CN112552238A - Novel trimeric rare earth europium complex and preparation method thereof - Google Patents
Novel trimeric rare earth europium complex and preparation method thereof Download PDFInfo
- Publication number
- CN112552238A CN112552238A CN202011216580.XA CN202011216580A CN112552238A CN 112552238 A CN112552238 A CN 112552238A CN 202011216580 A CN202011216580 A CN 202011216580A CN 112552238 A CN112552238 A CN 112552238A
- Authority
- CN
- China
- Prior art keywords
- formula
- rare earth
- complex
- compound shown
- compound
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
- 229910052761 rare earth metal Inorganic materials 0.000 title claims abstract description 52
- 150000002910 rare earth metals Chemical class 0.000 title claims abstract description 46
- 229910052693 Europium Inorganic materials 0.000 title claims abstract description 38
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title abstract description 12
- 238000010668 complexation reaction Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 67
- 239000000126 substance Substances 0.000 claims abstract description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 48
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- 238000003756 stirring Methods 0.000 claims description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 23
- 239000002904 solvent Substances 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- XKRFYHLGVUSROY-UHFFFAOYSA-N argon Substances [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 10
- 238000005406 washing Methods 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 5
- 229910020667 PBr3 Inorganic materials 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 238000013375 chromatographic separation Methods 0.000 claims description 5
- 235000015165 citric acid Nutrition 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 239000002244 precipitate Substances 0.000 claims description 5
- 230000001681 protective effect Effects 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 5
- PSELCIMQRLODQE-UHFFFAOYSA-N tert-butyl 6-bromohexanoate Chemical compound CC(C)(C)OC(=O)CCCCCBr PSELCIMQRLODQE-UHFFFAOYSA-N 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 claims description 2
- 238000001514 detection method Methods 0.000 abstract description 14
- 239000000463 material Substances 0.000 abstract description 7
- 230000008033 biological extinction Effects 0.000 abstract description 4
- 230000035945 sensitivity Effects 0.000 abstract description 4
- 239000007850 fluorescent dye Substances 0.000 abstract description 3
- 102000004169 proteins and genes Human genes 0.000 abstract description 3
- 239000000090 biomarker Substances 0.000 abstract description 2
- 108090000623 proteins and genes Proteins 0.000 abstract 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- 239000000243 solution Substances 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- -1 crown ether rare earth Chemical class 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 4
- 125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000002096 quantum dot Substances 0.000 description 3
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 3
- 108091005461 Nucleic proteins Proteins 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 239000002739 cryptand Substances 0.000 description 2
- 238000000295 emission spectrum Methods 0.000 description 2
- 238000001506 fluorescence spectroscopy Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- NLMDJJTUQPXZFG-UHFFFAOYSA-N 1,4,10,13-tetraoxa-7,16-diazacyclooctadecane Chemical compound C1COCCOCCNCCOCCOCCN1 NLMDJJTUQPXZFG-UHFFFAOYSA-N 0.000 description 1
- CWGFSQJQIHRAAE-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol tetrahydrochloride Chemical compound Cl.Cl.Cl.Cl.OCC(N)(CO)CO CWGFSQJQIHRAAE-UHFFFAOYSA-N 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000012154 double-distilled water Substances 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- GWQVMPWSEVRGPY-UHFFFAOYSA-N europium cryptate Chemical compound [Eu+3].N=1C2=CC=CC=1CN(CC=1N=C(C=CC=1)C=1N=C(C3)C=CC=1)CC(N=1)=CC(C(=O)NCCN)=CC=1C(N=1)=CC(C(=O)NCCN)=CC=1CN3CC1=CC=CC2=N1 GWQVMPWSEVRGPY-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 238000002189 fluorescence spectrum Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 150000008040 ionic compounds Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- RXNXLAHQOVLMIE-UHFFFAOYSA-N phenyl 10-methylacridin-10-ium-9-carboxylate Chemical compound C12=CC=CC=C2[N+](C)=C2C=CC=CC2=C1C(=O)OC1=CC=CC=C1 RXNXLAHQOVLMIE-UHFFFAOYSA-N 0.000 description 1
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/003—Compounds containing elements of Groups 3 or 13 of the Periodic Table without C-Metal linkages
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1044—Heterocyclic compounds characterised by ligands containing two nitrogen atoms as heteroatoms
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/18—Metal complexes
- C09K2211/182—Metal complexes of the rare earth metals, i.e. Sc, Y or lanthanide
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Materials Engineering (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
Abstract
The invention discloses a novel trimeric rare earth europium complex and a preparation method thereof, wherein the complex has a chemical structural formula shown as the following formula (I); wherein the chemical structural formula of the complex MO is shown as the following formula (II):
the novel trimeric rare earth europium complex provided by the invention is coordinated with rare earth europium through a poly cryptate compound to form a fluorescent material capable of being applied with a biomarker, and the molar extinction coefficient of the novel trimeric rare earth europium complex can be improved by about 4 times (80000M) compared with that of the conventional product‑1cm‑1) Can improve the sensitivity and the accuracy of detection, and is suitable for being used as a fluorescent dye molecule to mark nucleic acidAnd biomolecules such as proteins for use in detection in the biomedical field.
