A metal complex and its preparation method and application

Abstract

The present invention belongs to the technical field of organic complex synthesis, and specifically relates to a metal complex and its preparation method and application. The general formula of the metal complex is L-M, wherein L is a ligand, M is a metal salt, and the ligand is benzylquinine-3-ketoxime or benzylquinine-3-ketone-O-methyloxime ether. The benzylquinine-3-ketoxime is prepared from an ethanol solution containing ketone, hydroxylamine hydrochloride and anhydrous potassium carbonate; the benzylquinine-3-ketone-O-methyloxime ether is prepared from an ethanol solution containing ketone, methoxyamine hydrochloride and anhydrous potassium carbonate. The preparation method of the metal complex is to add an aqueous solution containing a metal salt dropwise to a methanol solution containing a ligand, carry out a coordination reaction, and filter to obtain a target product. The preparation method has the advantages of simple process, mild conditions, low cost, and easy industrialization. The metal complex provided by the present invention can be used to prepare an antibacterial agent, which has the advantages of high efficiency, low toxicity and environmental protection.

Description

Technical Field

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

[0002] The information disclosed in this background section is intended to enhance understanding of the overall background of the invention and should not necessarily be regarded as an admission or any form of suggestion that this information constitutes the prior art already known to those skilled in the art.

[0003] In recent years, with the development of crop cultivation and disease control technologies, a series of control agents have emerged, such as chlorothiazol, zinc thiazole, zhongshengmycin, and agricultural streptomycin sulfate. However, the control effect on plant diseases is not ideal. In 2018, Ren's group synthesized three zinc (II) complexes, [ZnL1 4(NO3)2]2H2O2EtOH (complex 1), [ZnL2 4(NO3)2] (complex 2), and [ZnL3 4(DMF)2](NO3)2 (complex 3), to screen for effective fungicides (L1 = paclobutrazol, L2 = diniconazole, and L3 = hexaconazole). (Ren GY, Li J, Zhou JH, et al. Enhanced antifungal activities of four Zn(II) complexes based on uniconazole[J]. Appl Organometal Chem, 2018, 32: 1-12.); In 2019, the Li group used two 1,2,4-triazole fungicides, paclobutrazol (L-1) and uniconazole (L-2), as raw materials to synthesize two Cu(II) complexes. (Li J, Ren GY, Zhang A, et al. Two Cu(II) complexes of 1,2,4-triazole fungicides with enhanced antifungal activities[J]. Polyhedron, 2019, 157: 163-169).

[0004] The preparation process of the above metal complexes is complicated and the cost is high. The biological activity and antibacterial properties need to be improved. In addition, there are few types of metal complexes currently available. Therefore, the development of a new metal complex has important application prospects. Summary of the Invention

[0005] In view of the problems existing in the prior art, the first object of the present invention is to provide a metal complex having significant antibacterial ability.

[0006] The second object of the present invention is to provide a method for preparing the above metal complex, which is simple and the raw materials are easily available.

[0007] The third object of the present invention is to provide the use of the metal complex, which can be used in the preparation of antibacterial agents.

[0008] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0009] A metal complex having the general formula LM;

[0010] Where L is a ligand and M is a metal salt;

[0011] The metal salt is a copper salt, a zinc salt, a manganese salt, an iron salt or a nickel salt; the copper salt is copper acetate, copper sulfate or copper trifluoromethanesulfonate, etc.; the zinc salt is zinc chloride, etc.; the manganese salt is manganese sulfate, etc.; the iron salt is ferrous sulfate heptahydrate, etc.; the nickel salt is nickel chloride, etc.

[0012] The ligand is benzylquinine-3-one oxime or benzylquinine-3-one-O-methyloxime ether; the structural formula of the benzylquinine-3-one oxime is shown in formula (I); the structural formula of the benzylquinine-3-one-O-methyloxime ether is shown in formula (II):

[0013]

[0014]

[0015] The preparation method of the metal complex comprises the following steps: adding a metal salt solution dropwise to a methanol solution containing a ligand to carry out a coordination reaction, and filtering to obtain the metal complex. Preferably, the addition time is 1 hour.

