CO₂ Capture and Use in a Novel Coal-Based Polygeneration System

A novel coal-based polygeneration system with CO₂ recycling for CO₂ capture is proposed. Two CO₂ recycling schemes exist in this system. In the first, CO₂ is recycled into the gasifier as the gasifying agent. In the second, CO₂ is recycled into the gas turbine as a diluent. Compared with conventional CCS systems, this new system avoids the use of water gas shift and CO₂ separation processes to capture CO₂, and, more importantly, a part of CO₂ can be converted into CO in coal gasification and be used to synthesize chemicals, improving carbon element utilization and chemical output. By means of exergy analysis, comparison with four conventional single production systems shows that the proposed system provides more than 11% in energy savings and more than 25% in capital investment saving. The exergy efficiency, CO₂ emission, and internal rate of return may be expected to reach 46.3%, 0.47 <i>t</i>·(<i>t</i>-coal)⁻¹ and 14.76%, respectively

Nucleic Acid-Induced Tetraphenylethene Probe Noncovalent Self-Assembly and the Superquenching of Aggregation-Induced Emission

Superquenching of aggregation-induced emission (AIE) has been utilized in biosensing for the first time. A positively charged tetraphenylethene derivative (compound <b>1</b>) showed no emission in an aqueous buffer solution. A single-stranded DNA (a polyanion) induced aggregation of compound <b>1</b>, and strong compound <b>1</b> aggregate emission was observed. When the DNA was labeled with a quencher molecule, compound <b>1</b> aggregate emission was efficiently quenched. On the basis of this observation, a new, simple, sensitive and selective DNA methyltransferase (MTase) assay has been developed. A quencher-labeled double-stranded DNA could induce aggregation of compound <b>1</b>, and superquenching of compound <b>1</b> AIE was observed. In the presence of MTase and an endonuclease, the DNA could be specifically methylated and cleaved into single-stranded DNA fragments. The quencher molecule was released, and a turn-on emission signal was detected

Real-Time Fluorometric Assay for Acetylcholinesterase Activity and Inhibitor Screening through the Pyrene Probe Monomer–Excimer Transition

A choline labeled pyrene probe (<b>Py-Ch</b>) was designed and synthesized. Poly(vinylsulfonate) (PVS) could induce <b>Py-Ch</b> aggregation. The aggregation and deaggregation process could be finely controlled by the acetylcholinesterase (AChE) enzymatic hydrolysis of <b>Py-Ch</b>. The resulting excimer–monomer transition provided a facile way for real-time AChE activity fluorometric assay and inhibitor screening

Biocompatible Surface-Coated Probe for <i>in Vivo</i>, <i>in Situ</i>, and Microscale Lipidomics of Small Biological Organisms and Cells Using Mass Spectrometry

Lipidomics is a significant way to understand the structural and functional roles that lipids play in biological systems. Although many mass spectrometry (MS)-based lipidomics strategies have recently achieve remarkable results, <i>in vivo</i>, <i>in situ</i>, and microscale lipidomics for small biological organisms and cells have not yet been obtained. In this article, we report a novel lipidomics methodology for <i>in vivo</i>, <i>in situ</i>, and microscale investigation of small biological organisms and cells using biocompatible surface-coated probe nanoelectrospray ionization mass spectrometry (BSCP-nanoESI-MS). A novel biocompatible surface-coated solid-phase microextration (SPME) probe is prepared, which possesses a probe-end diameter of less than 5 μm and shows excellent enrichment capacity toward lipid species. <i>In vivo</i> extraction of living biological organisms (e.g., zebrafishes), <i>in situ</i> sampling a precise position of small organisms (e.g., <i>Daphnia magna</i>), and even microscale analysis of single eukaryotic cells (e.g., HepG2) are easily achieved by the SPME probe. After extraction, the loaded SPME probe is directly applied for nanoESI-MS analysis, and a high-resolution mass spectrometer is employed for recording spectra and identifying lipid species. Compared with the conventional direct infusion shotgun MS lipidomics, our proposed methodology shows a similar result of lipid profiles but with simpler sample pretreatment, less sample consumption, and shorter analytical times. Lipidomics of zebrafish, <i>Daphnia magna</i>, and HepG2 cell populations were investigated by our proposed BSCP-nanoESI-MS methodology, and abundant lipid compositions were detected and identified and biomarkers were obtained via multivariate statistical analysis

Imaging GPCR Dimerization in Living Cells with Cucurbit[7]uril and Hemicyanine as a “Turn-On” Fluorescence Probe

