Reagent for analyzing dimethyl bipyridine molecular isomer and preparation method and analysis method thereof

Abstract

The invention relates to the field of analysis and testing, in particular to a reagent for analyzing dimethyl bipyridine molecular isomers and a preparation method and an analysis method of the reagent. The reagent comprises cyclodextrin, a cobalt ion-containing compound and a solvent; according to the analysis method, the problem that the types of dimethyl bipyridine isomer molecules cannot be analyzed and identified by mass spectrometry, spectral analysis and other methods is solved, and compared with a traditional isomer molecule type analysis technology and method, the analysis method is simple, rapid and accurate, and each isomer in a mixed sample and the content of each isomer can be analyzed; the analysis method disclosed by the invention is small in required sample amount and high in sensitivity, and has a wide application prospect in the fields of pharmacy, scientific research, chemical engineering and the like.

Description

Technical Field

[0001] The invention relates to the field of analysis and testing, and in particular to a reagent for analyzing dimethyl bipyridine molecular isomers and a preparation method and an analysis method thereof. Background Art

[0002] The basic unit of matter is atoms or molecules, and molecules are generally composed of two or more atoms. Each molecule has a special composition and structure. Molecules with the same atomic composition but different molecular structures are called "isomers", and positional isomers are a type of molecular isomers. It refers to a class of molecules in which specific atoms or functional groups in the molecule have different positions in the carbon chain or carbon ring but have the same elemental composition and atomic number. It is one of the common isomers.

[0003] Positional isomers may have significant differences in physical properties, chemical properties or biological activities due to the different arrangements of their atoms. Many isomers of benzene compounds are important intermediates or products in the chemical and pharmaceutical industries. For example, xylene has three positional isomers: o-xylene (o-xylene), m-xylene (m-xylene) and p-xylene (p-xylene). o-xylene and m-xylene are liquids at room temperature, while p-xylene is solid at room temperature. In addition, the products of the three xylenes in substitution reactions are quite different: the two methyl groups of o-xylene are located in adjacent positions of the benzene ring, and are more likely to produce ortho-substituted products; the two methyl groups of m-xylene are located in the middle position of the benzene ring, and are more likely to produce meta-substituted products; the two methyl groups of p-xylene are located in the symmetrical position of the benzene ring, and are more likely to produce para-substituted products. Therefore, identifying and separating these three positional isomers is very important in chemical production. However, positional isomers usually have similar physical and chemical properties, and it is often difficult to distinguish and separate them using traditional methods. Developing a method to effectively separate and identify molecular positional isomers has important application value.

[0004] So far, the main methods for separating and detecting positional isomers include liquid chromatography (HPLC), gas chromatography (GC), nuclear magnetic resonance (NMR), mass spectrometry (MS), etc., among which mass spectrometry is a powerful technology that can provide molecular mass and structural information. In mass spectrometry analysis, by converting molecules in the sample into ions and separating them in an electric field or a magnetic field, mass spectrometry can provide information about molecular mass and molecular dissociation fragments, but it has limited effect on special molecules such as isomers with exactly the same mass-to-charge ratio and very similar dissociation fragments. The emergence of ion mobility-mass spectrometry (IMS MS) technology developed in recent years has made up for this weakness of mass spectrometry technology to a certain extent. Ion mobility mass spectrometry is an advanced technology that combines ion migration time and mass spectrometry analysis. It provides spatial resolution and structural information on ion structure and mass by measuring ion migration time during ion migration and combining it with traditional mass spectrometry analysis. Its working principle is as follows: first, the sample ions are generated by the ion source, and then these ions are introduced into the ion drift tube, which is a region with an electric field. In this region, the ions will be accelerated by the electric field and collide with buffer gases, such as nitrogen and argon. Since different ions have different collision cross sections, the ions will be separated by size and shape. Finally, the mass analyzer separates and detects the ions in the order of mass-to-charge ratio to generate a mass spectrum. According to the drift time and mass-to-charge ratio of the ions, an ion mobility mass spectrum can be obtained, which can reflect the charge, mass and molecular spatial structure information. However, at present, the structural resolution of ion mobility mass spectrometry technology is not high. For small molecules and substances with small differences in molecular structure, such as chiral compounds and isomers, it is still difficult for ion mobility mass spectrometry to directly identify their structural differences.

