Metal complex as well as preparation method and application thereof

Abstract

The invention discloses a metal complex as well as a preparation method and application thereof, and belongs to the technical field of medical biological materials. The metal complex provided by the invention comprises metal ions and ligands complexed with the metal ions, the ligand is prepared by carrying out a reaction on 4-methyl thiosemicarbazide and alpha-ketoglutaric acid. The metal complex provided by the invention can optimize the properties of alpha-ketoglutaric acid, provide an excellent coordination environment, improve the complexing efficiency and form a stable ligand with excellent performance by utilizing the excellent coordination performance and chemical activity of 4-methyl thiosemicarbazide. When the thiosemicarbazide group is coordinated with metal ions through coordination bonds, the thiosemicarbazide group can have a synergistic effect with the metal ions, so that the thiosemicarbazide group can be used as a neutral molecule and can also be used as an anion ligand after deprotonation, various coordination modes are provided, rearrangement of a space structure is optimized, and excellent structural stability and remarkable anti-inflammatory and antibacterial properties are shown; the method has wide application potential in the field of biomedical material preparation.

Description

Technical Field

[0001] The present application belongs to the technical field of medical biomaterials, and in particular relates to a metal complex and a preparation method and application thereof. Background Art

[0002] With the development and progress of society, people have found that some trace metal elements with therapeutic effects cannot be directly applied in clinical practice due to their high toxicity, strong irritation, and difficulty in absorption. However, if they are turned into metal complexes, the toxicity and irritation of the metal itself can be reduced to a certain extent, and the absorption rate in the human body can be improved. Therefore, the status of metal coordination compounds in medicine is becoming more and more important.

[0003] Metal coordination compounds, also known as metal complexes, are a type of compound containing a central metal atom (ion) and several ligands formed by coordination bonds. Metal coordination compounds are usually generated by complexing metal ions with various ligands. However, the existing complexes have the following problems: first, the molecular structure is unstable due to the composition, and the purity of the complex is low and contains impurities; second, the antibacterial property is poor and the lack of anti-inflammatory properties will greatly reduce the wound healing rate. Therefore, it is necessary to develop materials with excellent comprehensive performance to promote the development of biomedical materials. Summary of the invention

[0004] The present application discloses a metal complex and a preparation method and application thereof, aiming to solve the technical problems of the existing complex having unstable molecular structure, low purity, poor antibacterial property and no anti-inflammatory property.

[0005] In order to achieve the above purpose, the technical solution of this application is:

[0006] The first aspect of the present application provides a metal complex, comprising: a metal ion and a ligand complexed with the metal ion;

[0007] The ligand is prepared by reacting 4-methylthiosemicarbazide with α-ketoglutaric acid.

[0008] In combination with the first aspect, preferably, the metal ion is Cu 2+ Mg 2+ , Mn 2+ 、Ni 2+ 、Co 2+ 、Zn 2+ , Fe 2+ Any one of .

[0009] In combination with the first aspect, preferably, the particle size of the metal complex is less than 1000 nm.

[0010] The second aspect of the present application provides a method for preparing the metal complex described in the first aspect, the preparation method comprising:

[0011] Dissolving 4-methylthiosemicarbazide and α-ketoglutaric acid in an organic solvent for reaction to obtain a ligand solution;

[0012] The ligand solution is reacted with the metal salt, the pH is adjusted, and the bottom precipitate is separated and collected to obtain the metal complex.

[0013] In combination with the second aspect, preferably, the molar ratio of the 4-methylthiosemicarbazide to α-ketoglutaric acid is 1-2:1.

[0014] In combination with the second aspect, preferably, the organic solvent is one or more of N,N-dimethylformamide, methanol, chlorobenzene and dimethyl sulfoxide.

[0015] In combination with the second aspect, preferably, the metal salt is one of acetate, halide, sulfate, nitrate and sulfonate.

[0016] In combination with the second aspect, preferably, the pH value is adjusted to a range of 6.0-8.0.

[0017] In combination with the second aspect, preferably, the molar ratio of the ligand solution to the metal salt is 1-2:1.

[0018] The third aspect of the present application provides the use of the metal complex described in the first aspect or the metal complex prepared by the preparation method described in the second aspect in the preparation of biomedical materials.

