WO2014034348A1 - Composé hétérocyclique, complexe métallique et sonde fluorescente - Google Patents

Composé hétérocyclique, complexe métallique et sonde fluorescente Download PDF

Info

Publication number
WO2014034348A1
WO2014034348A1 PCT/JP2013/070479 JP2013070479W WO2014034348A1 WO 2014034348 A1 WO2014034348 A1 WO 2014034348A1 JP 2013070479 W JP2013070479 W JP 2013070479W WO 2014034348 A1 WO2014034348 A1 WO 2014034348A1
Authority
WO
WIPO (PCT)
Prior art keywords
hydrogen atom
atom
group
fluorescent probe
metal complex
Prior art date
Application number
PCT/JP2013/070479
Other languages
English (en)
Japanese (ja)
Inventor
穣 人見
俊幸 武安
Original Assignee
学校法人同志社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 学校法人同志社 filed Critical 学校法人同志社
Publication of WO2014034348A1 publication Critical patent/WO2014034348A1/fr

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label

Definitions

  • the present invention relates to a heterocyclic compound, a metal complex containing this as a ligand, and a fluorescent probe for detecting hydrogen peroxide using this metal complex.
  • a bioimaging method using a fluorescent probe is mainly used.
  • a fluorescent probe for hydrogen peroxide a “molecule whose fluorescence intensity is increased by oxidative cleavage of carbon-boron” has been conventionally used (Patent Documents 1 and 2, Non-Patent Documents 1 to 10). reference.).
  • hydrogen peroxide is generated from a biomolecule in a sample by oxidoreductase, and then the generated hydrogen peroxide is reacted with a fluorescent probe in the presence of peroxidase, and the amount of fluorescence is measured. Measure indirectly.
  • this fluorescent probe does not fluoresce only by hydrogen peroxide, but fluoresces by a strong oxide generated by peroxidase and hydrogen peroxide.
  • Non-Patent Document 11 a heterocyclic compound described in Non-Patent Document 11 and a metal in which a nitrogen-containing ligand is coordinated to a central metal composed of a transition metal.
  • a compound formed by amide bond with a complex has already been synthesized.
  • this compound since this compound has low water resistance and cannot be used in water, there is a problem that it cannot be used for detection of hydrogen peroxide (see Non-Patent Document 12 and Non-Patent Document 13).
  • a metal complex in which a fluorescent dye is amide-bonded to a metal complex (hereinafter abbreviated as MBFh1), and peroxidized containing this MBFh1. It was confirmed that the hydrogen fluorescent probe can detect hydrogen peroxide in water and that the reaction rate in water is faster than the conventional “molecule whose fluorescence intensity is increased by oxidative cleavage of carbon-boron” (Patent Document 3). And non-patent document 14).
  • MBFh1 contains a fluorophore site containing an amide site, it itself emits weak fluorescence and its stability in water is insufficient. Therefore, MBFh1 has a problem that it cannot be used for measurement of biological samples containing various reactive oxygen species, such as cells and tissues.
  • the present invention is stable in water, and can be used for measurement of biological samples, and has a reaction rate faster than that of conventional fluorescent probes for detecting hydrogen peroxide and probe components. It is an object of the present invention to provide a certain metal complex and a heterocyclic compound which is a ligand of the metal complex.
  • the invention according to claim 1 of this application is a heterocyclic compound represented by the following general formula (I).
  • Xan is a xanthene dye
  • n is 0 to 6
  • R 1 is a hydrogen atom or a methyl group
  • R 2 , R 3 and R 6 are hydrogen atoms
  • R 4 is a hydrogen atom.
  • R 5 is hydrogen atom, methoxy group, ethoxycarbonylmethyl ether group (OCH 2 CO 2 CH 2 CH 3 ), and R 7 and R 9 are independent of each other
  • R 8 is a hydrogen atom, methyl group, chlorine atom, methoxy group or nitro group
  • R 10 is a hydrogen atom, methyl group, chlorine atom or fluorine atom.
  • the invention according to claim 2 is the heterocyclic compound according to claim 1 represented by the following general formula (II).
  • R X is independently a hydrogen atom, a chlorine atom, or a fluorine atom, and n is 0 to 6.
  • the invention according to claim 4 is a metal complex represented by the following general formula (III).
  • Xan is a xanthene dye
  • n is 0 to 6
  • R 1 is a hydrogen atom or a methyl group
  • R 2 , R 3 and R 6 are hydrogen atoms
  • R 4 is a hydrogen atom.
  • R 5 is hydrogen atom, methoxy group, ethoxycarbonylmethyl ether group (OCH 2 CO 2 CH 2 CH 3 ), and R 7 and R 9 are independent of each other
  • R 8 is a hydrogen atom, methyl group, chlorine atom, methoxy group, nitro group
  • R 10 is a hydrogen atom, methyl group, chlorine atom, fluorine atom
  • M is iron, manganese, cobalt, nickel, copper, ruthenium
  • L is chlorine ion, bromine ion, nitrate ion, trifluoromethanesulfonate ion.
  • each R X is independently a hydrogen atom, a chlorine atom or a fluorine atom
  • n is 0 to 6
  • M is iron, manganese, cobalt, nickel, copper or ruthenium
  • L is a chlorine ion. Bromine ion, nitrate ion, trifluoromethanesulfonate ion.
  • the invention described in claim 7 is a fluorescent probe containing the metal complex according to any one of claims 4 to 6, and the invention described in claim 8 is used for detecting hydrogen peroxide. It is a fluorescent probe.
  • the invention according to claim 9 is a bioassay kit including the fluorescent probe according to claim 7
  • the invention according to claim 10 is a bioimaging kit including the fluorescent probe according to claim 7.
  • the invention according to claim 11 is a clinical analysis kit including the fluorescent probe according to claim 7.
  • the invention according to claim 12 is a labeled antibody labeled with the fluorescent probe according to claim 7, and the invention according to claim 13 is a bioassay kit containing the labeled antibody according to claim 12.
  • the invention according to claim 14 is a bioimaging kit including the labeled antibody according to claim 12, and the invention according to claim 15 is a clinical analysis kit including the labeled antibody according to claim 12. is there.
  • the metal complex of the present invention for a fluorescent probe, even in biological samples such as cells and tissues, the generation mechanism and timing of hydrogen peroxide can be captured more accurately, and the role of hydrogen peroxide in the living body. Can be clarified in more detail. If this fluorescent probe is used for bioassay or bioimaging, the processing time of the specimen can be shortened and the examination efficiency can be improved.
  • heterocyclic compound of the present invention is represented by the following general formula (I).
  • Xan is a xanthene-based dye that fluoresces when separated from a metal complex part by oxidative decomposition, and includes rhodamine, tetramethylrhodamine and Texas red, eosin, fluorescein, and their reduced forms. It can be illustrated. Among these, a substituted form of resorufin represented by chemical formula (II) is more preferable because of its high oxidation resistance. n is 0 to 6, and 1 is preferable among them because of high reactivity.
  • R 1 is a hydrogen atom or a methyl group, and since the synthesis is simple, a hydrogen atom is preferable.
  • R 2 , R 3 and R 6 are hydrogen atoms.
  • R 4 is a hydrogen atom, a methyl group, a chlorine atom, a methoxy group, or a nitro group, and since the synthesis is simple, a hydrogen atom is preferable.
  • R 5 is a hydrogen atom, a methoxy group, or an ethoxycarbonylmethyl ether group (OCH 2 CO 2 CH 2 CH 3 ), and since the synthesis is simple, a hydrogen atom is preferable.
  • R 7 and R 9 are each independently a hydrogen atom, a methyl group, or a methoxy group, and since the synthesis is simple, a hydrogen atom is preferable.
