CN103936771B - Adamantyl pyridinecarboxylic amine complex, intermediate and its preparation method and application - Google Patents

Abstract

The invention discloses an adamantyl pyridine carboxamide complex, an intermediate and its preparation method and application. The structure of the complex is shown in formula (I), where n is 1-3, M It is a divalent metal cation, and N3 is selected from perchlorate ion, hexafluorophosphate ion or tetrafluoroborate ion; the complex provided by the invention or the complex prepared according to the method provided by the invention has excellent catalytic superoxide anion disproportionation activity.

Description

Adamantyl pyridine carboxamide complexes, intermediates, preparation methods and applications thereof

technical field

The invention relates to an adamantyl pyridine carboxamide complex, an intermediate for preparing the adamantyl pyridine carboxamide complex, a preparation method and application of the adamantyl pyridine carboxamide complex and the intermediate.

Background technique

The medical community generally believes that free radicals are the main cause of human aging and neurodegenerative diseases. Modern medicine has confirmed that excess superoxide ion free radicals (O ₂ · ^- ) produced in the process of biological oxidation can cause human aging and diseases such as cancer, cardiovascular and cerebrovascular diseases, and amyotrophic lateral sclerosis. Superoxide dismutase (SOD) is a specific enzyme for removing O ₂ · ^- in the body, known as "human body scavenger", and is used in clinical medicine to treat various diseases such as Alzheimer's disease and tumors. Widely used in skin care and health care products. However, the natural SOD has the disadvantages of difficult extraction, high cost, short half-life, easy to be hydrolyzed by protease, difficult to penetrate the cell membrane and heterogeneous antigenicity, which limits its clinical application.

Therefore, it is an effective way to prevent and treat diseases caused by SOD inactivation by carrying out SOD chemical simulation research and developing exogenous chemical drugs to scavenge O ₂ · ^- .

Contents of the invention

The purpose of the present invention is that the purpose of the present invention is to overcome the shortcomings of natural superoxide dismutase natural SOD in the prior art, such as difficult extraction, high cost, easy to be hydrolyzed by protease, difficult to penetrate cell membrane and heterogeneous antigenicity, and provide A SOD mimetic enzyme with adamantane and pyridinecarboxamide structures that is easy to prepare, low in cost, efficient and easy to permeate the cell membrane, that is, the adamantylpyridinecarboxamide complex, and at the same time provides the adamantylpyridinecarboxamide complex The preparation method and application of the compound also provide an intermediate for preparing the adamantyl pyridinecarboxamide complex and a preparation method thereof.

In order to achieve the above object, the present invention provides an adamantyl pyridine carboxamide complex, wherein the structure of the complex is shown in formula (I),

Formula (I), n is 1-3, M is a divalent metal cation, and N3 is selected from perchlorate ion, hexafluorophosphate ion or tetrafluoroborate ion.

Preferably, in formula (I), n is 1-3, M is Cu ²⁺ or Zn ²⁺ , and N3 is perchlorate ion; more preferably, the complex with the structure shown in formula (I) is formula (II ) complexes with the structure shown.

The present invention also provides an intermediate for preparing the adamantyl pyridinecarboxamide complex with the structure shown in formula (I), wherein the structure of the intermediate is shown in formula (L1),

In formula (L1), n is 1-3;

Preferably, the compound with the structure represented by formula (L1) is the compound with the structure represented by formula (L2).

The present invention also provides a method for preparing an intermediate of the adamantyl pyridine carboxamide complex with the structure shown in formula (L1), wherein, in the presence of carbonate, 1-adamantane The acid chloride is contacted with the compound shown in the formula (C1);

In formula (C1), n is 1-3, preferably, n is 1;

More preferably, the carbonate is potassium carbonate or sodium carbonate, and the organic solvent is acetonitrile or toluene;

Further preferably, the carbonate is potassium carbonate, and the organic solvent is toluene.

[ M(N3) ₂ ]·6H ₂ O for complexation reaction;

In formula (L1), n is 1-3, preferably, n is 1;

In the above formula, M is a divalent metal cation, and N3 is selected from perchlorate ion, hexafluorophosphate ion or tetrafluoroborate ion;

Preferably, M is Cu ²⁺ or Zn ²⁺ , and N3 is perchlorate ion;

More preferably, the [M(N3) ₂ ]·6H ₂ O is Cu(ClO ₄ ) ₂ ·6H ₂ O.

