Controlling 1D Nanostructures and Handedness by Polar Residue Chirality of Amphiphilic Peptides.

Peptide assemblies are promising nanomaterials, with their properties and technological applications being highly hinged on their supramolecular architectures. Here, how changing the chirality of the terminal charged residues of an amphiphilic hexapeptide sequence Ac-I4 K2 -NH2 gives rise to distinct nanostructures and supramolecular handedness is reported. Microscopic imaging and neutron scattering measurements show thin nanofibrils, thick nanofibrils, and wide nanotubes self-assembled from four stereoisomers. Spectroscopic and solid-state nuclear magnetic resonance (NMR) analyses reveal that these isomeric peptides adopt similar anti-parallel ß-sheet secondary structures. Further theoretical calculations demonstrate that the chiral alterations of the two C-terminal lysine residues cause the formation of diverse single ß-strand conformations, and the final self-assembled nanostructures and handedness are determined by the twisting direction and degree of single ß-strands. This work not only lays a useful foundation for the fabrication of diverse peptide nanostructures by manipulating the chirality of specific residues but also provides a framework for predicting the supramolecular structures and handedness of peptide assemblies from single molecule conformations.

Self-Sorting in Diastereomeric Mixtures of Functionalized Dipeptides.

Self-sorting in functionalized dipeptide systems can be driven by the chirality of a single amino acid, both at a high pH in the micellar state and at a low pH in the gel state. The structures formed are affected to some degree by the relative concentrations of each component showing the complexity of such an approach. The structures underpinning the gel network are predefined by the micellar structures at a high pH. Here, we describe the systems prepared from two dipeptide-based gelators that differ only by the chirality of one of the amino acids. We provide firm evidence for self-sorting in the micellar and gel phases using small-angle neutron scattering and cryo-transmission electron microscopy (cryo-TEM), showing that complete self-sorting occurs across a range of relative concentrations.

Peptide Self-Assemblies from Unusual α-Sheet Conformations Based on Alternation of d/l Amino Acids.

Peptide self-assembly is a hierarchical process during which secondary structures formed in the initial stages play a critical role in determining the subsequent assembling processes and final structural ordering. Unusual secondary structures hold promise as a source to develop novel supramolecular architectures with unique properties. In this work, we report the design of a new peptide self-assembly strategy based on unusual α-sheet secondary structures. In light of the strong propensity of leucine toward forming helical conformations and its high hydrophobicity, we design two short amphiphilic peptides Ac-LDLLDLK-NH2 and Ac-DLLDLLDK-NH2 with alternating l- and d-form amino acids. Microscopic imaging, neutron scattering, and spectroscopic measurements indicate that the two heterochiral peptides form highly ordered wide nanotubes and helical ribbons with monolayer thickness, in sharp contrast to twisted nanofibrils formed by the homochiral peptide Ac-LLLLK-NH2. Molecular dynamics simulations from monomers to trimers reveal that the two heteropeptides fold into α-sheets instead of ß-sheets, which readily pack into tubular architectures in oligomer simulations. Simulated circular dichroism spectra based on α-sheet oligomers validate the proposed α-sheet secondary structures. These results form an important basis for the rational design of higher-order peptide assemblies with novel properties based on unusual α-sheet secondary structures.

Profiling Parkinson's disease cognitive phenotypes via resting-state magnetoencephalography.

Aberrant brain oscillations are a hallmark of Parkinson's disease (PD) pathophysiology and may be related to both motor and nonmotor symptoms. Mild cognitive impairment (MCI) affects many people with PD even at the time of diagnosis and conversion risks to PD dementia (PDD) are very high. Unfortunately, pharmacotherapies are not addressing cognitive symptoms in PD. Profiling PD cognitive phenotypes (e.g., MCI, PDD, etc.) may therefore help inform future treatments. Neurophysiological methods, such as magnetoencephalography (MEG), offer the advantage of observing oscillatory patterns, whose regional and temporal profiles may elucidate how cognitive changes relate to neural mechanisms. We conducted a resting-state MEG cross-sectional study of 89 persons with PD stratified into three phenotypic groups: normal cognition, MCI, and PDD, to identify brain regions and frequencies most associated with each cognitive profile. In addition, a neuropsychological battery was administered to assess each domain of cognition. Our data showed higher power in lower frequency bands (delta and theta) observed along with more severe cognitive impairment and associated with memory, language, attention, and global cognition. Of the total 119 brain parcels assessed during source analysis, widespread group differences were found in the beta band, with significant changes mostly occurring between the normal cognition and MCI groups. Moreover, bilateral frontal and left-hemispheric regions were particularly affected in the other frequencies as cognitive decline becomes more pronounced. Our results suggest that MCI and PDD may be qualitatively distinct cognitive phenotypes, and most dramatic changes seem to have happened when the PD brain shows mild cognitive decline.NEW & NOTEWORTHY Can we better stage cognitive decline in patients with Parkinson's disease (PD)? Here, we provide evidence that mild cognitive impairment, rather than being simply a milder form of dementia, may be a qualitatively distinct phase in its development. We suggest that the most dramatic neurophysiological changes may occur during the time the PD brain transitions from normal cognition to MCI, then compensatory changes further occur as the brain "switches" to a dementia state.

