Molecular Architecture Effects on Bulk Nanostructure in Bis(Orthoborate) Ionic Liquids.

A series of 19 ionic liquids (ILs) based on phosphonium and imidazolium cations of varying alkyl-chain lengths with the orthoborate anions bis(oxalato)borate [BOB]- , bis(mandelato)borate, [BMB]- and bis(salicylato)borate, [BScB]- , are synthesized and studied using small-angle neutron scattering (SANS). All measured systems display nanostructuring, with 1-methyl-3-n-alkyl imidazolium-orthoborates forming clearly bicontinuous L3 spongelike phases when the alkyl chains are longer than C6 (hexyl). L3 phases are fitted using the Teubner and Strey model, and diffusely-nanostructured systems are primarily fitted using the Ornstein-Zernicke correlation length model. Strongly-nanostructured systems have a strong dependence on the cation, with molecular architecture variation explored to determine the driving forces for self-assembly. The ability to form well-defined complex phases is effectively extinguished in several ways: methylation of the most acidic imidazolium ring proton, replacing the imidazolium 3-methyl group with a longer hydrocarbon chain, substitution of [BOB]- by [BMB]- , or exchanging the imidazolium for phosphonium systems, irrespective of phosphonium architecture. The results suggest there is only a small window of opportunity, in terms of molecular amphiphilicity and cation:anion volume matching, for the formation of stable extensive bicontinuous domains in pure bulk orthoborate-based ILs. Particularly important for self-assembly processes appear to be the ability to form H-bonding networks, which offer additional versatility in imidazolium systems.

Intercalation of CO2 Selected by Type of Interlayer Cation in Dried Synthetic Hectorite.

Clay minerals are abundant in caprock formations for anthropogenic storage sites for CO2, and they are potential capture materials for CO2 postcombustion sequestration. We investigate the response to CO2 exposure of dried fluorohectorite clay intercalated with Li+, Na+, Cs+, Ca2+, and Ba2+. By in situ powder X-ray diffraction, we demonstrate that fluorohectorite with Na+, Cs+, Ca2+, or Ba2+ does not swell in response to CO2 and that Li-fluorohectorite does swell. A linear uptake response is observed for Li-fluorohectorite by gravimetric adsorption, and we relate the adsorption to tightly bound residual water, which exposes adsorption sites within the interlayer. The experimental results are supported by DFT calculations.

Modifying the Properties of Microemulsion Droplets by Addition of Thermoresponsive BAB* Copolymers.

Oil-in-water (O/W) microemulsions (ME) typically feature a low viscosity and exhibit ordinary viscosity reduction as a function of temperature. However, for certain applications, avoiding or even reverting the temperature trend might be required. This can be conceived by adding thermoresponsive (TR) block copolymers that induce network formation as the temperature increases. Accordingly, various ME-polymer mixtures were studied for which three different block copolymer architectures of BAB*-, B2AB*-, and B(AB*)2-types were employed. Here, "B" represents a permanently hydrophobic, "A" a permanently hydrophilic, and "B*" a TR block. For the TR-block, three different poly(acrylamide)s, namely poly(N-n-propylacrylamide) (pNPAm), poly(N,N-diethylacrylamide) (pDEAm), and poly(N-isopropylacrylamide) (pNiPAm), were used, which all exhibit a lower critical solution temperature. For a well-selected ME concentration, these block copolymers lead to a viscosity enhancement with increasing temperature. At a polymer concentration of about 22 g L-1, the most pronounced enhancement was observed for the pNPAm-based systems with factors up to 3, 5, and 8 for BAB*, B2AB*, and B(AB*)2, respectively. This phenomenon is caused by the formation of a transitory network mediated by TR-blocks, as evidenced by the direct correlation between the attraction strength and the viscosity enhancement. For applications requiring a high hydrophobic payload, which is attained via ME droplets, this kind of tailored temperature-dependent viscosity control of surfactant systems should therefore be advantageous.

Shall We Tune? From Core-Shell to Cloud Type Nanostructures in Heparin/Silica Hybrids.

