A simple and controlled oxidative decontamination of sulfur mustard and its simulants using ozone gas

A simple and efficient oxidative decontamination method was developed for sulfur mustard (HD), a potential chemical warfare agent. The method involves treatment of chemical warfare agent HD and its simulants, i.e., dimethyl sulfide, diethyl sulfide, and 2-chloroethyl ethyl sulfide with ozone gas at ambient conditions in acetonitrile solvent. Ozone gas readily oxidizes sulfur mustard in a controlled manner to give its corresponding nontoxic sulfoxide. This transformation is selective and takes place even at subzero temperatures. The oxidation products of HD and its simulants were monitored and quantified by gas chromatography and gas chromatography–mass spectrometry.     

Hadamard Homonuclear Broadband Decoupled TOCSY NMR: Improved Efficacy in Detecting Long‐range Chemical Shift Correlations

The importance of Hadamard encoding pulses in one‐dimensional pure shift yielded by the chirp excitation version of selective total correlation spectroscopy (1D PSYCHE–TOCSY) experiments is discussed for chemical‐shift analysis of complex natural products at ultrahigh resolution. Herein, we adapted H_n Hadamard matrices to 1D PSYCHE–TOCSY and observed an overall circa square root of n‐fold enhancement in the signal‐to‐noise (S/N) ratio when compared to conventional 1D PSYCHE–TOCSY recorded by refocusing only one spin at a time. This enhancement in S/N facilitates the observation of very weak long‐range chemical‐shift correlations from Hadamard‐encoded PSYCHE–TOCSY (HE–PSYCHE–TOCSY). The proposed method will have a significant impact on structure determination of complex isolated/ synthetic natural products.     

Liquid chromatography tandem mass spectrometry method for the quantification of rimonabant, a CB1 receptor antagonist, in human plasma

A sensitive high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of rimonabant in human plasma. Following liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a reverse-phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective (M+H)+ ions, m/z 463-363 for rimonabant and m/z 408-235 for the internal standard. The assay exhibited a linear dynamic range of 0.1-100 ng/mL for rimonabant in human plasma. The lower limit of quantification was 0.1 ng/mL with a relative standard deviation of less than 6%. With dilution integrity up to 10-fold, the upper limit of quantification was extendable up to 1000 ng/mL. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.0 min for each sample made it possible to analyze more than 250 human plasma samples per day. The validated method was successfully used to analyze human plasma samples for application in pharmacokinetic studies.     

Sensitive liquid chromatography tandem mass spectrometry method for the quantification of sitagliptin, a DPP-4 inhibitor, in human plasma using liquid-liquid extraction

A sensitive high-performance liquid chromatography-positive ion electrospray tandem mass spectrometry method was developed and validated for the quantification of sitagliptin, a DPP-4 inhibitor, in human plasma. Following liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a reverse-phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M + H](+) ions, m/z 408-235 for sitagliptin and m/z 310-148 for the internal standard. The assay exhibited a linear dynamic range of 0.1-250 ng/mL for sitagliptin in human plasma. The lower limit of quantification was 0.1 ng/mL with a relative standard deviation of less than 6%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.0 min for each sample made it possible to analyze more than 300 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic studies.     

Highly enantioselective carbon-carbon bond formation by Cu-catalyzed asymmetric [2,3]-sigmatropic rearrangement: application to the syntheses of seven-membered oxacycles and six-membered carbocycles

A concise route for the syntheses of enantioenriched functionalized scaffolds of medium-sized oxacycles and carbocycles employing the chiral auxiliary-mediated Cu-catalyzed ylide formation/[2,3]-sigmatropic rearrangement as a key step was developed.     

Catalyzed cyclizations leading to enrichment of functionality and chirality. A general approach to dibenzocyclooctadiene lignans from alpha,omega-diynes

The [B-Sn]-mediated cyclization of alpha,omega-diynes results in not only an increase in the functionalizable groups (incorporated as highly versatile vinyl-B and vinyl-Sn groups) but also an increase in new serviceable stereochemical elements. The alkylidene functionalities at C7 and C8 offer unprecedented opportunities for the synthesis of highly functionalized dibenzocyclooctadienes. Examples of interiotherins and gomisins are provided.     

Encapsulation of proteins in poly(l-lactide-co-caprolactone) fibers by emulsion electrospinning

This study was aimed at investigating emulsion electrospinning to prepare biodegradable fibrous mats with encapsulation of human-nerve growth factor (NGF). One of the best methods for fabricating a bio-functional tissue engineering scaffold is to load bioactive agent into the scaffold. In this work, the feasibility of incorporating NGF into poly(l-lactide-co-caprolactone) fibers by emulsion electrospinning has been studied. The release behavior of encapsulated bovine serum albumin (BSA) was investigated. The bioactivity of NGF released from fibrous mats was verified by testing the neurite outgrowth of rat pheochromocytoma cells (PC12). Furthermore, the process of fiber forming during emulsion electrospinning was discussed. The results demonstrate that emulsion electrospun fibers can successfully encapsulate proteins and release them in a sustained manner. The bioactivity of NGF released from emulsion electrospun fibers was confirmed by PC12 bioassays.     

Nanoparticle formation and ultrathin film electrodeposition of carbazole dendronized polynorbornenes prepared by ring-opening metathesis polymerization

We report on the synthesis, electropolymerization, and nanoparticle formation of a series of electroactive carbazole-terminated dendronized linear polynorbornenes prepared by living ring-opening metathesis polymerization (ROMP). The molecular weight (MW) of the dendronized polymers was controlled by varying the feed ratio between the dendronized monomer and first-generation Grubbs' catalyst. Ultrathin films were prepared by electrodeposition. The electrochemical behavior and viscoelastic properties of such films were found to be highly dependent on the dendron generation and linear polymer MW as studied by electrochemical quartz crystal microbalance (E-QCM). Moreover, nanoparticle formation and size/shape control were observed by tuning the surface wetting properties of the substrate during adsorption and by intramolecular cross-linking via chemical oxidation in solution.     

Simultaneous quantification of a non-nucleoside reverse transcriptase inhibitor efavirenz, a nucleoside reverse transcriptase inhibitor emtricitabine and a nucleotide reverse transcriptase inhibitor tenofovir in plasma by liquid chromatography positive ion electrospray tandem mass spectrometry

A high-performance liquid chromatography/positive ion electrospray tandem mass spectrometry method for the simultaneous quantification of efavirenz, emtricitabine and tenofovir was developed and validated with 100 microL human plasma. Following solid-phase extraction, the analytes were separated using a gradient mobile phase on a reverse-phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M + H]+ ions, m/z 316 to 168 for efavirenz, m/z 248-130 for emtricitabine and m/z 288-176 for tenofovir, m/z 482-258 for rosuvastatin (IS), m/z 260-116 for propranolol (IS). The method exhibited a 100-fold linear dynamic range for all the three analytes in human plasma (20-2000, 2-200 and 20-2000 ng/mL for efavirenz, emtricitabine and tenofovir respectively). The lower limit of quantification was 2 ng/mL for emtricitabine and 20 ng/mL for both efavirenz and tenofovir with a relative standard deviation of less than 11%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The total chromatographic run time of 4 min for each sample made it possible to analyze more than 250 human plasma samples per day. The method is precise and sensitive enough for its intended purpose. The method is also successfully applied to quantify efavirenz, emtricitabine and tenofovir concentrations in a rodent pharmacokinetic study.