CN108659022B - 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex and preparation method thereof - Google Patents
1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex and preparation method thereof Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 238000010668 complexation reaction Methods 0.000 title description 2
- 239000003446 ligand Substances 0.000 claims abstract description 42
- ULKLGIFJWFIQFF-UHFFFAOYSA-N 5K8XI641G3 Chemical compound CCC1=NC=C(C)N1 ULKLGIFJWFIQFF-UHFFFAOYSA-N 0.000 claims abstract description 31
- 239000011701 zinc Substances 0.000 claims abstract description 25
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims abstract description 18
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 9
- 239000011592 zinc chloride Substances 0.000 claims abstract description 9
- 235000005074 zinc chloride Nutrition 0.000 claims abstract description 9
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 36
- 239000013078 crystal Substances 0.000 claims description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
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- 238000005303 weighing Methods 0.000 claims description 15
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- 239000012266 salt solution Substances 0.000 claims description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 12
- 150000003751 zinc Chemical class 0.000 claims description 12
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- 238000001914 filtration Methods 0.000 claims description 9
- 238000010438 heat treatment Methods 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- -1 DPPH free radical Chemical class 0.000 claims description 8
- YHEKBXQMXRLCCX-UHFFFAOYSA-N 2h-benzotriazol-4-ylmethanol Chemical compound OCC1=CC=CC2=C1N=NN2 YHEKBXQMXRLCCX-UHFFFAOYSA-N 0.000 claims description 6
- WHCCOSVDXKJRKC-UHFFFAOYSA-N 4-(chloromethyl)-2h-benzotriazole Chemical compound ClCC1=CC=CC2=C1N=NN2 WHCCOSVDXKJRKC-UHFFFAOYSA-N 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 239000012043 crude product Substances 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 6
- 238000002329 infrared spectrum Methods 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
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- 238000010992 reflux Methods 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- LRXTYHSAJDENHV-UHFFFAOYSA-H zinc phosphate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O LRXTYHSAJDENHV-UHFFFAOYSA-H 0.000 claims description 6
- 229910000165 zinc phosphate Inorganic materials 0.000 claims description 6
- 239000012964 benzotriazole Substances 0.000 claims description 4
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims description 3
- 239000005457 ice water Substances 0.000 claims description 3
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 3
- 239000000047 product Substances 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
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- 210000004027 cell Anatomy 0.000 claims 1
- 210000002858 crystal cell Anatomy 0.000 claims 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 abstract description 26
- 229930003427 Vitamin E Natural products 0.000 abstract description 13
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 abstract description 13
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- 229940046009 vitamin E Drugs 0.000 abstract description 13
- 239000011709 vitamin E Substances 0.000 abstract description 13
- HHEAADYXPMHMCT-UHFFFAOYSA-N dpph Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1[N]N(C=1C=CC=CC=1)C1=CC=CC=C1 HHEAADYXPMHMCT-UHFFFAOYSA-N 0.000 abstract description 12
- 235000006708 antioxidants Nutrition 0.000 abstract description 6
- 230000002000 scavenging effect Effects 0.000 abstract description 5
- 230000003064 anti-oxidating effect Effects 0.000 abstract description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 16
- 229910052725 zinc Inorganic materials 0.000 description 16
- 150000003254 radicals Chemical class 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- MGJZITXUQXWAKY-UHFFFAOYSA-N diphenyl-(2,4,6-trinitrophenyl)iminoazanium Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1N=[N+](C=1C=CC=CC=1)C1=CC=CC=C1 MGJZITXUQXWAKY-UHFFFAOYSA-N 0.000 description 14
- 229910052723 transition metal Inorganic materials 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 150000003624 transition metals Chemical class 0.000 description 7
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- 125000000623 heterocyclic group Chemical group 0.000 description 5
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- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/003—Compounds containing elements of Groups 2 or 12 of the Periodic Table without C-Metal linkages
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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Abstract
The invention discloses a 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex and a preparation method and application thereof, wherein the molecular formula of the complex is [ Zn (C)13H15N5)2Cl2](ii) a Wherein, C13H15N5Is ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole). The 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex is prepared by taking 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) as a ligand and reacting with zinc chloride, has a stronger scavenging effect on DPPH free radicals, is higher than the scavenging effect of 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) on DPPH free radicals when the complex is singly used, and is also higher than the commonly used antioxidant vitamin E. The results show that the 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) has good antioxidation and is an innovation in antioxidation medicaments.
