Application of a chiral MOFs material in electrochemical recognition of histidine enantiomers

Abstract

The application provides application of a chiral MOFs material in electrochemical recognition of histidine enantiomers, and belongs to the technical field of chiral recognition. The inorganic metal center of the chiral MOFs material is a transition metal ion, and the organic ligand is a chiral carboxylic acid ligand and 4,4'-bipyridine. The principle of the chiral MOFs material for electrochemical recognition of histidine enantiomers is to construct a chiral microenvironment, to utilize the weak interaction between the chiral material and the guest molecules, and to realize the recognition of amino acid enantiomers by utilizing the stereoselectivity of host-guest interaction. The material can be used for chiral recognition of amino acid enantiomers, and the application range of the chiral MOFs material is expanded. Under the current recognition condition, the material has obvious chiral recognition effect on histidine enantiomers, and has good substrate selectivity for the recognition of histidine.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of chiral recognition, in particular to application of a chiral MOFs material in electrochemical recognition of histidine enantiomers. BACKGROUND

[0002] As enantiomers, D / L amino acids are similar in physical and chemical properties but different in physiological activities. L-type amino acids are basic units of proteins, and lack of L-type amino acids can cause a series of negative effects on human health; D-type amino acids play some unique physiological roles in organisms and have wide applications in fields such as medicine, cosmetics and food additives. Traditionally, enantiomeric amino acids are detected by chromatography, which is expensive and time-consuming. Therefore, it is of high value to develop a new detection method for enantiomeric amino acids to make up for the shortcomings.

[0003] Compared with the chromatography method, the electrochemical method is cheap, convenient, environmentally friendly and fast, and therefore it is of certain research value to recognize enantiomeric amino acids by the electrochemical method. The electrochemical chiral recognition mainly utilizes electrode materials with a chiral microenvironment to obtain corresponding chiral recognition effects through different degrees of interaction with chiral enantiomers. However, due to the deficiencies in the corresponding recognition mechanism and electrode sheet preparation process, new chiral electrode materials need to be further developed.

[0004] The chiral metal organic framework (MOFs) material has rich structures, stable and adjustable pore environment and inherent chiral center, and has unique advantages in recognition mechanism research. Therefore, it is of great significance to provide a chiral MOFs material with amino acid enantiomer recognition ability in the research of biopharmaceuticals and physiology. SUMMARY

[0005] The application aims to provide application of a chiral MOFs material in electrochemical recognition of histidine enantiomers, so as to solve the problems of expensive equipment and poor timeliness in traditional chromatography method for detecting enantiomeric amino acids.

[0006] In order to achieve the above application purposes, the application provides the following technical solutions.

[0007] The application provides application of a chiral MOFs material in electrochemical recognition of histidine enantiomers, wherein the inorganic metal center of the chiral MOFs material is a transition metal ion, and the organic ligand is a chiral carboxylic acid ligand and 4,4'-bipyridine.

[0008] The structure formula of the chiral carboxylic acid ligand is as follows:

[0009]

[0010] The molar ratio of the chiral carboxylic acid ligand, 4,4'-bipyridine and the transition metal ion is 1:0.5-2:0.5-4.

[0011] Preferably, the transition metal ion is hexacoordinated, including four oxygen atoms from the chiral carboxylic acid ligand and two nitrogen atoms from the 4,4'-bipyridine ligand.

[0012] Preferably, the transition metal ion is a nickel ion or a copper ion.

[0013] Preferably, the method of electrochemical recognition is:

[0014] The working electrode, the counter electrode and the reference electrode form a three-electrode system.

[0015] Preferably, the working electrode is a hydrophobic carbon paper electrode loaded with the chiral MOFs material.

[0016] Preferably, the preparation method of the working electrode comprises the following steps:

[0017] (1) mixing the chiral MOFs material, the Nafion·D-520 dispersion liquid and N,N-dimethylformamide by ultrasonic to obtain a suspension;

[0018] (2) dropping the suspension on the hydrophobic carbon paper material electrode to obtain the working electrode.

[0019] Preferably, the mass-volume ratio of the chiral MOFs material, the Nafion·D-520 dispersion liquid and N,N-dimethylformamide in step (1) is 2-4 mg:10-30 μL:200-500 μL.

[0020] Preferably, the dispersant of the Nafion·D-520 dispersion liquid is 1-propanol solution, and the mass concentration of the Nafion·D-520 dispersion liquid is 3-7%.

[0021] Preferably, the counter electrode is a graphite rod electrode, and the reference electrode is an Ag / AgCl electrode.

[0022] Preferably, the buffer solution for electrochemical recognition is a phosphate solution.

