Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

Fluorescent probes for imaging and detection of plant hormones and their receptors

Exploring plant behavior at the cellular scale in a minimally invasive manner is critical to understanding plant adaptation to the environment.Phytohormones play vital regulatory roles in multiple aspects of plant growth and development and acclimation to environmental changes.Since the biosynthesis,modification,transportation,and degradation of plant hormones in plants change with time and space,their content level and distribution are highly dynamic.To monitor the production,transport,perception,and distribution of phytohormones within undamaged tissues,we require qualitative and quantitative tools endowed with remarkably high temporal and spatial resolution.Fluorescent probes are regarded as excellent tools for widespread plant imaging because of their high sensitivity and selectivity,reproducibility,real-time in situ detection,and uncomplicated mechanism elucidation.In this review,we provide a systematical overview of the progress in the sensing and imaging of phytohormone fluorescent probes and fluorescently labeled phytohormones to their receptors in plants.Moreover,forthcoming viewpoints and possible applications of these fluorescent probes within the realm of plants are also presented.We hold the conviction that the new perspective brought by this paper can promote the development of fluorescent probes,enabling them to have better detection performance in plant hormone imaging.

Hydroxylated graphene quantum dots as fluorescent probes for sensitive detection of metal ions

Highly sensitive methods are important for monitoring the concentration of metal ions in industrial wastewater.Here,we developed a new probe for the determination of metal ions by fluorescence quenching.The probe consists of hydroxylated graphene quantum dots(H-GQDs),prepared from GQDs by electrochemical method followed by surface hydroxylation.It is a non-reactive indicator with high sensitivity and detection limits of 0.01μM for Cu2+,0.005μM for Al3+,0.04μM for Fe3+,and 0.02μM for Cr3+.In addition,the low biotoxicity and excellent solubility of H-GQDs make them promising for application in wastewater metal ion detection.

Recent development of organic small-molecule and nanomaterial fluorescent probes for hydrazine

Hydrazine,an essential chemical,has been used within a wide spectrum of industries,including pesticides,pharmaceuticals and even satellite-launching systems.However,the excessive consumption of hydrazine raised the risk of environmental pollution accidents and occurrence of diseases because of its high toxicity and volatility.This led to the discovery of diverse fluorescent probes for the monitoring of the dangerous substance,including those based on organic small molecules and emerging nanomaterials.Herein,we are going to present a comprehensive review of recently reported hydrazine fluorescent probes,and discuss their structure design strategies and detection mechanisms.In particular,both organic small-molecule and nanomaterial fluorescent probes for hydrazine will be discussed together for the first time.

Synthesis of 3-hydroxyflavone fluorescent probes and study of their fluorescence properties

Direct measurement of dipole potential in biological membranes has been impossible and 3-hydroxyflavones(3HFs) have allowed detection of changes in dipole potential in biological systems.In the present study,sixteen derivatives of 3HF with aliphatic hydrocarbon chains of different lengths at 4′-position and 6-position were synthesized.The basic fluorescence properties of 3HFs are maintained in all the probes in terms of strong blue shift in maximum fluorescence emission wavelength and>100 fold increase in quantum yield in organic solvents and in dioleoylphosphatidylcholine(DOPC) small unilamellar vesicles(SUV) in comparison to in aqueous Hepes buffer(15 mmol/L,pH 7.4).More importantly,the ability of the new compounds to report dipole potential changes in biological systems are also maintained,since all the new probes showed spectrum properties that are similar to yet different from that of F4N1,which potentially may allow more sensitive measurement of the dipole potential change in membranes.

STRUCTURAL INVESTIGATION OF A NEW POLYORGANOSILOXANE CONTAINING NANOTUBULAR CAVITIES USING ORGANIC FLUORESCENT PROBES

Fluorescent molecules - p-dimethylaminobenzonitrile (DMABN) and trans-stilbene (TSB ) - were used as probes to investigate the inner structure of the nanotubular cavities contained in a new polyorganosiloxane (POS) which was prepared by the hydrosilylation coupling reaction of cis-isotactic ladderlike polyvinylsilsesquioxane (Vi-T) with 1,1,3,3-tetramethyldisiloxane (H-MM) as coupling agent in the presence of catalyst dicyclopentadienyldichloroplatinum (Cp2PtCl2). The results from FTIR spectra and fluorescence spectra in combination with molecular simulation reveal that the cross-section of the nanotubular cavity is nearly rectangular in shape, and is about 0.62 nm in width and about 0.38 nm in height. This work gains in-depth knowledge into the inner structure of the nanotubular cavities of POS and furthermore provides a guide to the selection of proper guest molecules in constructing functional supramolecular clathrate based upon POS.

