CN106674221A - Novel organic ligand, preparation method thereof, novel ruthenium complex and fluorescent probe - Google Patents
Novel organic ligand, preparation method thereof, novel ruthenium complex and fluorescent probe Download PDFInfo
- Publication number
- CN106674221A CN106674221A CN201611228931.2A CN201611228931A CN106674221A CN 106674221 A CN106674221 A CN 106674221A CN 201611228931 A CN201611228931 A CN 201611228931A CN 106674221 A CN106674221 A CN 106674221A
- Authority
- CN
- China
- Prior art keywords
- preparation
- ruthenium complex
- organic ligand
- novel
- fpic
- 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.)
- Granted
Links
- 239000012327 Ruthenium complex Substances 0.000 title claims abstract description 36
- 239000013110 organic ligand Substances 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 239000007850 fluorescent dye Substances 0.000 title abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 39
- 239000003068 molecular probe Substances 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 229910001914 chlorine tetroxide Inorganic materials 0.000 claims description 29
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 29
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 20
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 19
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 19
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 16
- 229910052707 ruthenium Inorganic materials 0.000 claims description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 229910017053 inorganic salt Inorganic materials 0.000 claims description 9
- 238000001556 precipitation Methods 0.000 claims description 9
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 8
- 125000000129 anionic group Chemical group 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 239000012266 salt solution Substances 0.000 claims description 4
- 229910001488 sodium perchlorate Inorganic materials 0.000 claims description 4
- PCOJVRLVOOUDIS-UHFFFAOYSA-N C(=O)O.FC=1C=C2C=CNC2=CC1 Chemical compound C(=O)O.FC=1C=C2C=CNC2=CC1 PCOJVRLVOOUDIS-UHFFFAOYSA-N 0.000 claims description 3
- 125000002091 cationic group Chemical group 0.000 claims description 3
- 230000036571 hydration Effects 0.000 claims description 3
- 238000006703 hydration reaction Methods 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 238000011275 oncology therapy Methods 0.000 claims 1
- 150000003233 pyrroles Chemical class 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 12
- 238000012984 biological imaging Methods 0.000 abstract description 4
- 238000011160 research Methods 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 230000003287 optical effect Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 230000005281 excited state Effects 0.000 abstract description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 239000010413 mother solution Substances 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- ODFFPRGJZRXNHZ-UHFFFAOYSA-N 5-fluoroindole Chemical class FC1=CC=C2NC=CC2=C1 ODFFPRGJZRXNHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 238000002189 fluorescence spectrum Methods 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- TWHSOOOBPJANAX-UHFFFAOYSA-N 5-fluoro-N-(1,10-phenanthrolin-5-yl)-1H-indole-2-carboxamide Chemical compound FC=1C=C2C=C(NC2=CC=1)C(=O)NC1=C2C=CC=NC2=C2N=CC=CC2=C1 TWHSOOOBPJANAX-UHFFFAOYSA-N 0.000 description 1
- 0 CC(C1)=NCC2=*1C*(*)=CCC=C/C=C/C=NCC2*#C Chemical compound CC(C1)=NCC2=*1C*(*)=CCC=C/C=C/C=NCC2*#C 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000009878 intermolecular interaction Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000000954 titration curve Methods 0.000 description 1
- 125000001814 trioxo-lambda(7)-chloranyloxy group Chemical group *OCl(=O)(=O)=O 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
- C07F15/0053—Ruthenium compounds without a metal-carbon linkage
-
- 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
- C09K2211/18—Metal complexes
- C09K2211/185—Metal complexes of the platinum group, i.e. Os, Ir, Pt, Ru, Rh or Pd
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Physics & Mathematics (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Materials Engineering (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Pyridine Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention belongs to the technical field of complex, and in particular relates to a novel organic ligand, a preparation method thereof, a novel ruthenium complex and a fluorescent probe. The invention provides the novel organic ligand and the preparation method thereof. The invention also provides the novel ruthenium complex which comprises a compound as shown in Ru[M2(fpic)]X2 and/or hydrate thereof, wherein fpic refers to the novel organic ligand. The invention also provides the fluorescent probe and a pharmaceutical composition. The novel ruthenium complex has preferable water solubility, fine optical properties, long lifetime of excited state, good biocompatibility and simple synthesis steps, and can be used as a novel fluorescent molecular probe to be applied in the field of fluorescent biological imaging in research of life science.
