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。     

基于氧杂蒽结构可控官能化的荧光探针研究新进展

荧光分子探针技术在表达分子间识别行为及复杂生命和环境体系的内状态信息方面具有非常优异的性能,氧杂蒽及其衍生物螺连隐色体结构变化伴随的分子荧光变换模型,广泛且深入的应用于构建新型功能光敏探针分子.近年来此类探针的合成设计及功能化调控研究异常活跃,新的突破不断涌现.综述了新近基于氧杂蒽及其衍生物的荧光探针在金属阳离子、pH、阴离子识别检测方面的研究进展,并简要阐释了该类探针分子的构筑,识别检测机理以及探针在生物成像和环境监测等方面的应用.     

检测活性氮/活性氧的分子荧光探针

活性氮和活性氧是具有强生物活性的化学物质.在人体细胞中,由于酶促或非酶促过程均可生成过氧化物,该物种的异常水平会引起氧化损伤与衰老和各种疾病,如心血管疾病、神经性疾病、阿尔茨海默病、帕金森病甚至癌症.因此,发展选择性识别和高灵敏度的分子荧光探针,实现活性氮或活性氧的有效检测具有重要意义.分子荧光探针检测法与成像技术具有灵敏度高、选择性强、损伤性小和细胞相容性好等优点,并在阐述活性氮和活性氧的病理生理过程中起到重要作用,在生物和医学等领域应用广泛.然而,由于活性氮和活性氧自身的特殊性而存在许多难题,例如反应活性高、存在周期短等一直困扰研究人员.着重综述了近年来发展的分子荧光探针用于活性氮和活性氧的检测及细胞成像工作的研究进展,提出进一步构建新型分子荧光探针用于活性氮和活性氧检测面临的挑战、未来发展方向及展望.     

活性羰基化合物荧光探针的研究进展

活性羰基化合物一直以来被人们称为致癌物和人类毒物,当其浓度升高时,会导致多种疾病,因此,设计开发用于选择性识别和高灵敏检测生物体内的活性羰基化合物的技术具有十分重要的意义.近年来,荧光探针具有操作简单、灵敏度高、选择性好,响应时间短以及能实现实时检测等优势,在活性羰基化合物及其他活性物种如活性氧、活性氮、次氯酸以及硫醇等物质的检测方面获得了快速发展.鉴于活性羰基化合物荧光探针综述方面的报道很少,从探针分子与待测物之间发生的反应类别进行归纳和总结,概括了甲醛、甲基乙二醛、丙二醛以及丙烯醛等活性羰基化合物的荧光探针,并从设计理念、识别机理以及应用等方面进行了描述,还对活性羰基化合物荧光探针的设计和应用前景提出了展望.     

基于罗丹明染料的金属阳离子荧光探针

罗丹明是以氧杂蒽为母体的碱性呫吨染料,具有优良的光学性质,如延伸到可见光区的吸收及荧光、高的荧光量子产率及大的摩尔吸光系数等,使其成为制备荧光探针的理想生色团。本文综述了近年来用于检测金属阳离子的罗丹明类荧光探针的研究进展,特别是对基于螺酰胺环“关-开”机理、荧光共振能量转移(FRET)机理和光诱导电子转移(PET)机理的罗丹明类铜离子、汞离子、铁离子荧光探针进行了系统的阐述,包括结构特征、检测水平和应用范围。最后提出了这类荧光探针面临的问题与发展趋势。     

苯并噻唑基荧光探针的设计、合成与应用研究进展

苯并噻唑基团具有特征荧光,且结构中含有N和S杂原子,因而在荧光探针结构中常被视为荧光基团与识别基团,承担荧光信号输出与提供结合位点的重要作用.利用苯并噻唑基团的特点来设计合成性能更佳的荧光探针已逐渐成为荧光探针研究领域中瞩目的焦点.对近几年来报道的苯并噻唑基荧光探针按不同的检测对象分为金属阳离子、阴离子、含硫化合物及其它物种等四大类,综述了其设计、合成、作用机理及其相关检测应用,并展望了其未来的发展趋势.     

