Design,Synthesis and Biological Evaluation of Novel Selective Thiol-based Histone Deacetylase(HDAC) VI InhibitorsBearing Indeno[1,2-c]pyrazole or Benzoindazole Scaffold

A series of thiol-based indeno[1,2-c]pyrazoles and benzoindazole compounds was designed and synthesized according to the structural specificity of histone deacetylase VI(HDAC6) and the structural characteristics of HDAC inhibitors. The inhibitory activities of the target compounds against HDAC6 and HDAC1 were screened by fluorescence analysis. Most of the target compounds showed moderate inhibitory activity against HDAC6(IC₅₀=44—598 nmol/L). Among them, compound A-4 displayed the highest selectivity against HDAC6 and similar inhibitory activity(IC₅₀=44 nmol/L) to that of the positive drug SAHA(IC₅₀=41 nmol/L) against HDAC6.     

Hydrolysis of amide bond in histidine-containing peptides promoted by chelated amino acid palladium(II) complexes: dependence of hydrolytic pathway on the coordination modes of the peptides

Hydrolytic reactions between cis-[Pd( -Ala-N,O)Cl₂]⁻ and cis-[Pd( -Ala-N,O)(H₂O)₂]⁺, in which -Ala is alanine coordinated through N and O atoms, and N-acetylated peptides -histidylglycine (MeCO-His-Gly), glycyl- -histidine (MeCO-Gly-His), glycylglycyl- -histidine (MeCO-Gly-Gly-His) and glycyl- -histidylglycine (MeCO-Gly-His-Gly) were studied by ¹H NMR spectroscopy. All reactions were carried out in the pH range 2.0–2.5 and two different temperatures, 22 and 60°C. In the reactions of these two palladium(II) complexes with MeCO-His-Gly, complete hydrolysis of the amide bond involving carboxylic group of histidine occurs in less than 24 h. The cleavage is regioselective. With peptides containing free a carboxylic group of histidine, MeCO-Gly-His and MeCO-Gly-Gly-His, palladium(II) complex promote the cleavage of the MeCO–Gly and Gly–Gly amide bonds. No cleavage of the Gly–His amide bond was observed. The mechanism of these hydrolytic reactions involves release of -Ala ligand and aquation of the palladium(II) complex chelated to the substrate through the imidazole N-3 atom and deprotonated nitrogen atom of the amide bond involving amino group of histidine. This aqua complex represents a catalytically active form different from the initially added catalytically inactive complex. In the reactions of palladium(II) complexes with tripeptide MeCO-Gly-His-Gly, two amide bonds, MeCO–Gly and His–Gly, were cleaved. The mechanism of the cleavage of these amide bonds is correlated with two different palladium(II)–substrate catalytically active forms. These findings contribute to the better understanding of selective cleavage of peptides and proteins and must be taken into consideration in designing new reagents for this purpose.     

一种新型含酞侧基聚芳醚砜的稀溶液性质研究(Ⅰ)──溶解行为和M-H方程的测定

制备了窄分布的含酞侧基聚芳醚砜(PES-C)级份样品,用光散射法测定样品重均分子量,粘度法测定样品在DMF、CHCl₃和1,2-C₂H₄Cl₂中的特性粘数和Huggins参数k'值。k'值远大于0.5反映了体系中存在特殊的溶解行为。得到PES-C在3种溶剂中的Mark-Houwink方程: [η]=2.79× 10^-2M_w^0.615,r=0.999 8(DMF,25℃) [η]=3.96× 10^-2M_w^0.58,r=0.999 5(CHCl₃,25℃) [η]=7.40× 10^-2M_w^0.52,r=0.999 5(1,2-C₂H₄Cl₂,25℃).     

