抗癌药物喜树碱的功能化改性及研究进展

20-（S）-喜树碱（CPT）是一种具有广谱抗癌活性的生物碱。其抗癌活性主要体现在CPT的内酯环能够与DNA拓扑异构酶Ⅰ结合并异化DNA拓扑结构,进而诱导肿瘤细胞的凋亡。然而,喜树碱内酯环在生理环境下极易水解开环形成羧酸盐,导致药物失活;同时喜树碱本身所存在的水溶性差、对正常机体组织毒副作用大等缺点也极大限制了CPT的...     

铂催化环加成反应的研究进展

综述了近年来铂催化[3+2]、[4+2]、[4+3]、[2+2]和[2+1]等环加成反应的研究进展,并对部分环加成反应可能的机理进行了讨论,同时提出了铂催化环加成反应的特点.     

镧系金属催化不对称环加成反应研究进展

综述了近年来镧系金属催化不对称环加成反应的研究进展,主要包括[4+2]、[3+2]、[2+2]和[2+1]不对称环加成反应.并对部分环加成反应可能的机理进行了讨论.     

三组分环加成反应

Stanford大学教授P .A .Wender的实验室发现了一种金属催化环加成反应。他们发现在有些金属催化的 [6 +2 ]环加成反应中 ,有一个副产物是由 [6 +2 - 1]过程生成的七元环化合物。Wender立即想到 ,[5 +2 ]反应可能会通过 [5 +2 +1]过程生成八元环。他们在一个铑催化的反应中证实了这个设想。当用很容易合成的乙烯基环丙烷和市场上就能买到的炔的衍生物在CO气氛下反应时 ,得到了八元环的产物。如图所示 ,由最初加合物的跨环闭合生成的双环辛烷酮的产率相当好三组分环加成反应@宋琦…     

芳香聚芳醚酮大环化合物结构分析

大环化合物因其特有的环状结构,近些年来引起了人们的强烈关注.氮杂大环化合物[1]、二联苯和氨基酸构建的大环化合物[2]、赖氨酸衍生氮杂大环化合物[3]、酞菁、类酞菁类大环化合物[4]以及含吡啶大环化合物[5]相继报道.     

9,10-二(苯亚甲基-硫亚甲基)蒽的合成及其对Cu2+的识别

荧光分子开关和分子识别是超分子化学的重要组成部分。蒽环作为一个优良的荧光基团被广泛应用于分子开关的设计及分子识别中。Resorci-narenes母体衍生物的合成研究中采用蒽环作为荧光基团已被报道多次[1-4],Luigi Fabbrizzi合成的多氨基蒽衍生物[5]对Zn2 具有良好的PET效应。蒽系荧光分子在分子逻辑门系统中日益受到了研究者的重视,de Silva等在研究中发现一蒽环化合物[6]在Mg2 作用存在OR逻辑行为。在后续研究中发现两类蒽环化合物在一定条件下分别存在AND[7]和NOR[8]逻辑行为。在分子识别的研究中,Shin-ichi Sasaki合成的含穴状…     

葫[n]环联脲(n=5,6,7,8)与两种重氮氟硼酸盐的包合作用研究

用核磁共振氢谱和紫外-可见光谱滴定法考察了葫[n]环联脲(Cucurbit[n]uril,n=5,6,7,8)与对甲苯重氮氟硼酸盐和4,4′-联苯二重氮氟硼酸盐的配位情况,并用曲线拟合求得形成的包结配合物的稳定常数.结果表明,不同空腔的葫[n]环联脲对不同尺寸的重氮氟硼酸盐具有很显著的选择性包结作用.在相同条件下,与葫[6]环联脲相比,葫[7]环联脲更易于容纳苯环.同时,随着酸性的增强,葫[n]环联脲上的脲羰基质子化程度加大,使得其配位能力有所减弱.     