Description
Technical Field
The invention relates to a 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex, a preparation method and application thereof, and belongs to the technical field of medicines.
Background
With the rapid development of economy and medical hygiene in recent years, people are pursuing beauty more and more, and the attention on the aspects of resisting oxidation, resisting aging, removing freckles, preserving moisture and the like is high. The main reason for skin aging is the surplus of free radicals in the body, so that the elimination or inhibition of free radicals can have a certain slowing effect on skin aging. In addition, free radicals are closely related to various diseases such as cancer and cardiovascular diseases, as well as human aging. Therefore, the research on the antioxidant with the function of scavenging free radicals is more reluctant.
DPPH free radical is a stable free radical taking nitrogen as a center, has simple structure and easy operation of reaction, and is widely applied to screening antioxidants and evaluating the level of antioxidant activity. The principle is that the DPPH free alcohol solution is purple in color and has a maximum light absorption at a wavelength of 517 nm. When a radical scavenger is added to the DPPH radical solution, lone pair electrons are paired, the dark purple DPPH radical is reduced to a yellow DPPH-H non-radical form, and the degree of discoloration is in direct proportion to the radical scavenging activity.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide the 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex as well as the preparation method and the application thereof.
In order to achieve the purpose, the invention adopts the technical scheme that:
1- (benzotriazole)-1-methyl-1- (2-ethyl-4-methylimidazole) zinc complex with a molecular formula of [ Zn (C)13H15N5)2Cl2](ii) a Wherein, C13H15N5Is ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole), and the molecular structural formula is as follows:
the preparation method of the ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) comprises the following steps:
(1) mixing 50mmol of benzotriazole with 15mL of water and 15mL of formaldehyde, heating in water bath to 80 ℃, refluxing for 60min, cooling, filtering to obtain a white needle-shaped product, and recrystallizing with ethyl acetate to obtain a white crystal, namely hydroxymethyl benzotriazole;
(2) weighing 25mmol of hydroxymethyl benzotriazole, adding into a single-neck bottle, dropwise adding 12.5mL of thionyl chloride, mixing and stirring for 20min after dropwise adding, and refluxing at 80 ℃ for 180 min; evaporating the residual thionyl chloride by using a rotary evaporator to obtain a yellow white crystal, namely chloromethyl benzotriazole;
(3) dissolving 20mmol of 2-ethyl-4-methylimidazole in 10mL of DMSO (dimethylsulfoxide), adding 40mmol of crushed NaOH, heating to 60 ℃, adding 20mmol of chloromethyl benzotriazole, heating in a water bath at 60 ℃ for 60min, cooling to room temperature, pouring into 50g of ice water, stirring to generate precipitate, performing suction filtration, and washing the precipitate for 3 times by using water to obtain a crude product;
(4) and adding ethyl acetate into the crude product at 78 ℃ for recrystallization to obtain a yellow-white crystal, namely the ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole).
A preparation method of 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex comprises the following steps:
(1) accurately weighing 0.02-0.04mmol of zinc chloride, and dissolving in 4-6mL of solvent to obtain a zinc salt solution;
(2) accurately weighing 0.02-0.04mmol of ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) and dissolving in 4-6mL of solvent to obtain a ligand solution;
(3) adding the ligand solution into a zinc salt solution, uniformly mixing, filtering, adding a solvent into the filtrate to 10-12mL, and standing at room temperature until colorless rectangular crystals are precipitated, thus obtaining the zinc phosphate.
The solvent in the steps (1), (2) and (3) is one or a mixture of two of water, methanol, dimethyl sulfoxide and acetonitrile.
An application of 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex in inhibiting DPPH free radicals.
An application of 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex in preparing antioxidant drugs.
The invention has the beneficial effects that:
1. according to the invention, 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) is used as a ligand and reacts with zinc chloride to prepare the 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex which is a mononuclear complex, wherein zinc ions are four-coordinated and are respectively coordinated with two nitrogen atoms and two chloride ions on two ligands 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole), so that the problem of the combination of an asymmetric nitrogen heterocyclic compound serving as a ligand and transition metal zinc ions is effectively solved.