Description
Technical field
The invention belongs to coordination compound technical field, and in particular to a kind of organic ligand and preparation method thereof, New Ruthenium coordinate
Thing and fluorescent probe.
Background technology
Fluorescent probe refer to those can selective binding certain analyte, therewith the fluorescence spectrum of system occur certain
The molecule of change.When molecular probe is designed, luminous letter is regulated and controled by the change of chemical constitution, environment and intermolecular interaction
Number, act on so as to play the detection to measured object.Re (I), Ru (II), Ir (III), Pt (II) coordination compound are a class transition metal
Coordination compound, due to it, preferable using value is commonly used for the luminophore of molecular probe in terms of biological imaging, this kind of
Fluorescent probe has consumption due to its special optical physics and photochemical properties, and low, sensitivity is high, responding range is wide
Advantage, is widely used in each ambit.In recent years, the research and development with regard to transition metal fluorescent probe is rapid, many
Plant fluorescent probe to be designed to synthesize and be applied in the fields such as DNA, protein, gas sensor.
However, the problem of the unstable short life of existing fluorescent molecular probe generally existing fluorescent emission and poorly water-soluble, no
The biological imaging that can be applied to well in biomedical research.Therefore, it is this area to research and develop a kind of novel fluorescence probe
Technical staff's technical problem urgently to be resolved hurrily.
The content of the invention
In view of this, it is an object of the invention to provide a kind of stable novel fluorescence probe of fluorescent emission.For in realization
Purpose is stated, the concrete technical scheme of the present invention is as follows：
The invention provides a kind of novel organic ligand, with the structure shown in logical formula I：
Present invention also offers a kind of preparation method of novel organic ligand, including：
By 5- fluoro indole formic acid, thionyl chloride and 5- amino -1,10- Phens hybrid reaction in reaction dissolvent, obtain
To the novel organic ligand described in claim 1.
Preferably, the reaction dissolvent is benzene or pyridine.
Present invention also offers a kind of new ruthenium complex, including shown in the compound and/or formula II shown in formula II
Compound hydrate,
Ru[M2(fpic)]X2 (Ⅱ)；
Wherein, M is 1,10- Phens or 2,2'- bipyridyl；
X is inorganic salt anionic；The inorganic salt anionic is ClO4-, NO3- or Br-；
Fpic is organic ligand, and the organic ligand has as led to the structure shown in formula I：
Preferably, in the new ruthenium complex, when M is 1,10- Phens, the molecular structural formula of cationic moiety is such as
Shown in formula (III)：
In the new ruthenium complex, when M is 2,2'- bipyridyls, molecular structural formula such as formula (IV) institute of cationic moiety
Show：
Present invention also offers a kind of preparation method of new ruthenium complex, including：
Novel organic ligand, the organic coordination compound of ruthenium and second prepared by above-mentioned novel organic ligand or above-mentioned preparation method
Alcohol mixes, backflow, is cooled to room temperature, and inorganic salt solution is added after filtration, separates out precipitation, obtains above-mentioned new ruthenium complex.
Preferably, the organic coordination compound of the ruthenium is that two (2,2'- bipyridyl)-two chloro- two is hydrated ruthenium or two (1,10- is adjacent
Phenanthroline)-two chloro- two hydrations rutheniums.
Preferably, to flow back under a nitrogen atmosphere, the return time is 6h for the backflow.
Preferably, the inorganic salt solution is NaClO4Aqueous solution.
Present invention also offers a kind of fluorescent molecular probe, including：Above-mentioned new ruthenium complex and/or the New Ruthenium are matched somebody with somebody
The new ruthenium complex that the preparation method of compound is prepared.
