CN107488151A - A kind of compound for being used to detect copper ion or prepare preventing and treating Alzheimer disease drug and preparation method thereof and product - Google Patents

A kind of compound for being used to detect copper ion or prepare preventing and treating Alzheimer disease drug and preparation method thereof and product Download PDF

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CN107488151A
CN107488151A CN201710752415.8A CN201710752415A CN107488151A CN 107488151 A CN107488151 A CN 107488151A CN 201710752415 A CN201710752415 A CN 201710752415A CN 107488151 A CN107488151 A CN 107488151A
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copper ion
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CN107488151B (en
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于会娟
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Guangdong University of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour

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Abstract

The present invention relates to biological technical field, more particularly to a kind of compound for being used to detect copper ion and prepare preventing and treating Alzheimer disease drug and preparation method thereof and product.The structural formula of the compound is as shown in Formulas I or Formula II.Two kinds of compounds of the present invention, using raw material that is cheap, being easy to get, product can obtain by one-step synthesis, reaction condition is gentle, simple；There is high selectivity to copper ion, detection limit, can the horizontal change of Sensitive Detection intracellular copper ion up to nanomole level；Part can chelate copper ion simultaneously, effectively suppress the crosslinking of the amyloid beta of copper ion induction, significantly reduce neurotoxicity caused by amyloid beta crosslinking, have important potential value in Alzheimer disease drugs research and development field.

