排序方式: 共有20条查询结果,搜索用时 15 毫秒
1.
2.
Bharathi Avula Babu L. Tekwani Narayan D. Chaurasiya NP Dhammika Nanayakkara Yan‐Hong Wang Shabana I. Khan Vijender R. Adelli Rajnish Sahu Mahmoud A. Elsohly James D. McChesney Ikhlas A. Khan Larry A. Walker 《Journal of mass spectrometry : JMS》2013,48(2):276-285
Therapeutic efficiency and hemolytic toxicity of primaquine (PQ), the only drug available for radical cure of relapsing vivax malaria are believed to be mediated by its metabolites. However, identification of these metabolites has remained a major challenge apparently due to low quantities and their reactive nature. Drug candidates labeled with stable isotopes afford convenient tools for tracking drug‐derived metabolites in complex matrices by liquid chromatography‐tandem mass spectrometry (LC‐MS‐MS) and filtering for masses with twin peaks attributable to the label. This study was undertaken to identify metabolites of PQ from an in vitro incubation of a 1:1 w/w mixture of 13C6‐PQ/PQ with primary human hepatocytes. Acquity ultra‐performance LC (UHPLC) was integrated with QTOF‐MS to combine the efficiency of separation with high sensitivity, selectivity of detection and accurate mass determination. UHPLC retention time, twin mass peaks with difference of 6 (originating from 13C6‐PQ/PQ), and MS‐MS fragmentation pattern were used for phenotyping. Besides carboxy‐PQ (cPQ), formed by oxidative deamination of PQ to an aldehyde and subsequent oxidation, several other metabolites were identified: including PQ alcohol, predictably generated by oxidative deamination of PQ to an aldehyde and subsequent reduction, its acetate and the alcohol's glucuronide conjugate. Trace amounts of quinone‐imine metabolites of PQ and cPQ were also detected which may be generated by hydroxylation of the PQ/cPQ quinoline ring at the 5‐position and subsequent oxidation. These findings shed additional light on the human hepatic metabolism of PQ, and the method can be applied for identification of reactive PQ metabolites generated in vivo in preclinical and clinical studies. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
3.
pH‐controlled reaction divergence of decarboxylation versus fragmentation in reactions of dihydroxyfumarate with glyoxylate and formaldehyde: parallels to biological pathways
下载免费PDF全文
![点击此处可从《Journal of Physical Organic Chemistry》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Christopher J. Butch Jing Wang Jiande Gu Rebeca Vindas Jacob Crowe Pamela Pollet Leslie Gelbaum Jerzy Leszczynski Ramanarayanan Krishnamurthy Charles L. Liotta 《Journal of Physical Organic Chemistry》2016,29(7):352-360
The reactions of dihydroxyfumarate with glyoxylate and formaldehyde exhibit a unique pH‐controlled mechanistic divergence leading to different product suites by two distinct pathways. The divergent reactions proceed via a central intermediate (2,3‐dihydroxy‐oxalosuccinate, 3 , in the reaction with glyoxylate and 2‐hydroxy‐2‐hydroxymethyl‐3‐oxosuccinate, 14 , in the reaction with formaldehyde). At pH 7–8, products ( 7 , 8 , and 15 ) exclusively from a decarboxylation of the intermediate are observed, while at pH 13–14, products ( 9 , 10 , and 16 ) solely derived from a hydroxide‐promoted fragmentation of the intermediate are formed. The decarboxylative and fragmentation pathways are mutually exclusive and do not appear to coexist under the range of pH (7–14) conditions investigated. Herein, we employ a combination of quantitative 13C NMR measurements and density functional theory calculations to provide a rationale for this pH‐driven reaction divergence. These rationalizations also hold true for the reactions of dihydroxyfumarate produced in situ by the catalytic cyanide‐mediated dimerization of glyoxylate. In addition, the non‐enzymatic decarboxylation and fragmentation transformations of these central intermediates ( 3 and 14 ) appear to have intriguing parallels to the enzymatic reactions of oxalosuccinate and formation of glyceric acid derivatives in extant metabolism – the high and low pH mimicking the precise control exerted by the enzymes over reaction pathways. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
4.
Wilson SD Dai P Adroja DT Lee SH Chung JH Lynn JW Butch NP Maple MB 《Physical review letters》2005,94(5):056402
We used inelastic neutron scattering to study magnetic excitations of Sc1-xUxPd3 for U concentrations (x=0.25, 0.35) near the spin glass quantum critical point (QCP). The excitations are spatially incoherent, broad in energy (E=variant Planck's over 2piomega), and follow omega/T scaling at all wave vectors investigated. Since similar omega/T scaling has been observed for UCu5-xPdx and CeCu6-xAux near the antiferromagnetic QCP, we argue that the observed non-Fermi-liquid behavior in these f-electron materials arises from the critical phenomena near a T=0 K phase transition, irrespective of the nature of the transition. 相似文献
5.