Present invention also offers a kind of pharmaceutical composition, including：Described new ruthenium complex and/or the New Ruthenium is matched somebody with somebody
The new ruthenium complex that the preparation method of compound is prepared.
Present invention also offers the organic ligand or the new ruthenium complex or described pharmaceutical composition resist in preparation
Application in cancer drug.
Compared with prior art, the invention has the advantages that：
The invention provides a kind of new organic ligand, structure novelty, can synthesize a kind of new with the reaction of organic ruthenium complex
Type ruthenium complex structure is novel；The ruthenium complex has preferable water solublity, and optical property is excellent, and lifetime of excited state is long, raw
The thing compatibility is good, and synthesis step is simple, can be used as a kind of novel fluorescent molecular probe, the fluorescence being applied in life science
Bio-imaging field.
Description of the drawings
In order to be illustrated more clearly that the embodiment of the present invention or technical scheme of the prior art, below will be to embodiment or existing
The accompanying drawing to be used needed for having technology description is briefly described, it should be apparent that, drawings in the following description are only this
Inventive embodiment, for those of ordinary skill in the art, on the premise of not paying creative work, can be with basis
The accompanying drawing of offer obtains other accompanying drawings.
Fig. 1 be Ru [(phen)2(fpic)](ClO4)2·2H2Fluorescent strength determining results of the O in water；
Fig. 2 be Ru [(bpy)2(fpic)](ClO4)2·2H2Fluorescent strength determining results of the O in water；
Fig. 3 be Ru [(phen)2(fpic)](ClO4)2·2H2Fluorescence lifetime measurement results of the O in water；
Fig. 4 be Ru [(bpy)2(fpic)](ClO4)2·2H2Fluorescence lifetime measurement results of the O in water；
Fig. 5 be Ru [(phen)2(fpic)](ClO4)2·2H2Fluorescent strength determining results of the O in acetonitrile；
Fig. 6 be Ru [(bpy)2(fpic)](ClO4)2·2H2Fluorescent strength determining results of the O in acetonitrile；
Fig. 7 be Ru [(phen)2(fpic)](ClO4)2·2H2Fluorescence lifetime measurement results of the O in acetonitrile；
Fig. 8 be Ru [(bpy)2(fpic)](ClO4)2·2H2Fluorescence lifetime measurement results of the O in acetonitrile；
Fig. 9 be Ru [(phen)2(fpic)](ClO4)2·2H2Fluorescence lifetime measurement result after O and DNA combinations；
Figure 10 be Ru [(bpy)2(fpic)](ClO4)2·2H2Fluorescence lifetime measurement result after O and DNA combinations.
Specific embodiment
The invention discloses a kind of organic ligand fpic, with the structure shown in logical formula I：
The invention discloses a kind of can be used as the new ruthenium complex of fluorescent molecular probe, the new ruthenium complex is Ru
[M2(fpic)]X2, wherein, M is 1,10- Phens or 2,2'- bipyridyl；X is excellent not affect the water miscible ion of coordination compound
Elect NO as3 2-, the inorganic salt anionic, more preferably ClO4- such as Br-.
Compound of the structural formula as shown in formula I is the major ligand fpic of the new ruthenium complex, 5-Fluoro-1H-
Indole-2-carboxylic acid-1,10-phenanthrolin-5-ylamide (are translated into：The fluoro- 1- indole -2- acetyl of 5-
Base -1,10- o-phenanthroline -5- amine), it is a kind of novel organic ligand；
The preparation method of fpic is specially：During 5- fluoro indole formic acid is added to into benzene or pyridine, thionyl chloride is slowly added dropwise,
It is heated to reflux, is concentrated into crystal precipitation, be subsequently adding 5- amino -1,10- Phens, stirring is collected precipitation, is dried.Its change
Learning reaction equation is：
The mixing of part fpic, the organic coordination compound of ruthenium and reaction dissolvent ethanol, flow back under a nitrogen atmosphere 6h, is cooled to room
Temperature, filters, and NaClO is added in filtrate4Aqueous solution, separates out precipitation, and sucking filtration, washing is dried, and obtains the ruthenium complex.
