cis‐Peptide Bonds: A Key for Intestinal Permeability of Peptides?

Recent structural studies on libraries of cyclic hexapeptides led to the identification of common backbone conformations that may be instrumental to the oral availability of peptides. Furthermore, the observation of differential Caco‐2 permeabilities of enantiomeric pairs of some of these peptides strongly supports the concept of conformational specificity driven uptake and also suggests a pivotal role of carrier‐mediated pathways for peptide transport, especially for scaffolds of polar nature. This work presents investigations on the Caco‐2 and PAMPA permeability profiles of 13 selected N‐methylated cyclic pentaalanine peptides derived from the basic cyclo(‐D ‐Ala‐Ala₄‐) template. These molecules generally showed moderate to low transport in intestinal epithelia with a few of them exhibiting a Caco‐2 permeability equal to or slightly higher than that of mannitol, a marker for paracellular permeability. We identified that the majority of the permeable cyclic penta‐ and hexapeptides possess an N‐methylated cis‐peptide bond, a structural feature that is also present in the orally available peptides cyclosporine A and the tri‐N‐methylated analogue of the Veber–Hirschmann peptide. Based on these observations it appears that the presence of N‐methylated cis‐peptide bonds at certain locations may promote the intestinal permeability of peptides through a suitable conformational preorganization.     

Influence of Halogen Substitution in the Ligand Sphere on the Antitumor and Antibacterial Activity of Half‐sandwich Ruthenium(II) Complexes [RuX(η6‐arene)(C5H4N‐2‐CH=N‐Ar)]+

New complexes [(η⁶‐p‐cymene)Ru(C₅H₄N‐2‐CH=N–Ar)X]PF₆ [X = Br ( 1 ), I ( 2 ); Ar = 4‐fluorophenyl ( a ), 4‐chlorophenyl ( b ), 4‐bromophenyl ( c ), 4‐iodophenyl ( d ), 2,5‐dichlorophenyl ( e )] were prepared, as well as 3a – 3e (X = Cl) and the new complexes [(η⁶‐arene)RuCl(N‐N)]PF₆ (arene = C₆H₅OCH₂CH₂OH, N‐N = 2,2′‐bipyridine ( 4 ), 2,6‐(dimethylphenyl)‐pyridin‐2‐yl‐methylene amine ( 5 ), 2,6‐(diisopropylphenyl)‐pyridin‐2‐yl‐methylene amine ( 6 ); arene = p‐cymene, N‐N = 4‐(aminophenyl)‐pyridin‐2‐yl‐methylene amine ( 7 )]. X‐ray diffraction studies were performed for 1a , 1b , 1c , 1d , 2b , 5 , and 7 . Cytotoxicities of 1a – 1d and 2 were established versus human cancer cells epithelial colorectal adenocarcinoma (Caco‐2) (IC₅₀: 35.8–631.0 μM), breast adenocarcinoma (MCF7) (IC₅₀: 36.3–128.8.0 μM), and hepatocellular carcinoma (HepG2) (IC₅₀: 60.6–439.8 μM), 3a – 3e were tested against HepG2 and Caco‐2, and 4 – 7 were tested against Caco‐2. 1 – 7 were tested against non‐cancerous human epithelial kidney cells. 1 and 2 were more selective towards tumor cells than the anticancer drug 5‐fluorouracil (5‐FU), but 3a – 3e (X = Cl) were not selective. 1 and 2 had good activity against MCF7, some with lower IC₅₀ than 5‐FU. Complexes with X = Br or I had moderate activity against Caco‐2 and HepG2, but those with Cl were inactive. Antibacterial activities of 1a , 2b , 3a , and 7 were tested against antibacterial susceptible and resistant Gram‐negative and ‐positive bacteria. 1a , 2b , and 3a showed activity against methicillin‐resistant S. aureus (MIC = 31–2000 μg · mL^–1).     

