Preparation method and application of imidazoline metal complex

Abstract

The synthesis method comprises the following steps: respectively weighing 0.2673 g of N, N '-thiocarbonyldiimidazole, putting the N, N'-thiocarbonyldiimidazole into a 100mL round-bottom flask, respectively adding 0.1454 g of nickel nitrate hexahydrate, 0.0682 g of zinc chloride and 0.0682 g of nickel chloride hexahydrate, dissolving the materials in 30mL of absolute methanol, heating and refluxing for 24 hours, carrying out hot filtration on a reaction solution, and drying to obtain the tetraimidazoline copper chloride complex I, the hexaimidazoline nickel chloride complex II and the hexaimidazoline nickel chloride complex III. Crystals are separated out after natural volatilization for several days; the crystal is washed with petroleum ether and normal hexane for three times, vacuum drying is carried out for 30 min, a target product is obtained, the chemical formula of the crystal is as shown in # imgabs0, the crystal complex II shows good inhibitory activity in resisting cancer cells such as liver cancer SMMC-7721 (uM), and the anti-cancer inhibition rate of the crystal complex II is 91.19 + / -2.14%.

Description

Technical Field

[0001] The invention relates to a method for preparing a metal organic coordination compound, in particular to a method for synthesizing a metal organic complex containing imidazoline and its application, more specifically to a method for synthesizing an imidazoline nickel nitrate complex and a monohydrate imidazoline zinc chloride complex and its application. Background Art

[0002] With the development of organic chemistry, the application of metal organic compounds in organic synthesis is becoming more and more extensive. It is one of the most active fields in organic chemistry and has been widely used in organic synthesis reactions. The synthesis reaction catalyzed by imidazoline ligands and transition metal complexes has greatly accelerated the research of drugs. In recent years, the synthesis and application research of imidazoline and metal zinc and nickel complexes have appeared one after another, see references [1-2].

[0003] References:

[0004] 1. Design and anticancer behaviour of cationic / neutral half-sandwichiridium(III)imidazole-phenanthroline / phenanthrene complexes, Lv, Ao; Li, Guangxiao; Zhang, Pei; Tao, Rui; Li, Xiaoshuang; Ren, Xueyan; Li, Peixuan; Liu, Xicheng; Yuan, Xiang-Ai; Liu, Zhe, Journal of Inorganic Biochemistry (2024), 257, 112612;

[0005] 2.Synthesis and characterization of indazolederived Schiff baseligands and their metal complexes: Biological and computational studies Arora, Tanisha; Devi, Jai; kumar, Binesh; Rani, Manju, Inorganic Chemistry Communications (2024), 166, 112585 Summary of the invention

[0006] The present invention aims to provide a transition metal organic complex for application in the field of catalysis, and the technical problem to be solved is to select N,N'-thiocarbonyldiimidazole as a ligand to synthesize an imidazoline metal complex in one step.

[0007] The nickel complex referred to in the present invention is a complex shown in the following chemical formula prepared by heating N,N'-thiocarbonyldiimidazole and nickel nitrate hexahydrate in 30 mL of anhydrous methanol under reflux for 24 hours:

[0008]

[0009] Chemical name: Hexaimidazole nickel nitrate complex, referred to as complex (I).

[0010] The synthesis method of the complex I includes synthesis and separation. The synthesis is as follows: weigh 0.2673g N,N'-thiocarbonyldiimidazole and put it into a 100mL round-bottom flask, add 30mL anhydrous methanol and stir to dissolve it; add 0.1454g nickel nitrate hexahydrate to the above solution, heat and reflux for 24h; after the reaction is completed, filter the reaction solution while hot, and the filtrate evaporates naturally, and crystals precipitate after a few days. Rinse the crystals with petroleum ether and n-hexane for 3 times, and vacuum dry for 30min to obtain the target product. The synthesis route of the complex is as follows:

[0011]

[0012] The nickel complex referred to in the present invention is a complex shown in the following chemical formula prepared by heating N,N'-thiocarbonyldiimidazole and anhydrous zinc chloride in 30 mL of anhydrous methanol under reflux for 24 hours:

[0013]

[0014] Chemical name: Hexaimidazoline zinc chloride monohydrate complex, referred to as complex (II).

[0015] The synthesis method of the complex II includes synthesis and separation. The synthesis is as follows: weigh 0.2673g N,N'-thiocarbonyldiimidazole and put it into a 100mL round-bottom flask, add 30mL anhydrous methanol and stir to dissolve it; add 0.0682g zinc chloride to the above solution, heat and reflux for 24h; after the reaction is completed, filter the reaction solution while hot, and the filtrate evaporates naturally. After a few days, crystals are precipitated. The synthesis route is as follows:

[0016]

[0017] The nickel complex referred to in the present invention is a complex shown in the following chemical formula prepared by heating N,N'-thiocarbonyldiimidazole and anhydrous zinc chloride in 30 mL of anhydrous methanol under reflux for 24 hours:

[0018]

[0019] Chemical name: Hexaimidazoline zinc chloride monohydrate complex, referred to as complex (II).