Nanostructuring with Surfactants: The Self-Assembly of a New Poly(thiophene-phenylene) Conjugated Polymer Bearing Azacrown Ether Pendant Groups.

We report the synthesis of a new conjugated polymer bearing crown ether moieties, poly[(N(1-aza-[18]crown-6)carbamido)thiophene-2,5-diyl-alt-1,4-phenylene] (BG2). In water, BG2 forms a dispersion with a slightly cloudy appearance. We have studied the effect of adding surfactants, with different polar head groups, on these polymer-polymer aggregates. Special attention is given to the system with the anionic surfactant, sodium dodecyl sulfate (SDS). The combination of photophysical techniques with electrical conductivity, NMR (1H, 13C, and 27Na), DFT calculations, molecular dynamics simulations, and small-angle neutron scattering (SANS) provides a detailed picture on the behavior of the SDS/BG2 system in aqueous solution and in thin films. NMR, electric conductivity, and DFT results suggest that hydrophilic interactions occur between the polar headgroup of the surfactant (OSO3- Na+) and the aza-[18]-crown-6 moiety. DFT calculations confirmed the capability of BG2 to form stable complexes with the Na+ cations, where the cation can be either inside the azacrown cavity or sandwiched between the cavity and the polymer chain, which seem to determine the position of the surfactant hydrocarbon chain and, therefore, be responsible for the disruption of the BG2 aggregates and subsequent increase in the photoluminescence quantum yields. SANS measurements, made with hydrogenated and deuterated SDS in D2O, clearly show how micron-sized aggregates of BG2 are broken down by SDS and then how BG2 becomes preferentially incorporated within joint colloidal particles of BG2 and SDS with increasing [SDS]/[BG2] molar ratio.

Small-angle neutron scattering from mixtures of long- and short-chain 3-alkyl-1-methyl imidazolium bistriflimides.

The preparation of mixtures of ionic liquids (ILs) represents an attractive strategy to tune their properties, an important aspect of which is to understand how the structure of the bulk varies with composition. In this study, small-angle neutron scattering (SANS) was used to probe mixtures of methylimidazolium-based ionic liquids [Cnmim][Tf2N] with [C2mim][Tf2N]) (n = 4, 6, 8 and 10) and of [Cmmim][Tf2N] with [C12mim][Tf2N] (m = 2, 4, 6 and 8). Mixtures were prepared in both contrasts, which is to say that one component would be fully hydrogenated while the other was fully deuterated, and vice versa. Data were fitted using a range of appropriate models, of which the Teubner-Strey model provided most useful information and the pure materials showed a nascent Polar Non-polar Peak (PNPP) for n = 6, which became more evident as n increased. In the mixtures [Cnmim]x[C2mim]1-x[Tf2N], the PNPP was evident for n = 10 and 8, nascent for n = 6 and absent for n = 4, with percolation showing a very strong dependence on the chain length of the added IL, [Cnmim][Tf2N]. In contrast, while the ability of [C12mim][Tf2N] to form percolated structures was damped when mixed with [Cmmim][Tf2N], as m increased from 2 to 6, this effect was less strong. However, data obtained for mixtures of [C12mim][Tf2N] and [C8mim][Tf2N], both of which percolate as pure materials, did not fit easily in any of the models applied to the previous systems and gave results that depended on the contrast used. Complementary small-angle X-ray scattering (SAXS) data, however, showed the expected evolution and behaviour of the PNPP, COP and CP, revealing that the unexpected observations were due to an adventitious matching out of isotopic contrasts. As well as revealing details of the structures of these IL mixtures, the results also point to complementary strategies for generating bulk percolated structures as a function of cation chain length.