Two pseudo‐enantiomeric forms of N‐benzyl‐4‐hydroxy‐1‐methyl‐2,2‐dioxo‐1H‐2λ6,1‐benzothiazine‐3‐carboxamide and their analgesic properties

The fact that molecular crystals exist as different polymorphic modifications and the identification of as many polymorphs as possible are important considerations for the pharmaceutic industry. The molecule of N‐benzyl‐4‐hydroxy‐1‐methyl‐2,2‐dioxo‐1H‐2λ⁶,1‐benzothiazine‐3‐carboxamide, C₁₇H₁₆N₂O₄S, does not contain a stereogenic atom, but intramolecular hydrogen‐bonding interactions engender enantiomeric chiral conformations as a labile racemic mixture. The title compound crystallized in a solvent‐dependent single chiral conformation within one of two conformationally polymorphic P2₁2₁2₁ orthorhombic chiral crystals (denoted forms A and B). Each of these pseudo‐enantiomorphic crystals contains one of two pseudo‐enantiomeric diastereomers. Form A was obtained from methylene chloride and form B can be crystallized from N,N‐dimethylformamide, ethanol, ethyl acetate or xylene. Pharmacological studies with solid–particulate suspensions have shown that crystalline form A exhibits an almost fourfold higher antinociceptive activity compared to form B.     

Synthesis and properties of carbamate‐ and amine‐containing poly(phenylacetylenes)

The 3‐ and 4‐aminophenylacetylenes protected by t‐butoxycarbonyl (t‐Boc) and 9‐fluorenylmethoxycarbonyl (Fmoc) groups ( 3a – 6a ) were synthesized and polymerized using [(nbd)RhCl]₂ ( 1 ) and [(nbd)Rh⁺‐η⁶‐PhB^?Ph₃] ( 2 ) catalysts. The t‐Boc‐containing polymers [poly( 3a ) and poly( 4a )] were obtained in high yield (82–91%). Among the Fmoc‐protected monomers, the para‐derivative polymerized well [poly( 6a ); yield = 85–94%], whereas its meta‐substituted analogue did not afford high molecular weight polymer in good yield [poly( 5a ); yield = 10–15%]. The use of KN(SiMe₃)₂ as a cocatalyst in conjunction with 1 led to a dramatic increase in the molecular weight of the polymers. The acid‐ and base‐catalyzed removal of the t‐Boc and the Fmoc groups, respectively, generated primary amine‐containing polymers [poly( 3b )–poly( 6b )] which cannot be obtained directly by the polymerization of the corresponding monomers. The solubility characteristics of the polymers bearing protected amino groups were quite different from those of the unprotected ones, the former being soluble in polar solvents, whereas the latter displayed poor solubility even in polar protic or highly polar aprotic solvents. The attempts to accomplish the free‐standing membrane fabrication by solution casting were successful only for poly( 3a ), and an augmentation in the gas permeability and CO₂/N₂ permselectivity was discerned in comparison with the unsubstituted poly(phenylacetylene) and poly(m‐t‐butyldimethylsiloxyphenylacetylene). © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1853–1863, 2009     

Gas transport properties of poly(ether‐b‐amide) segmented block copolymers

The permeation properties of H₂, N₂, and CO₂ were determined at 35 °C and pressures up to 15 atm in phase‐separated polyether‐b‐polyamide segmented block copolymers. These polymers contain poly(ethylene oxide) [PEO] or poly(tetramethylene oxide) [PTMEO] as the rubbery polyether phase and nylon‐6 [PA6] or nylon‐12 [PA12] as the hard polyamide phase. Extremely high values of polar (or quadrupolar)/nonpolar gas selectivities, coupled with high CO₂ permeability coefficients, were observed. CO₂/H₂ selectivities as high as 9.8 and CO₂/N₂ selectivities as high as 56 were obtained in polymers with CO₂ permeability coefficients of approximately 220 × 10⁻¹⁰ cm³(STP) cm/(cm² s cmHg). As the amount of polyether increases, permeability increases. Gas permeability is higher in polymers with less polar constituents, PTMEO and PA12, than in those containing the more polar PEO and PA6 units. CO₂/N₂ and CO₂/H₂ selectivities are higher in polymers with higher concentrations of polar groups. These high selectivity values derive from large solubility selectivities in favor of CO₂. Because CO₂ is larger than H₂ and has, therefore, a lower diffusion coefficient than H₂, the weak size‐sieving ability of the rubbery polyether phase, which is the locus of most of the gas permeation, also contributes to high CO₂/H₂ selectivity. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 2051–2062, 2000     

