CN106008591A - Synthesis, characterization and anticancer activity determination method of coordination compound - Google Patents
Synthesis, characterization and anticancer activity determination method of coordination compound Download PDFInfo
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 70
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 21
- 230000001093 anti-cancer Effects 0.000 title claims abstract description 20
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 19
- 238000000034 method Methods 0.000 title claims description 20
- 238000012512 characterization method Methods 0.000 title claims description 5
- 229910001914 chlorine tetroxide Inorganic materials 0.000 claims abstract description 61
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims abstract description 23
- 239000000843 powder Substances 0.000 claims abstract description 21
- 230000000694 effects Effects 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 15
- 229940079593 drug Drugs 0.000 claims abstract description 10
- 239000013078 crystal Substances 0.000 claims abstract description 8
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 8
- 231100000053 low toxicity Toxicity 0.000 claims abstract description 5
- 239000000126 substance Substances 0.000 claims abstract description 3
- 210000004027 cell Anatomy 0.000 claims description 42
- 239000000243 solution Substances 0.000 claims description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 31
- 239000007864 aqueous solution Substances 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 230000006907 apoptotic process Effects 0.000 claims description 18
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 238000002474 experimental method Methods 0.000 claims description 12
- 210000001700 mitochondrial membrane Anatomy 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 8
- 150000002500 ions Chemical class 0.000 claims description 7
- 238000011275 oncology therapy Methods 0.000 claims description 7
- 230000003647 oxidation Effects 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 238000002390 rotary evaporation Methods 0.000 claims description 6
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 238000004088 simulation Methods 0.000 claims description 5
- 238000012460 anticancer assay Methods 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 230000007246 mechanism Effects 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- 229910001626 barium chloride Inorganic materials 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 238000002329 infrared spectrum Methods 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 229910001488 sodium perchlorate Inorganic materials 0.000 claims description 3
- 208000027418 Wounds and injury Diseases 0.000 claims description 2
- 238000002447 crystallographic data Methods 0.000 claims description 2
- 230000006378 damage Effects 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims description 2
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- 208000014674 injury Diseases 0.000 claims description 2
- 239000002574 poison Substances 0.000 claims description 2
- 231100000614 poison Toxicity 0.000 claims description 2
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 2
- 229910052720 vanadium Inorganic materials 0.000 abstract description 11
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 abstract description 11
- 229960004316 cisplatin Drugs 0.000 abstract description 7
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 abstract description 7
- 206010073071 hepatocellular carcinoma Diseases 0.000 abstract description 5
- 231100000225 lethality Toxicity 0.000 abstract description 3
- 239000002246 antineoplastic agent Substances 0.000 abstract 3
- 229940041181 antineoplastic drug Drugs 0.000 abstract 3
- 230000001644 anti-hepatocarcinoma Effects 0.000 abstract 1
- 239000013081 microcrystal Substances 0.000 abstract 1
- 239000012531 culture fluid Substances 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 238000004043 dyeing Methods 0.000 description 7
- 238000011160 research Methods 0.000 description 7
- 238000010586 diagram Methods 0.000 description 6
- 239000000975 dye Substances 0.000 description 6
- 230000003834 intracellular effect Effects 0.000 description 6
- 238000001514 detection method Methods 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- XDFNWJDGWJVGGN-UHFFFAOYSA-N 2-(2,7-dichloro-3,6-dihydroxy-9h-xanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1C2=CC(Cl)=C(O)C=C2OC2=CC(O)=C(Cl)C=C21 XDFNWJDGWJVGGN-UHFFFAOYSA-N 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
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- 239000012071 phase Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 230000002508 compound effect Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000012447 hatching Effects 0.000 description 3
- 210000003470 mitochondria Anatomy 0.000 description 3
- 239000003642 reactive oxygen metabolite Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 102000018832 Cytochromes Human genes 0.000 description 2
- 108010052832 Cytochromes Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 230000001640 apoptogenic effect Effects 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Inorganic materials [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000010523 cascade reaction Methods 0.000 description 2
- 239000012930 cell culture fluid Substances 0.000 description 2
- 239000013553 cell monolayer Substances 0.000 description 2
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- 229910002804 graphite Inorganic materials 0.000 description 2