  • R 8 is a hydrogen atom, a methyl group, a chlorine atom, a methoxy group, or a nitro group, and since the synthesis is simple, a hydrogen atom is preferable.
  • R 10 is a hydrogen atom, a methyl group, a chlorine atom, or a fluorine atom, and since the synthesis is simple, a hydrogen atom is preferable.
  • R X is independently a hydrogen atom, a chlorine atom, or a fluorine atom. Atoms are preferred.
  • the heterocyclic compound of the present invention can be synthesized, for example, by combining the following chemical reactions (A) to (D).
  • A chemical reactions
  • D chemical reactions
  • resorufin is used as the fluorescent material, but the heterocyclic compound of the present invention is not limited to this.
  • the heterocyclic compound of this invention is not limited to what was manufactured by the following synthetic methods.
  • Metal Complex The metal complex of this invention is represented by the following general formula (III).
  • M is a central metal of the metal complex and is any one of iron, manganese, cobalt, nickel, copper, and ruthenium. Among them, iron is preferable because of its high reactivity.
  • L is a ligand, and can be exemplified by chlorine ion, bromine ion, nitrate ion, and trifluoromethanesulfonate ion. Among these, chlorine ions, bromine ions, and nitrate ions are preferable because synthesis is simple. Since R 1 to R 10 and Xan are the same as the heterocyclic compound of the present invention, description thereof is omitted. Further, when the metal complex of the present invention is represented by the following general formula (IV), the description is omitted because R X is the same as the heterocyclic compound of the present invention.
  • the metal complex catalyst of the present invention can be produced using a known method in which the heterocyclic compound of the present invention is coordinated to a metal as a ligand. Specifically, a salt containing a metal ion serving as a central metal is dissolved in a polar organic solvent such as methanol (hereinafter abbreviated as MeOH) or acetonitrile (hereinafter abbreviated as MeCN), If a heterocyclic compound solution in which the heterocyclic compound of the invention is dissolved in a polar organic solvent is prepared, and the metal ion solution and the heterocyclic compound solution are mixed and stirred, crystals of the complex can be precipitated. If this crystal is washed with a polar organic solvent, a crystal with higher purity can be obtained.
  • a polar organic solvent such as methanol (hereinafter abbreviated as MeOH) or acetonitrile (hereinafter abbreviated as MeCN)
  • the metal complex of the present invention is rapidly decomposed into xanthene fluorescent dyes, metal complexes and the like when reacted with active oxygen species such as hydroxyl radical, peroxynitrite and hydrogen peroxide. If this fluorescent compound is detected by a visible ultraviolet intensity meter or the like, the generation of active oxygen species can be detected. Therefore, the metal complex of the present invention can be used as a fluorescent probe for detecting active oxygen species, particularly hydrogen peroxide. Moreover, this fluorescent probe can be combined with a monoclonal or polyclonal antibody by a known method, and an antibody labeled with this fluorescent probe can be used as a fluorescent probe.
  • Fluorescent probe, labeled antibody, etc. The fluorescent probe of this invention and the antibody labeled with this fluorescent probe can be used for any application without any particular limitation.
  • a bioassay kit, a bioimaging kit, a clinical test kit, etc. are constructed by combining this fluorescent probe or an antibody labeled with this fluorescent probe with a known reagent, etc., and bioassay, bioimaging, clinical test, etc. It can be used for such as.
  • These kits have a short reaction time until the fluorescent probe fluoresces, and are not easily affected by the inhibitor. Therefore, by using these kits, the inspection time can be shortened and a highly accurate inspection result can be obtained as compared with conventional kits.
  • bioassay kit examples include an ELISA method kit using a glucose oxidase-labeled antibody, glucose oxidase, phospholipase, cholesterol oxidase, sphingomerase, glutamate oxidase, acetylcholine oxidase, monoamine oxidase, galactose oxidase, xanthine oxidase, etc. And a kit for quantifying an enzyme that generates hydrogen peroxide.
  • bioimaging kit examples include use of the enzyme that generates hydrogen peroxide as a fluorescent imaging agent in a cell.
  • Examples of the clinical test kit include a clinical test kit for detecting the generation of hydrogen peroxide, such as a catalase determination kit in body fluids of humans and animals, a catalase determination kit in food, and cholesterol used in combination with cholesterol oxidase. And a kit for quantitative determination of acetylcholine used in combination with acetylcholinesterase and acetylcholine oxidase.
  • the fluorescent probe of the present invention generates fluorescence also by hydrogen peroxide having a weak oxidizing power generated from a substrate by oxidoreductase. Therefore, when the fluorescent probe of the present invention is combined with an oxidoreductase or the like, it can be used for measurement of glucose, galactose, cholesterol, uric acid, inorganic phosphate, inorganic pyrophosphate, and the like. Especially, since it is hard to receive the influence of an inhibitor, it is suitable for the kit for blood glucose level determination of the diabetic patient under drug treatment.
  • kits used in these kits and the sample processing procedures using the kits are not particularly limited except that the fluorescent probe of the present invention is used, and any known reagents, processing procedures, etc. may be used in appropriate combinations. Good.
  • metal complex A metal complex according to the present invention was prepared. Specifically, an iron complex was prepared after synthesizing a ligand along the reaction path of FIG. In addition, in order to make it easy to understand, in the following description, the same symbol as FIG. 1 was used about the same compound.
  • Reagent N- (2-Nitrobenzenesulfonyl) -2- (aminomethyl) pyridine (hereinafter abbreviated as compound c) has already been reported (D. Schols et al., J. Med. Chem., 2010, 53, 1250). -1260.), 8-Aminoquinolyl-2-bromoacetoamide (hereinafter abbreviated as compound f) is another report (Y. Hitomi et al., Angew. Chem. Int. Ed., 2012, 51 (14), 3448-3452.) was used. Regarding other reagents, commercially available reagents were used.
  • FIG. 3 shows that as the concentration of hydrogen peroxide increases, the temporal change in fluorescence intensity, that is, the decomposition rate of the iron complex increases. It was also found that the fluorescence intensity did not change until hydrogen peroxide was added, and that the fluorescence intensity hardly changed during the measurement time when the hydrogen peroxide concentration was 0 ⁇ M. That is, it was confirmed that MBFh2 was stable in water.
  • MBFh1 and MBFh2 The stability and reaction rate of MBFh1 which is a conventional metal complex and MBFh2 which is a metal complex of the present invention in water were compared. Specifically, the comparison was made as follows. MBFh1 used was synthesized according to Patent Document 3.
  • FIG. 4 shows that the MBFh1 fluorescence intensity increased with time without adding hydrogen peroxide.
  • the fluorescence intensity of MBFh2 remained constant until hydrogen peroxide was added, and that the fluorescence intensity changed more drastically than MBFh1 when hydrogen peroxide was added. That is, it was confirmed that MBFh2 was more stable in water than MBFh1, and the reaction rate with hydrogen peroxide was faster.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

