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Herein, by optimizing phenyl selenide-based BODIPYs, BDP-Se-MOS was obtained, which possessed resistance to ROS and could selectively detect Cys. BDP-Se-MOS could not only discriminate between normal and cancer cells, but also image Cys levels in tumor-bearing mice in real time as well as image the fluctuations of Cys levels in an APAP-induced DILI model. [ABSTRACT FROM AUTHOR]

Lipid metabolism disorder and oxidative stress play an essential role in the occurrence and development of metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). Here, we constructed an ONOO-activatable and lipid drops (LDs) traced near-infrared (NIR) fluorescent probe BDP-NIR-Py + through structural modification, and evaluated oxidative stress and lipid metabolism disorders in relevant disease by monitoring changes in ONOO and LDs levels in cells and mice. With the dual monitoring of ONOO and LDs, BDP-NIR-Py + realized real-time visualization of the occurrence and development of NAFLD and T2DM, and early diagnosis of liver injury, which is faster and more sensitive than tissue analysis and blood detection. Collectively, the ability of BDP-NIR-Py + to simultaneously monitor ONOO and LDs makes it has unlimited potential in the early diagnosis and mechanism research of diseases such as NAFLD and T2DM in which oxidative stress and lipid metabolism disorder interact. [Display omitted] • The ONOO–-activatable and LD-traced NIR fluorescent probe BDP-NIR-Py + was constructed. • BDP-NIR-Py + could sensitively monitor the abnormality of ONOO– and LDs in NAFLD cell model. • BDP-NIR-Py + could diagnose NAFLD earlier than blood testing and tissue analysis. • BDP-NIR-Py + realized real-time imaging of the occurrence and development of T2DM and its complications. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is recognized as an endogenous gaseous signaling agent in many biological activities. Lysosomes are the main metabolic site and play a pivotal role in cells. Herein, we designed and synthesized two new fluorescent probes BDP‐DNBS and BDP‐DNP with a BODIPY core to distinguish H2S. The sensing mechanism is based on the inhibition‐recovery of the photo‐induced electron transfer (PET) process. Through comparing the responsive behaviors of the two probes toward H2S, BDP‐DNBS showed a fast response time (60 s), low limit of detection (LOD, 51 nM), high sensitivity and selectivity. Moreover, the reaction mechanism was demonstrated by mass spectrometry and fluorescence off‐on mechanism was proved by density functional theory (DFT). Significantly, confocal fluorescence imaging indicated that BDP‐DNBS was successfully used to visualize H2S in lysosomes in living HeLa cells. [ABSTRACT FROM AUTHOR]

Fluorescent probes for biothiols have aroused increasing interest owing to their potential to enable better understanding of the diverse physiological and pathological processes related to the biothiol species. BODIPY fluorophores exhibit excellent optical properties, which can be readily tailored by introducing diverse functional units at various positions of the BODIPY core. In the present review, the development of fluorescent probes based on BODIPYs for the detection of biothiols are systematically summarized, with emphasis on the preferable detection of individual biothiols, as well as simultaneous discrimination among cysteine (Cys), homocysteine (Hcy), reduced glutathione (GSH). In addition, organelle‐targeting probes for biothiols are also highlighted. The general design principles, various recognition mechanisms, and biological applications are elaboratively discussed, which could provide a useful reference to researchers worldwide interested in this area. [ABSTRACT FROM AUTHOR]

Our previous discovery suggested that substituents on the 1,7 positions delicately modulate the sensing ability of the meso‐arylmercapto boron‐dipyrromethene (BODIPY) to biothiols. In this work, the impact of delicate modulations on the sensing ability is investigated. Therefore, 1,7‐dimethyl, 3,5‐diaryl substituted BODIPY is designed and developed and its conformationally restricted species with a meso‐arylmercapto moiety (DM‐BDP‐SAr and DM‐BDP‐R‐SAr) as selective fluorescent probes for Cys. Moreover, the lysosome‐target probes (Lyso‐S and Lyso‐D) based on DM‐BDP‐SAr carrying one or two morpholinoethoxy moieties were developed. They were able to detect Cys selectively in vitro with low detection limits. Both Lyso‐S and Lyso‐D localized nicely in lysosomes in living HeLa cells and exhibited red fluorescence for Cys. Moreover, a novel fluorescence quenching mechanism was proposed from the calculations by density functional theory (DFT). The probes may go through intersystem crossing (from singlet excited state to triplet excited state) to result in fluorescence quenching. [ABSTRACT FROM AUTHOR]

