Fine-tuning of membrane permeability by reversible photoisomerization of aryl-azo derivatives of thymol embedded in lipid nanoparticles.

Responsiveness of liposomes to external stimuli, such as light, should allow a precise spatial and temporal control of release of therapeutic agents or ion transmembrane transport. Here, some aryl-azo derivatives of thymol are synthesized and embedded into liposomes from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine to obtain light-sensitive membranes whose photo-responsiveness, release behaviour, and permeability towards Cl- ions are investigated. The hybrid systems are in-depth characterized by dynamic light scattering, atomic force microscopy and Raman spectroscopy. In liposomal bilayer the selected guests undergo reversible photoinduced isomerization upon irradiation with UV and visible light, alternately. Non-irradiated hybrid liposomes retain entrapped 5(6)-carboxyfluorescein (CF), slowing its spontaneous leakage, whereas UV-irradiation promotes CF release, due to guest trans-to-cis isomerization. Photoisomerization also influences membrane permeability towards Cl- ions. Data processing, according to first-order kinetics, demonstrates that Cl- transmembrane transport is enhanced by switching the guest from trans to cis but restored by back-switching the guest from cis to trans upon illumination with blue light. Finally, the passage of Cl- ions across the bilayer can be fine-tuned by irradiation with light of longer λ and different light-exposure times. Fine-tuning the photo-induced structural response of the liposomal membrane upon isomerization is a promising step towards effective photo-dynamic therapy.

First Evidence of the Double-Bond Formation by Deoxydehydration of Glycerol and 1,2-Propanediol in Ionic Liquids.

Deoxydehydration (DODH) reaction of glycerol (GL) and 1,2-propanediol (1,2-PD), in ionic liquids (ILs), catalyzed by methyltrioxorhenium (MTO) and Re2O7, was studied in detail. To better understand the ability of ILs to improve the catalytic performance of the rhenium catalyst, several experiments, employing eight different cations and two different anions, were carried out. Among the anions, bis(trifluoromethylsulfonyl)imide (TFSI) appears to be more appropriate than PF6 -, for its relatively lower volatility of the resulting IL. Regarding the choice of the most appropriate cation, the presence of a single aromatic ring seems to be a necessary requirement for a satisfying and convenient reactivity. With the aim to extend the recyclability of the catalyst, experiments involving the readdition of polyol to the terminal reaction mixture were carried out. Worthy of interest is the fact that the presence of the IL prevents the inertization process of the catalyst, allowing us to obtain the alkene also after a readdition of fresh polyol.

Umbelliprenin as a novel component of the phytochemical pool from Artemisia spp.

Plants belonging to Artemisia spp. are known to biosynthesize a wide panel of 3,3-dimethylallyl- and sesquiterpenyl- substituted coumarins. In this short communication we applied a novel extraction methodology based on the use of subcritical butane under a counter-current mode to further characterize the presence of selected biologically active oxyprenylated phenylpropanoids, namely coumarins and ferulic acid derivatives, in extracts deriving from aerial parts of Artemisia vulgaris L. (commonly known as "common mugwort") (Asteraceae). In the mean time, we assessed the efficiency of the above mentioned extractive methodology with other routes like maceration and ultrasounds and microwaves-based methods using absolute EtOH as the solvents. UHPLC analysis coupled to UV/Vis detection revealed that, among the 5 pure chemical standard assayed, only umbelliprenin (7-farnesyloxycoumarin) was recorded, while boropinic acid, 4'-geranyloxyferulic acid, 7-isopentenyloxycoumarin, and auraptene were not detected. The best extractive yield (0.18 %) was obtained after extaction with subcritical butane. The presence of umbelliprenin in Artemisia plant species has been reported herein for the first time. This coumarin may represent the biosynthetic precursors of sesquiterpenyloxycoumarins with more complex structures typically found in this genus.

A novel and efficient subcritical butane extraction method and UHPLC analysis of oxyprenylated phenylpropanoids from grapefruits peels.

