CN117946186A - Synthesis method and application of Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex - Google Patents
Synthesis method and application of Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex Download PDFInfo
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- -1 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt Chemical compound 0.000 title claims abstract description 38
- 238000001308 synthesis method Methods 0.000 title claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- 239000005725 8-Hydroxyquinoline Substances 0.000 claims description 17
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Abstract
A novel Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex synthesis method and application relate to the technical field of medicines. The invention provides a synthesis method and application of a novel Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex (Br-Co), and examines the proliferation inhibition activity of the novel Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex on Hep-G2 cell strains. The study finds that when Br-Co and H 2O2 are incubated together, the anti-tumor activity of the complex is higher than that when Br-Co acts on the HepG-2 liver cancer cells alone, and proves that the complex Br-Co can generate a large amount of OH through Co 2+ -mediated Fenton-like reaction of H 2O2, so that oxidative stress in mitochondria is stimulated and cell death is finally caused. Confocal imaging finds that Br-Co can be enriched in mitochondria of HepG-2 liver cancer cells, and shows blue fluorescence, and researches show that Br-Co can be potentially used for biomedical mitochondrial imaging and CDT anticancer drugs.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a synthesis method and application of a novel Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex.
Background
Chemotherapy (CDT) has received attention because of its unique means of generating reactive oxygen species. Based on the Fenton/Fenton-like reaction, CDT converts hydrogen peroxide overexpressed in tumor microenvironment into highly toxic hydroxyl radicals (OH), thereby inducing severe oxidative damage to cancer cells. CDT reagents based on complexes of Mn 2+,Fe2+ and Cu + have been developed, and research has found that they trigger CDT and increase its antitumor activity. It is worth mentioning that, unlike the conventional Fenton reaction, the reaction of Co 2+ +L+hydrogen peroxide→Co 3+ +L+OH+OH (L is a ligand) is suppressed due to the high redox potential (1.82 eV) of Co 2+/Co3+. Therefore, hydrogen peroxide replaces water molecules on Co 2+ first, then O-O bonds are broken and dissociated to generate OH, and the problem that the conversion rate of Fe 3+→Fe2+ of the traditional Fenton reagent is low can be avoided in the reaction process, so that OH can be generated efficiently. Cobalt-based complexes are therefore a good choice for CDT.
In recent years, studies have reported that some metal complexes containing mixed ligands of 8-hydroxyquinoline and 1, 10-phenanthroline derivatives have good antitumor activity, but only a few 8-hydroxyquinolines and their complexes have been used for cell imaging and CDT (Yang Y, wang CM, pan FH, qin QP, xie QJ, chen Q, liang H.Dalton Trans.2021; 50:16273-16280.). Based on the background, the 5, 7-dibromo-2-methyl-8-Hydroxyquinoline (HL) is taken as a main ligand, bipyridyl phenazine (DPPZ) is taken as an auxiliary ligand, and the 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex (Br-Co) is synthesized by a solvothermal method: co (L) 2 (DPPZ), the use of Br-Co in cell imaging and chemo-kinetic therapy was investigated.
Disclosure of Invention
The invention aims to provide a novel Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex synthesis method and application, and the specific invention scheme is as follows:
A method for synthesizing Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex comprises the following specific steps:
s1, mixing cobalt chloride, 5, 7-dibromo-2-methyl-8-Hydroxyquinoline (HL), bipyridyl phenazine (DPPZ), methanol and acetonitrile according to a certain proportion;
S2, putting the mixed solution into an oven for heating, and then slowly cooling to obtain reddish brown crystals, namely Br-Co.
Further, the reagent in the step S1 is placed in a Pyrex tube;
further, the heating time in the step S2 is 70-80h.
The mass ratio of bipyridophenazine (DPPZ), cobalt chloride and 5, 7-dibromo-2-methyl-8-Hydroxyquinoline (HL) in S1 is 1:1:1-1:3:2.
Furthermore, the solvent in the S1 reaction, methanol, needs to be present, and the target product is only present, wherein the proper ratio of methanol to acetonitrile is 2:1-5:1.
The suitable temperature for the S2 reaction is 85.0-95.0 ℃.
Further, after the S2 reaction is completed, the temperature is slowly reduced, and the reddish brown crystals are obtained, and the yield is 45.0-65.0%.
Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex is prepared by the method.
Application of novel Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex in preparation of anti-tumor cell imaging and CDT drugs.