[0023] The pH of the phosphate solution is 3-4, and the concentration is 0.005-0.015 mol / L.

[0024] The present application has the following advantages:

[0025] The principle of the chiral MOFs material of the application for electrochemically recognizing histidine enantiomers is to build a chiral microenvironment, to utilize the stereoselectivity of host-guest interaction through the weak interaction between the chiral material and the guest molecules, and to realize the recognition of amino acid enantiomers. The material can be used for chiral recognition of amino acid enantiomers, and expands the application range of chiral MOFs materials. Under the current recognition conditions, the material has obvious chiral recognition effect on histidine enantiomers. Meanwhile, the material has good substrate selectivity for the recognition of histidine. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 The preparation flowchart of the chiral carboxylic acid ligand S-H2L in Example 1 is shown in the figure.

[0027] Figure 2 The electrochemical recognition effect diagram of the chiral S-Cu-MOFs material on D / L-histidine in Example 1 is shown in the figure.

[0028] Figure 3 The electrochemical recognition effect diagram of the chiral R-Cu-MOFs material on D / L-histidine in Example 2 is shown in the figure.

[0029] Figure 4 The electrochemical recognition effect diagram of the chiral S-Ni-MOFs material on D / L-histidine in Example 3 is shown in the figure.

[0030] Figure 5 The electrochemical recognition effect diagram of the chiral R-Ni-MOFs material on D / L-histidine in Example 4 is shown in the figure. DETAILED DESCRIPTION

[0031] The application provides an application of a chiral MOFs material in electrochemically recognizing histidine enantiomers, wherein the inorganic metal center of the chiral MOFs material is a transition metal ion, and the organic ligand is a chiral carboxylic acid ligand and 4,4'-bipyridine.

[0032] The structural formula of the chiral carboxylic acid ligand is as follows:

[0033]

[0034] The molar ratio of the chiral carboxylic acid ligand, 4,4'-bipyridine and the transition metal ion is 1:0.5-2:0.5-4.

[0035] In the application, the molar ratio of the chiral carboxylic acid ligand, 4,4'-bipyridine and the transition metal ion is preferably 1:0.7-1.8:1-3.5, further preferably 1:1-1.5:1.5-3, and more preferably 1:1.2-1.3:2-2.5.

[0036] In the present application, the transition metal ion is preferably hexacoordinated, including four oxygen atoms from the chiral carboxylic acid ligand and two nitrogen atoms from the 4,4'-bipyridine ligand.

[0037] In the present application, the transition metal ion is preferably a nickel ion or a copper ion.

[0038] In the present application, the method of electrochemical recognition is:

[0039] A three-electrode system is formed using a working electrode, a counter electrode, and a reference electrode.

[0040] In the present application, the working electrode is preferably a hydrophobic carbon paper electrode loaded with a chiral MOFs material.

[0041] In the present application, the method for preparing the working electrode comprises the following steps:

[0042] (1) mixing a chiral MOFs material, a Nafion·D-520 dispersion liquid, and N,N-dimethylformamide under ultrasonication to obtain a suspension;

[0043] (2) adding the suspension to a hydrophobic carbon paper material electrode to obtain a working electrode.

[0044] In the present application, the mass-volume ratio of the chiral MOFs material, the Nafion·D-520 dispersion liquid, and N,N-dimethylformamide in step (1) is 2-4 mg: 10-30 μL: 200-500 μL, further preferably 2.5-3.5 mg: 15-25 μL: 250-350 μL, and more preferably 3 mg: 20 μL: 280 μL.

[0045] In the present application, the dispersant of the Nafion·D-520 dispersion liquid is preferably a 1-propanol solution, and the mass concentration of the Nafion·D-520 dispersion liquid is preferably 3-7%, further preferably 4-6%, and more preferably 5%.

[0046] In the present application, after mixing under ultrasonication in step (1), sedimentation and drying are sequentially performed to obtain the suspension. The time for mixing under ultrasonication is preferably 0.5-2 h, further preferably 0.7-1.5 h, and more preferably 1 h. The time for sedimentation is preferably 0.5-60 min, further preferably 10-30 min, and more preferably 15 min. The time for drying is preferably 12-48 h, further preferably 18-36 h, and more preferably 24 h.

[0047] In the present application, the counter electrode is preferably a graphite rod electrode, and the reference electrode is preferably an Ag / AgCl electrode.

[0048] In the present application, the buffer solution for electrochemical recognition is preferably a phosphate solution.

