Synthesis and Molecular Recognition of Molecularly Imprinted Polymer with Ibuprofen as Template

Ibuprofen and ketoprofen are chemically similar non‐steroidal anti‐inflammatory drugs widely used in the treatment of arthritis. Using a molecular imprinting technique, a simple and rapid method was developed for the simultaneous separation and determination of ibuprofen and ketoprofen. Molecular imprinting introduces artificial binding sites into a synthetic polymer matrix, allowing it to exhibit selective rebinding of template molecules. Imprinted polymers can be regarded as an HPLC stationary phase, important for pharmaceutical analysis. Most molecularly imprinted polymers (MIPs) are synthesized by free radical polymerization of functional monomers, resulting in an excess of crosslinking monomers. In this study, MIPs have been prepared with a ibuprofen template, which can form intramolecular hydrogen bonds. Methacrylic acid (MAA) and ethyleneglycol dimethacrylate (EGDMA) were used as the functional monomer and cross‐linker, respectively. Bulk polymerization was carried out at 4 °C under UV radiation. The resulting MIP was ground into 25?44 μm particles, which were slurry‐packed into analytical columns. Template molecules were removed by methanol‐acetic acid (9:1, v/v). We evaluated the template binding performance of the MIP using HPLC, with ultraviolet (UV) detection at 234 nm. Chromatographic resolution of ibuprofen and ketoprofen on the MIPs were appraised using buffer/acetonitrile (45/55, v/v) as the mobile phase. Results show that the MIPs prepared using ibuprofen as the template had a significant molecular imprinting effect. The method was successfully applied to the separation and analysis of ibuprofen and ketoprofen in pharmaceuticals.     

Simultaneous determination of selenium and antimony compounds by capillary electrophoresis with indirect fluorescence detection

Capillary electrophoresis (CE) with indirect fluorescence detection was used to analyze selenium (selenite, selenate, selenomethionine, and selenocystine) and antimony (antimonite and antimonate) compounds. The separation was achieved by CE in 6 min with a 1.2 mM fluorescein solution at pH 9.5. Fluorescein also functioned as a background fluorophore for the indirect detection of these nonfluorescent species. Linearity of more than two orders of magnitude was generally obtained. Precision of migration times and peak areas was less than 1.0% and 7.2%, respectively. The concentration limits of detection (CLODs) was in the microM range. The detection sensitivity was generally dependent upon the transfer ratio (TR, defined as the number of moles of fluorescein ions displaced by one mole of analyte ions) of each species.     

Influence of catalyst depletion or deactivation on polymerization kinetics. III. Solution polymerization of acrylonitrile in N,N-dimethylformamide at −30°C.

The experimental results on homogeneous polymerization of acrylonitrile initiated with the sodium triethylthioisopropoxyaluminate, NaAlEt₃S(i-Pr), catalyst in DMF at ?30°C. are compared with the prediction of equations based on a postulated mechanism. The agreement between the calculated and observed number-average molecular weight combined with the kinetic data and the relationship between the conversion and the initial catalyst concentration provides a rigorous test concerning the validity of the equations and the mechanism of the polymerization. A plausible mechanism is postulated as follows: The initiation must be relatively fast in accordance with the rate equations and the growing polymer undergoes propagation, transfer (to monomer), and deactivation simultaneously. The infrared spectrum of the low molecular weight polymer prepared at a high catalyst concentration showed strong absorption at 2337, 2205, and 1620 cm.^?1 but no absorption at 900 cm.^?1, indicating that there are two nitriles in the polymer, one of which is conjugated. The possibility of having ? CH?CH₂ groups in the polymer is ruled out by the absence of the band at 900 cm.^?1. In view of these facts, it is concluded that the polymer has a ? CH?CHCN endgroup resulting from the transfer reaction.     

