CN104370821A - Benzimidazole ligand and preparation method and application of dinuclear complexes of benzimidazole ligand - Google Patents
Benzimidazole ligand and preparation method and application of dinuclear complexes of benzimidazole ligand Download PDFInfo
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- CN104370821A CN104370821A CN201410673890.2A CN201410673890A CN104370821A CN 104370821 A CN104370821 A CN 104370821A CN 201410673890 A CN201410673890 A CN 201410673890A CN 104370821 A CN104370821 A CN 104370821A
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- benzimidazoles
- dinuclear complex
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- complex
- zinc
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Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 239000003446 ligand Substances 0.000 title claims abstract description 11
- 239000011701 zinc Substances 0.000 claims abstract description 33
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 23
- 239000000463 material Substances 0.000 claims abstract description 8
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 5
- 229940041181 antineoplastic drug Drugs 0.000 claims abstract description 5
- 150000001556 benzimidazoles Chemical class 0.000 claims description 40
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 28
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 26
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 16
- 229910052793 cadmium Inorganic materials 0.000 claims description 13
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 claims description 13
- 239000003513 alkali Substances 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 9
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 8
- 239000001273 butane Substances 0.000 claims description 8
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 claims description 8
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 claims description 5
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 5
- 201000004101 esophageal cancer Diseases 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 3
- 239000000376 reactant Substances 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 230000000259 anti-tumor effect Effects 0.000 abstract description 8
- 238000002474 experimental method Methods 0.000 abstract description 3
- 238000000338 in vitro Methods 0.000 abstract description 3
- 238000001308 synthesis method Methods 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 7
- 238000001514 detection method Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 5
- 229910052697 platinum Inorganic materials 0.000 description 5
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- -1 atom organic compound Chemical class 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000002411 thermogravimetry Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000003637 basic solution Substances 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 230000009036 growth inhibition Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- QFEZYQQHYKLHIO-UHFFFAOYSA-N CCc1c(C=C)[nH]c(CC(C(Cc2nc(cccc3)c3[nH]2)c2nc3ccccc3[nH]2)c2nc(cccc3)c3[nH]2)n1 Chemical compound CCc1c(C=C)[nH]c(CC(C(Cc2nc(cccc3)c3[nH]2)c2nc3ccccc3[nH]2)c2nc(cccc3)c3[nH]2)n1 QFEZYQQHYKLHIO-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- CEKJAYFBQARQNG-UHFFFAOYSA-N cadmium zinc Chemical compound [Zn].[Cd] CEKJAYFBQARQNG-UHFFFAOYSA-N 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000002189 fluorescence spectrum Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and 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
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/06—Zinc compounds
-
- 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
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/08—Cadmium compounds
-
- 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
-
- 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
- C09K2211/188—Metal complexes of other metals not provided for in one of the previous groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a benzimidazole ligand and a preparation thereof. The benzimidazole ligand has the advantages that the synthesis method is simple, the aftertreatment operation is easy, the product purity is high, the yield is high and the cost is low. The benzimidazole ligand can be further used for preparing a benzimidazole ligand/zinc dinuclear complex and a benzimidazole ligand/zinc dinuclear complex. The dinuclear complexes are stable in structure, good in heat stability, can emit blue-fluorescence, can be used for preparing blue fluorescent material. In vitro cell experiment shows that the benzimidazole ligand/zinc dinuclear complex has an antitumor activity and can be used for preparing novel antitumor drug.
Description
Technical field
The invention belongs to blue fluorescent material technical field and field of antineoplastic medicaments, be specifically related to the preparation method and application of a kind of benzimidazoles part and dinuclear complex thereof.
Background technology
In recent years, nitrogenous miscellany part and title complex thereof have become very active research field, and luminous nitrogenous miscellany ligand-complexes is at chemistry; biology, the field such as medical science and Materials science has a wide range of applications [Xiao L., Chen Z.; Qu B., Luo J., Kong S.; Gong, Q.; Kido J.,
adv. Mater. 2011, 23,926 – 952; Lo K. K. W., Louie M. W., Zhang K. Y.,
coord. Chem. Rev. 2010, 254,2603 – 2622; Zhao Q., Li F., Huang C.,
chem. Soc. Rev. 2010, 39,3007 – 3030].Design emitting complexes a strategy be by have large π-electron structure containing can ligating atom organic compound with there is d
10the metal ions such as the zinc cadmium of electronic structure are combined into metal complexes.Benzimidazoles compound be a class have large π-electron structure containing N organic ligand, two atom N of its imidazoles can generate benzimidazole metal complex with the effective coordination of metal ion.Such title complex has wide practical use in fields such as biological activity, catalysis and functional materials [Xie Q., Liu S. G., Li X. L., Wu Q., Luo Z. D., Fu X. Y., Cao W. Q., Lan G.Q., Li D., Zheng W. J., Chen T. F.