- 239000010439 graphite Substances 0.000 description 2
- -1 hydrazone compounds Chemical class 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
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- 239000002244 precipitate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- UUUGYDOQQLOJQA-UHFFFAOYSA-L vanadyl sulfate Chemical compound [V+2]=O.[O-]S([O-])(=O)=O UUUGYDOQQLOJQA-UHFFFAOYSA-L 0.000 description 2
- 229910000352 vanadyl sulfate Inorganic materials 0.000 description 2
- DRGAZIDRYFYHIJ-UHFFFAOYSA-N 2,2':6',2''-terpyridine Chemical compound N1=CC=CC=C1C1=CC=CC(C=2N=CC=CC=2)=N1 DRGAZIDRYFYHIJ-UHFFFAOYSA-N 0.000 description 1
- JFJNVIPVOCESGZ-UHFFFAOYSA-N 2,3-dipyridin-2-ylpyridine Chemical compound N1=CC=CC=C1C1=CC=CN=C1C1=CC=CC=N1 JFJNVIPVOCESGZ-UHFFFAOYSA-N 0.000 description 1
- UGTJLJZQQFGTJD-UHFFFAOYSA-N Carbonylcyanide-3-chlorophenylhydrazone Chemical compound ClC1=CC=CC(NN=C(C#N)C#N)=C1 UGTJLJZQQFGTJD-UHFFFAOYSA-N 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 235000007926 Craterellus fallax Nutrition 0.000 description 1
- 229910017488 Cu K Inorganic materials 0.000 description 1
- 229910017541 Cu-K Inorganic materials 0.000 description 1
- 230000007035 DNA breakage Effects 0.000 description 1
- 240000007175 Datura inoxia Species 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 208000003468 Ehrlich Tumor Carcinoma Diseases 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229910021549 Vanadium(II) chloride Inorganic materials 0.000 description 1
- VQNOGBXVHYFAGJ-UHFFFAOYSA-N [V].N1=CC=CC2=CC=CC=C12 Chemical compound [V].N1=CC=CC2=CC=CC=C12 VQNOGBXVHYFAGJ-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- ZGNIYAPHJAPRMA-UHFFFAOYSA-N chlorine azide Chemical compound ClN=[N+]=[N-] ZGNIYAPHJAPRMA-UHFFFAOYSA-N 0.000 description 1
- ZCDOYSPFYFSLEW-UHFFFAOYSA-N chromate(2-) Chemical compound [O-][Cr]([O-])(=O)=O ZCDOYSPFYFSLEW-UHFFFAOYSA-N 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 150000001845 chromium compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000005564 crystal structure determination Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical class C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- LGZXYFMMLRYXLK-UHFFFAOYSA-N mercury(2+);sulfide Chemical compound [S-2].[Hg+2] LGZXYFMMLRYXLK-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000000633 nuclear envelope Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 230000032895 transmembrane transport Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- IBYSTTGVDIFUAY-UHFFFAOYSA-N vanadium monoxide Chemical compound [V]=O IBYSTTGVDIFUAY-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
Classifications
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- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/005—Compounds of elements of Group 5 of the Periodic Table without metal-carbon linkages
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Organic Chemistry (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Toxicology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a coordination compound, which has a chemical formula of [VO2(tpy)]ClO4. The compound has specific anticancer activity and is expected to become a low toxicity and high efficiency anticancer drug. Synthesis of the coordination compound [VO2(tpy)]ClO4 includes synthesis of [VO2(tpy)]ClO4 single crystal and [VO2(tpy)]ClO4 microcrystal or powder. With specific anticancer activity, the coordination compound especially has particularly strong lethality to hepatoma cell BEL-7402, and has IC50 of 0.4+/-0.2microM, while under the same conditions the traditional anticancer drug cisplatin has an IC50 value of 11.5+/-1.3microM to the BEL-7402 cell, the anti-hepatoma activity of the coordination compound is nearly 30 times that of cisplatin, and drugs with such anticancer activity are very rare at present, and the anticancer activity is closely related to the unique structure of the coordination compound and the multi-oxidation state properties of vanadium element, as the IC50 value is close to a human body allowable concentration 0.3microM, the compound is expected to be developed into a novel low toxicity and high efficiency anti-cancer drug.
Description
Technical field
The invention belongs to coordination compound technical field, relate to the synthesis of a kind of coordination compound, sign and active anticancer
Assay method.
Background technology
Vanadium is one of trace element important in organism, and in human body, the concentration of vanadium reaches 0.3 μ Μ, and its compound is
It is proved the pathogeny with human diseases and maintains normal physiological function closely related[1-3].From Kieler J report in 1986
Road cyclopentadiene complexes Cp2VCl2Since application in treatment ehrlich ascites tumor disease[4], the active anticancer of vanadium-containing compound
Gradually cause the extensive attention of people.Research shows the vanadium oxygen [V of tetravalence vanadiumIVO]2+Many pyridine coordinations compound is expected to become high
Effect, wide spectrum, low toxic and side effects cancer therapy drug[5,6], wherein (double-4,7-dimethyl-1,10 is adjacent luxuriant and rich with fragrance for compound Metvan
Quinoline vanadium oxysulfate) have been enter into clinical experimental stage[7].But research to the multi-pyridine ligand of pentavalent vanadium is relatively fewer, and mesh
Synthesized by before is electroneutral molecule or the compound containing complex anion, containing complex cation [VVO2]+Multi-pyridine ligand also
Have no report.
