阅读说明：本技术 一种含多个配位点的NNO型喹啉Fe(II)配合物及其制备方法和应用 (NNO type quinoline Fe (II) complex containing multiple coordination sites and preparation method and application thereof ) 是由 苑娟 杨欢欢 曾岱 邢爱萍 褚意新 万焱 李恺昊 兰海荣 于 2020-07-23 设计创作，主要内容包括：本发明公开了一种含多个配位点的NNO型喹啉Fe(II)配合物及其制备方法和应用,该配合物为喹啉-2-甲醛-苯甲酰腙Fe(II)配合物,分子式为Fe(C<Sub>17</Sub>H<Sub>12</Sub>ON<Sub>3</Sub>)<Sub>2</Sub>。本发明以含三个配位点的NNO型喹啉-2-甲醛-苯甲酰腙作为螯合配体,以Fe(II)作为中心金属离子,通过溶液中的自组装反应制备NNO型喹啉Fe(II)配合物,有效解决了新型喹啉类衍生物作为配体,与过渡金属Fe(II)结合的问题。本发明制备的喹啉-2-甲醛-苯甲酰腙Fe(II)配合物,对DPPH自由基具有较强的清除作用,清除率远远高于维生素E和对照例的喹啉铁(II)配合物。该实验表明,本发明配合物具有优异的体外抗氧化作用,可有效用于制备抗衰老药物,有望进一步研究药理和生理活性。(The invention discloses an NNO type quinoline Fe (II) complex containing multiple coordination sites, a preparation method and an application thereof, wherein the complex is a quinoline-2-formaldehyde-benzoyl hydrazone Fe (II) complex, and the molecular formula is Fe (C) 17 H 12 ON 3 ) 2 . The NNO type quinoline Fe (II) complex is prepared by taking NNO type quinoline-2-formaldehyde-benzoyl hydrazone containing three coordination sites as a chelating ligand and taking Fe (II) as a central metal ion through self-assembly reaction in a solution, so that the problem that a novel quinoline derivative is taken as a ligand and combined with a transition metal Fe (II) is effectively solved. The quinoline-2-formaldehyde-benzoyl hydrazone Fe (II) complex prepared by the invention has stronger scavenging effect on DPPH free radicals, and the scavenging rate is far higher than that of vitamin E and quinoline iron (II) complexes prepared by a comparison example. The experiment shows that the complex has excellent in-vitro antioxidant effect and can be effectively used for preparing anti-aging medicamentsAnd is expected to further research the pharmacological and physiological activities.)

1. The NNO type quinoline Fe (II) complex containing multiple coordination sites is characterized in that the NNO type quinoline Fe (II) complex is a quinoline-2-formaldehyde-benzoyl hydrazone Fe (II) complex, and the molecular formula of the complex is Fe (C)₁₇H₁₂ON₃)₂(ii) a Wherein, C₁₇H₁₂ON₃Is ligand quinoline-2-formaldehyde-benzoyl hydrazone, and the molecular structural formula is as follows:

2. the NNO quinoline fe (ii) complex as claimed in claim 1 wherein the NNO quinoline fe (ii) complex belongs to the triclinic system, P-1 space group, and has the unit cell parameter of

3. The NNO-type quinoline fe (ii) complex as claimed in claim 1 wherein the process for the preparation of the ligand quinoline-2-carboxaldehyde-benzoylhydrazone comprises the steps of:

(1) respectively dissolving 1mmol of quinoline-2-formaldehyde and 1mmol of benzoyl hydrazine in methanol, then mixing, dropwise adding 2 drops of glacial acetic acid, and carrying out reflux reaction for 2 hours to obtain light yellow clarified liquid;

(2) concentrating the yellowish clear solution under reduced pressure to separate out precipitate, and performing suction filtration to obtain a crude product;

(3) washing the crude product with diethyl ether to obtain white powder, namely the ligand quinoline-2-formaldehyde-benzoyl hydrazone.