The present invention also provides the application of the above-mentioned adamantyl pyridine carboxamide complex or the adamantyl pyridine carboxamide complex prepared by the above-mentioned method in eliminating superoxide anion free radicals.

Protein engineering studies have shown that the SOD active center of bovine erythrocytes has a structure formed by the coordination of divalent copper or zinc cations with nitrogen atoms, thus inferring the adamantyl pyridinecarboxamide complex with the structure shown in formula (II) provided by the present invention It may have the activity of eliminating superoxide anion free radicals, and the adamantyl pyridine carboxamide complex with the structure shown in formula (II) has adamantane and pyridine structures. Adamantane is a cage compound containing three spirocyclic saturated alkanes with 10 carbon atoms and 16 hydrogen atoms. It has the characteristics of high structural symmetry, good stability, strong lipophilicity and biocompatibility. Amantadine and its derivatives can inhibit influenza A virus from penetrating into the epithelial cells of the respiratory tract, peel off the outer membrane of the virus and release the nucleic acid of the virus into the host cell; it can also promote the release of dopamine from the dopaminergic nerve endings in the striatum (DA ), strengthen the role of DA and catecholamine in the central nervous system, and increase the DA content of neurons. Amantadine and its derivatives have been used as clinical drugs, widely used in the treatment and prevention of influenza A virus infectious diseases and Parkinson's disease and other diseases. Pyridine derivatives, which are easy to assemble with metal ions, have various structures and unique physical and chemical properties. It can be inferred that the complex provided by the present invention may have excellent stability, strong lipophilic transmembrane property, and biocompatibility, so that the complex may have anti-malarial, anti-tumor, bactericidal, anti-inflammatory, high blood pressure and other drugs. effect; the pyridine structure also makes the method for preparing the adamantyl pyridine carboxamide complex with the structure shown in formula (II) relatively simple, and the raw materials are easy to obtain.

Other features and advantages of the present invention will be described in detail in the following detailed description.

Description of drawings

The accompanying drawings are used to provide a further understanding of the present invention, and constitute a part of the description, together with the following specific embodiments, are used to explain the present invention, but do not constitute a limitation to the present invention. In the attached picture:

Figure 1 is a schematic diagram of the determination of the activity of the complex to catalyze the disproportionation of superoxide anion O ₂ · ^- by the riboflavin-methionine light method;

Figure 2 is a single crystal diffraction pattern of the adamantyl pyridinecarboxamide complex with the structure shown in formula (II);

Fig. 3 is the test result diagram of the activity of the adamantyl pyridinecarboxamide complex and BeSOD catalyzing the disproportionation of superoxide anion with the structure shown in formula (II);

Fig. 4 is the test result diagram of the electrochemical properties of the adamantyl pyridinecarboxamide complex of the structure shown in formula (II); and

Fig. 5 is a mechanism diagram of the disproportionation of superoxide anion catalyzed by the adamantyl pyridinecarboxamide complex with the structure represented by formula (II).

detailed description

Specific embodiments of the present invention will be described in detail below. It should be understood that the specific embodiments described here are only used to illustrate and explain the present invention, and are not intended to limit the present invention.

The present invention provides an adamantyl pyridine carboxamide complex, wherein the structure of the complex is shown in formula (I),

Formula (I), n is 1-3, M is a divalent metal cation, and N3 is selected from perchlorate ion, hexafluorophosphate ion or tetrafluoroborate ion;

Preferably, in formula (I), n is 1-3, M is Cu ²⁺ or Zn ²⁺ , and N3 is perchlorate ion;

More preferably, the complex with the structure shown in formula (I) is the complex with the structure shown in formula (II).

The present invention also provides an intermediate for preparing the adamantyl pyridine carboxamide complex with the structure shown in formula (I), wherein the structure of the intermediate is shown in formula (L1),

In the formula (L1), n is 1-3, preferably, the compound with the structure shown in the formula (L1) is the compound with the structure shown in the formula (L2).

