Preparation and application of tetrapyridine copper oxalate metal complex

Abstract

A synthesis method of the tetrapyridine copper oxalate metal complex comprises the following steps: weighing 0.5 g of chromone 2-formic acid (2.6 mmol) and 0.48 g of copper perchlorate hexahydrate (1.3 mmol), putting the weighed chromone 2-formic acid and copper perchlorate hexahydrate into a 250mL round-bottom flask, dissolving the weighed chromone 2-formic acid and copper perchlorate hexahydrate into a 30mL ethanol solution, carrying out ultrasonic uniform dissolution for 3 minutes, and adding equivalent pyridine until the solution is dark blue. Putting the flask on a heating and stirring sleeve, stirring, refluxing and heating, reacting for 28 hours, then taking out, and carrying out hot filtration, so that blue crystals can be separated out in about 30 minutes; the complex shows certain performance in anti-tumor activity of lung cancer. The inhibition rate of the anti-lung cancer activity reaches 43.56%.

Description

Technical Field

[0001] The invention relates to the preparation and application of a pyridine copper complex, in particular to the preparation and application of tetrapyridine copper oxalate. Background Art

[0002] Chromocarb is a vascular protective agent with a molecular formula of C 10 H6O4 is used to treat venous reflux disorders and microvascular infections. It can be used for biochemical research and pharmaceutical intermediates. Copper tetrapyridine oxalate metal complex is a new type of copper complex that can be used as an anticancer agent. There are many similar literature reports, see references [1-3]:

[0003] References:

[0004] 1.Veronica JM,Chris D,Francisco M R.Robust Lanthanoid Picolinate-Based Coordination Polymers for Lu minescence and Sensing Applications[J].Inorganic Chemistry,2021,60(36):10572-10584.

[0005] 2. M.;Petrova,M.;Dobrikov,GM;Grancharov,G.;Momekova,D.;Petrov,PD;Ugrinova,I.

[0006] 3. Shengke Li; Yan Gao; Yuanfu Ding; Anni Xu; Huaping Tan; Supramolecular nano drug delivery systems mediated via host-guest chemistry of cucurbit[n]uril(n=6and 7)[J]; Chinese Chemical Letters; Issue 01, 2021 4. Xiao Mengjun; Gao Zhihui; Wei Jianhe; Research progress on biological activity and biosynthesis of 2-(2-phenylethyl) chromone compounds[J]; Chinese Journal of Pharmacy; Issue 23, 2019. Summary of the invention

[0007] The present invention aims to provide a synthesis method for the field of asymmetric synthesis, especially for preparing chiral drug compounds. The technical problem to be solved is to select suitable ligands to synthesize binuclear nickel metal complexes in one step.

[0008] (I) The compound referred to in the present invention is prepared by reacting 0.5 g of chromone-2-carboxylic acid, 0.48 g of copper perchlorate hexahydrate and an equivalent amount of pyridine in 30 mL of ethanol solution under reflux for 28 hours to obtain a complex represented by the following chemical formula (I):

[0009]

[0010] Its chemical name: tetrapyridine binuclear copper perchlorate metal complex, referred to as complex (I).

[0011] The reaction mechanism of this reaction can be speculated as follows:

[0012] Ligand: After 28 hours of reflux reaction under the catalytic influence of Lewis acid metal salt, the ligand first decomposes into oxalic acid intermediate. Then it quickly forms the target crystal complex with pyridine in one step. Its structure is determined by X-diffraction, NMR, IR and elemental analysis. The complex shows certain performance in the anti-tumor activity of lung cancer. Its anti-lung cancer activity inhibition rate reaches 43.56%. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 It is the crystal structure diagram of target compound I. DETAILED DESCRIPTION