dalton Trans.,
2014, 43,6973-6976; Liu S. G., Cao W. Q., Yu L. L., Zheng W.J., Li L. L., Fan C. D., Chen T. F.,
dalton Trans. 2013, 42,5932-5940; Liu S.G., Zhou X.T., Ji H.B.,
catalysis Communications,
2013, 37,60-63; Zhou X.T., Ji H.B., Liu S.G.,
tetrahedron Letters,
2013, 54,3882-3885.
liu S.G.,zuo J.L., Wang Y., Li Y.Z., You X.Z.,
journal of Physics and Chemistry of Solids,
2005, 66,735 – 740].The mononuclear coordination compound utilizing benzimidazoles to carry out coordination is at present studied a lot of, but dinuclear complex research still more rare [Xie Q., the Liu S. G. containing benzimidazoles, Li X. L., Wu Q., Luo Z. D., Fu X. Y., Cao W.Q., Lan G. Q., Li D., Zheng W. J., Chen T. F.
dalton Trans.,
2014, 43,6973-6976], the dinuclear complex of research benzimidazoles coordination and can have bioactive drug discovery and opens up new approach for development of new fluorescent material.
Summary of the invention
The object of the invention is to open a kind of benzimidazoles part.
Second object of the present invention is the preparation method of openly a kind of benzimidazoles part.
3rd object of the present invention is to disclose two kinds of benzimidazoles dinuclear complexs.
4th object of the present invention is the preparation method of open benzimidazoles dinuclear complex.
5th object of the present invention is that open benzimidazoles dinuclear complex is preparing the application in blue fluorescent material.
6th object of the present invention is that open benzimidazoles zinc dinuclear complex is preparing the application in antitumor drug.
Above-mentioned purpose of the present invention is achieved by following technical solution:
A kind of benzimidazoles part, the structural formula of described benzimidazoles part is as follows:
。
The name of described benzimidazoles part formula I is called 1,2,3,4-tetra-(1H-benzimidazolyl-2 radicals-) butane, is called for short tbb.
The preparation method of described benzimidazoles part is as follows:
1,2,3,4-tetracarboxylic acid butane and O-Phenylene Diamine are mixed in phosphoric acid, heating reflux reaction, generate green reaction thing, thin up after cooling, is neutralized to alkalescence with alkali lye, obtains white solid, then obtain described benzimidazoles part through purifying.
Described purifying is according to this area Conventional compounds purification process, and concrete purification step comprises filtration, washing, recrystallization.
Because benzimidazoles part solvability in basic solution significantly diminishes, thus add alkali lye in reaction solution to be neutralized to alkalescence product benzimidazole class part can be made to separate out, as a kind of preferred version, described alkali lye is neutralized to alkalescence and is specially that to be neutralized to pH with alkali lye be 8.
As a kind of concrete embodiment, the preparation method of described benzimidazoles part is: take 1,2,3,4-tetracarboxylic acid butane and O-Phenylene Diamine, mix in appropriate phosphoric acid, heating reflux reaction, generates green reactant, adds distilled water diluting after being cooled to room temperature, and to be neutralized to pH with alkali lye be 8, obtain the solid of white, then filter, obtain desired product as white solid 1,2 with distilled water wash, DMF recrystallization, 3,4-tetra-(1H-benzimidazolyl-2 radicals-) butane.
As a kind of preferred version, the mole dosage of described 1,2,3,4-tetracarboxylic acid butane and O-Phenylene Diamine is than being 1:4.
As a kind of preferred version, the concrete steps of described reflux are heat 3 hours under 180 DEG C of conditions.
Phosphoric acid of the present invention directly can adopt commercially available pure phosphoric acid reagent, and without the need to dilution, the Phosphoric Acid purity range of this area routine is 82% ~ 98%, and the phosphoric acid of this concentration all can realize synthesis object of the present invention.
Alkali lye of the present invention adopts the conventional neutralization basic solution in this area, and as a kind of preferred version, described alkali lye is sodium hydroxide solution, sodium carbonate solution, potassium hydroxide solution, solution of potassium carbonate or ammonia soln.
