Gd-TCPP metal organic framework compound as well as preparation method and application thereof
By preparing Gd-TCPP metal organic framework compounds, the problem of insufficient application of rare earth metalporphyrin MOF materials in the prior art is solved, and bifunctional as magnetic resonance imaging contrast agent and photodynamic therapy sensitizer are realized, and high yields are achieved. and potential industrial applications.
Patent Information
- Application Number
- CN202411401696.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-09
- Publication Date
- 2024-12-27
AI Technical Summary
The lack of rare earth metalporphyrin MOF materials that can be used as both magnetic resonance imaging contrast agents and photodynamic therapy sensitizers in the prior art limits the multi-faceted synergistic application of metalporphyrin MOF.
Using the preparation method of Gd-TCPP metal organic framework compound, 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin and gadolinium salt are reacted in N,N-dimethylacetamide and hydrochloric acid aqueous solution , control reaction conditions such as temperature, time and cooling rate to produce Gd-TCPP metal organic framework compounds for sensitizing singlet oxygen generation and magnetic resonance imaging.
The dual functionality of Gd-TCPP metal organic framework compounds has been realized, and the application of photodynamic therapy sensitizer and magnetic resonance imaging contrast agent has been used to extend the life of Gd and has a description of the material flow state in the field of propellant compression molding. Track potential applications, simple preparation method and high yield.
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Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of magnetic resonance imaging contrast agents and photodynamic therapy sensitizers, relates to rare earth metal organic framework compounds, and specifically relates to a Gd-TCPP metal organic framework compound, a preparation method and an application thereof. Background Art
[0002] Porphyrin is a class of organic compounds with large conjugated structures. Porphyrin molecules have high extinction coefficients and are very efficient in converting from the ground state to the excited state. The electron mobility within the porphyrin ring is large, and it can effectively absorb the energy of ultraviolet and visible light, and transition triplet oxygen in the ground state to the excited state to produce singlet oxygen. Singlet oxygen has a strong oxidizing ability. In the dominant photodynamic type II reaction, singlet oxygen is the main body of treatment. It has strong phototoxicity and has a good photodynamic therapy effect on hypoxic cancer cells.
[0003] Magnetic resonance imaging has high spatial resolution for soft tissues and does not involve radiation, and has been widely used in hospitals for non-invasive imaging of solid tumors. Different tissues have different MRI signals due to differences in water density and proton relaxation time in the magnetic field. In clinical medicine, paramagnetic contrast agents can improve the contrast of tumor imaging. Gd-based chelates, such as pentacyclic Gd(III)-diethylenetriaminepentaacetic acid and 12-membered ring structure Gd(III)-1,4,7,10-tetraacetic acid, are the most commonly used paramagnetic contrast agents. However, due to the low molecular weight of these chelates, their lifetime is short.
[0004] Most of the existing rare earth metal porphyrin MOF materials use metal elements such as Zn\Cu\Ni\Al\Ca\Ag\Au as ligands, and most of the synthesized MOF materials have only one-sided applications such as fluorescence and photocatalysis. However, there are few studies on rare earth metal porphyrin MOF materials that can be used as magnetic resonance imaging contrast agents and photodynamic therapy sensitizers at the same time, which limits the multi-faceted synergistic application of metal porphyrin MOF. Summary of the invention
[0005] In view of the defects and shortcomings of the prior art, the purpose of the present invention is to provide a Gd-TCPP metal organic framework compound, a preparation method and its application, so as to solve the technical problem in the prior art that there is a lack of rare earth metal porphyrin MOF materials that can be used as both magnetic resonance imaging contrast agents and photodynamic therapy sensitizers.
[0006] In order to solve the above technical problems, the present invention adopts the following technical solutions to achieve the above problems:
[0007] A preparation method of a Gd-TCPP metal organic framework compound is characterized in that the method comprises: dissolving 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin in N,N-dimethylacetamide to obtain a solution of a compound containing a porphyrin group; dissolving a gadolinium salt in an aqueous hydrochloric acid solution to obtain a metal precursor solution; transferring the solution of the compound containing a porphyrin group and the metal precursor solution to a reaction container, stirring, and then keeping the temperature at 110-130°C for 48-96h, and cooling at a rate of 5-10°C / h after heating to obtain the Gd-TCPP metal organic framework compound.
[0008] The present invention also has the following technical features:
[0009] Specifically, the molecular formula of the Gd-TCPP metal organic framework compound is Gd 16 O 104 N 56 H 384 C 600 Its crystals belong to the monoclinic system and the C12 / c1 space group.