Description
Technical Field
The invention relates to the technical field of coordination compound preparation, in particular to a novel trimeric rare earth europium coordination compound and a preparation method thereof.
Background
Time-resolved fluorescence resonance energy transfer techniques utilize energy transfer of two fluorophores, referred to as an (energy) donor and an (energy) acceptor, respectively, wherein the donor is excited by an external energy source (e.g., a flash lamp or a laser) and can transfer energy resonance to the acceptor if it is within a sufficiently close distance from the acceptor; the receptor is excited to emit light of a specific wavelength. The technology mainly utilizes a long-life fluorescence donor combined with a time-resolved detection method to eliminate biological autofluorescence (fluorescence lifetime of a few nanoseconds) interference. Its advantages are high sensitivity and reliability, and low false positive rate of test result. And the experimental mode is easy to operate, and the experimental time and the cost are saved. The key point of the technology is how to select a proper fluorescent marker as a donor, and the fluorescent markers which are researched more at home and abroad can be divided into organic molecular fluorescent compounds (such as acridinium ester and luminol for chemiluminescence) Quantum Dots (QDs) and metal fluorescent complexes (such as terpyridyl ruthenium for electrochemiluminescence). The organic compound type fluorescent marker generally has the problems of high quenching rate, instability under the illumination condition and the like. The quantum dots have the problems of much nonspecific adsorption and poor interference resistance in complex biological samples.
The rare earth fluorescent complex is an ideal material as a fluorescence donor in a time-resolved fluorescence resonance energy transfer technology due to the characteristics of small molecular weight, easy modification, good light excitation stability, strong anti-interference capability and the like. These types of fluorescent complexes have several basic properties: 1) the fluorescent material has longer fluorescence lifetime, and can eliminate the interference of background fluorescence; 2) the method has high fluorescence quantum yield and improves the utilization rate of light energy; 3) the ligand and the central metal ion can form a stable structure, and the stability of the marker molecule in a complex biological environment is guaranteed. Therefore, the fluorescent complex is an ideal material as a fluorescence donor in the time-resolved fluorescence resonance energy transfer technology and is the most critical part for improving the sensitivity of the technology. The rare earth fluorescent complex can be divided into crown ether rare earth complex, beta-diketone rare earth complex, cryptand ether rare earth complex, calixarene rare earth complex and the like. The cryptate has a three-dimensional cavity, metal ions can be strongly pulled into a space lattice to form a stable rare earth complex, and the cryptate has strong fluorescence. The complex formed by the cryptate and the rare earth metal is an ionic compound, and the cryptate structure contains hydrophilic oxygen atoms, so that the cryptate is easy to label in a cell environment and is an ideal material of a fluorescence donor.
At present, although various cave-shaped coordination compounds have been reported at home and abroad, the practical application is not so much, and an ideal cave-shaped coordination compound must have high molar absorption coefficient, high luminous efficiency, long fluorescence life, good water solubility and excited state chemical stability (difficult to quench by ocean gas, water and the like), and easy biomolecular labeling.