Heparin plays multiple biological roles depending on the availability of active sites strongly influenced by the conformation and the structure of polysaccharide chains. Combining different components at the molecular scale offers an extraordinary chance to easily tune the structural organization of heparin required for exploring new potential applications. In fact, the combination of different material types leads to challenges that cannot be achieved by each single component. In this study, hybrid heparin/silica nanoparticles were synthesized, and the role of silica as a templating agent for heparin supramolecular organization was investigated. The effect of synthesis parameters on particles compositions was deeply investigated by Fourier Transform Infrared Spectroscopy (FTIR) and Thermogravimetric Analysis (TGA). Transmission Electron Microscopy (TEM) reveals a different supramolecular organization of both components, leading to amazing organic-inorganic nanoparticles with different behavior in drug encapsulation and release. Furthermore, favorable biocompatibility for healthy human dermal fibroblasts (HDF) and tumor HS578T cells has been assessed, and a different biological behavior was observed, ascribed to different surface charge and morphology of synthesized nanoparticles.

Investigating Aggregation Using In Situ Electrochemistry and Small-Angle Neutron Scattering.

Using small-angle neutron scattering to investigate the aggregation of self-assembling molecules is well established. Some of these molecules are electrochemically useful, for example, in electrochromic devices. Electrochemistry can also be used in some cases to induce aggregation. Here, we describe an approach whereby electrochemistry can be directly carried out on a sample in the neutron beam, allowing us to monitor changes directly in situ. We exemplify with two examples but highlight that there are many other potential opportunities.

CO2 Adsorption Enhanced by Tuning the Layer Charge in a Clay Mineral.

Due to the compact two-dimensional interlayer pore space and the high density of interlayer molecular adsorption sites, clay minerals are competitive adsorption materials for carbon dioxide capture. We demonstrate that with a decreasing interlayer surface charge in a clay mineral, the adsorption capacity for CO2 increases, while the pressure threshold for adsorption and swelling in response to CO2 decreases. Synthetic nickel-exchanged fluorohectorite was investigated with three different layer charges varying from 0.3 to 0.7 per formula unit of Si4O10F2. We associate the mechanism for the higher CO2 adsorption with more accessible space and adsorption sites for CO2 within the interlayers. The low onset pressure for the lower-charge clay is attributed to weaker cohesion due to the attractive electrostatic forces between the layers. The excess adsorption capacity of the clay is measured to be 8.6, 6.5, and 4.5 wt % for the lowest, intermediate, and highest layer charges, respectively. Upon release of CO2, the highest-layer charge clay retains significantly more CO2. This pressure hysteresis is related to the same cohesion mechanism, where CO2 is first released from the edges of the particles thereby closing exit paths and trapping the molecules in the center of the clay particles.

Periodic bilayer organization in the complexes of Beta-2 Glycoprotein I with anionic lipid membranes.

ß2 glycoprotein I (ß2GPI) is a soluble protein that participates in blood coagulation, clearance of apoptotic bodies and generation of antigens in antiphospholipid syndrome among many other functions. We studied the aggregates formed by ß2GPI with the anionic phospholipids palmitoyloleoylphosphatidyl glycerol, dimyristoylphosphatidyl glycerol, dipalmitoylphosphatidyl glycerol and cardiolipin using small angle X-ray scattering. The complexes obtained in a medium containing 0.01 M NaCl showed Bragg peaks up to the sixth order in a well-defined integer sequence indicating the presence of a lamellar stacking with a periodicity of 17.8 nm and with largely reduced membrane fluctuations. Modeling the complex signal allowed us to conclude that the coherence length was only two bilayers and that about 15% of the total surface was actually stacked. The space between bilayers allows accommodating an extended ß2GPI molecule making a bridge between the interacting bilayers. The interactions between membranes mediated by ß2GPI was favored when the membranes were in the liquid crystalline state.

The Nanostructure of Water-in-Salt Electrolytes Revisited: Effect of the Anion Size.

The increasing interest in developing safe and sustainable energy storage systems has led to the rapid rise in attention to superconcentrated electrolytes, commonly called water-in-salt (WiS). Several works indicate that the transport properties of these liquid electrolytes are related to the presence of nanodomains, but a detailed characterization of such structure is missing. Here, the structural nano-heterogeneity of lithium WiS electrolytes, comprising lithium trifluoromethanesulfonate (LiTf) and bis(trifluoromethanesulfonyl)imide (LiTFSI) solutions as a function of concentration and temperature, was assessed by resorting to the analysis of small-angle neutron scattering (SANS) patterns. Variations with the concentration of a correlation peak, rather temperature-independent, in a Q range around 3.5-5 nm-1 indicate that these electrolytes are composed of nanometric water-rich channels percolating a 3D dispersing anion-rich network, with differences between Tf and TFSI anions related to their distinct volumes and interactions. Furthermore, a common trend was found for both systems' morphology above a salt volume fraction of ∼0.5. These results imply that the determining factor in the formation of the nanostructure is the salt volume fraction (related to the anion size), rather than its molality. These findings may represent a paradigm shift for designing WiS electrolytes.

