N-[2,6-二氯-4-(1,2,4-噁二唑-3-基)苯基]-2-甲氧基烟酰胺的合成、晶体结构及抗肿瘤活性研究

报道一种新型1,2,4-噁二唑衍生物,N-[2,6-二氯-4-(1,2,4-噁二唑-3-基)苯基]-2-甲氧基烟酰胺（C15H10Cl2N4O3）的合成,其结构通过1H NMR、13C NMR、HRMS以及X-射线单晶衍射进行表征。该晶体结构属于三斜晶系, P 1(—) 空间群,晶胞参数 a = 7.1291 (9), b = 8.4352 (10), c = 14.0021 (18) ?, α = 73.834 (3), β = 77.407 (3), γ = 70.019 (3)°, Mr = 366.18, V = 752.97 (16) ?3, Z = 2, Dc = 1.611 g/cm3, μ(MoKα) = 0.454 mm-1, F(000) = 372.0 , 晶体尺寸为 0.36 × 0.2 × 0.1 mm,Rint = 0.023。初步活性研究发现,该化合物对LoVo, A549, SK-BR-3, HeLa这四种肿瘤细胞株具有明显的抑制作用,尤其是对HeLa细胞的抑制活性与阳性药物5-氟尿嘧啶 (5-FU)相当。     

Inhibitor Development against p7 Channel in Hepatitis C Virus

Hepatitis C Virus (HCV) is the key cause of chronic and severe liver diseases. The recent direct-acting antiviral agents have shown the clinical success on HCV-related diseases, but the rapid HCV mutations of the virus highlight the sustaining necessity to develop new drugs. p7, the viroporin protein from HCV, has been sought after as a potential anti-HCV drug target. Several classes of compounds, such as amantadine and rimantadine have been testified for p7 inhibition. However, the efficacies of these compounds are not high. Here, we screened some novel p7 inhibitors with amantadine scaffold for the inhibitor development. The dissociation constant (Kd) of 42 ARD-series compounds were determined by nuclear magnetic resonance (NMR) titrations. The efficacies of the two best inhibitors, ARD87 and ARD112, were further confirmed using viral production assay. The binding mode analysis and binding stability for the strongest inhibitor were deciphered by molecular dynamics (MD) simulation. These ARD-series compounds together with 49 previously published compounds were further analyzed by molecular docking. Key pharmacophores were identified among the structure-similar compounds. Our studies suggest that different functional groups are highly correlated with the efficacy for inhibiting p7 of HCV, in which hydrophobic interactions are the dominant forces for the inhibition potency. Our findings provide guiding principles for designing higher affinity inhibitors of p7 as potential anti-HCV drug candidates.     

1.3 GHz超导腔磁通排出效应研究

设计并搭建了一套高精度的磁场测量和补偿系统,并结合中国科学院高能物理研究所（IHEP）的2K超导腔垂直测试平台对1.3 GHz 单加速间隙超导腔的磁通排出效应开展了实验研究：利用研制的磁场测量和补偿系统能够精密地测量超导腔赤道位置磁场,并能够将磁场补偿至小于5.0×10⁻⁸ T;并对超导腔不同表面温度梯度下的磁通排出效应进行了测量分析;对钉扎了磁场的超导腔进行了射频性能测试,研究了超导腔电阻对磁通钉扎的敏感度,以及在不同电场梯度下超导腔的表面电阻变化情况。结果表明,研制的高精度磁场测量和补偿系统能够满足超导腔磁通排出研究的需求;高的超导腔表面温度梯度有利于磁通的排出;磁通钉扎电阻的敏感度随着加速电场梯度的增加而增大,导致超导腔的性能下降。此实验研究也为后续超导腔的研制奠定了一定基础。     

煤气管道沉积物的分析

以苯－乙醇为溶剂，在对煤气管道沉积物提取，分离后，采用２５ｍ＊０．２４ｍｍＩ．Ｄ．的石英毛细管ＯＶ－１０１柱进行了ＧＣ，ＧＣ－ＭＳ分析，鉴定出１９种有机成分，并用归一法作了定量分析，并用采用ＩＲ、点滴试验等方法对其无机物作了定性鉴定。     

A first-principles investigation on interactions between various surface-terminated diamond films

To elucidate the influence of different terminations on diamond surface interaction, the geometry and electronic structures of the diamond films modified by different terminations (H, F, O, NH₂, and OH) are studied by using the first principles method. Strong bonding is formed between the clean diamond surfaces, which suggest an obvious interface interaction. Both H and F terminals have significant effects on the reduction of the interface interactions. Due to the larger difference in electronegativity between C and F, the F termination layer has a higher electron density coverage to give a larger repulsive force. Therefore, the interaction between the F-terminated diamond interfaces is stronger than that between the H-terminated diamond interfaces. The O-terminated diamond surfaces are unstable. The NH₂- and OH-terminals have weak interaction due to the presence of large functional group atoms that leads to an electronic offset.     