When the organic coordination compound of the ruthenium is that two (1,10- Phen)-two chloro- two is hydrated ruthenium, the New Ruthenium coordinates
Shown in the molecular structure of thing such as formula (a)：
The organic coordination compound of the ruthenium is that two (2,2'- bipyridyl)-two chloro- two is hydrated ruthenium, the new ruthenium complex
Shown in molecular structure such as formula (b)：
The new ruthenium complex that the present invention is provided possesses preferable water solublity, stable fluorescent emission, higher fluorescence volume
Sub- efficiency, can be applied to biological imaging technique as a kind of new long-life phosphors molecular probe, answer with extensive
Use prospect.It is the probe that can be used in living imaging that the new ruthenium complex is developed, the offer measured matter of real-time in-situ
Dynamic process in vivo will serve good facilitation for the fluorescence molecule detection research in life sciences.
Technical scheme is clearly and completely described below in conjunction with the specific embodiment of the invention, it is clear that
Described embodiment is a part of embodiment of the invention, rather than the embodiment of whole.Those skilled in the art should manage
Solution, modifies to the specific embodiment of the present invention or some technical characteristics is replaced on an equal basis, without deviating from the present invention
The spirit of technical scheme, all should cover in the scope of protection of the invention.
The synthesis of the organic ligand fpic of embodiment 1
During 5- fluoro indoles -2- formic acid (1.27g, 9.0mmol) is added to benzene, it is heated to reflux, is slowly added dropwise thionyl chloride,
And the suspension is heated to reflux into min；Then, it is mixture is concentrated in vacuo until the precipitation of pistac crystal, obtains 5- fluorine Yin
Diindyl -2- acyl chlorides.The benzole soln of 5- fluoro indole -2- acyl chlorides is dropwise added drop-wise to into 5- amino -1,10- o-phenanthrolines (1.9g,
In pyridine solution 9.0mmol), and gained mixture is stirred at room temperature overnight；Staticly settle, filter and collect precipitation,
Then crystallize in ethanol solution, obtain khaki solid, yield is 2.918g, yield 91%.
Fpic-1H NMR(400MHz,DMSO,ppm):δ 12.04 (3H, s), 10.96 (3H, s), 9.25 (4H, d, J=
3.3Hz),9.22-9.14(3H,m),8.97-8.72(7H,m),8.35(3H,s),8.16-7.95(7H,m),7.62(3H,d,J
=1.5Hz), 7.57-7.40 (8H, m), 7.26 (1H, d, J=17.4Hz), 7.20-6.99 (4H, m), 5.37-2.06 (95H,
M), 2.50 (18H, d, J=1.6Hz), 2.35 (21H, dd, J=119.7,52.0Hz), 2.10-0.52 (3H, m).
The coordination compound Ru of embodiment 2 is [(phen)2(fpic)](ClO4)2·2H2The preparation of O
By the Ru (phen) of 0.568g (1mmo1)2Cl2·2H2The fpic of O, 0.356g (1mmo1) is added in there-necked flask,
Ethanol is added, the mixture of gained is flowed back under a nitrogen atmosphere 6h, be cooled to room temperature, filtered.Add in filtrate
NaClO4, standing, sucking filtration, precipitation washed with water, ether and is vacuum dried afterwards for several times, obtains Orange red solid product, and yield is
2.918g, yield is 75%.
Ru[(phen)2(fpic)]-1H NMR(400MHz,DMSO,ppm):δ 11.98 (22H, d, J=18.2Hz),
10.95(20H,s),8.93-8.73(129H,m),8.62(23H,s),8.40(84H,s),8.23-8.00(126H,m),
7.99-7.70 (130H, m), 7.67-7.38 (79H, m), 7.28 (7H, s), 7.13 (28H, dtd, J=24.7,9.2,
2.5Hz), 3.35 (629H, s), 2.47 (303H, d, J=29.2Hz), 2.36-1.23 (33H, m), 1.61 (21H, d, J=
304.8Hz), 1.23 (11H, s), 1.00 (9H, d, J=118.3).
