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1.
Low-flow chromatography has a rich history of innovation but has yet to reach widespread implementation in bioanalytical applications. Improvements in pump technology, microfluidic connections, and nano-electrospray sources for MS have laid the groundwork for broader application, and innovation in this space has accelerated in recent years. This article reviews the instrumentation used for nano-flow LC, the types of columns employed, and strategies for multidimensionality of separations, which are key to the future state of the technique to the high-throughput needs of modern bioanalysis. An update of the current applications where nano-LC is widely used, such as proteomics and metabolomics, is discussed. But the trend toward biopharmaceutical development of increasingly complex, targeted, and potent therapeutics for the safe treatment of disease drives the need for ultimate selectivity and sensitivity of our analytical platforms for targeted quantitation in a regulated space. The selectivity needs are best addressed by mass spectrometric detection, especially at high resolutions, and exquisite sensitivity is provided by nano-electrospray ionization as the technology continues to evolve into an accessible, robust, and easy-to-use platform. 相似文献
2.
Brandon C. Presley Marisol S. Castaneto Barry K. Logan Susan A. Jansen-Varnum 《Biomedical chromatography : BMC》2020,34(9):e4884
FUB-AMB, an indazole carboxamide synthetic cannabinoid recreational drug, was one of the compounds most frequently reported to governmental agencies worldwide between 2016 and 2019. It has been implicated in intoxications and fatalities, posing a risk to public health. In the current study, FUB-AMB was incubated with human liver microsomes (HLM) to assess its metabolic fate and stability and to determine if its major ester hydrolysis metabolite (M1) was present in 12 authentic forensic human blood samples from driving under the influence of drug cases and postmortem investigations using UHPLC–MS/MS. FUB-AMB was rapidly metabolized in HLM, generating M1 that was stable through a 120-min incubation period, a finding that indicates a potential long detection window in human biological samples. M1 was identified in all blood samples, and no parent drug was detected. The authors propose that M1 is a reliable marker for inclusion in laboratory blood screens for FUB-AMB; this metabolite may be pharmacologically active like its precursor FUB-AMB. M1 frequently appears in samples in which the parent drug is undetectable and can point to the causative agent. The results suggest that it is imperative that synthetic cannabinoid laboratory assay panels include metabolites, especially known or potential pharmacologically active metabolites, particularly for compounds with short half-lives. 相似文献
3.
Amphiphilic block copolymer self‐assemblies of poly(NVP)‐b‐poly(MDO‐co‐vinyl esters): Tunable dimensions and functionalities 下载免费PDF全文
Guillaume G. Hedir A. Pitto‐Barry Andrew P. Dove Rachel K. O'Reilly 《Journal of polymer science. Part A, Polymer chemistry》2015,53(23):2699-2710
Functional, degradable polymers were synthesized via the copolymerization of vinyl acetate (VAc) and 2‐methylene‐1,3‐dioxepane (MDO) using a macro‐xanthate CTA, poly(N‐vinylpyrrolidone), resulting in the formation of amphiphilic block copolymers of poly(NVP)‐b‐poly(MDO‐co‐VAc). The behavior of the block copolymers in water was investigated and resulted in the formation of self‐assembled nanoparticles containing a hydrophobic core and a hydrophilic corona. The size of the resultant nanoparticles was able to be tuned with variation of the hydrophilic and hydrophobic segments of the core and corona by changing the incorporation of the macro‐CTA as well as the monomer composition in the copolymers, as observed by Dynamic Light Scattering, Static Light Scattering, and Transmission Electron Microscopy analyses. The concept was further applied to a VAc derivative monomer, vinyl bromobutanoate, to incorporate further functionalities such as fluorescent dithiomaleimide groups throughout the polymer backbone using azidation and “click” chemistry as postpolymerization tools to create fluorescently labeled nanoparticles. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2699–2710 相似文献
4.
