近红外二区有机小分子荧光探针

荧光成像凭借灵敏度高、特异性强等诸多优势在重大疾病的诊疗领域发挥着重要作用.然而传统的近红外一区（NIR-I,700~900 nm）荧光成像存在组织穿透性差等问题,限制了其临床应用.近红外二区（NIR-II,1000~1700 nm）荧光成像可以极大地减弱生物组织对光的吸收、散射和自发荧光,从而显著提升成像深度及成像效果.在众多NIR-II荧光探针中,有机小分子由于具有毒性低、代谢快等优点正成为该领域的研究热点.作者以近年来NIR-II有机小分子荧光探针的发展为主体,概括了提升探针荧光量子产率的策略,分别就可激活型、多模态成像型和诊疗一体化型NIR-II荧光探针进行分类讨论,系统介绍了近年来该领域内的研究成果,并针对NIR-II荧光探针未来的发展进行了展望.     

基于硝基苯并呋咱的荧光探针

硝基苯并呋咱(NBD)作为一种通常从4-氯-7-硝基-苯并呋咱衍生化的荧光团,在荧光分析中具有简便、高效、灵敏度高以及检测限低等显著优点,已广泛应用于化学、生物、医药和环境等诸多研究领域。基于NBD的荧光探针是检测和识别重要的无机/有机小分子化合物、酶和蛋白质的研究热点之一。本文综述了近年来NBD作为荧光团在重金属离子(Zn2+,Cu2+和Hg2+)、活性氧、DNA、细胞膜、小分子化合物(硫酚、糖类、金刚烷/胆酸、氟甲沙明/埃博霉素、双酚A、多胺、TNT和PPi)、酶和蛋白质等检测领域的新进展。在不久的将来,设计合成结构更加精巧的NBD探针分子仍将是荧光检测和生物成像领域的主要发展趋势之一。这些新颖的NBD探针分子的应用将为全面深入探索与理解复杂的生命过程提供强有力的研究工具。     

小分子荧光探针在绿色农药开发中的应用

小分子荧光探针以其灵敏度高、特异性强、稳定性好、操作便捷和成本低等特点在生命科学、医药化学和环境科学等领域得到了广泛的应用。在农药化学领域,小分子荧光探针常被用作农药残留及重金属污染的检测手段。近年来随着全球开发绿色农药战略需求的不断增强,作为靶向型药物设计和高通量筛选的重要分子工具,荧光探针在绿色农药新产品研发领域的应用不断普及和深化。本文从探针分子的化学设计、靶点识别及药物筛选的角度出发,围绕不同类型的绿色农药重要生物靶点,综述了小分子荧光探针在绿色农药开发领域的研究现状,并对其未来的发展趋势和应用前景进行了展望。     

基于硅杂蒽类染料的荧光探针及其应用

近年来,荧光成像技术为人们研究活体细胞及组织内的化学生物学过程提供了有效的研究工具,可以无损、实时、原位地以高时空分辨率实现对目标物进行生物荧光成像与分析。荧光成像技术在生物学、环境监测、临床诊断和药物发现等诸多研究领域发挥着越来越重要的作用。生物荧光成像技术的最新进展对发展新型小分子荧光染料及探针提出了更高的要求。激发和发射波长位于近红外光区（600~900 nm）的荧光染料及探针由于具有光毒性低、生物分子自发荧光干扰小、光散射低、组织穿透能力强等优点,非常适合用于生物荧光成像领域。通过将罗丹明分子中O桥原子用Si代替,得到了一类新型的探针分子--硅杂蒽类荧光探针。这类染料分子在保留了氧杂蒽荧光染料优越的光学性质的同时,光谱发生明显红移,满足了近红外荧光检测的要求,具有良好的生物相容性。本文综述了近年来基于硅杂蒽及其衍生物荧光探针的合成及在金属离子、pH值、小分子、生物酶等检测方面的研究进展,并且简要阐述了基于硅杂蒽类探针分子的识别检测机理以及其在生物成像等方面的应用。     

小分子生物硫醇荧光探针研究进展

半胱氨酸(Cys)、同型半胱氨酸(Hcy)和还原型谷胱甘肽(GSH)等小分子生物硫醇在人的生理活动中起着重要作用.近年来,生物和环境样品中小分子生物硫醇的检测引起科学家们极大的兴趣,生物硫醇荧光探针和比色传感器得到快速发展.根据探针与生物硫醇的反应机理,包括利用小分子生物硫醇中巯基与探针反应、巯基和氨基协同与探针反应,综述两年来生物硫醇小分子荧光探针的设计、合成与应用进展.     