荧光/化学发光探针成像检测超氧阴离子自由基的研究进展

超氧阴离子自由基(O·-2)是细胞内氧气单电子还原后最先产生的一类含氧的高活性物种(活性氧,ROS),与生命过程息息相关.正常稳态浓度的O·-2起重要的信号调控作用,包括细胞的增殖、分化、自噬等.但O·-2浓度的异常,又与癌症、神经退行性疾病、糖尿病等多种疾病的发生发展密切相关.因此,监测O·-2浓度的变化对揭示相关疾病的机理具有至关重要作用.由于荧光成像检测方法具有诸多优势,发展高灵敏、高选择性检测O·-2的荧光探针成为揭示相关疾病发生发展分子机制的关键切入点.近年来,随着荧光显微技术的发展,研究者开发了多种荧光/化学发光探针,实现了对细胞及活体内O·-2水平的可视化监测.本文综述了近五年用于检测O·-2的分子探针、纳米探针、蛋白探针以及化学发光探针的研究进展,并对其发展前景进行了展望.     

用于检测生物体系中线粒体活性氧的荧光探针（英文）

线粒体不仅是细胞的能量单元,还是重要的活性氧产生场所。线粒体内的活性氧与正常的生理功能和人类疾病具有紧密的联系,包括细胞信号传导,损伤核酸蛋白质以及诱导氧化应激。然而,线粒体活性氧和细胞病态之间的复杂联系还研究得不够透彻。有效检测线粒体内活性氧的手段有助于研究线粒体内活性氧在各种人类疾病中所起的作用。近年来,发展了许多具有高灵敏度和选择性的荧光探针用于检测线粒体内活性氧。基于这一点,我们综述了用于选择性检测线粒体内活性氧的小分子荧光探针的研究进展,并详细讨论了荧光探针的设计、合成、特点及其应用。     

肿瘤缺氧荧光探针的研究进展

缺氧是临床多种疾病共有的病理过程,研究缺氧的发生和发展规律,对恶性肿瘤及相关疾病的诊断具有重要的科学意义和应用价值.缺氧特异性荧光探针是指能对缺氧敏感物质进行选择性荧光检测进而评价相关体系缺氧状况的一类分析试剂,由于其检测的高灵敏性和高时空分辨能力,已成为研究热点之一.本文基于荧光探针检测肿瘤缺氧的不同反应机理,着重讨论了缺氧荧光探针的设计方法、检测机理及其生物应用,并对该类探针的发展趋势和应用前景进行了展望.     

检测活性氮物种的荧光探针

活性氮是一类具有高生物化学活性的含氮原子的化学物种。这类活性物种具有特殊的生理功能,并在生命体的生理和病理过程中起着至关重要的作用。因此,设计开发用于选择性识别和高灵敏检测生物体内的活性氮物种的技术具有十分重要的意义。荧光探针作为一种具有高灵敏度、高选择性、对生物样品损伤小的实时原位的可视化检测技术,为深入阐明活性氮物种在生理和病理过程中所起的作用提供了一个便利有效的检测手段,并已在检测活性氮物种领域中得到了广泛应用。活性氮物种荧光探针可以进一步阐述活性氮物种特殊的生理功能,提高人们对该类物种在细胞信号转导方面的认知。本文根据活性氮物种的种类对荧光探针进行了分类,详细介绍了近四年来用于检测活性氮物种的荧光探针的研究进展,主要探讨了探针的设计方法、荧光响应机制及其生物应用,并对探针的设计合成和应用前景进行了展望。     

用于检测生物体系中线粒体活性氧的荧光探针

In addition to being the energy powerhouse of the cell, mitochondria are an important source of reactive oxygen species (ROS) during the process of molecular oxygen metabolism. Mitochondrial ROS are closely associated with normal physiological functions as well as human diseases, and participate in cell signaling, nucleic acid and protein damage, and oxidative stress induction. However, the complicated interplay between mitochondrial ROS and the cellular pathological state has not been fully elucidated. It is expected that research on the mitochondrial ROS undertaking in the molecular pathogenesis of human diseases would benefit from development of efficient tools for the detection of these ROS. In recent years, an increasing number of fluorescent probes for mitochondrial ROS with high sensitivity and selectivity have been developed. Here, we present a review of the recent advances in small molecular fluorescent probes for selective detection of ROS inside the mitochondria. In this review, the design, synthesis, characteristics, and applications of the published fluorescent probes for mitochondrial ROS are discussed in detail.     

