CN110790778B - Copper compound with 2-thiophenecarboxaldehyde thiosemicarbazone as ligand and synthetic method thereof - Google Patents
Copper compound with 2-thiophenecarboxaldehyde thiosemicarbazone as ligand and synthetic method thereof Download PDFInfo
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- CN110790778B CN110790778B CN201911117732.8A CN201911117732A CN110790778B CN 110790778 B CN110790778 B CN 110790778B CN 201911117732 A CN201911117732 A CN 201911117732A CN 110790778 B CN110790778 B CN 110790778B
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- 239000003446 ligand Substances 0.000 title claims abstract description 42
- 239000005749 Copper compound Substances 0.000 title claims abstract description 26
- 150000001880 copper compounds Chemical class 0.000 title claims abstract description 26
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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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- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
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- 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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Abstract
The invention discloses a copper compound taking 2-thiophenecarboxaldehyde thiosemicarbazone as a ligand and a synthesis method thereof, wherein the synthesis method comprises the steps of taking thiosemicarbazone, adding absolute ethyl alcohol, stirring and dissolving, adding 2-thiophenecarboxaldehyde after dissolving, uniformly mixing, stirring the mixed solution at 70 ℃ in a water bath, volatilizing at room temperature, and separating out crystals to obtain the ligand; adding anhydrous ethanol into the prepared ligand, stirring for dissolving, adding CuBr after dissolving2·2H2And O, stirring in a water bath at 70 ℃, volatilizing at room temperature, and separating out crystals to obtain the Cu compound of the ligand. The invention further carries out in-vitro proliferation inhibition activity experiments on the synthesized copper compounds, and the results show that the synthesized series of copper compounds have generally better in-vitro activity, particularly have high specificity to human T24 and HeLa cells, show good inhibition activity, have small toxic effect on normal human cells, and are suitable for preparing high-efficiency and low-toxicity antitumor drugs.
Description
Technical Field
The invention relates to a copper compound, in particular to a copper compound taking 2-thiophenecarboxaldehyde thiosemicarbazone as a ligand and a synthesis method thereof.
Background
Cancer is a primary factor threatening the health of human beings, and is called "absolute disease" because the cure rate of cancer is very low at present. The treatment of cancer is classified into a variety of methods including surgical resection, radiotherapy, chemotherapy and targeted therapy, which have limitations according to the type, growth location and incidence of cancer. Immunotherapy, the first time it was used in 1997 for the treatment of cancer, has now become an important research direction for scientists. In recent years, immune-related tumor treatment schemes have seen promise in curing cancer, and the important role of metal elements in immune response and tumor treatment is receiving increasing attention and is an important direction for future development. However, most of the studies at present only stay in the phenomenon description stage, and it is difficult to elucidate the mechanism at the molecular level. There is increasing evidence that metallic elements play a key role in many aspects of the immune response in humans. First, immune signal transduction is the core process of immune response, and in recent years, various metal ions such as calcium, zinc, copper, manganese, magnesium and the like have been found to have a direct relationship with the activation of immune cells. Based on the pharmacological properties of different metals, copper complexes are undoubtedly the best choice, and copper, as an important element, is found in all organisms, is a key trace element in redox chemistry and growth and development, plays an extremely important role in participating in energy metabolism, respiration and immune regulation in organisms, and plays an important role in cell transportation, substrate oxidation and redox regulation.
Thiosemicarbazones can be obtained by condensing thiosemicarbazones with ketones or aldehydes. Thiosemicarbazone and its metal complex are favored because of their high antitumor activity. Many studies have shown that amino-schiff bases synthesized from aromatic and heterocyclic amines have good activity on human cancer cells. Over the last three decades, researchers have synthesized various copper schiff base complexes, such as thiosemicarbazones, pyridines, salicylaldehyde, and the like, and some of the drugs have been proposed as anticancer drugs. The existing treatment effect on common cancers such as lung cancer, gastric cancer, bladder cancer and the like is not ideal. For this reason, it is indispensable to develop a novel compound capable of preventing tumor proliferation. In recent three decades, however, due to their multidentate coordination with metal ions and broad pharmacological activity, extensive research has begun to be carried out in antiviral, antibacterial, and anticancer applications, and it has been found that the biological activity is derived primarily from the parent aldehyde or ketone moiety. The research of our subject group finds that the synthesized copper compound has interaction with PD-1 protein, and further increases our research on immunotherapy of tumor diseases.