Fracto-eutectogels: SDS fractal dendrites via counterion condensation in a deep eutectic solvent.

Glyceline, a deep eutectic solvent comprising glycerol and choline chloride, is a green nonaqueous solvent with potential industrial applications. Molecular mechanisms of surfactant self-assembly in deep eutectic solvents are expected to differ from those in their constituent polar components and are not well understood. Here we report the observation of self-assembled SDS fractal dendrites with dimensions up to ∼mm in glyceline at SDS concentrations as low as cSDS ∼ 0.1 wt%. The prevalence of these dendritic fractal aggregates led to the formation of a gel phase at SDS concentrations above ≥1.9 wt% (the critical gelation concentration cCGC). The gel microscopic structure was visualised using polarised light microscopy (PLM); rheology measurements confirmed the formation of a colloidal gel, where the first normal stress difference was negative and the elastic modulus was dominant. Detailed nano-structural characterisation by small-angle neutron scattering (SANS) further confirmed the presence of fractal aggregates. Such SDS aggregation or gelation has not been observed in water at such low surfactant concentrations, whereas SDS has been reported to form lamellar aggregates in glycerol (a component of glyceline). We attribute the formation of the SDS fractal dendrites to the condensation of counterions (i.e. the choline ions) around the SDS aggregates - a diffusion-controlled process, leading to the aggregate morphology observed. These unprecedented results shed light on the molecular mechanisms of surfactant self-assembly in deep eutectic solvents, important to their application in industrial formulation.

Fabrication and application of composite adsorbents made by one-pot electrochemical exfoliation of graphite in surfactant ionic liquid/nanocellulose mixtures.

Previously, surfactant-assisted exfoliated graphene oxide (sEGO) formed with the triple-chain surfactant TC14 (sodium 1,4-bis(neopentyloxy)-3-(neopentylcarbonyl)-1,4-dioxobutane-2-sulfonate) was applied in wastewater treatment. The extent of dye-removal and the adsorption capacity of the sEGO formed with this triple-chain surfactant outperformed those of two other systems, namely, the di-chain version of TC14 (AOT14; sodium 1,2-bis-(2,2-dimethyl-propoxycarbonyl)-ethanesulfonate) and the single-chain surfactant sodium n-dodecylsulfate. In the present study, to further optimise the surfactant chemical structure, the sodium ion of TC14 was substituted with 1-butyl-3-methyl-imidazolium (BMIM) generating surfactant ionic liquids (SAILs; 1-butyl-3-imidazolium 1,4-bis(neopentyloxy)-3-(neopentyloxycarbonyl)-1,4-dioxobutane-2-sulfonate), hereafter denoted as BMIM-TC14. This SAIL, together with nanofibrillated kenaf cellulose (NFC), was used to electrochemically exfoliate graphite, yielding BMIM-TC14 sEGO/NFC composites. These highly hydrophobic polymer composites were then used for the removal of methylene blue (MB) from aqueous solution. 1H NMR spectroscopy was used to elucidate the structure of the synthesised SAILs. The morphologies of the resulting nanocomposites were investigated using Raman spectroscopy, field-emission scanning electron microscopy, and high-resolution transmission electron microscopy. Analysis using small-angle neutron scattering was performed to examine the aggregation behaviour of sEGO and custom-made SAILs. Zeta potential, surface tension, and dynamic light-scattering measurements were used to study the aqueous properties and colloidal stability of the suspension. Amongst the surfactants tested, BMIM-TC14 sEGO/NFC exhibited the highest MB adsorption ability, achieving 99% dye removal under optimum conditions. These results highlight the importance of modifying the hydrophilic moieties of amphiphilic compounds to improve the performance of sEGO/NFC composites as effective adsorbents for wastewater treatment.

Ordered Nanofibers Fabricated from Hierarchical Self-Assembling Processes of Designed α-Helical Peptides.