Biologically active prenyoxyphenylpropanoids are well known to be biosynthesized by Citrus species, for which they have been found most abundantly in fruit peels. Although several extraction methodologies have been described, the development of novel and alternative extraction processes is a field of research of current interest. In this preliminary communication, we studied the performance of the subcritical butane promoted extraction of selected oxyprenylated phenylpropanoids from grapefruit peels under a counter-current mode using a handmade extraction apparatus coupled to UHPLC analysis. The application of such a method yielded 7-isopentenyloxycoumarin, auraptene, and boropinic acid in quantities higher than those recorded for other extraction methodologies like the ultrasound- and microwave-assisted macerations (0.234, 1.035, and 0.211 mg/g of dry extract respectively). The use of subcritical butane as the extraction solvent for oxyprenylated phenylpropanoids is reported herein for the first time and can be easily adopted for several other food matrices.

Water capacity and size data of reverse micelles formed by novel cationic surfactants.

This paper contains data of water capacity (in terms of w 0  = molwater/molsurfactant) in reverse micelles formed by several commercial and non-commercial cationic surfactants in cyclopentane, petroleum ether, and iso-octane. Also reported are hydrodynamic diameters of the respective reverse micelles formed. Tested surfactants were (i) single-chained cationics: cetyl benzyl diethanolammonium bromide (CBDB), cetyl benzyl dimethylammonium bromide (CBMB), cetyl dibutyl ethanolammonium bromide (CDBEB), cetyl cyclohexyl dimethylammonium bromide (CCDB); and (ii) twin-chained cationics: didodecyl dimethylammonium chloride (DDMC), didodecyl diethylammonium bromide (DDEB), didodecyl dipropylammonium bromide (DDPB), didodecyl diethylammonium chloride (DDEC), dodecyl benzyl dimethylammonium bromide (DBDMB). Also reported are sizes of reverse micelles as determined by dynamic light scattering.

Embedding calix[4]resorcinarenes in liposomes: Experimental and computational investigation of the effect of resorcinarene inclusion on liposome properties and stability.

Two calix[4]resorcinarenes, which differ in the length of the alkyl chain on the methylene bridge between the aromatic rings, have been embedded in unilamellar liposomes prepared from 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine in three host/guest ratios, following two different procedures. The effect of the insertion of the guests has been evaluated through the measurements of the viscosity and the kinetic stability of the liposomal systems by means of the fluorescent probes pyrene and 5(6)-carboxyfluorescein. The presence of the guests reduces the viscosity of the liposomes, suggesting a modification of the bilayer structure. However, this does not affect liposome stability. A calix[4]resorcinarene cavitand with a more rigid conformation compared to the parent resorcinarene, has been also synthetized and embedded in liposomes. The free energy of the insertion of the substrates in the lipid bilayer has been evaluated through Molecular Dynamics simulations.

Graphene Oxide Foils as an Osteoinductive Stem Cell Substrate.

The hydrophilic graphene derivative, graphene oxide (GO), is used to synthesize free-standing GO foils characterized by cross-linked GO sheets with enhanced mechanical properties and no tendency to release GO flakes in aqueous solution. These GO foils do not evidence cytotoxic effects toward dental pulp stem cells (DPSC). Rather, DPSC viability is significantly increased for cells grown on GO foil and SEM analyses evidence the synthesis of a consistent extracellular matrix by DPSCs with respect to cells grown on polystyrene. Gene expression of osteogenic markers and alkaline phosphatase (ALP) activity tests demonstrate DPSC differentiation toward the osteoblastic lineage. Indeed RUNX2, a key transcriptor factor associated with osteogenic differentiation, as well as SP7, responsible for triggering bone matrix mineralization, are significantly augmented after 7 and 14 days of culture on GO foil with respect to the control, respectively, underlying the capability of GO foil to promote a potential faster and better DPSC differentiation with respect to cells grown on polystyrene. This increase of rate differentiation is confirmed by SEM analyses of DPSCs evidencing a consistent extracellular matrix synthesis at the earliest time of culture (i.e., 3 and 14 days).

Reverse micelles enhance the formation of clathrate hydrates of hydrogen.

