CN108774252B - 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) zinc complex and preparation method thereof - Google Patents
1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) 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
- LLPKQRMDOFYSGZ-UHFFFAOYSA-N 2,5-dimethyl-1h-imidazole Chemical compound CC1=CN=C(C)N1 LLPKQRMDOFYSGZ-UHFFFAOYSA-N 0.000 claims abstract description 54
- 239000003446 ligand Substances 0.000 claims abstract description 40
- 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 12
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 10
- 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 claims abstract description 9
- 239000003814 drug Substances 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
- 229940079593 drug Drugs 0.000 claims abstract description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- 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
- 239000000243 solution Substances 0.000 claims description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 16
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- 238000005303 weighing Methods 0.000 claims description 15
- -1 DPPH free radical Chemical class 0.000 claims description 14
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- 150000003254 radicals Chemical class 0.000 claims description 13
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 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
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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
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 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
- 239000002244 precipitate Substances 0.000 claims description 6
- 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
- 238000002329 infrared spectrum Methods 0.000 claims description 5
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 claims description 3
- 239000012964 benzotriazole Substances 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
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- 239000000047 product Substances 0.000 claims description 3
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- 230000001419 dependent effect Effects 0.000 claims description 2
- 238000001228 spectrum Methods 0.000 claims 1
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- 229930003427 Vitamin E Natural products 0.000 abstract description 10
- 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 10
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- 230000002000 scavenging effect Effects 0.000 abstract description 4
- 230000003064 anti-oxidating effect Effects 0.000 abstract description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 16
- 229910052725 zinc Inorganic materials 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
- 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 12
- 229910052723 transition metal Inorganic materials 0.000 description 9
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- 238000000034 method Methods 0.000 description 7
- 150000003624 transition metals Chemical class 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 5
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- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 4
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- XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 2
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 2
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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
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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Abstract
The invention discloses a 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) zinc complex and a preparation method and application thereof, wherein the molecular formula of the complex is [ Zn (C)12H13N5)2Cl2](ii) a Wherein, C12H13N5Is ligand 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole). The 1- (benzotriazole-1-methyl) -1- (2, 4-dimethylimidazole) zinc complex is prepared by taking 1- (benzotriazole-1-methyl) -1- (2, 4-dimethylimidazole) as a ligand and reacting with zinc chloride, has a stronger scavenging effect on DPPH free radicals, is higher than the scavenging effect on DPPH free radicals by independently using 1- (benzotriazole-1-methyl) -1- (2, 4-dimethylimidazole), and is also stronger than a commonly used antioxidant vitamin E. The results show that the 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) zinc complex has good antioxidation and is an innovation in antioxidant medicines.
Description
Technical Field
The invention relates to a 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) zinc complex, a preparation method and application thereof, and belongs to the technical field of medicines.
Background
The rise of free radical biology in recent years makes people have new understanding on body pathological changes and cell aging. Radical biology mainly explores the composition, clearance and damage of free radicals to biological systems. A series of disease mechanisms caused by free radicals, such as atheroma, neurodegeneration, chronic depression, cancer and physiological aging, are now well established. Antioxidants are used in the food industry for inhibiting the oxidation of free radicals in order to retard or prevent the oxidation process of substances.
At present, the method for measuring the oxidation resistance is a DPPH colorimetric method. DPPH free radical is a stable organic free radical, when a free radical scavenger is added to DPPH free radical solution, lone pair electrons are paired, the deep purple DPPH free radical is reduced to yellow DPPH-H non-free radical form, the fading degree of the DPPH free radical is in direct proportion to the antioxidant activity of the substance to be detected, and therefore the DPPH free radical is often used for detecting the antioxidant activity of the substance in a laboratory.
The nitrogen-containing heterocyclic compound has a unique structure and strong biological activity, and has great application value in the fields of medicines, pesticides, materials and the like. In the process of generating the complex, the nitrogen-containing heterocycle can give electrons and is reassembled with various metal ions to form the metal complex with a relatively stable structure.
