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91.
Fast reduction of a copper center in laccase by nitric oxide and formation of a peroxide intermediate 总被引:3,自引:0,他引:3
Torres J Svistunenko D Karlsson B Cooper CE Wilson MT 《Journal of the American Chemical Society》2002,124(6):963-967
The rapid reduction of one of the copper atoms (type 2) of tree laccase by nitric oxide (NO) has been detected. Addition of NO to native laccase in the presence of oxygen leads to EPR changes consistent with fast reduction and slow reoxidation of this metal center. These events are paralleled by optical changes that are reminiscent of formation and decay of the peroxide intermediate in a fraction of the enzyme population. Formation of this species is only possible if the trinuclear copper cluster (type 2 plus type 3) is fully reduced. This condition can only be met if, as suggested previously, a fraction of the enzyme contains both type 3 coppers already reduced before addition of NO. Our data are consistent with this assumption. We have suggested recently that fast reduction of copper is the mechanism by which NO interacts with the oxidized dinuclear center in cytochrome c oxidase. The present experiments using laccase strongly support this view and suggest this reaction as a general mechanism by which copper proteins interact with NO. In addition, this provides an unexploited way to produce a stable peroxide intermediate in copper oxidases in which the full complement of copper atoms is present. This enables the O-O scission step in the catalytic cycle to be studied by electron addition to the peroxide derivative through the native electron entry site, type 1 copper. 相似文献
92.
Van den Bergh V Coeckelberghs H Vankerckhoven H Compernolle F Vinckier C 《Analytical and bioanalytical chemistry》2004,379(3):484-494
The oxidation of the terpenes - and -pinene, limonene and 3-carene by hydroxyl radicals has been investigated in a fast-flow reactor coupled to a liquid nitrogen trap for collecting the carbonyl compounds. Identification of the products was performed via 2,4-dinitrophenylhydrazone (DNPH) derivatization of the carbonyls to form the mono- and di-DNPH derivatives, which were analysed by high-performance liquid chromatographic (HPLC)-DAD (diode array detector) and HPLC-mass spectrometry (HPLC-MS). Both electrospray ionization [ESI(–)] and atmospheric pressure chemical ionization [APCI(–)] were suitable for the detection of the DNPH derivatives of formaldehyde, acetaldehyde, myrtanal, campholene aldehyde, perillaldehyde, acetone, nopinone, trans-4-hydroxynopinone and 4-acetyl-1-methylcyclohexene. Also the mono-DNPH derivatives of the dicarbonyl compounds pinonaldehyde, endolim and caronaldehyde could be identified. The MS2 spectra generated in the ion trap of the mass spectrometer allowed us to distinguish between aldehydes and ketones on the basis of the characteristic fragment ion m/z 163 for the aldehydes. For the quantitative analysis of the mono-DNPH derivatives, ESI(–) in combination with single ion monitoring (SIM) detection showed the lowest detection limits. For the quantification of the dicarbonyl compounds, the acid-sensitive di-DNPH derivatives had to be formed by keeping the acidity in the acid-catalysed derivatization reaction at about 1.7 mM H2SO4. Detection of these dicarbonyl compounds can only be performed by APCI(–) with somewhat lesser sensitivity than by HPLC-DAD. 相似文献
93.
Wu G Irvine J Luft C Pressley D Hodge CN Janzen B 《Combinatorial chemistry & high throughput screening》2003,6(4):303-312
Caspase proteases are familiar targets in drug discovery. A common format for screening to identify caspase inhibitors employs fluorogenic or colorimetric tetra-peptide substrates in 96, 384, or 1536 -well microtiter plates. The primary motivation for increasing the number of wells per plate is to reduce the reagent cost per test and increase the throughput of HTS operations. There are significant challenges, however, to moving into or beyond the 1536-well format, such as submicroliter liquid handling, liquid evaporation, increased surface area-to-volume ratios, and the potential for artifacts and interference from small air-borne particles such as lint. Therefore, HTS scientists remain keenly interested in technologies that offer alternatives to the ever-shrinking microtiter plate well. Microfluidic assay technology represents an attractive option that, in theory, consumes only subnanoliter volumes of reagents per test. We have successfully employed a microfluidic assay technology in fluorogenic screening assays for several caspase isoforms utilizing the Caliper Technologies Labchip platform. Caspase-3 is used as a representative case to describe microfluidic assay development and initial high-throughput screening results. In addition, microfluidic screening and plate-based screening are compared in terms of reagent consumption, data quality, and ease of operation. 相似文献
94.