核酸探针及其在生物分析中的应用

核酸探针由于具有结构可变,合成简单和易于修饰等特点,被广泛应用于酶、蛋白质、生物小分子、金属离子、核酸以及细胞等生物分析物的检测,成为生物分析领域中不可或缺的一种研究工具。基于核酸探针发展起来的核酸信号放大策略为检测低丰度的物质提供了重要平台,提高了核酸探针检测的灵敏度,对于生物医学研究,分子诊断和药物基因组学至关重要。对核酸探针的类型、核酸信号放大方法以及核酸探针在生物分析领域的应用进行了介绍,对核酸探针的发展进行了总结与展望。     

席夫碱型有机小分子荧光探针的制备与表征——推荐一个综合化学实验

介绍一个综合型创新实验——有机小分子荧光探针的制备与表征。内容包括有机配体的合成及表征、荧光光谱的测试、金属离子的检测等。通过本实验的实践,既可以让学生更好地掌握无机、有机和分析化学相关专业知识,提升实验操作技能,又能让学生了解有机小分子荧光探针这一科研前沿领域,激发学生对科学研究的兴趣,培养科研能力。建议将本实验纳入本科高年级综合化学实验课。     

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。     

线粒体荧光探针研究新进展

近年来,许多基于有机小分子既能定位于线粒体又能够检测线粒体内各类活性小分子的双功能线粒体荧光探针被相继报道,成功地实现了线粒体内多种活性物种的检测和可视化成像,这些物种包括活性氧、还原性物种、金属离子、质子、阴离子等.为进一步对线粒体内特定活性小分子进行组织及活体内无创检测与成像,性能优良的双光子及近红外探针的设计合成备受瞩目.围绕近年来出现的线粒体荧光探针依据检测对象进行总结与评述,展望了线粒体荧光探针在癌症等病症的前期诊断和后期治疗方面的发展趋势.     

内质网荧光探针研究进展

内质网作为亚细胞器在哺乳细胞生命活动中发挥重要作用.将内质网可视化,进一步检测其活性物质、微环境及生理过程,对于疾病的诊治具有重要的指导价值.近年来,内质网靶向荧光探针的设计与合成受到了越来越多的关注.当前已报道的内质网靶向荧光探针涵盖了单纯内质网成像、金属离子、小分子物质、大分子物质、微环境等.总结并介绍了近期报道的内质网靶向荧光探针的设计与合成工作,分析了内质网荧光探针在研究细胞生理过程中的应用,并展望了内质网靶向荧光探针的发展趋势.     

罗丹明荧光探针在生化分析中的应用

罗丹明荧光探针作为生物学研究中使用最广泛的荧光探针之一,广泛地应用于活体细胞内小分子的检验、生物大分子的分析以及复杂生物体系的研究等方面.罗丹明荧光探针在生化分析中的应用研究融合了分子生物学、分析化学、有机化学等多个学科.是当今化学研究的热点领域.本文综述了近年罗丹明荧光探针在生化分析中的应用进展,并对其未来的发展趋势进行了展望.     

Towards the optimal screening collection: a synthesis strategy

The development of effective small-molecule probes and drugs entails at least three stages: 1) a discovery phase, often requiring the synthesis and screening of candidate compounds, 2) an optimization phase, requiring the synthesis and analysis of structural variants, 3) and a manufacturing phase, requiring the efficient, large-scale synthesis of the optimized probe or drug. Specialized project groups tend to undertake the individual activities without prior coordination; for example, contracted (outsourced) chemists may perform the first activity while in-house medicinal and process chemists perform the second and third development stages, respectively. The coordinated planning of these activities in advance of the first small-molecule screen tends not to be undertaken, and each project group can encounter a bottleneck that could, in principle, have been avoided with advance planning. Therefore, a challenge for synthetic chemistry is to develop a new kind of chemistry that yields a screening collection comprising small molecules that increase the probability of success in all three phases. Although this transformative chemistry remains elusive, progress is being made. Herein, we review a newly emerging strategy in diversity-oriented small-molecule synthesis that may have the potential to achieve these challenging goals.     