L'invention concerne : une sonde fluorescente pour détecter le peroxyde d'hydrogène, qui est stable même dans l'eau et est ainsi apte à être utilisée pour la mesure d'un échantillon biologique, tout en ayant une vitesse de réaction supérieure aux sondes fluorescentes classiques ; un complexe métallique qui est un élément constituant de la sonde fluorescente ; et un composé hétérocyclique qui est un ligand du complexe métallique. Un composé hétérocyclique de la présente invention est représenté par la formule (I). (Dans la formule, Xan représente un colorant xanthène ; n représente un nombre de 0-6 ; R1 représente un atome d'hydrogène ou un groupe méthyle ; chacun parmi R2, R3 et R6 représente un atome d'hydrogène ; R4 représente un atome d'hydrogène, un groupe méthyle, un atome de chlore, un groupe méthoxy ou un groupe nitro ; R5 représente un atome d'hydrogène, un groupe méthoxy ou un groupe éthoxycarbonyl méthyl éther (OCH2CO2CH2CH3) ; chacun parmi R7 et R9 représente indépendamment un atome d'hydrogène, un groupe méthyle ou un groupe méthoxy ; R8 représente un atome d'hydrogène, un groupe méthyle, un atome de chlore, un groupe méthoxy ou un groupe nitro ; et R10 représente un atome d'hydrogène, un groupe méthyle, un atome de chlore ou un atome de fluor).
PCT/JP2013/070479 2012-08-27 2013-07-29 Composé hétérocyclique, complexe métallique et sonde fluorescente WO2014034348A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2012186647A JP5512764B2 (ja) 2012-08-27 2012-08-27 複素環化合物、金属錯体及び蛍光プローブ
JP2012-186647 2012-08-27