Enantioselective Radical‐Polar Crossover Reactions of Indanonecarboxamides with Alkenes

Highly efficient asymmetric intermolecular radical‐polar crossover reactions were realized by combining a chiral N,N′‐dioxide/Ni^II complex catalyst with Ag₂O under mild reaction conditions. Various terminal alkenes and indanonecarboxamides/esters underwent radical addition/cyclization reactions to afford spiro‐iminolactones and spirolactones with good to excellent yields (up to 99 %) and enantioselectivities (up to 97 % ee). Furthermore, a range of different radical‐mediated oxidation/elimination or epoxide ring‐opening products were obtained under mild reaction conditions. The Lewis acid catalysts exhibited excellent performance and precluded the strong background reaction.     

Thermally stable and organosoluble binaphthylene‐based poly(urea‐ether‐imide)s: one‐pot preparation and characterization

A new family of wholly aromatic poly(urea‐ether‐imide)s ( 4a–4f ) possessing binaphthylene‐twisted rings was prepared by diphenyl azidophosphate (DPAP)‐activated one‐pot polyaddition reaction of a preformed imide heterocyclic ring‐containing dicarboxylic acid, 2,2′‐bis(4‐trimellitimidophenoxy)‐ 1,1′‐binaphthyl ( 1 ) with various kinds of aromatic diamines ( 3a–3f ). At first, with due attention to structural similarity and to compare the characterization data, a model compound 2 was synthesized by the reaction of diimide‐dicarboxylic acid 1 with two mole equivalents of aniline. In this direct method, the polymers were prepared by polyaddition reactions of the in situ‐formed diisocyanate with the aromatic diamines. Molecular weights of the poly(urea‐ether‐imide)s obtained were evaluated viscometrically, and the inherent viscosities (η_inh) measured were in the range 0.10– 0.25 dl/g. All of the polymers were characterized by FT‐IR spectroscopic method and elemental analysis. All of the resulting polymers exhibited an excellent solubility in common polar solvents such as N‐methyl‐2‐pyrrolidone (NMP), dimethyl sulfoxide (DMSO), N,N‐dimethylformamide (DMF), and N,N‐dimethylacetamide (DMAc). Crystallinity of the resulted polymers was evaluated by wide‐angle X‐ray diffraction (WXRD) method, and they exhibited nearly a non‐crystalline nature as evidenced by their diffractograms. The glass transition temperatures (T_g) of the polymers determined by differential scanning calorimetry (DSC) thermograms were in the range of 274–302°C. The temperatures at 10% weight loss (T_d10%) from their thermogravimetric analysis (TGA/DTG) curves were found to be in the range of 389–414°C in nitrogen atmosphere. Copyright © 2008 John Wiley & Sons, Ltd.     

Novel aromatic polyamides and polyimides functionalized with 4‐tert‐butyltriphenylamine groups

A new triphenylamine‐containing diamine monomer, 4,4′‐diamino‐4″‐tert‐butyltriphenylamine, was successfully synthesized by the cesium fluoride‐mediated N,N‐diarylation of 4‐tert‐butylaniline with 4‐fluoronitrobenzene, followed by the reduction of the nitro group. The obtained diamine monomer was reacted with various aromatic dicarboxylic acids and tetracarboxylic dianhydrides to produce two series of novel triphenylamine‐based polyamides and polyimides with pendent tert‐butyl substituents. Most of the polymers were readily soluble in polar organic solvents, such as N‐methyl‐2‐pyrrolidone and N,N‐dimethylacetamide (DMAc), and could be solution cast into tough and flexible polymer films. These polymers showed high glass transition temperatures between 282 and 320 °C, and they were fairly stable up to a temperature above 450 °C (for polyamides) or 500 °C (for polyimides). These polymers exhibited UV absorption maxima around 308 to 361 nm. The photoluminescence spectra of the polyamides in DMAc exhibited a peak emission wavelength in the blue at 421–433 nm. Cyclic voltammograms of polyamides and polyimides showed an oxidation wave at 1.0–1.1 V versus Ag/AgCl in an acetonitrile solution. All the polyamides and polyimides exhibited excellent reversibility of electrochromic characteristics by continuous several cyclic scans between 0.0 and 1.1–1.3 V, with a color change from the original pale yellowish neutral form to the green or blue oxidized forms. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4579–4592, 2006     

