Chiral metal-organic framework compound and preparation method and application thereof

Abstract

The application discloses a kind of chiral metal organic framework compounds and preparation method and application thereof, belong to metal organic framework material technical field.The chiral metal organic framework compound provided by the application includes central metal, organic ligand I and organic ligand II;The central metal is cobalt, the organic ligand I is dipyridyl, and the organic ligand II is chiral tartaric acid, and the tartaric acid includes L-tartaric acid or D-tartaric acid.A kind of chiral metal organic framework compound is synthesized, which has the advantages of stable physical and chemical properties, simple, green and economical synthesis method, lower preparation cost, wider application of preparation method, etc.The prepared chiral MOF uses carbonyl in chiral tartaric acid as chiral recognition site, can selectively recognize polar chiral drugs, so it has great application prospect in drug analysis and drug metabolism.

Description

Technical Field

[0001] This invention belongs to the field of metal-organic framework materials technology, and particularly relates to a chiral metal-organic framework compound, its preparation method and application. Background Technology

[0002] Metal-organic frameworks (MOFs) are a class of compounds composed of metal ions or clusters that coordinate with organic ligands to form one-dimensional, two-dimensional, or three-dimensional structures. To date, chiral analysis remains a significant technical challenge. The stable structure, permanent porosity, and multifunctional signal transduction capabilities of MOFs make them ideal materials for fabricating advanced sensors. In recent years, chiral MOFs have shown great potential for enantioselectivity. The design and synthesis of chiral materials with high surface area and multiple active sites are crucial for high-performance analysis.

[0003] Chiral molecules play a crucial role in chemical synthesis, environmental chemistry, and medicinal chemistry, and their qualitative and quantitative detection has become an important aspect of academic and industrial research. The analysis of chiral drugs holds an extremely important position in the pharmaceutical industry, as their enantiomers often exhibit different pharmacological and toxicological properties. Therefore, the identification of chiral drugs is of great significance in the life sciences and pharmaceutical fields. Gas chromatography, liquid chromatography, and nuclear magnetic resonance (NMR) are commonly used methods for identifying enantiomers and determining eee. However, these methods are time-consuming, require expensive and bulky instruments, and require specialized personnel to operate. Developing simple and easy-to-operate analytical methods for chiral drugs is of great importance. Summary of the Invention

[0004] In order to overcome the problems existing in the prior art, one of the objectives of the present invention is to provide a chiral metal-organic framework compound with stable physicochemical properties, a simple, green and economical synthesis method, and the ability to selectively recognize chiral drugs.

[0005] A second objective of this invention is to provide a method for preparing the above-mentioned chiral metal-organic framework compound.

[0006] A third objective of this invention is to provide an application of the above-mentioned chiral metal-organic framework compound as a catalyst in the luminol-hydrogen peroxide chemiluminescence reaction.

[0007] The fourth objective of this invention is to provide an application of the above-mentioned chiral metal-organic framework compound in the recognition of chiral drugs.

[0008] The fifth objective of this invention is to provide an application of the above-mentioned chiral metal-organic framework compound in the detection of chiral drug concentrations in biological samples.

[0009] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0010] A first aspect of the present invention provides a chiral metal-organic framework compound comprising a central metal, an organic ligand I, and an organic ligand II; wherein the central metal is cobalt, the organic ligand I is bipyridine, and the organic ligand II is chiral tartaric acid, wherein the tartaric acid comprises L-tartaric acid or D-tartaric acid.

[0011] Preferably, in the chiral metal-organic framework compound, the cobalt is divalent cobalt.

[0012] Preferably, in the chiral metal-organic framework compound, the bipyridine includes 2'2-bipyridine, 4'4-bipyridine, or a combination thereof; more preferably, it is 2'2-bipyridine.

[0013] Preferably, the crystal cell parameters of the chiral metal-organic framework compound are: α = (80–100)°, β = (80–100)°, γ = (80–100)°; more preferably, the crystal cell parameters of the chiral metal-organic framework compound are: α=(85~95)°, β=(85~95)°, γ=(85~95)°.

[0014] In the chiral metal-organic framework compound of the present invention, the two N atoms of bipyridine coordinate with the central metal Co, and the O atom of chiral tartaric acid coordinates with the central metal Co.