Disclosure of Invention
The invention aims to provide a copper compound taking 2-thiophenecarboxaldehyde thiosemicarbazone as a ligand and a synthesis method thereof.
The technical scheme for realizing the purpose of the invention is as follows:
a copper compound using 2-thiophenecarboxaldehyde thiosemicarbazone as a ligand has a structural formula shown as C1-C4:
the synthetic route of the copper compound shown as C1-C4 is as follows:
the synthetic method of the copper compound comprises the following steps:
(1) taking thiosemicarbazide, adding absolute ethyl alcohol, stirring for dissolving, adding 2-thiophenecarboxaldehyde after dissolving, uniformly mixing, stirring the mixed solution at 70 ℃ in a water bath, volatilizing at room temperature, and separating out crystals to obtain a ligand;
(2) adding anhydrous ethanol into the prepared ligand, stirring for dissolving, adding CuBr after dissolving2·2H2And O, stirring in a water bath at 70 ℃, volatilizing at room temperature, and separating out crystals to obtain the Cu compound of the ligand.
The thiosemicarbazide in the step (1) comprises 4-methyl-3-thiosemicarbazide, 4-phenyl-3-thiosemicarbazide and N, N-2-ethyl-3-thiosemicarbazide; the molar ratio of the thiosemicarbazide to the 2-thiophenecarboxaldehyde is 1:1.
The ligand in the step (2) and CuBr2In a molar ratio of 1: 1.5.
The copper compound of the invention can be synthesized by adopting the following specific steps:
(1) weighing 1mmol of thiosemicarbazide, pouring the thiosemicarbazide into a 100mL flask, adding magnetons, adding 25mL of absolute ethyl alcohol, stirring for half an hour, weighing 1mmol of 2-thiophenecarboxaldehyde according to the proportion of 1:1 by using a pipette, adding the mixture into the flask, stirring for 2 hours at 70 ℃ in a water bath, placing the mixture into a 50mL beaker, placing the beaker in a fume hood, slowly volatilizing at room temperature for 4-6 days to separate out crystals to obtain a ligand;
(2) weighing 0.5mmol of ligand, pouring into a 100mL flask, adding magneton, adding 25mL of anhydrous ethanol, stirring for half an hour, adding 0.75mmol of CuBr2·2H2And O, stirring for 2 hours in a water bath at 70 ℃, placing in a 50ml beaker, placing in a fume hood, slowly volatilizing at room temperature for 6-8 days to precipitate crystals, and obtaining the Cu compound of the ligand.
In the actual synthesis, the dosage of each raw material can be expanded or reduced by times according to the dosage of a specific step.
According to the invention, 2-thiophenecarboxaldehyde and thiosemicarbazide are selected for condensation reaction to obtain a ligand, the ligand is chelated with Cu in a human body or a cell to form a Cu compound, and research results show that the compound can influence the expression quantity of protein, such as the regulation of Cyclin family expression (such as Cyclin), Cyclin-dependent kinase, Bcl family protein (such as Bcl-2, Bcl-xl), apoptosis-related protein (such as Caspase-3, Caspase-9) and the like, and the regulation gene N-myc. Also has effects on the PD-1/PD-L1 pathway of immunotherapy.
The invention further carries out in vitro proliferation inhibition activity experiments on the synthesized copper compounds C1-C4, and the results show that the synthesized series of copper compounds have generally good in vitro activity, particularly have high specificity on human T24 and HeLa cells, show good inhibition activity, have small toxic effect on normal cells of human, and are suitable for preparing high-efficiency and low-toxicity antitumor drugs.
Drawings
FIG. 1 is a single crystal structural diagram of a C1 copper compound synthesized in example 1.
FIG. 2 is a single crystal structural diagram of a C2 copper compound synthesized in example 2.
FIG. 3 is a single crystal structural diagram of a C3 copper compound synthesized in example 3.
FIG. 4 is a single crystal structural view of a C4 copper compound synthesized in example 4.
Detailed Description
The present disclosure will be better understood from the following detailed description taken in conjunction with the accompanying drawings, which are set forth below, but are not intended to limit the present disclosure to the following embodiments.
