排序方式: 共有16条查询结果,搜索用时 15 毫秒
1.
Dr. Jeanette E. Stok Dr. Sharon Chow Dr. Elizabeth H. Krenske Clementina Farfan Soto Csongor Matyas Prof. Raymond A. Poirier Prof. Craig M. Williams Prof. James J. De Voss 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(13):4408-4412
The cytochromes P450 are hemoproteins that catalyze a range of oxidative C?H functionalization reactions, including aliphatic and aromatic hydroxylation. These transformations are important in a range of biological contexts, including biosynthesis and xenobiotic biodegradation. Much work has been carried out on the mechanism of aliphatic hydroxylation, implicating hydrogen atom abstraction, but aromatic hydroxylation is postulated to proceed differently. One mechanism invokes as the key intermediate an arene oxide (and/or its oxepin tautomer). Conclusive isolation of this intermediate has remained elusive and, currently, direct formation of phenols from a Meisenheimer intermediate is believed to be favored. We report here the identification of a P450 [P450cam (CYP101A1) and P450cin (CYP176A1)]‐generated arene oxide as a product of in vitro oxidation of tert‐butylbenzene. Computations (CBS‐QB3) predict that the arene oxide and oxepin have similar stabilities to other arene oxides/oxepins implicated (but not detected) in P450‐mediated transformations, suggesting that arene oxides can be unstable terminal products of P450‐catalyzed aromatic oxidation that can explain the origin of some observed metabolites. 相似文献
2.
Oscar B. Torres Rashmi Jalah Kenner C. Rice Fuying Li Joshua F. G. Antoline Malliga R. Iyer Arthur E. Jacobson Mohamed Nazim Boutaghou Carl R. Alving Gary R. Matyas 《Analytical and bioanalytical chemistry》2014,406(24):5927-5937
A potential new treatment for drug addiction is immunization with vaccines that induce antibodies that can abrogate the addictive effects of the drug of abuse. One of the challenges in the development of a vaccine against drugs of abuse is the availability of an optimum procedure that gives reproducible and high yielding hapten-protein conjugates. In this study, a heroin/morphine surrogate hapten (MorHap) was coupled to bovine serum albumin (BSA) using maleimide-thiol chemistry. MorHap-BSA conjugates with 3, 5, 10, 15, 22, 28, and 34 haptens were obtained using different linker and hapten ratios. Using this optimized procedure, MorHap-BSA conjugates were synthesized with highly reproducible results and in high yields. The number of haptens attached to BSA was compared by 2,4,6-trinitrobenzenesulfonic acid (TNBS) assay, modified Ellman’s test and matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Among the three methods, MALDI-TOF MS discriminated subtle differences in hapten density. The effect of hapten density on enzyme-linked immunosorbent assay (ELISA) performance was evaluated with seven MorHap-BSA conjugates of varying hapten densities, which were used as coating antigens. The highest antibody binding was obtained with MorHap-BSA conjugates containing 3–5 haptens. This is the first report that rigorously analyzes, optimizes and characterizes the conjugation of haptens to proteins that can be used for vaccines against drugs of abuse. The effect of hapten density on the ELISA detection of antibodies against haptens demonstrates the importance of careful characterization of the hapten density by the analytical techniques described. 相似文献
3.
The [Cp*IrCl(2)](2)-catalysed alkylation of amines with alcohols was investigated using a combination of experimental and theoretical methods. A Hammett study involving a series of para-substituted benzyl alcohols resulted in a line with a negative slope. This clearly documents that a positive charge is built up in the transition state, which in combination with the measurement of a significant kinetic isotope effect determines hydride abstraction as being the selectivity-determining step under these conditions. A complementary Hammett study using para-substituted anilines was also carried out. Again, a line with a negative slope was obtained suggesting that nucleophilic attack on the aldehyde is selectivity-determining. A computational investigation of the entire catalytic cycle with full-sized ligands and substrates was performed using density functional theory. The results suggest a catalytic cycle where the intermediate aldehyde stays coordinated to the iridium catalyst and reacts with the amine to give a hemiaminal which is also bound to the catalyst. Dehydration to the imine and reduction to the product amine also takes place without breaking the coordination to the catalyst. The fact that the entire catalytic cycle takes place with all the intermediates bound to the catalyst is important for the further development of this synthetic transformation. 相似文献
4.