HYPOTHESIS: Clathrate hydrates of hydrogen form at relatively low pressures (e.g., ca. 10 MPa) when a co-former compound is added. In that case, however, the gravimetric amount of stored hydrogen drops to less than 1 wt% from ca. 5.6 wt% without a co-former. Another factor hindering the entrapment of hydrogen into a clathrate matrix appears to be of a kinetic origin, in that the mass transfer of hydrogen into clathrates is limited by the macroscopic scale of the gas-water interfaces involved in their formation. Thus, the enhanced formation of binary (hydrogen + co-former) hydrates would represent a major achievement in the attempt to exploit those materials as a convenient means for storing hydrogen. EXPERIMENTS: Here, we present a simple process for the enhanced formation of binary hydrates of hydrogen and several co-formers, which is based on the use of reverse micelles for reducing the size of hydrate-forming gas-water interfaces down to tens of nanometers. This reduction of particle size allowed us to reduce the kinetic hindrance to hydrate formation. FINDINGS: The present process was able to (i) enhance the kinetics of the formation process; and (ii) assist clathrate formation when using water-insoluble coformers (e.g., cyclopentane, tetrahydrothiophene).

Optimizing the Interactions of Surfactants with Graphitic Surfaces and Clathrate Hydrates.

Surfactants are amphiphilic molecules active at the surface/interface and able to self-assemble. Because of these properties, surfactants have been extensively used as detergents, emulsifiers, foaming agents, and wetting agents. New perspectives have been opened by the exploitation of surfactants for their capacity to interact as well with simple molecules or surfaces. This feature article gives an overview of significant contributions in the panorama of the current research on surfactants, partly accomplished as well by our research group. We look at several recent applications (e.g., adsorption to graphitic surfaces and interactions with hydrate crystals) with the eye of physical organic chemists. We demonstrate that, from the detailed investigation of the forces involved in the interactions with hydrophobic surfaces, it is possible to optimize the design of the surfactant that is able to form a stable and unbundled carbon nanotube dispersion as well as the best exfoliating agent for graphitic surfaces. By studying the effect of different surfactants on the capacity to favor or disfavor the formation of a gas hydrate, it is possible to highlight the main features that a surfactant should possess in order to be devoted to that specific application.

Thermodynamic analysis of anion and cation effects on the keto-enol equilibrium in ionic liquids. A comparative study with conventional solvents.

A comparative thermodynamic investigation of the keto-enol interconversion reaction has been performed in several organic solvents and room-temperature ionic liquids (RTILs) to evaluate the role of the solvent and the effect of the ionic composition of RTILs. The tautomeric constant (KT) values at different temperatures have been analyzed in terms of the van't Hoff relationship to give the relevant thermodynamic parameters. The ΔG° values are the results of quite different combinations of the ΔH° and ΔS° values depending on the nature of the solvent. As expected, in conventional solvents, the tautomeric equilibrium is enthalpically disfavored and entropically favored by the increase in solvent polarity. In ionic liquids, the nature of the anion seems to play a primary role in the thermodynamics of the reaction that is endothermic and enthalpically driven in PF6- and TF2N-based RTILs and exothermic but entropically driven in BF4-based RTILs. The cation effect on the thermodynamics of the reaction is more complex and is consistent with a prevalence of the alkyl side chain segregation in the organization of the ILs.

Dispersion of SWCNTs with imidazolium-rich surfactants.

Starting from previous evidence on the crucial role of imidazolium ions, long alkyl chains, and aromatic rings in favoring the adsorption of surfactants onto carbon nanotube (CNT) walls, we have synthesized novel gemini surfactants with the aim to optimize and identify a reference structure for CNT dispersants. The efficiency of the novel surfactants has been evaluated, discussed, and compared with already well-investigated dispersants. The good affinity of the surfactants for the CNT sidewalls is highlighted by the presence of resonant van Hove absorption and highly resolved Raman and fluorescence spectra, while the strong hydrophobic interactions and favorable packing between the two alkyl chains of the investigated gemini surfactants and the CNT sidewalls ensure good CNT dispersion. Our results show no selectivity toward specific diameters/chiralities, confirming the twin heads of imidazolium surfactants are pointed toward the bulk water, while the alkyl chains are arranged on the CNT walls, improving water solubility at the expense of potential selectivity.