The present invention also provides a method for preparing an intermediate of the adamantyl pyridine carboxamide complex with the structure shown in formula (L1), wherein, in the presence of carbonate, 1-adamantane The acid chloride is contacted with the compound shown in the formula (C1);

In formula (C1), n is 1-3, preferably, n is 1.

According to the present invention, the organic solvent only needs to be an organic solvent capable of dissolving the reaction raw materials and not reacting with the reaction solvent. As such a reaction solvent, one or more of acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide and toluene may be mentioned. Preferred is toluene. More preferably, the above-mentioned organic solvent is an anhydrous solvent (ie, the water content is less than 50 ppm).

In the present invention, 1-adamantanyl chloride can be a commercially available product, or it can be synthesized and used immediately. In order to ensure the yield of the contact reaction, it is preferred that 1-adamantanyl chloride is synthesized and used immediately.

According to the present invention, the carbonate is preferably a carbonate that can be dissolved in the reaction system (that is, can be dissolved in the above-mentioned organic solvent). Examples of such carbonates include one or more of sodium carbonate, potassium carbonate, and cesium carbonate. It is preferably sodium carbonate or potassium carbonate, more preferably potassium carbonate.

According to the present invention, in order to control the contact reaction in a suitable pH range to ensure the yield of the contact reaction, relative to 1 mmol of 1-adamantanyl chloride, the amount of the carbonate used is 1-4 mmol.

According to the invention, the amount of compound C1 and the amount of organic solvent used can be varied within wide ranges. However, in order to improve the yield, it is preferred that the amount of the compound C1 used is 1-3 mmol, and the amount of the organic solvent used is 2-20 ml relative to 1 mmol of 1-adamantanamine hydrochloride.

In the preparation method of the above intermediate, in order to increase the yield of the contact reaction, preferably the contact reaction is carried out below 0°C, and the reaction temperature of the contact reaction is -10-0°C, preferably -3-0°C;

According to the present invention, in order to make the contact reaction fully proceed, the reaction time of the contact reaction is 3-20 h, preferably 10-15 h.

[ M(N3) ₂ ]·6H ₂ O for complexation reaction;

In formula (L1), n is 1-3, preferably, n is 1;

In the above formula, M is a divalent metal cation, and N3 is selected from perchlorate ion, hexafluorophosphate ion or tetrafluoroborate ion;

Preferably, M is Cu ²⁺ or Zn ²⁺ , and N3 is perchlorate ion;

More preferably, the [M(N3) ₂ ]·6H ₂ O is Cu(ClO ₄ ) ₂ ·6H ₂ O.

According to the present invention, the organic solvent only needs to be an organic solvent capable of dissolving the reaction raw materials and not reacting with the reaction solvent. Examples of such a reaction solvent include one or more of acetonitrile, N,N-dimethylformamide, C1-C3 alcohols, and dimethylsulfoxide. It is preferably a C1-C3 alcohol, more preferably ethanol. It is further preferred that the above-mentioned organic solvent is an anhydrous solvent (ie, the water content is less than 50 ppm).

According to the present invention, the amount of [M(N3) ₂ ]·6H ₂ O used can vary within a wide range. But in order to improve the yield, relative to 1 mmol of the intermediate, the amount of [M(N3) ₂ ]·6H ₂ O is 0.5-2 mmol; in order to further improve the yield, more preferably, relative to 1 mmol of the intermediate body, the amount of [M(N3) ₂ ]·6H ₂ O is 0.5-1 mmol.

According to the invention, the amount of organic solvent used can vary within wide ranges. But in order to improve yield, preferably, relative to 1mmol described intermediate, the consumption of described organic solvent is 20-400ml; In order to further improve yield, relative to 1mmol described intermediate, the consumption of described organic solvent is 40- 250ml.

According to the present invention, in order to increase the reaction speed of the complexation reaction, preferably, the complexation reaction is carried out under heating, preferably the reaction temperature of the complexation reaction is 40-100°C, more preferably 40-80°C.

According to the present invention, in order to enable the complexation reaction to proceed sufficiently, the reaction time of the complexation reaction is preferably 1-6 hours, more preferably 2-3 hours.

The present invention also provides the application of the above-mentioned adamantyl pyridine carboxamide complex or the adamantyl pyridine carboxamide complex prepared by the above-mentioned method in eliminating superoxide anion free radicals.

