含萘酰亚胺基元的水杨醛席夫碱的合成及其溶致变色效应

将N-2-（-2-羟乙氧基）乙基4肼基-1,8-萘酰亚胺与水杨醛缩合得到-种新型席夫碱化合物N-（2-（2-羟乙氧基）乙基）4-（2-羟基苯甲醛腙肼基）-1,8-萘酰亚胺（Ⅰ）,对化合物Ⅰ在不同溶剂中的光谱性质研究发现,其表现出特殊的紫外吸收和荧光双重溶致变色效应,可作为荧光分子探针获得应用．对化合物Ⅰ在不同pH值的乙醇水溶液中的光谱性质进行研究,发现该化合物不仅表现出酸碱变色行为,而且具有质子调控荧光分子开关功能及化学荧光传感器特性,有望在酸碱指示剂、分子开关和化学荧光传感器等方面获得应用．     

1,8-萘酰亚胺衍生物的设计、合成及其对半胱氨酸的识别研究

巯基氨基酸水平异常与多种疾病相关,其检测仍存在一定的局限,研究检测巯基氨基酸的荧光探针具有一定的价值.以苊为原料合成了61个1,8-萘酰亚胺衍生物,研究了该类化合物的荧光性能及其作为半胱氨酸含量测定的荧光探针的可能性.紫外光谱分析表明1,8-萘酰亚胺衍生物上N-取代基对最大吸收波长无明显影响;荧光光谱(FL)的性能测试显示硝基萘酰亚胺衍生物N-甲基-4-硝基-1,8-萘二甲酰亚胺(4a)～4-硝基-N-间氟苯基-1,8-萘二甲酰亚胺(4s)无荧光,氨基萘酰亚胺衍生物N-甲基-4-氨基-1,8-萘二甲酰亚胺(5a)～4-氨基-N-间氟苯基-1,8-萘二甲酰亚胺(5s)有强烈黄色荧光,而马来酰亚胺萘酰亚胺衍生物N-甲基-4-(1H-吡咯-2,5-二酮-1-基)-1,8-萘二甲酰亚胺(6a)～4-(1H-吡咯-2,5-二酮-1-基)-N-(间氟苯基)-1,8-萘二甲酰亚胺(6s)有微弱蓝色荧光,其中7个马来酰亚胺萘酰亚胺衍生物探针对半胱氨酸(Cys)溶液有荧光点亮效应.对7个探针加入21种其它氨基酸作为干扰项的测试显示探针对半胱氨酸检测有良好的选择性.研究了不同pH值下荧光强度,检测探针与半...     

N-羟基琥珀酰亚胺-3-吲哚乙酸酯柱前衍生高效液相色谱分离及荧光测定肽及其水解物

本文首次报道了一种新的羧酸活性酯试剂,N-羟基琥珀酰亚胺-3-吲哚乙酸酯作为柱前荧光衍生试剂,流动相为10mmol/L柠檬酸-Na₂HPO₄－pH 3.6的甲醇/水(20/80,V/V)溶液,C₁₈柱,于λ_cx/λ_cm＝278nm/355nm处进行荧光检测,高效液相色谱分离测定了谷胱甘肽、二甘肽、谷氨酸、胱氨酸、甘氨酸.当S/N＝3时,检出限为0.2至2.5Pmol.     

基于1,8-萘酰亚胺的半胱氨酸荧光探针的合成及在生物成像方面的应用

设计合成了一种用于检测半胱氨酸的新型荧光探针乙二醛(N-羟乙基-1,8-二甲酰亚胺-4-萘基)单腙(NAD),该荧光探针对半胱氨酸表现出较高的灵敏度和选择性.当半胱氨酸加入NAD溶液中,会形成分子内氢键,抑制C■N的异构化,导致荧光增强.此外,探针NAD可应用于细胞内半胱氨酸的检测,表明该类型探针在生物检测应用方面具有较大的潜力.     