Lipophilicity and bio‐mimetic properties determination of phytoestrogens using ultra‐high‐performance liquid chromatography

This paper presents lipophilicity and bio‐mimetic property determination of 15 phytoestrogens, namely biochanin A, daidzein, formononetin, genistein, genistein‐4,7‐dimethylether, prunetin, 3,4,7‐trihydroxyisoflavon, 4,6,7‐trihydroxyisoflavon, 4,6,7‐trimethoxyisoflavon, daidzin, genistin, ononin, sissotrin, coumestrol and coumestrol dimethylether. High‐performance liquid chromatography with fast gradient elution and Caco‐2 cell line were used to determine the physicochemical properties of selected phytoestrogens. Lipophilicity was determined on octadecyl‐sylane stationary phase using pH 2.0 and pH 7.4 buffers. Immobilized artificial membrane chromatography was used for prediction of interaction with biological membranes. Protein binding was measured on human serum albumin and α‐1‐acid‐glycoprotein (AGP) stationary phases. Caco‐2 assay was used as a gold standard for assessing in vitro permeability. The obtained results differentiate phytoestrogens according to their structure where aglycones show significantly higher lipophilicity, immobilized artificial membrane partitioning, AGP binding and Caco‐2 permeability compared with glucosides. However, human serum albumin binding was very high for all investigated compounds. Furthermore, a good correlation between experimentally obtained chromatographic parameters and in silico prediction was obtained for lipophilicity and human serum albumin binding, while the somewhat greater difference was obtained for AGP binding and Caco‐2 permeability.     

Synthesis and tuberculostatic activity of novel N′‐methyl‐4‐(pyrrolidin‐1‐yl)picolinohydrazide and N′‐methylpyrimidine‐2‐carbohydrazide derivatives

The synthesis of N′‐methyl‐4‐(pyrrolidin‐1‐yl)picolinohydrazide and N′‐methyl‐pyrimidine‐2‐carbohydrazide derivatives ( 5a and 5b ) was carried out. These compounds were used as starting materials to obtain methyl N′‐methylhydrazinecarbodithioates 6a and 6b , which, on reaction with either triethylamine or hydrazine, gave corresponding 1,3,4‐oxadiazioles 7a and 7b or 1,2,4‐triazoles 9a and 9b with the free NH₂ group at the N‐4 position, respectively. Compounds 8a – e , particularly containing cyclic amines at N‐4 of the 1,2,4‐triazole ring, were also obtained. Synthesized compounds were tested in vitro for their activity against Mycobacterium tuberculosis. The structure–activity relationship analysis for obtained compounds was done. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:223–230, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21008     

Zinc (II), palladium (II) and cadmium (II) complexes containing 4‐methoxy‐N‐(pyridin‐2‐ylmethylene) aniline derivatives: Synthesis,characterization and methyl methacrylate polymerization

A series of Zn (II), Pd (II) and Cd (II) complexes, [(L) _n MX ₂ ] _m (L = L‐a–L‐c; M = Zn, Pd; X = Cl; M = Cd; X = Br; n, m = 1 or 2), containing 4‐methoxy‐N‐(pyridin‐2‐ylmethylene) aniline ( L‐a ), 4‐methoxy‐N‐(pyridin‐2‐ylmethyl) aniline ( L‐b ) and 4‐methoxy‐N‐methyl‐N‐(pyridin‐2‐ylmethyl) aniline ( L‐c ) have been synthesized and characterized. The X‐ray crystal structures of Pd (II) complexes [L ₁ PdCl ₂ ] (L = L‐b and L‐c) revealed distorted square planar geometries obtained via coordinative interaction of the nitrogen atoms of pyridine and amine moieties and two chloro ligands. The geometry around Zn (II) center in [(L‐a)ZnCl ₂ ] and [(L‐c)ZnCl ₂ ] can be best described as distorted tetrahedral, whereas [(L‐b) ₂ ZnCl ₂ ] and [(L‐b) ₂ CdBr ₂ ] achieved 6‐coordinated octahedral geometries around Zn and Cd centers through 2‐equivalent ligands, respectively. In addition, a dimeric [(L‐c)Cd(μ ‐ Br)Br] ₂ complex exhibited typical 5‐coordinated trigonal bipyramidal geometry around Cd center. The polymerization of methyl methacrylate in the presence of modified methylaluminoxane was evaluated by all the synthesized complexes at 60°C. Among these complexes, [(L‐b)PdCl ₂ ] showed the highest catalytic activity [3.80 × 10⁴ g poly (methyl methacrylate) (PMMA)/mol Pd hr^?1], yielding high molecular weight (9.12 × 10⁵ g mol^?1) PMMA. Syndio‐enriched PMMA (characterized using ¹H‐NMR spectroscopy) of about 0.68 was obtained with T_g in the range 120–128°C. Unlike imine and amine moieties, the introduction of N‐methyl moiety has an adverse effect on the catalytic activity, but the syndiotacticity remained unaffected.     