2. The 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex prepared by the invention has stronger scavenging effect on DPPH free radicals, is higher than the scavenging effect of 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) on DPPH free radicals by singly using 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) and is also stronger than common antioxidant vitamin E. The results show that the 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) has good antioxidation and is an innovation in antioxidation medicaments.
3. The preparation method is simple, convenient to operate, low in production cost, easy to popularize technologically and good in social and economic benefits.
Drawings
FIG. 1 shows a complex [ Zn (C) ]13H15N5)2Cl2]Structural unit diagram (2).
FIG. 2 shows a complex [ Zn (C) ]13H15N5)2Cl2]The stacked graph of (1).
FIG. 3 is a graph showing the trend of the DPPH radical scavenging rate of the same concentration (0.25mg/mL) of zinc complex, ligand and vitamin E.
FIG. 4 is a graph showing the trend of the DPPH radical scavenging rate of the same concentration (0.5mg/mL) of zinc complex, ligand and vitamin E.
FIG. 5 is a graph showing the trend of the DPPH radical clearance rate of the same concentration (1mg/mL) of zinc complex, ligand and vitamin E.
FIG. 6 is a bar graph of DPPH radical clearance for each compound at 6.5 h.
Detailed Description
The following examples further illustrate the embodiments of the present invention in detail.
Example 1
The preparation method of the ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) comprises the following steps:
(1) mixing 50mmol of benzotriazole with 15mL of water and 15mL of formaldehyde, heating in water bath to 80 ℃, refluxing for 60min, cooling, filtering to obtain a white needle-shaped product, and recrystallizing with ethyl acetate to obtain a white crystal, namely hydroxymethyl benzotriazole;
(2) weighing 25mmol of hydroxymethyl benzotriazole, adding into a single-neck bottle, dropwise adding 12.5mL of thionyl chloride, mixing and stirring for 20min after dropwise adding, and refluxing at 80 ℃ for 180 min; evaporating the residual thionyl chloride by using a rotary evaporator to obtain a yellow white crystal, namely chloromethyl benzotriazole;
(3) dissolving 20mmol of 2-ethyl-4-methylimidazole in 10mL of DMSO (dimethyl sulfoxide), adding 40mmol of crushed NaOH, heating to 60 ℃, adding 20mmol of chloromethyl benzotriazole, heating in a water bath at 60 ℃ for 60min, cooling to room temperature, pouring into 50g of ice water, stirring to generate a precipitate, carrying out suction filtration, and washing the precipitate for 3 times by using water to obtain a crude product;
(4) and adding ethyl acetate into the crude product at 78 ℃ for recrystallization to obtain a yellow-white crystal, namely the ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole).
The content of the prepared ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) is dependent on C13H15N5Meter (%), theoretical value (%): c64.70; h6.27; n29.03; experimental values (%): c64.97; h6.16; and (6) N28.87. Infrared Spectrum (cm)-1，KBr)：3331(s),3119(w),2978(m),2937(w),2440(w),2249(w),2072(w),1975(m),1936(w),1843(w),1804(w),1675(s),1613(m),1587(s),1555(w),1511(m),1496(m),1472(w),1407(w),1333(m),1296(m),1230(m),1163(m),1091(w),1067(w),972(w),860(w),828(s),752(s),694(w),626(m),568(w),535(w),470(m),432(s)。
Example 2
The preparation method of the 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex comprises the following steps:
(1) accurately weighing 0.02mmol of zinc chloride, and dissolving in 4mL of methanol to obtain a zinc salt solution;
(2) accurately weighing 0.02mmol of ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) and dissolving in 4mL of methanol to obtain a ligand solution;
(3) adding the ligand solution into a zinc salt solution, uniformly mixing, filtering, adding methanol into the filtrate to 10mL, and standing at room temperature until colorless rectangular crystals are precipitated, thus obtaining the zinc phosphate.