Recent advances in fluorescent probes for the detection of reactive oxygen species

Reactive oxygen species (ROS) have captured the interest of many researchers in the chemical, biological, and medical fields since they are thought to be associated with various pathological conditions. Fluorescent probes for the detection of ROS are promising tools with which to enhance our understanding of the physiological roles of ROS, because they provide spatial and temporal information about target biomolecules in in vivo cellular systems. ROS probes, designed to detect specific ROS with a high selectivity, would be desirable, since it is now becoming clear that each ROS has its own unique physiological activity. However, dihydro-compounds such as 2′,7′-dichlorodihydrofluorescein (DCFH), which have traditionally been used for detecting ROS, tend to react with a wide variety of ROS and are not completely photostable. Some attractive fluorescent probes that exhibit a high degree of selectivity toward specific ROS have recently been reported, and these selective probes are expected to have great potential for elucidating unknown physiological mechanisms associated with their target ROS. This review focuses on the design, detection mechanism, and performance of fluorescent probes for the detection of singlet oxygen (¹O₂), hydrogen peroxide (H₂O₂), hydroxyl radicals (^.OH), or superoxide anion (O₂ ^−.), a field in which remarkable progress has been achieved in the last few years.     

A Novel Phenoxazine-based Fluorescent Probe for the Detection of HOCl in Living Cells

Hypochlorous acid (HOCl), one of the reactive oxygen species (ROS), is a key microbicidal agent which is used for natural defense. However, it is also linked to varieties of human diseases owing to the overproduction of HOCl. Much effort has been made to exploit selective fluorescent sensors for the detection of HOCl, but most of them have some disadvantages such as short excitation wavelength, low selectivity, and slow response and so on. These restrict the biological application of the probes. In this work, BR-O was designed and synthesized on the base of phenoxazine for the detection of HOCl. BR-O exhibited a violent fluorescence enhancement in the presence of HOCl, showing excellent selectivity and high sensitivity. More importantly, the probe BR-O was capable of detecting exogenous and endogenous HOCl in living cells.     

线粒体靶向的近红外HClO/ClO-荧光探针的研究进展

HClO/ClO-作为细胞质中一种重要的活性氧(ROS),源自线粒体,参与各种生理和病理过程,因此快速有效检测HClO/ClO-具有重要的生物学及生理学意义.荧光分析法因其灵敏度高、响应时间快、选择性高、成本低和操作简便等优点而备受关注.更重要的是,使用荧光探针可以在体外和体内可视化检测.近年来,为了研究HClO/Cl...     

Fluorescent probes for visualizing ROS-associated proteins in disease

Abnormal expression of proteins, including catalytic and expression dysfunction, is directly related to the development of various diseases in living organisms. Reactive oxygen species (ROS) could regulate protein expression by redox modification or cellular signal pathway and thus influence the development of disease. Determining the expression level and activity of these ROS-associated proteins is of considerable importance in early-stage disease diagnosis and the identification of new drug targets. Fluorescence imaging technology has emerged as a powerful tool for specific in situ imaging of target proteins by virtue of its non-invasiveness, high sensitivity and good spatiotemporal resolution. In this review, we summarize advances made in the past decade for the design of fluorescent probes that have contributed to tracking ROS-associated proteins in disease. We envision that this review will attract significant attention from a wide range of researchers in their utilization of fluorescent probes for in situ investigation of pathological processes synergistically regulated by both ROS and proteins.

Abnormal proteins, influenced by reactive oxygen species (ROS), are directly related to the development of various diseases.     