The rare earth cryptate fluorescent complexes which have been commercialized are very few, such as developed by Cisbio of France and applied to drug screening Eu3+,Tb3+The cryptate complex can be sold, but the price is very expensive, the price is more than 1 ten thousand/mg, and the complex has more synthesis steps and extremely low yield; furthermore, the solubility of the compound is not ideal, which complicates the labeling process. For example, the rare earth cryptand ether fluorescent complex shown in the formula A has a molar extinction coefficient of 20000M-1cm-1Left and right, the detection limit can only reach 10 when the method is used for detecting the index-9g/L, can not meet the requirements of partial detection indexes.
In order to meet the requirements of more detection indexes, a novel fluorescent material which is high in molar extinction coefficient and easy to mark is urgently needed to be provided.
Disclosure of Invention
The technical problem to be solved by the present invention is to provide a novel trimeric rare earth europium complex and a preparation method thereof, aiming at the defects in the prior art.
In order to solve the technical problems, the invention adopts the technical scheme that: a novel trimeric rare earth europium complex is provided, which has a chemical structural formula shown as the following formula (I):
wherein the chemical structural formula of the complex MO is shown as the following formula (II):
the invention also provides a preparation method of the novel trimeric rare earth europium complex, and the synthetic route of the complex MO is as follows:
preferably, the preparation method of the complex MO comprises the following steps:
1) dissolving the compound shown as the formula (II-1) in ultra-dry tetrahydrofuran, and then dripping PBr3Stirring at room temperature, adding dichloromethane, washing the solution with water, draining the solvent, and recrystallizing to obtain the compound shown in formula (II-2);
2) dissolving the compound shown as the formula (II-2) in ultra-dry acetonitrile, slowly dropwise adding ethylenediamine in nitrogen protective atmosphere under ice bath condition, stirring at room temperature, draining the solvent, and recrystallizing to obtain the compound shown as the formula (II-3);
3) adding anhydrous EuCl into a dehydrated and deoxidized two-neck flask under the protection of argon3And dehydrated and deoxygenated methanol, stirring, dropwise adding an acetonitrile solution of the compound represented by the formula (II-3) into the obtained white suspension, and stirring at room temperature overnight; after the reaction is finished, filtering, and washing the solid with diethyl ether to obtain the compound shown as the formula (II), namely the compound MO.
Preferably, the preparation method of the complex MO comprises the following steps:
1) dissolving the compound shown as the formula (II-1) in ultra-dry tetrahydrofuran, and then dripping PBr3Stirring for 2h at room temperature, adding dichloromethane, washing the solution with water, draining the solvent, and recrystallizing to obtain the compound shown in the formula (II-2);
2) dissolving the compound shown as the formula (II-2) in ultra-dry acetonitrile, slowly dropwise adding ethylenediamine in nitrogen protective atmosphere under ice bath condition, stirring for 3h at room temperature, draining the solvent, and recrystallizing to obtain the compound shown as the formula (II-3);
3) adding anhydrous EuCl into a dehydrated and deoxidized two-neck flask under the protection of argon3And dehydrated and deoxidized methanol, stirring for 0.5h, adding an acetonitrile solution of the compound shown in the formula (II-3) dropwise into the obtained white suspension, and stirring at room temperature overnight; after the reaction is finished, filtering, and washing the solid by using ethyl ether to obtain the compound shown as the formula (II), namely the compound MO.
Preferably, the novel trimeric rare earth europium complex is characterized by comprising the following synthetic route:
preferably, the preparation method of the novel trimeric rare earth europium complex comprises the following steps:
step 2, dissolving the compound shown as the formula (I-1) in methanol, adjusting pH, separating out a precipitate, filtering, and drying filter residues to obtain the compound shown as the formula (I-2);
and 3, dissolving the compound and the complex MO shown as the formula (I-2) in ultra-dry dichloromethane at room temperature, dropwise adding a dichloromethane solution of DCC, stirring, draining the solvent, and performing chromatographic separation to obtain the novel trimeric rare earth europium complex shown as the formula (I).