Ketenes in polymer-assisted synthesis

Since its inception, ketene chemistry has developed into a unique and well-established source of useful transformations for conventional synthetic organic chemistry. It is, therefore, not surprising that soon after their movement from the realm of peptide and peptoid libraries to that of small molecules, combinatorial chemists have sought the benefits of ketene chemistry to satisfy their own synthetic needs. The ability of these versatile molecules to undergo reactions with nucleophiles, and to participate in cycloadditions and cyclocondensations, has been utilized for the preparation of diverse heterocyclic compounds, and has added to the advantages of polymer-assisted synthesis for rapid purification. Different types of ketenes and different methods for their generation have been involved, which illustrates the potential diversity of the chemistry. There is now a better grasp of the effect of the fragility of these sometimes transient molecules on the reactions involving solid supports, and this augurs well for the application of some of the more recent developments in ketene chemistry to the generation of small-molecule libraries.     

Synthetic ligands discovered by in vitro selection

The recognition and catalytic properties of biopolymers derive from an elegant evolutionary mechanism, whereby the genetic material encoding molecules with superior functional attributes survives a selective pressure and is propagated to subsequent generations. This process is routinely mimicked in vitro to generate nucleic-acid or peptide ligands and catalysts. Recent advances in DNA-programmed organic synthesis have raised the possibility that evolutionary strategies could also be used for small-molecule discovery, but the idea remains unproven. Here, using DNA-programmed combinatorial chemistry, a collection of 100 million distinct compounds is synthesized and subjected to selection for binding to the N-terminal SH3 domain of the proto-oncogene Crk. Over six generations, the molecular population converges to a small number of novel SH3 domain ligands. Remarkably, the hits bind with affinities similar to those of peptide SH3 ligands isolated from phage libraries of comparable complexity. The evolutionary approach has the potential to drastically simplify and accelerate small-molecule discovery.     

分子识别中质子客体的荧光传感和开关研究进展

分子识别是超分子化学的核心概念 ,而荧光开关PET体系又是分子识别中的重要组成部分 ,是超分子化学和光物理学科相结合的成就 ,作为一种全新的客体识别分析手段由于其独特的应用价值 ,近十年以惊人的速度在向前发展。本文综合 1 998年以前的文献对质子客体的荧光开关PET体系进行了全面介绍。     

Microfluidics in Inorganic Chemistry

The application of microfluidics in chemistry has gained significant importance in the recent years. Miniaturized chemistry platforms provide controlled fluid transport, rapid chemical reactions, and cost‐saving advantages over conventional reactors. The advantages of microfluidics have been clearly established in the field of analytical and bioanalytical sciences and in the field of organic synthesis. It is less true in the field of inorganic chemistry and materials science; however in inorganic chemistry it has mostly been used for the separation and selective extraction of metal ions. Microfluidics has been used in materials science mainly for the improvement of nanoparticle synthesis, namely metal, metal oxide, and semiconductor nanoparticles. Microfluidic devices can also be used for the formulation of more advanced and sophisticated inorganic materials or hybrids.     

Combinatorial library synthesis of antioxidant compounds

Since oxidative cellular damage contributes to the development of cancers, heart disease and ageing, the synthesis of antioxidative agents which are able to either prevent or mitigate oxidative stress to cells is an important area of investigation. Combinatorial chemistry has had a profound impact on the discovery and optimisation of potential lead compounds, especially in the medicinal field. This review details recent examples of combinatorial chemistry dealing with the synthesis of novel antioxidants with an emphasis on solid phase compound synthesis and parallel library synthesis.     

Small-molecule analysis by surface-assisted laser desorption/ionization mass spectrometry

In order to meet the challenges facing modern chemistry, biology, and medicine, methods are required capable of performing rapid and reliable analysis of both individual compounds and complex mixtures at the molecular level. Matrix-assisted laser de-sorption/ionization mass spectrometry meets these requirements; however, some limitations complicate its application for the analysis of small molecules. Recently, small-molecule analysis has greatly progressed owing to development of surface-assisted laser desorption/ionization mass spectrometry involving approaches which combine the unique properties of nanostructured surface chemistry and morphology. This review examines such approaches and their specific application in small-molecule mass analysis.     

咪唑环番仿生新体系研究进展

仿生化学是当今化学的挑战性领域之一。咪唑环番是构筑仿生体系的优良基体,但迄今研究工作极少。本文简要评述了咪唑的选择性反应和咪唑衍生物的选择性合成、新型咪唑环番和咪唑鎓环番的设计合成及仿生功能研究的一些新进展。