肝靶向荧光探针用于HepG2细胞中ONOO-的特异性检测

过氧亚硝酸根(ONOO^-)作为重要的生物活性分子,在细胞信号转导和稳态调节等过程中发挥着重要的作用。实现生物体ONOO^-的精准靶向检测,对于深入探索其生理病理机制至关重要。本文以1,8-萘二甲酰亚胺作为荧光发色团、熊去氧胆酸作为肝靶向单元,制备荧光探针N-丙基-4-(4-3α,7β-二羟基-5β-胆甾烷-24-酰肼基)-1,8-萘二甲酰胺(NA),用于人肝癌细胞(HepG2)中ONOO^-的特异性检测。该探针与ONOO^-响应后,其绿色荧光显著增强,且荧光强度与ONOO^-浓度在0～14.0μmol/L范围内呈现较好的线性关系,检测限为0.27μmol/L。该探针具有选择性强、受pH环境影响小和生物相容性好等优点。细胞荧光成像结果表明,该探针对肝癌细胞HepG2具有较好的靶向性,可以对HepG2细胞中外源性和内源性ONOO^-浓度进行特异性检测。     

N-(1-萘基)-琥珀酰亚胺光谱性质与构象的计算机模拟

首次采用Materialsstudio软件中不同的交换-相关势能函数对N-(1-萘基)-琥珀酰亚胺进行密度泛函理论计算,通过与文献报道的B3LYP/6-311G**常规计算方法进行比较,以及MP2/6-311G**方法进行单点能计算,确认所采用方法计算N-(1-萘基)-琥珀酰亚胺分子最低能量构象更接近整个势能面的全局最小点;振动频率理论分析结果与N-(1-萘基)-琥珀酰亚胺化合物羰基振动双重分裂的红外光谱特征相吻合,表明红外光谱可以作为琥珀酰亚胺类化合物的重要表征方法;根据对N-(1-萘基)-琥珀酰亚胺、萘和萘胺的轨道分布和电荷密度进行理论分析,解释了N-(1-萘基)-琥珀酰亚胺化合物溶液的紫外和荧光的光谱特征,并进而可推断N-(1-萘基)-琥珀酰亚胺分子在溶液中的构象和理论计算得到的真空中最低能量构象相同,其二面角为94.995°。     

萘酰亚胺类荧光分子探针的研究进展

荧光分子探针作为一种有效的金属离子检测手段,不仅使用方便,而且具有高灵敏度,高选择性等突出的优点.作者综述了萘酰亚胺类荧光分子探针的最新研究进展;指出萘酰亚胺化合物具有独特的荧光化学性质(如荧光量子产率高、荧光发射波长适中、斯托克斯位移大、光稳定性好、结构易于修饰等),因此被广泛应用于荧光探针研究领域,并且在合成、离子识别、检测及细胞成像等方面不断取得新的应用.     

基于萘酰亚胺的次氯酸荧光探针的合成及细胞成像性能研究

以萘酰亚胺结构为荧光发色团,设计开发了一种含C=C双键的、具有分子内电荷转移(ICT)效应的新型水溶性优化的次氯酸荧光探针3-(2-氰基丙烯酸乙酯基)-4-羟基-N-正丙基-1,8-萘酰亚胺(NAEC).添加次氯酸后,探针分子NAEC中的C=C双键被氧化,生成醛基,探针NAEC原有的ICT效应被破坏,产生荧光信号.经核磁、质谱、荧光发射光谱和UV-Vis吸收光谱对其结构和检测性能进行了研究.结果表明,在pH=7.4的N,N-二甲基甲酰胺(DMF)/磷酸缓冲盐溶液(PBS)(V∶V=1∶19)缓冲体系中,探针NAEC可在10s内完成对次氯酸的检测,荧光分析检测限为2.4nmol/L,斯托克斯位移为100nm;探针NAEC显示出较强的抗干扰性,能在其他活性氧、小分子生物硫醇及常见阴离子等22种干扰物存在下完成次氯酸的专一检测.同时,该探针分子的膜透性与生物相容性良好,具备较好的活体内源性ClO-荧光成像能力,在生物检测及环境监控等领域具有良好的应用前景.     