[0016] The ligand is benzylquinine-3-one oxime or benzylquinine-3-one-O-methyloxime ether; the metal salt is a copper salt, a zinc salt, a manganese salt, an iron salt or a nickel salt; the copper salt is copper acetate, copper sulfate or copper trifluoromethanesulfonate, etc.; the zinc salt is zinc chloride, etc.; the manganese salt is manganese sulfate, etc.; the iron salt is ferrous sulfate heptahydrate, etc.; the nickel salt is nickel chloride, etc.

[0017] Furthermore, the benzylquinine-3-one oxime is prepared by heating, cooling, filtering, desolventizing and drying an ethanol solution containing ketone, hydroxylamine hydrochloride and anhydrous potassium carbonate. The reaction process is shown in the following formula:

[0018]

[0019] The molar ratio of the ketone, hydroxylamine hydrochloride and anhydrous potassium carbonate is 1:2:2; and the heating conditions are a temperature of 50° C. and a time of 5 hours.

[0020] Furthermore, the benzylquinine-3-one-O-methyloxime ether is prepared by heating, cooling, filtering, desolventizing and drying an ethanol solution containing ketone, methoxyamine hydrochloride and anhydrous potassium carbonate. The reaction process is shown in the following formula:

[0021]

[0022] The molar ratio of the ketone, methoxyamine hydrochloride and anhydrous potassium carbonate is 1:2:2; and the heating conditions are a temperature of 50° C. and a time of 5 hours.

[0023] Furthermore, the molar ratio of the ligand to the metal salt is 1:2.

[0024] Furthermore, the molar volume ratio of the ligand to methanol in the methanol solution containing the ligand is 1 mmoL:1 mL; and the mass ratio of the metal salt to water in the aqueous solution containing the metal salt is 2 mmoL:(0.416-4) mL.

[0025] Furthermore, the coordination reaction temperature is 50-60° C. and the time is 3 hours.

[0026] The application of the metal complex is in the preparation of an antibacterial agent.

[0027] Furthermore, the antibacterial agent can be used to inhibit or kill at least one of apple rot pathogen, cucumber wilt pathogen, wheat take-all pathogen, peanut root rot pathogen, tomato wilt pathogen and peanut white rot pathogen.

[0028] Beneficial effects:

[0029] The metal complex described in the present invention uses a ligand of benzylquinine-3-one oxime or benzylquinine-3-one-O-methyloxime ether, which forms a complex with a metal salt and can greatly enhance the bactericidal ability of the metal complex. The preparation methods of benzylquinine-3-one oxime and benzylquinine-3-one-O-methyloxime ether are simple and easy to obtain. The metal complex provided by the present invention has significant antibacterial ability and can be used to inhibit or kill apple rot pathogen, cucumber wilt pathogen, wheat take-all pathogen, peanut root rot pathogen, tomato wilt pathogen, and peanut white rot pathogen. Moreover, the preparation process of the metal complex has readily available raw materials, high yield, low cost, high antibacterial activity, and extremely high application development value. DETAILED DESCRIPTION

[0030] To make the purpose, technical solutions and advantages of this application more clear, the embodiments of the present invention will be described in detail below. It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of this application can be combined with each other in any way.

