Effect of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on surfactant monolayers

In the present study, the effects of an amphiphilic polymer, d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on model surfactant monolayers dipalmitoylphosphatidylcholine (DPPC), a binary mixture of DPPC with palmitoyloleoyl phosphatidylglycerol (DPPC-POPG) 9:1 (w/w) and binary mixture of DPPC and oleic acid (DPPC-OA) were evaluated. The ability of TPGS to act as an antioxidant adjuvant for pulmonary surfactants was also evaluated. Compression isotherms of surfactant monolayers at 37 °C in a Langmuir-Blodgett trough showed that DPPC and DPPC:TPGS mixed monolayers (1:0.25-1:1, w/w) exhibited low minimum surface tensions (MST) of 1-2 mN/m. Similarly [DPPC:POPG (9:1, w/w)]:TPGS mixed films of 1:0.25-1:1 weight ratios reached 1-2 mN/m MST. DPPC:POPG:TPGS liposomes adsorbed to surface tensions of 29-31 mN/m within 1s. While monolayers of DPPC:OA (1:1, w/w) reached high MST of ～11 mN/m, DPPC:OA:TPGS (1:1:0.25, w/w) film reached near zero MST suggesting that low concentrations of TPGS reverses the effect of OA on DPPC monolayer. Capillary surfactometer studies showed DPPC:TPGS and [DPPC:POPG (9:1, w/w)]:TPGS liposomes maintained 84-95% airway patency. Fluorescence spectroscopy of Laurdan loaded DPPC:TPGS and DPPC:POPG:TPGS liposomes revealed no segregation of lipid domains in the lipid bilayer. Addition of TPGS to soybean liposome significantly reduced thiobarbituric acid reactive substance (TBARS) by 29-39% confirming its antioxidant nature. The results suggest a potential use of TPGS as an adjuvant to improve the surfactant activity as well as act as an antioxidant by scavenging free radicals.     

Structure-based study of antiamyloidogenic cyclic d,l-α-peptides

Protein misfolding and aggregation are the hallmarks of many devastating diseases. We have previously shown that cyclic d,l-α-peptide CP-2 reacts and stabilizes less toxic forms of amyloid β (Aβ), and protects the cells from Aβ-induced toxicity. Here, we performed extensive structure-based studies on CP-2 to elucidate the contribution of each residue to the total antiamyloidogenic activity and determine the interactions that are involved between CP-2 and Aβ. We showed that the hydrophobicity of CP-2 analogs correlates with their antiamyloidogenic potency, however, aromatic interactions are even more important for this activity. The antiamyloidogenic activity of CP-2 analogs also correlates with their ability to self-assemble, as shown by the critical micelle concentration measurements. The cell survival studies performed on rat pheochromocytoma PC-12 cells suggest that incorporation of an additional aromatic residue to the CP-2's sequence increases its protective effect against Aβ42-induced toxicity.     

Direct quantification of mono- and di-D-α-tocopherol polyethylene glycol 1000 succinate by high performance liquid chromatography

A simple and direct reversed-phase high performance liquid chromatography (RP-HPLC) method with UV detection was developed and validated for the determination of mono- and di-D-α-tocopherol polyethylene glycol 1000 succinate (TPGS 1000) in TPGS mixture. Before the HPLC analysis, mono- and di-TPGS 1000 were separated by simulated moving bed (SMB) chromatography system and characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The mass spectrometric results confirmed that the molar mass distribution of TPGS prepared in our laboratory was very close to that of the product of Eastman Chemical Company with similar nˉ (average polymerization degree), M(n)ˉ (number-average molecular weight) and M(w)ˉ (weight-average molecular weight). The HPLC analysis was carried out on a C30 analytical column with mobile phases comprised of acetonitrile (A) and isopropanol (B) in gradient conditions. Validation of the analytical method was done on the following parameters: system suitability, linearity, limits of detection and quantification, accuracy and precision, method robustness and solution stability. The linearity of the calibration curves for mono- and di-TPGS 1000 from both sources was found to be good (r(2)>0.9996). The recovery values were from 94.6% to 103.3% for mono-TPGS, and 93.5% to 103.3% for di-TPGS. This method could be successfully used in the direct quantification of mono- and di-TPGS in TPGS 1000 mixture using TPGS standards with similar molecular mass distributions although derived from different sources.     