The metal coordination compound is a compound with complex structure and special function, which is very important in the application of medicine, material, cosmetics and the like. The biological activity of the nitrogen heterocyclic metal complex is mainly embodied in the aspects of antibiosis, anticancer, diabetes, DNA cracking, DNA connection and the like. In recent years, studies on zinc complexes as antioxidants have attracted attention from a large number of researchers. It is known that zinc is an essential trace element in the human body and has many pharmacological and physiological activities. The supplement of most zinc has low absorptivity and high toxicity, and the single use of the nitrogenous heterocycle has low oxidation resistance. Therefore, the zinc complex generated by combining zinc and nitrogen-containing heterocycle is expected to develop a new antioxidant drug with high efficiency and low toxicity.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide the 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) zinc complex, and 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, 4-dimethyl imidazole) zinc complex with molecular formula of [ Zn (C)12H13N5)2Cl2](ii) a Wherein, C12H13N5Is ligand 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole), and the molecular structural formula is as follows:
the preparation method of the ligand 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) 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, 4-dimethylimidazole in 10mL of DMSO, 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 with water for 3 times 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, 4-dimethyl imidazole).
A preparation method of 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) 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, 4-dimethyl imidazole), 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, ethanol and dimethyl sulfoxide.
An application of 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) zinc complex in inhibiting DPPH free radical.
An application of 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) zinc complex in preparing antioxidant drugs.
The invention has the beneficial effects that:
1. according to the invention, 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) is used as a ligand to react with zinc chloride to prepare the 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) zinc complex, the complex is a mononuclear complex, and zinc ions are in four coordination and are respectively coordinated with two nitrogen atoms and two chloride ions on two ligands 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole), 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, 4-dimethyl imidazole) 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, 4-dimethyl imidazole) on DPPH free radicals which is singly used, and is also stronger than the commonly used antioxidant vitamin E. The results show that the 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) zinc complex has good antioxidation and is an innovation in antioxidant medicines.
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) ]12H13N5)2Cl2]Structural unit diagram (2).
FIG. 2 shows a complex [ Zn (C) ]12H13N5)2Cl2]The stacked graph of (1).
FIG. 3 is a graph showing the trend of the DPPH radical scavenging rate of the same concentration (0.5mg/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 (1mg/mL) of zinc complex, ligand and vitamin E.
FIG. 5 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, 4-dimethyl imidazole) 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, 4-dimethylimidazole in 10mL of DMSO, 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 with water for 3 times 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, 4-dimethyl imidazole).
The content of the prepared ligand 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) element is dependent on C12H13N5Meter (%), theoretical value (%): c63.41; h5.76; n30.82; experimental values (%): c63.21; h5.82; and (6) N30.97. Infrared Spectrum (cm)-1，KBr)：3406(s),3094(w),3068(w),2963(w),2915(w),2419(s),2072(m),1919(w),1674(s),1596(m),1552(m),1496(w),1453(m),1394(w),1357(w),1289(m),1190(w),1008(w),965(m),806(w),729(w),716(m),691(w),659(m),629(w),530(s),431(w)。
Example 2
The preparation method of the 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) 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, 4-dimethyl imidazole), 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 good crystal form is selected, an X-ray diffraction experiment is carried out on an Xcalibur, Gemini CCD single crystal diffractometer, Mo-k alpha ray position (lambda is 0.71073A) which is monochromatically changed by graphite 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 transition metal zinc complex is shown in figures 1 and 2, the complex belongs to a monoclinic system, C1 space group, and the unit cell parameter a is
b is
c is
Alpha is 90 deg., beta is 93.994(2) °, gamma is 90 deg., and volume V is
Z is 4 and the density is 1.482Mg m-3Theta is 3.8620to 26.5320 DEG, the limiting factors are-11-h 11, -14-k 14, -30-l 21, F (000) is 1216, R1＝0.0353，wR20.0745. The element content is according to C24H26N10Cl2Zn meter (%), theoretical value (%): c48.78; h4.44; n23.71; experimental values (%): c49.10; h4.60; n23.60.