[0020] The synthesis method of the complex II includes synthesis and separation. The synthesis is as follows: weigh 0.2673g N,N'-thiocarbonyldiimidazole and put it into a 100mL round-bottom flask, add 30mL anhydrous methanol and stir to dissolve it; add 0.0682g zinc chloride to the above solution, heat and reflux for 24h; after the reaction is completed, filter the reaction solution while hot, and the filtrate evaporates naturally. After a few days, crystals are precipitated. The synthesis route is as follows:

[0021] The synthesis method of the complex III is as follows: 0.2673g of N,N'-thiocarbonyldiimidazole is weighed and put into a 100mL round-bottom flask, 30mL of anhydrous methanol is added and stirred to dissolve; 0.1189g of nickel chloride hexahydrate is added to the above solution, and heated to reflux for 18h; after the reaction is completed, the reaction solution is filtered while hot, and the filtrate evaporates naturally, and crystals are precipitated after a few days. The synthesis route is as follows:

[0022]

[0023] The complexes I, II, and III showed certain inhibitory activity in experiments on cancer cells such as lung cancer (A-549) (uM), liver cancer (SMMC-7721) (uM), and colon cancer (SW480) (uM), with inhibition rates of 7.38±0.26 for lung cancer (A-549) and 21.29±1.01 for SMMC-7721; complex II showed certain inhibitory activity in experiments on cancer cells such as lung cancer (A-549), liver cancer (SMMC-7721), and colon cancer (SW480) (uM). In the cancer (SW480) (uM) test, the inhibition rates were 21.29±1.01 and 91.19±2.14 and 24.66±1.79 for SMMC-7721 respectively; the complex III showed certain inhibitory activity in the test of cancer cells such as lung cancer A-549 and liver cancer (SMMC-7721), and the inhibition rates were 8.88±0.84 and 38.61±1.39 for SMMC-7721 respectively. The crystal data of nickel complex I are as follows:

[0024] Empirical formula C18H24 N14O6 Ni

[0025] Molecular weight 591.22

[0026] Temperature 200(2)K

[0027] wavelength

[0028] Crystal system, space group triclinic, R-3

[0029] Unit cell parameters α=90°.

[0030] β=90°.

[0031] γ=120°.

[0032] volume

[0033] Charge density 3, 1.528Mg / m^3

[0034] Absorption correction parameter 4.480 mm^-1

[0035] The number of electrons in a unit cell is 918

[0036] Crystal size 0.300x 0.200x 0.100mm

[0037] Theta angle range 4.459 to 72.218

[0038] HKL indicator collection range: -15<=h<=16, -17<=k<17, -20<=l<=20 Collected / independent diffraction data 10050 / 1286 [R(int)=0.0514]

[0039] Theta = 30.5 Data integrity 100.0%

[0040] Absorption Correction Methods Multi-slice Scanning

[0041] The maximum and minimum transmittance are 0.957 and 0.923

[0042] The method used for refinement is the matrix least squares method of F^2.

[0043] Number of data / number of usage restrictions / number of parameters 1286 / 0 / 61

[0044] Method used for refinement 1.103

[0045] The consistency factor of the diffraction point is R1 = 0.0377, ωR2 = 0.1003

[0046] The match factor of the observed diffraction is R1 = 0.0420, ωR2 = 0.1025

[0047] The maximum peak and valley on the difference Fourier plot are 0.308 and Typical bond length data for crystals:

[0048]

[0049]

[0050] Typical bond angle data of crystals:

[0051]

[0052]

[0053] The crystal data of zinc complex II are as follows:

[0054] Empirical formula C16H18 N2O10Zn2

[0055] Molecular weight 529.00

[0056] Temperature 100(2)K

[0057] wavelength

[0058] Crystal system, space group monoclinic, C2 / c

[0059] Unit cell parameters α=90°.

[0060] β=94.421(4)°.

[0061] γ=90°.