[0015] A second aspect of the present invention provides a method for preparing the chiral metal-organic framework compound described in the first aspect of the present invention, comprising the following steps: taking an aqueous mixture containing cobalt salt, bipyridine and chiral tartaric acid, and performing a hydrothermal reaction to obtain the chiral metal-organic framework compound.

[0016] Preferably, in the preparation method, the molar ratio of cobalt salt, bipyridine and chiral tartaric acid is 1:(1-1.5):(1-1.5); more preferably 1:(1-1.2):(1-1.2); and even more preferably 1:(1-1.1):(1-1.1).

[0017] Preferably, in the preparation method, the temperature of the hydrothermal reaction is 100-140°C; more preferably 110-130°C; and even more preferably 115-125°C.

[0018] Preferably, in the preparation method, the hydrothermal reaction time is 50-62 h; more preferably 52-60 h; and even more preferably 54-58 h.

[0019] Preferably, in the preparation method, the cobalt salt includes at least one of cobalt acetate, cobalt chloride, cobalt sulfate, or cobalt nitrate; more preferably, in the preparation method, the cobalt salt includes at least one of cobalt acetate, cobalt chloride, or cobalt sulfate; even more preferably, in the preparation method, the cobalt salt includes cobalt acetate, cobalt chloride, or a combination thereof.

[0020] Preferably, in the preparation method, the cobalt salt and bipyridine are first dissolved in water, and then chiral tartaric acid is added for further dissolution to obtain the aqueous mixture. Before the hydrothermal reaction, the solid raw materials must be completely dissolved.

[0021] Preferably, in the preparation method, washing is performed after the hydrothermal reaction.

[0022] Preferably, the washing is performed 2 to 5 times; the washing liquid is water.

[0023] A third aspect of the present invention provides the use of the chiral metal-organic framework compound described in the first aspect of the present invention as a catalyst in the luminol-hydrogen peroxide chemiluminescence reaction.

[0024] Preferably, the application of the chiral metal-organic framework compound as a catalyst in the luminol-hydrogen peroxide chemiluminescence reaction includes the following steps: placing the chiral metal-organic framework compound in a chemiluminescence reaction device, adding luminol solution and hydrogen peroxide solution to the reaction device, and carrying out the chemiluminescence reaction.

[0025] Preferably, the concentration of the luminol solution is (0.5~2)×10⁻⁶. -5 mol / L; more preferably (0.8~1.5)×10 -5 mol / L.

[0026] Preferably, the concentration of the hydrogen peroxide solution is (0.5~2)×10⁻⁶. -4 mol / L; more preferably (0.8~1.5)×10 -4 mol / L.

[0027] A fourth aspect of the present invention provides the use of the chiral metal-organic framework compound described in the first aspect of the present invention in the recognition of chiral drugs.

[0028] Preferably, the chiral drug comprises at least one of L-penicillamine / D-penicillamine, L-methyldopa / D-methyldopa, or quinine / quinidine. The slashes ( / ) represent a group of chiral drugs.

[0029] Preferably, the application of the chiral metal-organic framework compound in identifying chiral drugs includes the following steps: placing the chiral metal-organic framework compound in a chemiluminescence reaction device, adding luminol solution, hydrogen peroxide solution and a chiral drug sample to the reaction device, performing a chemiluminescence reaction, and identifying the chiral drug based on the different luminescence signals.

[0030] Preferably, the concentration of the luminol solution is (0.5–2.0) × 10⁻⁶. -5 mol / L; more preferably (0.8~1.5)×10 -5 mol / L.

[0031] Preferably, the concentration of the hydrogen peroxide solution is (0.5–2.0) × 10⁻⁶. -4 mol / L; more preferably (0.8~1.5)×10 -4 mol / L.

[0032] The fifth aspect of the present invention provides the use of the chiral metal-organic framework compound described in the first aspect of the present invention in the detection of chiral drug concentrations in biological samples.

[0033] Furthermore, the biological sample includes urine samples, blood samples, or combinations thereof.

[0034] Furthermore, the chiral drug includes at least one of L-penicillamine / D-penicillamine, L-methyldopa / D-methyldopa, or quinine / quinidine. The slashes ( / ) represent a group of chiral drugs.