An antitumor drug comprises the novel Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex as an active ingredient.
Compared with the prior art, the application has the following advantages and effects:
The invention provides a synthesis method and application of a novel Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex (Br-Co), and examines the proliferation inhibition activity of the novel Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex on Hep-G2 cell strains. The study shows that when Br-Co and H 2O2 are incubated together, the anti-tumor activity of the complex is higher than that when Br-Co acts on the HepG-2 liver cancer cells alone, and the complex Br-Co can generate a large amount of OH through Co 2+ -mediated Fenton-like reaction, so that oxidative stress in mitochondria is stimulated and cell death is finally caused. Confocal imaging shows that Br-Co can be enriched in mitochondria of HepG-2 liver cancer cells, and blue fluorescence is presented. Overall, studies have shown that Br-Co can potentially be used in biomedical mitochondrial imaging and CDT anticancer drugs.
In a word, the complex Br-Co has better potential medicinal value and is expected to be used for preparing various antitumor drugs.
The foregoing description is only an overview of the present application, and is intended to provide a better understanding of the technical means of the present application, so that the present application may be practiced according to the teachings of the present specification, and so that the above-mentioned and other objects, features and advantages of the present application may be better understood, and the following detailed description of the preferred embodiments of the present application will be presented in conjunction with the accompanying drawings.
The above and other objects, advantages and features of the present application will become more apparent to those skilled in the art from the following detailed description of the specific embodiments of the present application when taken in conjunction with the accompanying drawings.
Drawings
In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, and it is obvious that the drawings in the following description are some embodiments of the present application, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art. Like elements or portions are generally identified by like reference numerals throughout the several figures. In the drawings, elements or portions thereof are not necessarily drawn to scale.
FIG. 1 is a chemical structural diagram of a novel Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex;
FIG. 2 is a synthetic scheme for a novel Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex;
FIG. 3 is (a) an ultraviolet-visible absorption spectrum of MB degradation; (b) EPR spectroscopy;
FIG. 4 shows ROS production following (a) flow cytometry and (b) fluorescent imaging of HepG-2 cells incubated with Br-Co or Br-Co+hydrogen peroxide (10.0. Mu.M);
FIG. 5 is (a) cellular uptake; (b) cell imaging;
FIG. 6 shows the cell viability of HepG-2/HL-7702 cells after 48h treatment with Br-Co at various concentrations (a). (b) Cell viability after Br-Co incubation with HepG-2 with or without hydrogen peroxide. (c) Flow cytometry analysis of apoptosis of HepG-2 cells after 24h incubation with Br-Co or Br-Co+hydrogen peroxide.
FIG. 7 is an X-ray single crystal diffraction spectrum of Br-Co;
FIG. 8 is an infrared spectrum of Br-Co;
FIG. 9 is a mass spectrum of Br-Co;
FIG. 10 is the ultraviolet stability of Br-Co;
FIG. 11 is a fluorescence spectrum of Br-Co;
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present application more apparent, the technical solutions of the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present application, and it is apparent that the described embodiments are some embodiments of the present application, but not all embodiments of the present application. In the following description, specific details such as specific configurations and components are provided merely to facilitate a thorough understanding of embodiments of the application. It will therefore be apparent to those skilled in the art that various changes and modifications can be made to the embodiments described herein without departing from the scope and spirit of the application. In addition, descriptions of well-known functions and constructions are omitted in the embodiments for clarity and conciseness.
It should be appreciated that reference throughout this specification to "one embodiment" or "this embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present application. Thus, the appearances of the "one embodiment" or "this embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.
Furthermore, the present application may repeat reference numerals and/or letters in the various examples. This repetition is for the purpose of simplicity and clarity and does not in itself dictate a relationship between the various embodiments and/or configurations discussed.
The term "and/or" is herein merely an association relationship describing an associated object, meaning that there may be three relationships, e.g., a and/or B, may represent: the terms "/and" herein describe another associative object relationship, indicating that there may be two relationships, e.g., a/and B, may indicate that: the character "/" herein generally indicates that the associated object is an "or" relationship.
The term "at least one" is herein merely an association relation describing an associated object, meaning that there may be three kinds of relations, e.g., at least one of a and B may represent: a exists alone, A and B exist together, and B exists alone.
It is further noted that relational terms such as first and second, and the like are used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Moreover, the terms "comprise," "include," or any other variation thereof, are intended to cover a non-exclusive inclusion.
