氨基酸酯Katritzky盐用于β,γ-不饱和酯和γ-酮酯合成的研究

β,γ-不饱和酯和γ-酮酯是重要的合成中间体, 从丰富的氨基酸衍生的Katritzky吡啶盐出发, 在可见光照射下, 合成了一系列的β,γ-不饱和酯和γ-酮酯, 该方法具有反应条件温和, 操作简单等优点, 且有良好的官能团兼容性, 所得的产物可进一步转化.     

多功能Aβ有机小分子探针的构建及诊疗应用进展

阿尔茨海默症(AD)是最主要的进行性神经类疾病之一. β-淀粉样蛋白(Aβ)的形成、 错误折叠和聚集沉积被认为是该类疾病的重要病理学标志. 近年来, 研究人员基于荧光成像灵敏度高、 操作简便及副作用小的优点, 围绕脑部特殊的血脑屏障(BBB)系统和Aβ蛋白结构, 开发了一系列多功能Aβ探针应用于AD的诊疗研究. 本文分别从检测和治疗两个角度出发, 综合评述了Aβ诊疗探针的脑靶向设计、 波长调控和诊疗一体化的化学调控策略, 并展望了功能性荧光探针在该领域的应用前景.     

2-氰基苄基诱导的葡萄糖醛酸β糖苷键立体选择性

以2,3-O-(2-氰基苄基)-4-O-氯乙酰基-β-对甲基苯基-D-葡萄糖醛酸硫苷等7个单糖模块作为糖基供体, 以甲醇等醇类化合物作为糖基受体, 分别在二氯甲烷和甲苯溶剂中进行了糖基化反应, 研究了葡萄糖醛酸C2位引入2-氰基苄基(BCN)以及溶剂效应对糖苷键α/β选择性的影响. 通过对糖基产物的 ¹H NMR, ¹³C NMR和HSQC等谱图分析发现, BCN可以有效提高糖苷键的β选择性, 其中部分糖基化产物的糖苷键α/β比例最高可达1/50. 为磺达肝癸钠分子中葡萄糖醛酸的β糖苷键的构建方法做出了初步探索.     

明胶中α、β和γ三种构象的全分析

由文献表明:迄今为止,用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)测定明胶分子量分布,只能分出<α,α₁,α₂和β组份,而γ及>γ的组份未能检出。也就是说,大约30万以上的分子量组份未能进入凝胶板内(以下简称“入板”)。这对明胶构象的全分析和对明胶质量的正确判断是一个严重的缺陷。 本文主要探讨和研究γ及>γ组份的入板问题。所采取的方法是:控制丙烯酰胺和甲叉丙烯酰胺(交联剂)的相对含量,选择合适的交联度梯度,使之既适用于α和β组份迁移,也能让γ及>γ的组份入板。此外,在小的交联度和大孔径的情况下,还能符合凝胶板对凝胶强度的基本要求。     

聚金属氧酸盐在阿尔兹海默症治疗中的新进展

从聚金属氧酸盐(POMs)对β-淀粉样蛋白(Aβ)聚集的调控作用、 水解及光动力治疗等方面介绍其在阿尔兹海默症(AD)治疗中的最新研究进展, 为进一步研究POMs抗AD药物活性提供了参考.     

纳米通道单分子检测P53蛋白与DNA的弱相互作用

利用基于α-溶血素(α-HL)的纳米通道单分子检测技术在单分子水平上探测位于肿瘤抑制蛋白P53 DNA结合域的多肽分子(P53-P)与含有p21^waf1/cip1基因结合域的双链DNA (B40)之间弱相互作用. 在电场力的作用下, 单个P53-P/B40复合物被α-HL纳米通道捕获并限制在其前庭中. 通过空间限域作用, P53-P与B40之间的弱相互作用被放大为具有显著电压依赖性的复合物-α-HL间强烈的相互作用, 从而产生极易分辨的离子流特征阻断信号. 统计分析特征阻断信号显示P53-P与B40之间的弱相互作用使得B40产生微小的构型变化. 分子对接模拟进一步证明, P53-P能够插入B40的小沟并使得小沟间距变窄. 因此, 基于α-HL的纳米通道单分子检测技术可以作为研究单个生物大分子间弱相互作用的超灵敏分析方法.     