A flexible, pyridine-functionalized diaza-crown ether was self-assembled into discrete supramolecules of differing stoichiometries upon combination with various organoplatinum molecules. They are characterized by electrospray ionization mass spectrometry and (31)P[(1)H] and (1)H NMR. In one case, (1)H-(1)H NOE enhancements of a [1 + 1] assembled structure demonstrate the puckered shape of the macrocyclic ring. Despite its inherent flexibility, the dipyridyl-substituted 18-membered diaza-crown ligand prefers to self-assemble into closed systems when reacted with platinum-containing acceptors. 相似文献
95.
William W. Ward Hugh J. Prentice Amy F. Roth Chris W. Cody Sue C. Reeves 《Photochemistry and photobiology》1982,35(6):803-808
Abstract— In the jellyfish Aequorea, the green-fluorescent protein (GFP) functions as the in vivo bio-luminescence emitter via energy transfer from the photoprotein aequorin. Accumulated evidence has indicated that the Aequorea GFP is a relatively inflexible protein. Present evidence, however, indicates that the chromophore environment is readily accessible to a variety of external perturbants. Native Aequorea GFP has an absorbance maximum at 395 nm and a shoulder at 470 nm. In low ionic strength buffer at neutral pH and room temperature the 395/470 nm absorbance ratio is about 2.0. We show that this ratio is highly variable depending upon temperature, ionic strength, protein concentration, and pH. A maximum ratio of 6.5 (at a protein concentration of 18.6 mg/m/) and minimum of 0.42 (at a pH of 12.2) have been measured. In the latter case, the resulting absorption and excitation spectra resemble those of Renilla GFP in spectral shape (but not wavelength maximum). In all cases as the perturbant is varied the resulting spectra pass through a sharp isosbestic point, suggesting a relatively simple two-state mechanism. These spectral perturbations are fully reversible. On the basis of these results, we suggest that the chromophore binding site is conformationally flexible. pH-Dependent changes in the near-UV and visible circular dichroism spectra plus spectrophotometric titration of tyrosine residues lend additional support to this hypothesis. 相似文献
96.
Lei Liu Wes Lee Mingbin Yuan Chris Acha Michael B. Geherty Brandon Williams Osvaldo Gutierrez 《Chemical science》2020,11(12):3146
Design and implementation of the first (asymmetric) Fe-catalyzed intra- and intermolecular difunctionalization of vinyl cyclopropanes (VCPs) with alkyl halides and aryl Grignard reagents has been realized via a mechanistically driven approach. Mechanistic studies support the diffusion of alkyl radical intermediates out of the solvent cage to participate in an intra- or intermolecular radical cascade with a range of VCPs followed by re-entering the Fe radical cross-coupling cycle to undergo (stereo)selective C(sp2)–C(sp3) bond formation. This work provides a proof-of-concept of the use of vinyl cyclopropanes as synthetically useful 1,5-synthons in Fe-catalyzed conjunctive cross-couplings with alkyl halides and aryl/vinyl Grignard reagents. Overall, we provide new design principles for Fe-mediated radical processes and underscore the potential of using combined computations and experiments to accelerate the development of challenging transformations.Design and implementation of the first (asymmetric) Fe-catalyzed intra- and intermolecular difunctionalization of vinyl cyclopropanes (VCPs) with alkyl halides and aryl Grignard reagents has been realized via a mechanistically driven approach. 相似文献
97.