Example 1
The embodiment introduces a synthetic method and application of Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex, and referring to fig. 1 and 2, fig. 1 is a chemical structural formula diagram of novel Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex; FIG. 2 is a synthetic scheme for a novel Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex;
A synthetic method of Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex is shown in figure 2, and comprises the following specific steps:
s1, mixing cobalt chloride, 5, 7-dibromo-2-methyl-8-Hydroxyquinoline (HL), bipyridyl phenazine (DPPZ), methanol and acetonitrile according to a certain proportion;
s2, putting the mixed solution into an oven for heating, and then slowly cooling to obtain reddish brown crystals, namely Br-Co, wherein the chemical structural formula of the Br-Co is shown in figure 1.
Further, the reagent in the step S1 is put into a Pyrex tube to be mixed;
further, the heating time in the step S2 is 70-80h.
The mass ratio of bipyridophenazine (DPPZ), cobalt chloride and 5, 7-dibromo-2-methyl-8-Hydroxyquinoline (HL) in S1 is 1:1:1-1:3:2.
Furthermore, the solvent in the reaction of S1 and S2, methanol must exist, and the target product exists, wherein the proper proportion of methanol acetonitrile is 2:1-5:1.
The suitable temperature for the S2 reaction is 85.0-95.0 ℃.
Further, after the S2 reaction is completed, the temperature is slowly reduced, and the reddish brown crystals are obtained, and the yield is 45.0-65.0%.
Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex is prepared by the method.
Application of novel Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex in preparation of anti-tumor cell imaging and CDT drugs.
An antitumor drug comprises the novel Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex as an active ingredient.
Example 2
The embodiment introduces a solvothermal method for synthesizing a target product on the basis of the embodiment, and is combined with figures 7, 8, 9, 10 and 11, and figure 7 is an X-ray single crystal diffraction spectrum chart of Br-Co; FIG. 8 is an infrared spectrum of Br-Co; FIG. 9 is a mass spectrum of Br-Co; FIG. 10 is the ultraviolet stability of Br-Co; FIG. 11 is a fluorescence spectrum of Br-Co.
Cobalt chloride (0.1 mmol), HL (0.2 mmol), DPPZ (0.1 mmol), methanol (3 mL) and acetonitrile (1.5 mL) are mixed, put into a Pyrex tube of 15.0mL, then put into an oven of 85 ℃ for heating for 72h, and then cooled slowly, so that a dark reddish brown crystal which is Br-Co is obtained, and the yield is 46.31%. The characterization data are as follows:
(1) The X-ray single crystal diffraction spectrum is shown in figure 7. The complex Br-Co is a twisted octahedral geometry that is hexacoordinated by chelation of two deprotonated 5, 7-dibromo-2-methyl-8-hydroxyquinoline ligands and one ancillary ligand bipyridyl phenazine. Single crystal bond length of Br-Co And bond angles (°) are shown in tables 1 to 3, their bond lengths/>And bond angles (°) are both within normal ranges. The stability of Br-Co was tested by ultraviolet absorption spectroscopy. As shown in FIG. 10, the ultraviolet spectrum result shows that the ultraviolet absorption peak of the Br-Co (2.0X10 -3 mol/L) solution at room temperature after 4 time points has no red shift or blue shift, so that the Br-Co can stably exist at room temperature within 48 hours.
TABLE 1 crystallographic and structural modification data for the complex Br-Co
aR1＝Σ||Fo|–|Fc||/Σ|Fo|;bwR2＝[Σw(Fo 2–Fc 2)2/Σw(Fo 2)2]1/2.
TABLE 2 health of complex Br-Co
TABLE 3 bond angle of complex Br-Co [ ° ]
(2) The elemental analysis results are shown in table 4.
TABLE 4 elemental analysis (C 38H23Br4CoN6O2) results of the complex Br-Co in the examples
(3) The infrared spectrum is shown in figure 8, and the infrared data are shown below.
IR(KBr):623,733,926,1356,1426,1542,2859,2920,3452cm-1.
(4) Electrospray mass spectrum, the spectrum of which is shown in FIG. 9, and the analysis of which is shown below.
ESI-MS M/z 1050.2[ Br-Co+DMSO-2H + ], where M is the molecular weight of the complex Br-Co.
Thus, the resulting product was identified as Co (L) 2 (DPPZ) having the chemical structural formula Br-Co as shown in FIG. 1.