光生电荷梯度连续传递链的构筑及对光催化性能的增强作用

选取能带位置匹配的γ-Bi₂O₃, α-Bi₂O₃和Bi₄Ti₃O₁₂, 采用等体积浸渍法原位构筑了具有梯度能级的Bi₄Ti₃O₁₂@α/γ-Bi₂O₃三元同素结光催化剂. 光催化降解高浓度罗丹明B(RhB)和四氯苯酚(4-CP)的实验结果表明, 相比于γ-Bi₂O₃和α/γ-Bi₂O₃, Bi₄Ti₃O₁₂@α/γ-Bi₂O₃显示出优异的光催化活性, 其中0.5%Bi₄Ti₃O₁₂@α/γ-Bi₂O₃显示了最佳的光催化性能, 光降解RhB(或4-CP)的活性是γ-Bi₂O₃的32倍(或10.4倍)和α/γ-Bi₂O₃的4.4倍(或2.2倍). 光电性质表征结果证实, Bi₄Ti₃O₁₂@α/γ-Bi₂O₃三元同素结具有高效的光生电荷分离和迁移效率, 这是Bi₄Ti₃O₁₂@α/γ-Bi₂O₃三元同素结具有较高光催化性能的主要原因之一.     

芳香取代基结构对螺旋聚乙炔高效液相色谱手性固定相手性识别性能的影响

设计合成了3种源于脯氨酸的手性乙炔基单体——(S)-2-乙炔基-N-芳香胺基甲酰基吡咯烷. 在氯化降冰片二烯铑二聚体{[Rh(nbd)Cl]₂}-三乙胺催化下, 3种单体被转化为相应的光学活性螺旋聚合物. 用高效液相色谱评估了3种聚合物作为手性固定相(CSPs)对9种底物的手性识别性能. 以正己烷/异丙醇(体积比9∶1)为流动相时, 3种聚合物对3对种氢键给体分子苯偶姻(α=1.35~1.44)、 三氟-1-(9-蒽基)乙醇(α=1.11~1.53)、 2,2′-二羟基-1,1′-联萘(α=1.09~1.11)及乙酰丙酮钴(α=1.84~2.38)表现出很好的手性识别能力; 当以正己烷为流动相时, 3种聚合物都能立体选择性地识别氢键给体分子2,2-二甲基-1-苯基-1-丙醇(α=1.12~1.22), 聚[(S)-2-乙炔基-N-(2′-萘基胺基甲酰基)吡咯烷]能识别氢键受体分子2-苯基环己酮(α=1.11). 结合核磁共振波谱、 拉曼光谱、 旋光测试、 紫外吸收光谱和圆二色光谱及液相色谱等方法, 系统研究了芳香侧基结构与连接位置对聚合物螺旋构象和对映体选择性拆分能力的影响. 分子对接模拟结果表明, 1-萘基的空间位阻大于2-萘基且可促进形成更强的分子内氢键, 不利于大尺寸底物(如联萘酚)的手性拆分. 与苯基相比, 引入萘基有利于增强聚合物与底物间的π-π相互作用, 提高聚合物的立体选择性和手性识别能力.     