Abstract Biothiols, such as glutathione (GSH), homocysteine (Hcy) and cysteine (Cys), are important biomarkers and play crucial roles in many physiological processes. Thus, the detection of biothiols is highly important for early diagnosis of diseases and evaluation of disease progression. Herein, new types of BODIPY-based fluorescent probes (probe 1, probe 2 and probe 3) capable of cysteine (Cys)/homocysteine (Hcy) sensing with high selectivity over other amino acids were developed. In addition, we further studied the influence of different electronegativity substituents on these probes to sensing Cys/Hcy. Ultimately, we concluded that the electron withdrawing group on probe 1 can accelerate the probe response to Cys/Hcy, and probe 1 was successfully applied for selective imaging Cys/Hcy in living cells. Graphical abstract fx1 Highlights • A series of novel BODIPY-based fluorescent probes for cysteine and homocysteine were developed. • All three fluorescent probes have advantage of high sensitivity and selectivity. • Probe 1 was capable of detecting Cys/Hcy in living cells. [ABSTRACT FROM AUTHOR]

Biological thiols, especially low molecular weight thiols, including cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), play a pivotal role in physiological and pathological systems. Thus, the detection of biothiols is highly important for early diagnosis of diseases and evaluation of disease progression. Herein, we developed a highly selective and sensitive ratiometric fluorescent 8-Cl BODIPY-based probe with high fluorescence quantum yields. The probe displayed a sensitive response to Cys and Hcy over other biothiols, which can be visualized colorimetrically and/or fluorescently. The probe was successfully applied to detect Cys in human plasma, demonstrating its great value for practical application in biological sample analysis. [ABSTRACT FROM AUTHOR]

The liver, which is an important internal organ and digestive gland of the human body, plays essential roles in metabolism and detoxifictaion. Due to frequently expose to toxic substances, the liver is susceptible to injury. Peroxynitrite (ONOO−) is a kind of ROS/RNS, which generally formed by the diffusion-limited reaction of O 2 •‒ and NO. Some evidences have been confirmed that the production of ONOO− was related to the drug-induced liver injury (DILI). Therefore, developing accurate analytical methods for detecting ONOO− of DILI-related diseases will further ascertain the mechanisms of drug-induced hepatotoxicity. In this work, probe BDPP with fast reponse, high selectivity and good senstivity was successfully constructed and utilized for detecting peroxynitrite in live cells and zebrafish. What's more, in the APAP-induced hepatotoxicity model cells, the probe BDPP could detect the up-regulated expression of ONOO− and evaluate the remediation of NAC. The probe BDPP may as a promising tool for the detection of ONOO− during drug-induced hepatotoxicity related assays. [Display omitted] • A novel BODIPY-based probe BDPP for selective and sensitive detection of ONOO− was designed and synthesized. • BDPP could monitor exogenous and exogenous ONOO− in live cells as well as in zebrafish. • BDPP could trace the up-regulation of ONOO− in the APAP-Induced hepatotoxicity in different cells. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury (DILI) as an acute liver disease has caused serious concern in public health problems. As a kind of reactive oxygen species, HClO has come into scientists' vision as a marker of DILI. Herein, we construct a BODIPY-based near-infrared (NIR) fluorescent probe (BDP-R-ClO) for the selective and sensitive response of hypochlorous acid. The probe could realize the rapid detection of HClO, with a 20-fold fluorescence enhancement at 661 nm and the detection value of which was only 1.8 nM. Moreover, BDP-R-ClO could diagnose and visualize DILI by monitoring the fluctuation of HClO concentration in vitro and in vivo , and evaluate the detoxification of hepatoprotective drugs. Through the visualization of HClO in the mice liver injury models, BDP-R-ClO not only proved its applicability but also indicated that it had great potential in the diagnosis and monitoring of HClO-related diseases. [Display omitted] ● A novel BODIPY-based NIR fluorescent probe for detection of HClO was developed. ● Probe exhibited favorable selectivity and sensibility towards HClO. ● Probe could be utilized to visualize HClO via fluorescence imaging in live cells and in vivo. ● Probe realized the diagnosis of APAP-induced hepatotoxicity, and evaluated the detoxification of hepatoprotective drugs. [ABSTRACT FROM AUTHOR]

