Magnetic resonance imaging material, preparation method and application

Abstract

The invention belongs to the technical field of magnetic functional materials. The invention discloses a magnetic resonance imaging material, a preparation method and application. The chemical formula of the magnetic resonance imaging material is [Gd2Mn4 (HL) 4 (OAc) 6]. 4EtOH. 4H2O, and the ligand HL is formed by dehydrogenation of a compound 2-(1-naphthalene-amido)-2-(hydroxymethyl)-1-propanol. The magnetic resonance imaging material can be used as a contrast agent material in the field of magnetic resonance imaging. Compared with a traditional Gd contrast agent, the paramagnetism of the Mn ions in the magnetic resonance imaging material can cooperate with the Gd ions to improve the longitudinal relaxation rate, strengthen the Tweighted imaging contrast ratio and expand multi-parameter diagnosis information, and kidney-derived systemic fibrosis induced by Gd ion deposition can also be reduced.

Description

Technical Field

[0001] The present application belongs to the technical field of magnetic functional materials, and in particular relates to a magnetic resonance imaging material, a preparation method and an application thereof. Background Art

[0002] Magnetic resonance imaging materials are a type of material used in magnetic resonance imaging (MRI) technology that enhances imaging quality or provides specific imaging functions by changing the relaxation time of tissues. They have the characteristics of enhanced image contrast, chemical stability, biocompatibility and low toxicity. Due to their unique magnetic properties, they show excellent application potential in the field of magnetic resonance imaging. However, existing contrast agents have problems such as large clinical dosages, easy to cause nephrotoxicity and poor imaging effects. Summary of the invention

[0003] Purpose of the invention: This application provides a magnetic resonance imaging material, preparation method and application. The magnetic resonance imaging material of this application can be used as a contrast agent in the field of magnetic resonance imaging, which can solve the problems of existing contrast agents such as large clinical dosage, easy to cause nephrotoxicity and poor imaging effect.

[0004] Technical solution: The present invention provides a magnetic resonance imaging material in an embodiment of the present application. The chemical formula of the magnetic resonance imaging material is: [Gd2Mn4(HL)4(OAc)6]·4EtOH·4H2O, wherein the ligand HL is formed by dehydrogenation of the compound 2-(1-naphthyl-amino)-2-(hydroxymethyl)-1-propanol.

[0005] In some embodiments, the structure of the magnetic resonance imaging material is composed of 2 Gd (III) ions, 4 Mn (II) ions, 4 HL 2- Ligand, 6 OAc - ions, 4 EtOH molecules and 4 H2O molecules; 2 Gd(III) ions and 4 Mn(II) ions are μ 3-OH - Ligand and 8 μ 2-OH - The ligands are connected to form a hexanuclear framework structure, in which four shared Mn(II) ions are located on a parallelogram plane; the Gd(III) ions are connected to the three HL 2- Ligand and 3 OAc - The oxygen atoms of the ions are coordinated to form a three-capped triangular prism geometry.

[0006] In some embodiments, the magnetic resonance imaging material is of the triclinic system, Space group, unit cell parameters of MRI material are: a =12.5351(7)Å, b=13.3226(4)Å, c =13.8249(8)Å, α= 91.608(3)º, β= 115.143(5)º, γ = 93.302(3)º.

[0007] In some embodiments, the magnetic resonance imaging material is prepared by the following method: Gd(NO)3·6H2O, Mn(OAc)2·4H2O, 2-hydroxy-1-naphthaldehyde and 3-amino-1,2-propanediol were weighed and dissolved in an organic solvent to obtain a mixed solution, which was heated to obtain [Gd2Mn4(HL)4(OAc)6]·4EtOH·4H2O.

[0008] The embodiment of the present application also discloses a method for preparing a magnetic resonance imaging material, comprising the following steps: weighing Gd(NO)3·6H2O, Mn(OAc)2·4H2O, 2-hydroxy-1-naphthaldehyde, and 3-amino-1,2-propanediol, dissolving them in an organic solvent to obtain a mixed solution, heating the solution to react, and obtaining [Gd2Mn4(HL)4(OAc)6]·4EtOH·4H2O.

[0009] In some embodiments, the temperature of the heating reaction is 55°C to 65°C, and the time of the heating reaction is 15h to 25h.

[0010] In some embodiments, the organic solvent comprises anhydrous ethanol and acetonitrile in a volume ratio of 1:(1-2).