The most conventional research, the Research Significance of this work is far-reaching.On the one hand, with [VIVO]2+Coordination compound compare,
[VVO2]+Coordination compound as cancer therapy drug more advantage: (1) under solution and physiological condition, containing [VVO2]+Reagent more
Stable so that it is to have time enough identification in vivo and act on target cell；(2) [VVO2]+Have highly efficient anticancer
Activity, dosage also can reduce, and decreases the physical impairment to patient and the risk of chemotherapy that toxic and side effects is brought.This is
Because the antitumaous effect of the coordination compound of vanadium is by producing active oxygen (ROS) in body, and thus causes a series of chain type
Reaction and signal transmit, and ultimately result in cancer cell-apoptosis or death, and the active oxygen of generation is the most, and drug effect is the most notable.Due to [VVO2
]+Meet nucleophobic energy force rate [VIVO]2+Higher, the chromium compound (chromate) being similar to high price produces active oxygen in organism
Effect[8], therefore will produce more ROS in body.On the other hand, with neutrality or the moon of the in the past pentavalent vanadium of synthesis
The reagent of ion is compared, [the V of this work synthesisVO2(tpy)]+The advantage of (tpy=2,2':6', 2''-terpyridine)
It is: the cationic complexes of monovalence, is more easy to through cell membrane, even nuclear membrane, be thus susceptible to be absorbed by cell and produce relatively
The biochemical reaction of horn of plenty and excellent activity.This is because the interaction of cation-π in organism is extremely widespread
For important, complex cation and the pi-electron system of the aromatic rings with four dipoles in transmembrane protein produce stronger mutual
Effect, it is thus possible to be better achieved transmembrane transport[9].From the point of view of another angle, tpy is the part that lipophilic sequestering power is strong,
Only the complex ion volume containing a part tpy is little and not only has hydrophilic but also have lipotropy so that it is be also easy to be given birth to as medicine
Object absorbs and transhipment.Therefore, this compounds is as novel cancer therapy drug great potential, and achievement in research is expected to cancer
Chemotherapy plays immeasurable impetus.
Synthesis is containing [V the most in the worldVO2]+Compound, master is the hydrazone compounds coordination compound as part, by
In the ion L that such part is negative one valency-1, therefore synthesized compound [VVO2L] be neutral molecule, it is impossible to obtain joining sun from
Sub-coordination compound[10-13].2000, Claudia Pifferi et al. synthesized [VO (tpy) SO4], although containing tpy, but due to
Sulfate radical and V have stronger combination, have therefore had to the terpyridyl coordination compound of tetravalence vanadium[14], do not obtain closing with this technology
The similar compound become.The most do not occur that the synthesis of terpyridyl vanadium (V) coordination compound and biological activity are relevant in China
Research paper.
Attached: list of references
[1] D. Rehder, The potentiality of vanadium in medicinal applications,Future Med. Chem., 2012, 4, 1823-1837.
[2] D. Rehder, The coordination chemistry of vanadium as related to its
biological functions, Coord. Chem. Rev., 1999, 182, 297-322.
[3] M. T. Pepato, N. M. Khalil, M. P. Giocondo, I. L. Brunetti, Vanadium
and its complexes: the renewed interest in its biochemistry, Lat. Amer. J. Pharm., 2008, 27,468-76.
[4] P. Köpf-Maier, H. Köpf, Metallocene complexes: organometallic
antitumor agents. Drugs Future, 1986, 11, 297-319.
[5] A. Bishayee, A. Waghray, M.A. Patel, M. Chatterjee, Vanadium in the
detection, prevention and treatment of cancer: The in vivo evidence, Cancer
Letters, 2010, 294,1-12.
[6] M.W. Makinen, M. Salehitazangi, The structural basis of action of
vanadyl (VO2+) chelates in cells, Coord. Chem. Rev., 2014, 279, 1-22.
[7] O.J. D’Cruz, F.M. Uckun, Metvan: a novel oxovanadium (IV) complex
with broad spectrum anticancer activity, Expert Investig. Drugs, 2002, 11,
1829-1836.
[8] K. Jomova, M. Valko, Advances in metal-induced oxidative stress and
human disease, Toxicology, 2011, 283, 65-87.
[9] D.A. Dougherty, Cation-π interactions in chemistry and biology: a new
view of benzene, Phe, Tyr, and Trp, Science, 1996, 271, 163-167.
[10] M.R. Maurya, A.A. Khan, A. Azam, S. Ranjan, N. Mondal, A. Kumar, F.
Avecilla, J.C. Pessoa, Vanadium complexes having [VIVO]2+ and [VVO2]+ cores
with binucleating dibasic tetradentate ligands: synthesis, characterization,
catalytic and antiamoebic activities, Dalton Trans., 2010, 39, 1345-1360.
[11] P.I.S. Maia, F.R. Pavan, C.Q.F. Leite, S.S. Lemos, G.F. Sousa, A.A.
Batista, O.R. Nascimento, J. Ellena, E.E. Castellano, E. Niquet, V.M. Deflon,
Vanadium complexes with thiosemicarbazones: synthesis, characterization,
crystal structures and anti-mycobacterium tuberculosis activity, Polyhedron,
2009, 28, 298-406.
[12] M.R. Maurya, S. Agarwal, M. Abid, A. Azam, C. Bader, M. Ebel, D.
Rehder, synthesis, characterization, reactivity and in vitro antiamoebic
activity of hydrazone based oxovanadium(IV), oxovanadium(V) and µ-bis(oxo)bis
{oxovanadium(V)} complexes, Dalton Trans., 2006, 937-947.