Structural investigation of dibromobis(benzimidazole)Zn(II) complex

The molecular structure of the title complex [ZnBr₂(C₇H₆N₂)₂] was investigated by X-ray diffraction and IR spectroscopy methods. Molecules of zinc(II) complex crystallize in the triclinic crystal system with cell constants a=7.526(2) Å, b=7.8971(8) Å, c=13.431(1) Å, Z=2 and V=791.3(2) Å³. In the molecular structure, the Zn atom is coordinated tetrahedrally by two Br⁻ anions and two benzimidazole ligands. Intramolecular steric repulsions between Br⁻ anions and benzimidazole groups have been caused to cis configuration around the central metal atom.     

分光光度法研究二羟基二过碘酸合镍(Ⅳ)氧化三乙醇胺的反应动力学及机理

在碱性介质中,用分光光度法研究了二羟基二过碘酸合镍(Ⅳ)配离子氧化三乙醇胺的动力学.结果表明,反应对Ni(Ⅳ)为准一级反应,速率常数kobs=(k₁+k₂[OH^-])K₁K₂[OH^-][TEA]/{[H₂IO₆^3-]+K₁[OH^-]+K₁K₂[OH^-][TEA]},对还原剂三乙醇胺为正非整数级,表观速率常数随[OH^-]的增加而增加,随[IO₄^-]的增加而减小.据此提出了Ni(Ⅳ)和还原剂所形成的活化配合物的内部电子转移的反应机理.并求得28℃时前期平衡常数和速控步骤的速率常数分别为K₁=2.063,K₂=36.471L·mol^-1;k₁=8.008×10^-2s^-1,k₂=0.2896mol^-1·L·s^-1.     

氮杂大环双核铜锌金属配合物的合成结构及溶液中配位稳定性研究

在合成模型化合物之前 ,有必要先了解合成的大环配体在溶液中与金属离子的配位行为及其稳定性 ,以便选择不同结构的大环配体和控制反应的 p H值合成出结构和催化性能较好的模型化合物 [1～ 3] .本文报道了大环配体与 Cu( )和 Zn( )形成的配合物 ,对其结构和溶液中的配位稳定性进行了研究 .1　实验部分1 .1　试剂与仪器配体 L以 2 ,6-吡啶二甲醛和二乙烯三胺为原料 ,按文献 [4]报道的方法经 2 + 2合成得到 .其纯度经元素分析、红外光谱、核磁共振氢谱和质谱鉴定 .其它试剂均为分析纯 . p H滴定采用二次蒸馏水 .Perkin- Elmer 2 4 0型元…     

HDAC对接研究:苯甲酰胺类抑制剂结合方式推测

通过计算机模拟的对接过程研究，发现了MS-275— 一种苯甲酰胺类的组蛋白去乙酰酶（HDAC）抑制剂与酶的可能的全新结合方式.这种结合方式与已经阐明的组蛋白去乙酰酶类似蛋白（HDLP）与曲古柳菌素A(trichostatin A, TSA)和suberoylanilide hydroxamic acid(SAHA)形成的复合物晶体结构中配体与酶的作用方式完全不同.从对接结果看，MS-275的作用靶点在酶活性口袋的最狭窄部位，而不是直接作用于锌离子.这似乎能够解释MS-275的低毒性特点，并且为设计和筛选全新的HDAC抑制剂提供了新思路.     

Interaction of heterocyclic thioamides with tellurium(II) and tellurium(IV). Syntheses and crystal structures of bis[2-(2-thioxo-1,3- thiazolidin-3-yl)-4,5-dihydro-1,3- thiazolium]hexabromotellurate(IV) and tris(1- methylimidazole-2-(3H)-thione)tellurium(II) bromide

Reaction of 1,3-thiazolidine-2-thione with tellurium(IV) in hydrobromic acid medium gave the hexabromotellurate, [C₆H₉N₂S₃]₂²⁺[Te^IVBr₆]²⁻ (3). Reaction of 1-methylimidazoline-2-(3H)-thione (L″) with tellurium(IV), in hydrobromic acid medium, gave the mixed-ligand tellurium(II) complex [Te^IIL″₃Br]⁺Br⁻ (4). The structures of [C₆H₉N₂S₃]₂²⁺[Te^IVBr₆]²⁻ (3) and [Te^IIL″₃Br]⁺Br⁻ were determined by single crystal X-ray diffraction methods. In 3 the unit cell contains [TeBr₆]²⁻ anions and two [C₆H₉N₂S₃]⁺ cations. There is no direct bonding between the metal atom and the cations. In the anion only slight angular deviations from the perfect octahedral geometry are observed. The lone pair of electrons on tellurium(IV) is found to be stereochemically inert. In the cation the two five-membered heterocyclic rings adopt different conformations. In complex 4, in the solid state, the planar [Te^IIL″₃Br]⁺ cation and Br⁻ anion are held together by ionic interactions. In the cation, L″ is bonded to the central tellurium atom through the sulphur atom.     

