可见光氧化还原钴催化立体发散性合成1,4-二烯

1,4-二烯是一类重要的烯烃化合物,其分子骨架广泛存在于药物和天然产物中.由于1,4-二烯分子在有机合成中具有重要作用,目前其合成方法已被广泛研究,包括1,3-二烯的氢烯基化、炔烃的氢烯丙基化、乙烯基和烯丙基试剂的交叉偶联等.然而,由于1,4-二烯的热力学稳定性,现有的合成方法主要倾向于生成E-立体选择性的产物,而Z-异构体的生成则相对困难.值得注意的是,通过同一组底物同时构建1,4-二烯的Z和E异构体的立体发散性合成策略鲜有报道.因此,发展新型催化体系,以同时构建1,4-二烯的Z和E异构体具有十分重要的意义和应用前景.本文报道了一种高效的可见光光致氧化还原/钴协同催化策略,该策略以联烯与炔烃为原料,通过调控反应溶剂即可实现立体发散性地构建Z,E-和E,E-1,4-二烯化合物.该反应在室温下,以2,4,5,6-四(9-咔唑基)-间苯二腈(4CzIPN)作为光敏剂,4,6-双(二苯基膦基)-10H-吩噁嗪为配体,H_(2)O和DIPEA作为氢源,实现了1,4-二烯的高效合成.值得一提的是,通过简单地调控溶剂可以直接控制产物的立体选择性,即以乙腈为溶剂时可得到Z,E-1,4-二烯产物,而使用2-MeTHF作为溶剂时,则得到E,E-1,4-二烯产物.此外,该反应对炔烃底物具有良好的兼容性,包括乙基、硅醚、羟基和环丙基等非对称的芳基烷基内炔,均能与联烯有效偶联,以较高收率得到目标产物.此外,芳基上带有各种富电子和缺电子基团的炔烃也能很好地参与反应.联烯底物研究结果表明,联烯上的酯基对反应效率有显著影响,具有较小酯取代基的联烯,如甲基和乙基,反应活性较低,相应的产物收率较低;而具有较大酯基的联烯,如异丙基、苄基和叔丁基,则能获得更高的产率.此外,当使用苯基、酸酐、二苯基氧化膦或磺酰基等其他官能团取代的联烯时,反应无法发生.通过氘代实验、荧光猝灭实验等一系列控制实验以及密度泛函理论计算,揭示了该反应机制.反应过程涉及五元钴环戊烯中间体的分解,并通过光催化的能量转移过程实现了E,E-1,4-二烯的E→Z异构化,最终实现Z,E-1,4-二烯的立体选择性合成.综上所述,本文提出了一种新的钴催化炔烃-联烯的选择性还原偶联反应.通过结合可见光光致氧化还原与钴协同催化策略,在温和的条件下,以H_(2)O和DIPEA作为氢源,实现了具有良好区域选择性和立体选择性的Z,E-和E,E-1,4-二烯的立体发散性合成.通过控制反应溶剂来实现立体选择性,本研究为立体发散性合成1,4-二烯化合物提供了一种简单有效的新途径.

Neuronal nitric oxide synthase/reactive oxygen species pathway is involved in apoptosis and pyroptosis in epilepsy

Dysfunction of neuronal nitric oxide synthase contributes to neurotoxicity,which triggers cell death in various neuropathological diseases,including epilepsy.Studies have shown that inhibition of neuronal nitric oxide synthase activity increases the epilepsy threshold,that is,has an anticonvulsant effect.However,the exact role and potential mechanism of neuronal nitric oxide synthase in seizures are still unclear.In this study,we performed RNA sequencing,functional enrichment analysis,and weighted gene coexpression network analysis of the hippocampus of tremor rats,a rat model of genetic epilepsy.We found damaged hippocampal mitochondria and abnormal succinate dehydrogenase level and Na+-K+-ATPase activity.In addition,we used a pilocarpine-induced N2a cell model to mimic epileptic injury.After application of neuronal nitric oxide synthase inhibitor 7-nitroindazole,changes in malondialdehyde,lactate dehydrogenase and superoxide dismutase,which are associated with oxidative stress,were reversed,and the increase in reactive oxygen species level was reversed by 7-nitroindazole or reactive oxygen species inhibitor N-acetylcysteine.Application of 7-nitroindazole or N-acetylcysteine downregulated the expression of caspase-3 and cytochrome c and reversed the apoptosis of epileptic cells.Furthermore,7-nitroindazole or N-acetylcysteine downregulated the abnormally high expression of NLRP3,gasdermin-D,interleukin-1βand interleukin-18.This indicated that 7-nitroindazole and N-acetylcysteine each reversed epileptic cell death.Taken together,our findings suggest that the neuronal nitric oxide synthase/reactive oxygen species pathway is involved in pyroptosis of epileptic cells,and inhibiting neuronal nitric oxide synthase activity or its induced oxidative stress may play a neuroprotective role in epilepsy.