N—羟基琥珀酰亚胺—3—吲哚乙酸酯柱前衍生高效液相色谱分离…

本文首次报道了一种新的羧酸活性酯试剂，Ｎ－羟基琥珀酰亚胺－３－吲哚乙酸酯作为柱前荧光衍生试剂，流动相为１０ｍｍｏｌ／Ｌ柠檬酸－ＮａＨＰＯ４－ｐＨ３．６的甲醇／水溶液，Ｃ１８柱，于λｅｘ／λｅｍ＝２７８ｎｍ／３５５ｎｍ处进行荧光检测高效液相色谱分离测定了谷胱甘肽，二甘肽，谷氨酸，胱氨酸，甘氨酸，当Ｓ／Ｎ＝３时，检出限为０．２至２．５ｐｍｏｌ。     

9,10-二氢蒽-9,10-桥-α,β-琥珀酰亚胺的N-曼尼希碱的制备

9,10-二氢蒽-9,10-桥-α,β-琥珀酰亚胺在碱性条件下,易与甲醛缩合成N-羟甲基化合物,此N-羟甲基-9,10-二氢蒽-9,10-桥-α,β-琥珀酰亚胺与各种胺反应制得一系列新的化合物——18种9,10-二氢蒽-9,10-桥-α,β-琥珀酰亚胺的N-曼尼希碱。     

手术导航用荧光探针

荧光成像技术因具有操作简便、分辨率高、安全性好且可实时成像等优势,在术中导航中具有广阔的应用前景。虽然目前还没有靶向荧光探针在临床上得到批准,但已经有相当一部分荧光探针进入了临床试验阶段。最早进入临床试验的是一些偶联肿瘤靶向配体的荧光染料,例如近红外菁染料(IRDye800CW)标记的肿瘤特异抗体,叶酸标记的异硫氰酸荧光素(EC17)等。近来,结构更复杂的荧光探针如酶反应激活型探针和PET/荧光双模态探针也逐步进入临床试验。本文依据近年来手术导航用荧光探针的最新研究进展,分别就受体介导的靶向荧光探针、可激活型靶向荧光探针、近红外二区(NIR-Ⅱ)荧光探针、多模态荧光探针和诊疗一体化探针进行了分类讨论,重点对正在进行临床研究及具有临床转化前景的荧光探针的分子设计原理进行了分析与总结,并对手术导航用荧光探针未来的发展进行了展望。     

近红外荧光探针及其在生物分析中的应用进展

本文评述了自1999年以来近红外荧光探针和标记试剂及其在生物分析中的应用进展。包括:菁染料、噻嗪和噁嗪染料、含四吡咯基团染料(酞菁和卟啉)、罗丹明类、BODIPY、稀土离子配合物和量子点等。描述了它们在荧光测定和毛细管分离荧光检测以及免疫荧光分析方面的应用。引用文献75篇。     

The LB Films of Dansyl Chloride Labeled Octadecylamine and Its Fluorescence Lifetime

IntroductionFluorescent probe labeling 1, 2, microchip and LB (Langmuir-Blodgett) films of DNA and proteins3 are important in molecular electronic and biotechnological applications such as information processing and molecular recognition. As an imitated and simplified model of above complex cases, here we prepare the LB films of dansyl chloride (5-dimethylaminonaphthalene-1-sulfonyl chloride, denoted as DNS) labeled octadecyl amine (AM). A molecule based naphthalene sulfonate is well kno…     

生物硫醇荧光探针的研究进展

生物硫醇(包含半胱氨酸、高半胱氨酸和谷胱甘肽)在生命活动中扮演了重要的角色,其浓度的异常变化与某些疾病息息相关,因此对硫醇的检测具有重要意义.荧光探针因具有灵敏度高、时空分辨率好、无损伤、可视化等优势,在生物硫醇的检测方面得到了高度重视.利用硫醇在分子结构上的共同点(含巯基的氨基酸)和差异(分子大小、亲核性、空间位阻、细胞内含量),可通过迈克尔加成、亲核芳基取代、加成环化等反应实现对硫醇的选择性检测.综述了近3年来硫醇荧光探针领域的研究进展.首先介绍了对硫醇有选择性识别的荧光探针,随后分类讨论了对半胱氨酸、高半胱氨酸和谷胱甘肽各具有特异性检测的荧光探针,并重点介绍了分子设计、识别机理、荧光性质和成像应用,初步探讨了部分探针在监测细胞生命活动中的作用,同时还对本领域的发展提出了展望.     

