Total synthesis of bis-（2,3-dibromo-4,5-dihydroxyphenyl）-methane as potent PTP1B inhibitor

Protein tyrosine phosphatase 1B （PTP1B） plays an important role as a negative regulator and has been proved to be an effective target for the treatment of type 2 diabetes mellitus. Bis-（2,3-dibromo-4,5-dihydroxyphenyl）-methane 7 was first reported as a natural bromophenol with significant inhibition against PTP1B which was isolated from red algae Rhodomela conrervoides. Intrigued by its astonishing activity （IC50 = 2.4 μmol/L）, compound 7 was synthesized with the overall yield of 24% and evaluated for its PTPIB inhibitory activity compared with natural compound.     

由抑制剂引起的高反差机理研究

本文利用吸附曲线及电化学的方法,研究了一系列抑制剂在银及溴化银上的吸附行为,将这些吸附性质与显影过程中相应的抑制剂存在时的显影结果对比,实验表明:只有当抑制剂在银上为中等的吸附,而在溴化银上吸附很小时,才可能利用抑制剂达到高反差。相应的机理及抑制剂在银上的吸附性质在文中也作了讨论。     

Similar Structural Dynamics for the Degradation of CH3NH3PbI3 in Air and in Vacuum

We investigate the degradation path of MAPbI₃ (MA=methylammonium) films over flat TiO₂ substrates at room temperature by means of X‐ray diffraction, spectroscopic ellipsometry, X‐ray photoelectron spectroscopy, and high‐resolution transmission electron microscopy. The degradation dynamics is found to be similar in air and under vacuum conditions, which leads to the conclusion that the occurrence of intrinsic thermodynamic mechanisms is not necessarily linked to humidity. The process has an early stage, which drives the starting tetragonal lattice in the direction of a cubic atomic arrangement. This early stage is followed by a phase change towards PbI₂. We describe how this degradation product is structurally coupled with the original MAPbI₃ lattice through the orientation of its constituent PbI₆ octahedra. Our results suggest a slight octahedral rearrangement after volatilization of HI+CH₃NH₂ or MAI, with a relatively low energy cost. Our experiments also clarify why reducing the interfaces and internal defects in the perovskite lattice enhances the stability of the material.     

Quantitation of sunitinib,an oral multitarget tyrosine kinase inhibitor,and its metabolite in urine samples by nonaqueous capillary electrophoresis time of flight mass spectrometry

A rapid, sensitive, and specific method was developed and validated using a nonaqueous‐capillary electrophoresis method with TOF‐MS for determination of sunitinib and N‐desethyl sunitinib in human urine. In order to avoid ionic suppression a urine samples dilution with methanol 1:10 previous step was used. This was the only treatment step to urine samples before the injection. Despite this dilution of the urine, the detection limit was as low as 0.07 mg/L for sunitinib and 0.15 mg/L for N‐desethyl sunitinib. Separation of compounds was achieved with a mixture of 5 mM ammonium formate in methanol. The calibration curves were linear over the range of 0.5–50.0 mg/L for the two analyzed compounds. The within‐run and between‐run precisions were within 5%, while the accuracy ranged from 96.0 to 100.4%. This method can be used in routine clinical practice to monitor sunitinib and N‐desethyl sunitinib drugs in the urine of cancer patients treated with once daily administration.     

Stereoselective Synthesis of the Non‐Lactonic Portion of (Z)‐Cryptofolione and Approaches towards Its Conversion to (Z)‐Cryptofolione

The stereoselective synthesis of the non‐lactonic part of the natural G₂ checkpoint inhibitor, (Z)‐cryptofolione, has been accomplished. Butane‐1,4‐diol was used as the starting material, and the stereogenic centers were generated through L ‐proline‐catalyzed α‐aminoxylation and Maruoka asymmetric allylation. We attempted to convert this non‐lactonic moiety to (Z)‐cryptofolione via olefin cross‐metathesis reaction, but by this approach another naturally occurring lactonic compound, goniothalamin, was obtained.     

Novel Method for the Fabrication of a Charge‐Transfer Complex Crystal by Photoirradiation

A novel method for the fabrication of a charge‐transfer complex crystal was developed. Photoirradiation of a solution of TPP[Co(tbp)(CN)₂] and TPP[Co(Pc)(CN)₂] (tbp=tetrabenzoporphyrin, Pc=phthalocyanine, TPP=tetraphenylphosphonium) gave a molecular conducting crystal of a charge‐transfer complex TPP[Co(tbp)(CN)₂]₂, which was produced by the process in which the photoexcited electron in tbp was transferred from the LUMO of tbp to that of Pc.     