[0062] volume

[0063] Charge density 8, 1.714 Mg / m^3

[0064] Absorption correction parameter 2.235(7) mm^-1

[0065] The number of electrons in a unit cell is 2144

[0066] Crystal size 0.120x 0.100x 0.100mm

[0067] Theta angle range 3.626 to 54.875

[0068] HKL indicator collection range: -10<=h<=10, -31<=k<31, -22<=l<=22 Collected / independent diffraction data 19445 / 2616 [R(int)=]

[0069] Theta = 30.5 Data integrity 98.9%

[0070] Absorption Correction Methods Multi-slice Scanning

[0071] The maximum and minimum transmittances are 0.7168 and 0.5352

[0072] The method used for refinement is the matrix least squares method of F^2. Number of data / number of usage restrictions / number of parameters 19445 / 0 / 282

[0073] Method used for refinement 1.059

[0074] The consistency factor of the diffraction point is R1 = 0.0665, ωR2 = 0.1836 The match factors of the observed diffraction are R1 = 0.0739, ωR2 = 0.1891 The maximum peak and valley on the difference Fourier plot are 0.931 and Typical bond length data for crystals:

[0075]

[0076]

[0077] Typical bond angle data of crystals:

[0078]

[0079]

[0080]

[0081]

[0082] The crystal data of nickel chloride complex III are as follows:

[0083] Empirical formula C18H32Cl2N12O4 Ni

[0084] Molecular weight 610.16

[0085] Temperature 200(2)K

[0086] wavelength

[0087] Crystal system, space group triclinic, P-1

[0088] Unit cell parameters α=75.300(2)°.

[0089] β=83.097(2)°.

[0090] γ=61.627(2)°.

[0091] volume

[0092] Charge density 1, 1.430Mg / m^3

[0093] Absorption correction parameter 4.480 mm^-1

[0094] The number of electrons in a unit cell is 318

[0095] Crystal size 0.120x 0.100x 0.090mm

[0096] Theta angle range 3.786 to 72.183

[0097] HKL index collection range -11<=h<=11, -11<=k<11, -13<=l<=13 Collection / independent diffraction data 3424 / 1286 [R(int)=0.0506]

[0098] Theta=30.5 data integrity 99.7%

[0099] Absorption Correction Methods Multi-slice Scanning

[0100] The maximum and minimum transmittance are 0.957 and 0.923

[0101] The method used for refinement is the matrix least squares method of F^2. Number of data / number of usage restrictions / number of parameters 3424 / 1 / 81

[0102] Method used for refinement 1.230

[0103] The consistency factor of the diffraction point is R1 = 0.0448, ωR2 = 0.1131 The match factors of the observed diffraction are R1 = 0.0753, ωR2 = 0.1257 The maximum peak and valley on the difference Fourier plot are 0.543 and Typical bond length data for crystals:

[0104]

[0105]

[0106] Typical bond angle data of crystals:

[0107]

[0108] BRIEF DESCRIPTION OF THE DRAWINGS

[0109] Figure 1 X-ray diffraction analysis of nickel complex I.

[0110] Figure 2 X-ray diffraction analysis of zinc complex II.

[0111] Figure 3 X-ray diffraction analysis of nickel chloride complex III. DETAILED DESCRIPTION

[0112] 1. Preparation of imidazoline nickel nitrate complex I

[0113] Weigh 0.2673g N,N'-thiocarbonyldiimidazole into a 100mL round-bottom flask, add 30mL anhydrous methanol and stir to dissolve; add 0.1454g nickel nitrate hexahydrate to the above solution, heat and reflux for 24h; filter the reaction solution while hot after the reaction is completed, the filtrate evaporates naturally, and crystals precipitate after a few days; rinse the crystals with petroleum ether and n-hexane for 3 times, and vacuum dry for 30min to obtain the target product with a yield of 45% and a melting point of 168-172℃. Elemental analysis data C18 H24 Ni N14 O6, theoretical value: C: 36.5%; H: 4.1%; N: 33.2%; measured value: C: 36.3%; H: 4.5%; N: 33.0%; infrared spectrum data (KBr, cm -1 ):3136;1610;1535;1384;1326;1072;937;846;746;668;615.

[0114] 2. Preparation of imidazoline zinc complex II

[0115] Weigh 0.2673g N,N'-thiocarbonyldiimidazole into a 100mL round-bottom flask, add 30mL anhydrous methanol and stir to dissolve; add 0.0682g zinc chloride to the above solution, heat and reflux for 24h; filter the reaction solution while hot after the reaction is completed, the filtrate evaporates naturally, and crystals precipitate after a few days; rinse the crystals with petroleum ether and n-hexane for 3 times, and vacuum dry for 30min to obtain the target product with a yield of 80% and a melting point of 33-36℃. Elemental analysis data C18 H32 Cl2 Zn N12 O4, theoretical value: C: 35.1%; H: 5.2%; N: 27.3%; measured value: C: 35.5%; H: 4.8%; N: 27.0%; infrared spectrum data (KBr, cm -1): 3397; 3132; 1624; 1544; 1327; 1263; 1071; 956; 835; 758; 656; 617.

