Lapatinib is required as a therapy for advanced or metastatic breast cancer. However, its reactive metabolite (RM) nitroso was implicated in idiosyncratic hepatotoxicity. Density functional theory was performed to explore the metabolism of nitroso formation. Primary hydroxylation amine is a critical intermediate to produce nitroso. Three pathways from secondary alkylamine lapatinib to primary hydroxylation amine were designed and discussed. Calculation results show that it is difficult to form primary hydroxylation amine through common proposed hydrolysis nitrone with a barrier of 36.67 kcal/mol (path A), but it is smoothly formed by paths B and C with moderate determined barriers of 15.09 kcal/mol and 16.56 kcal/mol, respectively. Subsequently, we demonstrate that the mechanism of nitroso formation from primary hydroxylation amine should be a double hydrogen atom transfer rather than the previously proposed hydrolysis primary dihydroxylation amine. The barrier of the former is obviously lower than the latter. Based on metabolism results and structure analysis, several lapatinib derivatives are designed. Molecular docking of designed compounds with epidermal growth factor receptor (EGFR) shows that they share a similar binding mode with lapatinib. In particular, 2a to 2d show similar binding energy to lapatinib. This work showed metabolism details of nitroso formation from lapatinib and its structure modification, which can enrich the metabolism of amine drugs and provide guidance for drug optimization and design. 相似文献
Tumor progressions such as metastasis are complicated events that involve abnormal expression of different miRNAs and enzymes. Monitoring these biomolecules in live cells with computational DNA nanotechnology may enable discrimination of tumor progression via digital outputs. Herein, we report intracellular entropy‐driven multivalent DNA circuits to implement multi‐bit computing for simultaneous analysis of intracellular telomerase and microRNAs including miR‐21 and miR‐31. These three biomolecules can trigger respective DNA strand displacement recycling reactions for signal amplification. They are visualized by fluorescence imaging, and their signal outputs are encoded as multi‐bit binary codes for different cell types. The results can discriminate non‐tumorigenic, malignant and metastatic breast cells as well as respective tumors. This DNA computing circuit is further performed in a microfluidic chip to differentiate rare co‐cultured cells, which holds a potential for the analysis of clinical samples. 相似文献
A novel synthesized Ag/C fibrous catalyst based on in situ thermally induced redox reaction of PVA/AgNO3 composite fibers was proposed. Utilizing the plasticization and complexation of AgNO3 solution, the melt spinning of PVA/AgNO3 composites was accomplished. Through the in situ thermally induced redox reaction on PVA/AgNO3 composite fibers combined with carbonization of PVA and reduction of Ag+, the synthesized Ag/C fibrous catalyst was prepared with nanosilver particles with average diameter of 130 nm immobilized on the loose microstructural carbon layers. The synthesized Ag/C fibrous catalyst exhibited excellent catalytic activity and reused for at least five cycles for the reduction of 4‐nitrophenol, which may hold great promise in effective and eco‐friendly waste water treatment. 相似文献
Russian Journal of Coordination Chemistry - A new V-centered Keggin polyoxometalate-based inorganic-organic hybrid (HPpz)3[VW12O40] (I) (Ppz = piperazine) has been hydrothermal synthesized and... 相似文献
To investigate the effects of ionic liquids (ILs) on the oxidative combustion characteristics of coal, the oxidation characteristics of ILs on coal, such as characteristic temperature, thermal mass loss rate, and oxidation kinetics characteristic parameters, were determined. The results the [BMIm][I]-treated coal samples increased cracking temperature (T1), maximum oxidization mass gain (T2), ignition temperature (T3), burnout temperature (T4), minimum thermal rate (Ta), maximum thermal energy (Tb), and maximum thermal rate (Tc) by 33.2, 29.3, 20.7, 42.8, 11.4, 23.0, and 27.9 °C, respectively. The increase mass ratio of coal samples treated with ILs increased and decreased at the water evaporation and thermal decomposition stages, respectively. The apparent activation energy (Ea) of coal samples treated with ILs increased, and the mechanism function also changed accordingly. These showed that the ILs improved the thermal stability of the coal samples in the stages of absorbing oxygen and increased mass, and the loss of combustion. The ILs caused damage to the molecular structure of the coal and ultimately effected changes in the combustion performance. In addition, the [BMIm][BF4] hardly weakens the inhibitory effectiveness of the coal sample over time; coal spontaneous combustion could be effectively inhibited.
Capacitive energy storage has advantages of high power density, long lifespan, and good safety, but is restricted by low energy density. Inspired by the charge storage mechanism of batteries, a spatial charge density (SCD) maximization strategy is developed to compensate this shortage by densely and neatly packing ionic charges in capacitive materials. A record high SCD (ca. 550 C cm?3) was achieved by balancing the valance and size of charge‐carrier ions and matching the ion sizes with the pore structure of electrode materials, nearly five times higher than those of conventional ones (ca. 120 C cm?3). The maximization of SCD was confirmed by Monte Carlo calculations, molecular dynamics simulations, and in situ electrochemical Raman spectroscopy. A full‐cell supercapacitor was further constructed; it delivers an ultrahigh energy density of 165 Wh L?1 at a power density of 150 WL?1 and retains 120 Wh L?1 even at 36 kW L?1, opening a pathway towards high‐energy‐density capacitive energy storage. 相似文献