CN111961070A - Novel copper metal complex, preparation method and application thereof - Google Patents
Novel copper metal complex, preparation method and application thereof Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 14
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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
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
- C07F1/08—Copper compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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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
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
- C07F1/005—Compounds containing elements of Groups 1 or 11 of the Periodic Table without C-Metal linkages
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Abstract
The invention provides a novel copper metal complex, a preparation method and application thereof, belonging to the technical field of drug synthesis. The structure of the coordination of the copper complex is shown in FIG. 1. The preparation method of the novel copper metal complex comprises the following steps: weighing 4-chloro-3-nitrobenzoic acid and 2, 2' -bipyridine, placing in a beaker, adding a solvent, stirring and dissolving to prepare a mixed solution; putting copper nitrate trihydrate into a beaker, and adding a solvent to dissolve the copper nitrate to obtain a bluish clear copper nitrate solution; under the stirring state, dropwise adding a copper nitrate solution into the mixed solution; and adjusting the pH value to be within the range of 5-7, sealing a film, pricking holes, standing for 6-9d to obtain a blue crystal, namely the novel copper metal complex. The novel copper metal complex provided by the invention has good anticancer activity and a simple preparation method.
Description
[ technical field ] A method for producing a semiconductor device
The invention relates to the technical field of drug synthesis, in particular to a novel copper metal complex, and a preparation method and application thereof.
[ background of the invention ]
Cancer is usually treated by radiation, surgery, chemotherapy and targeted therapy or a combination of these methods, and surgery and radiation therapy can only ensure that no residual cancer cells exist in the operation region. Chemotherapy is a treatment method for killing cancer cells by using some chemical substances, and the drugs used in chemotherapy generally identify cancer cells through high-speed cell division, so that high-speed growing cells (bone marrow cells, hair follicle cells and the like) are also affected by the chemotherapeutic drugs, and chemotherapy complications occur. Targeted therapy is a treatment method with the ability to identify targets, cancer cell surfaces usually contain specific proteins not found in normal cells, and targeting drugs can identify cancer cells and kill them by using these proteins, while normal cells without specific proteins cannot identify them, so that their side effects are much smaller than chemotherapy.
At present, the metal drugs as anticancer drugs are mainly platinum anticancer drugs. The compound has strong anticancer activity, wide action spectrum and unique action mechanism, does not generate cross drug resistance with non-platinum anticancer drugs, is a first choice drug for treating a plurality of tumors, and is widely used. However, platinum anticancer drugs have large toxic and side effects, and patients with cancer to be treated usually have severe toxic and side effects such as low platelet, nausea and vomiting, renal and nerve injury and the like, so that the research on non-platinum anticancer drugs with small toxicity is still one of the main directions for the research on anticancer drugs.
[ summary of the invention ]
The invention aims to: aiming at the problems, the invention provides a novel copper metal complex, a preparation method and application thereof.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
a novel copper metal complex has the following coordination structure:
wherein the unit structure of the complex is as follows:
the invention also provides a preparation method of the novel copper metal complex, which comprises the following steps: weighing 4-chloro-3-nitrobenzoic acid and 2, 2' -bipyridine, placing in a beaker, adding a solvent, stirring and dissolving to prepare a mixed solution; putting copper nitrate trihydrate into a beaker, and adding a solvent to dissolve the copper nitrate to obtain a bluish clear copper nitrate solution; under the stirring state, dropwise adding a copper nitrate solution into the mixed solution; and adjusting the pH value to be within the range of 5-7, sealing the membrane, pricking holes and standing for 6-9d to obtain blue crystals, namely the novel copper metal complex.
In the present invention, it is preferable that the molar ratio of 4-chloro-3-nitrobenzoic acid, 2' -bipyridine, copper nitrate trihydrate is 3: 0.8-1.2: 0.8-1.2.
In the present invention, the dropping time of the copper nitrate solution is preferably 20 to 40 min.