Early diagnosis and detection of drug-induced liver injury (DILI) is great significance for the effective prevention and treatment of patients with liver injury. Studies indicate that the up-regulation of peroxynitrite (ONOO−) levels in liver is profoundly involved in acetaminophen (APAP)-induced liver injury. Herein, we constructed diketopyrrolopyrrole (DPP)-based ratiometric fluorescent probes (DPP-DH-P and DPP-DEG-P) for detecting and imaging ONOO−. Comparing two probes, DPP-DEG-P exhibited higher signal-to-noise ratio (2750-fold) and lower detection limit (3.5 nM) for tracking ONOO− in solution. DPP-DH-P possessing better biocompatibility had been successfully applied to monitor the fluctuation of ONOO− in LPS/IFN-γ or APAP-treated hepatocytes with a high signal-to-noise ratio (20-fold) by ratiometric imaging. Moreover, the probe was used to evaluate the repair effect of glutathione on DILI. We unexpectedly discovered that DPP-DH-P and DPP-DH targeted lysosomes and mitochondria, respectively. Based on the change of ONOO− induced by APAP, we observed that DPP-DH-P and the generated DPP-DH diffused from lysosome into cytoplasm, and DPP-DH did not target mitochondria due to the effect of endogenous ONOO−, these indirectly reflected the dysfunction of organelles. Observably, this work will accelerate a deeper comprehending for the pathogenesis of DILI, and furnish an effective tool for the diagnosis and treatment of DILI. [Display omitted] • Two ratiometric fluorescent probes DPP-DH-P and DPP-DEG-P with ICT characteristic for imaging ONOO− were reported. • DPP-DEG-P exhibited higher signal-to-noise ratio (2750-fold vs 353-fold) and lower detection limit (3.5 nM vs 8.4 nM). • DPP-DH-P could be used to visualize ONOO− by ratiometric fluorescence imaging in living cells and in vivo. • DPP-DH-P realized the diagnosis and detection of APAP-induced hepatotoxicity, and also evaluated the repair effect of GSH. • The changes in the targeting ability of DPP-DH-P and generated DPP-DH indirectly reflected the dysfunction of organelles. [ABSTRACT FROM AUTHOR]

Abstract: A new benzimidazole-based quinazoline derivative (1) has been designed and synthesized as a fluorescent probe. Probe 1 exhibits high selectivity and sensitivity to Cu2+ as fluorescence ‘on–off’ behavior in HEPES-buffered CH3OH/H2O (1:1, v/v, pH=7.0) solution. The in situ formed 1-Cu2+ complex is further utilized to sense the cyanide ions with high selectivity and fluorescence enhancement performance. [Copyright &y& Elsevier]