Ning Z Molnár M Chen Y Friberg P Gan L Ågren H Fu Y 《Physical chemistry chemical physics : PCCP》2011,13(13):5848-5854
In order to study the role of surface ligands in determining optical properties of colloidal quantum dots (QDs), we have selectively fabricated and studied CdSe/CdS core-shell QDs with strongly confined electron and hole states attached with commonly used surface ligands. Optical properties, viz. absorption and fluorescence of these QDs, are characterized from which salient changes have been observed for different ligand substitutions which, through theoretical analysis, can be associated with electronic structure properties of the QD-ligand composite systems, in particular localization of wave functions of electrons and holes in the QDs and the band matching of the HOMO-LUMO gap of the ligands. The findings can be utilized to facilitate the understanding and optimization of properties of QD biomarkers with functionalizing surface ligands for targeting cellular objects. 相似文献
5.
Building‐related health effects are frequently observed. Several factors have been listed as possible causes including temperature, humidity, light conditions, presence of particulate matter, and microorganisms or volatile organic compounds. To be able to link exposure to specific volatile organic compounds to building‐related health effects, powerful and comprehensive analytical methods are required. For this purpose, we developed an active air sampling method that utilizes dual‐bed tubes loaded with TENAX‐TA and Carboxen‐1000 adsorbents to sample two parallel air samples of 4 L each. For the comprehensive volatile organic compounds analysis, an automated thermal desorption comprehensive two‐dimensional gas chromatography high‐resolution time‐of‐flight mass spectrometry method was developed and used. It allowed targeted analysis of approximately 90 known volatile organic compounds with relative standard deviations below 25% for the vast majority of target volatile organic compounds. It also allowed semiquantification (no matching standards) of numerous nontarget air contaminants using the same data set. The nontarget analysis workflow included peak finding, background elimination, feature alignment, detection frequency filtering, and tentative identification. Application of the workflow to air samples from 68 indoor environments at a large hospital complex resulted in a comprehensive volatile organic compound characterization, including 178 single compounds and 13 hydrocarbon groups. 相似文献
6.
Kurt L. Komarek Peter Matyas Johann Mikler 《Monatshefte für Chemie / Chemical Monthly》1975,106(1):73-84
The enthalpies of formation of solid Co?Te alloys were determined at room temperature with an isoperibol solution calorimeter of the submarine type. Co?Te alloys and mechanical mixtures of the pure components were dissolved in separate experiments in a saturated hydrochloric acid (8.000n)—bromine mixture and the enthalpies of formation obtained by difference. For the NiAs-type β-phase ΔH f o(NTe)=(4.079–15.017N Te) kcal·g-atom?1 and for the marcasitetype γ-phase ΔH f o(N Te)=(3.787–14.400N Te) kcal·g-atom?1. Combining these results with data from the literature integral thermodynamic properties of solid Co—Te alloys were calculated at room temperature and at 600°C. 相似文献
7.
Silke I. Nitsche Edwin Weber Wilhelm Seichter Matyas Czugler Wolfram Palitzsch Gerhard Roewer 《Silicon Chemistry》2003,2(1-2):45-54
New organooligosiloxanes 1–5 (Scheme 1) featuring α ,ω -arylethynyl moieties have been synthesized. Complex ensembles of weak intramolecular interactions lead to the formation of interesting architectures, exhibiting the unusual U-shaped molecular geometry of compounds 1, 2 and 4, which has not been found previously example. Replacement of the methyl groups in 1 by phenyl substituents in the disiloxane 4 gives rise to the formation of hydrophobic monolayers different from the bilayer packing behavior of the analogous compound 1. Incorporation of methoxy substituted arene units in the α ,ω -positions completely abolishes intramolecular interactions as indicated in compound 5, which alsoshows the lowest degree of supramolecular contacts (while all the other packing structures are dominated by π -stacking andC-H···π interactions). 相似文献
8.