Example 3
In order to fully illustrate the use of the 1 Fenton-like 5, 7-dibromo-2-methyl-8-hydroxyquinoline-bipyridyl phenazine cobalt complex Br-Co in pharmacy, the applicant conducted the following experiments.
1. Fenton-like catalytic activity test of Br-Co
(1) Experimental procedure
The Fenton-like catalytic activity of Br-Co was detected by methylene blue degradation (MB) and electron spin resonance. The complex Br-Co (10 μm), H 2O2 (10 μm), MB (20 μm) was added to Tris-HCl buffer solution (ph=7.4) in a total volume of 3ml at 37 ℃ and the change in absorption wavelength at 665nm was monitored at different times with an uv-vis spectrophotometer. The complex Br-Co (10. Mu.M), H 2O2 (10. Mu.M), MB (20. Mu.M) was added to tris-HCl buffer (pH=7.4) using 5, 5-dimethyl-1-pyrrolidine-N-oxide (DMPO) as a trapping agent, the total volume of the solution was 3mL, and the formation of OH was detected by an EPR spectrometer.
(2) Experimental results:
As shown in FIG. 3a, the absorbance change of MB at 665nm was negligible when Br-Co alone was present. However, when both Br-Co and hydrogen peroxide were present in the solution, sustainable degradation of MB was observed over 0-240 min, changing the color of the MB solution from dark blue to colorless. This degradation process shows that Br-Co can drive a Fenton-like catalytic reaction to degrade MB by catalyzing hydrogen peroxide to produce OH. In addition, when 5, 5-dimethyl-1-pyrrolidine-n-oxide (DMPO) was used as an OH-capturing agent, br-Co was incubated with hydrogen peroxide, the EPR spectrum shown by the test showed a pronounced 4-wire hydroxyl radical signal of 1:2:2:1 (FIG. 3 b), also confirming that OH was generated by the Fenton-like catalytic reaction. In summary, br-Co can catalyze hydrogen peroxide to generate a large amount of OH through the Fenton-like reaction, which provides possibility for Br-Co to react with hydrogen peroxide in cells to generate OH in the cells through the Fenton-like reaction, thereby effectively killing tumors.
2. Intracellular active oxygen assay of Br-Co
(1) Experimental procedure
In view of the fact that Br-Co can effectively produce OH through the Fenton-like reaction, further, DCFH-DA is used as a probe to measure intracellular ROS level, and whether Br-Co can produce a large amount of ROS in HepG-2 cells is verified. 1X 10 6 logarithmic cells were inoculated on a 6-well plate, placed in an incubator for culturing for 24 hours, then treated with Br-Co (5. Mu.M) for 24 hours, and stained with DCFH-DA probe for 30 minutes. Finally, the change of the active oxygen is detected by a flow cytometer at the wavelength of Ex/Em=506 nm/526nm or by a fluorescence microscope.
(2) Experimental results
As shown in fig. 4, neither the blank group nor the hydrogen peroxide group significantly fluoresces; in contrast, the Br-Co set can see significant fluorescence, and in the reaction set pretreated with hydrogen peroxide (50 mM) for 30min, a stronger green fluorescence was observed, i.e., when hydrogen peroxide Co-stimulated HepG-2 cells with Br-Co, a strong ROS signal was generated. The result is consistent with the previous MB degradation experiment result, and clearly shows that Br-Co can catalyze hydrogen peroxide reaction in cells to generate OH in the HepG-2 cells through Fenton-like reaction, thereby causing oxidative damage of the cells.
3. Ability of Br-Co to cellular uptake and cellular imaging
(1) Experimental procedure
To verify whether intracellular ROS are caused by the Fenton-like reaction caused by Br-Co in mitochondria, uptake and imaging of Br-Co in HepG-2 cells was quantitatively assessed using ICP-MS. Cellular uptake: 1X 10 6 logarithmic cells were inoculated on a 6-well plate, placed in an incubator for culturing for 24 hours, treated with Br-Co (5. Mu.M) for 6,12,24,48 hours, respectively, and the mitochondrial fraction was extracted with the kit. Crushing with NaOH (1 m,1.0 mL) for 30min, followed by digestion with HNO 3 (V/v=5%) (5 mL), and measuring the metal content using ICP-MS instrument. Cell imaging: 1X 10 6 logarithmic cells were seeded on confocal dishes, incubated in an incubator for 24h, treated with Br-Co (5. Mu.M) for 12h, and then the treated cells were imaged in confocal mode and compared to commercial cell mitochondrial imaging reagent (Mito-TRACKER RED).