Infrared Spectrum (cm)-1，KBr)：3422(s),3116(m),2361(s),2072(m),1615(w),1595(w),1493(m),1451(w),1398(s),1369(m),1304(w),1288(w),1271(w),1196(w),1157(s),1075(m),959(m),861(m),822(w,781(w),743(m),703(w),675(w),659(w),630(w),534(s)。
Example 3
The preparation method of the 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) 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, 4-dimethyl imidazole), 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, C1 space group, and the unit cell parameter a is
b is
c is
Alpha is 90 deg., beta is 93.994(2) °, gamma is 90 deg., and volume V is
Z is 4 and the density is 1.482Mg m-3Theta is 3.8620to 26.5320 DEG, the limiting factors are-11-h 11, -14-k 14, -30-l 21, F (000) is 1216, R1＝0.0353，wR20.0745. The element content is according to C24H26N10Cl2Zn meter (%), theoretical value (%): c48.78; h4.44; n23.71; experimental values (%): c49.10; h4.60; n23.60.
Infrared Spectrum (cm)-1，KBr)：3422(s),3116(m),2361(s),2072(m),1615(w),1595(w),1493(m),1451(w),1398(s),1369(m),1304(w),1288(w),1271(w),1196(w),1157(s),1075(m),959(m),861(m),822(w,781(w),743(m),703(w),675(w),659(w),630(w),534(s)。
Example 4
The preparation method of the 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) 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, 4-dimethyl imidazole), and dissolving in a mixed solution of 4mL of methanol and 2mL of ethanol 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 ring transition metal zinc complex is shown in figures 1 and 2, and the complex belongs to a monoclinic systemC1 space group, cell parameter a is
b is
c is
Alpha is 90 deg., beta is 93.994(2) °, gamma is 90 deg., and volume V is
Z is 4 and the density is 1.482Mg m-3Theta is 3.8620to 26.5320 DEG, the limiting factors are-11-h 11, -14-k 14, -30-l 21, F (000) is 1216, R1＝0.0353，wR20.0745. The element content is according to C24H26N10Cl2Zn meter (%), theoretical value (%): c48.78; h4.44; n23.71; experimental values (%): c49.10; h4.60; n23.60.
Infrared Spectrum (cm)-1，KBr)：3422(s),3116(m),2361(s),2072(m),1615(w),1595(w),1493(m),1451(w),1398(s),1369(m),1304(w),1288(w),1271(w),1196(w),1157(s),1075(m),959(m),861(m),822(w,781(w),743(m),703(w),675(w),659(w),630(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 6 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 AiValue (blank to correct absorbance before measuring absorbance).
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 radical inhibitory activity of the complexes, ligands and vitamin E of the present invention is shown in the following table.
Table 1: DPPH radical scavenging efficiency (in%)
The trend of the same concentration of zinc complex, ligand and vitamin E in the elimination of DPPH radicals is plotted, and the results are shown in fig. 3 and 4. As can be seen from fig. 3 and 4, at the same concentration, the DPPH radical clearance rate of the zinc complex and the ligand tends to increase with time, while the vitamin E tends to be relatively stable, and at the same concentration, the DPPH radical clearance rate of the zinc complex is greater than that of the vitamin E and is far greater than that of the ligand 1- (benzotriazole-1-methyl) -1- (2, 4-dimethylimidazole).
The DPPH radical clearance for each compound at 6.5h is plotted as a bar graph, and the results are shown in FIG. 5. As shown in FIG. 5, from the results of in vitro antioxidant activity tests, the azacyclo-transition metal zinc complex of the present invention has a stronger inhibitory effect on DPPH free radicals, and is stronger than the commonly used antioxidant vitamin E at the same concentration. And only the test solution of 1- (benzotriazole-1-methyl) -1- (2, 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 (9)
1. A1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) zinc complex with DPPH free radical inhibiting effect is characterized in that the molecular formula is [ Zn (C)12H13N5)2Cl2](ii) a Wherein, C12H13N5Is ligand 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole), and the molecular structural formula is as follows:
the 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) zinc complex belongs to a monoclinic system, C1 space group and unit cell parameter a is
b is
c is
Alpha is 90 degrees, beta is 93.994(2) degrees, and gamma is 90 degrees; the element content is according to C24H26N10Cl2Zn meter (%), theoretical value (%): c48.78; h4.44; n23.71; experimental values (%): c49.10; h4.60; n23.60.