Analysis of ephedra-alkaloids using sweeping and cation-selective exhaustive injection and sweeping micellar electrokinetic chromatography methods

Two stacking methods of capillary electrophoresis (CE) were developed for the separation of very dilute solutions of ephedra-alkaloids, namely ephedrine, pseudoephedrine, methylephedrine, methylpseudoephedrine, norephedrine, and norpseudoephedrine. A sweeping method which uses a carrier comprised of phosphoric acid, sodium dodecyl sulfate (SDS), diethylamine and acetonitrile permits the detection of the alkaloids down to the 10(-1) microg/mL level, and the cation-selective exhaustive injection and sweeping micellar electrokinetic chromatography (CSEI-Sweep-MEKC) method using phosphoric acid, SDS, and acetronitrile as electrolytes can detect down to the 10(-3) microg/mL level. The former requires the conductance of the sample solution to be adjusted beforehand, and only five peaks were observed, two of which were overlapped. The latter is capable of separating the six alkaloids but has a somewhat poorer reproducibility. Using an optimized injection time, it was found that the more diluted a solution is, the greater the sweeping effect will be. The CSEI-Sweep-MEKC method with a 600 s injection time and a 10(-1) microg/mL solution concentration provides an amplification effect of approximately 10(4). The method is suitable for analyses of dilute herb drug extracts and mouse sera. The effect of buffers on the separation and validation of the methods in this study are also discussed.     

Synthesis of an s-butyldibenz[a,h]acridine. Alkyl migration in the bernthsen reaction

The Bernthsen reaction between N-1-naphthyl-2-naphthylamine and 2-methylbutanoic acid and its anhydride at 200–230° for seven hours gives a low yield of 12- or 13-s-butyldibenz[a,h]acridine, instead of the expected 14-isomer. The parent molecule dibenz[a,h]acridine results from the same reaction conducted at 270° for thirteen hours. It is suggested that alkyl migration may have occurred in some other cases where the Bernthsen reaction was reported to yield 14-alkyldibenz[a,h]acridines.     

Flash photolytic generation and study of p-quinone methide in aqueous solution. An estimate of rate and equilibrium constants for heterolysis of the carbon-bromine bond in p-hydroxybenzyl bromide

Flash photolysis of p-hydroxybenzyl acetate in aqueous perchloric acid solution and formic acid, acetic acid, biphosphate ion, and tris(hydroxymethyl)methylammonium ion buffers produced p-quinone methide as a short-lived species that underwent hydration to p-hydroxybenzyl alcohol in hydronium ion catalyzed (k(H(+)) = 5.28 x 10(4) M(-1) s(-1)) and uncatalyzed (k(uc) = 3.33 s(-1)) processes. The inverse nature of the solvent isotope effect on the hydronium ion-catalyzed reaction, k(H(+))/k(D(+)) = 0.41, indicates that this process occurs by rapid and reversible protonation of the quinone methide on its carbonyl carbon atom, followed by rate-determining capture of the p-hydroxybenzyl carbocation so produced by water, while the magnitude of the rate constant on the uncatalyzed process indicates that this reaction occurs by simple nucleophilic addition of water to the methylene group of the quinone methide. p-Quinone methide also underwent hydronium ion-catalyzed and uncatalyzed nucleophilic addition reactions with chloride ion, bromide ion, thiocyanate ion, and thiourea. The solvent isotope effects on the hydronium ion-catalyzed processes again indicate that these reactions occurred by preequilibrium mechanisms involving a p-hydroxybenzyl carbocation intermediate, and assignment of a diffusion-controlled value to the rate constant for reaction of this cation with thiocyanate ion led to K(SH) = 110 M as the acidity constant of oxygen-protonated p-quinone methide. In a certain perchloric acid concentration range, the bromide ion reaction became biphasic, and least-squares analysis of the kinetic data using a double-exponential function provided k(Br(-)) = 3.8 x 10(8) M(-1) s(-1) as the rate constant for nucleophilic capture of the p-hydroxybenzyl carbocation by bromide ion, k(ionz) = 8.5 x 10(2) s(-1) for ionization of the carbon-bromine bond of p-hydroxybenzyl bromide, and K = 4.5 x 10(5) M(-1) as the equilibrium constant for the carbocation-bromide ion combination reaction, all in aqueous solution at 25 degrees C. Comparisons are made of the reactivity of p-quinone methide with p-quinone alpha,alpha-bis(trifluoromethyl)methide as well as p-quinone methide with o-quinone methide.     