Synthesis and Spectral Characterization of Novel Sulfhydryl-reactive Benzimidazole Fluorescent Probes

Three sulfhydryl-reactive fluorescent probes, which contain 2-（1H-benzoimidazol-2-yl）-phenol and maleimide group, were synthesized and their structures were characterized by IR and ^1H NMR. Their photo-physical properties and the specificity to sulfhydryl group in the 2-mercapto-ethanol as well as the L-cysteine adducts were indicated by fluorescence intensity. Preliminary tests revealed that the probes could react selectively with the cysteine molecules, suggesting that these probes might be generally useful in biomedical researches.

Optical Properties and Response Mechanism Analysis of Multi-branched Fluorescent Probes Based on Intramolecular Charge Transfer

In this work, the optical properties of fluorescent probes used for detection of biothiol were studied by employing time-dependent density functional theory. By calculating the single photon absorption and emission properties of probe Mol.1, Mol.2 and Mol.3 before and after reaction with cysteine and homocysteine, we have investigated the effect of carboncarbon triple bond and benzene ring on the properties of fluorescent probes. It is found that the oscillator strength of probe molecules increases gradually with the improvement of the structure of the electron donor triphenylamine and the addition of carbon-carbon triple bonds, and better properties of fluorescence probes have also been demonstrated. At the same time, the effect of different number of side branches on the molecular properties of the probe was also studied. The results showed that compared with single-branched molecule Z1 and tribranched probe Mol.3, two side probe molecules Z2 had higher oscillator strength and better detection effect. In addition, the new single-branched probe Mol.4 with the addition of carbon-carbon triple bonds and benzene rings has better probe properties and simpler structure than the tribranched probe Mol.3.

Responsive mechanism and molecular design of di-2-picolylamine-based two-photon fluorescent probes for zinc ions

The properties of one-photon absorption（OPA）, emission and two-photon absorption（TPA） of a di-2-picolylaminebased zinc ion sensor are investigated by employing the density functional theory in combination with response functions.The responsive mechanism is explored. It is found that the calculated OPA and TPA properties are quite consistent with experimental data. Because the intra-molecular charge transfer（ICT） increases upon zinc ion binding, the TPA intensity is enhanced dramatically. According to the model sensor, we design a series of zinc ion probes which differ by conjugation center, acceptor and donor moieties. The properties of OPA, emission and TPA of the designed molecules are calculated at the same computational level. Our results demonstrate that the OPA and emission wavelengths of the designed probes have large red-shifts after zinc ions have been bound. Comparing with the model sensor, the TPA intensities of the designed probes are enhanced significantly and the absorption positions are red-shifted to longer wavelength range. Furthermore, the TPA intensity can be improved greatly upon zinc ion binding due to the increased ICT mechanism. These compounds are potential excellent candidates for two-photon fluorescent zinc ion probes.

Fluorescent probes for the detection of biogenic amines,nitrite and sulfite in food:Progress,challenges and perspective

Foodborne contaminants such as biogenic amines(BAs),nitrite and sulfite are harmful to human health.To safeguard food safety,the content of BAs,nitrite and sulfite should be strictly controlled.Small-molecule fluorescent probes are a promising analytical tool for monitoring BAs,nitrite and sulfite because they are highly sensitive and selective,offer simplicity of operation,and can enable optical signal visualization of the analyte.In this review,we summarize the most recent progress on the development of fluorescent probes for selectively detecting BAs,nitrite,and sulfite.In particular,we discuss the working mechanisms,sensing performance,and practical applications of various fluorescent probes that have been developed in recent years for detecting BAs,nitrite,and sulfite,with a particular emphasis on the utilization of these probes in food.Lastly,we discuss the research directions,trends,and prospects of molecular fluorescent probes in food applications in the future.We hope this review can offer conceptual and design guidance for researchers and practitioners to develop novel fluorescent probes for food safety.

Recent progress on fluorescent probes for viruses

Viruses are ubiquitous in human life. Some viruses can be used as vectors of genetic engineering and specific pesticides. Other viruses trigger a variety of diseases in humans, animals and plants, resulting in high infection rates and mortality. Therefore, convenient, accurate and rapid detection of viruses is of great significance for the diagnosis and treatment of subsequent diseases. In contrast to traditional methods of detection, which rely on time-consuming and complex techniques such as polymerase chain reaction (PCR), fluorescent probes and imaging methods generate real-time results, with high specificity, and have been widely used in viral detection. In this review, the application of viral fluorescent probes in analyzing the molecular structure, detection and biological imaging is discussed. In particular, we categorized the probes based on their specificity for human and plant viruses, reviewing the latest findings and analyzing their limitations. The potential of fluorescent molecular probes in the treatment of viral disease and environmental analysis, and their possible combinations with protein and immune technology are discussed.