In this work, a new resorufin-based turn-on fluorescent probe (RFP) carrying phosphinate recognition group [–P(O)Ph 2 ] as a good trigger group was designed and synthesized. The probe exhibited highly selectivity and sensitivity for detecting endogenous ONOO– in RAW264.7 cells and inflammatory mice. [Display omitted] • A novel Resorufin-based fluorescent probe for selective detection of ONOO– were developed. • Probe displayed high selectivity towards to ONOO–. • Probe could sense intracellular ONOO– by fluorescent imaging in living cells and inflammatory mice. Peroxynitrite (ONOO−) plays essential roles on various physiological and pathological processes of living systems as a short-lived and highly reactive nitrogen (RNS) specie. The construction of novel long-wavelength fluorescent probes with high specificity towards ONOO− for imaging in vivo is still demand urgently. About this work, a novel resorufin-based red-emitting fluorescent probe for tracking ONOO− has been constructed. The probe RFP exhibited high selectivity towards ONOO− anion over other analytes. Utilizing the probe, ONOO− could be directly observed by the naked eye. Furthermore, RFP was successfully applied for imaging endogenous ONOO– in RAW264.7 cells and inflammatory mice. This work offers a convenient method for monitoring the intercellur ONOO– that be expected to be applied for explaining the bio-functional roles of ONOO− in living system. [ABSTRACT FROM AUTHOR]

Cysteine (Cys) is a crucial bio-thiol attributing to its significant role in many physiological and pathological processes and maintaining redox dynamic balance. In mitochondria, ROS can cause oxidative damage, and Cys can solve this problem by acting as an antioxidant. Herein, we designed and synthesized a series of meso-pyridin and meso-pyridinium substituted BODIPY dyes as fluorescent probes to distinguish Cys. Through screening the responsive behaviors of the all probes toward biothiols, we obtained an appropriate mitochondria-targeted probe BDP-S- o -Py + for Cys-specific detection. Density functional theory (DFT) calculations were used to demonstrate the different reactivity of the probes. BDP-S- o -Py + could detect Cys with fast response under biological environment. The probe BDP-S- o -Py + had a low limit of detection (LOD, 72 nM) at the linear dynamic range from 0 to 50 μM. In particularly, BDP-S- o -Py + could be used for imaging of mitochondrial Cys in living cells, and was capable of monitoring endogenous Cys in vivo, successfully. Image 1 • An appropriate mitochondria-targeted probe BDP-S- o -Py + for detection of Cys was obtained by screening synthesized dyes • The different reactivity of probes was demonstrated by density functional theory (DFT) calculations. • BDP-S- o -Py + could detect Cys with fast response, high sensitivity and selectivity. • BDP-S- o -Py + was successfully used to image mitochondrial Cys in HeLa cells. • BDP-S- o -Py + was capable of monitoring endogenous Cys in vivo. [ABSTRACT FROM AUTHOR]

Keywords: biothiols; BODIPY; fluorescent probes; organelle-targeting EN biothiols BODIPY fluorescent probes organelle-targeting 1 1 1 04/03/20 20200401 NES 200401 B To enable better understanding b of the diverse physiological and pathological processes related to the biothiol species, fluorescent probes have experienced an increasing interest. The BODYPI-based probes demonstrate excellent optical properties, which can be modulated through the introduction of various functional groups at different positions within the BODIPY core. Biothiols, BODIPY, fluorescent probes, organelle-targeting. [Extracted from the article]

Highlights from the article: Frontispiece: Development of Lysosome-Targeted Fluorescent Probes for Cys by Regulating the Boron-dipyrromethene (BODIPY) Molecular Structure Keywords: BODIPY; cysteine; fluorescent probes; lysosome targeted B As important biomolecules, biothiols such as cysteine (Cys) b , homocysteine (Hcy), and glutathione (GSH) play vital roles in a wide range of physiological and pathological processes arising from their biological redox chemistry.