The experimental conditions and results of the X-ray single crystal diffraction structure of the complex of the invention are as follows:
a single crystal sample with a better crystal form is selected, an X-ray diffraction experiment is carried out on an Xcaliibur, Gemini CCD single crystal diffractometer, Mo-k alpha ray position (lambda is 0.71073A) monochromatically processed by a graphite monochromator is used as a diffraction light source, and diffraction points are collected in an omega-2 theta scanning mode. The crystal structure is solved by a direct method, the crystal structure is expanded by a Fourier technology, correction is carried out according to anisotropy, finally a full matrix least square method is adopted for correction to obtain unit cell parameters, and single crystal data are solved by a difference Fourier electron density map by a SHELX-97 direct method.
The single crystal structure of the prepared nitrogen heterocyclic ring transition metal zinc complex is shown in figures 1 and 2, and the complex belongs toMonoclinic system, C2/C space group, cell parameter a is
b is
c is
α 90 DEG, β 93.807 DEG, gamma 90 DEG, and a volume V of
Z is 8 and the density is 1.402Mg m-3Theta is 4.0270to27.5870 DEG, the limiting factor is-36 ≤ h ≤ 36, -9 ≤ k ≤ 11, -27 ≤ l ≤ 28, F (000) is 2568, R1＝0.0435，wR20.0860. The element content is according to C26H30N10Cl2Zn meter (%), theoretical value (%): c50.45; h4.88; n22.63; experimental values (%): c50.20; h4.69; and (3) N23.03.
Infrared Spectrum (cm)-1，KBr)：3422(s),3119(s),3019(w),2979(w),2361(s),2073(m),1616(m),1484(m),1455(m),1400(s),1288(w),1161(s),1075(s),961(m),860(m),778(w),746(w),615(w),534(s)。
Example 3
The preparation method of the 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex comprises the following steps:
(1) accurately weighing 0.03mmol of zinc chloride, and dissolving in 4mL of water to obtain a zinc salt solution;
(2) accurately weighing 0.03mmol of ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) and dissolving in 6mL of methanol to obtain a ligand solution;
(3) adding the ligand solution into a zinc salt solution, uniformly mixing, filtering, adding methanol into the filtrate to 12mL, and standing at room temperature until colorless rectangular crystals are precipitated, thus obtaining the zinc phosphate.
The single crystal structure of the prepared nitrogen heterocyclic transition metal zinc complex is shown in figures 1 and 2, the complex belongs to a monoclinic system, C2/C space group and unit cell parameter aIs composed of
b is
c is
α 90 DEG, β 93.807 DEG, gamma 90 DEG, and a volume V of
Z is 8 and the density is 1.402Mg m-3Theta is 4.0270to27.5870 DEG, the limiting factor is-36 ≤ h ≤ 36, -9 ≤ k ≤ 11, -27 ≤ l ≤ 28, F (000) is 2568, R1＝0.0435，wR20.0860. The element content is according to C26H30N10Cl2Zn meter (%), theoretical value (%): c50.45; h4.88; n22.63; experimental values (%): c50.20; h4.69; and (3) N23.03.
Infrared Spectrum (cm)-1，KBr)：3422(s),3119(s),3019(w),2979(w),2361(s),2073(m),1616(m),1484(m),1455(m),1400(s),1288(w),1161(s),1075(s),961(m),860(m),778(w),746(w),615(w),534(s)。
Example 4
The preparation method of the 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex comprises the following steps:
(1) accurately weighing 0.04mmol of zinc chloride, and dissolving the zinc chloride in a mixed solution of 4mL of methanol and 2mL of water to obtain a zinc salt solution;
(2) accurately weighing 0.04mmol of ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) and dissolving the ligand in a mixed solution of 4mL of methanol and 2mL of acetonitrile to obtain a ligand solution;
(3) adding the ligand solution into a zinc salt solution, uniformly mixing, filtering, adding dimethyl sulfoxide into the filtrate to 18mL, and standing at room temperature until colorless rectangular crystals are precipitated, thus obtaining the zinc phosphate.