[13] V.M. Deflon, D.M. Oliveira, G.F. Sousa, A.A. Batista, L.R. Dinelli,
E.E. Castellano, Oxovanadium(IV,V) complexes with 2-acetylpyridine-2-
furanoylhydrazone (Hapf) as ligand. X-ray crystal structures of [VO2(apf)]
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Summary of the invention
For overcoming above-mentioned technical disadvantages, the present invention provides the synthesis of a kind of coordination compound, characterizes and survey with active anticancer
Determining method, it, it can be avoided that use anion ligand and the strong anion of coordination ability as counter ion counterionsl gegenions, is reacted by control
Condition, the vanadium complex making tetravalence is fully oxidized, has the active anticancer of uniqueness, especially has hepatoma carcinoma cell BEL-7402
The strongest lethality.
The present invention solves the technical method that its technical problem used: a kind of coordination compound, its chemical formula is [VO2
(tpy)]ClO4, this coordination compound has anti-cancer herb activity and is expected to become the efficient cancer therapy drug of low toxicity, this coordination
Compound [VO2(tpy)]ClO4Synthesis include [VO2(tpy)]ClO4Monocrystalline synthesis and [VO2(tpy)]ClO4Crystallite or powder close
Become, wherein [VO2(tpy)]ClO4Monocrystalline synthesis step is:
First VOSO is chosen4Aqueous solution and Ba (ClO4)2Solution mixes, and obtains [VO (H after agitated filtration2O)5](ClO4)2Water
Solution, to this [VO (H2O)5](ClO4)2Aqueous solution adds tpy ethanol solution and obtains [VO (H2O)2(tpy)](ClO4)2Ethanol, water
Mixed solution, then remove ethanol acquisition [VO (H by rotary evaporation2O)2(tpy)](ClO4)2Aqueous solution, should [VO (H2O)2
(tpy)](ClO4)2Aqueous solution then oxidation by air formation [VO under the process of stirring2(tpy)]ClO4Aqueous solution, eventually passes
Slow evaporation prepares [VO2(tpy)]ClO4Monocrystalline；
At [VO2(tpy)]ClO4Crystallite or powder building-up process are then by Ba (ClO4)2Solution replaces to BaCl2Solution, warp
Agitation and filtration generates [VO (H2O)5]Cl2Aqueous solution, then to [VO (H2O)5]Cl2Aqueous solution adds tpy ethanol solution and obtains [VO
(H2O)2(tpy)]Cl2Ethanol, water mixed solution, then remove ethanol acquisition [VO (H through rotary evaporation2O)2(tpy)]Cl2Water-soluble
Liquid, should [VO (H2O)2(tpy)]Cl2Aqueous solution oxidation by air formation [VO under the process of stirring again2(tpy)] Cl aqueous solution,
To [VO2(tpy)] Cl aqueous solution adds saturated NaClO4And be stirred continuously and finally prepare [VO2(tpy)]ClO4Crystallite or powder
End.
The sign of coordination compound includes [VO2(tpy)]ClO4Monocrystalline characterizes and [VO2(tpy)]ClO4Crystallite or powder table
Levy, wherein [VO2(tpy)]ClO4The sign of monocrystalline then obtains molecular structure bond parameter and crystallography number by X-ray single crystal diffraction
According to and generate powder diffraction simulation drawing, [VO2(tpy)]ClO4Crystallite or Powder characterization with X-ray powder diffraction and with the powder of monocrystalline
End diffraction simulation drawing compares, and determines containing of complex ion formula weight and elementary analysis measuring C, H, N in conjunction with Electrospray Mass Spectrometry
Amount, so that it is determined that the composition of powder sample, structure and purity, and determine structure of functional groups by infrared spectrum.
The active anticancer assay method of this coordination compound, its determination step is: first carry out coordination compound [VO2
(tpy)]ClO4Cancerous cell poison is tested, and measures IC50Determine this coordination compound [VO2(tpy)]ClO4Most sensitive cell, by work
Property oxygen measure the generation determining coordination compound whether initiating activity oxygen, determine apoptosis rate by apoptosis experiment, pass through mitochondrion
The mensuration of transmembrane potential determines that circuit carries the degree of injury of film, determines apoptosis situation by comet, finally by above-mentioned
Measure and obtain mechanism of apoptosis.
The invention has the beneficial effects as follows: first with neutral terpyridine ligand, use the moon that contends with of weak coordination
Ion and fully oxidized under conditions of synthesized (pH is about 7) the most stable the containing under nearly physiological condition of solid phase and solution
The coordination compound of pentavalent vanadium terpyridyl complex cation and monocrystalline thereof, such coordination compound is at home, the world is not reported；Secondly close
The coordination compound become has the active anticancer of uniqueness, especially has the strongest lethality, its IC to hepatoma carcinoma cell BEL-740250
=0.4 ± 0.2 M, and conventional anti-cancer medicines cisplatin is under identical condition, the IC to BEL-7402 cell50Value is 11.5
± 1.3 M, therefore the resisting liver cancer activity of coordination compound of present invention synthesis is nearly 30 times of cisplatin, can reach such active anticancer
Medicine at present the most rare, this is that the character of multiple oxidation states of the structure unique by coordination compound and v element is closely related
, due to IC50Concentration 0.3 M that value is allowed close to human body, this compounds and be expected to exploitation be novel low toxicity, efficiently
Cancer therapy drug.