Preferably, the preparation method of the novel trimeric rare earth europium complex comprises the following steps:
step 2, dissolving the compound shown as the formula (I-1) in methanol, adjusting the pH value to 1-2 by using HCl, separating out a precipitate, filtering, and drying filter residues to obtain the compound shown as the formula (I-2);
and 3, dissolving the compound and the complex MO shown as the formula (I-2) in ultra-dry dichloromethane at room temperature, dropwise adding a dichloromethane solution of DCC, stirring for 2 hours, draining the solvent, and performing chromatographic separation to obtain the novel trimeric rare earth europium complex shown as the formula (I).
The invention has the beneficial effects that: the novel trimeric rare earth europium complex provided by the invention is coordinated with rare earth europium through a poly cryptate compound to form a fluorescent material capable of being applied with a biomarker, and the molar extinction coefficient of the novel trimeric rare earth europium complex can be improved by about 4 times (80000M) compared with that of the conventional product-1cm-1) The method can improve the sensitivity and accuracy of detection, and is suitable for being used as fluorescent dye molecules to mark biomolecules such as nucleic acid and protein for detection in the field of biomedicine.
Drawings
FIG. 1 shows the results of H-NMR detection of the compound (II-2) in example 2 of the present invention;
FIG. 2 is a result of H-NMR measurement of the compound (II-3) in example 2 of the present invention;
FIG. 3 is a result of H-NMR measurement of the compound (I-1) in example 2 of the present invention;
FIG. 4 shows the result of H-NMR detection of the compound (I-2) in example 2 of the present invention;
FIG. 5 is an absorption spectrum of the novel trimeric rare earth europium complex in example 3 of the invention;
FIG. 6 is a graph showing the emission spectrum of the novel trimeric rare earth europium complex in example 3 of the present invention.
Detailed Description
The present invention is further described in detail below with reference to examples to enable those skilled in the art to practice the invention with reference to the description.
It will be understood that terms such as "having," "including," and "comprising," as used herein, do not preclude the presence or addition of one or more other elements or groups thereof.
Example 1
This example provides a novel trimeric rare earth europium complex, which has the following chemical structural formula (I):
wherein the chemical structural formula of the complex MO is shown as the following formula (II):
example 2
This example provides a method for preparing a novel trimeric rare earth europium complex as described in example 1, wherein the synthetic route is as follows:
the synthetic route of the complex MO is as follows:
in a preferred embodiment, the preparation method of the novel trimeric rare earth europium complex comprises the following steps:
firstly, synthesizing a complex MO:
1) the compound represented by the formula (II-1) (0.69g,1.07mmol) was dissolved in 15ml of ultra-dry tetrahydrofuran, followed by dropwise addition of PBr3(1.28mmol), stirring at room temperature for 2h, adding 150ml of dichloromethane, washing the solution with water, draining the solvent, and recrystallizing to obtain the compound shown in the formula (II-2); the results of H-NMR measurement are shown in FIG. 1, and the data for structural confirmation are:1H-NMR(400MHz,CDCl3): 1.19(m,36H,CH3),3.62，3.65(s,8H,CH2),4.38(s,2H,CH2),6.53.6.29(d,8H, CH2CH2),7.72-7.97(m,3H,Ar)；
2) dissolving a compound shown as a formula (II-2) (1mmol) in ultra-dry acetonitrile, slowly dropwise adding ethylenediamine (1ml) in nitrogen protective atmosphere under ice bath condition, stirring for 3h at room temperature, draining the solvent, and recrystallizing to obtain a compound shown as a formula (II-3); the H-NMR result is shown in FIG. 2, and the nuclear magnetic data is as follows:1H-NMR(400MHz,CDCl3):1.19(m,36H,CH3),2.77(m,4H, NHCH2CH2NH2),3.62，3.52(s,8H,CH2),4.25(s,2H,CH2),6.57.6.30(d,8H, CH2CH2),7.75-7.93(m,3H,Ar)；
3) adding anhydrous EuCl into a dehydrated and deoxidized 100mL two-neck flask under the protection of argon3(0.1496mmol) and dehydrated and deoxygenated methanol (30mL) were stirred for 0.5h, and then an acetonitrile solution (20 mL) of the compound represented by the formula (II-3) (0.0499mmol) was added dropwise to the resulting white suspension, followed by stirring at room temperature overnight; after the reaction is finished, filtering, and washing the solid by using no diethyl ether to obtain the compound shown as the formula (II), namely the compound MO.