The coordination compound Ru of embodiment 3 is [(bpy)2(fpic)](ClO4)2·2H2The preparation of O
By the Ru (bpy) of 0.480g (1mmo1)2Cl2·2H2The fpic of O, 0.356g (1mmo1) is added in there-necked flask,
Ethanol is added, the mixture of gained is flowed back under a nitrogen atmosphere 6h, be cooled to room temperature, filtered.Add in filtrate
NaClO4, standing, sucking filtration, precipitation washed with water, ether and is vacuum dried afterwards for several times, obtains Orange red solid product, and yield is
2.918g, yield is 78%.
Ru[(bpy)2(fpic)]-1H NMR(400MHz,DMSO,ppm):δ12.00(1H,s),10.94(1H,s),
8.93-8.68(7H,m),8.62(1H,s),8.30-8.01(7H,m),8.01-7.68(5H,m),7.68-7.50(8H,m),
7.39 (2H, dd, J=12.3,5.2Hz), 7.26-7.04 (1H, m), 3.36 (94H, s), 2.42 (13H, d, J=69.8Hz),
2.10-1.96(1H,m),1.23(1H,s)。
Embodiment 4
Respectively compound concentration is the Ru of 10umol/L [(phen)2(fpic)](ClO4)2·2H2O and Ru are [(bpy)2
(fpic)](ClO4)2·2H2The aqueous solution of O, determines its absorbance and draws absorbing light and set a song to music with ultraviolet-uisible spectrophotometer
Line, so as to obtain the characteristic absorption peak wavelength of coordination compound, using wavelength as excitation wavelength, is then surveyed respectively using fluorescence spectrophotometer
The fluorescence intensity and fluorescence lifetime of two kinds of coordination compounds of examination.
As shown in Figures 1 to 4, both coordination compounds send strong fluorescence in water, and its fluorescence intensity is respectively
3.87×106cps、2.26×106cps.And, during with water as solvent, the fluorescence lifetime of both coordination compounds all meets double indexes
Attenuation curve, wherein, Ru is [(phen)2(fpic)](ClO4)2·2H2The fluorescence lifetime of O be 215.45ns, 590.76ns, Ru
[(bpy)2(fpic)](ClO4)2·2H2The fluorescence lifetime of O is 306.52ns, 544.82ns.
Embodiment 5
Using the acetonitrile Ru that respectively compound concentration is 10umol/L [(phen)2(fpic)](ClO4)2·2H2O and Ru
[(bpy)2(fpic)](ClO4)2·2H2The acetonitrile solution of O, determines its absorbance and draws suction with ultraviolet-uisible spectrophotometer
The curve of spectrum is received, so as to obtain the characteristic absorption peak wavelength of coordination compound, using wavelength as excitation wavelength, then using fluorescence spectrum
Instrument tests respectively the fluorescence intensity and fluorescence lifetime of two kinds of coordination compounds.
As shown in Fig. 5 to Fig. 8, both coordination compounds send strong fluorescence in acetonitrile, and its fluorescence intensity is respectively
1.31×106cps、8.96×105cps.And, during with acetonitrile as solvent, the fluorescence lifetime of both coordination compounds all meets double fingers
Number attenuation curve, wherein, Ru is [(phen)2(fpic)](ClO4)2·2H2The fluorescence lifetime of O be 111.81ns, 301.71ns, Ru
[(bpy)2(fpic)](ClO4)2·2H2The fluorescence lifetime of O is 144.18ns, 224.07ns.
Embodiment 6
Prepare the buffer of Tris containing 5mM and 50mM NaCl (hydrochloric acid adjusts pH value to 7.0).Take appropriate buffer solution to add
Appropriate DNA, is made into 5mg/mL DNA mother solutions.