[0035] Preferably, the application of the chiral metal-organic framework compound in detecting the concentration of chiral drugs in biological samples includes the following steps: placing the chiral metal-organic framework compound in a chemiluminescence reaction device, adding luminol solution, hydrogen peroxide solution and a biological sample containing a chiral drug to the reaction device, performing a chemiluminescence reaction, and detecting the concentration of the chiral drug based on the different luminescence signals.

[0036] The beneficial effects of this invention are as follows: This invention synthesizes a chiral metal-organic framework compound (chiral MOF), which has the advantages of stable physicochemical properties, a simple, green, and economical synthesis method, low preparation cost, and wide applicability of the preparation method. The prepared chiral MOF uses the carbonyl group in chiral tartaric acid as a chiral recognition site, enabling selective recognition of polar chiral drugs, thus showing great application potential in drug analysis and drug metabolism.

[0037] Specifically, compared with the prior art, the present invention has the following advantages:

[0038] (1) The chiral metal-organic framework compounds of the present invention are made from inexpensive raw materials, have mild preparation conditions, do not require the use of organic solvents, and have the advantages of being environmentally friendly and capable of being prepared in large quantities.

[0039] (2) The chiral metal-organic framework compound of the present invention can catalyze the luminol-hydrogen peroxide reaction and generate multi-level signals in a cyclic chemiluminescence system.

[0040] (3) The interaction between the chiral metal-organic framework compound of the present invention and the chiral drug will affect the chemiluminescence reaction rate, regulate the multi-level signal, and realize the rapid recognition of chiral drugs such as L-penicillamine / D-penicillamine, L-methyldopa / D-methyldopa or quinine / quinidine.

[0041] (4) The chiral metal-organic framework compounds of the present invention can also be used to detect the concentration of chiral drugs in biological samples. Attached Figure Description

[0042] Figure 1 The reaction equation for the preparation of the chiral MOF in Example 1 is shown.

[0043] Figure 2 The structural formula of Co-120-L in Example 1 is shown.

[0044] Figure 3 The structural formula of Co-120-D in Example 1 is shown.

[0045] Figure 4 X-ray powder diffraction pattern of the chiral MOF prepared in Example 1.

[0046] Figure 5 Scanning electron microscope (SEM) images of the chiral MOF prepared in Example 1; where a and b are Co-120-L, and c and d are Co-120-D.

[0047] Figure 6 Nitrogen adsorption chromatogram of Co-120-L prepared in Example 1.

[0048] Figure 7 Nitrogen adsorption chromatogram of Co-120-D prepared in Example 1.

[0049] Figure 8 The circular dichroism chromatogram of the chiral MOF prepared in Example 1.

[0050] Figure 9 The cyclic chemiluminescence signal diagram of the Co-120-L catalyzed luminol-hydrogen peroxide reaction in Example 1 is shown.

[0051] Figure 10 The cyclic chemiluminescence signal diagram of the Co-120-D catalyzed luminol-hydrogen peroxide reaction in Example 1 is shown.

[0052] Figure 11 Multilevel signal diagram of the Co-120-L catalytic luminol-hydrogen peroxide reaction in Example 1, for the preparation of chiral penicillamine.

[0053] Figure 12 Multilevel signal diagram of the Co-120-D catalytic luminol-hydrogen peroxide reaction in Example 1, for the preparation of chiral penicillamine.

[0054] Figure 13 Multilevel signal diagram of the Co-120-L catalytic luminol-hydrogen peroxide reaction in Example 1 for the preparation of chiral methyldopa.

[0055] Figure 14 Multilevel signal diagram of the Co-120-D catalytic luminol-hydrogen peroxide reaction in Example 1 for the preparation of chiral methyldopa.

[0056] Figure 15 Multilevel signal diagram of the Co-120-L catalytic luminol-hydrogen peroxide reaction in Example 1, used to regulate the preparation of quinine and quinidine.

[0057] Figure 16 Multilevel signal diagram of the Co-120-D catalytic luminol-hydrogen peroxide reaction in Example 1, used to regulate the preparation of quinine and quinidine.

[0058] Figure 17 The graph shows the relationship between the amount of L-penicillamine added and the k value in urine samples under Co-120-L catalysis.

[0059] Figure 18 The graph shows the relationship between the amount of D-penicillamine added and the k value in urine samples under Co-120-L catalysis.

[0060] Figure 19 The graph shows the relationship between the amount of L-penicillamine added and the k value in urine samples under Co-120-D catalysis.