Direct Anisotropic Growth of CdS Nanocrystals in Thermotropic Liquid Crystal Templates for Heterojunction Optoelectronics

The direct growth of CdS nanocrystals in functional solid‐state thermotropic liquid crystal (LC) small molecules and a conjugated LC polymer by in situ thermal decomposition of a single‐source cadmium xanthate precursor to fabricate LC/CdS hybrid nanocomposites is described. The influence of thermal annealing temperature of the LC/CdS precursors upon the nanomorphology, photophysics, and optoelectronic properties of the LC/CdS nanocomposites is systematically studied. Steady‐state PL and ultrafast emission dynamics studies show that the charge‐transfer rates are strongly dependent on the thermal annealing temperature. Notably, annealing at liquid‐crystal state temperature promotes a more organized nanomorphology of the LC/CdS nanocomposites with improved photophysics and optoelectronic properties. The results confirm that thermotropic LCs can be ideal candidates as organization templates for the control of organic/inorganic hybrid nanocomposites at the nanoscale level. The results also demonstrate that in situ growth of semiconducting nanocrystals in thermotropic LCs is a versatile route to hybrid organic/inorganic nanocomposites and optoelectronic devices.     

HPLC‐MS/MS method for quantitative determination of the novel dual inhibitor of FGF and VEGF receptors E‐3810 in tumor tissues from xenograft mice and human biopsies

We developed and validated a high‐performance liquid chromatography–tandem mass spectrometry analytical method to measure E‐3810, a novel dual inhibitor of fibroblast growth factor receptor 1 and vascular endothelial growth factor receptor 1–3 in tissues and determined the drug concentration in a biopsy of human breast cancer for the first time. The method is a modification of our previous one in plasma to study the clinical pharmacokinetics of the drug during the phase I/II trial. In view of the changes in matrix, we applied a partial validation protocol to determine recovery, sensitivity, range of linearity, precision, accuracy and stability of the method over three runs in a mouse tumor tissue and liver. The recovery of E‐3810 from liver or tumor homogenate was >69%, and the lower limit of quantification was 5 ng/ml. The method was linear in the concentration range 5.0–500.0 ng/ml, as demonstrated by a determination coefficient R² ≥ 0.9955. The range of the calibration curve was appropriate for the analysis, as demonstrated by the accuracy, which was between 91.4% and 106.7%. Interday precision and accuracy on quality control samples at 9, 30 and 300 ng/ml were 3.1‐11.2% and 98.3–111.4%, respectively. The assay was applied successfully to determine the intratumor concentration of E‐3810 in different mouse xenograft tumor models and in a biopsy of a patient with breast cancer included in the phase I/II trial of the drug. In mouse tumors, the concentrations of E‐3810 were higher than necessary to exert antitumor activity in vitro (1 µM). Even more of interest was the result obtained in a human biopsy of few milligrams, where E‐3810 reached 4.9 µg/g (11 µM). Copyright © 2014 John Wiley & Sons, Ltd.     

流动条件下两种不同亲水基团咪唑啉型缓蚀剂的缓蚀性能

选择了两种含有不同亲水基团的咪唑啉型缓蚀剂, 即1-胺乙基-2-十一烷基咪唑啉(AEI-11)和1-羟乙基-2-十一烷基咪唑啉(HEI-11), 分别在静态及动态条件下,采用失重法、极化曲线法、电化学阻抗谱法研究了上述缓蚀剂对N80钢在CO2饱和的3%(w)NaCl溶液中的缓蚀性能. 研究结果表明, 无论在静态和动态条件下, HEI-11均表现出更佳的缓蚀性能, 即咪唑啉型缓蚀剂的缓蚀性能与亲水基团的极性成正比; 在流动条件为5 m·s-1时, 缓蚀剂的缓蚀效率显著降低. 为了进一步研究缓蚀剂的缓蚀性能与其结构的关系, 运用量子化学法计算了缓蚀剂的EHOMO(最高占有分子轨道)、ELUMO(最低空分子轨道), 结果表明缓蚀剂的缓蚀效率与EHOMO成正比, 与ELUMO及ELUMO与EHOMO的差值驻E成反比.     

Controlled synthesis of ZnO with adjustable morphologies from nanosheets to microspheres

The synthesis of ZnO with different morphologies (hexagonal prisms, nanosheets, microspheres and quasi-flowers) was realized through a solvothermal method. During the synthetic procedure, the decomposition of hexamethylenetetramine at the temperature ≥100 °C provided (OH)⁻¹ ions at the rate of good distribution, and sodium dodecyl sulfate was used as templates. By adjusting the basicity in the synthetic system, ZnO nanosheets, or microspheres with nanosheet assemblies were obtained. Adjusting the concentration of surfactant, ZnO hexagonal crystals were formed; by adjusting the synthetic temperature, ZnO quasi-flowers with some nanosheet assemblies were produced. Based on experimental observation and analysis, the forming mechanism was discussed.