Accompanying drawing explanation
Fig. 1 is synthetic compound [VO2(tpy)]ClO4Monocrystalline frame structure schematic diagram；
Fig. 2 is synthetic compound [VO2(tpy)]ClO4(crystallite or powder) frame structure schematic diagram；
Fig. 3 is to cooperate with thing [VO2(tpy)]ClO4Monocrystalline and [VO2(tpy)]ClO4Crystallite or Powder characterization schematic diagram；
Fig. 4 is to cooperate with thing [VO2(tpy)]ClO4The mensuration scheme schematic diagram of active anticancer；
Fig. 5 is the cellular construction figure of the X-ray diffraction mensuration of monocrystal coordination compound；
Fig. 6 is the blank group of mitochondrial membrane potential determination experiment (a) of cell BEL-7402, and (b) (c) is respectively with 0.5 M and 1.0
The comparison figure of M；
Fig. 7 is to cooperate with thing [VO2(tpy)]ClO4Crystal data and structure refinement Parameter Map；
Fig. 8 is bond distance and the bond angle schematic diagram of complex cation；
Fig. 9 is powder diffraction spectrum；
Figure 10 is to cooperate with thing to selected cell strain IC50Value schematic diagram；
Figure 11 is the control group of EB dyeing comet (a) the EB dyeing of cell BEL-7402, and (b) adds the coordination compound of 0.5 M
Hatching 24 hours, the cell in b presents obvious comets tail comparison figure.
Detailed description of the invention
Below in conjunction with the accompanying drawings and embodiment the present invention is further described.
Embodiment 1:
Coordination compound [VO2(tpy)]ClO4Single crystal preparation and the mensuration of mono-crystalline structures
Seeing Fig. 1, preparation process is: first take 0.6 mmol VOSO4∙3H2O is dissolved in 25 ml water obtaining solution A, weighs 0.6
mmol Ba(ClO4)2It is dissolved in 25 ml water obtaining solution B, under stirring, solution B is slowly dropped in solution A, produce BaSO4In vain
Color precipitates, and filters to obtain blue solution C.By the ethanol solution (15 ml) of the tpy containing 0.5 mmol, under agitation it is added drop-wise to solution
In C, being stirred at room temperature 30 minutes, obtain a green solution, rotary evaporation, to about about 25 ml, is stirred at room temperature 5 days, becomes to solution
Orange-yellow, to filter, filtrate is at room temperature slowly freely evaporated, and within about 45 days, obtains orange bulk crystals [VO2(tpy)]ClO4。
See Fig. 3, single crystal structure determination: be bonded on glass fiber by complex monocrystal, after inserting copper pipe, be placed on
On the sample stage of Bruker SMART 1000 CCD four-circle diffractometer, with Mo-K α (λ=0.71073 of graphite monochromator light splitting
) ray as light source, be measured under 296K.Use ω scanning technique to collect in the range of 1.78 < θ < 25.00 ° to spread out
Penetrate intensity data, collect 4009 point diffractions.The direct method of crystal structure SHELXTL-97 solves, and uses a complete matrix young waiter in a wineshop or an inn
Multiplication existsF 2 On carry out an anisotropy correction.Finally to 2745 observation stations (F ≥ 4.0 σ(F)) and the essence of 235 variablees
Repair acquisition convergence.After to all of non-hydrogen atom anisotropy displacement parameter refine, the seat to the hydrogen atom on part
Mark and displacement parameter thereof carry out isotropic refine.In refine, hydrogen atom will be relatively fixed on its parent, with mother
The movement of atom and move, i.e. ride on parent, the distance of hydrogen atom and carbon atom utilize the preset value C H of program=
0.96 Å.All hydrogen atoms all carry out isotropic temperature factor correction.Relevant crystallographic data and structure refinement parameter are shown in
Fig. 7.The part bond distance of coordination compound cation, bond angle is listed in Fig. 8, sees Fig. 5.
Embodiment 2:
Coordination compound [VO2(tpy)]ClO4Crystallite preparation and sign
See Fig. 2, preparation: take 0.6 mmol VOSO4∙3H2O is dissolved in 25 ml water obtaining solution A, weighs 0.6 mmol BaCl2
It is dissolved in 25 ml water obtaining solution B, under stirring, solution B is slowly dropped in solution A, produce BaSO4White precipitate, filters
Blue solution C.By the ethanol solution (15 ml) of the tpy containing 0.5 mmol, under agitation it is added drop-wise in solution C, is stirred at room temperature
30 minutes, obtaining a green solution, rotary evaporation removes ethanol, is diluted with water to cumulative volume 80 ml of solution, is stirred at room temperature 7 days,
Become orange-yellow to solution, filter, under stirring condition, filtrate drips saturated NaClO4Solution, to precipitation completely, continues
It is stirred at room temperature 4 hours, obtains orange crystallite, sucking filtration, wash with water 3 times (each 5 ml), then by washing with alcohol twice (each 5
Ml), put in vacuum desiccator 3 days and obtain product, yield 42%.