Peptide self-assembly is fast evolving into a powerful method for the development of bio-inspired nanomaterials with great potential for many applications, but it remains challenging to control the self-assembling processes and nanostrucutres because of the intricate interplay of various non-covalent interactions. A group of 28-residue α-helical peptides is designed including NN, NK, and HH that display distinct hierarchical events. The key of the design lies in the incorporation of two asparagine (Asn) or histidine (His) residues at the a positions of the second and fourth heptads, which allow one sequence to pack into homodimers with sticky ends through specific interhelical Asn-Asn or metal complexation interactions, followed by their longitudinal association into ordered nanofibers. This is in contrast to classical self-assembling helical peptide systems consisting of two complementary peptides. The collaborative roles played by the four main non-covalent interactions, including hydrogen-bonding, hydrophobic interactions, electrostatic interactions, and metal ion coordination, are well demonstrated during the hierarchical self-assembling processes of these peptides. Different nanostructures, for example, long and short nanofibers, thin and thick fibers, uniform metal ion-entrapped nanofibers, and polydisperse globular stacks, can be prepared by harnessing these interactions at different levels of hierarchy.

Design of Surfactant Tails for Effective Surface Tension Reduction and Micellization in Water and/or Supercritical CO2.

The interfacial properties and water-in-CO2 (W/CO2) microemulsion (µE) formation with double- and novel triple-tail surfactants bearing trimethylsilyl (TMS) groups in the tails are investigated. Comparisons of these properties are made with those for analogous hydrocarbon (HC) and fluorocarbon (FC) tail surfactants. Surface tension measurements allowed for critical micelle concentrations (CMC) and surface tensions at the CMC (γCMC) to be determined, resulting in the following trend in surface activity FC > TMS > HC. Addition of a third surfactant tail gave rise to increased surface activity, and very low γCMC values were recorded for the double/triple-tail TMS and HC surfactants. Comparing effective tail group densities (ρlayer) of the respective surfactants allowed for an understanding of how γCMC is affected by both the number of surfactant tails and the chemistry of the tails. These results highlight the important role of tail group chemical structure on ρlayer for double-tail surfactants. For triple-tail surfactants, however, the degree to which ρlayer is affected by tail group architecture is harder to discern due to formation of highly dense layers. Stable W/CO2 µEs were formed by both the double- and the triple-tail TMS surfactants. High-pressure small-angle neutron scattering (HP-SANS) has been used to characterize the nanostructures of W/CO2 µEs formed by the double- and triple-tail surfactants, and at constant pressure and temperature, the aqueous cores of the microemulsions were found to swell with increasing water-to-surfactant ratio (W0). A maximum W0 value of 25 was recorded for the triple-tail TMS surfactant, which is very rare for nonfluorinated surfactants. These data therefore highlight important parameters required to design fluorine-free environmentally responsible surfactants for stabilizing W/CO2 µEs.

Water-in-CO2 Microemulsions Stabilized by an Efficient Catanionic Surfactant.

To facilitate potential applications of water-in-supercritical CO2 microemulsions (W/CO2 µEs) efficient and environmentally responsible surfactants are required with low levels of fluorination. As well as being able to stabilize water-CO2 interfaces, these surfactants must also be economical, prevent bioaccumulation and strong adhesion, deactivation of enzymes, and be tolerant to high salt environments. Recently, an ion paired catanionic surfactant with environmentally acceptable fluorinated C6 tails was found to be very effective at stabilizing W/CO2 µEs with high water-to-surfactant molar ratios (W0) up to ∼50 (Sagisaka, M.; et al. Langmuir 2019, 35, 3445-3454). As the cationic and anionic constituent surfactants alone did not stabilize W/CO2 µEs, this was the first demonstration of surfactant synergistic effects in W/CO2 microemulsions. The aim of this new study is to understand the origin of these intriguing effects by detailed investigations of nanostructure in W/CO2 microemulsions using high-pressure small-angle neutron scattering (HP-SANS). These HP-SANS experiments have been used to determine the headgroup interfacial area and volume, aggregation number, and effective packing parameter (EPP). These SANS data suggest the effectiveness of this surfactant originates from increased EPP and decreased hydrophilic/CO2-philic balance, related to a reduced effective headgroup ionicity. This surfactant bears separate C6F13 tails and oppositely charged headgroups, and was found to have a EPP value similar to that of a double C4F9-tail anionic surfactant (4FG(EO)2), which was previously reported to be one of most efficient stabilizers for W/CO2 µEs (maximum W0 = 60-80). Catanionic surfactants based on this new design will be key for generating superefficient W/CO2 µEs with high stability and water solubilization.