Reaction-based small-molecule fluorescent probes for endoplasmic reticulum-and mitochondria-targeted biosensing and bioimaging

Fluorescent probes have revolutionized modern biological research by making it possible to observe and measure an extensive range of cellular and subcellular processes.Among the subcellular compartments,the endoplasmic reticulum(ER)and mitochondria(MT)remain exciting targets owing to the information they reveal about the cellular processes.Consequently,monitoring pH,polarity,viscosity,metal ions,reactive nitrogen species(RNS),reactive sulfur species(RSS)and reactive oxygen species(ROS)in ER and MT with fluorescent probes is of great importance to understand the cellar and subcellular process.Recent years,redox-sensitive probes and ion probes are designed and synthesized for the detection and quantification of RNS/RSS/ROS(collectively as reactive oxygen/nitrogen/sulfur species,RONSS)and metal ions within ER and MT.These probes provide powerful tools for the researchers to learn more about the complex relationship between cellular redox homeostasis and organelle function,and understand the mechanism of disease processes and pathogenesis for developing potential treatments.In this review,the design principles,synthesis methods,targeting mechanism for ER-and MT-targeted RONSS,and metal-ionspecific fluorescent probes are discussed.The recent progress for the synthesis and applications of ER/MT-targeted probes,and their applications for monitoring cellular and subcellular processes are summarized,and the development trends and application prospects of the probes are analyzed.

Fluorescent Probes for Cysteine and Cysteine Oxidation Imaging

Cysteine is an important regulator of redox processes.Due to the nucleophilic and oxidative sensitivity,cysteine residues in proteins can be oxidized by intracellular reactive oxygen species(ROS),which can lead to protein structural and functional changes.Hence,the development of fluorescent probes to image cysteine and cysteine oxidation is of great significance for the study of redox homeostasis in living system.In this review,the development of fluorescent probes for imaging cysteine and cysteine oxidation was summarized.Moreover,we further analyzed defects of the reported fluorescent probes and made suggestions for the future development of fluorescent probes.We expect that this review can not only provide a deeper understanding of the role of cysteine and cysteine oxidation in oxidative stress,but also broaden the application of fluorescent probes in imaging cysteine and cysteine oxidation.

Recent advances in formaldehyde-responsive fluorescent probes

Formaldehyde, as one of the simplest reactive carbonyl species（RCS）, is regarded as a potential carcinogen and a sick house syndrome gas. Recent studies have shown that abnormally high levels of formaldehyde may result in cognitive decline and spatial memory deficits, asthmatic symptoms,Alzheimer＇s disease, and cancer. Due to the harmfulness of high levels of formaldehyde in nature and humans, it is of great significance to further elucidate the roles and functions of formaldehyde by a noninvasive detection approach. Fluorescence imaging has become a powerful and popular tool in monitoring bio-species owing to their high sensitivity and selectivity, excellent spatiotemporal resolution and non-invasion nature. Therefore, fluorescent probes are widely applied to track and detect formaldehyde in vitro and in vivo which have attracted more and more interest recently. This review focuses on various strategies to design the fluorescent probes for detecting formaldehyde based on different recognition groups.

Fluorescent probes for the detection of disease-associated biomarkers

Fluorescent probes have emerged as indispensable chemical tools to the field of chemical biology and medicine.The ability to detect intracellular species and monitor physiological processes has not only advanced our knowledge in biology but has provided new approaches towards disease diagnosis.In this review,we detail the design criteria and strategies for some recently reported fluorescent probes that can detect a wide range of biologically important species in cells and in vivo.In doing so,we highlight the importance of each biological species and their role in biological systems and for disease progression.We then discuss the current problems and challenges of existing technologies and provide our perspective on the future directions of the research area.Overall,we hope this review will provide inspiration for researchers and prove as useful guide for the development of the next generation of fluorescent probes.

Biothiol-specific fluorescent probes with aggregation-induced emission characteristics

Biothiols are important species in physiological processes such as regulating protein structures, redox homeostasis and cell signalling. Alternation in the biothiol levels is associated with various pathological processes, therefore non-invasive fluorescent probes with high specificity to biothiols are highly desirable research utilities. Meanwhile, fluorescent probes with aggregationinduced emission properties(AIEgens) possess unique photophysical properties that allow modulation of the sensing process through controlling the aggregation-disaggregation or the intramolecular rotational motions of the fluorophores. Herein we review the recent progress in the development of biothiol-specific AIEgens. In particular, the molecular design principles to target different types of biothiols and the corresponding sensing mechanisms are discussed, along with the potential of the future design and development of multi-functional bioprobes.