The single crystal structure of the prepared nitrogen heterocyclic transition metal zinc complex is shown in figures 1 and 2, the complex belongs to a monoclinic system, C2/C space group,cell parameter a is
b is
c is
α 90 DEG, β 93.807 DEG, gamma 90 DEG, and a volume V of
Z is 8 and the density is 1.402Mg m-3Theta is 4.0270to27.5870 DEG, the limiting factor is-36 ≤ h ≤ 36, -9 ≤ k ≤ 11, -27 ≤ l ≤ 28, F (000) is 2568, R1＝0.0435，wR20.0860. The element content is according to C26H30N10Cl2Zn meter (%), theoretical value (%): c50.45; h4.88; n22.63; experimental values (%): c50.20; h4.69; and (3) N23.03.
Infrared Spectrum (cm)-1，KBr)：3422(s),3119(s),3019(w),2979(w),2361(s),2073(m),1616(m),1484(m),1455(m),1400(s),1288(w),1161(s),1075(s),961(m),860(m),778(w),746(w),615(w),534(s)。
Examples of the experiments
The nitrogen heterocyclic ring transition metal zinc complex is used for inhibiting DPPH free radicals, and the inhibition rate determination method comprises the following steps:
1. reagent preparation
Preparation of DPPH radical solution: the DPPH radical was precisely weighed to 0.0039g by a balance, and then 100mL was made by absolute ethanol to prepare a DPPH radical solution having a concentration of 0.1 mmol/L.
2. Taking 9 penicillin bottles, adding 2mL of 0.1mmol/L DPPH free radical solution, and adding 2mL of the following reagents according to the setting:
mixing, standing at room temperature in dark place, and measuring absorbance at 517nm at 0.5h, 1.5h, 2.5h, 3.5h, 4.5h, 5.5h, and 6.5h, respectively, to obtain AiThe value is obtained. (the absorbance was corrected for a blank before the absorbance was measured).
The clearance was calculated according to the following formula:
P＝[1-(Ai-Aj)/Ac]×100％
note: a. thecReplacing the sample with a solvent (DMSO: ethanol volume ratio: 1:19)
AjReplacement of DPPH radical solution by absolute ethanol
The DPPH free radical inhibitory activity of the complexes, ligands and vitamin E of the present invention is shown in table 1 below:
table 1: DPPH radical scavenging efficiency (in%)
The trend of the same concentration of zinc complex, ligand and vitamin E in the DPPH radical clearance was plotted and the results are shown in fig. 3-5. As can be seen from fig. 3, 4 and 5, at the same concentration, the DPPH radical scavenging rate of the zinc complex and the ligand tends to increase with time, while vitamin E tends to be relatively stable. Under the concentration of 0.25mg/ml, the clearance rate of the zinc complex to DPPH free radicals is larger than that of vitamin E; under the concentration of 0.5mg/ml, the clearance rate of the zinc complex to DPPH free radicals is gradually increased along with the change of time and is more than that of vitamin E for about 3 hours; at a concentration of 1mg/ml, vitamin E has a greater clearance for DPPH radicals than does the zinc complex, but the two differ only slightly. Under the same concentration, the clearance rate of the zinc complex to DPPH free radicals is far greater than that of the ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole).
The DPPH radical clearance for each compound at 6.5h is plotted as a bar graph, and the results are shown in FIG. 6. As shown in FIG. 6, from the results of in vitro antioxidant activity tests, the azacyclo-transition metal zinc complex of the present invention has a strong inhibitory effect on DPPH free radicals, and is stronger than the commonly used antioxidant vitamin E at certain low concentrations. And only the test solution of 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) has a certain inhibition effect on DPPH free radicals, but the inhibition effect is obviously weaker and is lower than that of nitrogen heterocyclic transition metal zinc complexes and vitamin E. This shows that the nitrogen heterocyclic ring transition metal zinc complex synthesized by the invention has great superiority only in view of in vitro antioxidant activity. Based on the complex, the complex can be further researched for pharmacological and physiological activities.