63Cu NQR measurements of the 63Cu T1 are reported for the quantum critical point system CeCu5.9Au0.1 over temperatures ranging from 0.1 up to 4.2 K. Below approximately 1 K the magnetization recovery exhibits a stable, nonexponential decay function which we believe signals the onset of 2D quantum critical fluctuations, as has been noted in the literature. We find T1(-1) is proportional to T0.75 for the region T < 1 K. The observed temperature dependence is in agreement with a phenomenological model of non-Fermi liquid behavior based on the uniform susceptibility but is inconsistent with calculations based on susceptibility peaks identified via neutron scattering experiments. 相似文献
6.
Jiao P Zhou H Otto M Mu Q Li L Su G Zhang Y Butch ER Snyder SE Jiang G Yan B 《Journal of the American Chemical Society》2011,133(35):13918-13921
To conquer complex and devastating diseases such as cancer, more coordinated and combined attack strategies are needed. We suggest that these can be beautifully achieved by using nanoconstruct design. We present an example showing that neuroblastoma cells are selectively killed by a nanoconstruct that specifically targets neuroblastoma cells, pushes cells to the vulnerable phase of the cell cycle, and greatly enhances radiation-induced cell death. The success of this multipronged attack approach launched by cell-embedded nanoconstructs demonstrates the power and flexibility of nanotechnology in treating cancer, a difficult task for a small molecule. 相似文献
7.
The pressure dependence of the hidden order phase transition of URu2Si2 is shown to depend sensitively upon the quality of hydrostatic pressure conditions during electrical resistivity measurements. Hysteresis in pressure is demonstrated for two choices of pressure medium: the commonly used mixture of 1:1 Fluorinert FC70/FC77 and pure FC75. In contrast, no hysteresis is observed when the pressure medium is a 1:1 mixture of n-pentane/isoamyl alcohol, as it remains hydrostatic over the entire studied pressure range. Possible ramifications for the interpretation of the temperature–pressure phase diagram of URu2Si2 are discussed. 相似文献
8.
Bauer ED Zapf VS Ho PC Butch NP Freeman EJ Sirvent C Maple MB 《Physical review letters》2005,94(4):046401
The URu2-xRexSi2 system exhibits ferromagnetic order for Re concentrations 0.3 < x < or =1.0. Non-Fermi-liquid (NFL) behavior is observed in the specific heat for 0.15< or = x< or =0.6 [C/T proportional to, -lnT (or T(-0.1))], and also in the power-law T dependence of the electrical resistivity [rhoT proportional to, Tn] with n<2 for 0.15< or = x <0.8, at low T, providing strong evidence that the NFL behavior persists within the ferromagnetic phase. Furthermore, the deviation of the physical properties of URu2-xRexSi2 from Fermi-liquid behavior is most pronounced at the ferromagnetic quantum critical point, and the NFL behavior found in the ferromagnetic phase may be consistent with the Griffiths-McCoy phase model. 相似文献
9.
Zhu ZH Levy G Ludbrook B Veenstra CN Rosen JA Comin R Wong D Dosanjh P Ubaldini A Syers P Butch NP Paglione J Elfimov IS Damascelli A 《Physical review letters》2011,107(18):186405
The electronic structure of Bi(2)Se(3) is studied by angle-resolved photoemission and density functional theory. We show that the instability of the surface electronic properties, observed even in ultrahigh-vacuum conditions, can be overcome via in situ potassium deposition. In addition to accurately setting the carrier concentration, new Rashba-like spin-polarized states are induced, with a tunable, reversible, and highly stable spin splitting. Ab initio slab calculations reveal that these Rashba states are derived from 5-quintuple-layer quantum-well states. While the K-induced potential gradient enhances the spin splitting, this may be present on pristine surfaces due to the symmetry breaking of the vacuum-solid interface. 相似文献
10.
ABSTRACTWe use inelastic neutron scattering measurements to show that the energy gap in the magnetic excitations of URu2Si2, induced by the Hidden Order transition, is closed by Re substitution. The magnetic excitations remain ungapped in compositions where the specific heat anomaly associated with Hidden Order is no longer observed, which means that the entropy associated with Hidden Order is tied mostly to the magnetic gapping. Further, the onset of ferromagnetic order does not gap the excitations, reflecting the fact that Re substitution does not dramatically affect the Kondo lattice hybridisation. 相似文献