(2) Experimental results
As shown in FIG. 5a, br-Co was continuously enriched in mitochondria of HepG-2 cells with the lapse of incubation time; furthermore, co-localization experiments showed that when the complex was incubated with HepG-2 cells for 12h, purple fluorescent spots were clearly visible in mitochondria, which is a result of overlapping blue fluorescence of Br-Co with mitochondrial red fluorescence, indicating that Br-Co was efficiently absorbed into the cells and enriched in mitochondria (fig. 5 b). The test results clearly demonstrate that when Br-Co enters HepG-2 cells, br-Co is gradually enriched in mitochondria, and then is directly generated into OH through Fenton-like reaction and hydrogen peroxide reaction abundant in the cells.
4. Br-Co inhibition HepG-2 cell proliferation and apoptosis assay
(1) Experimental procedure
Since it has a good OH-producing ability in cells, MTT experiments were performed to evaluate the proliferation inhibiting ability of Br-Co to HepG-2 cells and normal cells HL-7702. Cell proliferation: log phase cells were taken and counted. Cells were seeded in 96-well plates, 100mL of cell culture medium was added, and then incubated in a cell incubator (37 ℃ C., 5% CO 2) for 24 hours, br-Co (1% by volume of DMSO in the final wells) was added, and the final Br-Co concentrations were 1.25,2.5,5,10,20. Mu.M, respectively. The control group was added with the same volume of PBS buffer, 5 composite wells per group. After addition of Br-Co, incubation was continued in the incubator for 48h. The medium was removed and 100. Mu.L of 10. Mu. LMTT solution containing a concentration of 5mg/mL was added to each well. After further incubation for 4h, the medium was discarded and DMSO (100 mL) was added to each well to dissolve the blue-violet crystals. Shaking up for 15 minutes. The absorbance at 490nm was recorded with a multifunctional microplate reader. Apoptosis: 1X 10 6 log phase cells were plated in 6 well plates. After 24h, the cells were treated with Br-Co (5. Mu.M), placed under an incubator for a further 12h, and analyzed for apoptosis by V-FITC staining.
(2) Experimental results
As shown in FIGS. 6 a-b, br-Co can inhibit proliferation of HepG-2 cells. As expected, when the complex Br-Co was applied to cells, the cell viability of the hydrogen peroxide pretreated HepG-2 cells was much lower than in the hydrogen peroxide-free group. These results are consistent with the results of intracellular production of OH, and it was clearly confirmed that Br-Co can catalyze the decomposition of hydrogen peroxide into OH by the Fenton-like reaction. On the other hand, the quantitative analysis of Br-Co induced apoptosis was performed by flow cytometry. The results showed that when the complex Br-Co was applied to the cells, the apoptosis rate of the hydrogen peroxide treated HepG-2 cells was higher than that of the hydrogen peroxide free group (FIG. 6 c). In conclusion, the complex Br-Co can gradually accumulate in mitochondria, and directly react with intracellular hydrogen peroxide to induce Fenton-like reaction to generate OH, so that cell death is promoted.
In summary, to stimulate intracellular OH production, the present invention designed and synthesized a well-defined CDT agent: co (L) 2 (DPPZ) (Br-Co). The complex Br-Co is highly stable in solution and has Fenton-like catalytic activity. The complex Br-Co can be positioned at the cell mitochondrial membrane potential and presents blue fluorescence; and continuously accumulated in mitochondria, and in situ generated OH with hydrogen peroxide in cells, thereby promoting oxidative stress and damaging mitochondria, and further inducing apoptosis. The complex Br-Co total body shows in-vitro activity and toxicity selectivity of anti-Hep-G2 cells, has good potential medicinal value, is a targeted anticancer drug with fluorescent localization targeting to Hep-G2 cell mitochondria and induction of cell death by chemo-dynamic therapy, and is expected to be used for preparing various anti-tumor CDT drugs.
The above description is only of the preferred embodiments of the present invention and it is not intended to limit the scope of the present invention, but various modifications and variations can be made by those skilled in the art. Variations, modifications, substitutions, integration and parameter changes may be made to these embodiments by conventional means or may be made to achieve the same functionality within the spirit and principles of the present invention without departing from such principles and spirit of the invention.
