Preferential solubilization of dodecanol from dodecanol-limonene binary oil mixture in sodium dihexyl sulfosuccinate microemulsions: effect on optimum salinity and oil solubilization capacity

Solubilization of dodecanol-limonene binary oil mixtures has been studied in saturated Winsor type I and III sodium dihexyl sulfosuccinate microemulsions. The systems showed different oil solubilization behavior below and above dodecanol volume fraction 0.2. Below 0.2 dodecanol volume fraction regular Winsor type microemulsions formed. The oil solubilization was characterized in this concentration range by the optimum salinity and the maximum characteristic length. Dodecanol showed Langmuirian-type surface excess adsorption at the vicinity of the surfactant layer. Variation of the optimum salinity and middle phase characteristic length with increasing dodecanol concentration could be linked to changes in the dodecanol surface excess. These relationships were used to develop new mathematical models for the optimum salinity and characteristic length as a function of oil phase composition. Both models yield excellent agreement with the data. Above dodecanol volume fraction 0.2 regular Winsor type III microemulsions are not formed. Therefore our new models are not applicable in this concentration range.     

Characterization of nanochannel delivery membrane systems for the sustained release of resveratrol and atorvastatin: new perspectives on promoting heart health

Novel drug delivery systems capable of continuous sustained release of therapeutics have been studied extensively for use in the prevention and management of chronic diseases. The use of these systems holds promise as a means to achieve higher patient compliance while improving therapeutic index and reducing systemic toxicity. In this work, an implantable nanochannel drug delivery system (nDS) is characterized and evaluated for the long-term sustained release of atorvastatin (ATS) and trans-resveratrol (t-RES), compounds with a proven role in managing atherogenic dyslipidemia and promoting cardioprotection. The primary mediators of drug release in the nDS are nanofluidic membranes with hundreds of thousands of nanochannels (up to 100,000/mm²) that attain zero-order release kinetics by exploiting nanoconfinement and molecule-to-surface interactions that dominate diffusive transport at the nanoscale. These membranes were characterized using gas flow analysis, acetone diffusion, and scanning and transmission electron microscopy (SEM, TEM). The surface properties of the dielectric materials lining the nanochannels, SiO₂ and low-stress silicon nitride, were further investigated using surface charge analysis. Continuous, sustained in vitro release for both ATS and t-RES was established for durations exceeding 1 month. Finally, the influence of the membranes on cell viability was assessed using human microvascular endothelial cells. Morphology changes and adhesion to the surface were analyzed using SEM, while an MTT proliferation assay was used to determine the cell viability. The nanochannel delivery approach, here demonstrated in vitro, not only possesses all requirements for large-scale high-yield industrial fabrication, but also presents the key components for a rapid clinical translation as an implantable delivery system for the sustained administration of cardioprotectants.     

Enantioselective synthesis of gabapentin analogues via organocatalytic asymmetric Michael addition of α-branched aldehydes to β-nitroacrylates

Michael addition reaction of α-branched aldehydes to β-nitroacrylates was successfully carried out by using a mixed catalyst consisting of a primary amino acid, L-phenylalanine, and its lithium salt to give β-formyl-β'-nitroesters having a quaternary carbon centre in good yields (up to 85%) with high enantioselectivity (up to 98% ee). By using benzyl β-nitroacrylates as Michael acceptors, the obtained β-formyl-β'-nitroesters were converted into various 4,4-disubstituted pyrrolidine-3-carboxylic acids including analogues of gabapentin (Neurotin(?)) in one step from the Michael adducts in high yields.     

Prins-type macrocyclizations as an efficient ring-closing strategy in natural product synthesis

Prins-type macrocyclizations have recently emerged as a successful strategy in the synthesis of polyketide-derived natural products. This reaction provides a concise and selective means to form tetrahydropyran-containing macrocyclic rings of varying size. A high degree of functionality within the macrocycle is tolerated and the yields for these transformations are typically good to excellent. Since the initial report of a Prins macrocyclization reaction in 1979, examples of this approach did not re-emerge until 2008. However, the use of this method in natural product synthesis has rapidly gained momentum in the synthetic community, with multiple examples of this macrocyclization tactic reported in the recent literature.     

Synthesis and cytotoxicity of 28-carboxymethoxy lupane triterpenoids. Preference of 28-O-acylation over 28-O-alkylation of betulin by ethyl bromoacetate

28-Carboxymethoxy lupane tritepenoids 3 and 4 were synthesized by alkylation of betulin with the THP protected 2-hydroxyethyl iodide followed by oxidation and reduction.Direct reaction of betulin (5) or betulone (10) with ethyl bromoacetate led to 28-O-acylation, instead of 28-O-alkylation.The targeted compounds 3 and 4 were not cytotoxic at the highest concentrationtested (75 mmol/L), suggesting that elongation of the chain length at the 28-position in both betulinic acid (1) and betulonic acid (2)was detrimental to the cytotoxicity.The acylation products 28-O-bromoacetates (8a, 8b and 11) and 28-O-methoxyacetate 13exhibited cytotoxicity against several cancer cell lines tested.     