Amphiphilic Inclusion Spaces for Various Guests and Regulation of Fluorescence Intensity of 1,8‐Bis(4‐aminophenyl)anthracene Crystals

A host framework for inclusion of various guest molecules was investigated by preparation of inclusion crystals of 1,8‐bis(4‐aminophenyl)anthracene (1,8‐BAPA) with organic solvents. X‐ray crystallographic analysis revealed construction of the same inclusion space incorporating 1,8‐BAPA and eight guest molecules including both non‐polar (benzene) and polar guests (N,N‐dimethylformamide, DMF). Fluorescence efficiencies varied depending on guest molecule polarity; DMF inclusion crystals exhibited the highest fluorescence intensity (Φ_F=0.40), four times as high as that of a benzene inclusion crystal (Φ_F=0.10). According to systematic investigations of inclusion phenomena, strong host–guest interactions and filling of the inclusion space led to a high fluorescence intensity. Temperature‐dependent fluorescence spectral measurements revealed these factors effectively immobilised the host framework. Although hydrogen bonding commonly decreases fluorescence intensity, the present study demonstrated that such strong interactions provide excellent conditions for fluorescence enhancement. Thus, this remarkable behaviour has potential application toward sensing of highly polar molecules, such as biogenic compounds.     

Two new zinc(II) and mercury(II) complexes based on N,N′‐(cyclohexane‐1,2‐diylidene)bis(4‐fluorobenzohydrazide): synthesis,crystal structures and antibacterial activities

Reaction of N,N′‐(cyclohexane‐1,2‐diylidene)bis(4‐fluorobenzohydrazide), C₂₀H₁₈F₂N₄O₂, ( L^F ), with zinc chloride and mercury(II) chloride produced different types and shapes of neutral coordination complexes, namely, dichlorido[N,N′‐(cyclohexane‐1,2‐diylidene)bis(4‐fluorobenzohydrazide)‐κ²N,O]zinc(II), [ZnCl₂(C₂₀H₁₈F₂N₄O₂)], ( 1 ), and dichlorido[N,N′‐(cyclohexane‐1,2‐diylidene)bis(4‐fluorobenzohydrazide)‐κ⁴O,N,N′,O′]mercury(II), [HgCl₂(C₂₀H₁₈F₂N₄O₂)], ( 2 ). The organic ligand and its metal complexes are characterized using various techniques: IR, UV–Vis and nuclear magnetic resonance (NMR) spectroscopies, in addition to powder X‐ray diffraction (PXRD), single‐crystal X‐ray crystallography and microelemental analysis. Depending upon the data from these analyses and measurements, a typical tetrahedral geometry was confirmed for zinc complex ( 1 ), in which the Zn^II atom is located outside the bis(benzhydrazone) core. The Hg^II atom in ( 2 ) is found within the core and has a common octahedral structure. The in vitro antibacterial activities of the prepared compounds were evaluated against two different bacterial strains, i.e. gram positive Bacillus subtilis and gram negative Pseudomonas aeruginosa bacteria. The prepared compounds exhibited differentiated growth‐inhibitory activities against these two bacterial strains based on the difference in their lipophilic nature and structural features.     