PMBP与中性磷萃取剂对铽(Ⅲ)的协同萃取

本文研究了1-苯基-3-甲基-4-苯甲酰基吡唑啉酮-5(PMBP)与丁基膦酸二丁酯(DBBP)或磷酸三丁酯(TBP)的氯苯溶液在硝酸介质中对铽(Ⅲ)的协同萃取。测得了萃合物的组成及其萃取平衡常数,讨论了萃合物的可能结构式及协同萃取机理。     

Zn-Al-[V_(10)O_(28)]~(6-)双层氢氧化物掺杂对LY12铝合金表面溶胶-凝胶涂层性能的影响

采用共沉淀法制备Zn-Al-[V10O28]6-双层氢氧化物(以下简称LDH-V),研究不同添加浓度(0.0、0.25×10-3、0.75×10-3、1.5×10-3、3.0×10-3mol·L-1)的LDH-V对LY12铝合金溶胶-凝胶涂层形貌、耐蚀性的影响.采用扫描电子显微镜(SEM)和傅里叶变换红外(FTIR)光谱研究LDH-V对涂层形貌和结构的影响.运用中性盐雾实验对涂层进行耐蚀性评估.利用电化学方法对涂层在0.05 mol·L-1的NaCl溶液中的腐蚀行为进行研究.探讨加入LDH-V后溶胶-凝胶涂层的耐蚀机理.结果表明,一定量LDH-V的加入不仅可以提高溶胶-凝胶涂层的耐蚀性能,还可对涂层被破坏区域进行自修复,起到延缓铝合金基体腐蚀的作用.然而,当LDH-V的添加溶度超过一定值时,会破坏涂层的完整性并降低涂层的腐蚀防护性能.实验结果表明LDH-V最佳的添加浓度为1.5×10-3mol·L-1.     

Synthesis, spectral and structural characterization of three zinc(II) azide complexes with aminopyrazine

The reaction between zinc(II) azide, Zn(N₃)₂ and aminopyrazine (ampyz) afforded the complexes: [Zn(N₃)₂(ampyz)₂] (1), [Zn(N₃)₂(ampyz)]_n (2) and [Zn₃(N₃)₆(ampyz)₂]_n (3). These complexes are characterized by spectroscopic and crystallographic methods. The IR spectra of these compounds are measured and discussed. The structure of 1 consists of isolated tetrahedral zinc atom surrounded by two mono-dentate N-ampyz and two terminal azido ligands. Complex 2 features a zigzag chain of zinc centers in which each zinc is surrounded by alternate di-EO (end-on) and di-EE (end-to-end) azide bridges, the chain thus contains alternate four-membered Zn₂N₂ and eight-membered Zn₂(NNN)₂ rings. The two ampyz ligands are located in cis-arrangement and each of them further binds another zinc atom giving rise to a 3D network. Complex 3 contains two structurally different zinc atoms; the six-coordinate Zn(1) center links two di-EO azido bridges and two trans ampyz, thus having ZnN₆ chromophore. The five-coordinate Zn(2) center binds two di-EO bridging azido groups and the fifth position is occupied by an N atom from a bridging ampyz molecule. Both zinc centers, therefore participate in the formation of a 1D chain of cyclic Zn₂N₂ units. Each ampyz ligand binds another zinc atom via the second pyrazinic N atom giving another cross-chain and thus the structure consists of 2D sheets. In these three complexes the azido ligands of all types are asymmetric and linear within the experimental error.     