氮杂环丙烷[3+3]环加成反应研究进展

氮杂环丙烷作为一类具有生物活性的三元杂环化合物,由于其三元环高度的环张力而被广泛应用于[2+2]、 [3+1]、 [3+2]、 [3+3]、 [4+3]以及[5+2]等环加成反应中,近年来受到了研究学者们的广泛关注。本文主要综述了氮杂环丙烷与含C=C、 C=N、 C≡N、 C≡C、 C═•═C以及其它类化合物的[3+3]环加成反应的研究进展,并对其未来研究方向进行了展望。      

亚硝基化合物环加成反应的研究进展

综述了近几年来亚硝基化合物与含各种不饱和键化合物环加成反应的研究进展,主要包括[2+2]、[3+2]、[2+2+1]、[3+3]、[4+1]和[4+2]等环加成反应,并对其发展方向进行了展望.     

三种瓜环与药物乙酰胆碱的主客体相互作用

本文选取了三种具有不同空腔大小的瓜环:对称四甲基六元瓜环(TMeQ[6])、七元瓜环(Q[7])、八元瓜环(Q[8]),利用核磁共振技术以及质谱分析手段探究了这三种瓜环与药物分子乙酰胆碱(ACh)的相互作用。结果表明,ACh位于TMeQ[6]的端口,与空腔较小的TMeQ[6]形成端口作用,而进入了空腔相对更大的瓜环Q[7]、Q[8]的内腔,三者均以1∶1的作用比形成了主客体超分子药物包合物。     

盐酸环丙沙星与胰蛋白酶相互作用的光谱和分子模拟研究

运用荧光光谱和紫外光谱, 结合分子模拟法研究了盐酸环丙沙星(CPFX)与胰蛋白酶(Trypsin)在不同温度条件下(288, 298和308 K)的相互作用. 研究发现CPFX对Trypsin有较强的荧光猝灭作用, 且为静态猝灭类型. 根据双对数方程处理荧光猝灭数据得到了CPFX与Trypsin在不同温度下的结合常数K和结合位点数n. 利用紫外光谱定性讨论了CPFX对Trypsin构象的影响. 通过热力学方程求得了不同温度下CPFX与Trypsin作用的热力学参数, 表明它们之间的作用力主要是疏水作用和氢键, 这与分子模拟方法所得的结果是一致的.     

荧光光谱法研究2,4,6-三氯苯酚与胰蛋白酶的相互作用

运用荧光光谱法研究了2,4,6-三氯苯酚与胰蛋白酶的相互作用。结果表明:2,4,6-三氯苯酚通过静电和疏水作用力与胰蛋白酶形成基态复合物导致胰蛋白酶内源荧光猝灭,猝灭机理主要为静态猝灭。计算了该反应的表观结合常数K、结合位点数n及结合反应的热力学参数,并用同步荧光和三维荧光技术考察了2,4,6-三氯苯酚对胰蛋白酶构象的影响,酪氨酸和色氨酸残基所处微环境的疏水性增加。     

Fluorimetric study of interaction of merbromin with trypsin

Interaction of merbromin with trypsin is of bovine origin has been studied by monitoring the absorption steady-state and time-resolved fluorescence spectral properties of the dye. Studies have been done in media of varying pH at different trypsin concentrations. It has been observed that trypsin brings about a quenching of fluorescence of the dye. The quenching is static in nature and the equilibrium constant of dye-trypsin interaction in the ground-state has been determined from quenching studies. Steady-state anisotropy of the dye increases in presence of trypsin in the medium. Values of micro-viscosity in the vicinity of the fluorophore in media containing trypsin have been determined from measurements of fluorescence anisotropy. Time-resolved fluorescence studies indicate the existence of two decaying states for the dye. The fractional contribution to the time-resolved decay changes with pH. The average lifetime, however, does not depend on the concentration of trypsin.     