Small-Angle Neutron Scattering Characterization of SrCl2-ENG Composites for Thermochemical Heat Storage.

This work presents an in situ nanoscale structural characterization of a SrCl2-expanded natural graphite (ENG) composite during ammonia absorption and desorption using small-angle neutron scattering (SANS) together with X-ray powder diffraction and sorption measurements. For the processing of the composite material SANS patterns, we developed and implemented two methods, which showed comparable results. The study allowed following the evolution of the SrCl2 particles and the nanopores inside the particles during five sorption cycles. The structural changes were compared to the absorption and desorption kinetic measurements, allowing us to make qualitative analysis of the impact of the structural changes on the material properties, such as thermal conductivity and permeability. It was shown that the structural evolution of the composite material did not affect the desorption rate but significantly influenced the absorption rate after the first cycle. We also observed a significant improvement of the absorption kinetics due to the formation of nanopores in the fully deammoniated sample. In addition, the ENG matrix was shown to hinder the agglomeration of the SrCl2 particles during sorption processes, which is in contrast to literature findings reported for a nonsupported metal halide. The findings presented in this study can be of great interest in the research areas where SrCl2-ENG composites are widely studied, i.e., heat storage, heat pumps/refrigerators, deNOx removal, and solid-state ammonia storage.

Unmodified Clay Nanosheets at the Air-Water Interface.

Quasi-two-dimensional (2D) nanolayers, such as graphene oxide or clay layers, adhere to gas-liquid or liquid-liquid interfaces. Particularly, clays are of wide general interest in this context because of their extensive and crucial use as Pickering emulsion stabilizers, as well as for their ability to provide colloidosome capsules. So far, clays could only be localized at oil-water or air-saline-water interfaces in aggregated states, while our results now show that clay nanosheets without any modification can be located at air-deionized-water interfaces. The clay mineral used in the present work is synthetic fluorohectorite with a very high aspect ratio and superior quality in homogeneity and charge distribution compared to other clay minerals. This clay mineral is more suitable for achieving unmodified clay anchoring to fluid interfaces compared to other clay minerals used in previous works. In this context, we studied clay nanosheet organization at the air-water interface by combining different experimental methods: Langmuir-Blodgett trough studies, scanning electron microscopy (SEM) studies of film deposits, grazing-incidence X-ray off-specular scattering (GIXOS), and Brewster angle microscopy (BAM). Clay films formed at the air-water interface could be transferred to solid substrates by the Langmuir-Schaefer method. The BAM results indicate a dynamic equilibrium between clay sheets on the interface and in the subphase. Because of this dynamic equilibrium, the Langmuir monolayer surface pressure does not change significantly when pure clay sheets are spread on the liquid surface. However, also, GIXOS results confirm that there are clay nanosheets at the air-water interface. In addition, we find that clay sheets modified by a branched polymer are much more likely to be confined to the interface.

Annealing Supramolecular Gels by a Reaction Relay.

Supramolecular gels have potential in many areas. In many cases, a major drawback is that the gels are formed at a high rate. As a result, nonoptimal, kinetically trapped self-assembled structures are often formed, leading to gels that can be hard to reproduce and control. One method to get around kinetic trapping is annealing. Thermal annealing is one possibility, but it is not always desirable to heat the gels. Here, we describe a method to anneal pH-triggered gels after they are formed. We employ a reaction relay in a peptide-based hydrogel system to anneal the structures by a controlled and uniform pH change. Our method allows us to prepare gels with more controlled properties. We show that this can be used to enable homogeneous "molding and casting" of the hydrogels. This method of annealing is more effective in improving gel robustness than a conventional heat-cool cycle.

A nano-silicate material with exceptional capacity for CO2 capture and storage at room temperature.

In order to mitigate climate change driven by the observed high levels of carbon dioxide (CO2) in the atmosphere, many micro and nano-porous materials are being investigated for CO2 selectivity, capture and storage (CCS) purposes, including zeolites, metal organic frameworks (MOFs), functionalized polymers, activated carbons and nano-silicate clay minerals. Key properties include availability, non-toxicity, low cost, stability, energy of adsorption/desorption, sorbent regeneration, sorption kinetics and CO2 storage capacity. Here, we address the crucial point of the volumetric capture and storage capacity for CO2 in a low cost material which is natural, non-toxic, and stable. We show that the nano-silicate Nickel Fluorohectorite is able to capture 0.79 metric tons of CO2 per m3 of host material - one of the highest capacities ever achieved - and we compare volumetric and gravimetric capacity of the best CO2 sorbent materials reported to date. Our results suggest that the high capture capacity of this fluorohectorite clay is strongly coupled to the type and valence of the interlayer cation (here Ni2+) and the high charge density, which is almost twice that of montmorillonite, resulting in the highest reported CO2 uptake among clay minerals.