Secondly, synthesizing a novel trimeric rare earth europium complex:
step 2, dissolving the compound (1mmol) shown in the formula (I-1) in 15ml of methanol, adjusting the pH value to 1-2 by using 1M HCl, separating out a precipitate, filtering, and drying filter residues to obtain the compound shown in the formula (I-2); the H-NMR result is shown in FIG. 4, and the nuclear magnetic data is as follows:1H-NMR(400MHz, CDCl3):1.42(s,9H,CH3),1.64(m,6H,CH2CH2),2.33(s,4H,COCH2),3.55(m,2H, OCH2)；
and 3, dissolving the compound (0.1mmol) shown in the formula (I-2) and the complex MO (0.3mmol) in 100ml of ultra-dry dichloromethane at room temperature, dropwise adding a dichloromethane solution of DCC (0.3mmol of DCC in 50ml of ultra-dry dichloromethane), stirring for 2 hours, draining the solvent, and carrying out chromatographic separation to obtain the novel trimeric rare earth europium complex shown in the formula (I).
Example 3 fluorescence Spectroscopy detection of rare earth europium cryptate fluorescent Complex
The detection method comprises the following steps: a10.0 mL volumetric flask was charged with the dimethyl sulfoxide stock solution (10. mu.g/mL, 1mL) of the rare earth europium cryptate fluorescent complex synthesized in example 2, and Tris (hydroxymethyl) aminomethane-hydrochloric acid (Tris-HCl) buffer solution (1X 10)-3mol/L, 1mL) and double distilled water (3mL), diluted to the scale with dimethyl sulfoxide solution, shaken well, left at room temperature for L0min, transferred to an lcm quartz cuvette (Cary Eclipse fluorescence spectrophotometer, VARIAN, USA) for fluorescence spectroscopy.
The detection results are shown in fig. 5-6, fig. 5 is an absorption spectrum of the rare earth europium crypt ether fluorescent complex, and fig. 6 is an emission spectrum of the rare earth europium crypt ether fluorescent complex. It can be seen that the signal of fluorescence emission is stable, and can form fluorescence emission spectrum with specific peak form, and the peak value of fluorescence emission peak is high, so that it shows that rare earth europium cavity etherTrimer in fluorescent complex to Eu in rare earth metal ion3+The rare earth europium cryptate ether fluorescent complex is suitable for being used as a fluorescent dye molecule to mark biomolecules such as nucleic acid and protein and the like for detection in the field of biomedicine.
While embodiments of the invention have been disclosed above, it is not limited to the applications listed in the description and the embodiments, which are fully applicable in all kinds of fields of application of the invention, and further modifications may readily be effected by those skilled in the art, and the invention is thus not limited to the specific details without departing from the generic concept defined in the claims and the equivalent scope.
Claims (7)
1. A novel trimeric rare earth europium complex is characterized by having a chemical structural formula shown as the following formula (I):
wherein the chemical structural formula of the complex MO is shown as the following formula (II):
2. the method for preparing the novel trimeric rare earth europium complex as claimed in claim 1, wherein the synthesis route of the complex MO is as follows:
3. the method for preparing novel trimeric rare earth europium complex according to claim 2, wherein the method for preparing the complex MO comprises the following steps:
1) dissolving the compound shown as the formula (II-1) in ultra-dry tetrahydrofuran, and then dripping PBr3Stirring at room temperature, adding dichloromethane, washing the solution with water, draining the solvent, and recrystallizing to obtain a compound shown in formula (II-2);
2) dissolving the compound shown as the formula (II-2) in ultra-dry acetonitrile, slowly dropwise adding ethylenediamine in nitrogen protective atmosphere under ice bath condition, stirring at room temperature, draining the solvent, and recrystallizing to obtain the compound shown as the formula (II-3);
3) adding anhydrous EuCl into a dehydrated and deoxidized two-neck flask under the protection of argon3And dehydrated and deoxidized methanol, stirring, adding dropwise an acetonitrile solution of the compound represented by the formula (II-3) to the obtained white suspension, and stirring at room temperature overnight; after the reaction is finished, filtering, and washing the solid with diethyl ether to obtain the compound shown as the formula (II), namely the compound MO.