Surface modification of microporous polypropylene membranes by the grafting of poly(γ-stearyl-l-glutamate)

A polypeptide, poly(γ-stearyl-l-glutamate) (PSLG), was grafted on the surface of hydrophobic polypropylene hollow fiber membranes through the ring opening polymerization of N-carboxyanhydride (NCA) of γ-stearyl-l-glutamate initiated by amino groups which was generated by ammonia plasma. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), together with water contact angle and bovium serum albumin adsorption measurements were used to characterize the modified membrane surface. The XPS and FT-IR spectra demonstrated that polypeptide was actually grafted on the membrane surface despite of the low degree of graft polymerization due to the hydroxyl groups on the membrane surface. To subject the ammonia plasma-treated membrane with γ-(aminopropyl)triethanoxysilane (γ-APS) which can react with hydroxyl groups and leave amino groups, the degree of graft polymerization could be improved. The bovium serum albumin adsorption measurement was conducted to further examine the surface properties of modified and original membranes. Potential applications of the PSLG grafted membranes are expected for enantiomer separation and/or enzyme immobilization.     

Entry to nitrogen-containing heterocycles by based-promoted heterocyclization on allenylamides of l-α-aminoacids

Allenylamides of Boc-protected α-aminoacids easily gave in basic medium heterocyclic products arising from attack of the NH group on the inside C-C double bond of the 1,2-diene moiety, namely imidazolidinones, pyrazinones, and a pyrrole compound. The microwave-assisted heterocyclization occurred cleanly at C-β of the allenyl group with formation of pyrazin-2-ones having an endo- or exocyclic double bond.     

Blends as a strategy towards tailored hydrolytic degradation of poly(?-caprolactone-co-d,l-lactide)-poly(ethylene glycol)-poly(?-caprolactone-co-d,l-lactide) co-polymers

Binary blends were prepared from poly(?-caprolactone) (PCL), and P(CL-co-d,l-lactic acid)-P(ethylene glycol)-P(CL-co-d,l-lactic acid) co-polymers, where the d,l-LA content in the side chains varied from 0 to 70 mol%. Blend discs were fabricated by melt-molding, and the effect of blend composition on hydrolytic degradation was studied. Variations in medium pH were monitored, and morphological changes were observed using scanning electron microscopy. Blending of these co-polymers was found to constitute a simple means by which intermediate rates of water absorption and mass loss were obtained, compared to those observed in pure co-polymer preparations. In one of the blends, prepared from the two components containing 70 or 0 mol% d,l-LA in the side chains and thereby exhibiting large differences in degradation rate, hydrolysis resulted in the formation of a porous material over time. Furthermore, all blend samples maintained their initial shape throughout the study. Such materials may be interesting for further investigations for applications in cellular therapy and controlled release.     

Silane-based poly(ethylene glycol) as a primer for surface modification of nonhydrolytically synthesized nanoparticles using the Stöber method

This paper describes the use of methoxy-poly(ethylene glycol) silane (MPEG-sil) as a linker molecule for the synthesis of silica-coated nanoparticles by the St?ber method. While short alkane chain-based siloxanes including (acryloxypropyl)trimethoxysilane and 3-methacryloxypropyl-trimethoxysilane are popular molecules used in surface modification, they are not efficient for the silica coating of nanoparticles synthesized from organic solvents containing long carbon chain carboxylic acids or amines as capping agents. Here, we report the utilization of MPEG-sil to bridge this gap. Our approach is based on a two-phase system, in which ligand exchange takes place in a hydrophobic environment and the surface modification with silica is conducted in an ethanol-water mixture. Our results show that this two-phased approach was effective to coat monodisperse Fe2O3 nanoparticles capped with oleic acid and Ag nanoparticles capped with oleylamine with uniform SiO2 shells. The process was also demonstrated for double-shell nanostructures to produce SiO2-coated Pt@Fe2O3 core-shell nanoparticles. The results described in this work represent a new approach for the surface modification with silica coating of monodisperse nanoparticles synthesized from nonhydrolytic solutions and can potentially have a broad ramification in the development of water-dispersible nanoparticles for biological applications.     

Effect of partial crosslinking on morphology and properties of the poly(β-hydroxybutyrate)/poly(d,l-lactic acid) blends

Poly(β-hydroxybutyrate) (PHB) is a bio-based and biodegradable aliphatic polyester, however its application is limited by some disadvantages such as high price, brittleness, poor processability and low melt-strength due to serious thermal degradation. Partial crosslinking initiated by dicumyl peroxide (DCP) was applied in this work to improve the performance of poly(β-hydroxybutyrate)/poly(d,l-lactic acid) (PHB/PDLLA) blends. The partial crosslinking of the blends and its effect on the properties, morphology, rheology and thermal behavior of the blends were investigated. The tensile strength and impact toughness of the PHB were increased by incorporation of the PDLLA, which were improved further after the partial crosslinking because of an increased compatibility between the PHB and the PDLLA phases. The rheological study revealed that the storage modulus (G′) and complex viscosity (η*) of the blends were increased after addition of the DCP. On the other hand, the crystallization of PHB in the blends was restricted to a certain extent by the formation of partially crosslinked network while its crystal form was not modified.     