[0049] The pH of the phosphate solution is preferably 3-4, further preferably 3.2-3.8, and more preferably 3.5, and the concentration is preferably 0.005-0.015 mol / L, further preferably 0.008-0.012 mol / L, and more preferably 0.01 mol / L.

[0050] In the present application, the concentration of amino acid enantiomers in the phosphate solution is 0-1 mmol / L.

[0051] The preparation method of the chiral MOFs material according to the present application comprises the following steps:

[0052] (1) Under a protective atmosphere, 1,2-cyclohexanediamine, triethylamine and dichloromethane are mixed, and then oxalyl chloride monoethyl ester dichloromethane solution is added for reaction. After the reaction is completed, the product is extracted, dried and purified to obtain an intermediate product;

[0053] (2) The intermediate product is dissolved in a mixed solution of methanol and water, and then sodium hydroxide is added for reaction under heating. After the reaction is completed, the pH is adjusted to ≤1, and the product is obtained by rotary evaporation under reduced pressure. The product is filtered, washed and dried to obtain a chiral carboxylic acid ligand;

[0054] (3) The chiral carboxylic acid ligand, 4,4'-bipyridine are dissolved in N,N-dimethylformamide, and then a transition metal salt and water are added for reaction. After the reaction is completed, the product is filtered, washed and dried to obtain a chiral MOFs material.

[0055] In the present application, the 1,2-cyclohexanediamine in step (1) is preferably (1R,2R)-cyclohexane-1,2-diamine or (1S,2S)-cyclohexane-1,2-diamine.

[0056] In the present application, the molar ratio of 1,2-cyclohexanediamine, triethylamine and oxalyl chloride monoethyl ester in step (1) is preferably 1:1-5:1-6, further preferably 1:1.3-4.6:2-5, and more preferably 1:2:3.3.

[0057] In the present application, the volume ratio of dichloromethane and oxalyl chloride monoethyl ester dichloromethane solution in step (1) is preferably 4-6:1, further preferably 4.3-5.7:1, and more preferably 4.9:1.

[0058] In the present application, the concentration of oxalyl chloride monoethyl ester dichloromethane solution in step (1) is preferably 5-7 mol / L, further preferably 5.1-6.8 mol / L, and more preferably 5.9 mol / L.

[0059] In the present application, the protective atmosphere in step (1) is preferably argon; the temperature of the reaction is preferably -5-20℃, further preferably 1-4℃, more preferably 2℃; the time of the reaction is preferably 8-16h, further preferably 10-14h, more preferably 12h.

[0060] In the present application, the extractant of the extraction in step (1) is preferably dichloromethane; the drying agent of the drying is preferably anhydrous sodium sulfate.

[0061] In the present application, the purification in step (1) is preferably silica gel column purification; the eluent of the purification is preferably petroleum ether and ethyl acetate; the volume ratio of petroleum ether and ethyl acetate is preferably 1:1.

[0062] In the present application, the volume ratio of methanol and water in step (2) is preferably 1:1.

[0063] In the present application, the mass-volume ratio of the intermediate product and the mixed solution in step (2) is preferably 3-10g: 50-80mL, further preferably 4-9g: 55-76mL, more preferably 6g: 60mL.

[0064] In the present application, the molar ratio of the intermediate product and sodium hydroxide in step (2) is preferably 1:1-5, further preferably 1:2-4, more preferably 1:2.5.

[0065] In the present application, the temperature of the reaction in step (2) is preferably 80-90℃, further preferably 82-87℃, more preferably 85℃; the time of the reaction is preferably 8-16h, further preferably 10-14h, more preferably 12h.

[0066] In the present application, the molar ratio of the chiral carboxylic acid ligand, 4,4'-bipyridine and transition metal salt in step (3) is preferably 1:0.5-2:0.5-4, further preferably 1:0.7-1.6:1.1-3.2, more preferably 1:1.2:2.5.

[0067] In the present application, the molar volume ratio of the chiral carboxylic acid ligand, N,N-dimethylformamide and water in step (3) is preferably 0.2-1.8mmol: 10mL: 30-50mL, further preferably 0.5-1.5mmol: 10mL: 35-45mL, more preferably 1mmol: 10mL: 40mL.

[0068] In the present application, the temperature of the reaction in step (3) is preferably 80-120℃, further preferably 85-100℃, more preferably 90℃; the time of the reaction is preferably 1-5d, further preferably 1.2-4.5d, more preferably 3d.

[0069] In the present application, the transition metal salt in step (3) is preferably nickel sulfate hexahydrate or copper chloride dihydrate.

[0070] In the present application, the required raw materials for preparation are all commercially available products well known to those skilled in the art, unless otherwise specified.