4. The method for preparing novel trimeric rare earth europium complex according to claim 3, wherein the method for preparing the complex MO comprises the following steps:
1) dissolving the compound shown as the formula (II-1) in ultra-dry tetrahydrofuran, and then dripping PBr3Stirring for 2h at room temperature, adding dichloromethane, washing the solution with water, draining the solvent, and recrystallizing to obtain the compound shown in the formula (II-2);
2) dissolving the compound shown as the formula (II-2) in ultra-dry acetonitrile, slowly dropwise adding ethylenediamine in nitrogen protective atmosphere under ice bath condition, stirring for 3h at room temperature, draining the solvent, and recrystallizing to obtain the compound shown as the formula (II-3);
3) adding anhydrous EuCl into a dehydrated and deoxidized two-neck flask under the protection of argon3And dehydrated and deoxidized methanol, stirring for 0.5h, adding an acetonitrile solution of the compound represented by the formula (II-3) dropwise into the obtained white suspension, and stirring at room temperature overnight; after the reaction is finished, filtering, and washing the solid with diethyl ether to obtain the compound shown as the formula (II), namely the compound MO.
5. The method for preparing novel trimeric rare earth europium complex according to any one of claims 2 to 4, wherein the synthetic route of the novel trimeric rare earth europium complex is as follows:
6. the method for preparing novel trimeric rare earth europium complex as claimed in claim 5, which comprises the following steps:
step 1, adding 2-hydroxy propane-1, 2, 3-tricarboxylic acid, 6-bromohexanoic acid tert-butyl ester and EDC into toluene, refluxing and heating, cooling, standing, and separating to obtain a compound shown as a formula (I-1);
step 2, dissolving the compound shown as the formula (I-1) in methanol, adjusting pH, separating out a precipitate, filtering, and drying filter residues to obtain the compound shown as the formula (I-2);
and 3, dissolving the compound and the complex MO shown as the formula (I-2) in ultra-dry dichloromethane at room temperature, dropwise adding a dichloromethane solution of DCC, stirring, draining the solvent, and performing chromatographic separation to obtain the novel trimeric rare earth europium complex shown as the formula (I).
7. The method for preparing novel trimeric rare earth europium complex as claimed in claim 6, which comprises the following steps:
step 1, adding 2-hydroxy propane-1, 2, 3-tricarboxylic acid, 6-bromohexanoic acid tert-butyl ester and EDC into toluene, refluxing and heating at 90 ℃, cooling, standing, and separating to obtain a compound shown as a formula (I-1);
step 2, dissolving the compound shown as the formula (I-1) in methanol, adjusting the pH value to 1-2 by using HCl, separating out a precipitate, filtering, and drying filter residues to obtain the compound shown as the formula (I-2);
and 3, dissolving the compound and the complex MO shown as the formula (I-2) in ultra-dry dichloromethane at room temperature, dropwise adding a dichloromethane solution of DCC, stirring for 2 hours, draining the solvent, and performing chromatographic separation to obtain the novel trimeric rare earth europium complex shown as the formula (I).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011216580.XA CN112552238A (en) | 2020-11-04 | 2020-11-04 | Novel trimeric rare earth europium complex and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011216580.XA CN112552238A (en) | 2020-11-04 | 2020-11-04 | Novel trimeric rare earth europium complex and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112552238A true CN112552238A (en) | 2021-03-26 |
Family
ID=75042433
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011216580.XA Pending CN112552238A (en) | 2020-11-04 | 2020-11-04 | Novel trimeric rare earth europium complex and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112552238A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106432298A (en) * | 2016-09-05 | 2017-02-22 | 中国科学院苏州生物医学工程技术研究所 | Lanthanide metal ether complex and preparation method and application thereof |