Benzimidazoles dinuclear complex, structural formula is as follows:
。
The preparation method of above-mentioned benzimidazoles dinuclear complex, obtained by metal-salt and described benzimidazoles ligand reaction, described metal-salt is ZnCl
2or CdCl
2.
The preparation of benzimidazoles dinuclear complex adopts conventional solvent nature volatilization method can prepare monocrystalline title complex, as a kind of embodiment, concrete steps are: metal-salt and benzimidazoles part to be dissolved in a heated state in appropriate easy volatile solvent and to stir, naturally volatilize and within 3 days, obtain the complex monocrystal of white rectangular shape, i.e. benzimidazoles zinc dinuclear complex Zn
2(tbb) Cl
4or benzimidazoles cadmium dinuclear complex Cd
2(tbb) Cl
4.
As a kind of preferred version, described metal-salt is 2:1 with the mole dosage ratio of benzimidazoles part.
Described easy volatile solvent is methyl alcohol, ethanol or DMF (DMF).
Benzimidazoles zinc dinuclear complex obtained by the present invention and benzimidazoles cadmium dinuclear complex Heat stability is good, at ambient temperature, ultraviolet excitation can invent bright blue-fluorescence, can be applied further as blue fluorescent material.
The benzimidazoles zinc dinuclear complex that the present invention obtains has anti-tumor activity, has application prospect preparing in antitumor drug.Through experiment test, benzimidazoles zinc dinuclear complex of the present invention significantly can suppress the growth of esophagus cancer tumour cell.
Compared with prior art, the present invention has following beneficial effect:
The present invention discloses a kind of new benzimidazoles part and preparation method thereof, described benzimidazoles part synthetic method is simple, aftertreatment is easy, and product purity is high, and productive rate is high, cost is low, can be further used for preparing benzimidazoles zinc dinuclear complex and benzimidazoles cadmium dinuclear complex, gained dinuclear complex Stability Analysis of Structures, Heat stability is good, can blue-fluorescence be sent, can be applicable to prepare blue fluorescent material; In addition benzimidazoles zinc dinuclear complex also has anti-tumor activity, can be applicable to prepare novel antitumor drug.
Accompanying drawing explanation
Fig. 1 is the coordination class border single crystal structure formula of benzimidazoles zinc dinuclear complex of the present invention;
Fig. 2 is the coordination class border single crystal structure formula of benzimidazoles cadmium dinuclear complex of the present invention;
Fig. 3 is the thermogravimetric analysis figure of benzimidazoles zinc dinuclear complex of the present invention and benzimidazoles cadmium dinuclear complex;
Fig. 4 is benzimidazoles part of the present invention, benzimidazoles zinc dinuclear complex and the utilizing emitted light spectrogram of benzimidazoles cadmium dinuclear complex in DMF solvent (λ ex=314nm);
Fig. 5 is that benzimidazoles zinc dinuclear complex of the present invention and cis-platinum are to esophagus cancer Eca109 cell growth inhibition result figure.
Embodiment
Below in conjunction with specific embodiment, the present invention is further explained, but embodiments of the present invention is not limited in any way.Unless stated otherwise, involved in embodiment reagent, method are the conventional reagent in this area and method.
embodiment 1the synthesis of benzimidazoles part (tbb)
Building-up reactions formula is as follows:
By 1,2,3, it is in the phosphoric acid of 85% that 4-tetracarboxylic acid butane (2.34g, 0.01mol) and O-Phenylene Diamine (4.32g, 0.04mol) are blended in 10 milliliters of purity, heat 3 hours under 180 DEG C of conditions, generate green reactant, after cool to room temperature, add distilled water diluting, and obtain the solid of white with sodium carbonate solution neutralization, then distilled water wash is used 3 times, filter, DMF recrystallization, obtains white solid 1,2,3,4-tetra-(1H-benzimidazolyl-2 radicals-) butane, i.e. part (tbb).Output: 5.2 g, productive rate: 58.6%.
Ultimate analysis C
44h
62n
12o
8(tbb
.4DMF
.4H
2o), calculated value: C, 59.58%; H, 7.05%; N, 18.95%; Experimental value: C, 59.48%; H, 7.01%; N, 18.93%.Ir data (KBr, cm
-1): 3593,3150,1644,1531,1440,1,386 1274,1030,839,746.