[0011] In some embodiments, triethylamine is further added to the mixed solution of the present application.

[0012] In some embodiments, the volume molar ratio of triethylamine to Gd(NO)3·6H2O is 1 mL: (2-2.5) mmol.

[0013] In some embodiments, the molar ratio of Gd(NO)3·6H2O, Mn(OAc)2·4H2O, 2-hydroxy-1-naphthaldehyde, and 3-amino-1,2-propanediol is (0.8~1.2):(0.8~1.2):(1.8~2.2):(1.8~2.2).

[0014] The embodiments of the present application also provide the use of the magnetic resonance imaging material or the magnetic resonance imaging material prepared by the method for preparing the magnetic resonance imaging material in the preparation of a magnetic resonance contrast agent.

[0015] Beneficial effects: The present application provides a magnetic resonance imaging material, a preparation method and an application. The chemical formula of the magnetic resonance imaging material of the present application is: [Gd2Mn4(HL)4(OAc)6]·4EtOH·4H2O; wherein the ligand HL is formed by dehydrogenation of the compound 2-(1-naphthyl-amino)-2-(hydroxymethyl)-1-propanol. The magnetic resonance imaging material of the present application can be used as a contrast agent and has application value in the field of magnetic resonance. Compared with traditional Gd contrast agents, the paramagnetism of the Mn ions in the magnetic resonance imaging material of the present application can cooperate with the Gd ions to increase the longitudinal relaxation rate, enhance the T1-weighted imaging contrast, expand multi-parameter diagnostic information, and also reduce the nephrogenic systemic fibrosis induced by Gd ion deposition. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Picture 1 is a molecular structure diagram of the magnetic resonance imaging material prepared in Example 1 of the present invention; Picture 2 is a metal skeleton diagram of the magnetic resonance imaging material prepared in Example 1 of the present invention; Picture 3 The magnetic resonance imaging material prepared in Example 1 of the present invention is χ M , χ M T Temperature T Change curve chart; Picture 4 is an infrared spectrum of the magnetic resonance imaging material prepared in Example 1 of the present invention; Picture 5 is a powder X-ray diffraction (PXRD) pattern of the magnetic resonance imaging material prepared in Example 1 of the present invention; Picture 6 is a thermogravimetric analysis diagram of the magnetic resonance imaging material prepared in Example 1 of the present invention; Picture 7 This is a group of graphs showing the magnetic resonance imaging performance of the magnetic resonance imaging material prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0017] Example 1: Preparation of Magnetic Resonance Imaging Material [Gd2Mn4(HL)4(OAc)6]·4EtOH·4H2O Gd(NO)3·6H2O (0.1mmol, 0.0451g), Mn(OAc)2·4H2O (0.1mmol, 0.0245g), 2-hydroxy-1-naphthaldehyde (0.2mmol, 0.0344g), 3-amino-1,2-propanediol (0.2mmol, 0.0182g) were accurately weighed in a lead-free glass bottle, 4mL of acetonitrile and 2mL of anhydrous ethanol were added, and then 50μL of triethylamine was added, and the mixture was fully shaken to ensure uniform mixing, and then sealed in a 25mL heat-resistant glass bottle and heated at 60°C for 20h to obtain purple-black crystals. After 20h, the sample was taken out and cooled to ambient temperature in air for more than one day, and the purple crystals turned into black crystals.

[0018] Example 2: Performance measurement of magnetic resonance imaging materials (1) Structural characterization The single crystal complex prepared in Example 1 with good texture and regular crack-free structure was selected and the single crystal complex was subjected to the diffraction analysis using a SuperNova X-ray single crystal diffractometer on a graphite monochromator. Mo- Under Kα radiation (λ=0.7107Å), 293(2)K conditions, at a specific θ Range φ-ω Diffraction points were collected in a scanning mode for single crystal structure analysis and correction. All compounds were solved by direct method and refined by full matrix least squares method using ShelXL-2014 and SHELXL packages. All non-hydrogen atoms were refined by direct method. Detailed crystal determination data are shown in Table 1, and specific bond lengths and angles are shown in Table 2. Molecular structure is shown in Picture 1 shown.