Effects of GC temperature and carrier gas flow rate on on‐line oxygen isotope measurement as studied by on‐column CO injection

Although deemed important to δ¹⁸O measurement by on‐line high‐temperature conversion techniques, how the GC conditions affect δ¹⁸O measurement is rarely examined adequately. We therefore directly injected different volumes of CO or CO–N₂ mix onto the GC column by a six‐port valve and examined the CO yield, CO peak shape, CO–N₂ separation, and δ¹⁸O value under different GC temperatures and carrier gas flow rates. The results show the CO peak area decreases when the carrier gas flow rate increases. The GC temperature has no effect on peak area. The peak width increases with the increase of CO injection volume but decreases with the increase of GC temperature and carrier gas flow rate. The peak intensity increases with the increase of GC temperature and CO injection volume but decreases with the increase of carrier gas flow rate. The peak separation time between N₂ and CO decreases with an increase of GC temperature and carrier gas flow rate. δ¹⁸O value decreases with the increase of CO injection volume (when half m/z 28 intensity is <3 V) and GC temperature but is insensitive to carrier gas flow rate. On average, the δ¹⁸O value of the injected CO is about 1‰ higher than that of identical reference CO. The δ¹⁸O distribution pattern of the injected CO is probably a combined result of ion source nonlinearity and preferential loss of C¹⁶O or oxygen isotopic exchange between zeolite and CO. For practical application, a lower carrier gas flow rate is therefore recommended as it has the combined advantages of higher CO yield, better N₂–CO separation, lower He consumption, and insignificant effect on δ¹⁸O value, while a higher‐than‐60 °C GC temperature and a larger‐than‐100 µl CO volume is also recommended. When no N₂ peak is expected, a higher GC temperature is recommended, and vice versa. Copyright © 2015 John Wiley & Sons, Ltd.     

Influence of nitroxide structure on polystyrene brushes “grafted‐from” silicon wafers

Alkoxyamine derivatives based on 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO), N‐tert‐butyl‐N‐(1‐diethylphosphono‐(2,2‐dimethylpropyl)) nitroxide (SG1) and N‐tert‐butyl‐N‐(2‐methyl‐1‐phenylpropyl) nitroxide (TIPNO) containing a C₁₁ hydrophobic spacer and a reactive triethoxysilyl polar head, were synthesized and anchored to silicon wafers by the Langmuir–Blodgett reactive deposition technique at surface pressures ranging from 15 to 32 mN/m. Polystyrene brushes (M_n ～ 8500–66,400 g/mol) were grown from the alkoxyamine functionalized silicon wafers by nitroxide mediated radical polymerization and characterized by ellipsometry and water contact angle measurements. The main parameters influencing the grafting density and the degree of stretching of the brushes are the nitroxide polarity and, therefore, the behavior of the corresponding alkoxyamines at the air/water interface of the Langmuir–Blodgett trough. Depending on the alkoxyamine chemical structure and the surface pressure during Langmuir–Blodgett deposition, polystyrene brushes with grafting densities of 0.3–1.0 chains/nm² and stretching values of 40–70% were obtained. Regarding alkoxyamines deposited at high surface pressures, size exclusion chromatography experiments performed on both cleaved polystyrene brushes and chains simultaneously grown in the bulk revealed that the polymerization degree of the bulk and surface chains are significantly different, suggesting that steric constrains affect the polymerization kinetics occurring at the silicon surface. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3367–3374, 2008     

Synthesis and characterization of well‐defined,amphiphilic poly(N‐isopropylacrylamide)‐ b‐[2‐hydroxyethyl methacrylate‐poly(ϵ‐caprolactone)]n graft copolymers by RAFT polymerization and macromonomer method

The well‐defined, thermosensitive and biodegradable graft copolymers, poly(N‐isopropylacrylamide)‐b‐[2‐hydroxyethyl methacrylate‐poly(ε‐caprolactone)]_n (PNIPAAm‐b‐(HEMA‐PCL)_n) (n = 3 or 9), were synthesized by combining reversible addition‐fragmentation chain transfer polymerization and macromonomer method. The copolymers were able to self‐assemble into micelles in water with low critical micellar concentration and demonstrated temperature sensitivity with a lower critical solution temperature at around 36 °C. Transmission electron microscopy shows that the micelles exhibit a nanosized spherical morphology within a size range of 30–100 nm. The PNIPAAm‐b‐(HEMA‐PCL)₃ copolymer exhibited biodegradation and low cytotoxicity. The paclitaxel‐loaded PNIPAAm‐b‐(HEMA‐PCL)₃ micelles displayed thermosensitive controlled release behavior, which indicates potential as drug carriers. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5354–5364, 2007     