Sample cell for studying liquid interfaces with an in situ electric field using X-ray reflectivity and application to clay particles at oil-oil interfaces.

Commissioning results of a liquid sample cell for X-ray reflectivity studies with an in situ applied electrical field are presented. The cell consists of a Plexiglas container with lateral Kapton windows for air-liquid and liquid-liquid interface studies, and was constructed with grooves to accept plate electrodes on the walls parallel to the direction of the beam. Both copper and ITO plate electrodes have been used, the latter being useful for simultaneous optical studies. Commissioning tests were made at the I07 beamline of the Diamond Light Source.

Refractive index and thickness determination in Langmuir monolayers of myelin lipids.

Langmuir monolayers at the air/water interface are widely used as biomembrane models and for amphiphilic molecules studies in general. Under controlled intermolecular organization (lateral molecular area), surface pressure, surface potential, reflectivity (R) and other magnitudes can be precisely determined on these planar monomolecular films. However, some physical parameters such as the refractive index of the monolayer (n) still remain elusive. The refractive index is very relevant because (in combination with R) it allows for the determination of the thickness of the film. The uncertainties of n determine important errors that propagate non-linearly into the calculation of monolayers thickness. Here we present an analytical method for the determination of n in monolayers based on refractive index matching. By using a Brewster angle microscopy (BAM) setup and monolayers spread over subphases with variable refractive index (n2), a minimum in R is search as a function of n2. In these conditions, n equals n2. The results shown correspond to monolayers of myelin lipids. The n values remain constant at 1.46 upon compression and equals the obtained value for myelin lipid bilayers in suspension. The values for n and R allow for the determination of thickness. We establish comparisons between these thicknesses for the monolayer and those obtained from two X-ray scattering techniques: 1) GIXOS for monolayers at the air/water interface and 2) SAXS for bilayers in bulk suspension. This allows us to conclude that the thickness that we measure by BAM includes the apolar and polar headgroup regions of the monolayer.

Poloxamer 407/188 binary thermosensitive hydrogels as delivery systems for infiltrative local anesthesia: Physico-chemical characterization and pharmacological evaluation.

In this study, we reported the development and the physico-chemical characterization of poloxamer 407 (PL407) and poloxamer 188 (PL188) binary systems as hydrogels for delivering ropivacaine (RVC), as drug model, and investigate their use in infiltrative local anesthesia for applications on the treatment of post-operative pain. We studied drug-micelle interaction and micellization process by light scattering and differential scanning calorimetry (DSC), the sol-gel transition and hydrogel supramolecular structure by small-angle-X-ray scattering (SAXS) and morphological evaluation by Scanning Electron Microscopy (SEM). In addition, we have presented the investigation of drug release mechanisms, in vitro/in vivo toxic and analgesic effects. Micellar dimensions evaluation showed the formation of PL407-PL188 mixed micelles and the drug incorporation, as well as the DSC studies showed increased enthalpy values for micelles formation after addition of PL 188 and RVC, indicating changes on self-assembly and the mixed micelles formation evoked by drug incorporation. SAXS studies revealed that the phase organization in hexagonal structure was not affected by RVC insertion into the hydrogels, maintaining their supramolecular structure. SEM analysis showed similar patterns after RVC addition. The RVC release followed the Higuchi model, modulated by the PL final concentration and the insertion of PL 188 into the system. Furthermore, the association PL407-PL188 induced lower in vitro cytotoxic effects, increased the duration of analgesia, in a single-dose model study, without evoking in vivo inflammation signs after local injection.

Enhancement of chlorpromazine antitumor activity by Pluronics F127/L81 nanostructured system against human multidrug resistant leukemia.

The development of specific tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia (CML). However, chemoresistance of tumor cells to TKIs has already been described, and several mechanisms account for the multidrug resistance (MDR) phenotypes, including the overexpression of P-glycoprotein (P-gp). This decreases the rate of healing and complete tumor remission. Nanotechnological tools have been studied to allow advances in this field. Poloxamers (Pluronics(®)) have been proposed as drug carriers to improve therapeutic efficacy and decrease side effects, even in cancer therapy, due to their ability to inhibit P-gp. Antipsychotic phenothiazines have been described as potent cytotoxic drugs against several types of tumor cells in vitro. Here, we show that nanostructured micellar systems containing the phenothiazine derivative chlorpromazine (CPZ) potentiated the cytotoxicity of free CPZ and increased the selectivity against CML tumor cells, demonstrating the pharmacological potential of these poloxamer-based nanostructured systems containing CPZ in cancer therapy.

