CN112824888B - Analytical reagent and method for aminobenzenesulfonic acid positional isomer based on beta cyclodextrin - Google Patents

Abstract

The present invention relates to an analysis reagent based on sulfanilic acid positional isomers of beta cyclodextrin. ionic compounds. The method for analyzing the structure of different position isomers of aminobenzenesulfonic acid provided by the invention is simple, does not require pre-resolving or derivatization of the aminobenzenesulfonic acid molecule, and the chemical samples used are easy to obtain, cheap and non-toxic It is harmless and has many advantages compared to the currently commonly used methods.

Description

A kind of analytical reagent and method of aminobenzenesulfonic acid positional isomer based on beta cyclodextrin

technical field

The invention relates to the technical field of analysis and testing, in particular to an analysis reagent and method for the positional isomers of aminobenzenesulfonic acid based on beta cyclodextrin.

Background technique

Molecules are the most basic building blocks of the material world, and positional isomers are one of the basic properties of molecules. Compounds with the same composition but different positions of substituents or functional groups (including carbon-carbon double bonds and triple bonds) on the carbon frame (carbon chain or carbon ring) in the molecule are called positional isomers. Positional isomers are a kind of isomers due to the different positions of substituents or functional groups on the carbon chain or carbon ring.

Positional isomers are central concepts in organic chemistry that can have a dramatic effect on the properties of molecules. Many disubstituted benzene compounds are environmental pollutants, drug metabolites or intermediates in the chemical and pharmaceutical industries. Furthermore, positional isomerism often has different chemical and pharmaceutical properties. For example, three positional isomerizations of 2-aminobenzenesulfonic acid (2-ABSA), 3-ABSA and 4-ABSA, of which 4-ABSA is synthesized and characterized for sulfamethoxazole and sulfonamide proteins and lysine couples important compound of the compound. Acids used to study allergy to sulfonamide drugs, while 2-ABSA and 3-ABSA are reactive dye intermediates, while 3-ABSA is highly toxic. In this case, the separation of these three positional isomers is crucial. However, isomers often have similar physical and chemical properties, so their separation is one of the most challenging areas in separation science.

At present, the separation and detection of aminobenzenesulfonic acid esters is mainly performed by high performance liquid chromatography (HPLC), and C18 column is often used for separation, because aminobenzenesulfonic acid substances have strong polarity, and phosphate buffer solution is often used as the Mobile phase, and the retention time is short, it is difficult to separate from impurities, and even interferes with the accurate quantification of aminobenzenesulfonic acids. Therefore, it is very important to develop a simple and rapid method to separate and detect the content of positional isomers of aminobenzenesulfonic acids, and it is also one of the key issues in the current research of positional isomers.

Mass spectrometry is the most commonly used molecular or atomic mass analysis technology. It can quickly analyze the mass-to-charge ratio or mass information of different atoms or molecules, but for chiral molecules with exactly the same mass-to-charge ratio and molecular mass Powerless. The ion mobility spectrometry technique can analyze molecules with different structures, such as isomers. Its working principle and process are: firstly generate ions of the sample to be analyzed, and then introduce these ions into the ion mobility spectrum. Mobility spectroscopy was performed under low vacuum conditions. In the ion mobility spectrum, the sample ions do directional motion under the action of the electric field, and continuously collide with the inactive working gases in the mobility spectrum, such as nitrogen, argon, etc. Different ions are separated due to their different mobilities due to their different collision cross sections. Therefore, information on the ion or molecular structure can be obtained from the obtained separated ion mobility spectrum. However, due to the low resolving power of the current ion mobility spectrometry, the difference in molecular structure is small, or the molecule itself is very small, such as organic small molecules, small molecule drugs, etc., the ion mobility spectrometry technology is still unable to analyze their structural differences. In particular, the structural differences of different positional isomers, such as the positional structure analysis of aminobenzenesulfonic acids.

SUMMARY OF THE INVENTION

The purpose of the present invention is to overcome the defects of the prior art, and to provide an analytical reagent and method for the positional isomers of aminobenzenesulfonic acid based on β-cyclodextrin.

The technical solution for realizing the object of the present invention is: an analytical reagent for aminobenzenesulfonic acid positional isomers based on β-cyclodextrin, the analysis reagent comprises aminobenzenesulfonic acid isomer molecules mixed with solvent, β-cyclodextrin Refined and compounds containing monovalent lithium ions.

The concentration of the aminobenzenesulfonic acid isomer molecule in the above technical solution is 10 ^-12 to 1 mol/liter, the concentration of the β-cyclodextrin is 10 ^-12 to 1 mol/liter, and the compound containing monovalent lithium ions The concentration of β-cyclodextrin is 10 ⁻¹² to 1 mol/L, and the relative ratio between the aminobenzenesulfonic acid isomer molecule, the β-cyclodextrin and the compound containing monovalent lithium ion is not limited.