[0005] 4,4'-dimethyl-2,2'-bipyridine (4,4'-DMDP) and 6,6'-dimethyl-2,2'-bipyridine (6,6'-DMDP) are two different positional isomers, and the two different positional isomers are used in different fields. For example, 4,4'-DMDP is an important pharmaceutical intermediate. Omer Tamer et al. used 4,4'-DMDP to synthesize an important DNA reagent, while 6,6'-DMDP is an important proton receptor. Magdalena Rok et al. used 6,6'-DMDP as a proton receptor to synthesize a molecular complex. In this case, the identification and separation of these two isomers and other isomers have become very important in scientific research and practical applications. However, these isomers have similar physical and chemical properties, and it is difficult to correctly distinguish them using traditional separation and recognition techniques. Therefore, it is of great significance to develop a novel isomer recognition method. Summary of the invention

[0006] The purpose of the present invention is to provide a reagent and a preparation method and an analysis method thereof for high-sensitivity, rapid and accurate analysis and identification of several dimethyl bipyridine isomer molecules in view of the deficiencies in the prior art.

[0007] To achieve the above object, the technical solution adopted by the present invention is:

[0008] The first aspect of the present invention is to provide a reagent for analyzing dimethylbipyridine molecular isomers, comprising: cyclodextrin, a cobalt ion-containing compound and a solvent.

[0009] Preferably, the solvent includes: deionized water and an organic reagent.

[0010] More preferably, the organic reagent comprises at least one of methanol, ethanol, acetonitrile, ether, acetone, formic acid and acetic acid.

[0011] Preferably, the cyclodextrin includes at least one of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, α-cyclodextrin derivatives, β-cyclodextrin derivatives, and γ-cyclodextrin derivatives.

[0012] Preferably, the cobalt ion-containing compound comprises at least one of a salt containing divalent cobalt ions, a base containing divalent cobalt ions, and a complex containing divalent cobalt ions.

[0013] The second aspect of the present invention is to provide a method for preparing the above reagent, the steps comprising: weighing cyclodextrin and a cobalt ion compound, mixing them, and dissolving them in a solvent to obtain the reagent.

[0014] The third aspect of the present invention is to provide a method for analyzing dimethyl bipyridine molecular isomers, the steps comprising:

[0015] S1, mixing the dimethyl bipyridine molecular sample with the above reagent to prepare a test solution;

[0016] S2. Treat the test solution with an ionization device to generate complex gas-phase ions, and then measure the ion mobility or ion collision cross section of the complex gas-phase ions to distinguish the isomers of xylene bipyridine.

[0017] Preferably, in the test solution, the concentration of cyclodextrin molecules is 10 -10 mol / L-1mol / L; the concentration of cobalt ion compound is 10 -10 mol / L-1mol / L; the concentration of dimethylbenzene bipyridine molecules is 10 -10 mol / L-1mol / L.

[0018] Preferably, in step S1, the positional isomers in the dimethylbipyridine molecular sample include at least one of 4,4'-dimethyl-2,2'-bipyridine and 6,6'-dimethyl-2,2'-bipyridine.

[0019] Preferably, in step S2, the ionization device comprises: an electrospray ionization ion source, a matrix-assisted laser desorption ionization ion source, or a DESI ion source.

[0020] The present invention adopts the above technical solution, and has the following technical effects compared with the prior art:

[0021] The analysis method of the present invention overcomes the difficulty that mass spectrometry, spectral analysis and other methods are unable to analyze and identify the molecular types of dimethylbipyridine isomers. Compared with traditional isomer molecular type analysis techniques and methods, the analysis method of the present invention is simple, rapid and accurate, and can analyze each isomer and its content in a mixed sample; the analysis method of the present invention requires a small amount of sample and has high sensitivity, and has broad application prospects in the fields of pharmaceuticals, scientific research, chemical industry, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is a diagram of the molecular types and chemical structures of dimethylbipyridine.

[0023] Figure 2 is the ion mobility spectrometry (IMS) experimental result of dimethyl bipyridine molecular isomer complex; where a is the + ions; b is the ion mobility spectrometry results of the complex ions produced by γ-cyclodextrin and Co + Ion mobility spectrometry results of complex ions produced by ions.

[0024] Figure 3 The experimental results are for the quantitative analysis of two dimethylbipyridine molecular isomers in a mixture sample. DETAILED DESCRIPTION

[0025] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0026] It should be noted that, in the absence of conflict, the embodiments of the present invention and the features in the embodiments may be combined with each other.