Description

A kind of compound for being used to detect copper ion or prepare preventing and treating Alzheimer disease drug And preparation method thereof and product
Technical field
It is more particularly to a kind of to be used to detect copper ion or prepare preventing and treating Alzheimer the present invention relates to biological technical field Compound of disease drug and preparation method thereof and product.
Background technology
A kind of copper ion trace element necessary to be human body higher organs, is closed in many important physiology courses such as neurotransmitter Played an important role into being synthesized with metabolism, anti-oxidative defense, cellular respiration, bone.The metabolic disorder and alzheimer ' of copper ion The generation of the diseases such as silent disease, Parkinson's disease, Wei Ersenshi diseases, fatty liver, diabetes is closely related.Such as Alzheimer's disease, The copper ion of patient's brain higher concentration is one of key factor for causing amyloid-beta to be crosslinked and aoxidize.Copper ion detects Early diagnosis and treatment of the research of reagent and chelating agent to disease are significant.
At present the detection method of copper ion have atomic absorption spectrum, inductive atomic emission spectrum, inductive etc. from Daughter mass spectrum, electrochemical method, fluorescence spectrum etc..In numerous methods, fluorescence spectrum is as a kind of sensitive, quick, high flux Method be considered as optimal selection.A variety of copper ion fluorescence probe reports existing at present, such as Hongping Zhou reports Fluorescence off-on probes (Sensors and Actuators B 206 (2015) 640) based on triphenylamine skeleton, C.Huang, T.Kaur, Org etc. report rhodamine (Chem-Eur.J 14 (2008) 6892；Org Lett 14(2012) 14 406), and C.J.Fahrni etc. reports crown ether-like (Proc.Natl.Acad.Sci 102 (2005) 11179).These probes Alternative identification copper ion, and available for external and intracellular copper ion detection, but its shortcoming is synthesis step complexity, And detection limit is mostly micromole.Simultaneously current copper ion probe only possesses copper ion identification function, and can remove simultaneously Copper ion, suppress not having been reported that also for amyloid-beta (Amyloid β, A β) crosslinking.
The content of the invention
In view of this, the invention provides a kind of change for being used to detect copper ion or prepare preventing and treating Alzheimer disease drug Compound and preparation method thereof and product.Two kinds of compounds (saline parts) that the present invention reports, utilize original that is cheap, being easy to get Material, product can obtain by one-step synthesis, reaction condition is gentle, simple.Part has high selectivity, test limit to copper ion Degree, can the horizontal change of Sensitive Detection intracellular copper ion up to nanomole level.Part can chelate copper ion simultaneously, effectively suppress The crosslinking of the amyloid-beta of copper ion induction, neurotoxicity caused by amyloid-beta crosslinking is significantly reduced, in A Er Ci Haimo medicines research and development field has important potential value.
In order to realize foregoing invention purpose, the present invention provides following technical scheme：
The invention provides compound shown in a kind of Formulas I or Formula II, the structural formula of compound is as follows shown in Formulas I or Formula II：
Present invention also offers application of the compound in copper ion detection kit is prepared shown in Formulas I or Formula II.
Existing copper ion fluorescence probe synthesis step is complicated, and its detection limit is mostly micromole's level.What the present invention reported Two kinds of saline parts, using raw material that is cheap, being easy to get, product can obtain by one-step synthesis, reaction condition is gentle, letter It is single.Part has high selectivity to copper ion, and detection limit, can the horizontal change of Sensitive Detection intracellular copper ion up to nanomole level Change.
Present invention also offers compound shown in Formulas I or Formula II to prepare the application in preventing and treating Alzheimer disease drug.
Existing copper ion fluorescence probe can not suppress the amyloid-beta crosslinking of copper ion induction.The present invention report two Kind part can chelate copper ion, effectively suppress the crosslinking of the amyloid-beta of copper ion induction, significantly reduce beta amyloid Neurotoxicity caused by protein-crosslinking.
Present invention also offers a kind of preparation method of compound shown in Formulas I, and 2- imidazole formaldehydes and 1,2- phenylenediamine are existed Reacted in organic solvent, obtain compound shown in Formulas I.
Present invention also offers a kind of preparation method of compound shown in Formula II, by 4- imidazole formaldehydes and 1,2- phenylenediamine React in organic solvent, obtain compound shown in Formula II.
Preferably, organic solvent is absolute ethyl alcohol.
Preferably, the temperature of reaction is 75 DEG C~78 DEG C, the time of reaction is 12~14h.
In embodiment provided by the invention, the temperature of reaction is 78 DEG C, and the time of reaction is 12h.
In specific embodiment provided by the invention, the preparation method of compound is shown in Formulas I or Formula II：By 2- imidazoles first Aldehyde or 4- imidazole formaldehydes are dissolved by heating in absolute ethyl alcohol, and the ethanol solution containing 1,2- phenylenediamines, half an hour is added dropwise Add, mixed-liquor return reaction 12h；Reaction is precipitated after terminating, and is filtered, and solid is washed with absolute ethyl alcohol, absolute ether respectively Wash, be dried in vacuo.
Present invention also offers a kind of copper ion detection kit, including compound shown in Formulas I and/or Formula II.