| CN112174988A (en) * | 2020-11-04 | 2021-01-05 | 中国科学院苏州生物医学工程技术研究所 | Novel terbium trimerization complex and preparation method thereof |
| CN112300164A (en) * | 2020-11-04 | 2021-02-02 | 济南国科医工科技发展有限公司 | Rare earth samarium cryptand ether fluorescent complex and preparation method thereof |
| CN112341462A (en) * | 2020-11-04 | 2021-02-09 | 济南国科医工科技发展有限公司 | Rare earth dysprosium cryptate ether fluorescent complex and preparation method thereof |
-
2020
- 2020-11-04 CN CN202011216580.XA patent/CN112552238A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106432298A (en) * | 2016-09-05 | 2017-02-22 | 中国科学院苏州生物医学工程技术研究所 | Lanthanide metal ether complex and preparation method and application thereof |
| CN112174988A (en) * | 2020-11-04 | 2021-01-05 | 中国科学院苏州生物医学工程技术研究所 | Novel terbium trimerization complex and preparation method thereof |
| CN112300164A (en) * | 2020-11-04 | 2021-02-02 | 济南国科医工科技发展有限公司 | Rare earth samarium cryptand ether fluorescent complex and preparation method thereof |
| CN112341462A (en) * | 2020-11-04 | 2021-02-09 | 济南国科医工科技发展有限公司 | Rare earth dysprosium cryptate ether fluorescent complex and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108440475B (en) | Ratio type fluorescent probe for distinguishing lipid droplets with different polarities and preparation method and application thereof | |
| JP5090731B2 (en) | Fluorescent probe | |
| EP1931685B1 (en) | Method for obtaining highly luminescent lanthanide complexes | |
| GB2284809A (en) | A fluorescent phenylboronic acid for use in the detection of saccharides | |
| Kanimozhi et al. | Synthesis and photophysical and magnetic studies of ternary lanthanide (III) complexes of naphthyl chromophore functionalized imidazo [4, 5-f][1, 10] phenanthroline and dibenzoylmethane | |
| WO2016136718A1 (en) | Super-resolution fluorescent imaging probe | |
| Xue et al. | A europium complex with enhanced long-wavelength sensitized luminescent properties | |
| CN112341462A (en) | Rare earth dysprosium cryptate ether fluorescent complex and preparation method thereof | |
| Kasprzycka et al. | Lanthanide complexes with phosphorylated 2-naphthylsulfonamides ligands as electromagnetic radiation converters | |
| RU2296756C2 (en) | Chelate-forming dibenzo-containing five-membered cyclic compounds comprising two symmetric beta-dicarbonyl substitutes with fluorinated radicals | |
| Papkovsky et al. | Longwave luminescent porphyrin probes | |
| US8889839B2 (en) | Pyridine-bis (oxazoline)(“pybox”) moiety as a chelator and sensitizer for lanthanide ion (Ln (III)) Luminescence | |
| KR101298553B1 (en) | Fluorescence probe for selective cyanide detection, method for preparing the same and method for selective cyanide detection | |
| CN107759504B (en) | Dual-phase organic fluorescent material with strong fluorescence in solid and liquid states and preparation method thereof | |
| CN112174988B (en) | Tertiary rare earth terbium trimer and its preparation method | |
| WO2008010532A1 (en) | Compound or salt thereof, processes for producing these, aromatic azo compounds, and fluorescent material | |
| Hebbink et al. | Visible and near-infrared light emitting calix [4] arene-based ternary lanthanide complexes | |
| CN112300164A (en) | Rare earth samarium cryptand ether fluorescent complex and preparation method thereof | |
| CN112552238A (en) | Novel trimeric rare earth europium complex and preparation method thereof | |
| CN110272441B (en) | Biboroxadibenzo [ A, H ] anthracene derivatives and application thereof | |
| CN109336932B (en) | Amphiphilic platinum (II) complex, preparation thereof and application thereof in constructing white luminescent system | |
| CN114853656B (en) | Carbazole derivative with AEE characteristic, preparation method and application | |
| Starck et al. | Multifunctionalized luminescent lanthanide complexes from nonadentate phosphonylated bis-pyrazolyl-pyridine ligands | |
| CN110862420B (en) | Energy transfer luminescent material based on triplet donor material and acceptor material and application thereof | |
| CN112080156A (en) | Water-soluble dye containing pyrene and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210326 |