Example 1:
the synthesis of the copper complex C1 comprises the following steps:
(1) weighing 1mmol of thiosemicarbazide by using an electronic balance, pouring the thiosemicarbazide into a 100mL flask, adding magnetons, adding 25mL of absolute ethyl alcohol, stirring for half an hour, weighing 1mmol of 2-thiophenecarboxaldehyde by using a pipette according to the proportion of 1:1, adding the mixture into the flask, stirring for 2 hours at the temperature of 70 ℃ in a water bath, placing the mixture into a 50mL beaker, placing the beaker in a fume hood, and slowly volatilizing for about 5 days to separate out light yellow needle crystals to obtain a ligand L1; filtering, naturally drying, weighing with an electronic balance, and calculating the yield;
Yield:88％。Anal.Calcd for C6H7N3S2:C,38.90％；H,3,81％；N,22.68％；S,34.61％.IR,cm-1(main peaks):3411.42vs,3235.04s,2997.62s,1678.78m,1582.48s,1474.50s,1279.45m,1097.79m,920.94s,834.57vs,708.52vs,615.74s,525.03m,411.19s.ESI+m/z:calcd for C6H7N3S2,185.01[M-H]；
(2) weighing 0.5mmol of ligand by an electronic balance, pouring into a 100mL flask, adding magnetons, adding 25mL of absolute ethanol, stirring for half an hour, adding 0.75mmol of CuBr2·2H2O，Stirring for 2h in a water bath at 70 ℃, placing in a 50ml beaker, placing in a fume hood, slowly volatilizing for about 7d to precipitate yellow crystals to obtain a Cu compound of a ligand L1; filtering, drying at room temperature, weighing, and calculating the yield;
yield 83 percent. The structure of the metal complex with regular shape is measured by a single crystal diffractometer. Anal. Calcd for C36H42Br3Cu3N18S 12C, 27.99%; h, 2.94%; n, 16.32%; s, 24.9%; br, 15.52%. IR, cm-1(main peaks):3412.39S,3235.42M,3144.78S,2996.59w,1581.47S,1536.90vs,1474.73w,1323.48M,1278.57M,1098.26S,843.94S,707.79S,523.61M,411.28s.ESI + M/z: calcd for C36H42Br3Cu3N18S12:1539.59[ M-H ].
Example 2:
the synthesis of the copper complex C2 comprises the following steps:
(1) weighing 1mmol of 4-methyl-3-thiosemicarbazide by using an electronic balance, pouring the weighed 4-methyl-3-thiosemicarbazide into a 100mL flask, adding magnetons, adding 25mL of absolute ethyl alcohol, stirring for half an hour, weighing 1mmol of 2-thiophenecarboxaldehyde by using a pipette according to the proportion of 1:1, stirring for 2 hours at the temperature of 70 ℃ in a water bath, placing the mixture in a 50mL beaker, placing the beaker in a fume hood, and slowly volatilizing for 4-6 days to precipitate light yellow crystals to obtain a ligand L2; filtering, drying at room temperature, weighing, and calculating the yield;
Yield:82％。Anal.Calcd for C7H9N3S2:C,42.19％；H,4.55％；N,21.08％；S,32.18％.IR,cm-1(main peaks):3373.34m,3340.24m,3173.13s,2997.05m,1592.30m,1542.57vs,1379.21m,1271.24s,1224.31m,1086.88s,1036.38s,923.81s,717.54vs,561.97s.ESI+m/z:calcd for C7H9N3S2,199.02[M-H]；
(2) weighing 0.5mmol of ligand by an electronic balance, pouring into a 100mL flask, adding magnetons, adding 25mL of absolute ethanol, stirring for half an hour, adding 0.75mmol of CuBr2·2H2O, stirring for 2 hours in a water bath at 70 ℃, placing the mixture in a 50ml beaker and placing the beaker in a fume hood, and slowly volatilizing for 7 days to precipitate yellow crystals to obtain a Cu compound of a ligand L2; filtering, drying at room temperature, weighing, and calculating the yield;
89 percent of Yield. The structure of the metal complex with regular shape is measured by a single crystal diffractometer. Anal. Calcd for C28H38Br2Cu2N12S8Cu 2C, 30.96%; h, 3.53%; n, 15.48%; s,23.62 percent; br, 14.71%. IR, cm-1(main peaks):3318.72s,314.78s,3000.42s,2946.27M,1546.95vs,1435.29M,1259.67s,1092.38s,1034.97s,921.02M,819.52M,707.79s,635.09s,572.60m.ESI + M/z: calcd for C28H38Br2Cu2N12S8,1085.80[ M-H ].