Fever is the result of inflammation and the innate self-defense response of organisms, can cause abnormal changes in the activity of many enzymes in organisms, including the important carboxylesterase (CE). Monitoring the activity changes of CE in vivo during a fever will help to understand heat-related pathological mechanisms. In this paper, we designed diketopyrrolopyrrole-based ratiometric fluorescent probes DPP-FBC-P and DPP-FBO-P containing alkyl chain and diethylene glycol monomethyl ether chain respective for detection of CE. Both probes could realized fast response to CE and displayed good selectivity and high sensitivity. Compared with DPP-FBO-P , DPP-FBC-P had better biocompatibility, larger signal to noise ratio (225-fold vs 125-fold) and lower detection limit (1.6 × 10−5 U/mL vs 4.2 × 10−5 U/mL). Moreover, the probe DPP-FBC-P had been successfully applied to image the endogenous CE in HepG2 cells and solid tumors, and also visualized the over expressed CE in fever cells. Most importantly, the changes of CE level in the liver of fever mice model induced by LPS were monitored with the assistance of DPP-FBC-P via dual channel ratio imaging for the first time. In addition, fluorescence color signal in solution was captured by smart phone, and the linear relationship between RGB ratio (G/R) and CE concentration was established. This work will provide a potential approach for investigating the physiological and pathological processes of heat related diseases. [Display omitted] • Two ratiometric fluorescent probes for imaging carboxylesterase (CE) were developed. • Both probes could quickly, selectively and sensitively trace CE with ratiometric signal. • DPP-FBC-P could visualize CE by ratiometric imaging in HepG2 cells and solid tumors. • DPP-FBC-P was successfully used to visualize the over expressed CE in fever cells and mice. [ABSTRACT FROM AUTHOR]

Fluorescent probe technology has been widely used in biochemistry, medicine, environmental science and industry. Resorufin has been widely used in the design of small molecule fluorescent chemical sensors due to its excellent optical properties. It has found a wide range of applications in molecular recognition and molecular imaging in analytical chemistry, biology and medicine. In this review, we systematically summarize the development of resorufin-based fluorescent probes to detect biologically active substances such as enzymes, reactive oxygen species (ROS), reactive nitrogen species (RNS), reactive sulfur species (RSS), ions, etc. The design strategies and biological applications of various resorufin-based fluorescent probes are discussed in detail, so as to promote the development of more powerful fluorescent probes for extensive and exciting applications in the future. In addition, we also outlook on the development trend and the prospects of probes based on the resorufin platform. [Display omitted] • A review systematically summarizes the development of resorufin-based fluorescent probes. • The protection of 7-hydroxy group and substitution of N atom of resorufin are two general strategies to develop probes. • Resorufin-based probes could detect enzymes, ROS, RNS, RSS, ions, and target organelle. • NIR-I or NIR-II and ratiometric fluorescent probes could be the optimal pursuit. [ABSTRACT FROM AUTHOR]

Hypochlorous acid (HClO) is a key signaling molecule which involved in various pathological and physiological processes and the immune system. It had been proved that excess HClO in the organisms was closely associated with diabetes. In this paper, we constructed a series of BODIPY-based fluorophores modified with olefinic bond. With the assistance of theoretical calculations, the optimized near-infrared (NIR) dye BDP-ENE-S-Me , which possessed the longest wavelength (690 nm) and the best stability, was screened and synthesized. Based on BDP-ENE-S-Me , we further introduced N, N-dimethylcarbamate group to construct a NIR fluorescent probe BDP-ENE-ClO. BDP-ENE-ClO displayed excellent selectivity and sensitivity with a low detection limit (49 nM) towards HClO. Besides, the probe was successfully applied in monitoring concentration fluctuations of HClO in vitro and in vivo caused by various stimuli. Most importantly, the over-production of HClO in the type I, type II diabetes and diabetic liver disease mice models could be visualized and assessed precisely with the assistance of BDP-ENE-ClO. By comparing fluorescent intensity of diabetic mice models with that of diabetic liver disease mice models, the probe was competent to assess the progression of diabetes. [Display omitted] • Five NIR BODIPY containing 4-pyridyl and aryl vinyl were constructed. • BDP-ENE-S-Me possessing the longest wavelength and the best stability was screened. • BDP-ENE-ClO could monitor fluctuations of HClO concentration in vitro and in vivo. • BDP-ENE-ClO could visualize over-production of HClO in the type I and type II diabetic mice. • BDP-ENE-ClO was competent to assess the progression of diabetes. [ABSTRACT FROM AUTHOR]

