- Reaction-based two-photon probes for mercury ions: Fluorescence imaging with dual optical windows
-
For fluorescent imaging of mercury ions in living species, two-photon probes with dual optical windows are in high demand but remain unexplored. Several dithioacetals were evaluated, and a probe was found, which, upon reaction with mercury species, yielded a two-photon dye; this conversion accompanies ratiometric emission changes with a 97-nm shift, enabling fluorescent imaging of both the probe and mercury ions in cells by one- and two-photon microscopy for the first time.
- Rao, Alla Sreenivasa,Kim, Dokyoung,Wang, Taejun,Kim, Ki Hean,Hwang, Sekyu,Ahn, Kyo Han
-
-
Read Online
- Visualization of Lung Inflammation to Pulmonary Fibrosis via Peroxynitrite Fluctuation
-
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with short survival time. However, owing to the unknown etiology and the lack of sensitive and noninvasive methods, the diagnosis of IPF in the early stage is still full of challenges. Since the levels of oxidative stress in mitochondria are relevant to pulmonary fibrosis, we herein present a simultaneous near-infrared (NIR)-Ia window and ratiometic fluorescent probe, rTPONOO-1, with two-photon and mitochondria-targeting abilities to explore the potential biological roles of peroxynitrite (ONOO-) in different states of lung slices from healthy to lung inflammation and pulmonary fibrosis, and there is a good linear relationship between ratiometric fluorescence changes and the rate of pulmonary fibrosis from hematoxylin and eosin (H&E) and Masson staining. In addition, the therapeutic efficacy of aminoguanidine hemisulfate salt (AG) was also investigated. Thus, rTPONOO-1 has great potential in quickly predicting the progression of pulmonary fibrosis in the early stage and improving effective treatment.
- Zhan, Zixuan,Liu, Rui,Chai, Li,Dai, Yongcheng,Lv, Yi
-
-
Read Online
- Readily Accessible and Predictable Naphthalene-Based Two-Photon Fluorophore with Full Visible-Color Coverage
-
Herein we report 22 acedan-derived, two-photon fluorophores with synthetic feasibility and full coverage of visible wavelength emission. The emission wavelengths were predicted by computational analysis, which enabled us to visualize multicolor images by two-photon excitation with single wavelength, and to design a turn-on, two-photon fluorescence sensor for endogenous H2O2in Raw 264.7 macrophage and rat brain hippocampus ex vivo.
- Koo, Ja Young,Heo, Cheol Ho,Shin, Young-Hee,Kim, Dahahm,Lim, Chang Su,Cho, Bong Rae,Kim, Hwan Myung,Park, Seung Bum
-
-
Read Online
- Activatable Fluorescence Probe via Self-Immolative Intramolecular Cyclization for Histone Deacetylase Imaging in Live Cells and Tissues
-
Histone deacetylases (HDACs) play essential roles in transcription regulation and are valuable theranostic targets. However, there are no activatable fluorescent probes for imaging of HDAC activity in live cells. Here, we develop for the first time a novel activatable two-photon fluorescence probe that enables in situ imaging of HDAC activity in living cells and tissues. The probe is designed by conjugating an acetyl-lysine mimic substrate to a masked aldehyde-containing fluorophore via a cyanoester linker. Upon deacetylation by HDAC, the probe undergoes a rapid self-immolative intramolecular cyclization reaction, producing a cyanohydrin intermediate that is spontaneously rapidly decomposed into the highly fluorescent aldehyde-containing two-photon fluorophore. The probe is shown to exhibit high sensitivity, high specificity, and fast response for HDAC detection in vitro. Imaging studies reveal that the probe is able to directly visualize and monitor HDAC activity in living cells. Moreover, the probe is demonstrated to have the capability of two-photon imaging of HDAC activity in deep tissue slices up to 130 μm. This activatable fluorescent probe affords a useful tool for evaluating HDAC activity and screening HDAC-targeting drugs in both live cell and tissue assays.
- Liu, Xianjun,Xiang, Meihao,Tong, Zongxuan,Luo, Fengyan,Chen, Wen,Liu, Feng,Wang, Fenglin,Yu, Ru-Qin,Jiang, Jian-Hui
-
-
Read Online
- Naphthalene derivatives of a conformationally locked GFP chromophore with large stokes shifts
-
The active development of fluorescence microscopy requires an increase in the variety of the dyes and their characteristics. Compounds with a large Stokes shift, i.e., a large difference between the positions of the absorption and emission maxima, have at
- Baleeva, Nadezhda S.,Khavroshechkina, Anastasia V.,Zaitseva, Elvira R.,Myasnyanko, Ivan N.,Zagudaylova, Marina B.,Baranov, Mikhail S.