Spectroscopic probes with changeable π-conjugated systems

Spectroscopic probes have been extensively investigated and used widely in many fields because of their powerful ability to improve analytical sensitivity, and to offer greater temporal and spatial resolution (in some cases a molecule event may be visualized by the naked eye). So far, different photophysical mechanisms, such as charge transfer, photo-induced electron transfer and fluorescent resonance energy transfer, have been employed to develop various spectroscopic probes with superior properties. However, these photophysical mechanisms depend on the energy levels of molecular orbitals, which are usually difficult to accurately determine. This would lead to the poor prediction of analytical performance of the designed probe. Instead, the change of π-conjugated systems induced by chemical reactions is often accompanied by a distinct alteration in spectroscopic signal, which is more predictable and is of high signal/background ratio. This mechanism can serve as an effective measure for developing excellent spectroscopic probes, but to our knowledge, has not been systematically summarized. In this feature article, we review the development of spectroscopic probes with changeable π-conjugated systems, which is catalogued according to the fluorochromes: fluorescein, rhodamine, spiropyran, squaraine, coumarin, cyanine, etc. Two main strategies for constructing these spectroscopic probes, including ring-closing reaction and nucleophilic addition reaction, are summarized, and the merits and limitations of the probes are discussed.     

Recent developments in the detection of singlet oxygen with molecular spectroscopic methods

Singlet oxygen is a unique reactive oxygen species, as its chemical reactivity derives from its characteristic electronically-excited state. The involvement of singlet oxygen in many important atmospheric, physical, chemical, biological, and therapeutic processes has attracted intense research interest in recent years. The detection and the quantification of singlet oxygen are very important for understanding its mechanism of action in various processes.Due to its highly reactive nature, singlet oxygen has very few direct methods of determination. Only molecular phosphorescence at 1270 nm has been utilized. Indirect methods using spectrophotometric, fluorescent or chemiluminescent probes have therefore been extensively studied.This review reflects recent developments in singlet-oxygen detection with molecular spectroscopic methods. We begin with a brief introduction of the basic properties, the production and the applications of singlet oxygen. With this background information, we review the four molecular spectroscopic methods (i.e., emission, spectrophotometry, fluorescence and chemiluminescence). We pay special attention to attractive chemical probes with high selectivity and sensitivity in quantifying singlet oxygen.     

Plant Flavonoids: Chemical Characteristics and Biological Activity

In recent years, more attention has been paid to natural sources of antioxidants. Flavonoids are natural substances synthesized in several parts of plants that exhibit a high antioxidant capacity. They are a large family, presenting several classes based on their basic structure. Flavonoids have the ability to control the accumulation of reactive oxygen species (ROS) via scavenger ROS when they are formed. Therefore, these antioxidant compounds have an important role in plant stress tolerance and a high relevance in human health, mainly due to their anti-inflammatory and antimicrobial properties. In addition, flavonoids have several applications in the food industry as preservatives, pigments, and antioxidants, as well as in other industries such as cosmetics and pharmaceuticals. However, flavonoids application for industrial purposes implies extraction processes with high purity and quality. Several methodologies have been developed aimed at increasing flavonoid extraction yield and being environmentally friendly. This review presents the most abundant natural flavonoids, their structure and chemical characteristics, extraction methods, and biological activity.     

Fluorescent Probes for Selective Recognition of Hypobromous Acid: Achievements and Future Perspectives

Reactive oxygen species (ROS) have been implicated in numerous pathological processes and their homeostasis facilitates the dynamic balance of intracellular redox states. Among ROS, hypobromous acid (HOBr) has a high similarity to hypochlorous acid (HOCl) in both chemical and physical properties, whereas it has received relatively little attention. Meanwhile, selective recognition of endogenous HOBr suffers great challenges due to the fact that the concentration of this molecule is much lower than that of HOCl. Fluorescence-based detection systems have emerged as very important tools to monitor biomolecules in living cells and organisms owing to distinct advantages, particularly the temporal and spatial sampling for in vivo imaging applications. To date, the development of HOBr-specific fluorescent probes is still proceeding quite slowly, and the research related to this area has not been systematically summarized. In this review, we are the first to review the progress made so far in fluorescent probes for selective recognition and detection of HOBr. The molecular structures, sensing mechanisms, and their successful applications of these probes as bioimaging agents are discussed here in detail. Importantly, we hope this review will call for more attention to this rising field, and that this could stimulate new future achievements.