Surfactant hydrogels for the dispersion of carbon-nanotube-based catalysts.

Novel hydrogel phases based on positively charged and zwitterionic surfactants, namely, N-[p-(n-dodecyloxybenzyl)]-N,N,N-trimethylammonium bromide (pDOTABr) and p-dodecyloxybenzyldimethylamine oxide (pDOAO), which combine pristine carbon nanotubes (CNTs), were obtained, thus leading to stable dispersions and enhanced cross-linked networks. The composite hydrogel featuring a well-defined nanostructured morphology and an overall positively charged surface was shown to efficiently immobilise a polyanionic and redox-active tetraruthenium-substituted polyoxometalate (Ru4POM) by complementary charge interactions. The resulting hybrid gel has been characterised by electron microscopy techniques, whereas the electrostatic-directed assembly has been monitored by means of fluorescence spectroscopy and ζ-potential tests. This protocol offers a straightforward supramolecular strategy for the design of novel aqueous-based electrocatalytic soft materials, thereby improving the processability of CNTs while tuning their interfacial decoration with multiple catalytic domains. Electrochemical evidence confirms that the activity of the catalyst is preserved within the gel media.

Deracemization of bilirubin as the marker of the chirality of micellar aggregates.

The deracemization of bilirubin in micellar aggregates of structurally correlated chiral surfactants was studied by circular dichroism experiments and exploited as the marker of the expression of chirality of the aggregates. The obtained results suggest that the hydrophobic interactions control the transfer of chirality from the monomers to the aggregates, and that different regions of the same aggregate might feature opposite enantiorecognition capabilities.

Effect of head group size, temperature and counterion specificity on cationic micelles.

The critical micelle concentration (cmc) and ionisation degree (α), of micelles of cetyltrimethylammonium bromide (CTABr), cetyltrimethylammonium chloride (CTACl), cetyltripropylammonium bromide (CTPABr) and cetyltripropylammonium chloride (CTPACl) have been measured over a narrow temperature range at 2 degree intervals using electrical conductivity. CTPACl and CTPABr are very soluble in water and were measured in the temperature range 275.15-323.15K. The Krafft temperatures for CTABr and for CTACl are 293.15K and 284.15K, respectively and established a lower temperature limit for our studies on these two surfactants. The cmc vs temperature curves have a smooth minimum near room temperature and α linearly increases with temperature. The changes of cmc and α with temperature are smaller than those associated with the modification of head group size or counterion nature. Using these results, basic thermodynamic quantities associated with the phenomena of micellization have been evaluated. Thermodynamic properties of the surfactant solutions were discussed in terms of temperature dependence of the free energy, enthalpy and entropy of micellization. A close similarity between the effects of change in temperature on protein folding and micellization process appears from the data.

Influence of lipid composition on the thermotropic behavior and size distribution of mixed cationic liposomes.

Cationic liposomes are studied mainly as nonviral nucleic acid delivery systems and to a lesser extent as carriers/adjuvants of vaccines and as low-molecular-weight drug carriers. It is well established that the performance and the biological activity of liposomes in general are strongly related to their physicochemical properties. We investigated the thermotropic behavior and the size distribution of mixed cationic liposomes formulated with different percentages of 1,2 dimyristoyl-sn-glycero-3-phosphatidylcholine and one of four cationic amphiphiles characterized by a pyrrolidinium headgroup with the aim of achieving a better understanding of how the molecular structure of the cationic amphiphile and its mole percentage affect the physicochemical properties of the liposomes. Multilamellar vesicles and large unilamellar vesicles were studied by differential scanning calorimetry and turbidity, respectively, to characterize the thermotropic behavior and lipid phase, whereas dynamic light scattering was used to determine size distribution. This study shows that subtle modifications in the cationic amphiphile's molecular structure and in liposome composition may have dramatic effects on the organization of the liposome bilayer and hence on the morphological and physicochemical features of the liposomes, thus being highly relevant to the biological features investigated previously.

Interaction between DNA and cationic amphiphiles: a multi-technique study.