[0019] Compared with the prior art, the advantages or beneficial effects of the embodiments of the present application include at least:

[0020] The metal complex provided in the present application is prepared by reacting 4-methylthiosemicarbazide with α-ketoglutaric acid to form a ligand, which is then complexed with a metal ion. On the one hand, the excellent coordination performance and chemical activity of 4-methylthiosemicarbazide can be used to optimize the properties of α-ketoglutaric acid, provide an excellent coordination environment, improve the complexation efficiency, form a stable ligand with excellent performance, and coordinate with the metal ion through a coordination bond. The thiosemicarbazide group can cooperate with the metal ion as a neutral molecule or be deprotonated as an anionic ligand afterwards, and can provide a variety of coordination modes, optimize the rearrangement of the spatial structure, and have excellent structural stability. On the other hand, the metal complex can be endowed with excellent anti-inflammatory and antibacterial effects, and has broad application prospects in the preparation of biomedical materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments recorded in the present application, and for ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0022] Figure 1 The nuclear magnetic hydrogen spectrum of the ligand provided in the examples of the present application;

[0023] Figure 2 A high-resolution mass spectrum of the ligand provided in the embodiments of the present application;

[0024] Figure 3 This is a SEM image of the A1-copper coordination complex provided in the examples of the present application;

[0025] Figure 4 This is an EDS diagram of the A1-copper coordination complex provided in the examples of the present application;

[0026] Figure 5 The SEM image of the A2-nickel coordination complex provided in the examples of the present application;

[0027] Figure 6 This is a diagram showing the anti-inflammatory effect of the A1-copper coordination complex provided in the examples of the present application;

[0028] Figure 7 This is a diagram showing the antibacterial effect of the A1-copper coordination complex provided in the examples of the present application. DETAILED DESCRIPTION

[0029] The technical solutions in the embodiments of the present application will be described clearly and completely below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, rather than all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0030] In the following description of this embodiment, the term "and / or" is used to describe the association relationship of associated objects, indicating that there may be three relationships. For example, A and / or B can represent: A exists alone, B exists alone, and A and B exist at the same time. A and B can be singular or plural. The character " / " generally indicates that the associated objects before and after are in an "or" relationship.

[0031] In the following description of this embodiment, the term "at least one" refers to one or more, and "plurality" refers to two or more. "At least one of the following" or similar expressions refers to any combination of these items, including any combination of single items or plural items. For example, "at least one of a, b or c", or "at least one of a, b and c", can all represent: a, b, c, ab (i.e., a and b), ac, bc, or abc, where a, b, c can be single or multiple, respectively.

[0032] Those skilled in the art should understand that in the following description of the embodiments of the present application, the order of serial numbers does not mean the order of execution, some or all of the steps can be executed in parallel or sequentially, and the execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0033] The terms used in the embodiments of the present application are only for the purpose of describing specific embodiments, and are not intended to limit the present application. The singular forms "a", "an" and "the" used in the embodiments of the present application and the appended claims are also intended to include plural forms, unless the context clearly indicates other meanings.

[0034] Those skilled in the art will appreciate that the numerical ranges in the examples of the present application are to be understood as also specifically disclosing each intermediate value between the upper and lower limits of the range. Each smaller range between the intermediate values ​​in any stated value and stated range and any other stated value or intermediate value in the range is also included in the present application. The upper and lower limits of these smaller ranges may be independently included or excluded in the scope.

[0035] Unless otherwise stated, the technical / scientific terms used herein have the same meanings as those generally understood by those skilled in the art in the field described in the present application. Although the present application only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the embodiments or test cases of the present application. All documents mentioned in this specification are generally incorporated by reference to disclose and describe the methods and / or materials related to the documents. In the event of a conflict with any incorporated document, the content of the present application shall prevail.

[0036] It should be noted that all raw materials and reagents in the examples of the present application were purchased on the market or prepared according to conventional methods well known to those skilled in the art.

[0037] In a first aspect, the embodiments of the present application provide a metal complex, including: a metal ion and a ligand complexed with the metal ion;

[0038] The ligand is prepared by reacting 4-methylthiosemicarbazide with α-ketoglutaric acid.

[0039] Among them, on the one hand, the excellent coordination performance and chemical activity of 4-methylthiosemicarbazide can be used to optimize the properties of α-ketoglutaric acid, provide an excellent coordination environment, improve the complexation efficiency, form a stable and high-performance ligand, and coordinate with the metal ion through a coordination bond. The thiosemicarbazide group can cooperate with the metal ion as a neutral molecule or be deprotonated as an anionic ligand afterwards, and can provide a variety of coordination modes, which can optimize the rearrangement of the spatial structure and have excellent structural stability; on the other hand, it can give the metal complex excellent anti-inflammatory and antibacterial effects, and has broad application prospects in the preparation of biomedical materials.