Claims (10)
1. A1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex with DPPH free radical inhibiting effect is characterized in that the molecular formula is [ Zn (C)13H15N5)2Cl2](ii) a Wherein, C13H15N5Is ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole), and the molecular structural formula is as follows:
2. the 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex as claimed in claim 1, wherein the preparation method of the ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) comprises the following steps:
(1) mixing 50mmol of benzotriazole with 15mL of water and 15mL of formaldehyde, heating in water bath to 80 ℃, refluxing for 60min, cooling, filtering to obtain a white needle-shaped product, and recrystallizing with ethyl acetate to obtain a white crystal, namely hydroxymethyl benzotriazole;
(2) weighing 25mmol of hydroxymethyl benzotriazole, adding into a single-neck bottle, dropwise adding 12.5mL of thionyl chloride, mixing and stirring for 20min after dropwise adding, and refluxing at 80 ℃ for 180 min; evaporating the residual thionyl chloride by using a rotary evaporator to obtain a yellow white crystal, namely chloromethyl benzotriazole;
(3) dissolving 20mmol of 2-ethyl-4-methylimidazole in 10mL of DMSO (dimethylsulfoxide), adding 40mmol of crushed NaOH, heating to 60 ℃, adding 20mmol of chloromethyl benzotriazole, heating in a water bath at 60 ℃ for 60min, cooling to room temperature, pouring into 50g of ice water, stirring to generate precipitate, performing suction filtration, and washing the precipitate for 3 times by using water to obtain a crude product;
(4) and adding ethyl acetate into the crude product at 78 ℃ for recrystallization to obtain a yellow-white crystal, namely the ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole).
3. The 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex as claimed in claim 2, wherein the content of the element of the ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) is dependent on C13H15N5Meter (%), theoretical value (%): c64.70; h6.27; n29.03; experimental values (%): c64.97; h6.16; n28.87; infrared Spectrum (cm)-1，KBr)：3331(s),3119(w),2978(m),2937(w),2440(w),2249(w),2072(w),1975(m),1936(w),1843(w),1804(w),1675(s),1613(m),1587(s),1555(w),1511(m),1496(m),1472(w),1407(w),1333(m),1296(m),1230(m),1163(m),1091(w),1067(w),972(w),860(w),828(s),752(s),694(w),626(m),568(w),535(w),470(m),432(s)。
4. The 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex as claimed in claim 1, wherein the 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex belongs to a monoclinic system, C2/C space group, and unit cell parameter a is crystal cell parameter a
b is
c is
α is 90 degrees, β is 93.807 degrees, gamma is 90 degrees, and the element content is C26H30N10Cl2Zn meter (%), theoretical value (%): c50.45; h4.88; n22.63; experimental values (%): c50.20; h4.69; and (3) N23.03.
5. The 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex as claimed in claim 1, wherein the infrared spectrum (cm) of the 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex-1，KBr)：3422(s),3119(s),3019(w),2979(w),2361(s),2073(m),1616(m),1484(m),1455(m),1400(s),1288(w),1161(s),1075(s),961(m),860(m),778(w),746(w),615(w),534(s)。
6. The preparation method of the 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex as claimed in claim 1, characterized by comprising the following steps:
(1) accurately weighing 0.02-0.04mmol of zinc chloride, and dissolving in 4-6mL of solvent to obtain a zinc salt solution;
(2) accurately weighing 0.02-0.04mmol of ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) and dissolving in 4-6mL of solvent to obtain a ligand solution;
(3) adding the ligand solution into a zinc salt solution, uniformly mixing, filtering, adding a solvent into the filtrate to 10-12mL, and standing at room temperature until colorless rectangular crystals are precipitated, thus obtaining the zinc phosphate.
7. The preparation method of the 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex as claimed in claim 6, wherein the solvent in steps (1), (2) and (3) is one or a mixture of two of water, methanol, dimethyl sulfoxide and acetonitrile.
8. The preparation method of the 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex according to claim 7, which is characterized by comprising the following steps:
(1) accurately weighing 0.02mmol of zinc chloride, and dissolving in 4mL of methanol to obtain a zinc salt solution;
(2) accurately weighing 0.02mmol of ligand 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) and dissolving in 4mL of methanol to obtain a ligand solution;
(3) adding the ligand solution into a zinc salt solution, uniformly mixing, filtering, adding methanol into the filtrate to 10mL, and standing at room temperature until colorless rectangular crystals are precipitated, thus obtaining the zinc phosphate.
9. An application of the 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex as defined in claim 1 in preparation of a DPPH free radical inhibiting medicine.
10. An application of the 1- (benzotriazole-1-methyl) -1- (2-ethyl-4-methylimidazole) zinc complex as defined in claim 1 in preparing an antioxidant medicament.
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