Mechanistic investigation on binding interaction of bioactive imidazole with protein bovine serum albumin--a biophysical study

The interaction between bioactive imidazole derivative (PPP) and bovine serum albumin (BSA) was investigated using fluorescence and UV-vis spectral studies. The experimental results showed that the fluorescence quenching of BSA by imidazole derivative was the result of the formation of BSA-PPP complex and the effective quenching constants (K(SV)) were 2.66×10(4), 2.56×10(4), and 2.10×10(4) at 301, 310 and 318 K, respectively. Static quenching and non-radiative energy transfer were confirmed to the result in the fluorescence quenching. The binding site number n, apparent binding constant K(A) and corresponding thermodynamic parameters (ΔG, ΔH and ΔS) were measured at different temperatures. The process of binding of PPP molecule on BSA was a spontaneous molecular interaction procedure in which entropy increased and Gibbs free energy decreased.     

Mechanisms of tannin-induced trypsin inhibition: a molecular approach

Association of procyanidins with enzymes has drawn attention over the past few years. This work aimed to bring insights on interaction of the protease trypsin with the procyanidin dimer (B3). This interaction was characterized by fluorescence quenching, saturation transfer difference (STD) NMR, molecular modeling, and through an enzymatic inhibition assay. Further studies were conducted regarding the influence of pectin on the binding process. A general overview of the binding process may be outlined as follows: a) at low procyanidin concentrations (below the critical micellar concentration-(CMC)) a specific interaction probably driven by hydrogen bonds between the protein backbone and the procyanidin occurs and is associated with the reduction of both enzyme activity and fluorescence; b) at high procyanidin concentration (above the CMC) the interaction becomes nonspecific. This variation in both nature and extent of the interaction with the variation of procyanidin concentration shows how tannin self-association may affect the interaction between tannins and proteins. It was also shown that the mechanism through which pectin affects the interaction between procyanidin B3 and trypsin is of a competitive type.     

Analysis of binding interaction between vitamin B2 and trypsin

The interaction between vitamin B₂ (VB₂), a type of necessary nutrient for the body’s metabolism and repair, and trypsin, a serine protease found in the digestive system, has been investigated in vitro under a simulated physiological condition by UV–Vis spectrophotometry and fluorescence spectrometry. The intrinsic fluorescence intensity of trypsin was strongly quenched by VB₂. Spectrophotometric observations are rationalized in terms of a static quenching process at lower concentrations of VB₂ and a combined quenching (both dynamic and static) process at higher concentrations of VB₂. The binding parameters, such as the binding constants and the number of binding sites, can be evaluated by fluorescence quenching experiments. The apparent binding constants K between VB₂ and trypsin at different temperatures were 1.406, 1.264, and 0.543 × 10⁶ L mol^?1 and the numbers of binding sites n were 1.386, 1.391, and 1.319, which were all evaluated by the fluoresence quenching experiments. The negative values of ΔG for the formation of the trypsin–VB₂ complex implied that the binding was a spontaneous process. According to the van’t Hoff equation, the standard enthalpy change (ΔH) and standard entropy change (ΔS) for the reaction were calculated to be ?49.817 kJ mol^?1 and ?56.219 J mol^?1 K^?1, respectively, indicating that the hydrophobic interaction played a significant role in VB₂ binding to trypsin. In addition, the binding distance between VB₂ (acceptor) and trypsin (donor) was estimated to be 1.11 nm according to Förster’s resonance energy transfer theory. The results obtained here will be of biological significance in pharmacology and clinical medicine.     

Spectroscopic studies on ligand-enzyme interactions: complexation of alpha-chymotrypsin with 4',6-diamidino-2-phenylindole (DAPI).

In the present study, the interaction of two structurally related proteolytic enzymes trypsin and alpha-chymotrypsin (CHT) with 4',6-Diamidino-2-phenylindole (DAPI) has been addressed. The binding of DAPI to CHT has been characterized by steady-state and picosecond time-resolved spectroscopic techniques. Enzymatic activity of CHT and simultaneous binding of the well-known inhibitor proflavin (PF) in the presence of DAPI clearly rule out the possibility of DAPI binding at the catalytic site of the enzyme. The spectral overlap between the emission of DAPI and absorption of PF offers the opportunity to explore the binding site of DAPI using F?rster resonance energy transfer (FRET). FRET studies between DAPI and PF indicate that DAPI is bound to CHT with its transition dipole nearly perpendicular to that of PF. Competitive binding of DAPI with another fluorescent probe 2,6-p-toluidinonaphthalene sulfonate (TNS), having a well-defined binding site, indicates that DAPI and TNS bind at the same hydrophobic site of the enzyme CHT. The difference in the interactions of two well-studied, structurally similar enzymes with the same molecule may find its application in the design of specific substrate mimics or inhibitors of the enzymes.     