Rapid and sensitive determination of phosphorus-containing amino acid herbicides in soil samples by capillary zone electrophoresis with diode laser-induced fluorescence detection

A straightforward and sensitive method has been developed for the analysis of phosphorus-containing amino acid herbicides (glufosinate and aminomethylphosphonic acid, the major metabolite of glyphosate) in soil samples. For this purpose, the analytical features of two indocyanine fluorescent dyes, sulfoindocyanine succinimidyl ester (Cy5) and 1-ethyl-1-[5-(N-succinimidyl-oxycarbonyl)pentyl]-3,3,3,3-tetramethyl-indodicarbocyanine chloride, as labeling reagents for the determination of these herbicides by CZE with diode LIF detection were investigated. Practical aspects related to the labeling chemistry and CZE separation showed that the two probes behave similarly, Cy5 being the best choice for the determination of these herbicides on account of its higher sensitivity. The optimum procedure includes a derivatization step of the pesticides at 25 degrees C for 30 min and direct injection to CZE analysis, which is conducted within about 14 min using ACN in the running buffer. The lowest detectable analyte concentration ranged from 0.025 to 0.18 microg/L with a precision of 3.6-5.4%. These results indicate that indocyanine fluorescence dyes are useful as rapid and sensitive labels for the determination of these herbicides when compared with typical fluorescein dyes such as FITC and 5-(4,6-dichloro-s-triazin-2-ylamino) fluorescein, because they provide faster labeling reactions even at room temperature and the excess of reagent practically does not interfere the determination. Finally, the Cy5 method was successfully applied to soil samples without a preliminary clean-up procedure, and the herbicides were measured without any interference from coexisting substances. The recoveries of these compounds in these samples at fortification levels of 100-500 ng/g were 90-93%.     

Intracellular protein labeling with prodrug-like probes using a mutant β-lactamase tag

Intracellular protein labeling with small molecular probes that do not require a washing step for the removal of excess probe is greatly desired for real-time investigation of protein dynamics in living cells. Successful labeling of proteins on the cell membrane has been performed using mutant β-lactamase tag (BL-tag) technology. In the present study, intracellular protein labeling with novel cell membrane permeable probes based on β-lactam prodrugs is described. The prodrug-based probes quickly permeated the plasma membranes of living mammalian cells, and efficiently labeled intracellular proteins at low probe concentrations. Because these cell-permeable probes were activated only inside cells, simultaneous discriminative labeling of intracellular and cell surface BL-tag fusion proteins was attained by using cell-permeable and impermeable probes. Thus, this technology enables adequate discrimination of the location of proteins labeled with the same protein tag, in conjunction with different color probes, by dual-color fluorescence. Moreover, the combination of BL-tag technology and the prodrug-based probes enabled the labeling of target proteins without requiring a washing step, owing to the efficient entry of probes into cells and the fast covalent labeling achieved with BL-tag technology after bioactivation. This prodrug-based probe design strategy for BL-tags provides a simple experimental procedure with application to cellular studies with the additional advantage of reduced stress to living cells.     

