A magnetic resonance imaging material, preparation method and application

Abstract

This application belongs to the technical field of magnetic functional materials. This application discloses a magnetic resonance imaging material, a preparation method and an application thereof. The chemical formula of the magnetic resonance imaging material of this application is: [Gd2Mn4(HL)4(OAc)6]·4EtOH·4H2O, wherein the ligand HL is formed by dehydrogenation of the compound 2-(1-naphthylamino)-2-(hydroxymethyl)-1-propanol. The magnetic resonance imaging material of this application can be used as a contrast agent material in the field of magnetic resonance imaging. Compared with traditional Gd contrast agents, the paramagnetism of Mn ions in the magnetic resonance imaging material of this application can cooperate with Gd ions to improve the longitudinal relaxation rate, enhance the T₁-weighted imaging contrast, expand multi-parameter diagnostic information, and can also reduce nephrogenic systemic fibrosis induced by Gd ion deposition.

Description

Technical Field

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

[0002] Magnetic resonance imaging materials are a class of materials used in magnetic resonance imaging (MRI) technology, which enhance the imaging quality or provide specific imaging functions by changing the relaxation time of tissues. They have characteristics such as 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 a relatively large clinical dosage, easy occurrence of nephrotoxicity and poor imaging effects. Summary of the Invention

[0003] Object of the Invention: This application provides a magnetic resonance imaging material, a preparation method and an application thereof. The magnetic resonance imaging material of this application can be used as a contrast agent in the magnetic resonance field, and can solve problems such as a relatively large clinical dosage of existing contrast agents, easy occurrence of nephrotoxicity and poor imaging effects.

[0004] Technical Solution: An embodiment of the present invention provides a magnetic resonance imaging material, and 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-naphthylamino)-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- ligands, 6 OAc - ions, 4 EtOH molecules and 4 H2O molecules together; 2 Gd(III) ions and 4 Mn(II) ions are connected by 2 μ 3-OH - ligands and 8 μ 2-OH - ligands to form a hexanuclear framework structure, and four shared Mn(II) ions are located on a parallelogram plane; the Gd(III) ion coordinates with oxygen atoms from 3 HL 2- ligands and 3 OAc - ions to form a trigonal antiprismatic geometry with three capping atoms.

[0006] In some embodiments, the magnetic resonance imaging material belongs to the triclinic system, space group, and the unit cell parameters of the magnetic resonance imaging material are: a 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:

[0008] Weigh Gd(NO)3·6H2O, Mn(OAc)2·4H2O, 2-hydroxy-1-naphthaldehyde, and 3-amino-1,2-propanediol and dissolve them in an organic solvent to obtain a mixed solution. Heat the solution to obtain [Gd2Mn4(HL)4(OAc)6]·4EtOH·4H2O.

[0009] The embodiments of the present application also disclose a method for preparing a magnetic resonance imaging material, including the following steps: Weigh Gd(NO)3·6H2O, Mn(OAc)2·4H2O, 2-hydroxy-1-naphthaldehyde, and 3-amino-1,2-propanediol and dissolve them in an organic solvent to obtain a mixed solution. Heat and react the solution to obtain [Gd2Mn4(HL)4(OAc)6]·4EtOH·4H2O.

[0010] In some embodiments, the temperature of the heating reaction is 55 °C to 65 °C, and the time of the heating reaction is 15 h to 25 h.

[0011] In some embodiments, the organic solvent includes anhydrous ethanol and acetonitrile with a volume ratio of 1:(1 - 2).

[0012] In some embodiments, triethylamine is further added to the mixed solution of the present application.

[0013] In some embodiments, the volume molar ratio of triethylamine to Gd(NO)3·6H2O is 1 mL:(2 - 2.5) mmol.

[0014] 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).

[0015] The embodiments of the present application also provide the use of the above magnetic resonance imaging material or the magnetic resonance imaging material prepared by the above method for preparing a magnetic resonance contrast agent.

[0016] Beneficial effects: The present application provides a magnetic resonance imaging material, a preparation method, and an application thereof. 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-naphthylamino)-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 Mn ions in the magnetic resonance imaging material of the present application can cooperate with Gd ions to improve the longitudinal relaxation rate, enhance the T1-weighted imaging contrast, expand multi-parameter diagnostic information, and can also reduce gadolinium ion deposition-induced nephrogenic systemic fibrosis. Description of the Drawings

[0017] Figure 1 is the molecular structure diagram of the magnetic resonance imaging material prepared in Example 1 of the present invention;

[0018] Figure 2 is the metal skeleton diagram of the magnetic resonance imaging material prepared in Example 1 of the present invention;

[0019] Figure 3 is the χ M 、χ M T versus temperature T variation curve graph;