-
-
Read Online
- Intramolecular charge transfer enhancing strategy based MAO-A specific two-photon fluorescent probes for glioma cell/tissue imaging
-
MAO-A promotes the proliferation of human glioma cells. Herein, we report a series of MAO-A specific two-photon small molecular fluorescent probes (A1-5) based on an intramolecular charge transfer enhancing strategy. The activity of endogenous MAO-A can be selectively imaged using A3 as a representative probe in different biological samples including human glioma cells/tissues via two-photon fluorescence microscopy. The study provides new tools for the visual detection of glioma. This journal is
- Chen, Ding,Fang, Haixiao,Li, Lin,Lim, Kah-Leong,Lu, Xiaomei,Qu, Yunwei,Shi, Riri,Wu, Qiong,Yang, Xuekang,Zhang, Cheng-Wu
-
p. 11260 - 11263
(2021/11/09)
-
- ICT-based fluorescent ratiometric probe for monitoring mitochondrial peroxynitrite in living cells
-
Peroxynitrite (ONOO?) is a reactive oxygen species (ROS) that causes serious damage to living cells and is the cause of a series of human diseases. It is reported that mitochondria are the major site of ONOO?production. Therefore, accurate and rapid detection of intracellular ONOO?is important in pathological processes. Herein, a mitochondria-targeted ratiometric fluorescent probe (DMANI) has been rationally designed based on the coumarin-hemicyanine hybrid framework by regulating the intramolecular charge transfer (ICT) effect. TheDMANIcan capture ONOO?at low concentrationsviadirect addition with the CC bond to give an obvious fluorescent signal change from red to blue based on the ICT process. The possible mechanism for this electrophilic addition process was confirmed using electrospray ionization mass spectrometry (ESI-MS) and1H-NMR spectra.DMANIexhibited a good selectivity, a large Stokes shift (248 nm), a low detection limit (40 nM), and a rapid response (within 20 s) to ONOO?. More importantly,DMANIwas successfully used for ratiometric imaging and monitoring of the fluctuations of mitochondrial ONOO?in living cells.
- Du, Yuting,Wang, Hongliang,Zhang, Ting,Wei, Wen,Guo, Minmin
-
supporting information
p. 12915 - 12921
(2021/08/03)
-
- Multichromatic fluorescence towards aberrant proteinaceous aggregates utilizing benzimidazole-based ICT fluorophores
-
The pathological origin of Alzheimer’s disease (AD) remains uncharted terrain, despite intensive investigation. Discriminating aberrant proteinaceous deposits, such as β-amyloid (Aβ) and (hyperphosphorylated) tau protein by imaging methods, is a vital tool to support investigations towards the network of interacting features that results in AD pathology. In this context, multispectral fluorescence imaging (MSFI) has drawn much attention enabling the distinction of several analytes with merely a single fluorophore emitting a multichromatic fluorescent signal. Herein, we developed three kinds of benzimidazole-derived fluorescent dyes, BZ1–BZ3. The photophysical properties and intramolecular charge transfer (ICT) characteristics of the probes were evaluated in various solvents. Furthermore, a benzimidazole-associated polar-sensitivity displayed multichromatic behavior and enabled the visualization of minute differences in microenvironmental polarity between Aβ and tau aggregates, resulting in different maximal fluorescent emission wavelengths. Indeed, BZ2 demonstrated an approximately 30?nm bathochromic shift in maximal fluorescent emission. All these observations offer a potential for the development of a future generation of benzimidazole-derived ICT-based fluorescent probes.
- An, Jusung,Jangili, Paramesh,Lim, Sungsu,Kim, Yun Kyung,Verwilst, Peter,Kim, Jong Seung
-
p. 205 - 215
(2021/07/20)
-
- A Fluorescent Kinase Inhibitor that Exhibits Diagnostic Changes in Emission upon Binding
-
The development of a fluorescent LCK inhibitor that exhibits favourable solvatochromic properties upon binding the kinase is described. Fluorescent properties were realised through the inclusion of a prodan-derived fluorophore into the pharmacophore of an ATP-competitive kinase inhibitor. Fluorescence titration experiments demonstrate the solvatochromic properties of the inhibitor, in which dramatic increase in emission intensity and hypsochromic shift in emission maxima are clearly observed upon binding LCK. Microscopy experiments in cellular contexts together with flow cytometry show that the fluorescence intensity of the inhibitor correlates with the LCK concentration. Furthermore, multiphoton microscopy experiments demonstrate both the rapid cellular uptake of the inhibitor and that the two-photon cross section of the inhibitor is amenable for excitation at 700 nm.