Publications (1)

Publication Number Publication Date
WO2014034348A1 true WO2014034348A1 (fr) 2014-03-06

Family

ID=50183168

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2013/070479 WO2014034348A1 (fr) 2012-08-27 2013-07-29 Composé hétérocyclique, complexe métallique et sonde fluorescente

Country Status (2)

Country Link
JP (1) JP5512764B2 (fr)
WO (1) WO2014034348A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112174946A (zh) * 2020-11-05 2021-01-05 四川大学华西医院 一种脂滴荧光探针及其合成方法和应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001064664A1 (fr) * 2000-02-29 2001-09-07 Daiichi Pure Chemicals Co., Ltd. Reactifs destines au dosage de l'oxygene actif
JP2005047898A (ja) * 2003-07-11 2005-02-24 Osaka Industrial Promotion Organization スルホン酸エステル化合物およびそれを用いた蛍光プローブ
WO2009110487A1 (fr) * 2008-03-04 2009-09-11 国立大学法人東京大学 Sonde fluorescente spécifique du peroxyde d'hydrogène
WO2012023487A1 (fr) * 2010-08-18 2012-02-23 学校法人同志社 Complexe métallique, sonde fluorescente

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001064664A1 (fr) * 2000-02-29 2001-09-07 Daiichi Pure Chemicals Co., Ltd. Reactifs destines au dosage de l'oxygene actif
JP2005047898A (ja) * 2003-07-11 2005-02-24 Osaka Industrial Promotion Organization スルホン酸エステル化合物およびそれを用いた蛍光プローブ
WO2009110487A1 (fr) * 2008-03-04 2009-09-11 国立大学法人東京大学 Sonde fluorescente spécifique du peroxyde d'hydrogène
WO2012023487A1 (fr) * 2010-08-18 2012-02-23 学校法人同志社 Complexe métallique, sonde fluorescente