Determination of L-phenylalanine by cucurbit[7]uril sensitized fluorescence quenching method

The determination method of L-phenylalanine（LPA） by fluorescence quenching was developed.The assay was based on the combination of the cucurbit[7]uril（CB[7]） with palmatine hydrochloride（PAL） reaction.In the presence of CB[7],the fluorescence of PAL was quenched by LPA which can be employed to detect LPA.Under the optimal conditions,a linear range 3.63×10^-8- 9.68×10^-6mol/L and a detection limit 1.27×10^-8mol/L of LPA were obtained.The relative standard deviation（R.S.D） was 1.8%obtained from a series of 11 standards each containing 6.05×10^-6 mol/L of LPA.This paper also discusses the mechanism of fluorescence indicator probe.     

Non-Hydroxamate Zinc-Binding Groups as Warheads for Histone Deacetylases

Histone deacetylases (HDACs) remove acetyl groups from acetylated lysine residues and have a large variety of substrates and interaction partners. Therefore, it is not surprising that HDACs are involved in many diseases. Most inhibitors of zinc-dependent HDACs (HDACis) including approved drugs contain a hydroxamate as a zinc-binding group (ZBG), which is by far the biggest contributor to affinity, while chemical variation of the residual molecule is exploited to create more or less selectivity against HDAC isozymes or other metalloproteins. Hydroxamates have a propensity for nonspecificity and have recently come under considerable suspicion because of potential mutagenicity. Therefore, there are significant concerns when applying hydroxamate-containing compounds as therapeutics in chronic diseases beyond oncology due to unwanted toxic side effects. In the last years, several alternative ZBGs have been developed, which can replace the critical hydroxamate group in HDACis, while preserving high potency. Moreover, these compounds can be developed into highly selective inhibitors. This review aims at providing an overview of the progress in the field of non-hydroxamic HDACis in the time period from 2015 to present. Formally, ZBGs are clustered according to their binding mode and structural similarity to provide qualitative assessments and predictions based on available structural information.     

可视化检测次氯酸的苯并咪唑类 荧光增强型探针

合成了一种新型的苯并咪唑类荧光增强型探针2-{[4-(1H-苯并咪唑-2-基)苯亚甲基]氨基}-3-氨基马来腈(ZY12), 用光谱方法研究了其对次氯酸的识别作用. 实验结果表明, ZY12对ClO ^-表现出较高的选择性和灵敏度, 且响应快速, 抗干扰能力强; 将ClO ^-加入到ZY12溶液中后, 反应体系的荧光强度随ClO ^-浓度的增加而逐渐增强, 并伴随着荧光颜色由微蓝色到亮蓝色的变化, 可实现对ClO ^-的可视化检测; 在1.8×10 ^-6~3.4×10 ^-5 mol/L浓度范围内, ZY12能够定量检测ClO ^-, 检测限为2.8×10 ^-7 mol/L; ZY12可应用于不同水样中ClO ^-的检测, 并能对HeLa活细胞中的ClO ^-进行荧光成像.     

Neutral pyridylmethylamide ligands and their mononuclear copper(II) complexes

Mononuclear copper(II) complexes of a family of pyridylmethylamide ligands HL, HL^Me, HL^Ph, HL^Me3 and HL^Ph3, [HL = N-(2-pyridylmethyl)acetamide; HL^Me = N-(2-pyridylmethyl)propionamide; HL^Ph = 2-phenyl-N-(2-pyridylmethyl)acetamide; HL^Me3 = 2,2-dimethyl-N-(2-pyridylmethyl)propionamide; HL^Ph3 = 2,2,2-triphenyl-N-(2-pyridylmethyl)acetamide], were synthesized and characterized. The reaction of copper(II) salts with the pyridylmethylamide ligands yields complexes [Cu(HL)₂(OTf)₂] (1), [Cu(HL^Me)₂](ClO₄)₂ (2), [Cu(HL)₂Cl]₂[CuCl₄] (3), [Cu(HL^Me3)₂(THF)](OTf)₂ (4), [Cu(HL^Me3)₂(H₂O)](ClO₄)₂ (5a and 5b), [Cu(HL^Ph3)₂(H₂O)](ClO₄)₂ (6), [Cu(HL)(2,2′-bipy)(H₂O)](ClO₄)₂ (7), and [Cu(HL^Ph)(2,2′-bipy)(H₂O)](ClO₄)₂ (8). All complexes were fully characterized, and the X-ray structures vary from four-coordinate square-planar, to five-coordinate square-pyramidal or trigonal-bipyramidal. The neutral ligands coordinate via the pyridyl N atom and carbonyl O atom in a bidentate fashion. The spectroscopic properties are typical of mononuclear copper(II) species with similar ligand sets, and are consistent their X-ray structures.     