Novel high PSRR high-order temperature-compensated subthreshold MOS bandgap reference

Novel high power supply rejection ratio (PSRR) high-order temperature-compensated subthreshold metal-oxide-semiconductor (MOS) bandgap reference (BGR) is proposed in Semiconductor Manufacturing International Corporation (SMIC) 0.13 μm complementary MOS (CMOS) process. By adopting subthreshold MOS field-effect transistors (MOSFETs) and the piecewise-curvature temperature-compensated technique, the output reference voltage's temperature performance of the subthreshold MOS BGR is effectively improved. The subthreshold MOS BGR achieves high PSRR performance by adopting the technique of pre-regulator. Simulation results show that the temperature coefficient (TC) of the subthreshold MOS BGR is 1.38×10^?6/°C when temperature is changed from ?40 °C to 125 °C with a power supply voltage of 1.2 V. The subthreshold MOS BGR achieves the PSRR of ?104.54 dB, ?104.54 dB, ?104.5 dB, ?101.82 dB and ?79.92 dB at 10 Hz, 100 Hz, 1 kHz, 10 kHz and 100 kHz respectively.     

Single cell determination of nitric oxide release using capillary electrophoresis with laser-induced fluorescence detection

Measurements of nitric oxide (NO) release at single cell level are fundamental to understand the diverse physiological functions of this remarkable molecule. To achieve this purpose, capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) was originally described for the sensitive determination of NO release in individual neuron and mammalian cell after 8-(3,4-diaminophenyl)-2,6-bis(2-carboxyethyl)-4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (DAMBO-P(H)) was chosen as the fluorescent probe. Various parameters affecting NO trapping in vivo and CE separation were systematically studied. Under the optimal conditions, complete and fast separation of the resulted targeted high-fluorescent triazole (DAMBO-P(H)-T) was achieved in about 3 min (2.89 min), and the relative standard deviations (RSDs) values of migration time and peak area were less than 5% and 9% for intra-day and inter-day assays, respectively. The detection limit was 42 amol (at a signal-to-noise ratio of 3). The feasibility of application of the developed method was validated by successfully applied to the measurements of NO release from four single cell study models. This original application of this method in diverse samples represents a powerful tool to study the kinetics of NO release by neuronal cells during neurotransmission, as well as for the understanding of the pathobiological and therapeutic basis of this molecule for cardiovascular diseases and under oxidative stress.     

LEC-GaSb单晶生长技术研究

采用液封直拉(LEC)法进行了生长GaSb单晶的实验研究,对比了等摩尔比的(LiCl+KCl)和氧化硼(B2O3)两种液封剂作用下的生长控制效果。通过模拟了解了保温罩是如何改善系统温场的梯度,进而分析了温场对成晶的影响。对晶体单晶区域的测试结果给出了晶体内部的位错分布特点,X线衍射(XRD)的测试结果显示该区域的晶体质量较好。     

微波基板用陶瓷材料Li_2Mg_(1-x)Zn_xTi_3O_8微波性能研究

通过传统固相反应法制得三元系尖晶石结构的Zn掺杂的Li_2Mg_(1-x)Zn_xTi_3O_8(LMT)陶瓷。讨论了Zn掺杂对Li_2MgTi_3O_8陶瓷试样的相结构、显微结构及微波介电性能的影响。当Zn掺杂量为0.06时,Li_2Mg_(0.94)Zn_(0.06)Ti_3O_8陶瓷试样在1 075℃烧结4h可获得良好的显微结构与微波性能,其中介电常数适中(ε_r≈26.58),品质因数较高((Q×f)≈44 800GHz),谐振频率温度系数趋近于0(τ_f≈1.9μ℃~(-1))。该研究得到的陶瓷材料具有良好的微波介电性能,可作为无机填充材料运用于微波复合介质基板材料的研制中。