In the present invention, preferably, the solvent is methanol.
In the present invention, it is preferable to use a 1.0mol/L NaOH solution for adjusting the pH.
The experiment proves that the obtained complex has better anticancer activity, so the invention also provides the application of the novel copper metal complex in preparing the cancer treatment medicine. More particularly, the application in preparing the medicine for treating cervical cancer, lung cancer and liver cancer.
In summary, due to the adoption of the technical scheme, the invention has the beneficial effects that:
1. the invention provides a novel copper metal complex with anticancer activity and a preparation method thereof, and pharmacological analysis proves that the copper complex has better anticancer activity, and IC of cells after the copper complex reacts with cervical cancer cell Hela, lung cancer cell A549 and liver cancer cell HepG2 for 48 hours50The values were 44.85. mu.M, 35.92. mu.M, 24.46. mu.M, respectively; and the preparation method is simple, has low requirements on equipment, and is suitable for popularization and application in the field of anticancer.
2. The invention proves that the combination mode of the synthesized novel copper metal complex and the CT-DNA is insertion type through ultraviolet absorption spectrum, fluorescence spectrum and viscosity, has stronger combination with the CT-DNA and has the combination constant Ka＝6.98×103L·mol-1(ii) a Ultraviolet absorption spectrum and fluorescence spectrum prove that the combined mode of the synthesized novel copper metal complex and HSA is insertion type, and has stronger combination with HSA and a combination constant Ka＝1.84×103L·mol-1The number of binding sites is 1.
3. After the novel copper metal complex synthesized by the invention acts on HepG2 cells for 24h and 48h, the proportion of the number of cells in the G0/G1 phase is increased along with the increase of the concentration of the medicament, which indicates that the complex blocks the cycle of the HepG2 cells in the G0/G1 phase.
4. The copper complex synthesized by the invention has influence on apoptosis of HepG2 cells and can induce the apoptosis of HepG2 cells.
[ description of the drawings ]
FIG. 1 is a diagram showing the coordination structure of the novel copper metal complex synthesized by the present invention.
FIG. 2 is a unit structure diagram of the novel copper metal complex synthesized by the present invention.
FIG. 3 is the ultraviolet absorption spectrum of the interaction between the novel copper metal complex synthesized by the present invention and calf thymus DNA (CT-DNA).
FIG. 4 is a fluorescent spectrum of interaction of the novel copper metal complex synthesized by the present invention and calf thymus DNA (CT-DNA).
FIG. 5 is a diagram showing the change of the viscosity of calf thymus DNA (CT-DNA) after the novel copper metal complex synthesized by the present invention reacts with the CT-DNA.
FIG. 6 is a diagram showing the UV absorption spectrum of the interaction between the novel copper metal complex synthesized by the present invention and Human Serum Albumin (HSA).
FIG. 7 is a fluorescent spectrum of the interaction of the novel copper metal complex synthesized according to the present invention with Human Serum Albumin (HSA).
FIG. 8 is a cytotoxicity diagram of the novel copper metal complex synthesized by the invention after the novel copper metal complex has an effect on lung cancer cells A549, cervical cancer cells Hela and liver cancer cells HepG 2.
FIG. 9 is a diagram showing the results of the test of the effect of the novel copper metal complex synthesized by the present invention on the cell cycle of hepatoma cell HepG 2.
FIG. 10 is a diagram showing the results of the test of the effect of the novel copper metal complex synthesized by the present invention on the apoptosis of hepatoma cell HepG 2.
FIG. 11 shows the results of the test of the expression of the protein related to HepG2 cells from liver cancer cells by the novel copper metal complex synthesized by the present invention.
[ detailed description ] embodiments
It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments according to the present application. It will be further understood that the terms "comprises" and/or "comprising," when used in this specification, specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof.