[0019] Table 1 Crystallographic data of magnetic resonance imaging materials

[0020]

[0021]

[0022] Table 2 Bond lengths and angles of magnetic resonance imaging materials

[0023] like Picture 1 and Picture 2 As shown, the complex structure of the magnetic resonance imaging material of the present application is specifically composed of two HL 2- Ligands use their μ 3-OH - The O atoms (O6 and O6A) on the chelate are bridged with two Dy(III) ions and one Mn(II) ion. The two Gd(III) ions and four Mn(II) ions in the coordination unit are bridged by two μ 3-OH -Ligand and 8 μ 2- OH - The ligands are bridged to form a seesaw-like hexanuclear framework structure, in which four shared Mn(II) ions are located on a parallelogram plane. The Gd(III) ions are bridged with three Schiff base ligands HL 2- The N1O4 donor is composed of three Schiff base ligands HL 2- and three OAc - ions, and form a slightly distorted tetrahedral geometry with Mn1 and Mn1A ions, in which one N atom and four O atoms of Mn1 come from two Schiff base ligands HL 2- and an OAc - ions. The N1O5 donor consists of two Schiff base ligands HL 2- Ligand and two OAc - ions, and form a slightly distorted octahedral geometry with Mn2 and Mn2A in a hexacoordinate environment. The bond lengths of Mn1-O / N and Mn2-O / N range from 1.866 (8) to 2.244 (8) Å, and the bond angles range from 83.4 (3)° to 176.4 (3)°. The bond lengths of Gd(III)-O range from 2.338 (6) to 2.774 (7) Å, and the bond angles range from 52.7 (3)° to 153.7 (3)°.

[0024] (2) Determination of magnetic properties Under the conditions of a 1000 Oe external DC magnetic field and a temperature range of 2 K to 300 K, the variable temperature DC magnetic susceptibility of the magnetic resonance imaging material prepared in Example 1 was measured. Picture 3 As shown, the magnetic resonance imaging material prepared in Example 1 at room temperature χ M T The value is 33.25cm 3 K mol -1 , while the theoretical χ M T The value is very close to this value. When the temperature drops from 300K to 240K, χ M T The value remains almost unchanged, while when the temperature is reduced to 2K, the magnetic resonance imaging material prepared in Example 1 χ M T The value starts to decrease slowly, and then drops rapidly to the minimum and final value of 5.325cm3 K mol -1 In the entire test environment, the magnetic resonance imaging material χ M T The value distribution may be caused by thermal migration in Stark levels and their different magnetic interactions.

[0025] (3) Infrared spectroscopy analysis like Picture 4 As shown, the absorption peak of the magnetic resonance imaging material prepared in Example 1 is at 3340 cm -1 It is relatively wide and long near the center, and it is believed that this segment belongs to the signal peak generated by the stretching vibration of water molecules in the complex or the environment. The magnetic resonance imaging materials are at 1541cm -1 and 1561cm -1 There is a relatively strong peak at 1431cm, which belongs to the stretching vibration absorption peak of the naphthalene ring; the magnetic resonance imaging material is at 1431cm -1 and 1424cm -1 The peak belongs to the stretching vibration absorption peak of CC; the peak of magnetic resonance imaging material is 1067cm -1 and 1187cm -1 The absorption peak can be attributed to the stretching vibration absorption peak of CO.

[0026] (4) Powder diffraction analysis Under normal temperature conditions, the powder samples of MRI materials were tested in the range of 5º-50º at a scanning speed of 5º / min. The purity of MRI materials can be determined by X-ray powder diffraction analysis and fitting. The actual test result data obtained from the experiment was compared with the theoretical spectrum of single crystal structure simulation. Picture 5 The lower curve is the standard powder curve, and the upper curve is the measured curve of the powder sample. By observing the image, it can be found that the two curves show a high degree of similarity and good agreement, so it is concluded that the magnetic resonance imaging material is a pure phase substance.

[0027] (5) Thermogravimetric analysis like Picture 6 As shown, in a flowing nitrogen environment, at 5°C min -1 The temperature was slowly raised from 35°C to 1000°C at a heating rate to test the thermal stability of the magnetic resonance imaging material. The magnetic resonance imaging material showed a rapid decline in the range of 35°C to 118°C, and its weight loss rate was 11.72%, which was attributed to the loss of solvent molecules. As the temperature continued to rise, the magnetic resonance imaging material entered a stable plateau at 118°C to 219°C. As the temperature gradually increased, the skeleton of the magnetic resonance imaging material gradually collapsed, but until the temperature reached 1000°C, the Schiff base ligand was not completely decomposed.