Microfluidic Assembly of pDNA/Cationic Liposome Lipoplexes with High pDNA Loading for Gene Delivery.

Microfluidics offers unique characteristics to control the mixing of liquids under laminar flow. Its use for the assembly of lipoplexes represents an attractive alternative for the translation of gene delivery studies into clinical trials on a sufficient throughput scale. Here, it was shown that the microfluidic assembly of pDNA/cationic liposome (CL) lipoplexes allows the formation of nanocarriers with enhanced transfection efficiencies compared with the conventional bulk-mixing (BM) process under high pDNA loading conditions. Lipoplexes generated by microfluidic devices exhibit smaller and more homogeneous structures at a molar charge ratio (R±) of 1.5, representing the ratio of lipid to pDNA content. Using an optimized model to fit small-angle X-ray scattering (SAXS) curves, it was observed that large amounts of pDNA induces the formation of aggregates with a higher number of stacked bilayers (N ∼ 5) when the BM process was used, whereas microfluidic lipoplexes presented smaller structures with a lower number of stacked bilayers (N ∼ 2.5). In vitro studies further confirmed that microfluidic lipoplexes achieved higher in vitro transfection efficiencies in prostate cancer cells at R ± 1.5, employing a reduced amount of cationic lipid. The correlation of mesoscopic characteristics with in vitro performance provides insights for the elucidation of the colloidal arrangement and biological behavior of pDNA/CL lipoplexes obtained by different processes, highlighting the feasibility of applying microfluidics to gene delivery.

An Abraded Surface of Doxorubicin-Loaded Surfactant-Containing Drug Delivery Systems Effectively Reduces the Survival of Carcinoma Cells.

An effective antitumor remedy is yet to be developed. All previous approaches for a targeted delivery of anticancer medicine have relied on trial and error. The goal of this study was to use structural insights gained from the study of delivery systems and malignant cells to provide for a systematic approach to the development of next-generation drugs. We used doxorubicin (Dox) liposomal formulations. We assayed for cytotoxicity via the electrical current exclusion method. Dialysis of the samples yielded information about their drug release profiles. Information about the surface of the delivery systems was obtained through synchrotron small-angle X-ray scattering (SAXS) measurements. SAXS measurements revealed that Dox-loading yielded an abraded surface of our Dox liposomal formulation containing soybean oil, which also correlated with an effective reduction of the survival of carcinoma cells. Furthermore, a dialysis assay revealed that a higher burst of Dox was released from soybean oil-containing preparations within the first five hours. We conclude from our results that an abraded surface of Dox-loaded drug delivery system increases their efficacy. The apparent match between surface geometry of drug delivery systems and target cells is suggested as a steppingstone for refined development of drug delivery systems. This is the first study to provide a systematic approach to developing next-generation drug carrier systems using structural insights to guide the development of next-generation drug delivery systems with increased efficacy and reduced side effects.

Characterization of a Pt mirror to be used to deflect synchrotron radiation beam onto Langmuir monolayers.

A homemade mirror for X-rays has been built to prepare a diffraction beamline for liquid surface diffraction and scattering measurements. This simple approach is in operation at the XRD2 bending-magnet beamline at the Brazilian Synchrotron Light Laboratory.

Association between cationic liposomes and low molecular weight hyaluronic acid.

This work presents a study of the association between low molecular weight hyaluronic acid (16 kDa HA) and cationic liposomes composed of egg phosphatidylcholine (EPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). The cationic liposome/HA complexes were evaluated to determine their mesoscopic structure, average size, zeta potential, and morphology as a function of the amount of HA in the system. Small angle X-ray scattering results revealed that neighboring cationic liposomes either stick together after a partial coating of low concentration HA or disperse completely in excess of HA, but they never assemble as multilamellar vesicles. Cryo-transmission electron microscopy images confirm the existence of unilamellar vesicles and large aggregates of unilamellar vesicles for HA fractions up to 80% (w/w). High concentrations of HA (> 20% w/w) proved to be efficient for coating extruded liposomes, leading to particle complexes with sizes in the nanoscale range and a negative zeta potential.