Liping Zhu Samantha Powell Stephen G. Boyes 《Journal of polymer science. Part A, Polymer chemistry》2015,53(8):1010-1022
Well‐defined tertiary amine‐based pH‐responsive homopolymers and block copolymers were synthesized via reversible addition‐fragmentation chain transfer (RAFT) polymerization using 4‐cyanopentanoic acid dithiobenzoate (CPAD) as the RAFT agent for homopolymers and a poly(ethylene glycol) (PEG) macro‐RAFT agent for the block copolymers. 1H NMR and gel permeation chromatography results confirmed the successful synthesis of these homopolymers and block copolymers. Kinetics studies indicated that the formation of both the homopolymers and the block copolymers were well defined. The pKa titration experiments suggested that the homopolymers and the related block copolymers have a similar pKa. The dynamic light scattering investigation showed that all of the block copolymers underwent a sharp transition from unimers to micelles around their pKa and the hydrodynamic diameter (Dh) was not only dependent on the molecular weight but also on the composition of the block copolymers. The polymer solution of PEG‐b‐PPPDEMA formed the largest micelle compare to the PEG‐b‐PDPAEMA and PEG‐b‐PDBAEMA with a similar molecular weight. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1010–1022 相似文献
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Chris H. Hill Agnete H. Viuff Samantha J. Spratley Stéphane Salamone Stig H. Christensen Randy J. Read Nigel W. Moriarty Henrik H. Jensen Janet E. Deane 《Chemical science》2015,6(5):3075-3086
Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe a new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease. 相似文献
7.
Cyanide Bridged Platinum-Iron Complexes as Cisplatin Prodrug Systems: Design and Computational Study
Dr. Ariela W. Kaspi-Kaneti Srijana Bhandari Dr. Alexander Schubert Prof. Songping D. Huang Prof. Barry D. Dunietz 《Chemphyschem》2021,22(1):106-111
The potential role of cyanide-bridged platinum-iron complexes as an anti-cancer Pt(IV) prodrug is studied. We present design principles of a dual-function prodrug that can upon reduction dissociate and release concurrently six cisplatin units and a ferricyanide anion per prodrug unit. The prodrug molecule is a unique complex of hepta metal centers consisting of a ferricyanide core with six Pt(IV) centers each bonded to the Fe(III) core through a cyano ligand. The functionality of the prodrug is addressed through density functional theory (DFT) calculations. 相似文献
8.
Nonlinear Dynamics - We investigate the control of friction-induced vibration in a precision motion stage under the effect of the LuGre friction dynamics. We consider a lumped parameter model of... 相似文献
9.
X-ray Photoelectron Spectroscopy was used to study a ferroan platinum crystal from the Kondyor Massif, Russian Far East. Prior to the X-ray Photoelectron Spectroscopic analyses, the nature of the crystal was confirmed by X-ray diffraction. The survey scan showed mainly the presence of Pt and Fe, with smaller amounts of O and Si. The high resolutions spectra of the Pt 4f and Fe 2p showed 18.3 atom% Fe in the crystal, which puts the composition on the lower boundary for ferroan platinum and confirms earlier analyses using other methods such as Scanning Electron Microscopy-Energy Dispersive X-ray analysis/microprobe. The binding energy of the Pt 4f5/2 was 74.0?eV and Pt 4f7/2 70.5?eV, while the Fe 2p3/2 for metallic Fe was observed at 707.2?eV. The Fe 2p3/2 for metallic Fe was significantly sharper than that of Fe 2p3/2 at 710.7?eV associated with surface material. The Raman spectrum was dominated by the Pt–Pt stretching mode at 253?cm?1. Changed orientation resulted in the observation of two bands at 127 and 139?cm?1, interpreted as being due to stretching modes of two Pt–Pt bonds with the third bond to Fe and Pt fixed. The presence of Ca-Fe-Al-Mg-Si-O on the surface was probably associated with the presence of a clinopyroxene. These minerals can be expected since the crystal came originally from a clinopyroxenite-dunite matrix. The spectra showed a variety of interferences, e.g. Al 2p with Pt 4f, Mg 2p with Fe 3p, and Ca 2p1/2 with Mg Auger, making exact determinations of the ratios of these elements difficult. 相似文献
10.
Dr. Samantha A. Orr Dr. Emily C. Border Prof. Philip C. Andrews Dr. Victoria L. Blair 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(51):11876-11882
By exploring lithium–bromide exchange reactivity of aromatic Schiff's bases with tert-butyllithium (tBuLi), we have revealed unprecedented competitive intermolecular and intramolecular cascade annulation pathways, leading to valuable compounds, such as iso-indolinones and N-substituted anthracene derivatives. A series of reaction parameters were probed, including solvent, stoichiometry, sterics and organolithium reagent choice, in order to understand the influences that limit such ring-closing pathways. With two viable reactivity options for the organolithium on the imine; namely, nucleophilic addition or lithium–bromide exchange, a surprising competitive nature was observed, where nucleophilic addition dominated, even under cryogenic conditions. Considering the most commonly used solvents for lithium–bromide exchange, tetrahydrofuran (THF) and diethyl ether (Et2O), contrasting reactivity outcomes were revealed with nucleophilic addition promoted in THF, while Et2O yielded almost double the conversion of cyclic products than in THF. 相似文献