Example 3:
the synthesis of the copper complex C3 comprises the following steps:
(1) weighing 1mmol of 4-phenyl-3-thiosemicarbazide by using an electronic balance, pouring the weighed 4-phenyl-3-thiosemicarbazide into a 100mL flask, adding magnetons, adding 25mL of absolute ethyl alcohol, stirring for half an hour, weighing 1mmol of 2-thiophenecarboxaldehyde according to the proportion of 1:1 by using a liquid transfer gun, slowly adding the weighed 2-thiophenecarboxaldehyde into the flask while stirring, reacting for 2 hours under the condition of water bath at 70 ℃, taking out the obtained product, filtering, placing the obtained product in a 50mL beaker, placing the obtained product in a fume hood, and slowly volatilizing the obtained product for 5 days to separate out light yellow crystals to obtain a ligand; filtering, drying at room temperature, weighing, and calculating the yield;
Yield:89％。Anal.Calcd for C12H11N3S2：C,55.41％；H,4.24％；N,16.08％；S,24.54％.IR,cm-1(main peaks):3300.11s,3141.10s,2986.89s,1591.61m,1545.22vs,1444.40m,1386.97s,1272.00s,1204.98s,1074.91m,923.03s,705.34s,524.10s.ESI+m/z:calcd for C12H11N3S2,261.04[M-H]；
(2) weighing 0.5mmol of ligand by using an electronic balance, pouring the ligand into a 100mL flask, adding magnetons, adding 25mL of absolute ethyl alcohol, stirring for half an hour, adding 0.75mmol of CuBr2 & 2H2O, stirring for reacting for 2 hours at 70 ℃ in a water bath, taking out, filtering, placing the mixture in a 50mL beaker, placing the beaker in a fume hood, slowly volatilizing for 6 days to precipitate black crystals, and obtaining a Cu compound of the ligand L3; filtering, drying at room temperature, weighing, and calculating the yield;
yield is 86 percent. The structure of the metal complex with regular shape is measured by a single crystal diffractometer. Anal. Calcd for C48H32Cu4N12S 8C 44.05%; h, 3.64%; n, 12.84%; s,19.60 percent; cl, 4.33%. IR, cm-1(main peaks):3432.11M,3105.05s,2940.25M, 1554.79s,1498.37vs,1485.39s,1316.81s,1233.76s,939.16M,850.79s,696.86vs,612.78s.ESI + M/z: calcd for C48H32Cu4N12S8,1285.78[ M-H ].
Example 4:
the synthesis of the copper complex C4 comprises the following steps:
the synthesis method comprises the following steps:
(1) weighing 2mol of sodium diethyldithiocarbamate (trihydrate) by using an electronic balance, dissolving the sodium diethyldithiocarbamate (trihydrate) in 1L of ultrapure water, adding 2mol of sodium chloroacetate, adding a small amount of NaOH, stirring at room temperature for 24 hours, adding 6mol/L of hydrochloric acid until white precipitates are not increased any more, performing suction filtration, drying at room temperature, and weighing;
taking 80% hydrazine hydrate, wherein the ratio of the amount of the hydrazine hydrate to the amount of the diethyl hydroxymethyl thioformate is 1:1.8, heating the solution in an oil bath at 120 ℃ for 0.5h to turn the solution into red, cooling the solution to room temperature to separate out white crystals, heating the solution to 120 ℃, and repeating the heating for 3 to 4 times to finally obtain the white crystals, namely N, N-2-ethyl-3-thiosemicarbazide (N, N-2-ethyl-3-thiosemicarbazide is not sold in the market and is obtained by synthesis); performing suction filtration, naturally drying, and placing in an anhydrous CaCl2 glassware for later use;
(2) weighing 1mmol of N, N-2-ethyl-3-thiosemicarbazide by using an electronic balance, pouring the N, N-2-ethyl-3-thiosemicarbazide into a 100mL flask, adding magnetons, adding 25mL of absolute ethyl alcohol, stirring for half an hour, weighing 1mmol of 2-thiophenecarboxaldehyde by using a pipette according to the proportion of 1:1, adding the mixture into the flask, stirring for 2 hours at the temperature of 70 ℃ in a water bath, placing the mixture into a 50mL beaker, placing the beaker in a fume hood, and slowly volatilizing for 4 days to separate out light yellow crystals to obtain a ligand L4; filtering, drying at room temperature, weighing, and calculating the yield;