[0040] It should be noted that the ligand in the present application is prepared by reacting 4-methylthiosemicarbazide with α-ketoglutaric acid, and the α-ketoglutaric acid substituted thiosemicarbazide ligand is obtained by reacting the carbonyl group of α-ketoglutaric acid with the amino group on 4-methylthiosemicarbazide, and the reaction process is shown in formula (1). The α-ketoglutaric acid substituted thiosemicarbazide ligand is then subjected to coordination reaction with a metal salt in an organic solvent to obtain Cu 2+ Taking coordination complexation as an example, the copper atom in the target complex is coordinated in a 4+1 pyramid, with a water oxygen at the top position. The ligand is connected by a trident of S, N, and O on the base plane, and the fourth base position is occupied by the carboxylic acid oxygen of the adjacent molecule along the x-axis, thus forming a polymer chain. The reaction process is shown in formula (2).

[0041]

[0042] In the present embodiment, the metal ion is preferably Cu 2+ Mg 2+ , Mn 2+ 、Ni 2+ 、Co 2+ 、Zn 2+ , Fe 2+ Wherein, these metal ions can react with the ligand to obtain metal complexes with different structures.

[0043] In the embodiment of the present application, the particle size of the metal complex is less than 1000 nm. Among them, the metal complex with a nano-sized structure can significantly improve its antibacterial and anti-inflammatory properties.

[0044] In a second aspect, the present application also provides a method for preparing the metal complex described in the first aspect, the preparation method comprising:

[0045] Dissolving 4-methylthiosemicarbazide and α-ketoglutaric acid in an organic solvent for reaction to obtain a ligand solution;

[0046] The ligand solution is reacted with the metal salt, the pH is adjusted, and the bottom precipitate is separated and collected to obtain the metal complex.

[0047] It should be noted that, in the present application, α-ketoglutaric acid is first subjected to a substitution reaction with thiosemicarbazide to obtain α-ketoglutaric acid substituted thiosemicarbazide; specifically, the carbonyl group of α-ketoglutaric acid is reacted with the amino group on 4-methylthiosemicarbazide to obtain. Then, α-ketoglutaric acid substituted thiosemicarbazide is subjected to a coordination reaction with a metal salt in a good solvent to obtain a metal complex. The excellent coordination performance and chemical activity of 4-methylthiosemicarbazide are utilized to optimize the properties of α-ketoglutaric acid, provide a suitable coordination environment, improve the complexation efficiency, and form a stable and high-performance metal coordination complex.

[0048] It should be noted that the preparation process provided in the present application is simple and easy, the reaction conditions are easy to control, the cost is low, it can improve the product quality of the metal complex, reduce the formation of impurities, the purity is high, and it can give the metal complex excellent stability, which provides a broad application prospect for promoting the development in the fields of biomedicine, chemistry, etc.

[0049] In an embodiment of the present application, the molar ratio of the 4-methylthiosemicarbazide to α-ketoglutaric acid is preferably 1:1. Among them, by controlling the molar ratio of 4-methylthiosemicarbazide to α-ketoglutaric acid, an optimized ligand structure can be obtained. The preparation method comprises the following process: a solution of α-ketoglutaric acid dissolved in an organic solvent is dripped into an equimolar amount of 4-methylthiosemicarbazide solution dissolved in the same solvent. After the reaction is completed, a white solid powder is precipitated, which is separated and analyzed by filtration. Using 1:1 (v / v) THF / acetone as the eluent, the purity of the product dissolved in the minimum organic solvent is determined by thin layer chromatography, and the ligand is recrystallized from the organic solvent solution to obtain crystals.

[0050] In an embodiment of the present application, the molar ratio of the ligand solution to the metal salt is preferably 1:1. Among them, by controlling the molar ratio of the ligand solution to the metal salt, the reaction can be promoted, and the ligand and the central metal original ion can be combined in a suitable proportion and manner, which can improve the stability of the complex and regulate the activity of the metal original ion, thereby generating a structurally stable complex. The preparation method includes the following process: in the ligand solution, first adjust the pH to 7 with NaOH solution, and then drip a solution containing an equal amount of a metal salt dissolved in an aqueous solvent. After the reaction is completed, microcrystalline powder or crystals are formed by slow evaporation of the solvent. And the target complex can be recrystallized in several solvents such as CH3OH, C2H5OH and THF.