[0020] Figure 4 is the infrared spectrum diagram of the magnetic resonance imaging material prepared in Example 1 of the present invention;

[0021] Figure 5 is the powder X-ray diffraction (PXRD) diagram of the magnetic resonance imaging material prepared in Example 1 of the present invention;

[0022] Figure 6 is the thermogravimetric analysis diagram of the magnetic resonance imaging material prepared in Example 1 of the present invention;

[0023] Figure 7 is the magnetic resonance imaging performance group diagram of the magnetic resonance imaging material prepared in Example 1 of the present invention. Detailed Embodiments

[0024] Example 1: Preparation of the magnetic resonance imaging material [Gd2Mn4(HL)4(OAc)6]·4EtOH·4H2O

[0025] Accurately weigh Gd(NO)3·6H2O (0.1 mmol, 0.0451 g), Mn(OAc)2·4H2O (0.1 mmol, 0.0245 g), 2-hydroxy-1-naphthaldehyde (0.2 mmol, 0.0344 g), and 3-amino-1,2-propanediol (0.2 mmol, 0.0182 g) in a lead-free glass bottle in sequence. Add 4 mL of acetonitrile and 2 mL of absolute ethanol, and then add 50 μL of triethylamine. Shake well to ensure uniform mixing, and then seal it in a 25 mL heat-resistant glass bottle. Heat it at 60 °C for 20 h to obtain purple-black crystals. After 20 h, take out the sample and cool it in the air to ambient temperature for more than one day. The purple crystals turn into black crystals.

[0026] Example 2: Performance Determination of Magnetic Resonance Imaging Material

[0027] (1) Structure Characterization

[0028] Select the single crystal complex with good texture and no cracks and regular shape prepared in Example 1. Use a SuperNova X-ray single crystal diffractometer under graphite monochromatized Mo- Kα radiation (λ = 0.7107 Å), 293(2) K conditions, within a specific θ range to φ-ω collect diffraction points in a Figure 1 scanning mode for single crystal structure analysis and refinement. All compounds are solved by the direct method and refined by full matrix least squares using the ShelXL-2014 and SHELXL program packages. All non-hydrogen atoms are refined using the direct method. The detailed crystal determination data are shown in Table 1, and the specific bond lengths and bond angles are shown in Table 2. The molecular structure is as

[0029] Table 1 Crystallographic Data of Magnetic Resonance Imaging Material

[0030]

[0031]

[0032] Table 2 Bond Lengths and Bond Angles of Magnetic Resonance Imaging Material

[0033]

[0034] As Figure 1 and Figure 2 shown, the complex structure of the magnetic resonance imaging material of the present application specifically consists of two HL 2- ligands using their μ 3-OH -The O atoms (O6 and O6A) on it bridge two Dy(III) ions and one Mn(II) ion. Two Gd(III) ions and four Mn(II) ions in the coordination unit are bridged by two μ 3-OH - ligands and eight μ 2- OH - ligands to form a seesaw-shaped hexanuclear framework structure, where four shared Mn(II) ions are located on a parallelogram plane. The Gd(III) ions coordinate with the oxygen atoms from three Schiff base ligands HL 2- and three OAc- ions to form a tricapped trigonal prism geometric topology. The N1O4 donor is assembled by three Schiff base ligands HL 2- and three OAc - ions and forms a slightly distorted tetrahedral geometry of a five-coordination environment with Mn1 and Mn1A ions. One N atom and four O atoms of Mn1 come from two Schiff base ligands HL 2- and one OAc - ion. The N1O5 donor is assembled by two Schiff base ligands HL 2- ligands and two OAc - ions and forms a slightly distorted octahedral geometry of a six-coordination environment with Mn2 and Mn2A. The bond lengths of Mn1-O / N and Mn2-O / N are in the range of 1.866(8)-2.244(8) Å, and the bond angles are in the range of 83.4(3)°-176.4(3)°. The bond lengths of Gd(III)-O are in the range of 2.338(6)-2.774(7) Å, and the bond angles are in the range of 52.7(3)°-153.7(3)°.

[0035] (2)Magnetic property measurement

[0036] Under the condition of an applied DC magnetic field of 1000 Oe and a temperature range of 2 K to 300 K, the temperature-dependent DC magnetic susceptibility of the magnetic resonance imaging material prepared in Example 1 was measured. As Figure 3 shown, the χ M T value of the magnetic resonance imaging material prepared in Example 1 at room temperature is 33.25 cm 3 K mol -1 , and the theoretical χ M T value of two Gd(III) ions and four Mn(II) is extremely close to this value. When the temperature drops from 300 K to 240 K, χ MT The value remains almost unchanged. When the temperature is reduced to 2K, the χ M T value of the magnetic resonance imaging material prepared in Example 1 begins to decrease slowly and then rapidly drops to the minimum value, which is also the final value of 5.325 cm 3 K mol -1 , and in the entire test environment, the χ M T value distribution of the magnetic resonance imaging material may be caused by thermal migration in the Stark energy levels and their different magnetic interactions.