Poly(methacrylic acid‐ethylene glycol dimethacrylate‐N‐vinylcarbazole) monolithic column for the enrichment of trace benzodiazepines from urine and beer samples

A sensitive microextraction method based on a new poly(methacrylic acid‐ethylene glycol dimethacrylate‐N‐vinylcarbazole) monolithic capillary column, coupled with gas chromatography and electron capture detection, was established for the determination of three benzodiazepines (estazolam, alprazolam, and triazolam) in urine and beer samples. Owing to the abundant π electrons and polar surface of N‐vinylcarbazole, N‐vinylcarbazole‐incorporated monolith showed a higher extraction performance than neat poly(methacrylic acid‐ethylene glycol dimethacrylate) because of the enhanced π–π stacking interactions derived from the π‐electron‐rich benzene groups from N‐vinylcarbazole. The monolith exhibited a homogeneous and continuous structure, good permeability, and a long lifetime. Factors affecting the extraction such as solution pH, salt concentration, sample volume, desorption solvent, and desorption volume were investigated. Under the optimized conditions, limits of detection of 0.011–0.026 ng/mL were obtained. The one‐column and column‐to‐column precision values were ≤7.2 and ≤9.8%, respectively. The real samples were first diluted with deionized water and then treated by the monolith microextraction before gas chromatography analysis. The recoveries were 81.4–93.3 and 83.3–94.7% for the spiked samples, with relative standard deviations of 4.1–8.1 and 3.8–8.5%, respectively. This method provides an accurate, simple, and sensitive detection platform for drug analysis.     

Effect of analyte lipophilicity on the resolution of α‐ and β‐amino acids on liquid chromatographic ligand exchange chiral stationary phases

Separation of the two enantiomers of racemic α‐ and β‐amino acids on two ligand exchange chiral stationary phases (CSPs) prepared previously by covalently bonding sodium N‐((S)‐1‐hydroxymethy‐3‐methylbutyl)‐N‐undecylaminoacetate or sodium N‐((R)‐2‐hydroxy‐1‐phenylethyl)‐N‐undecylaminoacetate on silica gel was studied with variation of the organic modifier (methanol) concentration in the aqueous mobile phase. In particular, the variation of retention factors with changing organic modifier concentration in the aqueous mobile phase was found to be strongly dependent on both the analyte lipophilicity and the stationary phase lipophilicity. In general, the retention factors of relatively lipophilic analytes on relatively lipophilic CSPs tend to increase with increasing organic modifier concentration in the aqueous mobile phases while those of less lipophilic or hydrophilic analytes tend to increase. However, only highly lipophilic analytes show decreasing retention factors with increasing organic modifier concentration in the aqueous mobile phase on less lipophilic CSPs. The contrasting retention behaviors on the two CSPs were rationalized by the balance of the two competing interactions, viz. hydrophilic interaction of analytes with polar aqueous mobile phase and the lipophilic interaction of analytes with the stationary phase.     

Racemic and chiral 1‐[N‐(chloro­acetyl)carbamoylamino]‐2,3‐dihydro‐1H‐inden‐2‐yl chloroacetate

In the racemic crystals of (1S,2R)‐ or (1R,2S)‐1‐[N‐(chloro­acetyl)­carbamoyl­amino]‐2,3‐di­hydro‐1H‐inden‐2‐yl chloro­acetate, C₁₄H₁₄Cl₂N₂O₄, (I), the enantiomeric mol­ecules form a dimeric structure via the N—H?O cyclic hydrogen bond of the carbamoyl moieties. In the chiral crystals of (—)‐(1S,2R)‐1‐[N‐(chloro­acetyl)­carbamoyl­amino]‐2,3‐di­hydro‐1H‐inden‐2‐yl chloro­acetate, C₁₄H₁₄Cl₂N₂O₄, (II), the N—­H?O intermolecular hydrogen bond forms a zigzag chain around the twofold screw axis. The melting points and calculated densities of (I) and (II) are 446 and 396 K, and 1.481 and 1.445 Mg m^?3, respectively.