薤中新的甾体皂苷类化学成分

从薤(Allium chinense G. Don)的乙醇提取物中分离得到6个新甾体皂苷类化合物, 通过波谱数据及理化性质分析, 鉴定其分别为5α-cholano-22,16-内酯-3-O-β-D-吡喃葡萄糖基-(1→2)-[β-D-吡喃葡萄糖基-(1→3)]-β-D-吡喃葡萄糖基(1→4)-β-D-吡喃半乳糖苷(1)、 6-酮-5α-cholano-22,16-内酯-3-O-β-D-吡喃木糖基-(1→4)-[α-L-吡喃阿拉伯糖基-(1→6)]-β-D-吡喃葡萄糖苷(2)、 (25R)-26-O-β-D-吡喃葡萄糖基-5α-呋喃甾烷-3β,26-二醇-3-O-β-D-吡喃葡萄糖基-(1→2)-[β-D-吡喃葡萄糖基-(1→3)]-β-D-吡喃葡萄糖基(1→4)-β-D-吡喃半乳糖苷(3)、 (25R)-6-酮-26-O-β-D-吡喃葡萄糖基-5α-呋喃甾烷-3β,22α,26-三醇-3-O-α-L-吡喃木糖基-(1→4)-β-D-吡喃葡萄糖苷(4)、 (25R)-6-酮-5α-呋喃甾烷-3β,22α,24β,26-四醇-3-O-β-D-吡喃木糖基-(1→4)-[α-L-吡喃阿拉伯糖基-(1→6)]-β-D-吡喃葡萄糖苷(5)和(25R)-5α-呋甾-2α,3β,22α, 26-四醇-26-O-β-D-吡喃葡萄糖苷(6). 化合物1和2的皂苷元骨架在天然产物中首次分离得到. 选用H₂O₂诱导PC12细胞神经氧化损伤模型, 初步考察了6种新的呋甾型化合物的抗氧化活性, 实验结果表明, 化合物3对由H₂O₂诱导的细胞氧化损伤有显著的保护效果.     

环状烯酮与环状1-氮杂二烯的非对映及对映选择性[4+2]环加成反应

有机胺能催化环状烯酮化合物在多个位点发生不对称合成反应. 最近,我们发展了手性伯胺催化β-取代2-环戊烯酮与从糖精衍生的1-氮杂二烯的α’,γ-区域选择性的[5+3]形式环加成反应. 这里我们将报道采用β-取代2-环己烯酮或β-未取代2-环戊烯酮时,在手性伯胺催化下却与相同1-氮杂二烯发生完全不同的α’,β-区域选择性的不对称[4+2]环加成反应,生成高度官能团化的手性[2.2.2]或[2.2.1]桥环骨架结构. 重要的是利用不同类型的手性伯胺催化剂能够实现非对映选择性的反转,分别制备高立体选择性的endo-或exo-环加成产物.     

Tryptophan Cluster Protects Human γD‐Crystallin from Ultraviolet Radiation‐Induced Photoaggregation In Vitro

Exposure to ultraviolet radiation (UVR) is a significant risk factor for age‐related cataract, a disease of the human lens and the most prevalent cause of blindness in the world. Cataract pathology involves protein misfolding and aggregation of the primary proteins of the lens, the crystallins. Human γD‐crystallin (HγD‐Crys) is a major γ‐crystallin in the nucleus of the human lens. We report here analysis of UVR‐induced damage to HγD‐Crys in vitro. Irradiation of solutions of recombinant HγD‐Crys with UVA/UVB light produced a rise in solution turbidity due to polymerization of the monomeric crystallins into higher molecular weight aggregates. A significant fraction of this polymerized protein was covalently linked. Photoaggregation of HγD‐Crys required oxygen and its rate was protein concentration and UVR dose dependent. To investigate the potential roles of individual tryptophan residues in photoaggregation, triple W:F mutants of HγD‐Crys were irradiated. Surprisingly, despite reducing UVR absorbing capacity, multiple W:F HγD‐Crys mutant proteins photoaggregated more quickly and extensively than wild type. The results reported here are consistent with previous studies that postulated that an energy transfer mechanism between the highly conserved pairs of tryptophan residues in HγD‐Crys could be protective against UVR‐induced photodamage.     

Ability of N‐acetylcarnosine to protect lens crystallins from oxidation and oxidative damage by radical probe mass spectrometry (RP‐MS)

The application of Radical Probe Mass Spectrometry based on protein footprinting studies is described to investigate the effectiveness of the antioxidant N‐acetylcarnosine (NAC) in preventing oxidative damage to lens crystallins present in the eye of mammals. Despite separate clinical trials which have reported the benefit of administering NAC to the eye as a 1% topical solution for the treatment of human cataract, no evidence was found to suggest that the antioxidant had any significant direct effect on reducing the levels of oxidation within the most abundant lens crystallins, α and β‐crystallin, at the molecular level at increasing concentrations of NAC. The results of this laboratory study suggest that the therapeutic benefit demonstrated in clinical trials is associated with the nature or formulation of the topical solution and/or that the mode of action of NAC as an antioxidant is not a direct one. Copyright © 2010 John Wiley & Sons, Ltd.     