Although multiple forms of dimers have been described for GPCR, their dynamics and function are still controversially discussed field. Fluorescence microscopy allows GPCR to be imaged within their native context; however, a key challenge is to site-specifically incorporate reporter moieties that can produce high-quality signals upon formation of GPCR dimers. To this end, we propose a supramolecular sensor approach to detect agonist-induced dimer formation of μ-opioid receptors (μORs) at the surface of intact cells. With the macrocyclic host cucurbit[7]uril and its guest hemicyanine dye tethered to aptamer strands directed against the histidine residues, the sensing module is assembled by host–guest complexation once the histidine-tagged μORs dimerize and bring the discrete supramolecular units into close proximity. With the enhanced sensitivity attributed by the “turn-on” fluorescence emission and high specificity afforded by the intermolecular recognition, in situ visualization of dynamic GPCR dimerization was realized with high precision, thereby validating the supramolecular sensing entity as a sophisticated and versatile strategy to investigate GPCR dimers, which represent an obvious therapeutic target

Characterization of ADME properties of [¹⁴C]asunaprevir (BMS-650032) in humans

<div><p></p><p>1. Asunaprevir (ASV, BMS-650032), a highly selective and potent NS3 protease inhibitor, is currently under development for the treatment of chronic hepatic C virus infection. This study describes <i>in vivo</i> biotransformation in humans and the identification of metabolic enzymes of ASV.</p><p>2. Following a single oral dose of [¹⁴C]ASV to humans, the majority of radioactivity (>73% of the dose) was excreted in feces with <1% of the dose recovered in urine. Drug-related radioactivity readily appeared in circulation and the plasma radioactivity was mainly attributed to ASV. A few minor metabolites were observed in human plasma and are not expected to contribute to the pharmacological activity because of low levels. The area under the curve (AUC) values of each circulating metabolite in humans were well below their levels in animals used in the long-term toxicological studies. In bile and feces, intact ASV was a prominent radioactive peak suggesting that both metabolism and direct excretion played important roles in ASV clearance.</p><p>3. The primary metabolic pathways of ASV were hydroxylation, sulfonamide hydrolysis and the loss of isoquinoline. <i>In vitro</i> studies with human cDNA expressed CYP enzymes and with human liver microsomes (HLM) in the presence of selective chemical inhibitors demonstrated that ASV was primarily catalyzed by CYP3A4 and CYP3A5.</p></div

Practical and Efficient Strategy for Evaluating Oral Absolute Bioavailability with an Intravenous Microdose of a Stable Isotopically-Labeled Drug Using a Selected Reaction Monitoring Mass Spectrometry Assay

A strategy of using selected reaction monitoring (SRM) mass spectrometry for evaluating oral absolute bioavailability with concurrent intravenous (IV) microdosing a stable isotopically labeled (SIL) drug was developed and validated. First, the isotopic contribution to SRM (ICSRM) of the proposed SIL drug and SIL internal standard (IS) was theoretically calculated to guide their chemical synthesis. Second, the lack of an isotope effect on drug exposure was evaluated in a monkey study by IV dosing a mixture of the SIL and the unlabeled drugs. Third, after the SIL drug (100 μg) was concurrently IV dosed to humans, at <i>T</i>_max of an oral therapeutic dose of the unlabeled drug, both drugs in plasma specimens were simultaneously quantified by a sensitive and accurate SRM assay. This strategy significantly improves bioanalytical data quality and saves time, costs, and resources by avoiding a traditional absolute bioavailability study or the newer approach of microdoses of a radio-microtracer measured by accelerator mass spectrometry

Synthesis of Biologically Active Piperidine Metabolites of Clopidogrel: Determination of Structure and Analyte Development

Clopidogrel is a prodrug anticoagulant with active metabolites that irreversibly inhibit the platelet surface GPCR P2Y₁₂ and thus inhibit platelet activation. However, gaining an understanding of patient response has been limited due to imprecise understanding of metabolite activity and stereochemistry, and a lack of acceptable analytes for quantifying in vivo metabolite formation. Methods for the production of all bioactive metabolites of clopidogrel, their stereochemical assignment, and the development of stable analytes via three conceptually orthogonal routes are disclosed

Discovery and Early Clinical Evaluation of BMS-605339, a Potent and Orally Efficacious Tripeptidic Acylsulfonamide NS3 Protease Inhibitor for the Treatment of Hepatitis C Virus Infection

The discovery of BMS-605339 (<b>35</b>), a tripeptidic inhibitor of the NS3/4A enzyme, is described. This compound incorporates a cyclopropyl­acylsulfonamide moiety that was designed to improve the potency of carboxylic acid prototypes through the introduction of favorable nonbonding interactions within the S1′ site of the protease. The identification of <b>35</b> was enabled through the optimization and balance of critical properties including potency and pharmacokinetics (PK). This was achieved through modulation of the P2* subsite of the inhibitor which identified the isoquinoline ring system as a key template for improving PK properties with further optimization achieved through functionalization. A methoxy moiety at the C6 position of this isoquinoline ring system proved to be optimal with respect to potency and PK, thus providing the clinical compound <b>35</b> which demonstrated antiviral activity in HCV-infected patients