[0014] 1. Preparation of Complex I

[0015] Weigh 0.5g of chromone-2-carboxylic acid (2.6mmol) and 0.48g of copper perchlorate hexahydrate (1.3mmol) into a 250mL round-bottom flask, then add 30mL of ethanol, and then ultrasonically dissolve evenly for 3min, then add an equivalent amount of pyridine, at which point the solution is dark blue. Place the flask on a heating and stirring jacket, stir and reflux, react for 28h, take it out, filter it hot, and blue crystals will be seen precipitated in about 30 minutes, with a melting point of about 230-242℃; ESI:C 20 H 20 C l2 CuN4O8, theoretical value: 393.6540; test value: 393.9497; infrared spectrum data (KBr, cm -1 ): 3473; 3068; 1736; 1572; 1466, 1450, 1364, 1306, 1268, 1242, 1019, 950, 855, 777, 756, 688, 627; ESI mass spectrum of tetrapyridine oxalate copper perchlorate (II): test value 578.9993, theoretical molecular weight 578.84;

[0016] The crystal data of the compound are as follows:

[0017] Empirical C 20 H 20 C l2 CuN4O8

[0018] Molecular weight 578.84

[0019] Temperature 100(2)K

[0020] wavelength

[0021] Crystal system, space group monoclinic, P 21 / c

[0022] Unit cell parameters alpha=90°.

[0023] beta=98.151(3)°.

[0024] gamma=90°.

[0025] volume

[0026] Charge density 1, 1.735g / m^3

[0027] Absorption correction parameter 9.073 mm^-1

[0028] The number of electrons in a unit cell is 1616

[0029] Crystal size 0.12 x 0.100 x 0.100 mm

[0030] Theta angle range 2.742 to 62.919°

[0031] HKL indicator collection range: -18<=h<=18, -5<=k<12, -30<=l<=30

[0032] Collected / independent diffraction data 31852 / 7360 [R(int)=0.0636]

[0033] Theta = 30.5 Data completeness 98.7%

[0034] Absorption Correction Methods Multi-slice Scanning

[0035] The method used for refinement is the matrix least squares method of F^2.

[0036] Number of data / number of usage restrictions / number of parameters 7360 / 0 / 419

[0037] Method used for refinement 1.018

[0038] The consistency factor of the diffraction point is R1 = 0.0440, wR2 = 0.1098

[0039] The observed diffraction matching factors are R1 = 0.0547, wR2 = 0.1153

[0040] The largest peaks and valleys on the difference Fourier plot

[0041] Table 1 Typical bond length data of crystals:

[0042]

[0043]

[0044]

[0045]

[0046]

[0047]

[0048] 2. Anticancer activity application

[0049] The palladium complexes synthesized according to the structure design of the active natural product in the present invention all show certain inhibitory activity in tests on cancer cells such as lung cancer A549. The anticancer activity test results are shown in Table 1.

[0050] 1. Initial screening results of compounds

[0051]

Claims

1. A tetrapyridine oxalate copper complex represented by the following chemical formula (I):

2. The crystal of the copper complex (I) according to claim 1, wherein the unit cell parameters are as follows: at 273 K, on ​​an Oxford X-ray single crystal diffractometer, using CuKα rays monochromatized by a graphite monochromator, diffraction data are collected in an ω-θ scanning mode, λ = wavelength Crystal system, space group: monoclinic, P 21 / c; unit cell parameters: α=90°; β=98.151(3)°; γ=90°.

3. The method for synthesizing the copper complex (I) crystal according to claim 1 comprises synthesis and separation, wherein the synthesis comprises: weighing 0.5 g of chromone-2-carboxylic acid (2.6 mmol) and 0.48 g of copper perchlorate hexahydrate (1.3 mmol) into a 250 mL round-bottom flask, adding 30 mL of ethanol, and then performing ultrasonic uniform dissolution for 3 min, and then adding an equivalent amount of pyridine, at which time the solution is dark blue; placing the flask on a heating stirring jacket, stirring and reflux heating, taking it out after reacting for 28 h, and filtering it hot, and blue crystals can be seen precipitated in about 30 minutes.

4. The use of the copper complex (I) according to claim 1, characterized in that: It can be used as an anticancer agent and showed inhibitory activity in lung cancer cell A549 test and liver cancer SMMC-7721 experiment, with IC50 values ​​of 43.56±1.03 and 14.95±0.95 for SMMC-7721 and 28.65±1.91 for colon cancer, respectively.

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