THE REACTION OF SINGLET OXYGEN WITH PROTEINS, WITH SPECIAL REFERENCE TO CRYSTALLINS

Photosensitized oxidation of the eye lens proteins, the crystallins, is thought to lead to protein crosslinks and high molecular weight aggregates. Such protein modifications may be important factors in the formation of lens opacities or cataracts. We focus attention here on type 2 photo-oxidation involving the reaction of singlet oxygen (1O2) with crystallins and some "control" proteins. We find that: (1) trp residues are oxidized to N-formyl kynurenine and related products, but this in itself does not lead to the production of high molecular weight protein aggregates of the protein; (2) tyr residues react with 1O2 but we do not detect dihydroxyphenylalanine or bityrosine nor are protein crosslinks formed as a result; (3) oxidation of his residues appears necessary for high molecular weight protein covalent aggregates to form. Proteins devoid of his, e.g. melittin or bovine pancreatic trypsin inhibitor, do not form high molecular weight products upon reaction with 1O2. Prior reaction and blocking of his inhibits the crosslinking reactions. (4) The oxidized protein is seen to be more acidic than the parent and has an altered tertiary structure. (5) Among the crystallins, reactivity towards 1O2 varies in the order gamma greater than beta greater than alpha and also gamma A/E greater than gamma D greater than gamma B crystallin.     

Deciphering In-vivo Cross-linking Mass Spectrometry Data for Dynamic Protein Structure Analysis

Protein structure and protein-protein interactions(PPIs) are crucial for regulating cellular activities required for cell viability and homeostasis. Chemical cross-linking coupled with mass spectrometry(CXMS) has become a versatile tool providing insights into both protein structure with distance restraints and protein-protein interactions with interface sites. Cross-links as the most information-rich data in a CXMS experiment are responsible for the structural model validation and integrative modeling with high throughput and sensitivity. In this work, ensemble refinement of the existing protein structure against the in-vivo cross-linking distance restraints was performed for dynamic protein structure modeling and protein interaction binding interface building in the intracellular environment. These results indicate great potential of in-vivo CXMS data for providing a molecular basis of protein structural dynamics exploration and function performance.     

Early Stage UV-B Induced Molecular Modifications of Human Eye Lens γD-Crystallin

In the human eye lenses, the crystallin proteins facilitate transparency, light refraction, as well as UV light protection. A deregulated balanced interplay between α-, β-, and γ-crystallin can cause cataract. γD-crystallin (hγD) is involved in the energy dissipation of absorbed UV light by energy transfer between aromatic side chains. Early UV-B induced damage of hγD with molecular resolution is studied by solution NMR and fluorescence spectroscopy. hγD modifications are restricted to Tyr 17 and Tyr 29 in the N-terminal domain, where a local unfolding of the hydrophobic core is observed. None of the tryptophan residues assisting fluorescence energy transfer is modified and hγD is remained soluble over month. Investigating isotope-labeled hγD surrounded by eye lens extracts from cataract patients reveals very week interactions of solvent-exposed side chains in the C-terminal hγD domain and some remaining photoprotective properties of the extracts. Hereditary E107A hγD found in the eye lens core of infants developing cataract shows under the here used conditions a thermodynamic stability comparable to the wild type but an increased sensitivity toward UV-B irradiation.     

Pd/γ-Al_2O_3催化剂催化氧化邻-二甲苯

利用纳米γ-Al_2O_3(10 nm)和普通γ-Al_2O_3(200-300 nm),采用浸渍法制备了1%(w)Pd/γ-Al_2O_3催化剂,考察了其催化氧化邻-二甲苯的性能以及催化剂的活性在氢气还原前后的区别。实验结果发现1%(w)Pd/γ-Al_2O_3(nano)在H_2还原后催化氧化邻-二甲苯的活性最高,T_(90)为150℃。利用X射线衍射(XRD)、比表面积(BET)、透射电镜(TEM)、X射线光电子能谱(XPS)等表征手段,研究了1%(w)Pd/γ-Al_2O_3催化剂物性结构与催化性能之间的构效关系。结果表明,还原态Pd是H_2还原后催化剂催化氧化邻-二甲苯的活性物种;Pd的颗粒大小与催化剂活性有显著的关系,小粒径有利于催化剂活性提高;纳米γ-Al_2O_3载体与Pd之间的相互作用强,有利于Pd的粒径控制和分散,从而提高1%(w)Pd/γ-Al_2O_3(nano)催化剂的活性。     