[0031] Example 1 Synthesis of Benzylquinine-3-Ketoximine

[0032] A 100 mL three-necked flask was added with ketone (1 g, 3.432 mmol), hydroxylamine hydrochloride (0.48 g, 6.864 mmol), and then anhydrous potassium carbonate (0.95 g, 6.864 mmol). 40 mL of ethanol was added to dissolve the mixture, and the mixture was stirred and dissolved at room temperature. The temperature was slowly raised to 50 ° C for reaction. The reaction was continued for 2 h. The raw material spot was still present when monitored by TLC. The temperature was maintained and the reaction was continued for 3 h. The reaction was monitored by TLC. The raw material spot disappeared. The mixture was filtered, the filtrate was desolvated, and dried to obtain 0.54 g of a white solid. The filter cake was washed with plenty of water. There was an insoluble white solid. The filter cake was filtered and the plate was found to be the same spot as the solid in the solution. 0.48 g of the solid was dried. A total of 1.02 g of white solid was obtained with a yield of 95.2%. 1H NMR (500MHz, CDCl3) δ7.25(t,J=8.1Hz,4H),7.19(dd,J=9.3,5.8Hz,4H),7.08(p,J=6.5,5.9Hz,2H),4.19(ddd,J=34.7,10.3,4.5Hz,2H),3.45–3.34(m, 1H),2.91(ddd,J=14.5,9.8,4.7Hz,1H),2.86–2.65(m,2H),2.44(ddt,J=15 .2,10.2,5.4Hz,1H),1.80–1.67(m,2H),1.60(qd,J=13.4,10.7,6.7Hz,2H). HRMS: m / z cacd for C20H22N2O[M+H]+:307.18127; found:307.18159. The synthetic route is as follows:

[0033]

[0034] Example 2 Synthesis of Benzylquinine-3-one-O-methyloxime ether

[0035] To a 100mL three-necked flask, add ketone (1g, 3.432mmol) and methoxyamine hydrochloride (0.57g, 6.864mmol), then add anhydrous potassium carbonate (0.95g, 6.864mmol). Dissolve in 30mL of ethanol and stir at room temperature. Slowly raise the temperature to 50°C and react for 2h. TLC monitoring shows that the starting material spot is still present. Maintain the temperature and continue the reaction for 3h. TLC monitoring shows that the starting material spot disappears. Cool to room temperature, filter, remove the solvent, and dry to obtain 1.01g of a light-colored solid (yield 91.8%). NMR (500MHz, CDCl3) δ7.44–7.35(m,4H),7.31(d,J=7.5Hz,4H),7.19(tt,J=7.3,3.1Hz, 2H),4.39(d,J=9.6Hz,1H),4.21(d,J=9.6Hz,1H),3.55(s,3H),3.38(p,J=3.1Hz,1H),3. 04 (ddd, J = 14.3, 10.0, 4.6 Hz, 1H), 2.95 (dddd, J = 13.4, 9.5, 6.2, 2.5 Hz, 1H), 2.81 (dddd, J = 14.6, 10.5, 4.5, 2.7 Hz, 1H), 2.54 (ddd, J = 14.4, 10.3, 6.3 Hz, 1H), 1.82–1.64 (m, 4H). The synthetic route is as follows:

[0036]

[0037] Example 3

[0038] In a 100mL round-bottom flask, 2mL of methanol and benzylquinine-3-one oxime (1mmol, 306mg) were added. The mixture was heated to 60°C and stirred for 30 minutes. If the mixture did not dissolve, 10 drops of DMF were added. Once dissolved, 416μL of an aqueous solution of zinc chloride (2mmol, 272.6mg) was added dropwise over 1 hour. After the addition was complete, the mixture was reacted at 50°C for 3 hours, allowed to stand for 1 hour, and filtered to obtain a metal complex, designated C1, in a 64% yield. The structural characterization data of the product are as follows: Anal. Calc / %: C, 54.26; H, 5.01; N, 6.33; Found: C, 54.45; H, 5.31; N, 6.54. The synthetic route is as follows:

[0039]

[0040] Example 4

[0041] In a 100mL round-bottom flask, 2mL of methanol and benzylquinine-3-one oxime (1mmol, 306mg) were added. The mixture was heated to 60°C and stirred for 30 minutes. If the mixture did not dissolve, 10 drops of DMF were added. Once dissolved, 416μL of an aqueous solution of copper acetate (2mmol, 399.3mg) was added dropwise over 1 hour. After the addition was complete, the mixture was reacted at 50°C for 3 hours, allowed to stand for 1 hour, and filtered to obtain a metal complex, designated C2, in a yield of 54%. The structural characterization data of the product are as follows: Anal. Calc / %: C, 59.07; H, 5.78; N, 5.74. Found: C, 59.36; H, 5.37; N, 5.45. The synthetic route is as follows:

[0042]