Potent and selective structure-based dibenzofuran inhibitors of transthyretin amyloidogenesis: kinetic stabilization of the native state

Transthyretin (TTR) amyloidogenesis requires rate-limiting tetramer dissociation and partial monomer denaturation to produce a misassembly competent species. This process has been followed by turbidity to identify transthyretin amyloidogenesis inhibitors including dibenzofuran-4,6-dicarboxylic acid (1). An X-ray cocrystal structure of TTR.1(2) reveals that it only utilizes the outer portion of the two thyroxine binding pockets to bind to and inhibit TTR amyloidogenesis. Herein, structure-based design was employed to append aryl substituents at C1 of the dibenzofuran ring to complement the unused inner portion of the thyroxine binding pockets. Twenty-eight amyloidogenesis inhibitors of increased potency and dramatically increased plasma TTR binding selectivity resulted. These function by imposing kinetic stabilization on the native tetrameric structure of TTR, creating a barrier that is insurmountable under physiological conditions. Since kinetic stabilization of the TTR native state by interallelic trans suppression is known to ameliorate disease, there is reason to be optimistic that the dibenzofuran-based inhibitors will do the same. Preventing the onset of amyloidogenesis is the most conservative strategy to intervene clinically, as it remains unclear which of the TTR misassembly intermediates results in toxicity. The exceptional binding selectivity enables these inhibitors to occupy the thyroxine binding site(s) in a complex biological fluid such as blood plasma, required for inhibition of amyloidogenesis in humans. It is now established that the dibenzofuran-based amyloidogenesis inhibitors have high selectivity, affinity, and efficacy and are thus excellent candidates for further pharmacologic evaluation.     

Synthesis, characterization and thermal properties of novel epoxy containing silicon and phosphorus nanocomposites by sol-gel method

Organic-inorganic hybrids were prepared using diglycidyl ether of bisphenol A (DGEBA) type epoxy and tetraethoxysilane via the sol-gel process. The DGEBA type epoxy was modified by a coupling agent to improve the compatibility of the organic and inorganic phases. The sol-gel technique was used successfully to incorporate silicon and phosphorus into the network of hybrids increasing flame retardance.Fourier transform infrared spectroscopy and ²⁹Si nuclear magnetic resonance spectroscopy were used to characterize the structure of the hybrids. In condensed siloxane species for TEOS, silicon atoms through mono-, di-, tri-, and tetra-substituted siloxane bonds are designated as Q¹, Q², Q³, Q⁴, respectively. For 3-isocyanatopropyltriethoxysilane and diethylphosphatoethyltriethoxysilane, mono-, di-, tri-, tetra-substituted siloxane bonds are designated as T¹, T², T³. Results revealed that Q⁴, Q³, T³ are the major environments forming a network structure. The morphology of the ceramer was examined by scanning electron microscopy and Si mapping. Particle sizes were below 100 nm. The hybrids were nanocomposites. The char yield of pure epoxy resin was 14.8 wt.% and that of modified epoxy nanocomposite was 31 wt.% at 800 °C. A higher char yield enhances the flame retardance. Values of limiting oxygen index of pure epoxy and modified epoxy nanocomposites are 24 and 32, respectively, indicating that modified epoxy nanocomposites possess better flame retardance than the pure epoxy resin.     

Tetracyclic triterpenoids from Melia azedarach, L.—III

From petroleum ether extracts of the bark of M. azedarach four novel tetracyclic triterpenoids have been isolated and characterized to be C₃₀ compounds of the euphane (20R) series. Previously known triterpenoids from Meliaceae have all been 20S compounds. Kulinone 1 is the first known euphane or tirucallane (20S) derivative oxygenated in the D ring; kulactone 2, kulolactone 3 and methyl kulonate 4 are additionally oxygenated in the side chain. Compounds 2 and 3 have a 2-oxa-trans-bicyclo[3,3,0]-octanone structure.