See Fig. 3, characterize:
(1) powder diffraction: data and experimental patterns are measured on Bruker D8 Advance X-ray diffraction instrument and obtain
Take, wherein Cu-K α target, λ=0.154 nm, graphite monochromator diffracted beam monochrome ratio, high pressure 50 KV, pipe flow 20 mA.Simulated diffraction
Collection of illustrative plates, according to X-ray single crystal data, uses SHELXTL-XPOW program to calculate and obtains.By experimental patterns (Experimental)
With simulation collection of illustrative plates (Simulated), seeing Fig. 9, position and the relative intensity at peak are highly consistent, and this explanation gained crystallite has monocrystalline
Same structure；
(2) infrared spectrum: utilize Bruker VECTOR22 FT-IR infrared spectrometer and KBr pressed-disc technique to be measured, respectively
Peak is assigned as (cm-1): 1600,1480 (C=Ctpy, C=Ntpy), 1080, 953 (V=O)；
(3) Electrospray Mass Spectrometry: Electrospray Mass Spectrometry (ES-MS) LCQ system (Finnigan MAT, USA) record, selects
DMSO makees flowing phase.[DMSO, m/z]: 316.6 ([VO2(tpy)]+), experiment value and theoretical calculation.
(4) elementary analysis: elementary analysis (C, H, N) Elementar Vario EL elemental analyser measures.Test knot
Really (%): C 43.37, H 2.81, N 10.05.Value of calculation (C15 H11 ClN3 O6 V, %): C 43.34, H 2.67,
N 10.11.Experiment value is basically identical with value of calculation.
See Fig. 4, coordination compound [VO2(tpy)]ClO4Antitumor activity
(1) vitro cytotoxicity experiment: collect the cell of exponential phase, adjusting concentration of cell suspension is 5 × 104 ~ 1
.5 ×105Individual/m L, takes 96 orifice plate every hole 100 μ L.96 orifice plates inoculated are placed in incubator and hatch (5% CO2,
37oC), when hole bill kept on file confluent monolayer cells length is to about 80%, discard culture fluid, add 1640 culture fluid 90 μ L and set concentration ladder
The medicine 10 μ L of degree, continues to hatch 48 h, discards culture fluid, add MTT (5 mg of 90 μ L1640 culture fluid and 10 μ L
m L-1), incubator continues hatch 4 h.Being taken out to outside incubator, discard culture fluid, every hole adds the DMSO of 100 μ L, shakes
Shake 10 min, measure the absorbance at its 490 nm by microplate reader, calculate IC50Value result is shown in that Figure 10, result show, this synthesis
Compound, better than the activity of now widely used cancer therapy drug cisplatin (cisplatin), especially to hepatoma carcinoma cell
BEL-7402, the active anticancer of this compound is nearly 30 times of cisplatin.Hereinafter experiment (2) to (5) all uses BEL-7402 cell.
(2) AO/EB dyeing detection apoptosis experiment: take 12 orifice plates, every hole inoculating cell 1 × 105 ~ 2×105Individual.Treat monolayer
When cell length is to about 90%, add the medicine of respective concentration.After hatching 24 h in incubator, discarding culture fluid, PBS washes twice.
Dropping AO/EB dyeing liquor (100 μ g m L-1) covering slide, 37oC dyes 30 min, discards dye liquor, and PBS washs three times, fluorescence
Basis of microscopic observation, Taking Pictures recording, coordination compound effect BEL-7402 cell 24 h of only 0.5 M, then cell is carried out AO/
The double dye of EB, cell is coloured to green by AO, and apoptotic cell chromatin pyknosis dyeing is deepened；But EB (could not go out through cell membrane
Now in Chinese red), the feature of this early apoptosis of cells just.Illustrate that this coordination compound can induce hepatoma carcinoma cell BEL-expeditiously
The apoptosis of 7402.
(3) comet: i.e. SCGE experiment, BEL-7402 cell under the coordination compound effect of 0.5 M,
37oC hatches 24 h, and collects cell by trypsinized method.Three-layer process prepares gel slab, and electrolyte is 300 mM NaOH,
1.2 mM EDTA, electrophoresis is carried out under 25 V, 300 mA.With 400 mM Tris after electrophoresis, the solution of HCl, pH 7.5 will
Offset plate is washed till neutrality, in the dark dyes 20 minutes with EB (20 μ g/m L), takes pictures with fluorescence microscope.See Figure 11, and comparison
Group compares, and comets tail all occurs in the cell processed through coordination compound, and this explanation coordination compound enters into nucleus, and DNA effect, and makes
The fragment of DNA break different length, this is the enabling signal that apoptosis is important.