[0043] Example 5

[0044] In a 100mL round-bottom flask, 2mL of methanol and benzylquinine-3-one oxime (1mmol, 306mg) were added. The mixture was heated to 60°C and stirred for 30 minutes. If the mixture did not dissolve, 10 drops of DMF were added. Once dissolved, 416μL of an aqueous solution of copper sulfate (2mmol, 318.42mg) was added dropwise over 1 hour. After the addition was complete, the mixture was reacted at 50°C for 3 hours, allowed to stand for 1 hour, and filtered to obtain a metal complex, designated C3, in a 61% yield. The structural characterization data of the product are as follows: Anal. Calc / %: C, 51.55; H, 4.76; N, 6.01. Found: C, 51.31; H, 4.97; N, 5.79. The synthetic route is as follows:

[0045]

[0046] Example 6

[0047] In a 100mL round-bottom flask, 2mL of methanol and benzylquinine-3-one oxime (1mmol, 306mg) were added. The mixture was heated to 60°C and stirred for 30min. If the mixture did not dissolve, 10 drops of DMF were added. Once dissolved, 416μL of an aqueous solution of manganese sulfate (2mmol, 302.00mg) was added dropwise over 1h. After the addition was complete, the mixture was reacted at 50°C for 3h, allowed to stand for 1h, and filtered to obtain a metal complex, designated C4, in a yield of 53%. The structural characterization data of the product are as follows: Anal. Calc / %: C, 52.52; H, 4.85; N, 6.12. Found: C, 52.73; H, 4.53; N, 6.52. The synthetic route is as follows:

[0048]

[0049] Example 7

[0050] In a 100 mL round-bottom flask, 2 mL of methanol and benzylquinine-3-one oxime (1 mmol, 306 mg) were added. The mixture was heated to 60°C and stirred for 30 minutes. If the mixture did not dissolve, 10 drops of DMF were added. Once dissolved, 416 μL of an aqueous solution of ferrous sulfate heptahydrate (2 mmol, 556.02 mg) was added dropwise over 1 hour. After the addition was complete, the mixture was reacted at 50°C for 3 hours, allowed to stand for 1 hour, and filtered to obtain a metal complex, designated C5, in a yield of 68%. The structural characterization data of the product are as follows: Anal. Calc / %: C, 52.41; H, 4.84; N, 6.11. Found: C, 52.20; H, 4.66; N, 6.51. The synthetic route is as follows:

[0051]

[0052] Example 8

[0053] In a 100mL round-bottom flask, add 2mL of methanol and benzylquinin-3-one-O-methyloxime ether (1mmol, 320mg). Heat to 60°C and stir for 30 minutes. Once the solution becomes clear, add a mixture of 2mmol, 399.30mg of copper acetate and 4mL of water dropwise. After complete addition, stir at 60°C for 3 hours. Let stand for 1 hour, then filter to obtain a metal complex, designated N1, in a 63% yield. The product's structural characterization data are as follows: Anal. Calc / %: C, 59.81; H, 6.02; N, 5.58. Found: C, 59.53; H, 6.23; N, 5.22. The synthetic route is as follows:

[0054]

[0055] Example 9

[0056] In a 100mL round-bottom flask, add 2mL of methanol and benzylquinin-3-one-O-methyloxime ether (1mmol, 320mg). Heat to 60°C and stir for 30 minutes. Once the solution becomes clear, add a mixture of manganese sulfate (2mmol, 302.00mg) and 4mL of water dropwise. After complete addition, stir at 60°C for 3 hours. Let stand for 1 hour, then filter to obtain a metal complex, designated N2, in a 55% yield. The structural characterization data of the product are as follows: Anal. Calc / %: C, 53.50; H, 5.13; N, 5.94. Found: C, 53.22; H, 5.42; N, 5.64. The synthetic route is as follows:

[0057]