Take appropriate buffer solution and be made into the Ru of 10umol/L [(phen)2(fpic)](ClO4)2·2H2The solution of O, Deca
5mg/mL DNA mother solutions, after adding DNA, determine the fluorescence intensity of coordination compound, Deca DNA solution are then continued to, until dropping to
Fluorescence intensity is basically unchanged, and tests its fluorescence lifetime.In the same manner, 10umol/L Ru are tested [(phen)2(fpic)](ClO4)2·
2H2The DNA titration curves of O and fluorescence lifetime.
As shown in Figure 9 and Figure 10, after with reference to DNA, the fluorescence lifetime of both coordination compounds remains in that double exponential dampinies
Pattern.Wherein, Ru is [(phen)2(fpic)](ClO4)2·2H2The fluorescence lifetime of O increases to 519.23ns, 1552.49ns, says
Bright coordination compound Ru is [(phen)2(fpic)](ClO4)2·2H2O is to combine front 2-3 times with reference to the fluorescence lifetime after DNA；Ru
[(bpy)2(fpic)](ClO4)2·2H2The fluorescence lifetime of O increases to 538.26ns, 1384.27ns, illustrates coordination compound Ru
[(bpy)2(fpic)](ClO4)2·2H2O is to combine front 1-2 times with reference to the fluorescence lifetime after DNA.
After DNA effects, the fluorescence intensity of the two coordination compounds is remarkably reinforced, and with the increase of DNA concentration, two coordinate
The fluorescence of thing gradually strengthens, and coordination compound Ru is [(phen)2(fpic)](ClO4)2·2H2O reaches when 440ul DNA mother solutions are dropped to
To saturation, fluorescence intensity increased about 13.2%, and coordination compound Ru is [(bpy)2(fpic)](ClO4)2·2H2O is dropping to 380ul
Saturation is reached during DNA mother solutions, fluorescence intensity increased about 25.6%, after illustrating that the two coordination compounds are combined with DNA, fluorescence intensity
With the enhancing that fluorescence lifetime has certain amplitude.
Claims (12)
1. a kind of novel organic ligand, it is characterised in that with as led to the structure shown in formula I：
2. a kind of preparation method of novel organic ligand, it is characterised in that include：
By 5- fluoro indole formic acid, thionyl chloride and 5- amino -1,10- Phens hybrid reaction in reaction dissolvent, obtain as
Novel organic ligand described in claim 1.
3. preparation method according to claim 2, it is characterised in that the reaction dissolvent is benzene or pyridine.
4. a kind of new ruthenium complex, it is characterised in that including the chemical combination shown in the compound and/or formula II shown in formula II
The hydrate of thing,
Ru[M2(fpic)]X2(Ⅱ)；
Wherein, M is 1,10- Phens or 2,2'- bipyridyl；
X is inorganic salt anionic；The inorganic salt anionic is ClO4 -、NO3 -Or Br-；
Fpic is organic ligand, and the organic ligand has as led to the structure shown in formula I：
5. new ruthenium complex according to claim 4, it is characterised in that in the new ruthenium complex, M is 1,10-
During Phen, shown in the molecular structural formula such as formula (III) of cationic moiety：
In the new ruthenium complex, when M is 2,2'- bipyridyls, shown in the molecular structural formula such as formula (IV) of cationic moiety：
6. a kind of preparation method of new ruthenium complex, including：
By described in novel organic ligand described in claim 1 or Claims 2 or 3 preparation method prepare novel organic ligand,
The organic coordination compound of ruthenium and ethanol mix, and backflow is cooled to room temperature, and inorganic salt solution is added after filtration, separates out precipitation, is weighed
Profit requires the new ruthenium complex described in 4 or 5.
7. preparation method according to claim 6, it is characterised in that the organic coordination compound of the ruthenium is two (2,2'- connection pyrroles
Pyridine)-two it is chloro- two hydration rutheniums or two (1,10- Phens)-two chloro- two hydration ruthenium.
8. the preparation method according to right wants 6, it is characterised in that the backflow to flow back under a nitrogen atmosphere, described time
The stream time is 6h.