The present invention will be described in detail through examples below, but the present invention is not limited to the following examples.

Drugs and solvents used in the following examples and test cases: riboflavin and methionine were purchased from Aladdin Reagents (China) Co., Ltd.; nitro blue tetrazolium (NBT) was purchased from Sarn Chemical Technology (Shanghai) Co., Ltd.; other reagents purchased from Sinopharm Chemical Reagent Co., Ltd.

The test methods in the following examples and test examples are: the elemental analysis is carried out by using the German elemental analyzer VarioELIIICHNanalyzer, the infrared spectrum test is carried out by using the Shimadzu Fourier transform infrared spectrometer IRPrestige-21, and the single crystal diffraction test is carried out by the German BrukerAXS single crystal diffraction The instrument Smol/LARTAPEX II was used for the visible-ultraviolet test by the Shimadzu ultraviolet-visible spectrophotometer UV-2450 photometer, the electrochemical property test was carried out by the CHI-440a electrochemical workstation, and the nuclear magnetic test was carried out by the German Bruker AV300 nuclear magnetic resonance instrument.

Preparation Example 1

Preparation of 1-adamantanyl chloride:

In a 250mL round-bottomed flask, add 10.0mmol of 1-adamantanecarboxylic acid solid and 60mL of anhydrous toluene solvent in sequence, and slowly add 20mL of thionyl chloride dropwise after magnetic stirring to dissolve, reflux at 80°C for 8 hours, and cool to 20°C , the solvent was removed by rotary evaporation, and 10 mL of anhydrous toluene was added three times, and the solvent and excess thionyl chloride were removed by rotary evaporation to obtain a light yellow crystalline powder.

Example 1-1

The preparation of the intermediate of structure shown in formula (L2):

In a 100mL round-bottomed flask, at 0°C, add 5.0mmol of 1-adamantanyl chloride and 25mL of anhydrous toluene in turn. After magnetically stirring to dissolve, add 10mmol of anhydrous potassium carbonate, and slowly add 2-methylaminopyridine 6.3 mmol, react under ice-bath conditions for 12 hours, filter, and obtain 1.154 g of light yellow crude product after removing the solvent by rotary evaporation under reduced pressure. The crude product was recrystallized from a mixed solvent of ethyl acetate and ether to obtain a white powder. Recrystallized in a mixed solvent of ethyl acetate and petroleum ether (v/v=1:3) to obtain 1.050 g of white powder with a yield of 76%. Its detection data are as follows.

The white powder was subjected to elemental analysis, and the result was C ₁₇ H ₂₂ N ₂ O: C, 75.36%; N, 10.18%; H, 8.47%; theoretically calculated values: C, 75.52%; N, 10.36%; H, 8.20% , indicating that the detected value is consistent with the theoretically calculated value; ¹ HNMR (CDCl ₃ , 300MHz): δ (ppm): 8.53 (m, 1H, NH), 7.65 (s, 1H, Py), 7.22-7.25 (m, 2H ,Py),6.98(s,1H,Py),4.52(d,2H,Py-CH ₂ ),2.05(d,3H,CH),1.91(d,6H,CH ₂ ),1.70(m,6H, CH ₂ ); IR (KBrdisc, cm ⁻¹ ): 3441, 2900, 2845, 1628, 1588, 1532, 1350, 747, 671.

Example 1-2

The preparation of the intermediate of structure shown in formula (L2):

According to the method of Example 1-1, the difference is that 2-methylaminopyridine is 10 mmol, and a white powder is obtained with a yield of 76%. Its detection data are as follows.

The white powder was subjected to elemental analysis, and the result was C ₁₇ H ₂₂ N ₂ O: C, 75.36%; N, 10.18%; H, 8.47%; theoretically calculated values: C, 75.52%; N, 10.36%; H, 8.20% , indicating that the detected value is consistent with the theoretically calculated value; ¹ HNMR (CDCl ₃ , 300MHz): δ (ppm): 8.53 (m, 1H, NH), 7.65 (s, 1H, Py), 7.22-7.25 (m, 2H ,Py),6.98(s,1H,Py),4.52(d,2H,Py-CH ₂ ),2.05(d,3H,CH),1.91(d,6H,CH ₂ ),1.70(m,6H, CH ₂ ); IR (KBrdisc, cm ⁻¹ ): 3441, 2900, 2845, 1628, 1588, 1532, 1350, 747, 671.