[0051] In the embodiment of the present application, the organic solvent is preferably one or more of N,N-dimethylformamide, methanol, chlorobenzene, and dimethyl sulfoxide, wherein these organic solvents can fully dissolve the raw materials, and can form solvent compounds with metal ions and ligands to promote the complexation reaction.

[0052] In the embodiments of the present application, the metal salt is preferably one of acetate, halide, sulfate, nitrate and sulfonate. Among them, these metal salts can dissociate metal ions and stably bind to the ligand through coordination bonds to form a complex. It should be noted that the present application can use any metal salt known to be used for preparing metal complexes without particular limitation.

[0053] In the embodiment of the present application, the pH value is preferably adjusted to a range of 6.0-8.0. By controlling the pH value of the solution, the metal ions can be prevented from hydrolyzing, the complexation reaction can be smoothly carried out, and the stability of the complex can be guaranteed.

[0054] The third aspect of the present application provides the use of the metal complex described in the first aspect or the metal complex prepared by the preparation method described in the second aspect in the preparation of biomedical materials. Based on the excellent antibacterial and anti-inflammatory properties and excellent biocompatibility of the metal complex prepared above, it has a wide range of application prospects in the preparation of biomedical materials.

[0055] The technical solution of the present application will be further described below in conjunction with specific embodiments.

[0056] Example 1

[0057] This embodiment provides a method for preparing an A1-copper coordination complex, which specifically comprises:

[0058] S101: dissolving α-ketoglutaric acid in methanol, adding a methanol solution of 4-methylthiosemicarbazide, stirring for 30 minutes, and monitoring the reaction by thin layer spot plate (TLC). After the reaction is completed, an α-ketoglutaric acid-substituted thiosemicarbazide ligand solution is obtained;

[0059] The white solid powder precipitated from the solution after the reaction was separated by filtration, and the purity of the product with the minimum CH3OH dissolved amount was determined by thin layer chromatography using 1:1 (v / v) THF / acetone as eluent, and the crystals were recrystallized from CH3OH solution to obtain α-ketoglutaric acid substituted thiosemicarbazide ligand, which was characterized and analyzed;

[0060] S102: Add NaOH solution to the α-ketoglutaric acid substituted thiosemicarbazide ligand solution to adjust the pH to 7, add CuCl2·2H2O aqueous solution, stir at room temperature for 1 hour, and slowly evaporate the solvent to form green or blue microcrystalline powder or crystals to obtain A1-copper coordination complex.

[0061] In order to verify the preparation of the α-ketoglutaric acid substituted thiosemicarbazide ligand prepared in the example, it was subjected to nuclear magnetic resonance testing. The results are as follows: Figure 1-2 shown.

[0062] according to Figure 1 It can be seen that the same type of atoms, due to being in different chemical environments, have different resonance peaks, and the difference between various peaks and a certain reference peak is called chemical shift. In the nuclear magnetic resonance hydrogen spectrum of compounds dissolved in heavy water solvent, the chemical shift value of the carboxyl group is usually between 10 and 13. Figure 1 The characteristic peak of carboxyl group can be clearly seen.

[0063] according to Figure 2 It can be seen that the molecular formula of α-ketoglutaric acid substituted thiosemicarbazide ligand is C7H 11 N3O4S, in the mass spectrum, except for the molecular ion composed of the lightest isotope, + In addition to the peak, there will be one or more molecular ion peaks composed of heavy isotopes, such as (M+1) + 、(M+2) + 、(M+3) + Such ion peaks are called isotope ion peaks. The corresponding m / z is represented by M+1, M+2, and M+3. Generally, the intensity of M and M+1, M+2, and M+3 peaks can be used to determine whether a compound contains these elements. + : 234.0543, and the corresponding peak 234.05341 appeared in the mass spectrum, proving that the α-ketoglutaric acid-substituted thiosemicarbazide ligand was successfully synthesized.

[0064] In order to verify the structural properties of the A1-copper coordination complex prepared in the example, SEM and EDS tests were performed on it. The results are as follows: Figure 3-4 shown.