[0116] 3. Preparation of imidazoline nickel chloride complex I

[0117] Weigh 0.2673g N,N'-thiocarbonyldiimidazole into a 100mL round-bottom flask, add 30mL anhydrous methanol and stir to dissolve; add 0.1189g nickel chloride hexahydrate to the above solution, heat and reflux for 18h; filter the reaction solution while hot after the reaction is completed, the filtrate evaporates naturally, and crystals precipitate after a few days; rinse the crystals with petroleum ether and n-hexane for 3 times, and vacuum dry for 30min to obtain the target product with a yield of 75% and a melting point of 122-128℃. Elemental analysis data C18 H32 Cl2 Ni N12O4, theoretical value: C: 35.4%; H: 5.2%; N: 27.5%; measured value: C: 35.7%; H: 5.4%; N: 27.3%; infrared spectrum data (KBr, cm -1 ): 3475; 3193; 1621; 1536; 1327; 1067; 852; 752; 664; 614.

[0118] 4. Anticancer activity of complexes I, II and III

[0119] The complex I synthesized according to the structure of the active natural product shows a certain inhibitory activity in the test of cancer cells such as lung cancer A-549, liver cancer (SMMC-7721) and colon cancer (SW480) (uM), and the inhibition rates are 7.38±0.26 and 21.29±1.01 for SMMC-7721 respectively; the complex II shows a certain inhibitory activity in the test of cancer cells such as lung cancer A-549, liver cancer (SMMC-7721) and colon cancer (SW480) (uM ) test, the inhibition rates were 21.29±1.01 and 91.19±2.14 and 24.66±1.79 for SMMC-7721 respectively; complex III showed certain inhibitory activity in tests on cancer cells such as lung cancer A-549 and liver cancer (SMMC-7721), the inhibition rates were 8.88±0.84 and 38.61±1.39 for SMMC-7721 respectively; the anticancer activity test results are shown in Table 1:

[0120] Anticancer activity data of complexes I-III (anticancer inhibition rate data of complexes)

[0121]

Claims

1. A tetraimidazoline copper chloride complex having the following chemical formula I and unit cell parameters, characterized in that: The synthesis method of the complex I includes synthesis and separation. The synthesis is as follows: 0.2673 g of N, N'-thiocarbonyldiimidazole is weighed and put into a 100 mL round-bottom flask, 30 mL of anhydrous methanol is added and stirred to dissolve; 0.1454 g of nickel nitrate hexahydrate is added to the above solution, and heated to reflux for 24 hours; after the reaction is completed, the reaction solution is filtered while hot, and the filtrate evaporates naturally, and crystals are precipitated after a few days; the crystals are rinsed with petroleum ether and n-hexane for 3 times, and vacuum dried for 30 minutes to obtain the target product; The unit cell parameters of the complex I are as follows: triclinic system, R-3; α=90°; β=90°; γ=120°.

2. A nickel hexaimidazoline complex having the following chemical formula II and unit cell parameters, characterized in that: The synthesis is as follows: 0.2673 g of N, N'-thiocarbonyldiimidazole is weighed and placed in a 100 mL round-bottom flask, 30 mL of anhydrous methanol is added and stirred to dissolve; 0.0682 g of zinc chloride is added to the above solution, and heated to reflux for 24 h; after the reaction is completed, the reaction solution is filtered while hot, and the filtrate evaporates naturally, and crystals precipitate after a few days. The unit cell parameters of the complex I are as follows: monoclinic system, C2 / c; unit cell parameters: α=90°; β=94.421(4)°; γ=90°.

3. A hexaimidazole nickel chloride complex represented by the following chemical formula III and unit cell parameters, characterized in that: The synthesis is as follows: 0.2673 g of N, N'-thiocarbonyldiimidazole is weighed and placed in a 100 mL round-bottom flask, 30 mL of anhydrous methanol is added and stirred to dissolve; 0.0682 g of zinc chloride is added to the above solution, and heated to reflux for 24 h; after the reaction is completed, the reaction solution is filtered while hot, and the filtrate evaporates naturally, and crystals precipitate after a few days. The unit cell parameters of the complex III: triclinic system, P-1; unit cell parameters: α=75.300(2)°; β=83.097(2)°; γ=61.627(2)°.

4. The use of the tetraimidazoline nitrate copper complex according to claim II is: the crystalline copper complex II shows a certain inhibitory activity against cancer cells such as liver cancer SMMC-7721 (uM), and its anticancer inhibition rate is 91.19±2.14%.

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