9. the preparation method according to right wants 6, it is characterised in that the inorganic salt solution is NaClO4Aqueous solution.
10. a kind of fluorescent molecular probe, it is characterised in that include：New ruthenium complex and/or power described in Claims 2 or 3
Profit requires the new ruthenium complex that the preparation method described in 5-9 any one is prepared.
11. a kind of pharmaceutical compositions, it is characterised in that include：New ruthenium complex and/or right described in claim 4 or 5
Require the new ruthenium complex that the preparation method described in 6 to 9 any one is prepared.
12. novel organic ligand prepared by organic ligand as claimed in claim 1 or preparation method described in Claims 2 or 3
Or New Ruthenium prepared by the new ruthenium complex described in claim 4 or 5 or preparation method described in claim 6-9 any one
Application of the pharmaceutical composition described in coordination compound or claim 11 in cancer therapy drug is prepared.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611228931.2A CN106674221B (en) | 2016-12-27 | 2016-12-27 | A kind of novel organic ligand and preparation method thereof, novel ruthenium complex and fluorescence probe |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611228931.2A CN106674221B (en) | 2016-12-27 | 2016-12-27 | A kind of novel organic ligand and preparation method thereof, novel ruthenium complex and fluorescence probe |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106674221A true CN106674221A (en) | 2017-05-17 |
| CN106674221B CN106674221B (en) | 2018-12-18 |
Family
ID=58873009
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611228931.2A Expired - Fee Related CN106674221B (en) | 2016-12-27 | 2016-12-27 | A kind of novel organic ligand and preparation method thereof, novel ruthenium complex and fluorescence probe |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106674221B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN112707903A (en) * | 2020-12-29 | 2021-04-27 | 广东省科学院化工研究所 | Metal organic coordination compound and preparation method and application thereof |
| CN115806677A (en) * | 2022-11-15 | 2023-03-17 | 广东工业大学 | Ruthenium polymer with photo-thermal conversion performance and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101701024A (en) * | 2009-10-30 | 2010-05-05 | 暨南大学 | Ruthenium complex, preparation method thereof and application thereof |
| CN103880890A (en) * | 2014-03-21 | 2014-06-25 | 同济大学 | Novel antitumor drug-ruthenium (Ru) (II) complex and preparation method thereof |
| CN105732723A (en) * | 2016-03-18 | 2016-07-06 | 同济大学 | Ruthenium (II) polypyridine complex and preparation method and application thereof |
-
2016
- 2016-12-27 CN CN201611228931.2A patent/CN106674221B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101701024A (en) * | 2009-10-30 | 2010-05-05 | 暨南大学 | Ruthenium complex, preparation method thereof and application thereof |
| CN103880890A (en) * | 2014-03-21 | 2014-06-25 | 同济大学 | Novel antitumor drug-ruthenium (Ru) (II) complex and preparation method thereof |
| CN105732723A (en) * | 2016-03-18 | 2016-07-06 | 同济大学 | Ruthenium (II) polypyridine complex and preparation method and application thereof |
Non-Patent Citations (6)
| Title |
|---|
| A.SRISHAILAM等: "Synthesis, characterization; DNA binding and antitumor activity of ruthenium(II) polypyridyl complexes", 《JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B: BIOLOGY》 * |
| ALAN E.FRIEDMAN等: "A molecular light switch for DNA Ru(bpy)2(DPPZ)2+", 《J.AM.CHEM.SOC.》 * |
| JACQUELINE K.BARTON等: "Tris(phenanthroline)ruthenium(II) stereoselectivity in binding to DNA", 《J. AM. CHEM. SOC》 * |
| JIE SHAO等: "A novel anion receptor employing the pyrrole and amide moieties in the cooperative binding of anions", 《J INCL PHENOM MACROCYCL CHEM》 * |
| XUE-WEN LIU等: "DNA-binding, photocleavage studies of ruthenium(II) complexes with 2-(2-quinolinyl) imidazo[4,5-f][1,10]phenanthroline", 《SPECTROCHIMICA ACTA PART A: MOLECULAR AND BIOMOLECULAR SPECTROSCOPY》 * |