(4) mitochondrial membrane potential detection: collect logarithmic (log) phase cell, adjusts concentration of cell suspension.Take 12 orifice plates, every hole inoculation 1
× 105 ~ 2 × 105Individual.When cell monolayer length to about 80%, add the medicine of respective concentration.Incubator is hatched 24
After h, the CCCP adding 1 μ L toward positive controls continues to hatch 20 min, discards the culture fluid in 12 orifice plates, washes with cold PBS
Wash three times, add 0.5 m L cell culture fluid and 0.5 m L JC-1 dyeing working solution fully mixes.Cell is placed in incubator
In 37oC hatches 20 min, meanwhile take 3 m L JC-1 dye solution add 12 mL distilled waters dilute 5 times be placed in ice
On.After hatching end, discard dyeing liquor, and wash twice with JC-1 dye solution, add 1 m L cell culture fluid,
Fluorescence microscopy Microscopic observation, Taking Pictures recording.The detection of mitochondrial membrane potential with JC-1 as fluorescent probe, intracellular mitochondrial film
When current potential is higher, JC-1 is present in mitochondrial matrix a red fluorescence in polymer form, and intracellular mitochondrial transmembrane potential is relatively
JC-1 fluoresced green presented in monomer time low, so the fluorescence of detection JC-1 just can detect mitochondrial membrane electricity
The change of position.In apoptosis cell mitochondrial in early days, membrane permeability can increase, and mitochondrial membrane potential can decline, once line
Mitochondrial membrane potential collapse cell just can only move towards apoptosis.After the coordination compound effect BEL-7402 cell of this method synthesis, JC-1 contaminates
Cytochrome, fluorescence microscope Taking Pictures recording, it is seen that mitochondrial membrane potential test experience result display coordination compound can make BEL-
7402 mitochondrial membrane potential in anoxics reduce.See Fig. 6:
This figure is the blank group of mitochondrial membrane potential determination experiment (a) utilizing JC-1 staining to analyze cell BEL-7402, (b)
C () hatches 24 hours with the coordination compound of 0.5 M and 1.0 M respectively, b, c group the most all becomes green fluorescence, and coordination compound is described
Effect make mitochondrial membrane potential decline, this is mitochondrion release cells pigment, and the pass of the chain reaction of trigger cell apoptosis
Key.
(4) active oxygen detection: collect logarithmic (log) phase cell, adjusts concentration of cell suspension.Take 6 orifice plates, every hole inoculation 4 ×
105Individual.When cell monolayer length to about 90%, add the medicine of respective concentration, after incubator is hatched 24 h, discard 6 orifice plates
In culture fluid, wash twice with PBS, 1 m L trypsinization, collect cell centrifugal in the EP pipe of 2 m L (3000 rpm, 5
Min), discard supernatant, add the 1 m L culture fluid re-suspended cell without serum, centrifugal (3000 rpm, 5 min), discard
Clear liquid, adds 1 1000 DCFH-DA that diluted, is placed in cell culture incubator 37oC hatches 20 min, overturns every 3 ~ 5 min
Mixing once, then washes twice with the culture fluid without serum, centrifugal (3000 rpm, 5 min), discards supernatant and adds
The culture medium of 300 μ L serum-frees mixes and moves into streaming pipe, upper machine testing.Coordination compound [VO2(tpy)]ClO4Effect BEL-7402
Dichlorofluorescin-acetoacetic ester (DCFH-DA) staining cell after cell, flow cytomery DCF fluorescence intensity,
DCFH-DA itself does not has fluorescence, can enter cell through cell membrane, be become DCFH by intracellular esterase hydrolyzed after entering cell,
And DCFH cannot pass through cell membrane, DCFH is oxidized to the DCF of fluoresced green further by intracellular active oxygen, it is possible to
Intracellular reactive oxygen species is reflected by the fluorescence intensity of DCF.Test result indicate that coordination compound can raise BEL-7402 thin
The reactive oxygen species of intracellular.See Fig. 7:
This figure is for utilizing H2DCF-DA as fluorescent probe group blank to the determination experiment (a) of BEL-7402 reactive oxygen species,
B () Rosup positive control group, (c) hatches 24 hours with the coordination compound of 0.5 M.C group, as b, sends the fluorescence of green,
This explanation enter cell coordination compound can induction of the generation of active oxygen, thus produce active oxygen make DCFH occur oxidation generate
The DCF fluoresced.
Comprehensive above active anticancer experiment, initial guess anticancer mechanism is: coordination compound enters nucleus, produces active oxygen, oxidation
DNA breakage, produces apoptotic signal, and is displaced to mitochondrion, make mitochondrial membrane potential collapse, further release release apoptosis letter
Number, such as cytochrome C, and cause a series of cascade reaction (such as caspase cascade reaction), cause cancer cell-apoptosis, relevant
Detailed and deep anticancer mechanism await further systematic research.
Conclusion: this method reproducible, product purity is high.Synthesized [VO2(tpy)]ClO4Have high anticancer
Activity, is expected to the exploitation chemotherapeutics for the treatment of cancer of novel efficient, wide spectrum, low toxic and side effects.