[0065] according to Figure 3 It can be seen that the A1-copper coordination complex is in the form of nanoclusters, indicating that the complex forms aggregates formed by multiple copper atoms or ions and ligand molecules through coordination bonds at the microscopic scale, and these aggregates have clear shapes and boundaries at the nanoscale. There may be strong interactions between the copper atoms or ions in the cluster, such as metal-metal bonds or metal-ligand bonds, which allow the cluster structure to exist stably.

[0066] according to Figure 4 It can be seen that the C, N, O, S, Cl, and Cu elements in the A1-copper coordination complex are evenly distributed on its surface, which also shows the structural uniformity of the complex at the nanoscale, the stability of the coordination bonds, and the absence of obvious phase separation.

[0067] According to the copper content in the copper coordination complex determined by ICP, the copper content in the copper coordination complex accounts for 23.13%. The test results are shown in Table 1:

[0068] Table 1A1 - Copper Content of Copper Coordination Complexes

[0069] element Average content (ppb) Average share copper 1156.3335 23.13％

[0070] Example 2

[0071] This embodiment provides a method for preparing the A2-nickel coordination complex, which specifically comprises:

[0072] S201: dissolving α-ketoglutaric acid in methanol, adding a methanol solution of 4-methylthiosemicarbazide, stirring for 30 minutes, and monitoring the reaction by thin layer spot plate (TLC). After the reaction is completed, an α-ketoglutaric acid-substituted thiosemicarbazide ligand solution is obtained;

[0073] S202: Add NaOH solution to the α-ketoglutaric acid substituted thiosemicarbazide ligand solution to adjust the pH to 7, add NiCl2·2H2O aqueous solution, stir at room temperature for 1 hour, and slowly evaporate the solvent to form green or blue-green microcrystalline powder or crystals to obtain A2-nickel coordination complex.

[0074] In order to verify the appearance morphology of the A2-nickel coordination complex prepared in the example, SEM test was performed on it, and the results are as follows: Figure 5 shown.

[0075] according to Figure 5 It can be seen that the A2-nickel coordination complex is in the form of nanoparticles, indicating that the particles formed by the nickel atoms or ions and the ligand molecules through coordination bonds have clear shapes and boundaries at the nanoscale. These particles may be spherical, cubic, etc., depending on the synthesis method and conditions. The coordination between the nickel atoms or ions and the ligand molecules also forms a stable structure. Compared with the copper coordination complex, the nanoparticle structure of the nickel coordination complex is more compact and regular, which is related to the electronic structure and coordination properties of the nickel atoms or ions.

[0076] According to the nickel content in the nickel coordination complex determined by ICP, the nickel content in the nickel coordination complex is 14.4%. The test results are shown in Table 2:

[0077] Table 2A2 - Nickel Content of Nickel Coordination Complexes

[0078] element Average content (ppb) Average share nickel 736.139 14.40％

[0079] To verify the anti-inflammatory property of the prepared A1-copper coordination complex, quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate the expression of pro-inflammatory factor interleukin-1β (IL-1β), anti-inflammatory factors interleukin-4 (IL-4), interleukin-10 (IL-10), and macrophage M1 inflammatory phenotype marker factor CD86.

[0080] according to Figure 6 It can be seen that C is a macrophage with a normal phenotype, LPS is a macrophage polarized to an inflammatory phenotype, CuCl2 is the raw material CuCl2·2H2O for preparing the copper coordination complex, ɑ-KG is the raw material α-ketoglutaric acid for preparing the copper coordination complex, and the copper coordination is the copper coordination complex. The expression of IL-1β in the copper coordination complex group was significantly lower than that in other groups, indicating that the copper coordination complex can inhibit the expression of the proinflammatory factor IL-1β. The expression of IL-4 and IL-10 in the copper coordination complex group was significantly higher than that in other groups, indicating that the copper coordination complex can promote the expression of anti-inflammatory factors. The expression of CD86 in the copper coordination complex group was significantly lower than that in other groups, indicating that the copper coordination complex can promote the reduction of M1 inflammatory phenotype macrophages. In summary, the qRT-PCR results show that the copper coordination complex has a significant effect on regulating the phenotype of macrophages and cytokine expression, indicating that the copper coordination complex has certain anti-inflammatory and immunomodulatory abilities.