O -phenylenediamine-BODIPY-based dual-responsive turn-on low-background fluorescence probe 1 for the detection both NO and nitrite has been successfully designed through attachment of a BODIPY dye at the meso position with the amino group of o -phenylenediamine. Probe 1 is intrinsically none fluorescent due to PET effect, however it turns quickly into highly fluorescent state upon treatment with NO in neutral condition or nitrite in acidic environment with high selectivity and low detection limit. The resulted 8-benzotriazolyl BODIPY dye could recognize biothiol such as Cys, Hcy, and GSH. In the cell imaging experiments, only blue fluorescence could be observed with probe 1 using DEA·NONOate as the source of NO and assisted by intracellular Cys and GSH. Our results may inspire and encourage researchers to use such a convenient tool for studying the effects of NO and nitrite in biological and pharmacological studies. [ABSTRACT FROM AUTHOR]

• A novel red-emitting fluorescent probe RFAc based on the deprotection α-keto amide group was constructed. • Probe RFAc displayed high selectivity and sensitivity for sensing ONOO‒. • Probe RFAc could image ONOO‒ in living cells and in an inflamed mouse model. Inflammation is a congenital immune protective response in living system which has tight association with various diseases. Peroxynitrite (ONOO‒) as a member of reactive oxygen species (ROS) family participates in the inflammation progress, therefore detecting ONOO‒ is very important for exploring the inflammatory-related diseases. In this work, we constructed a red-emitting fluorescent probe RFAc for monitoring ONOO‒. Utilizing the α-keto amide group as specific trigger, the probe RFAc realized selective determination of ONOO‒. Besides, it exhibited high sensitivity towards ONOO‒ with a low limit of detection (220 nM). Moreover, the detection mechanism was verified by Mass spectrometry and the intramolecular charge transfer (ICT) process was attested by density functional theory (DFT). It was important that RFAc could trace endogenous/exogenous ONOO‒ in living cells, as well detect the fluctuation of ONOO− levels in LPS-induced inflammation mouse model which could efficiently serve as a promising research tool for the inflammatory-related investigation. In this work, a novel resorufin-based fluorescent probe RFAc installing α-keto amide group as a specific trigger was elaborated constructed. The probe exhibited highly selectivity and sensitivity for detecting endogenous/exogenous ONOO‒ in living cells and was successfully employed for imaging inflammatory mice. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Two probes RF-IT-OC and RF-IT-EG were obtained triumphantly for highly selective detecting ONOO–. • RF-IT-EG exhibited better water solubility (3.2 mg/L) and faster response rate (60 s) to ONOO–. • RF-IT-EG could monitor ONOO– with larger signal-to-noise ratio (103-fold) and lower detection limit (87 nM). • Utilizing RF-IT-EG , the raised ONOO– was visualized successfully in the inflammatory process. Inflammation is a significant protective response in biological systems and associated with various diseases. Peroxynitrite (ONOO−) as a highly active oxidant participates in the inflammatory process of organisms. Thus, it is necessary to construct novel fluorescent probes for exploring inflammation-related diseases through detecting endogenous ONOO–. Resorufin-based fluorescent probes for testing ONOO− were rare and suffered from poor water solubility. In this work, we elaborately designed three resorufin-based incorporating isatin derivatives probes RF-ITs and successfully obtained two highly selective probes RF-IT-OC and RF-IT-EG for ONOO–. Comparing the other two probes, RF-IT-EG containing triethylene glycol monomethyl ether on isatin moiety displayed better water solubility (3.2 mg/L), faster response rate (60 s), larger signal-to-noise ratio (103-fold) and lower detection limit (87 nM) for monitoring ONOO–. The cells imaging results manifested that probe RF-IT-EG could be applied to trace endogenous ONOO− with inappreciable cytotoxicity. Moreover, the RF-IT-EG was capable of tracking the fluctuation of endogenous ONOO− in LPS-stimulated inflamed mouse leg models. This work will provide a faithful and promising probe for illustrating the roles of ONOO− in various inflammation-related diseases. [ABSTRACT FROM AUTHOR]