In order to obtain more complexes with higher anticancer activity, the invention provides a novel copper metal complex through research and verification, wherein the coordination structure diagram of the complex. In an exemplary embodiment of the present invention, a novel copper metal complex is provided, the coordination structure of which is shown in FIG. 1. Wherein the unit structure diagram of the complex is shown in figure 2.
In the embodiment, 4-chloro-3-nitrobenzoic acid and 2, 2' -bipyridine are taken as ligands and react with copper nitrate trihydrate to generate a hexa-coordination complex with copper ions as centers, and the structure improves the anticancer activity of the complex.
The novel copper metal complex with anticancer activity belongs to a monoclinic system, C12/C1 space group, the unit cell parameters are 21.7978(6) nm, b 13.8337(4) nm and C14.0676 (4) nm; α is 90 °, β is 100.120(2 °), γ is 90 °; z is 4, Dc＝1.613mg/m3F (000) ═ 2028, final structure residual factor R1＝0.0474，wR2＝0.1476。
In some embodiments of the present invention, there is also provided a method for preparing the above novel copper metal complex, comprising the steps of: weighing 4-chloro-3-nitrobenzoic acid and 2, 2' -bipyridine, placing in a beaker, adding a solvent, stirring and dissolving to prepare a mixed solution; putting copper nitrate trihydrate into a beaker, and adding a solvent to dissolve the copper nitrate to obtain a bluish clear copper nitrate solution; under the stirring state, dropwise adding a copper nitrate solution into the mixed solution; and adjusting the pH value to be within the range of 5-7, sealing the membrane, pricking holes and standing for 6-9d to obtain blue crystals, namely the novel copper metal complex.
In order to allow the ligand starting materials to react sufficiently and obtain the target complex, in some preferred embodiments, the molar ratio of 4-chloro-3-nitrobenzoic acid, 2' -bipyridine, copper nitrate trihydrate is 3: 0.8-1.2: 0.8-1.2.
In order to disperse ligand raw materials uniformly and fully, and improve the separation and purification efficiency of products, in some preferred embodiments, the solvent is methanol.
In order to precipitate the ligand compound, in some preferred embodiments, a 1.0mol/L NaOH solution is used to adjust the pH.
For better reaction, in some preferred embodiments, the dropping time of the copper nitrate solution is 20-40 min.
In order to make the technical solutions of the present application more clearly understood by those skilled in the art, the technical solutions of the present application will be described in detail below with reference to specific embodiments.
First, preparation example
Example 1
And (3) synthesis of a complex: weighing 4-chloro-3-nitrobenzoic acid (0.3mmol) and 2, 2' -bipyridine (0.08mmol) and placing in a beaker, adding 5mL of methanol, stirring and dissolving to prepare a mixed solution; putting copper nitrate trihydrate (0.08mmol) in a beaker, and adding 10mL of methanol for dissolving to obtain a bluish clear copper nitrate solution; under the stirring state, dropwise adding the copper nitrate solution into the mixed solution within 20 min; and adjusting the pH value to 5, sealing the membrane, pricking holes and standing for 6d to obtain blue crystals, namely the novel copper metal complex.
Example 2
And (3) synthesis of a complex: weighing 4-chloro-3-nitrobenzoic acid (0.3mmol) and 2, 2' -bipyridine (0.1mmol) and placing in a beaker, adding 5mL of methanol, stirring and dissolving to prepare a mixed solution; another copper nitrate trihydrate (0.1mmol) is placed in a beaker, and 10mL of methanol is added for dissolution to obtain a bluish clear copper nitrate solution; under the stirring state, dropwise adding the copper nitrate solution into the mixed solution within 30 min; adjusting the pH value to be within 6, sealing a membrane, pricking holes and standing for 7d to obtain blue crystals, namely the novel copper metal complex; the yield was about 52.3%.