Present invention also offers a kind of method of quick detection copper ion, will contain compound shown in Formulas I and/or Formula II Solution mixes with testing sample, observes solution colour, and solution colour becomes green, then contains copper ion in testing sample.
In embodiment provided by the invention, the solution containing compound shown in Formulas I is mixed with testing sample, observation is molten Liquid color, solution colour become yellow green, then contain copper ion in testing sample.
In embodiment provided by the invention, the solution containing compound shown in Formula II is mixed with testing sample, observed Solution colour, solution colour become light green color, then contain copper ion in testing sample.
Preferably, the composition containing the solution of compound shown in Formulas I and/or Formula II is：
Compound shown in Formulas I and/or Formula II：1~3mM；
DMSO：5~20% (v/v)；
Deionized water：Supply.
In embodiment provided by the invention, the composition containing the solution of compound shown in Formulas I and/or Formula II is：
Compound shown in Formulas I and/or Formula II：1mM；
DMSO：10% (v/v)；
Deionized water：Supply.
In quick detection copper ion method (colorimetric method) of the present invention, the detection of copper ion is limited to 1mM.
Present invention also offers a kind of method of fluoroscopic examination copper ion, will contain compound shown in Formulas I and/or Formula II Solution is mixed with testing sample, detects the fluorescence intensity change of solution, and the fluorescence intensity of solution is reduced, then contained in testing sample Copper ion.
In fluoroscopic examination copper ion method of the present invention, the detection of copper ion is limited to 10~40nM.
In the present invention, the copper ion detection of compound shown in Formulas I is limited to 10nM.
In the present invention, the copper ion detection of compound shown in Formula II is limited to 40nM.
In the present invention, the maximum excitation wavelength of fluoroscopic examination is 290~300nm, maximum emission wavelength is 340~ 360nm。
In embodiment provided by the invention, maximum excitation wavelength when detecting the fluorescence intensity of compound shown in Formulas I is 297nm, maximum emission wavelength 356nm.
In embodiment provided by the invention, maximum excitation wavelength when detecting the fluorescence intensity of compound shown in Formula II is 297nm, maximum emission wavelength 345nm.
In embodiment provided by the invention, the solution containing compound shown in Formulas I is mixed with testing sample, detection is molten The fluorescence intensity change of liquid, the fluorescence intensity of solution significantly reduce, then contain copper ion in testing sample.
In embodiment provided by the invention, the solution containing compound shown in Formula II is mixed with testing sample, detected The fluorescence intensity change of solution, the fluorescence of solution are quenched completely, then contain copper ion in testing sample.
Present invention also offers a kind of medicine, including compound shown in Formulas I and/or Formula II.
The invention provides it is a kind of be used for detect copper ion or prepare preventing and treating Alzheimer disease drug compound and its Preparation method and product.The structural formula of the compound is as shown in Formulas I or Formula II.The present invention at least has one of following advantage：
1st, two kinds of compounds (four tooth saline parts) of the invention, using raw material that is cheap, being easy to get, one-step synthesis is passed through Product is can obtain, reaction condition is gentle, simple.
2nd, two kinds of compound ligands of the invention have high selectivity to copper ion, and detection limit, can up to nanomole level The horizontal change of Sensitive Detection intracellular copper ion.
3rd, two kinds of compound ligands of the invention can chelate copper ion, effectively suppress β-amyloid of copper ion induction The crosslinking of albumen, significantly reduces neurotoxicity caused by amyloid-beta crosslinking, and field is researched and developed in Alzheimer disease drugs With important potential value.
Brief description of the drawings
Fig. 1 shows ligand L 1, L2 colorimetric detection copper ions；
Fig. 2 shows the fluoroscopic examination copper ion of ligand L 1；
Fig. 3 shows the fluoroscopic examination copper ion of ligand L 2；
Fig. 4 shows ligand L 1, L2 fluoroscopic examination intracellular copper ion change in concentration；
Fig. 5 shows that SDS-PAGE electrophoretic analysis part suppresses the A β that copper ion induces and is crosslinked, [A β]=10 μM, [CuSO4]= 5 μM, [L]=0-100 μM；Wherein 5-1 is electrophoretogram, and 5-2 is the block diagram that 5-1 is drawn according to fluorescence intensity；
Fig. 6 shows MTT test U251 cells and A β, A β-CuCl2、Aβ-CuCl2- L is incubated cell survival after 24 hours jointly Rate (A β:CuCl2:L=1:0.5:1, [A β]=10 μM).
Embodiment
The invention discloses it is a kind of be used for detect copper ion or prepare preventing and treating Alzheimer disease drug compound and its Preparation method and product, those skilled in the art can use for reference present disclosure, be suitably modified technological parameter realization.Especially need to refer to Go out, all similar replacements and change are apparent to those skilled in the art, and they are considered as including In the present invention.The method of the present invention and application are described by preferred embodiment, and related personnel can substantially not take off Method described herein and application are modified or suitably change and combine from present invention, spirit and scope, is come real Now and using the technology of the present invention.
Provided by the present invention for the compound and its preparation of detection copper ion or preparation preventing and treating Alzheimer disease drug Raw materials used or auxiliary material, reagent can be bought by market in method and product.