Example 1-3

The preparation of the intermediate of structure shown in formula (L2):

According to the method of Example 1-1, the difference is that 2-methylaminopyridine is 15 mmol, and a white powder is obtained with a yield of 76%. Its detection data are as follows.

The white powder was subjected to elemental analysis, and the result was C ₁₇ H ₂₂ N ₂ O: C, 75.36%; N, 10.18%; H, 8.47%; theoretically calculated values: C, 75.52%; N, 10.36%; H, 8.20% , indicating that the detected value is consistent with the theoretically calculated value; ¹ HNMR (CDCl ₃ , 300MHz): δ (ppm): 8.53 (m, 1H, NH), 7.65 (s, 1H, Py), 7.22-7.25 (m, 2H ,Py),6.98(s,1H,Py),4.52(d,2H,Py-CH ₂ ),2.05(d,3H,CH),1.91(d,6H,CH ₂ ),1.70(m,6H, CH ₂ ); IR (KBrdisc, cm ⁻¹ ): 3441, 2900, 2845, 1628, 1588, 1532, 1350, 747, 671.

Example 1-4

The preparation of the intermediate of structure shown in formula (L2):

According to the method of Example 1-1, the difference is that the potassium carbonate is 5 mmol, and a white powder is obtained with a yield of 75%. Its detection data are as follows.

The white powder was subjected to elemental analysis, and the result was C ₁₇ H ₂₂ N ₂ O: C, 75.36%; N, 10.18%; H, 8.47%; theoretically calculated values: C, 75.52%; N, 10.36%; H, 8.20% , indicating that the detected value is consistent with the theoretically calculated value; ¹ HNMR (CDCl ₃ , 300MHz): δ (ppm): 8.53 (m, 1H, NH), 7.65 (s, 1H, Py), 7.22-7.25 (m, 2H ,Py),6.98(s,1H,Py),4.52(d,2H,Py-CH ₂ ),2.05(d,3H,CH),1.91(d,6H,CH ₂ ),1.70(m,6H, CH ₂ ); IR (KBrdisc, cm ⁻¹ ): 3441, 2900, 2845, 1628, 1588, 1532, 1350, 747, 671.

Example 1-5

The preparation of the intermediate of structure shown in formula (L2):

Carry out according to the method of embodiment 1-1, difference is that potassium carbonate is 18mmol, obtains white powder, and yield is 74%. Its detection data are as follows.

The white powder was subjected to elemental analysis, and the result was C ₁₇ H ₂₂ N ₂ O: C, 75.36%; N, 10.18%; H, 8.47%; theoretically calculated values: C, 75.52%; N, 10.36%; H, 8.20% , indicating that the detected value is consistent with the theoretically calculated value; ¹ HNMR (CDCl ₃ , 300MHz): δ (ppm): 8.53 (m, 1H, NH), 7.65 (s, 1H, Py), 7.22-7.25 (m, 2H ,Py),6.98(s,1H,Py),4.52(d,2H,Py-CH ₂ ),2.05(d,3H,CH),1.91(d,6H,CH ₂ ),1.70(m,6H, CH ₂ ); IR (KBrdisc, cm ⁻¹ ): 3441, 2900, 2845, 1628, 1588, 1532, 1350, 747, 671.

Example 2

Preparation of complex shown in formula (II):

In a 100ml round bottom flask, add 0.037gCu(ClO ₄ ) ₂ ·6H ₂ O (0.1mmol), (2-picoline)-1-adamantanamide 0.054g (0.2mmol) and 15mL methanol successively, 20 After dissolving with magnetic stirring at ℃, reflux reaction at 50℃ for 2 hours to obtain a dark green clear solution, which was cooled to 20℃, filtered and the filtrate was naturally volatilized, and dark green blocky crystals were obtained after one week with a yield of 46%. Its detection data are as follows.