[0037] (3) Infrared spectroscopy analysis

[0038] As Figure 4 shown, the absorption peak of the magnetic resonance imaging material prepared in Example 1 is relatively wide and long near 3340 cm -1 , and it is considered that this section belongs to the signal peak generated by the stretching vibration of water molecules in the complex or the environment. The magnetic resonance imaging material has relatively strong sharp peaks at 1541 cm -1 and 1561 cm -1 respectively, which belong to the stretching vibration absorption peaks of the naphthalene ring; the magnetic resonance imaging material has a relatively strong sharp peak at 1431 cm -1 and 1424 cm -1 respectively, which belong to the stretching vibration absorption peaks of C-C; the absorption peaks of the magnetic resonance imaging material at 1067 cm -1 and 1187 cm -1 can be attributed to the stretching vibration absorption peaks of C-O.

[0039] (4) Powder diffraction analysis

[0040] Under normal temperature conditions, the powder sample of the magnetic resonance imaging material was tested at a scanning speed of 5º / min in the range of 5º - 50º. Through X-ray powder diffraction analysis fitting, the purity of the magnetic resonance imaging material can be determined. The actual test result data obtained from the experiment was compared with the theoretical spectrum diagram simulated by the single crystal structure. Figure 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 these two curves show a high degree of similarity and good coincidence. Therefore, it is concluded that the magnetic resonance imaging material is a pure-phase substance.

[0041] (5) Thermogravimetric analysis

[0042] As Figure 6 shown, in a flowing nitrogen environment, at 5°C min -1The heating rate slowly raises the temperature from 35°C to 1000°C for the thermal stability test of the magnetic resonance imaging material. The magnetic resonance imaging material shows a rapid decline in the range of 35°C - 118°C, with a weight loss rate of 11.72%, which is attributed to the loss of solvent molecules. As the temperature continues to rise, the magnetic resonance imaging material enters a stable plateau in the range of 118°C - 219°C. As the temperature gradually increases, the framework of the magnetic resonance imaging material gradually collapses, but even when the temperature reaches 1000°C, the Schiff base ligand is not completely decomposed.

[0043] (6)Magnetic resonance imaging test

[0044] As Figure 7 shown, the magnetic resonance imaging performance of the magnetic resonance imaging material is tested under a 0.5T magnetic resonance scanner. The T T1-weighted MR gray-scale image and the corresponding color image of the magnetic resonance imaging material show an obvious concentration-dependent change trend. The longitudinal relaxation rate of the magnetic resonance imaging material prepared in Example 1 reaches 1.95 mM -1 s -1 , and the transverse relaxation rate reaches 7.57 mM -1 s -1 . At a 0.5T magnetic field, r2 / r1 is 3.88, which is a typical T type I magnetic resonance contrast agent, indicating 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 agents.

[0045] The above has introduced in detail a magnetic resonance imaging material, its preparation method and application provided by the embodiments of the present application. Specific examples are used in this article to elaborate on the principle and implementation manner 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 those skilled in the art, according to the idea of the present application, there will be changes in the specific implementation manner and application scope. In summary, the content of this specification should not be construed as a limitation to the present application.

Claims

1. A magnetic resonance imaging material, 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 are weighed and dissolved in an organic solvent to obtain a mixed solution, and heated to obtain a magnetic resonance imaging material; 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.

2. The magnetic resonance imaging material according to claim 1, characterized in that The organic solvent includes anhydrous ethanol and acetonitrile in a volume ratio of 1:(1-2); the temperature of the heating reaction is 55°C-65°C, and the time of the heating reaction is 15h-25h.

3. The magnetic resonance imaging material according to claim 1, 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).

4. The magnetic resonance imaging material according to claim 1, characterized in that Triethylamine is also added to the mixed solution, and the volume molar ratio of triethylamine to Gd(NO)3·6H2O is 1mL: (2-2.5)mmol.

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 a magnetic resonance imaging material.

6. 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); the temperature of the heating reaction is 55°C-65°C, and the time of the heating reaction is 15h-25h.

7. The method for preparing a magnetic resonance imaging material according to claim 5, characterized in that: Triethylamine is also added to the mixed solution, and the volume molar ratio of triethylamine to Gd(NO)3·6H2O is 1mL: (2-2.5)mmol.

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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