In the examples below, compound is defined as L1 shown in Formulas I；Compound is defined as L2 shown in Formula II.
Formulas I Chinese：(1- (1H- imidazoles -2-) methylamine of N, N'- (1,2- phenylenes) two；
Formulas I English name：N,N'-(1,2-phenylene)bis(1-(1H-imidazol-2-yl)methanimine).
Formula II Chinese：(1- (1H- imidazoles -4-) methylamine of N, N'- (1,2- phenylenes) two；
Formula II English name：N,N'-(1,2-phenylene)bis(1-(1H-imidazol-4-yl) methanimine)。
With reference to embodiment, the present invention is expanded on further：
The L1 of embodiment 1 synthesis
10mM (0.96g) 2- imidazole formaldehydes are dissolved by heating in 10mL absolute ethyl alcohol, 10mL is added dropwise dissolved with 5mM The absolute ethyl alcohol of (0.54g) 1,2- phenylenediamines, solution colour gradually become yellow, and half an hour adds, and (78 DEG C) of mixed liquor returns Stream reaction 12h.Reaction obtains substantial amounts of white precipitate after terminating, and filters, and solid uses absolute ethyl alcohol respectively, and absolute ether washs, Vacuum drying, obtains white powdery solids, yield：62.1%, ES-MS (C2H5OH):265.1([M+H]+).Reflected through structure Fixed, the structure of ligand L 1 is shown in formula I：
The L2 of embodiment 2 synthesis
10mM (0.96g) 4- imidazole formaldehydes are dissolved by heating in 10mL absolute ethyl alcohol, 10mL is added dropwise dissolved with 5mM The absolute ethyl alcohol of (0.54g) 1,2- phenylenediamines, solution colour gradually become brown, and half an hour adds, and (78 DEG C) of mixed liquor returns Stream reaction 12h.Reaction obtains substantial amounts of taupe precipitation after terminating, filter, solid uses absolute ethyl alcohol respectively, and absolute ether is washed Wash, be dried in vacuo, obtain taupe crystallite, yield：50.2%, ES-MS (C2H5OH):265.1([M+H]+).Through Structural Identification, The structure of ligand L 2 is as shown in Formula II：
Embodiment 3 L1, L2 colorimetric detection copper ion
Compound concentration is 1mM ligand solution (10%DMSO, 90%H2O), it is molten that different metal ions M is added dropwise into solution Liquid (M=Li+、Na+、K+、Ca2+、Mg2+、Ba2+、Al3+、Cd2+、Co2+、 Hg2+、Fe2+、Ni2+、Zn2+、Cu2+, 10%DMSO, 90%H2O), solution colour change is observed, as shown in figure 1, solution colour greening person (L1 is changed into yellow green, and L2 is changed into light green color) As copper ion, copper ion concentration are about 1mM.
The L1 fluoroscopic examination copper ions of embodiment 4
Compound concentration is 10nM L1 solution (10%DMSO, 90%H2O), solution fluorescence spectrum (λ is testedex=297nm, λem=356nm), different metal ions M solution (M=Li is added dropwise into solution+、 Na+、K+、Ca2+、Mg2+、Ba2+、Al3+、Cd2+、 Co2+、Hg2+、Fe2+、Ni2+、Zn2+、Cu2+, 10%DMSO, 90%H2O), as shown in Fig. 2 add after the L1 fluorescence persons of significantly reducing For copper ion, copper ion concentration is about 10nM.
The L2 fluoroscopic examination copper ions of embodiment 5
Compound concentration is 10nM L2 solution (10%DMSO, 90%H2O), solution fluorescence spectrum (λ is testedex=297nm, λem=345nm), different metal ions (M) solution (M=Li is added dropwise into solution+、 Na+、K+、Ca2+、Mg2+、Ba2+、Al3+、Cd2 +、Co2+、Hg2+、Fe2+、Ni2+、Zn2+、Cu2+, 10%DMSO, 90%H2O), as shown in figure 3, L2 fluorescence is quenched completely after adding The person of going out is copper ion, and copper ion concentration is about 40nM.
Embodiment 6 L1, L2 fluoroscopic examination intracellular copper ion is horizontal
Cell is laid in 96 well culture plates, 4000-5000/ holes, after being incubated 24 hours in cell culture incubator, to culture medium Middle addition various concentrations Cu2+Solution, it is 25 μM, 50 μM, 100 μM, 200 μM to make copper ion concentration.After 37 DEG C are incubated 24 hours, Nutrient solution is sucked, adds the fresh medium containing 10 μM of L1/L2, is incubated 2 hours, is sucked nutrient solution, determine and match somebody with somebody under ELIASA Body fluorescence, as shown in figure 4, as intracellular copper ion concentration is higher, the fluorescence of part gradually reduces, and says that part can detect carefully Intracellular copper ion concentration changes.
SDS-PAGE electrophoresis detections L1, L2 of embodiment 7 suppress the A β crosslinking abilities of copper ion induction
Prepare A β, A β-CuCl2、Aβ-CuCl2Three groups of solution (A β of-L:CuCl2:L=1:0.5:1, [A β]=10 μM), 37 After DEG C lucifuge is incubated 2 hours, the change of SDS-PAGE electrophoretic analysis A beta monomers bands.As shown in figure 5, A β are mono- after adding copper ion The amount of body substantially reduces, and illustrates that copper ion can induce A β crosslinkings, the amount with the increase A beta monomers of ligand concentration gradually increases, said Bright part can effectively suppress the A β crosslinkings of copper ion induction.
The MTT of embodiment 8 measure L1, L2 suppress neurotoxicity caused by A β crosslinkings
Cell is laid in 96 well culture plates, 4000-5000/ holes, after being incubated 24 hours in cell culture incubator, be separately added into Aβ、Aβ-CuCl2、Aβ-CuCl2- L solution (A β:CuCl2:L=1:0.5:1, [A β]=10 μM).After 37 DEG C are incubated 24 hours, 20 μ L 5mg/mL MTT solution is added, continues to be incubated 4 hours, sucks nutrient solution, adds 100 μ L DMSO, the shake of shaking table low speed Swing 5 minutes, OD values at 579nm are determined under ELIASA, calculate cell survival rate, as shown in fig. 6, being incubated 24 hours jointly with A β Afterwards, cell survival rate 28%, after adding copper ion, cell survival rate is only 5%, and cell survival rate increases to after adding part 45% and 31%, illustrate that part can effectively suppress neurotoxicity caused by A β crosslinkings.
Described above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art For member, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications also should It is considered as protection scope of the present invention.