Example 3
And (3) synthesis of a complex: weighing 4-chloro-3-nitrobenzoic acid (0.3mmol) and 2, 2' -bipyridine (0.12mmol) and placing in a beaker, adding 5mL of methanol, stirring and dissolving to prepare a mixed solution; putting copper nitrate trihydrate (0.12mmol) in a beaker, and adding 10mL of methanol for dissolving to obtain a bluish clear copper nitrate solution; under the stirring state, dropwise adding the copper nitrate solution into the mixed solution within 40 min; and adjusting the pH value within 7, sealing the membrane, pricking holes and standing for 9d to obtain blue crystals, namely the novel copper metal complex.
Identification of bis, Complex
The blue bulk crystals prepared in examples 1 to 3 were subjected to XRD test, infrared test, elemental analysis test and crystallography test, and the results were as follows:
infrared data: r (KBr) v/cm-1:v(＝CH)3442,v(C＝O)1699,v(C＝C)1587,1457,v(C-N)1318,v(C-N-C)1038, 778。
Elemental analysis data: elemental analysis according to [ C38H12Cl4CuN6O16]C,45.02 in calculated value (%); h, 1.19; and N, 8.29. The experimental value (%) is C, 45.98; h, 1.14; and N, 8.20.
Crystallographic data: complex [ C38H12Cl4CuN6O16]The data of the crystallography, the key length and angle, the twist angle, etc. are shown in tables 1, 2 and 3, respectively.
TABLE 1 Main crystallographic parameters of the novel copper metal complexes synthesized according to the invention
TABLE 2 major bond lengths and bond angles for novel copper metal complexes synthesized in accordance with the present invention
Symmetric transformations for generating equivalent atoms:
#1-x+ 1,y,-z+ 1/2
TABLE 3 Primary torsion Angle of the novel copper Metal complexes synthesized according to the invention
Symmetric transformations for generating equivalent atoms:
#1-x+ 1,y,-z+ 1/2
third, the ultraviolet absorption spectrum of the interaction between the novel copper metal complex synthesized by the invention and DNA
Adding 3mL (Tris-HCl/NaCl) buffer solution into the blank pool and the sample pool respectively, correcting the base line, and changing the sample pool to the equal volume of 50 mu mol.L-1The complex solution scans the electron absorption spectrum within the wavelength range of 190-450nm, then 80 mu L of 2mmol/L CT-DNA solution is respectively added into a blank pool and a sample pool by a liquid-transferring gun for 8 times, the mixture is uniformly stirred and kept stand for 5min after each dropwise addition, and then the scanning of the electron absorption spectrum is carried out.
FIG. 3 is the ultraviolet absorption spectrum of the interaction between the novel copper metal complex synthesized by the present invention and calf thymus DNA (CT-DNA). It can be seen that the complex has a color-reducing property at 256nm as the concentration of CT-DNA increases, and thus it is presumed that the complex has an intercalation effect on CT-DNA. Calculating to obtain the binding constant K of the complex and the DNAb＝5.06×103L·mol-1。
Fourthly, the fluorescence spectrum of the action of the novel copper metal complex synthesized by the invention and CT-DNA
Mixing 8 mu mol/L-1Ethidium Bromide (EB) and 10. mu. mol. L-1And uniformly mixing the CT-DNA solution with the same volume, and reacting for 12 hours. Adding 2.5mL of EB-CT-DNA mixed solution into a sample cell, and scanning at 491nm and 240nm s-1Then, the emission spectrum in the wavelength range of 450 to 750nm is measured. Adding 20 mul of solution with the concentration of 1 mmol.L dropwise into an EB-CT-DNA system-1The complex solution of (4) was added dropwise 16 times in total. After each reaction for 5min, the emission spectrum was measured again.