[0058] Example 10

[0059] In a 100mL round-bottom flask, add 2mL of methanol and benzylquinin-3-one-O-methyloxime ether (1mmol, 320mg). Heat to 60°C and stir for 30 minutes. Once the solution becomes clear, add a mixture of zinc chloride (2mmol, 272.6mg) and 4mL of water dropwise. After complete addition, stir at 60°C for 3 hours. Let stand for 1 hour, then filter to obtain a metal complex, designated N3, in a 54% yield. The product's structural characterization data are as follows: Anal. Calc / %: C, 55.23; H, 5.30; N, 6.13. Found: C, 55.45; H, 5.53; N, 6.45. The synthetic route is as follows:

[0060]

[0061] Example 11

[0062] In a 100mL round-bottom flask, add 2mL of methanol and benzylquinin-3-one-O-methyloxime ether (1mmol, 320mg). Heat to 60°C and stir for 30 minutes. Once the solution becomes clear, add a mixture of copper sulfate (2mmol, 318.42mg) and 4mL of water dropwise. After complete addition, stir at 60°C for 3 hours. Let stand for 1 hour, then filter to obtain a metal complex, designated N4, in a 61% yield. The product's structural characterization data are as follows: Anal. Calc / %: C, 52.54; H, 5.04; N, 5.84. Found: C, 52.32; H, 5.43; N, 5.54. The synthetic route is as follows:

[0063]

[0064] Example 12

[0065] In a 100mL round-bottom flask, add 2mL of methanol and benzylquinin-3-one-O-methyloxime ether (1mmol, 320mg). Heat to 60°C and stir for 30 minutes. Once the solution becomes clear, add a mixture of ferrous sulfate heptahydrate (2mmol, 556.02mg) and 4mL of water dropwise. After complete addition, stir at 60°C for 3 hours. Let stand for 1 hour, then filter to obtain a metal complex, designated N5, in a yield of 58%. The product's structural characterization data are as follows: Anal. Calc / %: C, 53.40; H, 5.12; N, 5.93. Found: C, 53.73; H, 5.43, N, 5.67. The synthetic route is as follows:

[0066]

[0067] Example 13

[0068] In a 100mL round-bottom flask, add 2mL of methanol and benzylquinin-3-one-O-methyloxime ether (1mmol, 320mg). Heat to 60°C and stir for 30 minutes. Once the solution becomes clear, add a mixture of nickel chloride (2mmol, 259.20mg) and 4mL of water dropwise. After complete addition, stir at 60°C for 3 hours. Let stand for 1 hour, then filter to obtain a metal complex, designated N6, in a 65% yield. The product's structural characterization data are as follows: Anal. Calc / %: C, 56.05; H, 5.38; N, 6.22. Found: C, 56.35; H, 5.61; N, 6.52. The synthetic route is as follows:

[0069]

[0070] Example 14

[0071] In a 100mL round-bottom flask, add 2mL of methanol and benzylquinin-3-one-O-methyloxime ether (1mmol, 320mg). Heat to 60°C and stir for 30 minutes. Once the solution becomes clear, add a mixture of copper trifluoromethanesulfonate (2mmol, 723.36mg) and 4mL of water dropwise. After complete addition, stir at 60°C for 3 hours. Let stand for 1 hour, then filter to obtain a metal complex, designated N7, in a 51% yield. The structural characterization data of the product are as follows: Anal. Calc / %: C, 40.50; H, 3.55; N, 4.11. Found: C, 40.28; H, 3.34; N, 4.31. The synthetic route is as follows:

[0072] Example 15

[0073] First, seal the PDA prepared in a conical flask according to the proportion with a breathable sealing film, put it into a high-pressure sterilizer at a temperature of 120°C, and sterilize it for 30 minutes. Before inoculating the bacteria, different concentrations of target compound and control drug solutions must be prepared, using acetone as the solvent. In the experiment, each drug concentration culture dish was measured with 3 parallel replicates. The colony diameter was measured using the cross-cross method, and the inhibition rate was calculated. The formula for the inhibition rate of antibacterial activity is as follows: mycelium growth inhibition rate = (control colony diameter - treated colony diameter) / control colony diameter × 100%. The antibacterial activity of the metal complex prepared in Example 3-14 is shown in Table 1 and Table 2:

[0074] Table 1 Antibacterial activity of the metal complexes prepared in Examples 3-14 (inhibition rate %)

[0075]

[0076] Table 2 Antibacterial activity of the metal complexes prepared in Examples 3-14 (inhibition rate %)

[0077]

[0078]

[0079] The results showed that at a concentration of 100 mg / L, the 12 target compounds exhibited inhibition rates exceeding 40% against apple rot, cucumber wilt, wheat take-all pathogen, peanut root rot, tomato wilt, peanut southern rot, and strawberry gray mold. In particular, the inhibition rates against wheat take-all pathogen, cucumber wilt pathogen, and peanut southern rot were above 60%. At a concentration of 50 mg / L, most compounds exhibited inhibition rates exceeding 50% against peanut southern rot. Compounds C3, C4, and N4 exhibited significant inhibition against wheat take-all pathogen, while compounds C5 and N6 showed the best inhibition against apple rot pathogen. Compounds C1, C2, and N3 exhibited significant inhibition against cucumber wilt pathogen. Compound C1 exhibited the best inhibition against peanut root rot, compound C3 exhibited the best inhibition against strawberry gray mold, compound N3 exhibited the best inhibition against peanut southern rot, and compound N4 exhibited significant inhibition against tomato wilt pathogen.

Claims

1. A metal complex, characterized in that The general formula of the metal complex is LM; Wherein, L is a ligand and M is a metal salt; The ligand is benzylquinine-3-one oxime or benzylquinine-3-one-O-methyloxime ether; the structural formula of the benzylquinine-3-one oxime is shown in formula (I); the structural formula of the benzylquinine-3-one-O-methyloxime ether is shown in formula (II): (I)； (II); The metal salt is a copper salt, a zinc salt, a manganese salt, an iron salt or a nickel salt.

2. The metal complex according to claim 1, characterized in that The copper salt is copper acetate, copper sulfate or copper trifluoromethanesulfonate; the zinc salt is zinc chloride; the manganese salt is manganese sulfate; the iron salt is ferrous sulfate heptahydrate; and the nickel salt is nickel chloride.

3. A method for preparing the metal complex according to claim 1, characterized in that: The preparation method comprises the steps of dripping a metal salt solution into a methanol solution containing a ligand, performing a coordination reaction, and filtering to obtain the metal complex.

4. The preparation method according to claim 3, characterized in that The benzylquinine-3-one oxime is prepared by heating, cooling, filtering, desolventizing and drying an ethanol solution containing ketone, hydroxylamine hydrochloride and anhydrous potassium carbonate. The reaction process is shown in the following formula: Wherein, the molar ratio of the ketone, hydroxylamine hydrochloride and anhydrous potassium carbonate is 1:2:

2.

5. The preparation method according to claim 3, characterized in that The benzylquinine-3-one-O-methyloxime ether is prepared by heating, cooling, filtering, desolventizing and drying an ethanol solution containing ketone, methoxyamine hydrochloride and anhydrous potassium carbonate. The reaction process is shown in the following formula: The mass volume ratio of the ketone, methoxyamine hydrochloride and anhydrous potassium carbonate is 1:2:

2.

6. The preparation method according to claim 3, characterized in that The molar ratio of the ligand to the metal salt is 1:2; and the dropwise addition time is 1 hour.

7. The preparation method according to claim 3, characterized in that The molar volume ratio of the ligand to methanol in the methanol solution containing the ligand is 1 mmoL:1 mL; the molar volume ratio of the metal salt to water in the metal salt solution is 2 mmoL:(0.416-4) mL.

8. The preparation method according to claim 3, characterized in that The temperature of the coordination reaction is 50-60° C. and the time is 3 hours.

9. Use of the metal complex according to claim 1 or 2 or / and the metal complex prepared by the method according to any one of claims 3 to 8 in the preparation of an antibacterial agent, characterized in that: The antibacterial agent is used for inhibiting or killing at least one of apple rot pathogen, cucumber wilt pathogen, wheat take-all pathogen, peanut root rot pathogen, tomato wilt pathogen, peanut white rot pathogen and strawberry gray mold pathogen.

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