Claims (10)
- The synthesis method of the 8-hydroxyquinoline aldolisation N-O pyridine bisacylhydrazone tetranuclear dysprosium cluster compound (4-Dy) comprises the following steps:s1, synthesizing a novel 8-hydroxyquinoline aldol N-O pyridine bisacylhydrazone ligand (H 4 L);s2, synthesizing an 8-hydroxyquinoline aldol N-O pyridine bisacylhydrazone tetranuclear dysprosium cluster compound (4-Dy).
- 2. The method for synthesizing the 8-hydroxyquinoline aldehyde N-O pyridine bisacylhydrazone tetranuclear dysprosium cluster compound (4-Dy) according to claim 1, wherein the synthesizing step S1 is specifically as follows:S1.1, weighing and adding N-O pyridine dicarboxylic acid into a round-bottom flask, adding CH 3 OH and concentrated sulfuric acid, and obtaining N-O pyridine dicarboxylic acid dimethyl ester through esterification reaction;S1.2, adding CH 3 OH, N-O pyridine-dicarboxylic acid dimethyl ester and N 2H4·H2 O into the solid obtained in the S1, heating to 80 ℃, adding 8-hydroxyquinoline-2-formaldehyde twice, and reacting at 80 ℃;S1.3. the reaction mass in S2 was cooled and filtered to give 8-hydroxyquinoline aldol N-O pyridine bisacylhydrazone ligand (H 4 L).
- 3. The method for synthesizing 8-hydroxyquinoline aldehyde N-O pyridine bisacylhydrazone tetranuclear dysprosium cluster compound (4-Dy) according to claim 1 or 2, wherein the synthesizing step S2 specifically comprises:S2, adding 8-hydroxyquinoline aldehyde N-O pyridine bisacylhydrazone ligand (H 4L)、Dy(OAc)3·4H2 O, solvent and triethylamine) into a vacuum sealed container, standing and heating in an oven for 3-7 days, slowly cooling to obtain orange yellow crystals, and washing and drying the obtained crystals to obtain the 8-hydroxyquinoline aldehyde N-O pyridine bisacylhydrazone tetranuclear dysprosium cluster compound (4-Dy).
- 4. The method for synthesizing 8-hydroxyquinoline aldol N-O pyridine bisacylhydrazone tetranuclear dysprosium cluster compound (4-Dy) according to claim 2, wherein,The volume of CH 3 OH added into the S1.1 is 90-110ml, and the volume of concentrated sulfuric acid is 9-11ml;CH 3 OH used in the S1.2 is 48-52ml, N-O pyridine-dicarboxylic acid dimethyl ester 1mmol, N 2H4·H2 O is 9-11ml, 8-hydroxyquinoline-2-formaldehyde is 2mmol, and the reaction time is 12h.
- 5. The method for synthesizing 8-hydroxyquinoline aldehyde N-O pyridine bisacylhydrazone tetranuclear dysprosium cluster compound (4-Dy) according to claim 3, wherein the mass ratio of (H 4L)、Dy(OAc)3·4H2 O) in the S2 reaction is 1:2-1:5.
- 6. The method for synthesizing 8-hydroxyquinoline aldehyde N-O pyridine bisacylhydrazone tetranuclear dysprosium cluster compound (4-Dy) according to claim 3, wherein the target crystal form product is only obtained when the solvent in the S2 reaction and methanol are required to exist; generally, the amount of the mixed solvent is 1.5-3.0 mL, and the ratio of the most suitable methanol to other solvents is 2:1-5:1.
- 7. The method for synthesizing 8-hydroxyquinoline aldehyde N-O pyridine bisacylhydrazone tetranuclear dysprosium cluster compound (4-Dy) according to claim 3, wherein triethylamine in the S2 reaction is 10-30 μl.
- 8. The method for synthesizing 8-hydroxyquinoline aldehyde N-O pyridine bisacylhydrazone tetranuclear dysprosium cluster compound (4-Dy) according to claim 3, wherein the proper temperature for the S2 reaction is 80.0-95.0 ℃.
- 9. An 8-hydroxyquinoline aldehyde N-O pyridine bisacylhydrazone tetranuclear dysprosium cluster compound prepared by a synthesis method of the 8-hydroxyquinoline aldehyde N-O pyridine bisacylhydrazone tetranuclear dysprosium cluster compound (4-Dy) according to the claims 1-8.
- 10. The use of an 8-hydroxyquinoline aldol N-O pyridine bisacylhydrazone tetranuclear dysprosium cluster compound according to claim 9.
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