Time-resolved small-angle neutron scattering studies of the thermally-induced exchange of copolymer chains between spherical diblock copolymer nanoparticles prepared via polymerization-induced self-assembly.

Sterically-stabilized diblock copolymer nanoparticles (a.k.a. micelles) are prepared directly in non-polar media via polymerization-induced self-assembly (PISA). More specifically, a poly(lauryl methacrylate) chain transfer agent is chain-extended via reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of methyl methacrylate (MMA) to form sterically-stabilized spheres at 20% w/w solids in n-dodecane at 90 °C. Both fully hydrogenous (PLMA39-PMMA55 and PLMA39-PMMA94) and core-deuterated (PLMA39-d8PMMA57 and PLMA39-d8PMMA96) spherical nanoparticles with mean core diameters of approximately 20 nm were prepared using this protocol. After diluting each dispersion in turn to 1.0% w/w with n-dodecane, small-angle X-ray scattering studies confirmed essentially no change in spherical nanoparticle diameter after thermal annealing at 150 °C. Time-resolved small angle neutron scattering was used to examine whether copolymer chain exchange occurs between such nanoparticles at elevated temperatures. Copolymer chain exchange for a binary mixture of PLMA39-PMMA55 and PLMA39-d8PMMA57 nanoparticles produced hybrid (mixed) cores containing both PMMA55 and d8PMMA57 blocks within 3 min at 150 °C. In contrast, a binary mixture of PLMA39-PMMA94 and PLMA39-d8PMMA96 nanoparticles required 8 min at this temperature before no further reduction in neutron scattering intensity could be observed. These observations suggest that the rate of copolymer chain exchange depends on the degree of polymerization of the core-forming block. Relatively slow copolymer chain exchange was also observed at 80 °C, which is below the Tg of the core-forming PMMA block as determined by DSC studies. These observations confirm rapid exchange of individual copolymer chains between sterically-stabilized nanoparticles at elevated temperature. The implications of these findings are briefly discussed in the context of PISA, which is a powerful technique for the synthesis of sterically-stabilized nanoparticles.

Highly branched triple-chain surfactant-mediated electrochemical exfoliation of graphite to obtain graphene oxide: colloidal behaviour and application in water treatment.

The generation of surfactant-assisted exfoliated graphene oxide (sEGO) by electrochemical exfoliation is influenced by the presence of surfactants, and in particular the hydrophobic tail molecular-architecture. Increasing surfactant chain branching may improve the affinity for the graphite surfaces to provide enhanced intersheet separation and stabilisation of exfoliated sheets. The resulting sEGO composites can be readily used to remove of a model pollutant, the dye, methylene blue (MB), from aqueous solutions by providing abundant sites for dye adsorption. This article explores relationships between surfactant structure and the performance of sEGO for MB adsorption. Double-branched and highly branched triple-chain graphene-compatible surfactants were successfully synthesised and characterised by 1H NMR spectroscopy. These surfactants were used to produce sEGO via electrochemical exfoliation of graphite, and the sEGOs generated were further utilised in batch adsorption studies of MB from aqueous solutions. The properties of these synthesised surfactants were compared with those of a common single-chain standard surfactant, sodium dodecyl-sulfate (SDS). The structural morphology of sEGO was assessed using Raman spectroscopy and field emission scanning electron microscopy (FESEM). To reveal the links between the hydrophobic chain structure and the sEGO adsorption capacity, UV-visible spectroscopy, zeta potential, and air-water (a/w) surface tension measurements were conducted. The aggregation behaviour of the surfactants was studied using small-angle neutron scattering (SANS). The highly branched triple-chain surfactant sodium 1,4-bis(neopentyloxy)-3-(neopentylcarbonyl)-1,4-dioxobutane-2-sulfonate (TC14) displayed enhanced exfoliating efficiency compared to those of the single-and double-chain surfactants, leading to ∼83% MB removal. The findings suggest that highly branched triple-chain surfactants are able to offer more adsorption sites, by expanding the sEGO interlayer gap for MB adsorption, compared to standard single-chain surfactants.

Multicore Liquid Perfluorocarbon-Loaded Multimodal Nanoparticles for Stable Ultrasound and 19F MRI Applied to In Vivo Cell Tracking.