FIG. 4 is a fluorescent spectrum of interaction of the novel copper metal complex synthesized by the present invention and calf thymus DNA (CT-DNA). It can be seen that the fluorescence intensity gradually decreases at 596nm as the concentration of the complex increases. At different r ═ Complex]/[DNA]At this value, the initial fluorescence intensity dropped from 97.64% to 69.10%. The action mode of the complex and CT-DNA is similar to that of EB, and is a classical insertion mode. Obtaining a quenching rate constant Kq＝3.79×1011L·mol-1·s-1. ComplexesThe fluorescence quenching of EB-DNA is static quenching with a binding constant Ka＝6.98×103L·mol-1And the binding site n is 1.
Fifthly, the influence of the novel copper metal complex synthesized by the invention on the viscosity of CT-DNA
The reaction temperature is controlled at 29.0 +/-0.1 ℃ by using a constant-temperature water tank, the CT-DNA solution is added into an Ubbelohde viscometer, the concentration of the Complex solution is gradually increased, the concentration ratio of the Complex to the CT-DNA [ Complex ]/[ DNA ] is0, 0.05, 0.1, 0.15, 0.20, 0.25 and 0.30, the time(s) for the CT-DNA solution to flow through an effective scale of a capillary is recorded in sequence, each group of experiments is repeated for 3 times, and the average value is taken.
FIG. 5 is a diagram showing the change of the viscosity of calf thymus DNA (CT-DNA) after the novel copper metal complex synthesized by the present invention reacts with the CT-DNA. It can be seen that as the concentration of the complex increases, the viscosity of the DNA increases, indicating that the complex binds to the DNA in an intercalated manner.
Sixthly, ultraviolet absorption spectrum of action of novel copper metal complex synthesized by the invention and HSA
2.5mL of 1. mu. mol. L was added to the sample cell-1Adding a sample amount of Tris-HCl/NaCl buffer solution into the reference pool of the HSA solution, and measuring the ultraviolet spectrum of the HSA solution within 190-400 nm. 50 μ L of complex solution (1.2X 10) was added to each of the two wells-6 mol·L-1) And the total number of the components is 17, after each addition, the components are uniformly blown and stirred, and after the components are placed for 5min at room temperature, the components are scanned and measured in the same wavelength range.
FIG. 6 is a diagram showing the UV absorption spectrum of the interaction between the novel copper metal complex synthesized by the present invention and Human Serum Albumin (HSA). It can be seen that as the concentration of the complex increases, the absorption peak at 265nm undergoes a subtractive effect, indicating that the complex interacts with HSA.
Seventhly, the fluorescence spectrum of the action of the novel copper metal complex synthesized by the invention and HSA
2.5mL of HSA solution (5. mu. mol. L) was added to the sample cell-1) And measuring the fluorescence spectrum of the sample in the wavelength range of 280-450 nm under the excitation state of 280 nm. Then 2. mu.L of the complex solution (1.2mmol/L) was added to the sample cell, and14 times, each time after adding, blow and mix well, at room temperature for 5min, scan under the same conditions.
FIG. 7 is a fluorescent spectrum of the interaction of the novel copper metal complex synthesized according to the present invention with Human Serum Albumin (HSA). It can be seen that HSA has an increased concentration of the complex at 337nm, which is a strong absorption peak, and the absorption intensity decreases. At different r ═ Complex]/[DNA]At this value, the initial fluorescence intensity dropped from 66.77% to 29.90%. Constant value K of quenching rateq＝1.45×1013 L·mol-1·s-1The fluorescence quenching of the complex to HSA is static quenching with a binding constant Ka＝1.84×103L·mol-1The number of binding sites n is 1.