- Fleming, Cassandra L.,Sandoz, Patrick A.,Inghardt, Tord,?nfelt, Bj?rn,Gr?tli, Morten,Andréasson, Joakim
-
p. 15000 - 15004
(2019/09/17)
-
- A mitochondria-targeted two-photon fluorogenic probe for the dual-imaging of viscosity and H2O2 levels in Parkinson's disease models
-
Parkinson's disease (PD) is a neurodegenerative disease that seriously affects the quality of life of the patient. Many sources have shown that mitochondrial dysfunction is increasingly appreciated as playing a critical role in the pathogenesis of PD. The mitochondrial microenvironment and H2O2 level are two key parameters that are used to assess the function of mitochondria. Herein, we designed and synthesized a novel two-photon (TP) fluorogenic probe Mito-LX, which could simultaneously monitor changes in the mitochondrial viscosity and H2O2 levels using two different channels. This probe showed a significant response to viscosity changes with red emission at 730 nm and high sensitivity to H2O2 levels with orange emission at 585 nm. Moreover, Mito-LX was successfully applied to living systems (including living cells, zebrafish and Drosophila) for viscosity and H2O2 detection using one- and two-photon fluorescence confocal microscopy.
- Li, Hao,Xin, Chenqi,Zhang, Gaobin,Han, Xisi,Qin, Wenjing,Zhang, Cheng-Wu,Yu, Changmin,Jing, Su,Li, Lin,Huang, Wei
-
supporting information
p. 4243 - 4251
(2019/07/16)
-
- With the plaque and A β of the nerve fiber entanglement having affinity to the compound and its preparation method
-
The invention provides a compound provided with good affinity and tangled with an Abeta plaque and a nerve fiber. The structural general formula (I) of the compound is as shown in the specification, wherein W is a benzo-hexahydric aromatic ring or a hexah
- -
-
Paragraph 0057-0058
(2018/04/26)
-
- Histone deacetylase fluorescence probe, and preparation method and applications thereof
-
The invention provides a histone deacetylase fluorescence probe, and a preparation method and applications thereof. The structure formula of the histone deacetylase fluorescence probe is disclosed inthe invention. In synthesis, 6-(dimethylamino)-2-naphthaldehyde with two-photon effect is selected as a dye, so that further nucleophilic reaction is realized after deacetylation reaction, and fluorescence signals are generated; aldehyde group carbon is modified into cyanogroup alcohol structures, hydroxyl is connected with HDACs responsive groups, and the histone deacetylase fluorescence probe isused for detecting and imaging of the activity of histone deacetylase in tissue. According to the histone deacetylase fluorescence probe, cyanogroup with excellent electron-withdrawing capability isintroduced, so that after response of HDACs with the histone deacetylase fluorescence probe, intramolecular cyclization reaction is carried out rapidly, activation of fluorescence signals is realized,detecting and imaging on histone deacetylase in living cells and tissue are realized, and excellent clinical application value is achieved.
- -
-
Paragraph 0040; 0045-0047
(2018/07/30)
-
- Rational Design of in Vivo Tau Tangle-Selective Near-Infrared Fluorophores: Expanding the BODIPY Universe
-
The elucidation of the cause of Alzheimer's disease remains one of the greatest questions in neurodegenerative research. The lack of highly reliable low-cost sensors to study the structural changes in key proteins during the progression of the disease is a contributing factor to this lack of insight. In the current work, we describe the rational design and synthesis of two fluorescent BODIPY-based probes, named Tau 1 and Tau 2. The probes were evaluated on the molecular surface formed by a fibril of the PHF6 (306VQIVYK311) tau fragment using molecular docking studies to provide a potential molecular model to rationalize the selectivity of the new probes as compared to a homologous Aβ-selective probe. The probes were synthesized in a few steps from commercially available starting products and could thus prove to be highly cost-effective. We demonstrated the excellent photophysical properties of the dyes, such as a large Stokes shift and emission in the near-infrared window of the electromagnetic spectrum. The probes demonstrated a high selectivity for self-assembled microtubule-associated protein tau (Tau protein), in both solution and cell-based experiments. Moreover, the administration to an acute murine model of tauopathy clearly revealed the staining of self-assembled hyperphosphorylated tau protein in pathologically relevant hippocampal brain regions. Tau 1 demonstrated efficient blood-brain barrier penetrability and demonstrated a clear selectivity for tau tangles over Aβ plaques, as well as the capacity for in vivo imaging in a transgenic mouse model. The current work could open up avenues for the cost-effective monitoring of the tau protein aggregation state in animal models as well as tissue staining. Furthermore, these fluorophores could serve as the basis for the development of clinically relevant sensors, for example based on PET imaging.