[0028] (6) Magnetic resonance imaging test like Picture 7 As shown, the magnetic resonance imaging performance of the magnetic resonance imaging material was tested under a 0.5T magnetic resonance scanner. T The 1-weighted MR grayscale image and the corresponding color image showed an obvious concentration-dependent change trend. The longitudinal relaxation rate of the magnetic resonance imaging material prepared in Example 1 reached 1.95 mM. -1 s -1 , the transverse relaxation rate reaches 7.57mM -1 s -1 , r2 / r1 is 3.88 at 0.5T magnetic field, which is typical T Type 1 magnetic resonance contrast agent, which indicates that the magnetic resonance imaging material may play an important role in the field of magnetic resonance imaging and is an excellent material for preparing magnetic resonance imaging contrast agent.

[0029] The above is a detailed introduction to a magnetic resonance imaging material, a preparation method and an application provided in the embodiments of the present application. Specific examples are used herein to illustrate the principles and implementation methods of the present application. The description of the above embodiments is only used to help understand the method and its core idea of ​​the present application. At the same time, for technicians in this field, according to the idea of ​​the present application, there will be changes in the specific implementation method and application scope. In summary, the content of this specification should not be understood as a limitation on the present application.

Claims

1. A magnetic resonance imaging material, characterized in that: The chemical formula of the magnetic resonance imaging material is: [Gd2Mn4(HL)4(OAc)6]·4EtOH·4H2O, wherein the ligand HL is formed by dehydrogenation of the compound 2-(1-naphthyl-amino)-2-(hydroxymethyl)-1-propanol.

2. The magnetic resonance imaging material according to claim 1, characterized in that The structure of the magnetic resonance imaging material is composed of 2 Gd(III) ions, 4 Mn(II) ions, 4 HL 2- Ligand, 6 OAc - ions, 4 EtOH molecules and 4 H2O molecules; 2 Gd(III) ions and 4 Mn(II) ions are μ 3-OH - Ligand and 8 μ 2-OH - The ligands are connected to form a hexanuclear framework structure, in which four shared Mn(II) ions are located on a parallelogram plane; the Gd(III) ions are connected to the three HL 2- Ligand and 3 OAc - The oxygen atoms of the ions are coordinated to form a three-capped triangular prism geometry.

3. The magnetic resonance imaging material according to claim 1, characterized in that: The magnetic resonance imaging material belongs to the triclinic system, Space group, unit cell parameters of MRI material are: a =12.5351(7)Å, b =13.3226(4)Å, c =13.8249(8)Å, α= 91.608(3)º, β= 115.143(5)º, γ= 93.302(3)º.

4. The magnetic resonance imaging material according to claim 1, characterized in that The magnetic resonance imaging material is prepared by the following method: Gd(NO)3·6H2O, Mn(OAc)2·4H2O, 2-hydroxy-1-naphthaldehyde and 3-amino-1,2-propanediol were weighed and dissolved in an organic solvent to obtain a mixed solution, which was heated to obtain [Gd2Mn4(HL)4(OAc)6]·4EtOH·4H2O.

5. A method for preparing a magnetic resonance imaging material as claimed in claim 1, characterized in that: The method comprises the following steps: weighing Gd(NO)3·6H2O, Mn(OAc)2·4H2O, 2-hydroxy-1-naphthaldehyde and 3-amino-1,2-propylene glycol, dissolving them in an organic solvent to obtain a mixed solution, and heating the solution for reaction to obtain [Gd2Mn4(HL)4(OAc)6]·4EtOH·4H2O.

6. The method for preparing a magnetic resonance imaging material according to claim 5, characterized in that: The temperature of the heating reaction is 55°C to 65°C, and the time of the heating reaction is 15h to 25h.

7. The method for preparing a magnetic resonance imaging material according to claim 5, characterized in that: The organic solvent includes anhydrous ethanol and acetonitrile in a volume ratio of 1:(1-2).

8. The method for preparing a magnetic resonance imaging material according to claim 5, characterized in that: The molar ratio of Gd(NO)3·6H2O, Mn(OAc)2·4H2O, 2-hydroxy-1-naphthaldehyde and 3-amino-1,2-propylene glycol is (0.8-1.2): (0.8-1.2): (1.8-2.2): (1.8-2.2).

9. Use of the magnetic resonance imaging material according to any one of claims 1 to 4 or the magnetic resonance imaging material prepared by the method for preparing the magnetic resonance imaging material according to any one of claims 5 to 8 in preparing a magnetic resonance contrast agent.

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