Vinyl Groups Containing Tetraphenylethylene Derivatives as Fluorescent Probes Specific for Palladium and the Quenching Mechanism

We previously reported that a series of tetraphenylethylene(TPE)-containing all-hydrocarbon conjugated polymers exhibited a specific fluorescence quenching by palladium ions(Pd^(2+)).To understand the quenching mechanism,herein we investigate the quenching behaviors of three TPE derivatives in the presence of Pd^(2+).Each TPE derivative,consisting of TPE unit and terminal vinyl groups,shows an aggregation-induced emission(AIE)and its fluorescence turns off specifically to Pd^(2+).The sensitivity is enhanced with increasing numbers of vinyl groups in the molecules.By time-resolved fluorescence measurement,a dynamic quenching is observed where the fluorescence lifetime is reduced with Pd^(2+).Specifically,the quenching occurs via the electron transfer in the excited states,as suggested by the disappearance of the stimulated emission band in transient absorption spectra.A theoretical calculation on the excited states identifies intermolecular electron transfer from TPE derivatives to Pd,especially for electron-rich TPE derivative.The mechanism can be general for the design of novel AIE active chemosensors.

Recent advances in small molecule fluorescent probes for simultaneous imaging of two bioactive molecules in live cells and in vivo

The interrelationships and synergistic regulations of bioactive molecules play pivotal roles in physiological and pathological processes involved in the initiation and development of some diseases,such as cancer and neurodegenerative and cardiovascular diseases.Therefore,the simultaneous,accurate and timely detection of two bioactive molecules is crucial to explore their roles and pathological mechanisms in related diseases.Fluorescence imaging associated with small molecular probes has been widely used in the imaging of bioactive molecules in living cells and in vivo due to its excellent performances,including high sensitivity and selectivity,noninvasive properties,real-time and high spatial temporal resolution.Single organic molecule fluorescent probes have been successively developed to simultaneously monitor two biomolecules to uncover their synergistic relationships in living systems.Hence,in this review,we focus on summarizing the design strategies,classifications,and bioimaging applications of dual-response fluorescent probes over the past decade.Furthermore,future research directions in this field are proposed.

Design and applications of carbon dots-based ratiometric fluorescent probes:A review

Ratiometric fluorescence(FL)probes can eliminate the background interference and provide more accurate detection results than single emission intensity-based nanoprobes.Recently,carbon dots(CDs)-based ratiometric FL probes have received extensive research attention due to their excellent biocompatibility,water solubility,and multi-emission capabilities.In this review,we firstly summarize the construction strategies of CDs-based ratiometric FL probes,including physical mixing,nanohybrid,and dual-emitting CDs strategies.Additionally,we classify the sensing types of CDs-based ratiometric FL probes into five categories according to the difference in spectral variation caused by analytes:“single-response-ON”,“single-response-OFF”,“doubleresponses-ON”,“double-responses-OFF”,and“double-responses-Reverse”types.Finally,a thorough overview of CDs-based ratiometric FL probe applications in ions,molecules,pH,and temperature sensing is provided.We believe this review can show the latest research progress of CDs-based ratiometric FL sensing fields and provide perspectives on future developments for the construction of CDs-based ratiometric FL probes and their potential applications.

Recent progress in Michael addition-based fluorescent probes for sulfur dioxide and its derivatives

Sulfur dioxide（SO_2） is a harmful environmental pollutant. Inhaled SO_2 can be rapidly hydrated into its derivatives, bisulfite（HSO_3^-） and sulfite（SO_3^（2-））. SO_2 derivatives are well known as preservatives and antioxidants, which are used in food and beverages to prevent oxidation and bacterial growth. Although SO_2 can be endogenously generated in mammals and exhibits unique bioactivities in regulating cardiovascular function, excessive SO_2 and its derivatives have toxic effects on humans and animals for triggering adverse reactions and diseases. A large number of fluorescent probes for SO_2 and its derivatives have been designed and reported due to their high sensitivity and selectivity, high temporal and spatial resolution, non-invasive and non-destructive detection as well as real-time visualization in situ. In this review, we have summarized the recent progress of Michael addition-based fluorescent probes for SO_2 and its derivatives. These probes are categorized and concluded according to the different α,β-unsaturated compounds（i.e., Michael acceptors）. The design strategies, sensing performances, detection mechanisms and applications of these probes are discussed in detailed. Finally, a general overview about the design of probes for SO_2 and its derivatives is provided, which will facilitate the development of ideal probes for SO_2 and its derivatives.