Yield:79％。Anal.Calcd(％)for C10H15N3S2:C,49.76％；H,6.26％；N,17.41％；S,26.57％.IR,cm-1(main peaks):3443.42s,2937.45s,1580.96vs,1489.66s,1413.52s,1388.53s,1278.38s,1156.62s,1064.65s,714.83s,630.36m.ESI+m/z:calcd for C10H15N3S2,241.07[M-H]；
(3) weighing 0.5mmol of ligand by an electronic balance, pouring the ligand into a 100mL flask, adding magnetons, adding 25mL of absolute ethyl alcohol, stirring for half an hour, adding 0.75mmol of CuBr2 & 2H2O, stirring for 2 hours at 70 ℃ in a water bath, placing the mixture in a 50mL beaker, placing the beaker in a fume hood, slowly volatilizing for 8 days, and separating out black crystals to obtain a Cu compound of the ligand L4. Filtering, drying at room temperature, weighing, and calculating the yield;
65 percent of Yield. The structure of the metal complex with regular shape is measured by a single crystal diffractometer. Anal. Calcd for C20H31N6S4Cu: C, 43.89%; h, 5.71%; n, 15.36%; s, 23.43%. IR, cm-1(main peaks):3459.40vs,2973.25S,1605.49S,1499.85S,1433.52S,1380.49S,1269.33S,1142.02S,1059.68S,704.13S, 627.86m.ESI + M/z: calcd for C20H31N6S4Cu,546.08[ M-H ].
To illustrate the copper compounds of the present invention, the applicant conducted in vitro antitumor activity experiments on the copper compounds C1-C4 prepared in the above examples 1-4:
1. cell lines and cell cultures
A549, NCI-H460, T-24, HeLa and MGC-803 are selected and compared with different cancer cells, the activity of the compound on T24 and HeLa cells is found and activity exploration is carried out. All cell lines were cultured in RPMI-1640/DMEM medium containing 10% calf serum and 100U/mL streptomycin at 37 ℃ with 5% CO by volume2Culturing in an incubator.
2. Preparation of test Compounds
The purity of the used test drug is more than or equal to 95 percent, the DMSO stock solution is diluted by physiological buffer solution to be prepared into 5mmol/L final solution, wherein the concentration of the cosolvent DMSO is less than or equal to 1 percent, and the degree of inhibition of the compound on the growth of various tumor cells under the concentration is tested.
3. Cell growth inhibition assay (MTT method)
(1) Taking tumor cells in a logarithmic growth phase, digesting the tumor cells by trypsin, preparing a cell suspension with the concentration of 5000/mL by using a culture solution containing 10% calf serum, inoculating 180 mu L of the cell suspension into a 96-well culture plate, and enabling the concentration of cells to be detected to be 1000-10000/well (the marginal wells are filled with sterile PBS);
(2)5％CO2incubating for 24h at 37 ℃ until a cell monolayer is paved on the bottom of the hole, adding 20 mu L of medicine with a certain concentration gradient into each hole, and arranging 5 compound holes in each concentration gradient;
(3)5％CO2incubating at 37 ℃ for 48h toObserving under an inverted microscope;
(4) adding 10 μ L of MTT solution (5mg/mL PBS, i.e. 0.5% MTT) into each well, and culturing for 4-6 h;
(5) terminating the culture, carefully removing the culture solution in the wells, adding 100. mu.L of DMSO into each well to sufficiently dissolve formazan precipitate, mixing uniformly by using an oscillator, and measuring the optical density of each well by using an microplate reader at a wavelength of 570nm and a reference wavelength of 450 nm;
(6) the number of living cells was judged from the measured optical density values (OD values), and the larger the OD value, the stronger the cell activity.
Using the formula:
tumor cell growth inhibition (%) [ (1-mean OD of experimental group)/(mean OD of control group) ] ×%;
IC50and (3) determination: by using the method, each compound is required to be provided with a concentration gradient which comprises a plurality of (generally 5-8) concentrations, each concentration is also required to be provided with 3-5 secondary holes, the inhibition rate of each different concentration is obtained through experiments, and then the IC of the compound is calculated in SPSS software50The value is obtained.
Table 1: ligands and IC of Compounds on different cell lines50Values (. mu.M), lower values indicate better inhibitory activity of the compound.