[0027] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments, but they are not intended to limit the present invention.

[0028] Example

[0029] This embodiment provides a method for analyzing dimethyl bipyridine molecular isomers, the steps comprising:

[0030] S1. Weigh 4,4-DMDP, 6,6-DMDP, cobalt chloride (CoCl2) and γ-cyclodextrin (γ-CD), dissolve 4,4-DMDP, 6,6-DMDP, CoCl2 and γ-CD in a mixed solution of methanol and water (methanol: water = 1:1) to prepare a mother solution with a concentration of 1 mmol / L; after the preparation is completed, take 10 μL of 4,4-DMDP mother solution, 6,6-DMDP mother solution, CoCl2 mother solution and γ-CD mother solution, add the mixed solution of methanol and water to dilute to 10 -5 mol / L and mix well to obtain the test solution;

[0031] S2, using electrospray ionization-trapped ion mobility spectrometry time-of-flight mass spectrometer (TIMS TOF MS, BrukerDaltonik, Germany) to ionize the test solution to produce [4,4-DMDP+γ-CD+Co] + 、[6,6-DMDP+γ-CD+Co] + The complex gas phase ions are measured by measuring the ion mobility or ion collision cross section of the complex gas phase ions, so as to obtain the types of dimethylbipyridine isomers contained in the test solution.

[0032] The analysis results are as follows Figure 2-3 As shown, different dimethylbipyridine isomers were clearly distinguished.

[0033] In summary, the analysis method of the present invention overcomes the difficulty that mass spectrometry, spectral analysis and other methods cannot analyze and identify the molecular types of dimethylbipyridine isomers. Compared with traditional isomer molecular type analysis techniques and methods, the analysis method of the present invention is simple, rapid and accurate, and can analyze each isomer and its content in a mixed sample; the analysis method of the present invention requires a small amount of sample and has high sensitivity, and has broad application prospects in the fields of pharmaceuticals, scientific research, chemical industry, etc.

[0034] The above description is only a preferred embodiment of the present invention, and does not limit the implementation mode and protection scope of the present invention. For those skilled in the art, it should be aware that all solutions obtained by equivalent substitutions and obvious changes made using the description and illustrations of the present invention should be included in the protection scope of the present invention.

Claims

1. A reagent for analyzing dimethyl bipyridine molecular isomers, characterized in that: include: Cyclodextrin, a cobalt ion-containing compound, and a solvent.

2. The reagent according to claim 1, characterized in that The solvent includes: deionized water and an organic reagent.

3. The reagent according to claim 2, characterized in that The organic reagent includes at least one of methanol, ethanol, acetonitrile, ether, acetone, formic acid and acetic acid.

4. The reagent according to claim 1, characterized in that The cyclodextrin includes at least one of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, α-cyclodextrin derivatives, β-cyclodextrin derivatives, and γ-cyclodextrin derivatives.

5. The reagent according to claim 1, characterized in that The cobalt ion-containing compound includes at least one of a salt containing divalent cobalt ions, a base containing divalent cobalt ions, and a complex containing divalent cobalt ions.

6. A method for preparing the reagent according to claims 1-5, characterized in that: The steps include: The reagent is obtained by weighing cyclodextrin and a cobalt ion compound, mixing them, and dissolving them in a solvent.

7. A method for analyzing dimethyl bipyridine molecular isomers, characterized in that the steps include: S1. Mixing a dimethyl bipyridine molecular sample with a reagent according to any one of claims 1 to 5 to prepare a test solution; S2. Treating the test solution with an ionization device to generate composite gas-phase ions, and then measuring the ion mobility or ion collision cross section of the composite gas-phase ions to distinguish the isomers of xylene bipyridine.

8. The analysis method according to claim 7, characterized in that In the test solution, the concentration of cyclodextrin molecules is 10 -10 mol / L-1mol / L; the concentration of cobalt ion compound is 10 -10 mol / L-1mol / L; the concentration of dimethylbenzene bipyridine molecules is 10 -10 mol / L-1mol / L.

9. The analysis method according to claim 7, characterized in that In step S2, the positional isomers in the dimethyl bipyridine molecular sample include at least one of 4,4'-dimethyl-2,2'-bipyridine and 6,6'-dimethyl-2,2'-bipyridine.

10. The analysis method according to claim 7, characterized in that In step S2, the ionization device includes: an electrospray ionization ion source, a matrix-assisted laser desorption ionization ion source, and a DESI ion source.

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