[0081] In order to verify the antibacterial property of the prepared A1-copper coordination complex, different groups of CuCl2·2H2O, 4-methylthiosemicarbazide, α-ketoglutaric acid substituted thiosemicarbazide ligand and copper coordination complex were co-cultured with Escherichia coli and Staphylococcus aureus for 12 hours, and the absorbance at OD=600nm was tested to calculate the antibacterial rate of each group of materials. The test results are shown in Figure 7 shown.

[0082] according to Figure 7 It can be seen that the CuCl2 group is the raw material CuCl2·2H2O for preparing the copper coordination complex, the thiourea group is the raw material 4-methylthiosemicarbazide for preparing the copper coordination complex, the precursor group is the ligand formed by replacing thiosemicarbazide with α-ketoglutaric acid, and the copper complex is the copper coordination complex. The antibacterial rate of the copper coordination complex group against Escherichia coli and Staphylococcus aureus reached more than 98%, showing significant antibacterial properties. In contrast, although the CuCl2·2H2O group also showed a certain antibacterial effect, the antibacterial rate was much lower than that of the copper coordination complex group. In addition, the antibacterial effect of the precursor group was higher than that of the thiourea group. The high antibacterial rate of the complex group indicates that the copper ions in the copper coordination complex successfully combined with the ligand to form a structure with high antibacterial activity. This coordination complex structure may achieve a bactericidal effect by destroying the cell wall or cell membrane of bacteria or interfering with the metabolic process of bacteria.

[0083] Therefore, the metal complex provided by the present application includes: a metal ion and a ligand complexed with the metal ion; the ligand is prepared by reacting 4-methylthiosemicarbazide with α-ketoglutaric acid. By utilizing the excellent coordination performance and chemical activity of 4-methylthiosemicarbazide, the properties of α-ketoglutaric acid can be optimized, an excellent coordination environment can be provided, the complexation efficiency can be improved, a stable and high-performance ligand can be formed, and the metal ion can be coordinated through a coordination bond. The thiosemicarbazide group can cooperate with the metal ion as a neutral molecule or be deprotonated as an anionic ligand afterwards, and a variety of coordination modes can be provided, which can optimize the rearrangement of the spatial structure, have excellent structural stability, excellent anti-inflammatory and antibacterial effects, and have broad application prospects in the preparation of biomedical materials.

[0084] The various embodiments in this specification are described in a progressive manner, and the same or similar parts between the various embodiments can be referenced to each other, and each embodiment focuses on the differences from other embodiments.

[0085] The above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit the present application. Although the present application has been described in detail with reference to the aforementioned embodiments, a person of ordinary skill in the art should understand that the technical solutions recorded in the aforementioned embodiments may still be modified, or some or all of the technical features therein may be replaced by equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the present application.

Claims

1. A metal complex, characterized in that include: Metal ions and ligands complexed with the metal ions; The ligand is prepared by reacting 4-methylthiosemicarbazide with α-ketoglutaric acid.

2. The metal complex according to claim 1, characterized in that The metal ion is Cu 2+ Mg 2+ , Mn 2+ 、Ni 2 + 、Co 2+ 、Zn 2+ , Fe 2+ Any one of .

3. The metal complex according to claim 1, characterized in that The particle size of the metal complex is less than 1000 nm.

4. A method for preparing the metal complex according to any one of claims 1 to 3, characterized in that: The preparation method comprises: Dissolving 4-methylthiosemicarbazide and α-ketoglutaric acid in an organic solvent for reaction to obtain a ligand solution; The ligand solution is reacted with the metal salt, the pH is adjusted, and the bottom precipitate is separated and collected to obtain the metal complex.

5. The method for preparing the metal complex according to claim 4, characterized in that: The molar ratio of the 4-methylthiosemicarbazide to α-ketoglutaric acid is 1-2:

1.

6. The method for preparing the metal complex according to claim 4, characterized in that: The organic solvent is one or more of N,N-dimethylformamide, methanol, chlorobenzene and dimethyl sulfoxide.

7. The method for preparing the metal complex according to claim 4, characterized in that: The metal salt is one of acetate, halide, sulfate, nitrate and sulfonate.

8. The method for preparing the metal complex according to claim 4, characterized in that: The pH value is adjusted to be in the range of 6.0-8.

0.

9. The method for preparing the metal complex according to claim 4, characterized in that: The molar ratio of the ligand solution to the metal salt is 1-2:

1.

10. Use of the metal complex according to any one of claims 1 to 3 or the metal complex prepared by the preparation method according to any one of claims 4 to 9 in the preparation of biomedical materials.

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