Mechler M Kukhlevsky SV Mechler A McNaughton D 《Physical chemistry chemical physics : PCCP》2011,13(46):20772-20778
Optical field distribution in micro-nano geometries of miniaturized optical devices is often significantly different from that in identical but macroscopic geometries. Plasmon effects and near-field diffraction can enhance the local field intensity, leading to enhanced cross section for light absorption and scattering, which can be utilized in substrate-enhanced spectroscopies for the detection of trace amounts of adsorbed chemicals. A specific problem is an ingenious but only empirically described way to enhance signal intensity in Raman spectroscopy by the use of a substrate patterned with gold coated micron size pyramidal pits. While Raman enhancement on nanostructured substrates is generally attributed to surface plasmons, here the micron size, and thus the sub-wavelength to near-wavelength dimensions suggest that resonant enhancement emanating from optical near-field diffraction might also play a role. To answer this question, light diffraction in a projection of the pyramidal pit: a V-groove, was modelled with a modified Neerhoff-Mur formalism suitable to calculate electromagnetic field distribution in sub-wavelength structures. Under the boundary conditions a perfect conductor screen was assumed, which excludes plasmon effects. The calculations show that interference in the cavity causes a modest resonant increase in local intensity and that near-field diffraction strongly influences the field distribution, which is explained with the electrodynamic edge effect. The magnitude of the resonant electric field on its own cannot account for the experimentally observed Raman enhancement. However, a resonant enhancement of a similar magnitude is expected for the emitted Stokes frequencies. In this case the geometry implements the conditions for the classical electromagnetic Raman enhancement, ~E(4), in a good agreement with experimental results. 相似文献
9.
Kraft lignin is an inexpensive and abundant byproduct of pulp mills that can be used in the synthesis of adhesives and carbon fibers along with energy production. Some of these material applications favor the utilization of high molecular weight (HMW) lignin. This study investigates the use of ultrasonics as a means to increase the degree of polymerization (DP) of highly purified Kraft lignin. Treated samples were characterized by gel permeation chromatography (GPC), Fourier transform infrared (FTIR) spectroscopy, 13C and 31P nuclear magnetic resonance (NMR). After 15 min of sustained cavitation, ultrasonicated lignin generated a high molecular-weight fraction (~35%) that had a weight-average molecular weight (Mw) over 450-fold greater than the initial Kraft lignin sample. 13C-NMR and 31P-NMR analysis indicated that the highly-polymerized fraction was enriched with C5 condensed phenolic structures. 相似文献
10.
Design,Synthesis, and In Vivo Evaluation of C1-Linked 4,5-Epoxymorphinan Haptens for Heroin Vaccines
Agnieszka Sulima Fuying Li Jeffrey Brian Morgan Phong Truong Joshua F. G. Antoline Therese Oertel Rodell C. Barrientos Oscar B. Torres Zoltan Beck Gregory H. Imler Jeffrey R. Deschamps Gary R. Matyas Arthur E. Jacobson Kenner C. Rice 《Molecules (Basel, Switzerland)》2022,27(5)
In our continuing effort to develop effective anti-heroin vaccines as potential medications for the treatment of opioid use disorder, herein we present the design and synthesis of the haptens: 1-AmidoMorHap (1), 1-AmidoMorHap epimer (2), 1 Amido-DihydroMorHap (3), and 1 Amido-DihydroMorHap epimer (4). This is the first report of hydrolytically stable haptenic surrogates of heroin with the attachment site at the C1 position in the 4,5-epoxymorophinan nucleus. We prepared respective tetanus toxoid (TT)–hapten conjugates as heroin vaccine immunogens and evaluated their efficacy in vivo. We showed that all TT–hapten conjugates induced high antibody endpoint titers against the targets but only haptens 2 and 3 can induce protective effects against heroin in vivo. The epimeric analogues of these haptens, 1 and 4, failed to protect mice from the effects of heroin. We also showed that the in vivo efficacy is consistent with the results of the in vitro drug sequestration assay. Attachment of the linker at the C1 position induced antibodies with weak binding to the target drugs. Only TT-2 and TT-3 yielded antibodies that bound heroin and 6-acetyl morphine. None of the TT–hapten conjugates induced antibodies that cross-reacted with morphine, methadone, naloxone, or naltrexone, and only TT-3 interacted weakly with buprenorphine, and that subtle structural difference, especially at the C6 position, can vastly alter the specificity of the induced antibodies. This study is an important contribution in the field of vaccine development against small-molecule targets, providing proof that the chirality at C6 in these epoxymorphinans is a vital key to their effectiveness. 相似文献