1HNMR (300MHz,
d 6 -DMSO)：2.72(s, 1H), 2.88(s, 1H), 2.95(s, 1H),3.00(s, 1H),3.53(m, 2H), 4.26(DMF-CH
3), 4.44 (DMF-CH
3), 6.99 (m, 4H), 7.06 (m, 4H), 7.35 (s, 4H), 7.44 (s, 4H),8.29 (DMF-CHO),12.16 (s,2H),12.61(s,2H)。
embodiment 2benzimidazoles zinc dinuclear complex (Zn
2(tbb) Cl
4) synthesis
Building-up reactions formula is as follows:
。
By ZnCl
2(0.272g, 0.02mol) with benzimidazoles part (0.886g, 0.01mol) be dissolved in a heated state in the DMF solvent of 50ml, mixture is stirred, naturally volatilization obtains the complex monocrystal of white rectangular shape for 3 days, and obtained 1,2,3,4-tetra-(1H-benzimidazolyl-2 radicals-) zinc dinuclear complex Zn
2(tbb) Cl
4 .4DMF, i.e. benzimidazoles zinc dinuclear complex.Output 0.69g, productive rate 63.48%.
Ultimate analysis: C
44h
54cl
4n
12o
4zn
2([Zn
2(tbb) Cl
4]
.4DMF
.3H
2o), calculated value: C, 48.59%; H, 5.00%; N, 15.45%; Experimental value: C, 48.48%; H, 4.91%; N, 15.33%.Ir data (KBr, cm
-1): 3479,2924,1651,1454,1387,1281,1105,1064,847,768,671.
The monocrystalline molecular structure obtained in DMF as shown in Figure 1.Main single crystal data:
mr=1087.53, crystallographic system, Monoclinic, spacer, P21/n,
a=9.2307 (12)
b=11.3748 (14)
c=23.874 (3),
β=90.489 (0) °,
v=2506.6 (5)
3,
z=2,
dc=1.441 g/cm
3,
λ=0.71073 nm,
μ(MoK α)=1.224mm
– 1,
f(000)=1124,
s=1.037, Final R indices [I>2sigma (I)], R1=0.0676, wR2=0.1814.
embodiment 3benzimidazoles cadmium dinuclear complex (Cd
2(tbb) Cl
4) synthesis
Building-up reactions formula is as follows:
。
By CdCl
2(0.336g, 0.02mol) with benzimidazoles part (0.886g, 0.01mol) be dissolved in a heated state in the DMF solvent of 50ml, mixture is stirred, naturally volatilization obtains the complex monocrystal of white rectangular shape for 3 days, and obtained 1,2,3,4-tetra-(1H-benzimidazolyl-2 radicals-) cadmium dinuclear complex Cd
2(tbb) Cl
44DMF3H
2o, i.e. benzimidazoles cadmium dinuclear complex.Output 0.82g, productive rate 67.10%.
Ultimate analysis C
44h
49cl
4cd
2n
12o
7([Cd
2(tbb) Cl
4]
.4DMF
.3H
2o), calculated value: C, 43.16%; H, 4.03%; N, 13.73%; Experimental value: C, 43.29%; H, 4.01%; N, 13.53%.Ir data (KBr, cm
-1): 3518,3025,1655,1537,1426,1395,1324,1270,1206,1086,1034,971,743,656.
The monocrystalline molecular structure obtained in DMF as shown in Figure 2.Main single crystal data:
mr=1224.55, crystallographic system, Monoclinic, spacer, C2/c,
a=29.563 (3)
b=14.2580 (17)
c=26.355 (3),
β=97.036 (2) °,
v=11025 (2)
3,
z=8,
dc=1.475g/cm
3,
λ=0.71073 nm,
μ(MoK α)=1.021mm
– 1,
f(000)=4936,
s=1.047, Final R indices [I>2sigma (I)], R1=0.0680, wR2=0.1832.
embodiment 4performance Detection
The benzimidazoles zinc dinuclear complex obtain embodiment 2 and embodiment 3 and benzimidazoles cadmium dinuclear complex carry out conventional thermogravimetric analysis detection and fluorescence emission spectra detection, as shown in Figure 3, in DMF solvent, luminescent spectrum detected result as shown in Figure 4 for thermogravimetric analysis detected result.