The intramolecular conjugate addition of benzylamine to a d-glucose derived α,β-unsaturated ester: an efficient synthesis of trihydroxylated pyrrolidine alkaloids as potential glycosidase inhibitors

A short and efficient synthesis of 1,4,5-trideoxy-1,4-imino-l-xylo-hexitol 2a and 1,4,5-trideoxy-1,4-imino-d-arabino-hexitol 2b is reported using the intramolecular conjugate addition of in situ generated benzylamine to the α,β-unsaturated ester 4, derived from d-glucose, as the key step.     

Reliable evaluation of molecular structure of methyl 3-O-nitro-α-d-glucopyranoside and its intermediates by means of solid-state NMR spectroscopy and DFT optimization in the absence of appropriate crystallographic data

In this paper the comparative structural analysis of a series of compounds (methyl α-d-glucopyranoside, methyl 4,6-O-ethylidene-α-d-glucopyranoside (2), methyl 2,3-di-O-nitro-4,6-O-ethylidene-α-d-glucopyranoside and methyl 3-O-nitro-4,6-O-ethylidene-α-d-glucopyranoside) by way of synthesis leading to methyl 3-O-nitro-α-d-glucopyranoside (5) is reported. The title compound (5) is a novel d-glucosidic mononitrate having potential biological activity against cardiovascular diseases. The structural analysis was supported by single-crystal X-ray diffraction (XRD), ¹³C CP/MAS NMR spectroscopy and DFT calculations. In the case of 2 and 5, XRD analysis could not be performed due to the fact that 2 is highly hygroscopic and 5 forms improper crystals. However, the molecular structures of 2 and 5 were obtained on the basis of experimental (existing XRD data for similar compounds) and theoretical (DFT optimization) approaches. This showed of very good agreement with the ¹³C CP/MAS NMR spectral data.     

The pH-specific synthesis,spectroscopic, structural,and magnetic properties of a new Ni(II) species containing the plant physiological binder d-(−)-quinic acid: Association with the aqueous speciation of the binary Ni(II)–quinate system

Nickel is an element present in the abiotic and biological world. In its capacity to promote chemistry at the cellular level, Ni(II) interacts with physiological ligands, thus influencing physiological or pathological conditions. Efforts to comprehend the underlying chemistries led to the investigation of Ni(II) reactivity toward the physiological d-(−)-quinic acid, under pH-specific conditions, facilitating the isolation of a new species Na[Ni(C₇H₁₁O₆)₃] · 2.75H₂O (1). Compound 1 was characterized by elemental analysis, spectroscopic techniques (FT-IR, UV–Visible), magnetic susceptibility studies, and X-ray crystallography. The lattice of 1 reveals the presence of an octahedral Ni(II) complex bound to three quinate ligands through the α-hydroxycarboxylate group, thus projecting a stable entity. Concurrent aqueous speciation studies on the Ni(II)–quinate binary system unravel the nature and properties of species arising from Ni(II)–quinate interactions. To this end, the structural and spectroscopic properties of 1, in the solid state and in solution, are in line with the aqueous speciation, exemplifying key features of Ni(II) interactions with the low molecular mass quinic acid in biologically relevant fluids. The overall physicochemical profile of 1 projects well-defined soluble and potentially bioavailable Ni(II) species that could be involved in specific chemical processes and (bio)chemical reactivity patterns at the physiological or molecular toxicity level.     

d- and l-Serine, useful synthons for the synthesis of 24-hydroxyvitamin D3 metabolites. A formal synthesis of 1α,24R,25-(OH)3-D3, 24R,25-(OH)2-D3 and 24S,25-(OH)2-D3

d- and l-Serine have been used for the enantioselective synthesis of tosylates 7a and 7b, useful building blocks for the synthesis of triols 5a and 5b which have already been obtained via a diastereoselective synthesis and used for the synthesis of 2a, 2b and 2c. We have thus performed a formal synthesis of 24S,25-(OH)₂-D₃, 24R,25-(OH)₂-D₃ and 1α,24R,25-(OH)₃-D₃.