Claims (10)

  1. A kind of 1. compound shown in Formulas I or Formula II：
  2. 2. the answering in preparing copper ion detection kit or preventing and treating Alzheimer disease drug of compound shown in Formulas I or Formula II With.
  3. 3. the preparation method of compound shown in a kind of Formulas I, it is characterised in that by 2- imidazole formaldehydes and 1,2- phenylenediamine organic molten Reacted in agent, obtain compound shown in Formulas I.
  4. 4. the preparation method of compound shown in a kind of Formula II, it is characterised in that by 4- imidazole formaldehydes and 1,2- phenylenediamine organic Reacted in solvent, obtain compound shown in Formula II.
  5. 5. the preparation method according to claim 3 or 4, it is characterised in that the organic solvent is absolute ethyl alcohol.
  6. 6. the preparation method according to claim 3 or 4, it is characterised in that the temperature of the reaction is 75 DEG C~78 DEG C, instead The time answered is 12~14h.
  7. 7. a kind of copper ion detection kit, it is characterised in that including compound shown in Formulas I and/or Formula II.
  8. A kind of 8. method of quick detection copper ion, it is characterised in that by the solution containing compound shown in Formulas I and/or Formula II Mixed with testing sample, observe solution colour, solution colour becomes green, then contains copper ion in testing sample.
  9. A kind of 9. method of fluoroscopic examination copper ion, it is characterised in that by the solution containing compound shown in Formulas I and/or Formula II Mixed with testing sample, detect the fluorescence intensity change of solution, the fluorescence intensity of solution reduces, then in testing sample containing copper from Son.
  10. 10. a kind of medicine, it is characterised in that including compound shown in Formulas I and/or Formula II.
CN201710752415.8A 2017-08-28 2017-08-28 It is a kind of for detecting the compound and preparation method thereof and product of copper ion or preparation prevention and treatment Alzheimer disease drug Expired - Fee Related CN107488151B (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109946280A (en) * 2019-03-29 2019-06-28 南京工业大学 A method of with ratio metering type fluorescence probe quantitative detection solubility amyloid beta
CN111808096A (en) * 2020-06-30 2020-10-23 广东工业大学 Novel ligand for copper ion detection, preparation thereof, novel ruthenium complex and near-infrared long-life fluorescent probe
KR20210114790A (en) * 2020-03-11 2021-09-24 한국과학기술원 Composition for preventing, improving or treating Alzheimer's disease comprising N,N′-Diacetyl-p-phenylenediamine as an active ingredient