[0010] Preferably, the heating conditions are: heating temperature is 120° C., heating time is 72 h, and cooling at a rate of 5° C. / h after heating.
[0011] Specifically and preferably, the molar ratio of the 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin to the gadolinium in the gadolinium salt is 0.0125:0.025.
[0012] Specifically and preferably, the concentration of the aqueous hydrochloric acid solution is 1.8 mol / L, and the volume ratio of the aqueous hydrochloric acid solution to N,N-dimethylacetamide is 5:6.25.
[0013] Specifically, the gadolinium salt is GdCl3·6H2O.
[0014] Specifically, the temperature is lowered to 20-45° C. after the heating is completed.
[0015] Specifically, the stirring time is 10 to 20 minutes.
[0016] The present invention also protects the Gd-TCPP metal organic framework compound as described above.
[0017] The present invention also protects the Gd-TCPP metal organic framework compound prepared by the preparation method of the Gd-TCPP metal organic framework compound as described above.
[0018] The present invention also protects the use of the Gd-TCPP metal organic framework compound as described above for sensitizing singlet oxygen generation.
[0019] The beneficial technical effects of the present invention compared with the prior art are as follows:
[0020] (I) The Gd-TCPP metal organic framework compound synthesized by the present invention is a class of rare earth porphyrin metal organic framework compounds. The ligand porphyrin can sensitize the production of singlet oxygen. The coordinated metal Gd can be used as a magnetic resonance imaging contrast agent. The MOF structure prolongs the life of Gd as a contrast agent. It is a class of dual-functional materials that can be used for photodynamic therapy and magnetic resonance imaging at the same time. On the other hand, the magnetic resonance imaging properties of the MOF material make it have potential application prospects in the tracing of material flow states in the field of propellant extrusion molding.
[0021] (II) The present invention uses N,N-dimethylformamide and hydrochloric acid aqueous solution as mixed reaction solvents, selects a suitable reaction solvent ratio, reacts in a reactor, adjusts the stirring and dissolving time, reaction temperature, reaction time, cooling rate and other reaction conditions, and obtains purple flaky crystals after cooling to room temperature. The obtained crystals are washed, filtered and dried to obtain the target product. The preparation method of the present invention is simple, has a high yield (yield of more than 60%), and is easy to realize industrialization. BRIEF DESCRIPTION OF THE DRAWINGS
[0022] Figure 1 is the crystal structure of the Gd-TCPP metal organic framework compound in Example 1; Figure 1 In the figure, (a) is the TCPP structure diagram, (b) is the coordination structure diagram, and (c) and (d) are two-dimensional diagrams in two directions.
[0023] Figure 2 These are the results of XRD simulation and actual measurement of the Gd-TCPP metal organic framework compound in Example 1.
[0024] Figure 3 This is the FTIR result of the Gd-TCPP metal organic framework compound in Example 1.
[0025] Figure 4 This is the TG curve of the Gd-TCPP metal organic framework compound in Example 1.
[0026] Figure 5 This is the singlet oxygen spectrum of the Gd-TCPP metal organic framework compound in Example 1. DETAILED DESCRIPTION
[0027] In the present invention: MOF refers to metal organic framework, and DMF refers to N,N-dimethylacetamide.
[0028] It should be noted that all raw materials used in the present invention, unless otherwise specified, are raw materials known in the art. For example, 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) is a compound known in the prior art, and its CAS code is 14609-54-2.
[0029] In accordance with the above technical scheme, specific embodiments of the present invention are given below. It should be noted that the present invention is not limited to the following specific embodiments, and all equivalent changes made on the basis of the technical scheme of this application fall within the protection scope of the present invention.
[0030] Embodiment 1:
[0031] This embodiment provides a preparation method of a Gd-TCPP metal organic framework compound, which specifically includes the following processes: 9.88 mg of 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (molecular weight 790.79 / 0.0125 mmol) is dissolved in 6.25 mL of N,N-dimethylacetamide to obtain a solution of a compound containing a porphyrin group; 9.29 mg of GdCl3·6H2O (molecular weight 371.70 / 0.025 mmol) is dissolved in 5 mL of aqueous hydrochloric acid solution (1.8 mol / L) to obtain a metal precursor solution; the solution of the compound containing a porphyrin group and the metal precursor solution are transferred to a reactor with a volume of 25 mL, and stirred for 10 minutes with an electromagnetic stirrer; the reactor is placed in an oven, heated to 120°C, kept warm for 72 hours, and then cooled to 30°C at a rate of 5°C / h. In this embodiment, based on the relative molecular mass of DMF being 87.12 and the density being 0.937 g / mL, the amount of DMF is approximately 67.22 mmol, and the molar ratio of hydrochloric acid to DMF is approximately 9:67.22.
