the progression of atherosclerosis and cardiovascular diseases accounting for a vast majority of deaths in westernized civilizations. For the development of new treatment strategies, it is important to have a detailed picture of LDL nanoparticles on a molecular basis. Through the combination of X-ray and neutron small-angle scattering (SAS) techniques with high hydrostatic pressure (HHP) this study describes structural features of normolipidemic, triglyceride-rich and oxidized forms of LDL. Due to the different scattering contrasts for X-rays and neutrons, information on the effects of HHP on the internal structure determined by lipid rearrangements and changes in particle shape becomes accessible. Independent pressure and temperature variations provoke a phase transition in the lipid core domain. With increasing pressure an inter-related anisotropic deformation and flattening of the particle are induced. All LDL nanoparticles maintain their structural integrity even at 3000 bar and show a reversible response toward pressure variations. The present work depicts the complementarity of pressure and temperature as independent thermodynamic parameters and introduces HHP as a tool to study molecular assembling and interaction processes in distinct lipoprotein particles in a nondestructive manner.

Improved Optical and Morphological Properties of Vinyl-Substituted Hybrid Silica Materials Incorporating a Zn-Metalloporphyrin.

This work is focused on a novel class of hybrid materials exhibiting enhanced optical properties and high surface areas that combine the morphology offered by the vinyl substituted silica host, and the excellent absorption and emission properties of 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin-Zn(II) tetrachloride as a water soluble guest molecule. In order to optimize the synthesis procedure and the performance of the immobilized porphyrin, silica precursor mixtures of different compositions were used. To achieve the requirements regarding the hydrophobicity and the porous structure of the gels for the successful incorporation of porphyrin, the content of vinyltriacetoxysilane was systematically changed and thoroughly investigated. Substitution of the silica gels with organic groups is a viable way to provide new properties to the support. An exhaustive characterization of the synthesized silica samples was realised by complementary physicochemical methods, such as infrared spectroscopy (FT-IR), absorption spectroscopy (UV-Vis) and photoluminescence, nuclear magnetic resonance spectroscopy (29Si-MAS-NMR) transmission and scanning electron microscopy (TEM and SEM), nitrogen absorption (BET), contact angle (CA), small angle X ray and neutron scattering (SAXS and SANS). All hybrids showed an increase in emission intensity in the wide region from 575 to 725 nm (Q bands) in comparison with bare porphyrin. By simply tuning the vinyltriacetoxysilane content, the hydrophilic/hydrophobic profile of the hybrid materials was changed, while maintaining a high surface area. Good control of hydrophobicity is important to enhance properties such as dispersion, stability behaviour, and resistance to water, in order to achieve highly dispersible systems in water for biomedical applications.