[0071] The technical solutions provided by the present application will be described in detail below in conjunction with the examples, but they should not be understood as limiting the scope of protection of the present application.

[0072] Example 1

[0073] The chiral MOFs material, Nafion·D-520 dispersion liquid and N,N-dimethylformamide were mixed at 3 mg: 20 μL: 280 μL, ultrasonic treatment for 1 h, and then settled for 15 min to obtain a suspension. The stable suspension was added dropwise to a hydrophobic carbon paper material electrode, and then dried for 24 h to obtain a working electrode.

[0074] The test substance D / L histidine enantiomer was configured into a 1 mmol / L solution using a 0.01 mol / L phosphate buffer solution with a pH of 3.5; a three-electrode system was formed using the working electrode, an Ag / AgCl reference electrode and a graphite rod counter electrode; and electrochemical testing was performed using linear sweep voltammetry, with the LSV conditions being: a potential range of -1.5 V to 1.5 V, a scanning speed of 0.05 V / s, and a sensitivity of 1 mA.

[0075] The preparation method of the chiral S-Cu-MOFs material comprises the following steps:

[0076] (1) Preparation of chiral carboxylic acid ligand S-H2L:

[0077] Under argon protection, (1S, 2S)-cyclohexane-1, 2-diamine (4.57 g, 0.04 mol) and triethylamine (18.0 mL, 0.13 mol) were dissolved in anhydrous dichloromethane (100 mL) to form a colorless transparent mixed solution; then a solution containing oxalyl chloride monoethyl ester (11.3 g, 0.08 mol) in anhydrous dichloromethane (20 mL) was added dropwise; after the dropwise addition was completed, the mixture was stirred at 0°C for 12 h to obtain a light yellow solid-liquid mixture; after the reaction was quenched with saturated NaHCO3 solution, the yellow organic phase was separated by dichloromethane extraction, and the organic phase was dried with anhydrous Na2SO4, then rotary evaporated and purified by silica gel column (eluent: PE and EA at a volume ratio of 1:1) to obtain the intermediate product S-1 (11.6 g, yield 92.3%);

[0078] (2) Preparation of chiral carboxylic acid ligand S-H2L: Intermediate S-1 (6.28 g, 0.02 mol) was dissolved in a mixed solution of methanol (50 mL) and water (50 mL), and sodium hydroxide (2 g, 0.05 mol) was added, and heated to 85°C for 12h. After the reaction was completed, the pH was adjusted to ≤1 using hydrochloric acid, and filtered and washed with water 3 times, and dried to obtain chiral carboxylic acid ligand S-H2L (4.23 g, yield 81.9%).

[0079] The preparation flow chart of chiral carboxylic acid ligand S-H2L is shown in Figure 1 .

[0080] (3) Preparation of chiral S-Cu-MOFs material: Chiral carboxylic acid ligand S-H2L (25.8 mg, 0.1 mmol), 4,4'-dipyridine (15.6 mg, 0.1 mmol) were dissolved in 1 mL of N,N-dimethylformamide, and copper chloride dihydrate (17.8 mg, 0.1 mmol) and 4 mL of water were added, and heated to 90°C for 72h. After the reaction was completed, the product was filtered, washed with methanol 5 times, and dried to obtain chiral S-Cu-MOFs material (23.8 mg, yield 46%).

[0081] The electrochemical recognition results of the above chiral S-Cu-MOFs material on D / L-histidine are shown in Figure 2 . It can be seen from Figure 2 that the detection working electrode loaded with chiral S-Cu-MOFs material has chiral recognition effect on L-histidine. At a potential of -1.5V, the current of L-histidine is attenuated by 32.5% compared with the background current, and the current of D-histidine is attenuated by 2.4% compared with the background current.

[0082] Example 2

[0083] The preparation method of the chiral MOFs material in Example 1 is basically the same, the only difference is that 1,2-cyclohexanediamine is (1R,2R)-cyclohexane-1,2-diamine, and the final product is R-Cu-MOFs material.

[0084] The process of electrochemically recognizing histidine enantiomers is the same as in Example 1. The recognition results are shown in Figure 3 .

[0085] It can be seen from Figure 3 that the detection working electrode loaded with chiral R-Cu-MOFs material has chiral recognition effect on D-histidine. At a potential of -1.5V, the current of L-histidine is attenuated by 1.8% compared with the background current, and the current of D-histidine is attenuated by 27.2% compared with the background current.

[0086] Example 3

[0087] The preparation method is basically the same as that of chiral MOFs material in Example 1, except that copper chloride dihydrate is replaced with nickel sulfate hexahydrate, and the final product is S-Ni-MOFs material.