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107043353A (en) * 2016-11-16 2017-08-15 齐鲁工业大学 A kind of imidazoles benzaldehyde-p-phenylenediamine bi-schiff base and preparation method thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107043353A (en) * 2016-11-16 2017-08-15 齐鲁工业大学 A kind of imidazoles benzaldehyde-p-phenylenediamine bi-schiff base and preparation method thereof

Non-Patent Citations (11)

* Cited by examiner, † Cited by third party
Title
ASHIS K. PATRA ET AL.: "Stable Eight-Coordinate Iron(III/II) Complexes", 《INORG. CHEM.》 *
DURAISAMY UDHAYAKUMARI ET AL.: "Colorimetric and Fluorescent chemosensors for Cu2+. A comprehensive review from the year 2013-15", 《ANALYTICAL METHODS》 *
JEANET CONRADIE ET AL.: "Square-Antiprismatic Eight-Coordinate Complexes of Divalent First-Row Transition Metal Cations: A Density Functional Theory Exploration of the Electronic-Structural Landscape", 《INORG. CHEM.》 *
JINN-FWU SHEU ET AL.: "Magnetic Properties and Mossbauer Spectra of Binuclear Copper(lI) and Tetranuclear Diiron(III)-porphyrin-dicopper(II) Complexes with Schiff-Base Ligands of 2-lmidazolealdehyde and Acetylpyrazine", 《JOURNAL OF THE CHINESE CHEMICAL SOCIETY》 *
JUAN BU ET AL.: "Fluorescence sensors for Cu2+ based on conjugated indole Schiff base", 《RES CHEM INTERMED》 *
KOUSTUBH S. DUBE ET AL.: "Structure and properties of an eight-coordinate Mn(II) complex that demonstrates a high water relaxivity", 《DALTON TRANS.》 *
PREETI SALUJA ET AL.: "A benzimidazole-based fluorescent sensor for Cu2+ and its complex with a phosphate anion formed through a Cu2+ displacement approach", 《TETRAHEDRON LETTERS》 *
SANDRA W. S. CHOY ET AL.: "Cooperative Catalysis: Large Rate Enhancements with Bimetallic Rhodium Complexes", 《ORGANOMETALLICS》 *
XINGJIAN WANG ET AL.: "Schiff based fluorescence probes for Cu2+ based on imidazole and benzimidazole", 《SENSORS AND ACTUATORS B》 *
于会娟等: "基于Saline四齿配体的铜离子荧光探针及β-淀粉样蛋白交联抑制剂研究", 《中国化学会第八届全国配位化学会议论文集—口头报告》 *
姜招峰: "《阿尔茨海默病发病机理及其相关生物活性物质研究》", 30 June 2016 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109946280A (en) * 2019-03-29 2019-06-28 南京工业大学 A method of with ratio metering type fluorescence probe quantitative detection solubility amyloid beta
KR20210114790A (en) * 2020-03-11 2021-09-24 한국과학기술원 Composition for preventing, improving or treating Alzheimer's disease comprising N,N′-Diacetyl-p-phenylenediamine as an active ingredient
CN111808096A (en) * 2020-06-30 2020-10-23 广东工业大学 Novel ligand for copper ion detection, preparation thereof, novel ruthenium complex and near-infrared long-life fluorescent probe
CN111808096B (en) * 2020-06-30 2022-10-21 广东工业大学 Novel ligand for copper ion detection, preparation thereof, novel ruthenium complex and near-infrared long-life fluorescent probe

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