Indole-Based Long-Wavelength Fluorescent Probes for Bioimaging of S-Nitrosylation in Mitochondria

S-Nitrosylation has been found to play an important role in regulating mitochondrial function. However, probes for detection of protein S-nitrosylation in mitochondria remain unexplored. Herein, a novel 4-(pyridin-4-yl)vinyl-substituted indole was designed, exhibiting a long-wavelength emission and a high fluorescent quantum yield. Functionalization of the 7-position of the indole ring with an arylphosphine ester resulted with probes with efficient mitochondria-targeting ability. Furthermore, the indole-arylphosphine displayed a significant fluorescence enhancement upon exposure to S-nitrosoglutathione (GSNO) at low micromolar concentrations in A431 cells. Taken together, this study provides a new indole-based fluorescent probe with a unique long-wavelength emission for direct detection of S-nitrosylation in mitochondria, which may represent a powerful tool for understanding the critical roles of S-nitrosylation within mitochondria of living organisms.     

用于一氧化氮检测的小分子荧光探针研究进展

生物小分子NO以其重要的生理学和病理学作用受到科学家们的广泛关注。高选择性、高灵敏度、低毒性NO分子荧光探针的设计和开发,在环境检测、食品安全及人体内NO检测等领域具有重要意义。本文以小分子荧光探针对NO的识别机制为主线,从唑环的形成、螺内酰胺开环、还原脱氨、二氢吡啶的芳构化、NO与金属络合物的反应、与非金属Se的反应和亚硝胺的形成出发,综述了近年来NO小分子荧光探针的研究进展。对NO探针设计及其识别性能研究方面的工作进行了总结,并讨论了NO荧光探针今后的设计思路和重点研究方向。     

Donor and Ring-Fusing Engineering for Far-Red to Near-Infrared Triphenylpyrylium Fluorophores with Enhanced Fluorescence Performance for Sensing and Imaging

Fluorescent probes have become an indispensable tool in the detection and imaging of biological and disease-related analytes due to their sensitivity and technical simplicity. In particular, fluorescent probes with far-red to near-infrared (FR-NIR) emissions are very attractive for biomedical applications. However, many available FR-NIR fluorophores suffer from small Stokes shifts and sometimes low quantum yields, resulting in self-quenching and low contrast. In this work, we describe the rational design and engineering of FR-NIR 2,4,6-triphenylpyrylium-based fluorophores ( TPP-Fluors ) with the help of theoretical calculations. Our strategy is based on the appending of electron-donating substituents and fusing groups onto 2,4,6-triphenylpyrylium. In contrast to the parent TPP with short emission wavelength, weak quantum yields, and low chemical stability, the obtained novel TPP-Fluors display some favorable properties, such as long-wavelength emission, large Stokes shifts, moderate to high quantum yields, and chemical stability. TPP-Fluors demonstrate their biological value as mitochondria-specific labeling reagents due to their inherently positive nature. In addition, TPP-Fluors can also be applied to develop ratiometric fluorescent probes, as the electron-donating ability of the 2,6-phenyl substituents is closely correlated with their emission wavelength. A proof-of-concept ratiometric probe has been developed by derivatizing the amino groups of TPP-Fluor for the detection and imaging of nitroreductase in vitro and in hypoxic cells.     

用于检测多硫化氢和亚硝酰氢的小分子荧光探针

多硫化氢（H₂S_n）和亚硝酰氢（HNO）在一系列生理病理过程中起着重要的作用,包括调节细胞内氧化还原信号传递过程、增强心肌的收缩能力、抑制血小板聚集等。H₂S_n可以通过硫化氢（H₂S）与活性氧物种反应得到。一氧化氮（NO）和HNO可以在超氧化物歧化酶（SOD）作用下相互转化,H₂S和NO反应可以生成H₂S_n和HNO,调控酶的活性以及蛋白与蛋白之间的相互作用,从而影响蛋白质的生理功能。因此,实时检测生物体内H₂S_n和HNO的浓度具有十分重要的生物医学意义。在各种生物检测技术中,荧光探针具有选择性好,灵敏度高,可以实时原位检测,对样品损伤小等优点,受到了广泛关注。本文将按照探针响应基团的反应类型,将近几年用于定性定量检测H₂S_n和HNO荧光探针进行分类和总结,重点概述探针的设计理念、响应机制和生物应用,并对探针的应用前景进行了展望。同时,本文也关注了硫化氢和其他硫烷硫类物种荧光检测的近期进展。