The above dark green bulk crystals were subjected to elemental analysis, and the result was C ₃₄ H ₄₆ N ₄ O ₁₁ Cl ₂ Cu: C, 49.56%; N, 6.67%; H, 5.89%; theoretically calculated value: C, 49.73%; N , 6.82%; H, 5.65%, indicating that the detected value is consistent with the theoretically calculated value; IR (KBrdisc, cm ^-1 ): 2900, 2851, 1588, 1539, 1353, 1100, 780, 617.

The single crystal diffraction of complex II is shown in Figure 2. From Figure 2, it can be seen that complex II is a mononuclear copper complex, divalent copper ions and two N, one O in H ₂ O and two The O on the carbonyl at the 1 position of adamantane is coordinated to form a complex with 5 coordination bonds, and the two adamantane structures are axisymmetrically distributed about the central axis of complex II.

test case 1

The principle of riboflavin-methionine light method for the determination of the complex’s catalytic superoxide anion O ₂ ^{-disproportionation} activity is shown in Figure _1. In the absence of SOD or SOD simulants in the solution, riboflavin and The superoxide anion free radical O ₂ · ^- produced by methionine, mainly O ₂ · ^- can react with nitro blue tetrazolium NBT to form a blue compound (can be detected at λ _max =560nm in the UV-visible spectrophotometer detection). When there is SOD or simulants in the solution, O ₂ · ^- will be partially catalyzed to generate H ₂ O ₂ and O ₂ , and the amount of blue formazan compound produced by reacting with NBT will be reduced, so it can pass λ=560nm The change of absorbance with time was used to measure the activity of SOD and simulants in catalyzing the disproportionation of O ₂ · ^- . The specific experimental method is as follows:

Prepare a 0.05mol/L phosphate buffer solution with a pH of 7.8 with double distilled water, and use the phosphate buffer solution as a solvent to prepare 8.25×10 ^-5 mol/L riboflavin, 0.25mol/L methionine, and 1.15×10 ^-3 mol/L of NBT. In the determination of the activity of various concentrations of SOD or simulants, take 1 mL each of the above riboflavin, methionine and NBT solutions in turn, mix with different concentrations of SOD or simulants, dilute to 25 mL with phosphate buffer, and then mix the solution Put it in a constant temperature tank at 25±0.1°C for 10 minutes in the dark and keep it in a constant temperature box for light. Take out 3mL of the solution every 0.5 minutes within 3.5 minutes and measure the absorbance A of the solution at a wavelength of 560nm with a UV-2450 photometer (using phosphate buffer solution as a blank) with a Shimadzu ultraviolet-visible spectrophotometer. Use the riboflavin-methionine method to measure the change of absorbance with time at different concentrations of the complex, and fit a straight line to the data of absorbance at a certain concentration with time. The slope of the obtained line is the change value of absorbance per unit time. ΔA/Δt. When the concentration of SOD or simulant in the solution is zero, the obtained ΔA/Δt is (ΔA/Δt)0, when the concentration of SOD or simulant in the solution is mol/L, the measured ΔA/Δt is (ΔA/Δt ) m, the percentage of inhibition rate of SOD or simulant at this concentration is obtained from the following formula.

Take the complex concentration as the abscissa and the inhibition rate as the ordinate, and calculate the concentration of the complex with an inhibition rate of 50%, that is, the SOD activity parameter IC ₅₀ of the complex II, which is the concentration of one active unit. The smaller the _IC50 value of the mimic, the higher the activity.

The activities of natural bovine erythrocyte superoxide dismutase (BeSOD) and complex II in catalyzing the disproportionation of superoxide anion radicals were determined according to the method described above. As shown in Figure 3, the concentration of the complex when the inhibition rate is 50%, that is, the IC ₅₀ value, can be obtained from the variation curve of the inhibition rate with the concentration of different complexes. The activity of the complex was judged by comparing the IC ₅₀ value, and the smaller the IC ₅₀ value, the higher the activity of the complex.