Effect of nanosized NbC precipitates on hydrogen-induced cracking of high-strength low-alloy steel

We investigated the effect of nanosized NbC precipitates on hydrogen-induced cracking(HIC)of high-strength low-alloy steel by conducting slow-strain-rate tensile tests(SSRT)and performing continuous hydrogen charging and fracture analysis.The results reveal that the HIC resistance of Nb-bearing steel is obviously superior to that of Nb-free steel,with the fractured Nb-bearing steel in the SSRT exhibiting a smaller ratio of elongation reduction(Iδ).However,as the hydrogen traps induced by NbC precipitates approach hydrogen saturation,the effect of the precipitates on the HIC resistance attenuate.We speculate that the highly dispersed nanosized NbC precipitates act as irreversible hydrogen traps that hinder the accumulation of hydrogen at potential crack nucleation sites.In addition,much like Nb-free steel,the Nb-bearing steel exhibits both H-solution strengthening and the resistance to HIC.

3D geo-cellular static virtual outcrop model and its implications for reservoir petro-physical characteristics and heterogeneities

Geostatistical data plays a vibrant role for surface-based reservoir modeling through outcrop analogues,which is used to understand three-dimensional(3D)variability of petrophysical properties.The main purpose of this study is to improvise the surface-based 3D geo-modeling to demonstrate petrophysical characteristics and heterogeneities of Sandakan reservoirs,NW Borneo.We used point cloud data from Light Detection and Ranging(Li DAR)to build high-resolution virtual outcrop modeling(VOM)onto which we mapped 6 different lithofacies.Porosity and permeability of core plugs were measured to determine the average variance of petrophysical properties for each lithofacies.By utilizing the integration of VOMs analogues and petrophysical properties in Petrel^(TM),we demonstrated the distribution and associations of all lithofacies in pseudo wells that have inherent thin beds heterogeneities in 3D geocellular model.The results concluded that the heterogeneity of thin beds in lithofacies is dependent on porosity and permeability with input dataset.According to the final model,cross-bedding sandstone(CBS),hummocky cross-stratified sandstone(HCSS)and trough cross-bedding sandstone(TCBS)show good reservoir quality due to high porosity ranging from:25.6%to 20.4%and,19.3%-14.5%,and permeability ranging from:74.03 mD to 66.84 mD and,64.86 mD to 21.01 mD.In contrast,massive to weak laminae sandstone(MWLS)and bioturbated sandstone(BS)show fair to poor reservoir quality,caused baffling of surrounding mud sediments in the reservoir lithofacies.Results also revealed that Li DAR based VOM with petrophysical properties can significantly reduce the risk and minimize the cost of reservoir modeling in petroleum industry.

Task planning in robotics:an empirical comparison of PDDL-and ASP-based systems

Robots need task planning algorithms to sequence actions toward accomplishing goals that are impossible through individual actions. Off-the-shelf task planners can be used by intelligent robotics practitioners to solve a variety of planning problems. However, many different planners exist, each with different strengths and weaknesses,and there are no general rules for which planner would be best to apply to a given problem. In this study, we empirically compare the performance of state-of-the-art planners that use either the planning domain description language(PDDL) or answer set programming(ASP) as the underlying action language. PDDL is designed for task planning, and PDDL-based planners are widely used for a variety of planning problems. ASP is designed for knowledge-intensive reasoning, but can also be used to solve task planning problems. Given domain encodings that are as similar as possible, we find that PDDL-based planners perform better on problems with longer solutions,and ASP-based planners are better on tasks with a large number of objects or tasks in which complex reasoning is required to reason about action preconditions and effects. The resulting analysis can inform selection among general-purpose planning systems for particular robot task planning domains.