The aminobenzenesulfonic acid isomer molecules described in the above technical solution include 2-aminobenzenesulfonic acid, 3-aminobenzenesulfonic acid and 4-aminobenzenesulfonic acid.

The compound containing monovalent lithium ions described in the above technical solution is lithium halide (except F), lithium nitrate, lithium chlorate, lithium perchlorate, lithium bicarbonate, lithium dihydrogen phosphate, lithium gluconate, lithium hydrogen phosphate, lactic acid One of lithium, a lithium ion-containing alkali, and a lithium ion-containing complex.

The β-cyclodextrins described in the above technical solutions include derivatives of β-cyclodextrins.

The solvent described in the above technical solution is one or more of deionized water, methanol, ethanol, ether, acetic acid, acetonitrile and formic acid water.

A kind of analysis method of aminobenzenesulfonic acid positional isomer based on beta cyclodextrin, has the following steps:

S1, the aminobenzenesulfonic acid isomer molecule, β-cyclodextrin and the compound containing monovalent lithium ions that need to be analyzed for isomers are added into a solvent to prepare aminobenzenesulfonic acid-β-cyclodextrin-lithium ion-containing compound mixture;

S2, the mixture of aminobenzenesulfonic acid-β-cyclodextrin-lithium ion is used as an ion source to generate aminobenzenesulfonic acid-βcyclodextrin-monovalent positive ion containing lithium ion, namely [C ₆ H ₇ NO ₃ S -βCD-Li] ⁺ , the mass-to-charge ratio is m/z=1314.4;

S3, measure the ion collision cross section of aminobenzenesulfonic acid-β-cyclodextrin-monovalent positive ions containing lithium ions, or use an experimental device including ion mobility The ion mobility spectrum of the monovalent positive ion can obtain the positional isomer structure information of sulfamic acid molecule.

In the above technical solution S1, the ion source is one of an electrospray ionization ion source ESI, a laser-assisted desorption ionization ion source MALDI and a desorption electrospray ionization ion source DESI.

The experimental device described in the above technical solution is one of the ion mobility spectrum and the composite experimental device including the ion mobility spectrum.

After adopting above-mentioned technical scheme, the present invention has following positive effect:

The invention provides an analytical reagent and method for the positional isomers of aminobenzenesulfonic acid based on β ^- cyclodextrin. ) compounds, such as LiCl, etc., are prepared into mixed solutions, and then electrospray ionization is used to generate "aminobenzenesulfonic acid-β-cyclodextrin-monovalent cations containing lithium ions, namely [C ₆ H ₇ NO ₃ S-βCD -Li] ⁺ , and then use the ion mobility spectrometry technique to measure its ion mobility spectrum to obtain the structural information of aminobenzenesulfonic acid at different positions of the molecule. Further, if the sample contains aminobenzenesulfonic acid with different positional isomers at the same time molecules, the methods given in the present invention can also obtain information on their relative amounts.

The method for analyzing the structure of different position isomers of aminobenzenesulfonic acid provided in the present invention is simple, does not require pre-resolution or derivatization of the aminobenzenesulfonic acid molecule, and the chemical samples used are easy to obtain, cheap and non-toxic harmless. Compared with the commonly used methods, it has many advantages.

Description of drawings

In order to make the content of the present invention easier to understand clearly, the present invention will be described in further detail below according to specific embodiments and in conjunction with the accompanying drawings, wherein

Fig. 1, the chemical structure schematic diagram of three positional isomers aminobenzenesulfonic acid;

Fig. 2, chemical structure schematic diagram of β-cyclodextrin;

Figure 3. Mass spectrometry detection diagram of three mixtures of aminobenzenesulfonic acid, lithium chloride and β-cyclodextrin;

Figure 4. TIMS separation diagram of the mixture of three positional isomers aminobenzenesulfonic acid, lithium chloride and β-cyclodextrin (a) [2-ABSA-βCD-Li] ⁺ ; (b) [3-ABSA- βCD-Li] ⁺ ; (c) [4-ABSA-βCD-Li] ⁺ ; (d) [ABSA _- βCD-Li] ⁺ .

Detailed ways

In order to make the purposes, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments These are some embodiments of the present invention, but not all embodiments. The components of the embodiments of the invention generally described and illustrated in the drawings herein may be arranged and designed in a variety of different configurations.

The inventor used a commercial ion mobility spectrometry-mass spectrometry instrument - TIMS-TOFMS instrument produced by Bruke Company to analyze the positional isomer structure of aminobenzenesulfonic acid molecule, and the first-order mass spectrometry results are shown in Figure 3 It can be seen that the complex [C ₆ H ₇ NO ₃ S-βCD-Li] ⁺ formed by three different positional isomers of sulfamic acid, β-cyclodextrin and metal salt LiCl cannot be separated. After TIMS, the three positional isomer species were well separated (Figure 4). It is clear from the experimental results that the three sulfanilic acid molecules with different positional isomers can be easily distinguished.