- Verwilst, Peter,Kim, Hye-Ri,Seo, Jinho,Sohn, Nak-Won,Cha, Seung-Yun,Kim, Yeongmin,Maeng, Sungho,Shin, Jung-Won,Kwak, Jong Hwan,Kang, Chulhun,Kim, Jong Seung
-
p. 13393 - 13403
(2017/10/05)
-
- Highly Sensitive Near-Infrared Fluorophores for in Vivo Detection of Amyloid-β Plaques in Alzheimer's Disease
-
Alzheimer's disease (AD) is pathologically characterized by the accumulation of β-amyloid (Aβ) deposits in the parenchymal and cortical brain. In this work, we designed, synthesized, and evaluated a series of near-infrared (NIR) probes with electron donor-acceptor end groups interacting through a π-conjugated system for the detection of Aβ deposits in the brain. Among these probes, 3b and 3c had excellent fluorescent properties (emission maxima > 650 nm and high quantum yields) and displayed high sensitivity and high affinities to Aβ aggregates (3b, Kd = 8.8 nM; 3c, Kd = 1.9 nM). Both 3b and 3c could readily penetrate the blood-brain barrier with high initial brain uptake and fast to moderate washout from the brain. In vivo NIR imaging revealed that 3b and 3c could efficiently differentiate transgenic and wild-type mice. In summary, our research provides new hints for developing smarter and more activatable NIR probes targeting Aβ.
- Fu, Hualong,Cui, Mengchao,Zhao, Liu,Tu, Peiyu,Zhou, Kaixiang,Dai, Jiapei,Liu, Boli
-
p. 6972 - 6983
(2015/09/22)
-
- Discovery of a sensitive, selective, and tightly binding fluorogenic substrate of bovine plasma amine oxidase
-
(Chemical Equation Presented) We report a novel fluorogenic substrate of bovine plasma amine oxidase (BPAO), namely, (2-(6-(aminomethyl)naphthalen-2- yloxy)ethyl)trimethylammonium (ANETA), which displays extremely tight binding to BPAO (Km 183 ± 14 nM) and yet is metabolized fairly quickly (kcat 0.690 ± 0.010 s-1), with the aldehyde turnover product (2-(6-formylnaphthalen-2-yloxy)ethyl)trimefhylammonium serving as a real time reporting fluorophore of the enzyme activity. This allowed for the development of a fluorometric noncoupled assay that is 2 orders of magnitude more sensitive than the spectrophotometric benzylamine assay. The discovery of ANETA involved elaboration of the lead compound 6-methoxy-2-naphthalene- methaneamine by structure-based design, which recognized the ancillary cation binding site of BPAO as the most significant structural features controlling binding affinity. Structure-based design further ensured a high level of selectivity: ANETA is a good substrate of BPAO but is not a substrate of either porcine kidney diamine oxidase (pkDAO) or rat liver monoamine oxidase (MAO-B). ANETA represents the first highly sensitive, selective, and tight binding fluorogenic substrate of a copper amine oxidase that is able to respond directly to the enzyme activity in real time.
- Ling, Ke-Qing,Sayre, Lawrence M.
-
supporting information; experimental part
p. 339 - 350
(2009/04/11)
-
- Prodan-containing nucleotide and use thereof
-
A compound represented by formula (1): wherein R1 is a substituent represented by formula (2): wherein R2 is ═O or —NH2, with the proviso that when R2 is ═O, H is attached to the 1-position N of the pyrimidine ring, and the bond between the 1-position N and the 6-position C is a single bond; or a substituent represented by formula (3): wherein R3 is —OH, ═O, or —NH2, with the proviso that when R3 is —OH or —NH2, R4 is H; when R3 is ═O, R4 is —NH2; and when R3 is ═O, H is attached to the 1-position N of the purine ring, and the bond between the 1-position N and the 6-position C is a single bond.
- -
-
Page/Page column 18; sheet 2
(2008/06/13)
-
- Method for releasing a product comprising chemical oxidation, method for detecting said product and uses thereof
-
This invention has as its object a method for releasing a product by subjecting a compound of Formula (II′): R′7R′8(HX)C1-C2(YH)R′9R′10 to a chemical oxidation that cleaves the bond C1-C2 to obtain the product. In the compound of Formula (II′): R′7 to R′10, which are identical or different, correspond to a hydrogen atom, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted functional group; X and Y, which are identical or different, are an oxygen atom, a sulfur atom, or an amine of Formula -NR11R12, wherein R11 is a hydrogen atom, an alkyl group, or a substituted or unsubstituted aryl group, and R12 is not a hydrogen atom. The invention also has as its object a method for releasing a product that comprises, before the chemical oxidation stage, a first step for preparing the compound of Formula (II′). The released product can be a volatile molecule or an active substance or else a specific product. The invention also relates to a method for detecting the released product as well as its applications, in particular for detecting catalytic or enzymatic activities.
- -
-
-