The interaction of cationic amphiphiles with calf thymus DNA has been investigated by physicochemical techniques (surface tension, conductometry, UV spectroscopy, thermal denaturation) and morphological microscopies (AFM and TEM). The cationic molecules were the amphiphiles cetyltrimethylammonium and cetyltributylammonium bromides (CTAB and CTBAB, respectively), compared to the nonamphiphilic tetramethyl- and tetrabutylammonium bromides (TMAB and TBAB, respectively) and, as a transfection-efficient comparison, a commercial poliethyleneimine (PEI). As a result, well below their critical micelle concentrations (cmc), CTAB and CTBAB showed a peculiar, nonlinear adsorption profile with the nucleic acid, which showed a correlation with the melting temperatures and morphological changes observed with AFM and TEM microscopies. On the other hand, TMAB and TBAB interact much less with the DNA duplexes and do not induce any modifications of the structures. The same behavior was observed with PEI; however, CTAB and CTBAB proved much less effective in condensing the nucleic acid.

Synthesis of novel 5'-uridine-head amphiphiles as model for DNA molecular recognition.

Here we describe uridine functionalization in the 5' position, which provides new classes of cationic and nonionic amphiphiles specifically designed as DNA transfection agents. The synthetic procedures developed to obtain the cationic uridine-head surfactants prevented intramolecular cyclization that occurs when uridine is functionalized in this position without using protecting groups in the uracil.

Specific anion binding to sulfobetaine micelles and kinetics of nucleophilic reactions.

With fully micellar bound substrates reactions of OH- with benzoic anhydride, Bz(2)O, and of Br- with methyl naphthalene-2-sulfonate, MeONs, in micellized sulfobetaines are strongly inhibited by NaClO4 which displaces the nucleophilic anions from the micellar pseudophases. Micellar incorporations of ClO4- and Br- are estimated with an ion-selective electrode and by electrophoresis, and partitioning of Br- between water and micelles is related to changes in NMR spectral (79)Br- line widths. Extents of inhibition by ClO4- of these nucleophilic reactions in the micellar pseudophase are related to quantitative displacement of the reactive anions from the micelles by ClO4-. The kinetic data are correlated with physical evidence on the strong interactions between sulfobetaines and ClO4-, which turn sulfobetaine micelles anionic and effectively provoke displacement of OH- and Br-.

Premicellar accelerated decarboxylation of 6-nitrobenzisoxazole-3-carboxylate ion and its 5-tetradecyloxy derivative.

Didodecyldialkylammonium chloride and bromide (alkyl = Me, Et, n-Pr, n-Bu) accelerate the spontaneous decarboxylation of 6-nitrobenzisoxazole-3-carboxylate ion, 1,H, and its 5-tetradecyloxy derivative, 1,OTD. With most of these surfactants, first-order rate constants, kobs, go through maxima in very dilute surfactant and then decrease and go through minima as association colloids form. These phenomena are not explicable in terms of substrate-induced micellization. However, kobs increases in the N-alkyl sequence Me < Et < n-Pr < n-Bu, as is typical of decarboxylations in association colloids of single-chain surfactants. Reaction in premicelles is accelerated by an initial increase in 1,H. The factors that control relative rates of spontaneous reactions in premicelles and in the association colloids, in particular, depletion of water at the reaction center and association of substrate and quaternary ammonium centers, are discussed with respect to the roles of substrate and surfactant hydrophobicities.

Role of the spacer stereochemistry on the aggregation properties of cationic gemini surfactants.

The preparation and characterization of three stereoisomeric cationic gemini surfactants, 2,3-dimethoxy-1,4-bis(N-hexadecyl-N,N-dimethylammonio)butane dibromide, are described. The aggregation properties have been studied by fluorescence, electrical conductivity, and quasi-elastic light scattering. A conformational study of the surfactant headgroups has been performed by molecular mechanics calculations to investigate the effect of the stereogenic centers on the surfactant molecular shape and therefore on the different organizations of the monomers in the aggregates. Results show that the stereochemistry of the spacer strongly influences the aggregation behavior of the diasteromeric gemini in water.