[0088] The electrochemical recognition process for histidine enantiomers was the same as in Example 1. The recognition results are as follows: Figure 4 As shown.

[0089] Depend on Figure 4 It can be seen that the detection working electrode loaded with chiral S-Ni-MOFs material has a chiral recognition function for L-histidine. At a potential of -1.5V, the L-histidine current decreases by 10.5% compared to the background current, and the D-histidine current decreases by 24.8% compared to the background current.

[0090] Example 4

[0091] The preparation method is basically the same as that of the chiral MOFs material in Example 3, except that the 1,2-cyclohexanediamine is (1R,2R)-cyclohexane-1,2-diamine, and the final product is R-Ni-MOFs material.

[0092] The electrochemical recognition process for histidine enantiomers was the same as in Example 1. The recognition results are as follows: Figure 5 As shown.

[0093] Depend on Figure 5 It can be seen that the detection working electrode loaded with chiral R-Ni-MOFs material has a chiral recognition function for D-type histidine. At a potential of -1.5V, the L-type histidine current decreases by 5.6% compared to the background current, and the D-type histidine current decreases by 27.2% compared to the background current.

[0094] As can be seen from the above embodiments, the present invention provides an application of chiral MOFs materials in the electrochemical recognition of histidine enantiomers, wherein the inorganic metal center of the chiral MOFs material is a transition metal ion, and the organic ligands are a chiral carboxylic acid ligand and 4,4'-bipyridine, and the molar ratio of the chiral carboxylic acid ligand, 4,4'-bipyridine and the transition metal ion is 1:0.5-2:0.5-4. This material can be used for chiral recognition of amino acid enantiomers, expanding the application range of chiral MOFs materials; and, under current recognition conditions, this material has a significant chiral recognition effect on histidine enantiomers; at the same time, the material has good substrate selectivity for histidine recognition.

[0095] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. Use of a chiral MOFs material for the electrochemical recognition of the enantiomers of histidine, characterized in that, The inorganic metal center of the chiral MOF material is a transition metal ion, and the organic ligands are chiral carboxylic acid ligands and 4,4'-bipyridine. The structural formula of the chiral carboxylic acid ligand is: or ; The molar ratio of the chiral carboxylic acid ligand, 4,4'-bipyridine, and transition metal ion is 1:0.5~2:0.5~4; The transition metal ion is a nickel ion or a copper ion.

2. Use of chiral MOFs material according to claim 1 for electrochemical recognition of histidine enantiomers, characterized in that, The transition metal ion is six-coordinated, comprising four oxygen atoms from a chiral carboxylic acid ligand and two nitrogen atoms from a 4,4'-bipyridine ligand.

3. Use of chiral MOFs material according to claim 2 for electrochemical recognition of histidine enantiomers, characterized in that, The electrochemical recognition method is as follows: A three-electrode system is constructed using a working electrode, a counter electrode, and a reference electrode.

4. Use of chiral MOFs material according to claim 3 for electrochemical recognition of histidine enantiomers, characterized in that, The working electrode is a hydrophobic carbon paper electrode loaded with chiral MOFs material.

5. Use of chiral MOFs material according to claim 4 for electrochemical recognition of histidine enantiomers, characterized in that, The method for preparing the working electrode includes the following steps: (1) Chiral MOFs material, Nafion D-520 dispersion and N,N-dimethylformamide were mixed and sonicated to obtain a suspension; (2) The above suspension is added to the hydrophobic carbon paper material electrode to obtain the working electrode.

6. Use of chiral MOFs material according to claim 5 for electrochemical recognition of histidine enantiomers, characterized in that, In step (1), the mass-to-volume ratio of chiral MOFs material, Nafion D-520 dispersion and N,N-dimethylformamide is 2~4 mg: 10~30 μL: 200~500 μL.

7. Use of chiral MOFs material according to claim 6 for electrochemical recognition of histidine enantiomers, characterized in that, The dispersant for the Nafion D-520 dispersion is a 1-propanol solution, and the mass concentration of the Nafion D-520 dispersion is 3-7%.

8. Use of the chiral MOFs material according to claim 7 for electrochemical recognition of histidine enantiomers, characterized in that, The counter electrode is a graphite rod electrode, and the reference electrode is an Ag / AgCl electrode.

9. Use of the chiral MOFs material according to claim 8 for electrochemical recognition of histidine enantiomers, characterized in that, The buffer solution for electrochemical recognition is a phosphate solution; The phosphate solution has a pH of 3-4 and a concentration of 0.005-0.015 mol / L.

Images