| 吴宇雄等: "5-丙烯酰胺基-1,10-邻菲罗啉的合成", 《现代化工》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN112707903A (en) * | 2020-12-29 | 2021-04-27 | 广东省科学院化工研究所 | Metal organic coordination compound and preparation method and application thereof |
| CN115806677A (en) * | 2022-11-15 | 2023-03-17 | 广东工业大学 | Ruthenium polymer with photo-thermal conversion performance and preparation method thereof |
| CN115806677B (en) * | 2022-11-15 | 2023-09-01 | 广东工业大学 | Ruthenium polymer with photo-thermal conversion performance and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106674221B (en) | 2018-12-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Liu et al. | Bipyridine-based nanosized metal–organic framework with tunable luminescence by a postmodification with Eu (III): an experimental and theoretical study | |
| Pyle et al. | Synthesis and characterization of physical, electronic, and photochemical aspects of 9, 10-phenanthrenequinonediimine complexes of ruthenium (II) and rhodium (III) | |
| Han et al. | Water-stable Eu6-cluster-based fcu-MOF with exposed vinyl groups for ratiometric and fluorescent visual sensing of hydrogen sulfide | |
| CN105623645B (en) | A kind of fluorescence probe based on aggregation-induced emission principle and preparation method thereof, application and detection endotoxin method | |
| CN106674221A (en) | Novel organic ligand, preparation method thereof, novel ruthenium complex and fluorescent probe | |
| CN105153203B (en) | A kind of organic inorganic hybridization compound of isopolymolybdic acid salt and preparation method thereof | |
| CN108384018B (en) | MOF (metal organic framework) complex, synthesis thereof and application thereof in fluorescent recognition of iron ions | |
| CN111995580B (en) | Fluorescent dye with tetraphenyl ethylene imidazole ring structure and application thereof | |
| CN103289684A (en) | Fluorescent silver nanocluster as well as preparation method and application thereof | |
| CN111690150B (en) | Rare earth europium (III) coordination polymer with network structure and preparation method and application thereof | |
| Lü et al. | Multinuclear NIR luminescent 1, 4-BDC bridged Schiff-base complexes of Nd (III) | |
| CN111205470B (en) | Azole functionalized divalent copper frame coordination material, preparation method and application thereof, and p-nitrophenol detection method | |
| CN102391150B (en) | Iron-ion fluorescent probe compound and preparation method thereof | |
| CN108997433B (en) | Manganese-based luminescent metal organic framework material and preparation method and application thereof | |
| CN104198451B (en) | A kind of sensor array and the application in metal ion auxiliary is identified thereof | |
| CN112321841B (en) | Metal organic framework material based on biomolecules as well as preparation method and application thereof | |
| CN106478731A (en) | The double emission ratios type oxygen probe of one class and application | |
| Jin et al. | Sonochemical effect on two new Ruthenium (II) complexes with ligand (E)-N-((6-bromopyridin-2-yl) methylene)-4-(methylthio) aniline precursors for synthesis of RuO2 nanoparticles | |
| CN102731479B (en) | Organic ligand, rare earth organic fluorescent probe material thereof and preparation method thereof | |
| CN110283330B (en) | Zinc-based luminescent metal organic framework material and preparation method and application thereof | |
| Yang et al. | Synthesis of multi-emission MOF composites for multi-dimensional sensing application | |
| CN108191920B (en) | A kind of half sandwich complex of iridium and preparation method thereof of the rhodamine B modification with fluorescent characteristic, application | |
| CN102890076B (en) | The method of the twin-channel detection platinum ion of a kind of fluorescence-phosphorescence based on schiff bases | |
| CN109232616B (en) | (-) -2- (4' -pyridyl) -4, 5-pinene-pyridine chiral silver complex and preparation method thereof | |
| CN109912633B (en) | Eu-complex fluorescent probe and preparation method and application 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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20181218 Termination date: 20211227 |