Ultrasound is the most commonly used clinical imaging modality. However, in applications requiring cell-labeling, the large size and short active lifetime of ultrasound contrast agents limit their longitudinal use. Here, 100 nm radius, clinically applicable, polymeric nanoparticles containing a liquid perfluorocarbon, which enhance ultrasound contrast during repeated ultrasound imaging over the course of at least 48 h, are described. The perfluorocarbon enables monitoring the nanoparticles with quantitative 19F magnetic resonance imaging, making these particles effective multimodal imaging agents. Unlike typical core-shell perfluorocarbon-based ultrasound contrast agents, these nanoparticles have an atypical fractal internal structure. The nonvaporizing highly hydrophobic perfluorocarbon forms multiple cores within the polymeric matrix and is, surprisingly, hydrated with water, as determined from small-angle neutron scattering and nuclear magnetic resonance spectroscopy. Finally, the nanoparticles are used to image therapeutic dendritic cells with ultrasound in vivo, as well as with 19F MRI and fluorescence imaging, demonstrating their potential for long-term in vivo multimodal imaging.

Water-in-CO2 Microemulsions Stabilized by Fluorinated Cation-Anion Surfactant Pairs.

High-water-content water-in-supercritical CO2 (W/CO2) microemulsions are considered to be green, universal solvents, having both polar and nonpolar domains. Unfortunately, these systems generally require environmentally unacceptable stabilizers like long and/or multifluorocarbon-tail surfactants. Here, a series of catanionic surfactants having more environmentally friendly fluorinated C4-C6 tails have been studied in terms of interfacial properties, aggregation behavior, and solubilizing power in water and/or CO2. Surface tensions and critical micelle concentrations of these catanionic surfactants are, respectively, lowered by ∼9 mN/m and 100 times than those of the constituent single fluorocarbon-tail surfactants. Disklike micelles in water were observed above the respective critical micelle concentrations, implying the catanionic surfactants have a high critical packing parameter, which should be suitable for the formation of reverse micelles. Based on visual observation of phase behavior and Fourier transform infrared spectroscopic and small-angle neutron scattering studies, one of the three catanionic surfactants tested was found to form transparent single-phase W/CO2 microemulsions with a water-to-surfactant molar ratio of up to ∼50. This is the first successful demonstration of the formation of W/CO2 microemulsions by synergistic ion-pairing of anionic and cationic single-tail surfactants. This indicates that catanionic surfactants offer a promising approach to generate high-water-content W/CO2 microemulsions.

In Situ Monitoring of Latex Film Formation by Small-Angle Neutron Scattering: Evolving Distributions of Hydrophilic Stabilizers in Drying Colloidal Films.

The distribution of hydrophilic species, such as surfactants, in latex films is of critical importance for the performance of adhesives, coatings, and inks, among others. However, the evolution of this distribution during the film formation process and in the resulting dried films remains insufficiently elucidated. Here, we present in situ (wet) and ex situ (dry) small-angle neutron scattering (SANS) experiments that follow the film formation of two types of latex particles, which differ in their stabilizer: either a covalently bonded poly(methacrylic acid) (PMAA) segment or a physically adsorbed surfactant (sodium dodecyl sulfate, SDS). By fitting the experimental SANS data and combining with gravimetry experiments, we have ascertained the hydrophilic species distribution within the drying film and followed its evolution by correlating the size and shape of stabilizer clusters with the drying time. The evolution of the SDS distribution over drying time is being driven by a reduction in the interfacial free energy. However, the PMAA-based stabilizer macromolecules are restricted by their covalent bonding to core polymer chains and hence form high-surface area disclike phases at the common boundary between particles and PMAA micelles. Contrary to an idealized view of film formation, PMAA does not remain in the walls of a continuous honeycomb structure. The results presented here shed new light on the nanoscale distribution of hydrophilic species in drying and ageing latex films. We provide valuable insights into the influence of the stabilizer mobility on the final structure of latex films.

On the Mechanical Properties of N-Functionalised Dipeptide Gels.

The properties of a hydrogel are controlled by the underlying network that immobilizes the solvent. For gels formed by the self-assembly of a small molecule, it is common to show the primary fibres that entangle to form the network by microscopy, but it is difficult to access information about the network. One approach to understand the network is to examine the effect of the concentration on the rheological properties, such that G'∝ cx, where G' is the storage modulus and c is the concentration. A number of reports link the exponent x to a specific type of network. Here, we discuss a small library of gels formed using functionalized dipeptides, and describe the underlying networks of these gels, using microscopy, small angle scattering and rheology. We show that apparently different networks can give very similar values of x.