[0032] After the reaction was completed, the reactor was taken out and purple crystals were seen after opening. The crystals were collected and washed and dried with N,N-dimethylacetamide to obtain crystals with the chemical formula of Gd4(TCPP)3(DMF)2(H2O)2 (i.e., Gd-TCPP metal organic framework compound). The above product was characterized and identified, and the results are shown in Table 1. Figure 1 , Figure 2 and Figure 3 Based on the above characterization results, it can be determined that the target product has been synthesized.
[0033] Table 1. Crystal data of the Gd-TCPP metal organic framework compound of Example 1
[0034]
[0035] In this embodiment, the yield of the Gd-TCPP metal organic framework compound is 65.7%, and its crystal structure is shown in Figure 1 The crystal belongs to the monoclinic system and the C12 / c1 space group. 3+ Coordination Figure 1 a), the carboxyl groups of the porphyrin monomers are coordinated in four different ways. One is that the carboxyl group (denoted as carboxyl group 1) bridges two Gd 3+ (denoted as Gd1); the other is the carboxyl group (denoted as carboxyl 2) with only one O and Gd 3+ (denoted as Gd2) coordination; the third is the carboxyl group (denoted as carboxyl group 3) chelating with Gd2 and bridging Gd1 and Gd2; the fourth is the carboxyl group (denoted as carboxyl group 4) chelating with Gd2. Figure 1 b) The crystal shows a coordinated structure, in which Gd1 is seven-coordinated, with 4 O atoms coming from four carboxyl groups 1, 1 O coming from DMF, and 2 O atoms coming from carboxyl groups 3. The longest Gd-O bond is The shortest Gd-O bond is Gd2 is nine-coordinated, with 4 O atoms coming from two carboxyl groups 3, 2 O atoms coming from H2O, 2 O atoms coming from one carboxyl group 4, and 1 O atoms coming from carboxyl group 2. The longest Gd-O bond is The shortest Gd-O bond is The two-dimensional graph is a grid structure ( Figure 1 c) The carboxyl group of porphyrin on the bc surface and Gd 3+ Connected into a two-dimensional plane structure. The two-dimensional structure in the a direction ( Figure 1 d) shows the staggered connection between Gd and porphyrin. The carboxyl group of a porphyrin unit is not connected to a layer of Gd in Figure c. 3+ coordination, but one of the carboxyl groups is coordinated with the Gd 3+ Coordination, thereby forming a MOF material with a three-dimensional structure.
[0036] Analysis of the physicochemical properties of Example 1:
[0037] Figure 4 is the thermogravimetric curve of Gd-TCPP metal organic framework compound. Figure 4 It can be seen that when the temperature is between 25 and 300°C, the Gd-TCPP metal organic framework compound slowly loses weight, with a total weight loss of about 14%, which is the weight loss of the solvent molecules DMF and H2O in the Gd-TCPP metal organic framework compound; when the temperature continues to rise to about 500°C, the organic metal framework begins to decompose. Thermogravimetric analysis proves that the Gd-TCPP metal organic framework compound is very stable.
[0038] Embodiment 2:
[0039] This example shows the application of the Gd-TCPP metal organic framework compound prepared in Example 1 for sensitizing singlet oxygen generation. The application specifically includes the following process: 1 mg of the Gd-TCPP metal organic framework compound is added to 10 mL of deuterated chloroform and soaked for 48 hours to allow part of the solvent in the MOF to exchange with the deuterated solvent. The Gd-TCPP metal organic framework compound is then filtered out and dried, and the near-infrared emission spectrum of the material is tested using an FLS920 steady-state transient fluorescence spectrometer. The test results are shown in FIG. Figure 5 shown.
[0040] from Figure 5 It can be seen that a peak of singlet oxygen transition to the ground state was detected at around a wavelength of 1270 nm, indicating that the porphyrin group in the Gd-TCPP metal organic framework compound acts as an antenna molecule to sensitize the generation of singlet oxygen.
[0041] Comparative Example 1 (different solvents):
[0042] This comparative example provides a method for preparing a Gd-TCPP metal organic framework compound, which is basically the same as Example 1, except that: in this comparative example, N,N-dimethylacetamide is not used, but 9.88 mg of 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin and 9.29 mg of GdCl3·6H2O are directly dissolved in 5 mL of aqueous hydrochloric acid solution (1.8 mol / L).
[0043] In this comparative example, the Gd-TCPP metal organic framework compound could not be prepared because the structure of the Gd-TCPP metal organic framework compound requires the participation of DMF molecules, and the absence of DMF results in the inability to generate MOF crystals.