Performance test results shows, the thermostability of benzimidazoles zinc dinuclear complex and benzimidazoles cadmium dinuclear complex is all higher than 250 DEG C, and two kinds of dinuclear complexs all have the character that fluoresces, at the optical excitation exhibits blue fluorescence of 314nm, maximum emission wavelength 450nm.
embodiment 5benzimidazoles zinc dinuclear complex (Zn
2(tbb) Cl
4) anti tumor activity in vitro detection
Esophagus cancer Eca109 cell is adopted to evaluate title complex anti-tumor activity, using the cis-platinum of this area routine as positive control in vitro in active testing.Adopt conventional mtt assay to carry out cell viability detection, observe sample on the impact of tumor cell activity to evaluate title complex antitumous effect, concrete steps are as follows:
By preliminary experiment measure cell growth rate, inoculation certain number logarithmic phase cell in 96 orifice plates, to control the OD value about about 1.0 of the cellular control unit when drug effect stops.After cell attachment, drug dilution is become certain gradient concentration, every concentration establishes 3 multiple holes, point experimental group, solvent control group and the dosing of zeroing group, observation of cell growing state under inverted microscope Taking Pictures recording.After 48 h, adopt mtt assay to carry out cell viability detection, every hole adds 20 μ L MTT solution, continues cultivation 4 h, and liquid in careful absorption hole, avoid contact hole intercrystalline thing, every hole adds the DMSO of 100 ml, and on constant speed shaking table, lucifuge is rocked.After thing to be crystallized fully dissolves, microplate reader reads OD value (wavelength 570 nm, reference wavelength 630 nm), records absorbance A value.The calculation formula of growth inhibition ratio is: growth inhibition ratio (%)=(1-OD experimental group/OD control group) × 100%.Can map according to the inhibiting rate of each concentration and obtain dose response curve, mapping software is GraphPad Prism 5, can estimate to obtain the half-inhibition concentration IC of medicine from figure
50, adopt the IC of Logit method accurate calculation medicine
50.
Zn complex and cis-platinum are to esophagus cancer Eca109 cell growth inhibition as shown in Figure 5.As can be seen from Figure 5, the anti-tumor activity of Zn complex is apparently higher than cis-platinum, and this Zn complex is to Eca109 cell half-inhibition concentration IC
50value is 22.1 ± 6.7 μMs, lower than the IC of cis-platinum
50(62.5 ± 12.4 μMs), and free ligand IC
50(24.7 ± 7.8 μMs), this Zn complex has obvious anti-tumor activity.
Claims (10)
1. a benzimidazoles part, is characterized in that, the structural formula of described benzimidazoles part is as follows:
。
2. the preparation method of benzimidazoles part described in claim 1, it is characterized in that, step is as follows:
1,2,3,4-tetracarboxylic acid butane and O-Phenylene Diamine are mixed in phosphoric acid, heating reflux reaction, thin up after reactant cooling, is neutralized to alkalescence with alkali lye, then obtains described benzimidazoles part through purifying.
3. the preparation method of benzimidazoles part according to claim 2, is characterized in that, described alkali lye is neutralized to alkalescence and is specially that to be neutralized to pH with alkali lye be 8.
4. the preparation method of benzimidazoles part according to claim 2, it is characterized in that, described alkali lye is sodium hydroxide solution, sodium carbonate solution, potassium hydroxide solution, solution of potassium carbonate or ammonia soln.
5. benzimidazoles dinuclear complex, is characterized in that, structural formula is as follows:
Formula II is benzoglyoxaline ring zinc dinuclear complex, and formula III is benzoglyoxaline ring cadmium dinuclear complex.
6. the preparation method of benzoglyoxaline ring dinuclear complex described in claim 5, it is characterized in that, step is as follows:
Obtained by benzimidazoles ligand reaction described in metal-salt and claim 1, described metal-salt is ZnCl
2or CdCl
2.
7. the preparation method of benzimidazoles dinuclear complex according to claim 6, it is characterized in that, concrete steps are: metal-salt and benzimidazoles part to be dissolved in a heated state in appropriate easy volatile solvent and to stir, naturally volatilize and within 3 days, obtain the complex monocrystal of white rectangular shape, i.e. benzimidazoles zinc dinuclear complex Zn
2(tbb) Cl
4or benzimidazoles cadmium dinuclear complex Cd
2(tbb) Cl
4.
8. benzimidazoles dinuclear complex described in claim 5 is preparing the application in blue fluorescent material.
9. the application of benzimidazoles zinc dinuclear complex described in claim 5 in the anti-antitumor drug of preparation.
10. apply according to claim 9, it is characterized in that, described tumour is esophagus cancer tumour.
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