Take three positional isomerized aminobenzenesulfonic acid standard products, β-cyclodextrin and LiCl in a ratio of 1:1:1 to form a mixed solution with a concentration of 10 ^-4 mol/L, and the solvent is 50% Methanol and 50% formic acid water, the formic acid water solution is 0.1% formic acid water solution. The prepared solution is directly tested and analyzed by TIMS-TOF. The ion source voltage is 2.5-4.5kV, the injection flow rate is 1-5 μL/min; the nebulizer pressure is 0.3bar; the drying gas is at 200°C The lower temperature is 3 L/min, and the detection results are analyzed. The analysis results are shown in Figure 3 and Figure 4.

The specific embodiments described above further describe the purpose, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above descriptions are only specific embodiments of the present invention, and are not intended to limit the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims (8)

1. An analytical method of aminobenzenesulfonic acid positional isomer based on beta cyclodextrin is characterized in that: the analytical reagent comprises aminobenzenesulfonic acid isomer molecules mixed with a solvent, beta cyclodextrin and a compound containing univalent lithium ions;

the use of the assay reagent has the following steps:

s1, adding a solvent into aminobenzenesulfonic acid isomer molecules, beta cyclodextrin and a compound containing monovalent lithium ions to be subjected to isomer analysis to prepare an aminobenzenesulfonic acid-beta cyclodextrin-lithium ion-containing mixture;

s2, the mixture of aminobenzenesulfonic acid-beta-cyclodextrin-lithium-containing ions uses an ion source to generate univalent positive ions of aminobenzenesulfonic acid-beta-cyclodextrin-lithium-containing ions, namely [ C₆H₇NO₃S-βCD-Li]⁺Mass to charge ratio of m/z = 1314.4;

s3, measuring the ion collision cross section of the monovalent positive ions of the aminobenzenesulfonic acid-beta cyclodextrin-lithium-containing ions, or measuring the ion mobility spectrum of the monovalent positive ions of the aminobenzenesulfonic acid-beta cyclodextrin-lithium-containing ions by using an experimental device comprising an ion mobility spectrum, so as to obtain the position isomeric structure information of aminobenzenesulfonic acid molecules.

2. The method for analyzing aminobenzenesulfonic acid positional isomer based on beta-cyclodextrin as claimed in claim 1, wherein: the concentration of aminobenzenesulfonic acid isomer molecules is 10^-12About 1 mol/l, the concentration of the beta cyclodextrin is 10^-12About 1 mol/l, concentration of the compound containing monovalent lithium ion is 10^-12-1 mole/liter, the relative proportions between said aminobenzenesulfonic acid isomer molecules, said beta-cyclodextrin and said compound containing monovalent lithium ions being not limited.

3. The method for analyzing aminobenzenesulfonic acid positional isomer based on beta-cyclodextrin as claimed in claim 1, wherein: the aminobenzenesulfonic acid isomer molecules comprise three types of 2-aminobenzenesulfonic acid, 3-aminobenzenesulfonic acid and 4-aminobenzenesulfonic acid.

4. The method for analyzing aminobenzenesulfonic acid positional isomer based on beta-cyclodextrin as claimed in claim 1, wherein: the compound containing monovalent lithium ions is one of lithium halide, lithium nitrate, lithium chlorate, lithium perchlorate, lithium bicarbonate, lithium dihydrogen phosphate, lithium gluconate, lithium hydrogen phosphate, lithium lactate, lithium ion-containing alkali and lithium ion-containing complex except for F.

5. The method for analyzing aminobenzenesulfonic acid positional isomer based on beta-cyclodextrin as claimed in claim 1, wherein: the beta cyclodextrin includes derivatives of beta cyclodextrin.

6. The method for analyzing aminobenzenesulfonic acid positional isomer based on beta-cyclodextrin as claimed in claim 1, wherein: the solvent is one or more of deionized water, methanol, ethanol, diethyl ether, acetic acid acetonitrile and formic acid water.

7. The method for analyzing aminobenzenesulfonic acid positional isomer based on beta-cyclodextrin as claimed in claim 1, wherein: in S1, the ion source is one of an electrospray ionization ion source ESI, a laser assisted desorption ionization ion source MALDI, and a desorption electrospray ionization ion source DESI.

8. The method for analyzing aminobenzenesulfonic acid positional isomer based on beta-cyclodextrin as claimed in claim 1, wherein: the experimental device is one of an ion mobility spectrometry and a composite experimental device comprising the ion mobility spectrometry.

Images