The experimental results show that: for these 5 cancer cells, CuCl alone was used2、Cu2+And the activity of the thiophene formaldehyde thiosemicarbazone ligand is not high, and the activity is greatly improved after the thiophene formaldehyde thiosemicarbazone ligand is coordinated with copper ions. The copper complex C1 of the example has the highest activity, which is higher than C2, C3 and C4. The copper complex has high specificity to T-24 and HeLa cells, shows good inhibitory activity, has little toxic effect on normal cells of human bodies, and is suitable for preparing high-efficiency and low-toxicity antitumor drugs.
Claims (2)
1. A synthetic method of a copper compound taking 2-thiophenecarboxaldehyde thiosemicarbazone as a ligand is characterized in that the structural formula of the copper compound is shown as the following formula C1-C3:
C1
C2
C3
the synthetic route of the copper compound shown as C1-C3 is as follows: wherein the CuBr in the reaction formula2Using CuBr2·2H2O；
The method for synthesizing the copper compound shown as C1-C3 comprises the following steps:
(1) taking thiosemicarbazide, 4-methyl-3-thiosemicarbazide or 4-phenyl-3-thiosemicarbazide, adding absolute ethyl alcohol, stirring for dissolving, adding 2-thiophenecarboxaldehyde after dissolving, uniformly mixing, stirring the mixed solution at 70 ℃ in a water bath, volatilizing at room temperature, and separating out crystals to obtain a ligand;
the mol ratio of the thiosemicarbazide, the 4-methyl-3-thiosemicarbazide or the 4-phenyl-3-thiosemicarbazide to the 2-thiophenecarboxaldehyde is 1:1
(2) Adding anhydrous ethanol into the prepared ligand, stirring for dissolving, adding CuBr after dissolving2·2H2O, stirring in a water bath at 70 ℃, volatilizing at room temperature, and separating out crystals to obtain a Cu compound of the ligand;
the ligand is reacted with CuBr2·2H2The molar ratio of O is 1: 1.5.
2. The method for synthesizing a copper compound according to claim 1, wherein: the synthesis method comprises the following specific steps:
(1) weighing 1mmol of thiosemicarbazide, 4-methyl-3-thiosemicarbazide or 4-phenyl-3-thiosemicarbazide, pouring the thiosemicarbazide, the 4-methyl-3-thiosemicarbazide or the 4-phenyl-3-thiosemicarbazide into a 100mL flask, adding magnetons, adding 25mL of absolute ethyl alcohol, stirring for half an hour, weighing 1mmol of 2-thiophenecarboxaldehyde by using a pipette according to the proportion of 1:1, adding the mixture into the flask, stirring for 2 hours under the condition of water bath at 70 ℃, placing the flask in a ventilation cabinet, slowly volatilizing for 4-6 days to precipitate crystals;
(2) weighing 0.5mmol of ligand, pouring into a 100mL flask, adding magneton, adding 25mL of anhydrous ethanol, stirring for half an hour, adding 0.75mmol of CuBr2·2H2And O, stirring for 2 hours in a water bath at 70 ℃, placing the mixture in a 50ml beaker, placing the beaker in a fume hood, and slowly volatilizing for 6-8 days to precipitate crystals to obtain the Cu compound of the ligand.
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| CN109796497A (en) * | 2019-01-16 | 2019-05-24 | 广西师范大学 | It is a kind of using 2- acetyl group -3- ethyl pyrazine thiosemicarbazones as the bismuth compound of ligand and its synthetic method |
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| CN109796497A (en) * | 2019-01-16 | 2019-05-24 | 广西师范大学 | It is a kind of using 2- acetyl group -3- ethyl pyrazine thiosemicarbazones as the bismuth compound of ligand and its synthetic method |
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| Mitochondria-localizing N-heterocyclic thiosemicarbazone copper complexes with good cytotoxicity and high antimetastatic activity;ShanShan Gu等;《European Journal of Medicinal Chemistry》;20190108;第164卷;第654-664页 * |
| Synthesis, structure investigation and biological evaluation of 2-thiophene N(4)-phenylthiosemicarbazone and its three metal derivatives;Zilang Wang等;《Journal of Molecular Structure》;20150717;第1100卷;第376-383页 * |
| Zilang Wang等.Synthesis, structure investigation and biological evaluation of 2-thiophene N(4)-phenylthiosemicarbazone and its three metal derivatives.《Journal of Molecular Structure》.2015,第1100卷 * |
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