4. A process for the preparation of NNO-type quinoline fe (ii) complexes as claimed in any one of claims 1 to 3, characterized in that it comprises the following steps:

(1) dissolving a ligand quinoline-2-formaldehyde-benzoyl hydrazone in methanol, and adding sodium hydroxide to obtain a ligand solution;

(2) dissolving ferrous perchlorate hydrate in methanol to obtain Fe (II) salt solution;

(3) and filtering the ligand solution and the Fe (II) salt solution, mixing and sealing, and carrying out mutual diffusion reaction at room temperature until a gray flaky crystal is separated out, namely the NNO type quinoline Fe (II) complex.

5. The process for the preparation of NNO-type quinoline fe (ii) complexes as claimed in claim 4 wherein the molar ratio of the ligand quinoline-2-carboxaldehyde-benzoylhydrazone, sodium hydroxide and ferrous perchlorate hydrate is 2: 2: 1.

6. use of a quinoline fe (ii) complex of NNO type according to any one of claims 1 to 3 for scavenging DPPH radicals.

7. Use of an NNO-type quinoline fe (ii) complex as claimed in any one of claims 1 to 3 for the preparation of a medicament for scavenging DPPH radicals.

8. Use of the NNO-type quinoline fe (ii) complex as claimed in any one of claims 1 to 3 for the preparation of an antioxidant medicament.

9. Use of the NNO-type quinoline fe (ii) complex as claimed in any one of claims 1 to 3 for the preparation of an anti-ageing drug.

Technical Field

The invention relates to an NNO type quinoline Fe (II) complex containing multiple coordination sites, a preparation method and application thereof, and belongs to the field of medicines.

Background

Free radicals are in dynamic equilibrium with continuous generation and continuous removal throughout the life activities of human beings. Free radicals in the body can cause damage to other biomolecules such as DNA, lipids, proteins and the like, thereby further causing diseases such as senile dementia, Parkinson's disease, craniocerebral injury, heart disease, cancer and the like. Because of its unique efficacy, the antioxidant can rapidly and effectively remove free radicals, and can achieve the purposes of delaying human aging and preventing certain diseases, thereby attracting a large number of researchers to research the antioxidant.

N heterocycles are a class of important compounds with a variety of biological activities, such as: antioxidation, antitumor, anti-inflammatory, etc. It has been reported in the literature that quinoline compounds, which are one of the N-heterocyclic compounds (partial derivatives synthesized with a quinoline ring as a skeleton), exhibit excellent antitumor activity as tyrosine kinase (EGFR) inhibitors, c-MET inhibitors, Tubulin polymerization (Tubulin) inhibitors, and the like. After forming a complex with the transition metal ions, the complex can improve the inhibition effect on tumor cells and enhance the biological activity. In addition, many transition metal complexes such as Cu (II), Zn (II) and the like have obvious antioxidant activity. Iron is an important trace element in a living body, and the deficiency of iron in cells can cause anemia, diabetes, heart disease, damage to the kidney and liver and the like; many neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease are directly related to abnormal Fe (II) concentration. Therefore, the successful synthesis of the novel quinoline derivatives and the construction of the metal Fe (II) complexes thereof are effective ways for finding safe and efficient antioxidants.

Disclosure of Invention

In order to solve the problems, the invention aims to provide an NNO type quinoline Fe (II) complex containing multiple coordination sites, a preparation method and an application thereof.