Eighthly, the novel copper metal complex synthesized by the invention has cytotoxicity to tumor cells
And (3) determining the cytotoxicity of the complex on the cervical cancer cell Hela, the lung cancer cell A549 and the liver cancer cell HepG2 by using an enzyme-labeling instrument. FIG. 8 is a cytotoxicity diagram of the novel copper metal complex synthesized by the invention after the novel copper metal complex has an effect on lung cancer cells A549, cervical cancer cells Hela and liver cancer cells HepG 2. Calculating to obtain the IC of the cell after the complex reacts with lung cancer cell A549, cervical cancer cell Hela and liver cancer cell HepG2 for 48 hours50The values were 44.85. mu.M, 35.92. mu.M, and 24.46. mu.M, respectively. The novel copper metal complex synthesized by the invention has better anticancer activity on tumor cells, so that the novel copper metal complex can be applied to the preparation of cancer treatment medicines, particularly cervical cancer, lung cancer and liver cancer treatment medicines.
Ninth, the novel metal complex synthesized by the invention has influence on the cell cycle of liver cancer cells HepG2
The influence of the metal complex on the cell cycle of the liver cancer cell HepG2 is determined by a flow cytometer, and FIG. 9 is a test result diagram of the influence of the novel copper metal complex synthesized by the invention on the cell cycle of the liver cancer cell HepG 2. After the novel copper metal complex acts on HepG2 cells for 24 hours and 48 hours, the proportion of the number of the cells in the G0/G1 phase is gradually increased along with the increase of the concentration of the medicament, which indicates that the complex blocks the cycle of the HepG2 cells in the G0/G1 phase.
Tenth, the metal complex synthesized by the invention has the effect on the apoptosis of liver cancer cell HepG2
The influence of the novel metal complex on the apoptosis of the liver cancer cell HepG2 is determined by a flow cytometer, and FIG. 10 is a diagram showing the influence of the novel copper metal complex synthesized by the invention on the apoptosis of the liver cancer cell HepG 2. The result shows that the metal complex has influence on the apoptosis of HepG2 cells and can induce the apoptosis of HepG2 cells.
Eleven, the novel copper metal complex synthesized by the invention expresses the liver cancer cell HepG2 related protein:
(1) glue filling
The glass plate is cleaned by distilled water and dried vertically.
Preparing 10mL of 12% separation glue, adding 10 mu L of TEMED and 100 mu L of 10% ammonium persulfate, mixing uniformly, pouring the glue immediately until the lower edge of the comb is 2-3 mm (marked in advance), sealing the liquid level with deionized water to remove bubbles and isolate air, and standing at room temperature for 45min until the glue is completely polymerized.
Thirdly, after the separation gel is completely polymerized, pouring the deionized water on the top of the separation gel, and sucking the water by using filter paper.
Fourthly, 5mL of 6% concentrated glue is prepared, 5 mu L of TEMED and 50 mu L of 10% APS are added, the mixture is evenly mixed and immediately filled with glue, the glue is filled to the top, a Teflon comb is vertically inserted, and the mixture is stood for 20min at room temperature until the glue is polymerized.
Fifthly, after the gel is completely polymerized, the comb is pulled out, the gel is placed in an electrophoresis tank, electrophoresis buffer solution is added, and the sample loading hole is washed by the electrophoresis buffer solution to remove air bubbles.
(2) Electrophoresis
Taking each processed histone extract, adjusting the protein concentration to be 6 mug/mu L, and mixing the histone extract with an equal volume of sample loading buffer solution to obtain a sample loading solution.
② boiling the sample liquid in boiling water at 100 ℃ for 5min to denature protein, quenching on ice, and centrifuging at 3000 r/min for 1 min.
③ adding 15 mu L of sample liquid into each hole, and reserving one hole and adding 10 mu L of pre-dyed Marker. Filling the electrophoresis buffer solution, covering the cover of the groove, switching on the power supply, performing constant voltage electrophoresis at 80v for about 20min, performing constant voltage electrophoresis at 110v after the indicator bromophenol blue enters the separation gel, turning off the power supply when the indicator reaches a position about 0.5cm away from the lower end of the gel, and taking out the gel plate.
(3) Trans-proteins and immunoassays
Firstly, just before the end of electrophoresis, a PVDF membrane is soaked in methanol for 15s in advance and then is treated with ddH2Rinsing for 2min with O, soaking in transfer buffer for 5min, and starting subsequent operation.