氧化铝纳米线的制备及其形成机理

采用二次铝阳极氧化技术, 制备高度有序的铝阳极氧化膜(AAO模板). 经X射线衍射(XRD)分析, 模板为无定形结构. 将模板放入腐蚀液中, 可获得大量无定形结构的氧化铝纳米线. 模板在800 ℃下退火4 h后, 变为γ-Al2O3结构, 采用类似腐蚀液溶解模板, 得到大量γ-Al₂O₃纳米线. 研究了腐蚀液种类、腐蚀时间和模板晶体结构等因素对生成氧化铝纳米线的影响, 并利用扫描电子显微镜(SEM)、透射电子显微镜(TEM)和XRD对纳米线的形貌与结构进行了表征. 结果表明, 在多种腐蚀液中, 均可获得氧化铝纳米线; 随着腐蚀时间的增加, 纳米线的长度增加, 直径变小, 长径比增大; 氧化铝纳米线的晶体结构与所采用模板的晶体结构一致. 此外, 还采用原子力显微镜(AFM)和SEM对AAO膜的表面形貌及其结构特点进行了详细的观测, 并以此为基础讨论了氧化铝纳米线的形成机理, 认为AAO模板本身存在的花状微结构是形成纳米线的内因, 花瓣间的凹陷部位首先被腐蚀断裂, 形成氧化铝纳米线.     

g-CN体系的准粒子能带结构和光学特性

利用多体格林函数理论,本文研究了二维CN体系(包括triazine和tri-s-triazine)的激发态特性。通过GW方法,我们计算了准粒子的能量。考虑电子-空穴相互作用,通过求解Bethe-Salpeter方程,我们获得了激发态能量和光谱。我们发现,在这两种CN体系的价带中,σ轨道和π轨道之间的交换作用非常强烈。由于占据的σ轨道和π轨道之间的准粒子修正量非常不同,因此,为了得到准确的带隙值和光谱,我们需要对这两种轨道开展精确的GW计算。与单层的CN体系相比,双层结构中层与层之间的范德华相互作用使带隙值降低了0.6 eV,而光吸收谱红移了0.2 eV,这是由于双层结构具有更小的激子束缚能。我们计算的吸收峰的位置与实验结果符合很好。实验中的吸收峰主要是由深能级的π轨道到π^*轨道的跃迁形成的。π→π^*跃迁和σ→π^*跃迁之间的耦合能够在长波长范围产生弱的吸收尾巴,如果调整入射光的极化方向,由σ→π^*跃迁产生的高强度的吸收峰将会在更低能量处出现。     

介孔γ-Al2O3负载的高分散Ni-Ce-Zr氧化物的制备及其二氧化碳甲烷化研究

采用柠檬酸（CA）-浸渍法制备了介孔γ-Al₂O₃（γ-MA）负载的高分散Ni-Ce-Zr氧化物,并将其用于二氧化碳甲烷化反应。研究了柠檬酸加入量对催化剂物理化学性质及催化性能的影响。结果表明,柠檬酸的加入可明显提高Ni-Ce-Zr氧化物在γ-Al₂O₃表面的分散性,同时可以增加镍氧化物与载体间的相互作用。制备材料经氢气还原后得到Ni-Ce-Zr/γ-MA催化剂,镍纳米颗粒均匀分散于γ-Al₂O₃表面。Ni-Ce-Zr/γ-MA催化剂在二氧化碳甲烷化反应中表现出了较高的反应活性和几乎100%的甲烷选择性。反应活性随CA/（Ni+Ce+Zr）摩尔比的增加而增加,主要是由于镍颗粒尺寸的减小和Ni-Ce-ZrO_x物种电子和结构性质的提高。CA/（Ni+Ce+Zr）摩尔比为1的Ni-Ce-Zr/γ-MA催化剂在反应300 h内活性仅降低7%,并且没有明显积碳。表明催化剂在二氧化碳甲烷化反应中具有优异的反应稳定性和抗积碳性能。