3-溴丙酮酸与人血清白蛋白相互作用的光谱学研究

运用荧光光谱、紫外可见吸收光谱和圆二色光谱法研究了抗肿瘤药物3-溴丙酮酸(3-Bromopyruvic acid,3-BrPA)与人血清白蛋白(Human serum albumin,HSA)的相互作用.3-BrPA对HSA的猝灭机制属于静态猝灭,并发生分子间非辐射能量转移.热力学数据显示,二者之间的作用力主要为静电作用;同步荧光光谱表明,3-BrPA与蛋白质中接近色氨酸残基的区域发生了相互作用;荧光光谱研究发现,Zn2+存在时3-BrPA对HSA的猝灭程度进一步增强;圆二色光谱法研究蛋白二级结构结果显示,3-BrPA对HSA的结构影响非常小.     

Ab initio study on the noncovalent adsorption of camptothecin anticancer drug onto graphene, defect modified graphene and graphene oxide

The application of graphene and related nanomaterials like boron nitride (BN) nanosheets, BN-graphene hybrid nanomaterials, and graphene oxide (GO) for adsorption of anticancer chemotherapeutic camptothecin (CPT) along with the effect on electronic properties prior to functionalization and after functionalization has been reported using density functional theory (DFT) calculations. The inclusion of dispersion correction to DFT is instrumental in accounting for van der Waals π–π stacking between CPT and the nanomaterial. The adsorption of CPT exhibits significant strain within the nanosheets and noncovalent adsorption of CPT is thermodynamically favoured onto the nanosheets. In case of GO, surface incorporation of functional groups result in significant crumpling along the basal plane and the interaction is basically mediated by H-bonding rather than π–π stacking. Docking studies predict the plausible binding of CPT, CPT functionalized graphene and GO with topoisomerase I (top 1) signifying that CPT interacts through π stacking with AT and GC base pairs of DNA and in presence of nano support, DNA bases preferentially gets bound to the basal plane of graphene and GO rather than the edges. At a theoretical level of understanding, our studies point out the noncovalent interaction of CPT with graphene based nanomaterials and GO for loading and delivery of anticancer chemotherapeutic along with active binding to Top1 protein.     

Mechanism of interaction of vincristine sulphate and rifampicin with bovine serum albumin: A spectroscopic study

The mechanism of interaction of vincristine sulphate (VS) and rifampicin (RF) with bovine serum albumin (BSA) has been studied by quenching of BSA fluorescence by RF/VS. The Stern-Volmer plot indicates the presence of a static component in the quenching mechanism. Results also show that both the tryptophan residues of BSA are accessible to VS and RF. The high magnitude of rate constant of quenching indicates that the process of energy transfer occurs by intermolecular interaction and VS/RF-binding site is in close proximity to the tryptophan residues of BSA. Binding studies in the presence of a hydrophobic probe, 8-anilino-1-naphthalene-sulphonic acid sodium salt (ANS) indicate that the VS and RF compete with ANS for hydrophobic sites on the surface of BSA. Small decreases in critical micellar concentrations (CMC) of anionic surfactants in presence of VS/ RF show that the ionic character of VS/RF also contributes to binding. The temperature dependence of the association constant is used to estimate the values of the thermodynamic parameters involved in the interaction of VS/RF with BSA and the results indicate that hydrophobic forces play a significant role in the binding. Circular dichroism studies reveal that the change in helicity of BSA are due to binding of VS/RF to BSA.