A localized molecular orbital study on the bonding of> Mo3S4]2Mo> and> Mo3S4]CuI> versus (C6H6)2Cr and C6H6Cr(CO)3

The energy-localized CNDO/2 molecular orbitais have been calculated for the clusters containing molybdenum, > {Mo₃S₄₂Mo}⁸⁺ and> Mo₃S₄]CuI> ⁴⁺, versus the prototype arene-metal sandwich (C₆H₆)₂Cr and half-sandwich complexes C₆H₆Cr(CO)₃. The bonding characteristics of these compounds are described from a localization bonding viewpoint. There are two typical M-arene and M-[Mo₃S₄] bondings. One is formed by electron donation from the three-center two-electron π-bonds in the arene or [Mo₃S₄]⁴⁺ ligands into the vacant hybrid orbitais of the “stranger” metal atom. In the other M-arene or M-[Mo₃S₄] bond there is very little donation by the lone electron pair occupying the d AOs of the “stranger” metal atom to the arene or [Mo₃S₄]⁴⁺ ligands. The analogy of the ligand [Mo₃S₄]⁴⁺ in the clusters studied with the ligand benzene is also briefly discussed.     

自然轨道福井函数和成键活性描述符应用于解释苯硫醌和1, 3-二烯的[2+4]和[4+2]环加成反应中的成键机理

苯硫醌与脂肪族烯烃可以发生[2+4]和[4+2]环加成反应。为了解释这些环加成反应中的成键过程,本文使用了自然轨道福井函数(NOFF)与成键活性描述符。自然轨道福井函数揭示了苯硫醌和脂肪族烯烃的键或轨道的亲电性,表明电子供体的成键轨道和电子受体的反键/成键轨道之间发生了电子转移,然后成环,在这一过程中有两个共价键形成,得到了环状产物。成键活性描述符表明共价键比较容易在一个分子中具有较大f_k1⁺值的k1原子与另一个分子中具有较大f_k2^-值的k2原子之间形成。自然轨道福井函数与成键活性描述符都可以有效解释苯硫醌与1, 3-二烯之间的[2+4]与[4+2]环加成反应的机理。     

基于Nafion固定磷钼酸和石墨烯共修饰PEDOT膜电极的电化学过氧化氢传感器

以玻碳电极（GCE）为基底电化学聚合制得聚3,4-乙烯二氧噻吩（PEDOT）膜修饰电极,再通过Nafion共固定磷钼酸和石墨烯构建了一种新型的无酶电化学H₂O₂传感器. 利用扫描电子显微镜（SEM）表征制得的修饰电极,并通过循环伏安法和计时电流法研究了传感器对H₂O₂的响应性能. 结果表明,在优化条件下,该传感器对H₂O₂还原具有良好的电催化性能,检测H₂O₂的线性范围为2.91×10^-6 ~ 1.83×10^-2 mol•L^-1,检出限和灵敏度分别为9.90×10^-7 mol•L^-1（S/N = 3）和112.5 μA•（mmol•L^-1）^-1. 此外,该传感器还具有良好的重现性和选择性.     

Investigations of Thallium(Ⅰ) Underpotential Deposition on the Silver Rotating Disk Electrode and Its Analytical Application

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