In order to achieve the above object, one of the technical solutions of the present invention is:

an NNO type quinoline Fe (II) complex containing a plurality of coordination sites, which is a quinoline-2-formaldehyde-benzoyl hydrazone Fe (II) complex with a molecular formula of Fe (C)₁₇H₁₂ON₃)₂(ii) a Wherein, C₁₇H₁₂ON₃Is ligand quinoline-2-formaldehyde-benzoyl hydrazone, and the molecular structural formula is as follows:

the NNO type quinoline Fe (II) complex belongs to a triclinic system, a P-1 space group and has the unit cell parameter of α＝80.548(7)°，β＝70.866(10)°，γ＝88.424(8)°，

The preparation method of the ligand quinoline-2-formaldehyde-benzoyl hydrazone comprises the following steps:

(1) respectively dissolving 1mmol of quinoline-2-formaldehyde and 1mmol of benzoyl hydrazine in methanol, then mixing, dropwise adding 2 drops of glacial acetic acid, and carrying out reflux reaction for 2 hours to obtain light yellow clarified liquid;

(2) concentrating the yellowish clear solution under reduced pressure to separate out precipitate, and performing suction filtration to obtain a crude product;

(3) washing the crude product with diethyl ether to obtain white powder, namely the ligand quinoline-2-formaldehyde-benzoyl hydrazone.

One of the technical schemes of the invention is as follows: a preparation method of an NNO type quinoline Fe (II) complex comprises the following steps:

(1) dissolving a ligand quinoline-2-formaldehyde-benzoyl hydrazone in methanol, and adding sodium hydroxide to obtain a ligand solution;

(2) dissolving ferrous perchlorate hydrate in methanol to obtain Fe (II) salt solution;

(3) and filtering the ligand solution and the Fe (II) salt solution, mixing and sealing, and carrying out mutual diffusion reaction at room temperature until a gray flaky crystal is separated out, namely the NNO type quinoline Fe (II) complex.

The mol ratio of the ligand quinoline-2-formaldehyde-benzoyl hydrazone to the sodium hydroxide to the ferrous perchlorate hydrate is 2: 2: 1.

one of the technical schemes of the invention is as follows: application of NNO type quinoline Fe (II) complex in scavenging DPPH free radicals.

One of the technical schemes of the invention is as follows: application of NNO type quinoline Fe (II) complex in preparation of medicine for eliminating DPPH free radical.

One of the technical schemes of the invention is as follows: an application of NNO type quinoline Fe (II) complex in preparing antioxidant drugs.

One of the technical schemes of the invention is as follows: an application of NNO type quinoline Fe (II) complex in preparing anti-aging drugs.

The invention has the beneficial effects that:

1. the NNO type quinoline Fe (II) complex is prepared by taking NNO type quinoline-2-formaldehyde-benzoyl hydrazone containing three coordination sites as a chelating ligand and taking Fe (II) as a central metal ion through self-assembly reaction in a solution, so that the problem that a novel quinoline derivative is taken as a ligand and combined with a transition metal Fe (II) is effectively solved.

2. The quinoline-2-formaldehyde-benzoyl hydrazone Fe (II) complex prepared by the invention has stronger scavenging effect on DPPH free radicals, and the scavenging rate is far higher than that of vitamin E and quinoline iron (II) complexes prepared by a comparison example. The experiment shows that the complex has excellent in-vitro anti-oxidation effect.

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 is an infrared result chart of the ligand quinoline-2-formaldehyde-benzoylhydrazone of the present invention.

FIG. 2 shows the complex Fe (C) of the present invention₁₇H₁₂ON₃)₂Infrared result graph of (1).

FIG. 3 shows the complex Fe (C) of the present invention₁₇H₁₂ON₃)₂The main molecule of (1) is a structural diagram.

FIG. 4 shows the complex Fe (C) of the present invention₁₇H₁₂ON₃)₂The stacked graph of (1).

FIG. 5 shows the complex [ Fe (C) ] of comparative example₁₄H₁₁N₅)₂]^.BF₄ ^.CH₃OH^.3H₂Structure of main molecule of O.

FIG. 6 is a line graph showing the DPPH radical clearance rate of vitamin E in the ligands, complexes and controls of the present invention.

Detailed Description

The following examples further illustrate the embodiments of the present invention in detail.