The IC ₅₀ of BeSOD is 0.04μmol/L, and the IC ₅₀ of complex II is 0.12μmol/L. As shown in Figure 5, the two adamantane groups in the structure of the complex II are located on the same side to build a hydrophobic channel for synergistic catalysis. At the same time, the protonation of the amide nitrogen atom is positively charged, and the superoxide anion radical can be recognized during the catalytic process. Therefore, the complex II has an excellent IC ₅₀ , therefore, the complex II has a higher activity of catalyzing the disproportionation of superoxide anion radicals.

test case 2

The oxidation-reduction potential of complex II was determined by cyclic voltammetry on a CHI-440a electrochemical workstation, using a three-electrode system, a platinum wire electrode as an auxiliary electrode, a glassy carbon electrode as a working electrode, and a silver/silver chloride electrode as a reference. than the electrode. Complex II uses N,N'-dimethylformamide as a solvent, and tetrabutylammonium perchlorate with a concentration of 0.1mol/L as a supporting electrolyte. All the tests were carried out at room temperature under the protection of nitrogen, and the scanning speed was 100 mVS ^-1 . The electrochemical test results of complex II are shown in Figure 4: Epc is 0.240V and Epa is 0.390V, and its half-wave potential is 0.315V. The half-wave potential of complex II is in the potential range of -0.36V-0.69V (vsAg/AgCl) for catalyzing the disproportionation of superoxide anions. Therefore, it can be known from the chemical thermodynamics that copper complex II has the activity of catalyzing the disproportionation of superoxide anions.

The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solutions of the present invention. These simple modifications All belong to the protection scope of the present invention. In addition, it should be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable way if there is no contradiction. The combination method will not be described separately.

In addition, various combinations of different embodiments of the present invention can also be combined arbitrarily, as long as they do not violate the idea of the present invention, they should also be regarded as the disclosed content of the present invention.

Claims (13)

1. an adamantyl pyridinecarboxylic amine complex, it is characterised in that, the structure of described title complex such as formula shown in (I),

Formula (I), n is 1, M is Cu²⁺, N3 is selected from perchlorate.

2. the preparation method of the intermediate of the adamantyl pyridinecarboxylic amine complex of structure shown in a formula (L1), it is characterized in that, under the existence of carbonate, compound by structure shown in 1-diamantane acyl chlorides and formula (C1) carries out contact reacts in organic solvent;

In upper formula, n is 1; Described carbonate is salt of wormwood, and described organic solvent is toluene.

3. preparation method according to claim 2, wherein, relative to 1-diamantane acyl chlorides 1mmol, the consumption of described Compound C 1 is 1-3mmol, and the consumption of described organic solvent is 2-20ml, and the consumption of described carbonate is 1-4mmol.

4. preparation method according to Claims 2 or 3, wherein, the temperature of reaction of described contact reacts is-10-0 DEG C; The reaction times of described contact reacts is 3-20h.

5. preparation method according to claim 4, wherein, the temperature of reaction of described contact reacts is-3-0 DEG C; The reaction times of described contact reacts is 10-15h.

6. the preparation method of the adamantyl pyridinecarboxylic amine complex of structure shown in a formula as claimed in claim 1 (I), it is characterized in that, in presence of organic solvent, by the intermediate of structure shown in formula (L1) and [M (N3)₂]��6H₂O carries out complex reaction;

In formula (L1), n is 1, and in above-mentioned formula, M is Cu²⁺, N3 is selected from perchlorate; Described organic solvent is methyl alcohol.

7. preparation method according to claim 6, wherein, relative to intermediate described in 1mmol, described [M (N3)₂]��6H₂The consumption of O is 0.5-2mmol, and the consumption that described organic solvent is is 20-400ml.

8. preparation method according to claim 7, wherein, relative to intermediate described in 1mmol, described [M (N3)₂]��6H₂The consumption of O is 0.5-1mmol, and the consumption of described organic solvent is 40-250ml.

9., according to preparation method described in any one in claim 6-8, wherein, the temperature of reaction of described complex reaction is 40-100 DEG C.

10. preparation method according to claim 9, wherein, the temperature of reaction of described complex reaction is 40-80 DEG C.

11. according to preparation method described in any one in claim 6-8, and wherein, the reaction times of described complex reaction is 1-6h.

12. preparation methods according to claim 11, wherein, the reaction times of described complex reaction is 2-3h.

The application of 13. adamantyl pyridinecarboxylic amine complexes according to claim 1 in the preparation of the medicine for eliminating Superoxide radical anion.