2. The 1- (benzotriazole-1-methyl) -1- (2, 4-dimethylimidazole) zinc complex as claimed in claim 1, wherein the preparation method of the ligand 1- (benzotriazole-1-methyl) -1- (2, 4-dimethylimidazole) 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, 4-dimethylimidazole in 10mL of DMSO, 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 with water for 3 times 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, 4-dimethyl imidazole).
3. The 1- (benzotriazole-1-methyl) -1- (2, 4-dimethylimidazole) zinc complex as claimed in claim 2, wherein the content of the element of the ligand 1- (benzotriazole-1-methyl) -1- (2, 4-dimethylimidazole) is dependent on C12H13N5Meter (%), theoretical value (%): c63.41; h5.76; n30.82; experimental values (%): c63.21; h5.82; n30.97; infrared Spectrum (cm)-1，KBr)：3406(s),3094(w),3068(w),2963(w),2915(w),2419(s),2072(m),1919(w),1674(s),1596(m),1552(m),1496(w),1453(m),1394(w),1357(w),1289(m),1190(w),1008(w),965(m),806(w),729(w),716(m),691(w),659(m),629(w),530(s),431(w)。
4. The 1- (benzotriazole-1-methyl) -1- (2, 4-dimethylimidazole) zinc complex according to claim 1, which is characterized in thatInfrared spectrum (cm) of 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) zinc complex-1，KBr)：3422(s),3116(m),2361(s),2072(m),1615(w),1595(w),1493(m),1451(w),1398(s),1369(m),1304(w),1288(w),1271(w),1196(w),1157(s),1075(m),959(m),861(m),822(w,781(w),743(m),703(w),675(w),659(w),630(w),534(s)。
5. A preparation method of the 1- (benzotriazole-1-methyl) -1- (2, 4-dimethylimidazole) zinc complex as claimed in any one of claims 1 to 4, which is 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, 4-dimethyl imidazole), 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.
6. The preparation method of the 1- (benzotriazole-1-methyl) -1- (2, 4-dimethylimidazole) zinc complex according to claim 5, wherein the solvent in the steps (1), (2) and (3) is one or a mixture of two of water, methanol, ethanol and dimethyl sulfoxide.
7. The preparation method of the 1- (benzotriazole-1-methyl) -1- (2, 4-dimethylimidazole) zinc complex according to claim 6, 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, 4-dimethyl imidazole), 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.
8. An application of the 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) zinc complex as defined in claim 1 in preparation of medicines for inhibiting DPPH free radicals.
9. An application of the 1- (benzotriazole-1-methyl) -1- (2, 4-dimethyl imidazole) zinc complex as defined in claim 1 in preparing antioxidant drugs.
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| CN106188103A (en) * | 2016-07-14 | 2016-12-07 | 河南中医学院 | A kind of azacyclo-transition metal copper complex containing multiple coordination sites, preparation method and application |
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| CN106188103A (en) * | 2016-07-14 | 2016-12-07 | 河南中医学院 | A kind of azacyclo-transition metal copper complex containing multiple coordination sites, preparation method and application |
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| Title |
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| Bis{1-[(1H-benzotriazol-1-yl)methyl]-2-methyl-1H-imdazole-κN3}dichloride-zinc;Haiyan Yang等;《Acta Crystallographica Section E》;20121231;第E68卷;第m819,sup1-10页 * |
| Synthesis, crystal structures, and biological activities of silver(I) and cobalt(II) complexes with anazole derivative ligand;Chang-Xue An等;《Transition Met Chem》;20080711;第33卷;第835-841页 * |
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