Glycerol Solvates DPPC Headgroups and Localizes in the Interfacial Regions of Model Pulmonary Interfaces Altering Bilayer Structure.

The inclusion of glycerol in formulations for pulmonary drug delivery may affect the bioavailability of inhaled steroids by retarding their transport across the lung epithelium. The aim of this study was to evaluate whether the molecular interactions of glycerol with model pulmonary interfaces provide a biophysical basis for glycerol modifying inhaled drug transport. Dipalmitoylphosphatidylcholine (DPPC) monolayers and liposomes were used as model pulmonary interfaces, in order to examine the effects of bulk glycerol (0-30% w/w) on their structures and dynamics using complementary biophysical measurements and molecular dynamics (MD) simulations. Glycerol was found to preferentially interact with the carbonyl groups in the interfacial region of DPPC and with phosphate and choline in the headgroup, thus causing an increase in the size of the headgroup solvation shell, as evidenced by an expansion of DPPC monolayers (molecular area increased from 52 to 68 Å2) and bilayers seen in both Langmuir isotherms and MD simulations. Both small angle neutron scattering and MD simulations indicated a reduction in gel phase DPPC bilayer thickness by ∼3 Å in 30% w/w glycerol, a phenomenon consistent with the observation from FTIR data, that glycerol caused the lipid headgroup to remain oriented parallel to the membrane plane in contrast to its more perpendicular conformation adopted in pure water. Furthermore, FTIR measurements suggested that the terminal methyl groups of the DPPC acyl chains were constrained in the presence of glycerol. This observation is supported by MD simulations, which predict bridging between adjacent DPPC headgroups by glycerol as a possible source of its putative membrane stiffening effect. Collectively, these data indicate that glycerol preferentially solvates DPPC headgroups and localizes in specific areas of the interfacial region, resulting in structural changes to DPPC bilayers which may influence cell permeability to drugs.

Systematic study of the structural parameters affecting the self-assembly of cyclic peptide-poly(ethylene glycol) conjugates.

Self-assembling cyclic peptides (CP) consisting of amino acids with alternating d- and l-chirality form nanotubes by hydrogen bonding, hydrophobic interactions, and π-π stacking in solution. These highly dynamic materials are emerging as promising supramolecular systems for a wide range of biomedical applications. Herein, we discuss how varying the polymer conformation (linear vs. brush), as well as the number of polymer arms per peptide unimer affects the self-assembly of PEGylated cyclic peptides in different solvents, using small angle neutron scattering. Using the derived information, strong correlations were drawn between the size of the aggregates, solvent polarity, and its ability to compete for hydrogen bonding interactions between the peptide unimers. Using these data, it could be possible to engineer cyclic peptide nanotubes of a controlled length.

Alternative Route to Nanoscale Aggregates with a pH-Responsive Random Copolymer.

A random copolymer, poly(methyl methacrylate-co-2-dimethylaminoethyl methacrylate) (poly(MMA-co-DMAEMA)) is shown to form nanoscale aggregates (NAs) (∼20 nm) at copolymer concentrations ≥10% w/w, directly from the preformed surfactant-stabilized latex (∼120 nm) in aqueous solution. The copolymer is prepared by conventional emulsion polymerization. Introducing a small mole fraction of DMAEMA (∼10%) allows the copolymer hydrophilicity to be adjusted by the pH and external temperature, generating NAs with tuneable sizes and a defined weight-average aggregation number, as observed by dynamic light scattering (DLS) and small-angle neutron scattering (SANS). These NAs are different from the so-called mesoglobular systems and are insensitive to temperature at fixed pH. The relatively broad chemical composition distribution of the copolymer and lumpy (or blocky but not diblock) incorporation of DMAEMA mean that the NAs cannot be simply thought of as conventional polymer micelles. In the acidic pH regime, the amphiphilic copolymer exhibits a defined critical assembly concentration (CAC) and a minimum air-water surface tension of 45.2 mN m-1. This copolymer represents a convenient route to self-assembled NAs, which form directly in aqueous dispersions after pH and temperature triggers, rather than the typically applied (and time-consuming) water-induced micellization approach for common polymer micelles.