[0044] Comparative Example 2 (the ratio of DMF and aqueous hydrochloric acid solution is different):
[0045] This comparative example provides a method for preparing a Gd-TCPP metal organic framework compound, which is basically the same as Example 1, except that in this comparative example, the volume ratio of N,N-dimethylacetamide and aqueous hydrochloric acid solution is 1 / 1, and the molar ratio of hydrochloric acid to DMF is approximately 11.25:67.22.
[0046] In this comparative example, the Gd-TCPP metal organic framework compound could not be prepared because the change in the ratio of N,N-dimethylacetamide and the hydrochloric acid aqueous solution resulted in changes in the solvent environment and the pH value.
[0047] Comparative Example 3 (different reaction temperatures):
[0048] This comparative example provides a method for preparing a Gd-TCPP metal organic framework compound, which is basically the same as Example 1, except that in this comparative example, the reaction temperature is 100°C.
[0049] In this comparative example, the Gd-TCPP metal organic framework compound could not be prepared. This is because the temperature was too low, resulting in low solubility of each component in the solvent, and the thermal motion speed of each component was insufficient, making it difficult to generate MOF crystals.
[0050] Comparative Example 4 (different reaction times):
[0051] This comparative example provides a method for preparing a Gd-TCPP metal organic framework compound, which is basically the same as Example 1, except that in this comparative example, the reaction time is 36 hours.
[0052] In this comparative example, the yield of the Gd-TCPP metal organic framework compound was 52.7%. Compared with Example 1, the reason why the final yield in this comparative example was lower was that the reaction time was too short, the nucleation and growth process of the MOF crystals had not yet been completed, and the reaction was stopped prematurely.
[0053] Comparative Example 5 (different cooling rates):
[0054] This comparative example provides a method for preparing a Gd-TCPP metal organic framework compound, which is basically the same as Example 1, except that in this comparative example, the cooling rate is 20° C. / min.
[0055] Compared with Example 1, the Gd-TCPP metal organic framework compound obtained in this comparative example has small crystal particles and poor crystal structure, which is similar to powder. The reason is that the cooling rate is too fast, the MOF crystals do not have sufficient time to form, and the growth rate is too fast, resulting in poor crystal structure.
Claims
1. A method for preparing a Gd-TCPP metal organic framework compound, characterized in that: The method comprises: dissolving 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin in N,N-dimethylacetamide to obtain a solution containing a porphyrin group compound; dissolving a gadolinium salt in a hydrochloric acid aqueous solution to obtain a metal precursor solution; transferring the solution containing the porphyrin group compound and the metal precursor solution to a reaction container, stirring, and then keeping the temperature at 110 to 130°C for 48 to 96 hours, and cooling at a rate of 5 to 10°C / h after heating to obtain a Gd-TCPP metal organic framework compound.
2. The method for preparing the Gd-TCPP metal organic framework compound according to claim 1, characterized in that: The molecular formula of the Gd-TCPP metal organic framework compound is Gd 16 O 104 N 56 H 384 C 600 Its crystals belong to the monoclinic system and the C12 / c1 space group.
3. The method for preparing the Gd-TCPP metal organic framework compound according to claim 1, characterized in that: The heating conditions are as follows: heating temperature is 120° C., heating time is 72 h, and cooling is performed at a rate of 5° C. / h after heating.
4. The method for preparing the Gd-TCPP metal organic framework compound according to claim 1, characterized in that: The molar ratio of gadolinium in the 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin and gadolinium salt is 0.0125:0.
025.
5. The method for preparing the Gd-TCPP metal organic framework compound according to claim 1, characterized in that: The concentration of the hydrochloric acid aqueous solution is 1.8 mol / L, and the volume ratio of the hydrochloric acid aqueous solution to N,N-dimethylacetamide is 5:6.
25.
6. The method for preparing the Gd-TCPP metal organic framework compound according to claim 1, characterized in that: The gadolinium salt is GdCl3·6H2O.
7. The method for preparing the Gd-TCPP metal organic framework compound according to claim 1, characterized in that: After heating, cool to 20-45°C.
8. The method for preparing the Gd-TCPP metal organic framework compound according to claim 1, characterized in that: The stirring time is 10 to 20 minutes.
9. A Gd-TCPP metal organic framework compound prepared by the method for preparing a Gd-TCPP metal organic framework compound according to any one of claims 1 to 9.
10. Use of the Gd-TCPP metal organic framework compound according to claim 9 for sensitizing singlet oxygen generation.