Claims (3)
1. a coordination compound, its chemical formula is [VO2(tpy)]ClO4, this coordination compound has anti-cancer herb activity and has
Prestige becomes the efficient cancer therapy drug of low toxicity, it is characterized in that being, this coordination compound [VO2(tpy)]ClO4Synthesis include
[VO2(tpy)]ClO4Monocrystalline synthesis and [VO2(tpy)]ClO4Crystallite or powder synthesis, wherein [VO2(tpy)]ClO4Monocrystalline synthesizes
Step is:
First VOSO is chosen4Aqueous solution and Ba (ClO4)2Solution mixes, and obtains [VO (H after agitated filtration2O)5](ClO4)2Water
Solution, to this [VO (H2O)5](ClO4)2Aqueous solution adds tpy ethanol solution and obtains [VO (H2O)2(tpy)](ClO4)2Ethanol, water
Mixed solution, then remove ethanol acquisition [VO (H by rotary evaporation2O)2(tpy)](ClO4)2Aqueous solution, should [VO (H2O)2
(tpy)](ClO4)2Aqueous solution then oxidation by air formation [VO under the process of stirring2(tpy)]ClO4Aqueous solution, eventually passes
Slow evaporation prepares [VO2(tpy)]ClO4Monocrystalline；
At [VO2(tpy)]ClO4Crystallite or powder building-up process are then by Ba (ClO4)2Solution replaces to BaCl2Solution, through stirring
Mix filtration and generate [VO (H2O)5]Cl2Aqueous solution, then to [VO (H2O)5]Cl2Aqueous solution adds tpy ethanol solution and obtains [VO
(H2O)2(tpy)]Cl2Ethanol, water mixed solution, then remove ethanol acquisition [VO (H through rotary evaporation2O)2(tpy)]Cl2Water-soluble
Liquid, should [VO (H2O)2(tpy)]Cl2Aqueous solution oxidation by air formation [VO under the process of stirring again2(tpy)] Cl aqueous solution,
To [VO2(tpy)] Cl aqueous solution adds saturated NaClO4And be stirred continuously and finally prepare [VO2(tpy)]ClO4Crystallite or powder
End.
2. the sign of coordination compound is characterized in that as claimed in claim 1: includes [VO2(tpy)]ClO4Monocrystalline characterizes and [VO2
(tpy)]ClO4Crystallite or Powder characterization, wherein [VO2(tpy)]ClO4The sign of monocrystalline is then obtained by X-ray single crystal diffraction divides
Minor structure bond parameter and crystallographic data also generate powder diffraction simulation drawing, [VO2(tpy)]ClO4Crystallite or Powder characterization X-
Ray powder diffraction also compares with the powder diffraction simulation drawing of monocrystalline, determines complex ion formula weight and unit in conjunction with Electrospray Mass Spectrometry
Element analyzes the content of measuring C, H, N, so that it is determined that the composition of powder sample, structure and purity, and true by infrared spectrum
Determine structure of functional groups.
3. the active anticancer assay method of a coordination compound as claimed in claim 1, it is characterised in that determination step is: first
First carry out coordination compound [VO2(tpy)]ClO4Cancerous cell poison is tested, and measures IC50Determine this coordination compound [VO2(tpy)]
ClO4Most sensitive cell, determines the generation of coordination compound whether initiating activity oxygen by quantitation active oxygen, is determined by apoptosis experiment
By the mensuration of mitochondrial membrane potential, apoptosis rate, determines that circuit carries the degree of injury of film, determines cell by comet
Apoptosis situation, obtains mechanism of apoptosis finally by said determination.
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| CN109320730A (en) * | 2018-09-21 | 2019-02-12 | 重庆师范大学 | Barium-organic coordination polymer, preparation method and its application in ion detection and the compound film preparation of green light |
| CN110256482A (en) * | 2019-06-19 | 2019-09-20 | 吉林大学 | A kind of hetero-vanadate compound and preparation method thereof |
| CN111289424A (en) * | 2020-03-04 | 2020-06-16 | 浙江星博生物科技股份有限公司 | Method for detecting sperm mitochondrial membrane potential and active oxygen by double-standard method |
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2015
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| BABU BALAJI ET AL.: "Ferrocene-Conjugated Oxidovanadium(IV) Complexes as Potent Near-IR Light Photocytotoxic Agents", 《EUR. J. INORG. CHEM.》 * |
| JON ZUBIETA ET AL.: "Hydrothermal synthesis and structure of [VO2(terpy)][(VO2)2(PO4)],a novel network material (terpy=2,2":6",2"terpyridine)", 《SOLID STATE SCIENCES》 * |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109320730A (en) * | 2018-09-21 | 2019-02-12 | 重庆师范大学 | Barium-organic coordination polymer, preparation method and its application in ion detection and the compound film preparation of green light |
| CN109320730B (en) * | 2018-09-21 | 2021-04-16 | 重庆师范大学 | Barium-organic coordination polymer, preparation method thereof and application thereof in ion detection and green light composite film preparation |
| CN110256482A (en) * | 2019-06-19 | 2019-09-20 | 吉林大学 | A kind of hetero-vanadate compound and preparation method thereof |
| CN110256482B (en) * | 2019-06-19 | 2021-04-06 | 吉林大学 | Heteropoly vanadate compound and preparation method thereof |
| CN111289424A (en) * | 2020-03-04 | 2020-06-16 | 浙江星博生物科技股份有限公司 | Method for detecting sperm mitochondrial membrane potential and active oxygen by double-standard method |
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