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HITOMI, Y. ET AL.: "An Iron(III)-Monoamidate Complex Catalyst for Selective Hydroxylation of Alkane C-H Bonds with Hydrogen Peroxide", ANGEWANDTE CHEMIE, INTERNATIONAL EDITION, vol. 51, no. 14, April 2012 (2012-04-01), pages 3448 - 3452 *
HITOMI, Y.: "Hydrogen peroxide and metal complex - studies toward precise control of the reaction with hydrogen peroxide and sensitive detection of hydrogen peroxide", SCIENCE AND ENGINEERING REVIEW OF DOSHISHA UNIVERSITY, vol. 50, no. 4, 2010, pages 57 - 60 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112174946A (zh) * 2020-11-05 2021-01-05 四川大学华西医院 一种脂滴荧光探针及其合成方法和应用
CN112174946B (zh) * 2020-11-05 2023-03-21 四川大学华西医院 一种脂滴荧光探针及其合成方法和应用

Also Published As

Publication number Publication date
JP2014043417A (ja) 2014-03-13
JP5512764B2 (ja) 2014-06-04

Similar Documents

Publication Publication Date Title
Cao et al. Coumarin-based small-molecule fluorescent chemosensors
Chen et al. Fluorescent chemosensors based on spiroring-opening of xanthenes and related derivatives
Zhang et al. A colorimetric and ratiometric fluorescent probe for mercury (II) in lysosome
JP3345417B2 (ja) 巨環状希土類錯体，それを用いた螢光分析における干渉低減方法およびそれを用いて螢光分析における干渉を低減させる使用方法
Cho et al. Ratiometric fluorescence detection of Cu (II) with a keto-dipicolylamine ligand: A mechanistic implication
Cai et al. A chromenoquinoline-based two-photon fluorescent probe for the highly specific and fast visualization of sulfur dioxide derivatives in living cells and zebrafish
Qu et al. A fluorescence “switch-on” approach to detect hydrazine in aqueous solution at neutral pH
Zhang et al. A red-emitting fluorescent probe based on flavone for hydrazine detection and its application in aqueous solution
Sun et al. An efficient TP-FRET-based lysosome-targetable fluorescent probe for imaging peroxynitrite with two well-resolved emission channels in living cells, tissues and zebrafish
Sui et al. A BODIPY‐Based Water‐Soluble Fluorescent Probe for Mitochondria Targeting
Gogoi et al. NIR sensing of Zn (II) and subsequent dihydrogen phosphate detection by a benzothiazole functionalized ninhydrin based receptor
CN106749034A (zh) 对亚硫酸氢根和次氯酸根双响应比率型荧光标记试剂及其合成方法和应用
JP5800816B2 (ja) 金属錯体、蛍光プローブ
CN109897080A (zh) 高选择超灵敏肝癌特异性过氧化亚硝酸盐探针及其应用
Rabha et al. Cyclometalated iridium (iii) complex of a 1, 2, 3-triazole-based ligand for highly selective sensing of pyrophosphate ion
Farhi et al. Design and application of a tripodal on–off type chemosensor for discriminative and selective detection of Fe 2+ ions
Lv et al. A novel coumarin-benzopyrylium based near-infrared fluorescent probe for Hg2+ and its practical applications
CN109180716B (zh) 一种多信号比率型区分检测h2o2和h2s的荧光探针的设计、合成及应用
Sidhu et al. A naphthalimide-based novel “Turn-On” fluorescence approach for the determination of uric acid and monitoring of xanthine oxidase activity
JP5512764B2 (ja) 複素環化合物、金属錯体及び蛍光プローブ
Fang et al. Molecular Tweezers-like Calix [4] arene Based Alkaline Earth Metal Cation (Ca2+, Sr2+, and Ba2+) Chemosensor and Its Imaging in Living Cells and Zebrafish
Ahmmed et al. A deoxygenation-switch-based red-emitting fluorogenic light-up probe for the detection of highly toxic free bilirubin in human blood serum
Devasia et al. A Selective Excited‐State Intramolecular‐Proton‐Transfer (ESIPT) Sensor for Copper (II) Based on Chelation‐Enhanced Quenching and “Off‐On” Detection of Amino Acids
Rajalakshmi et al. A new recognition moiety diphenylborinate in the detection of pyruvate via Lewis acid/base sensing pathway and its bioimaging applications
Mohamed et al. A novel fluorescent probe with a pyrazolo [4, 3-c] quinoline core selectively recognizes c-MYC promoter G-quadruplexes

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13832850

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 13832850

Country of ref document: EP

Kind code of ref document: A1