[0061] Figure 20 The graph shows the relationship between the amount of D-penicillamine added and the k value in urine samples under Co-120-D catalysis.

[0062] Figure 21 The graph shows the relationship between the amount of L-penicillamine added and the k value in serum samples under Co-120-L catalysis.

[0063] Figure 22 The graph shows the relationship between the amount of D-penicillamine added and the k value in serum samples under Co-120-L catalysis.

[0064] Figure 23The graph shows the relationship between the amount of L-penicillamine added and the k value in serum samples under Co-120-D catalysis.

[0065] Figure 24 The graph shows the relationship between the amount of D-penicillamine added and the k value in serum samples under Co-120-D catalysis. Detailed Implementation

[0066] The following specific embodiments further illustrate the content of the present invention in detail. It should also be understood that the following embodiments are only for further explanation of the present invention and should not be construed as limiting the scope of protection of the present invention. Non-essential improvements and adjustments made by those skilled in the art based on the principles described herein are all within the scope of protection of the present invention. The specific process parameters, etc., in the following examples are merely examples within a suitable range; that is, those skilled in the art can make selections within a suitable range based on the description herein, and are not intended to be limited to the specific data in the examples below. Unless otherwise specified, the raw materials, reagents, or apparatus used in the following embodiments and comparative examples can be obtained from conventional commercial sources or by existing known methods.

[0067] Preparation Example 1

[0068] This example provides a chiral MOF with divalent cobalt as the central metal and 2',2-bipyridine and chiral tartaric acids (including L-tartaric acid and D-tartaric acid) as organic ligands.

[0069] The reaction equation for the preparation of the chiral MOF is as follows: Figure 1 As shown, the specific preparation method includes the following steps:

[0070] 1) Label two 50 mL reaction vessels “L” and “D”, and add 15.0 mL of ultrapure water to each. Dissolve 0.327 g cobalt acetate tetrahydrate (1.85 mmol) and 0.300 g 2'2-bipyridine (1.90 mmol) in the aqueous solutions of the two reaction vessels respectively. Then add 0.285 g L-tartaric acid (1.9 mmol) and 0.285 g D-tartaric acid (1.9 mmol) to the two corresponding reaction vessels respectively and stir for 1.0 h to completely dissolve the solid raw materials.

[0071] 2) Place the two reaction vessels in an oven and maintain the temperature at 120℃ for 56.0 h. After the reaction is completed, cool to room temperature and wash the product three times with ultrapure water to obtain the chiral MOFs, namely L-bipyridine tartrate MOF (Co-120-L) and D-bipyridine tartrate MOF (Co-120-D). Finally, store the products in an aqueous solution.

[0072] In this example, the two N atoms (N1 and N2) of 2'2-bipyridine coordinate with the central metal Co1, and the O1, O2, O4, and O5 atoms of L-tartaric acid coordinate with the central metal Co1 to form an L-tartaric acid bipyridine MOF (Co-120-L); the two N atoms (N1 and N2) of 2'2-bipyridine coordinate with the central metal Co1, and the O1, O2, O4, and O5 atoms of D-tartaric acid coordinate with the central metal Co1 to form a D-tartaric acid bipyridine MOF (Co-120-D). The structural formula of Co-120-L is as follows. Figure 2 As shown, the structural formula of Co-120-D is as follows: Figure 3 As shown.

[0073] The crystal cell parameters of Co-120-L obtained in this example are as follows: α = 90°, β = 90°, γ = 90°; the crystal cell parameters of Co-120-D are... α=90°, β=90°, γ=90°.

[0074] The prepared hand-type MOF was characterized using X-ray powder diffraction, and its X-ray powder diffraction pattern is shown below. Figure 4 As shown in the X-ray powder diffraction pattern, the chiral MOF structures are different: Co-120-L has a characteristic peak at 9.8°, while Co-120-D has no characteristic peak at 9.8°.

[0075] The prepared chiral MOF was characterized using scanning electron microscopy (SEM), and its SEM results are shown below. Figure 5 As shown, a and b are Co-120-L, and c and d are Co-120-D. From the scanning electron microscope images, it can be seen that the morphologies of these chiral MOFs are different. Co-120-L is spindle-shaped, while Co-120-D is octahedral.