Charles T. Currelly, first director of the Royal Ontario Museum, participated in excavations of the tomb of King Nebhepetre, now known as Mentuhotep II, (Dynasty XI) in Deir el-Bahri, Egypt in 1906. He brought to Canada many objects from the excavations, and objects that he purchased while in Egypt; these formed the initial collection of the museum. Among the objects were seven fragments of fine linen cloth with intricate pleat patterns. Recently, the cloths became the subject of a study to learn how they had retained their pleats for 4000 years. Samples were examined and analysed using polarised light microscopy, scanning electron microscopy-electron dispersive X-ray spectrometry, gas chromatography-mass spectrometry, and pyrolysis-gas chromatography-mass spectrometry. Three of the cloths were likely fragments of clothing re-purposed as bandages and were found to be saturated in mummification balms composed of Pinaceae resin, Pistacia resin, and an essential oil characterised by a high abundance of cedrol, possibly originating from a juniper species. All seven of the cloths were found to have traces of polysaccharides from two probable sources: an arabinogalactan gum such as gum arabic or a fruit gum, and a polyglucoside, possibly starch. 相似文献
98.
Chris D. Geddes Peter Douglas Christopher P. Moore Trevor J. Wear Peter L. Egerton 《Journal of fluorescence》1999,9(3):163-171
Fourteen thin-film optical sensors in which halide-sensitive fluorophores are immobilized in a thin copolymer film (50 m, dry) have been developed and characterized. The sensor films use rhodamine, 6-methoxyquinoline, and harmane dyes which have been functionalized and bound to a hydrophilic copolymer. The sensor films are reversibly capable of determining aqueous bromide and iodide with 4 and 2% accuracy, respectively, at concentrations of around 10–3 mol dm–3, and are more sensitive than previous plastic sensor fabrications. The 90% response time to molar iodide is 30–60 s. A combination of sensor films allows the simultaneous determination of both I– and Br– in a mixed-halide solution. The interference of several ions, including pseudo-halides, on the sensor films has been studied. 相似文献
99.
Williams C 《Molecular diversity》2006,10(3):311-332
Summary Recent research has shown that using data fusion rules in fingerprint-based similarity searching can improve results over traditional searches. Group fusion scores, which use multiple reference compounds, have in particular been shown to be quite effective in increasing enrichment rates over single reference structure based searches. In this paper, the effectiveness of using data fusion with multiple reference compounds to increase similarity search recall rates was investigated using 44 biological targets and four different 2D fingerprinting systems, including a new 2D typed triangle fingerprinting system introduced here. Scaffold-hopping abilities using data fusion rules were investigated using eight (8) different classes of scaffolds active against cGMP phosphodiesterase isoform 5 (PDE5). An approach to using the reference group for ranking and visualizing important fingerprints bits, or reverse fingerprinting, was presented, and used to score and visualize important pharmacophore features within sample active molecules. Finally, similarity statistics within the reference groups were investigated and compared to recall rates. 相似文献
100.
Tetiana Krachko Mark Bispinghoff Dr. Aaron M. Tondreau Dr. Daniel Stein Matthew Baker Dr. Andreas W. Ehlers Prof. Dr. J. Chris Slootweg Prof. Dr. Hansjörg Grützmacher 《Angewandte Chemie (International ed. in English)》2017,56(27):7948-7951
Phosphinidenes [R-P] are convenient P1 building blocks for the synthesis of a plethora of organophosphorus compounds. Thus far, transition-metal-complexed phosphinidenes have been used for their singlet ground-state reactivity to promote selective addition and insertion reactions. One disadvantage of this approach is that after transfer of the P1 moiety to the substrate, a challenging demetallation step is required to provide the free phosphine. We report a simple method that enables the Lewis acid promoted transfer of phenylphosphinidene, [PhP], from NHC=PPh adducts (NHC=N-heterocyclic carbene) to various substrates to produce directly uncoordinated phosphorus heterocycles that are difficult to obtain otherwise. 相似文献