Prying the glue in water, soaking the glue in a transfer buffer solution for balancing for 15min after glue repairing.
Preparing a transfer film sandwich in the sequence of black surface (negative electrode) → sponge → filter paper → glue → PVDF film → filter paper → sponge → red surface (positive electrode), and laying each layer, then removing bubbles and laying the other layer. The sandwich is prepared in a transfer buffer to avoid the generation of air bubbles.
And fourthly, connecting the positive electrode and the negative electrode, putting the transfer box into the electrotransfer instrument according to the direction from the membrane to the positive electrode, and adding a membrane transfer buffer solution.
Fifthly, placing the electric rotating instrument in ice water, and rotating the membrane for 1h at a constant voltage of 100 v.
Sixthly, after the membrane transfer is finished, quickly taking out the PVDF membrane, and putting 5% BSA for sealing for 2 hours at room temperature.
Seventhly, taking out the membrane, and washing the membrane for 5min multiplied by 3 times on a shaking table.
The bag is added with Caspase-3 (1: 1000), Bcl-2 (1: 1000), Bax (1: 1000) and GAPDH (1: 5000) diluted by TBST and incubated overnight at 4 ℃.
Ninthly, TBST washes the membrane for 5min × 3 times, and horseradish peroxidase (HRP) labeled secondary antibody (1: 2000) is incubated for 1h at room temperature.
Wash membrane 10min X3 times in TBST. The film and the chemiluminescence detection reagent react until bright strips appear in dark places, the film is taken out, redundant liquid is thrown away, a PVDF film is wrapped by a preservative film, and the film is subjected to light sensing, developing and fixing by an X film in a dark room.
FIG. 11 is a diagram showing the results of the test of the expression of the novel copper metal complex synthesized by the present invention on the protein associated with the liver cancer cell HepG2 cell. The result shows that the metal complex has influence on the apoptosis of HepG2 cells and can induce the apoptosis of HepG2 cells.
The above description is intended to describe in detail the preferred embodiments of the present invention, but the embodiments are not intended to limit the scope of the claims of the present invention, and all equivalent changes and modifications made within the technical spirit of the present invention should fall within the scope of the claims of the present invention.
Claims (9)
1. A novel copper metal complex is characterized in that the coordination structure of the complex is as follows:
2. a novel copper metal complex according to claim 1, having the unit structure:
3. the process for preparing a novel copper metal complex according to claim 1, comprising the steps of: weighing 4-chloro-3-nitrobenzoic acid and 2, 2' -bipyridine, placing in a beaker, adding a solvent, stirring and dissolving to prepare a mixed solution; putting copper nitrate trihydrate into a beaker, and adding a solvent to dissolve the copper nitrate to obtain a bluish clear copper nitrate solution; under the stirring state, dropwise adding a copper nitrate solution into the mixed solution; and adjusting the pH value to be within the range of 5-7, sealing the membrane, pricking holes and standing for 6-9d to obtain blue crystals, namely the novel copper metal complex.
4. A novel copper metal complex according to claim 1, characterized in that: the mol ratio of the 4-chloro-3-nitrobenzoic acid to the 2, 2' -bipyridine to the copper nitrate trihydrate is 3: 0.8-1.2: 0.8-1.2.
5. A novel copper metal complex according to claim 1, characterized in that: the dropping time of the copper nitrate solution is 20-40 min.
6. A novel copper metal complex according to claim 1, characterized in that: the solvent is methanol.
7. A novel copper metal complex according to claim 1, characterized in that: the pH value is adjusted by using 1.0mol/L NaOH solution.
8. Use of a novel copper metal complex according to claim 1 in the preparation of a medicament for the treatment of cancer.
9. Use of a novel copper metal complex according to claim 8 in the preparation of a medicament for the treatment of cervical, lung and liver cancer.
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