Py-GC/MS, GC/MS and FTIR investigations on LATE Roman-Egyptian adhesives from opus sectile: New insights into ancient recipes and technologies

An analytical protocol based on optical microscopy, Fourier transforms infrared spectroscopy (FTIR), analytical pyrolysis in the presence of hexamethyldisilazane followed by gas chromatographic/mass spectrometric analysis (Py-GC/MS) and gas chromatography/mass spectrometry after alkaline hydrolysis, solvent extraction and trimethylsilylation (GC/MS) was used in the chemical characterisation of the original adhesives used to fix monochrome and mosaic glass and stone plaques coming from the Late Roman archaeological site of Antinoopolis (Egypt).FTIR analysis demonstrated the presence of calcite fragments, and Py-GC/MS and GC/MS analyses provided detailed molecular compositions, highlighting the presence of a wide range of compound classes including diterpenoid acids, tricyclic abietanes with a high degree of aromatisation, mid- and long-chain monocarboxylic fatty acids, mono- and di-hydroxy acids, α,ω-dicaboxylic fatty acids, n-alkanols, and n-alkanes. Characteristic biomarkers and their distribution patterns indicated the presence of pine pitch in all the adhesives, which in some cases was admixed with beeswax and brassicaceae seed oil.The results provided new insights into the complex recipes used by artisans in ancient Egypt in the production of adhesives and in the sophisticated manufacture of opus sectile decorations.     

Double-layer capacitance of waste coffee ground activated carbons in an organic electrolyte

Using ZnCl₂ activation we prepared a series of carbon electrodes from waste coffee grounds to study the effect of mesopores on double-layer capacitance in a tetraethyl ammonium tetrafluoroborate/acetonitrile electrolyte. The activated carbon with the largest mesopore volume achieved an energy density of 34 Wh kg^?1 at low current loads, and significantly retained an energy density of 16.5 Wh kg^?1 and specific capacitance of more than 100 F g^?1 at fast charge–discharge rates (20 A g^?1). The effect of mesopores on capacitance at fast charge–discharge rates is discussed.     

Multienzymatic preparation of 3-[(1R)-1-hydroxyethyl]benzoic acid and (2S)-hydroxy(phenyl)ethanoic acid

The use of two oxidoreductases (an aldoketo reductase from Escherichia coli JM109 and an alcohol dehydrogenase from Lactobacillus brevis) has demonstrated that it is possible to prepare enatiomerically pure diols in a one-pot operation. The reactions were applied to the synthesis of (1R)-1-[3-(hydroxymethyl)phenyl]ethanol and (1S)-1-phenylethane-1,2-diol, using a two-step procedure. The yield is nearly quantitative and the enantiomeric purity is greater than 95%. A third step has been introduced by adding a cell biocatalyst showing dihydrodiol dehydrogenase activity from Pseudomonas fluorescens N3. This allows for the preparation of 3-[(1R)-1-hydroxyethyl]benzoic acid and (2S)-hydroxy(phenyl)ethanoic acid.     

Targeting cell surface receptors with ligand-conjugated nanocrystals

To explore the potential for use of ligand-conjugated nanocrystals to target cell surface receptors, ion channels, and transporters, we explored the ability of serotonin-labeled CdSe nanocrystals (SNACs) to interact with antidepressant-sensitive, human and Drosophila serotonin transporters (hSERT, dSERT) expressed in HeLa and HEK-293 cells. Unlike unconjugated nanocrystals, SNACs were found to dose-dependently inhibit transport of radiolabeled serotonin by hSERT and dSERT, with an estimated half-maximal activity (EC(50)) of 33 (dSERT) and 99 microM (hSERT). When serotonin was conjugated to the nanocrystal through a linker arm (LSNACs), the EC(50) for hSERT was determined to be 115 microM. Electrophysiology measurements indicated that LSNACs did not elicit currents from the serotonin-3 (5HT(3)) receptor but did produce currents when exposed to the transporter, which are similar to those elicited by antagonists. Moreover, fluorescent LSNACs were found to label SERT-transfected cells but did not label either nontransfected cells or transfected cells coincubated with the high-affinity SERT antagonist paroxetine. These findings support further consideration of ligand-conjugated nanocrystals as versatile probes of membrane proteins in living cells.     

Synthesis of the non-reducing end trisaccharide of the antithrombin-binding domain of heparin and its bioisosteric sulfonic acid analogues

A glucoronic acid-containing trisaccharide related to the antithrombin-binding DEFGH domain of heparin and its methanesulfonic acid analogues were synthesized. Trisaccharides without sulfonic acid content or possessing a sulfonatomethyl moiety at position 2 or 6 of unit F were prepared in high yields by [DE+F] couplings using the same disaccharide uronate donor, respectively. Synthesis of the trisaccharide with a 3-deoxy-3-sulfonatomethyl function was accomplished in three different pathways, from which a [D+EF] coupling and applying a non-oxidized precursor of the glucuronic acid afforded the trisaccharide in the highest yield.