[0076] The prepared chiral MOF was characterized by nitrogen adsorption. The nitrogen adsorption-desorption curve of Co-120-L is shown below. Figure 6 As shown, the nitrogen adsorption-desorption curve of Co-120-D is as follows: Figure 7 As shown in the adsorption-desorption curves, this chiral MOF has a strong adsorption capacity, and its adsorption curves belong to type IV isotherms.

[0077] The prepared Co-120-L and Co-120-D were characterized using circular dichroism spectroscopy, and their circular dichroism chromatograms are shown below. Figure 8 As shown in the circular dichroism chromatogram, this chiral MOF exhibits symmetrical optical rotation.

[0078] Application Example 1

[0079] In this example, the Co-120-L and Co-120-D prepared in Example 1 are used as catalysts for the luminol-hydrogen peroxide chemiluminescence reaction. The specific steps are as follows:

[0080] The Co-120-L and Co-120-D prepared in Example 1 were filled into the interior of a chemiluminescent reaction cell. A peristaltic pump provided power to inject luminol solution (1.0 × 10⁻⁶) into the system piping. -5 (mol / L). Record the equilibrium baseline signal and turn off the peristaltic pump. H2O2 (1.0×10⁻⁶ mol / L) -4 A quantitative circulation (10 μL) of luminol / L solution was filled. The peristaltic pump was started, and luminol was mixed with hydrogen peroxide solution. The luminol carried the hydrogen peroxide solution into the chemiluminescence reaction cell, where it circulated and contacted the catalyst, triggering a multi-stage chemiluminescence signal.

[0081] Figure 9 This is a cyclic chemiluminescence signal diagram of the Co-120-L catalyzed luminol-hydrogen peroxide reaction. Figure 10 This is a cyclic chemiluminescence signal diagram of the Co-120-D-catalyzed luminol-hydrogen peroxide reaction. Simulation results show that the multi-level signals follow a first-order exponential decay law, the mathematical expression of which is:

[0082] I n =A exp(-t / k)+I0

[0083] I n Let A be the maximum chemiluminescence signal intensity, k be the attenuation coefficient, t be the time, and I0 be the background value.

[0084] The mathematical expression for the multi-stage signal of Co-120-L is I = 31456exp(-t / 21.2) + 2085; the mathematical expression for the multi-stage signal of Co-120-D is I = 32942exp(-t / 24.4) + 1762.

[0085] Application Example 2

[0086] In this example, Co-120-L and Co-120-D prepared in Example 1 are used as chiral guests for the identification of hydrophilic chiral drugs L-penicillamine / D-penicillamine, L-methyldopa / D-methyldopa, or quinine / quinidine. The specific steps are as follows:

[0087] The Co-120-L and Co-120-D prepared in Example 1 were filled into the interior of a chemiluminescent reaction cell. A peristaltic pump provided power to inject luminol solution (1.0 × 10⁻⁶) into the system piping. -5 (mol / L). Record the equilibrium baseline signal and turn off the peristaltic pump. Chiral drug with H2O2 (1.0×10 mol / L). -4A quantitative circulation (10 μL) of luminol / L solution was filled. The peristaltic pump was started, and luminol was mixed with the hydrogen peroxide solution of the chiral drug. The luminol carried the hydrogen peroxide solution of the chiral drug into the chemiluminescence reaction cell, where it circulated and contacted the catalyst, triggering a multi-stage chemiluminescence signal.

[0088] Figure 11 A multi-level signal diagram for the Co-120-L catalytic luminol-hydrogen peroxide reaction in Example 1, prepared by regulating chiral penicillamines (L-penicillamine and D-penicillamine). Figure 12 A multi-level signal diagram for the Co-120-D catalytic luminol-hydrogen peroxide reaction in Example 1, prepared by regulating chiral penicillamines (L-penicillamine and D-penicillamine). Figure 13 A multi-level signal diagram for the Co-120-L catalytic luminol-hydrogen peroxide reaction in Example 1, prepared by the regulation of chiral methyldopa (L-methyldopa and D-methyldopa). Figure 14 A multi-level signal diagram for the Co-120-D catalytic luminol-hydrogen peroxide reaction in Example 1, prepared by the regulation of chiral methyldopa (L-methyldopa and D-methyldopa). Figure 15 Multilevel signal diagrams for the Co-120-L catalytic luminol-hydrogen peroxide reaction in Example 1, used to regulate the preparation of quinine and quinidine. Figure 16 A multi-level signal diagram for the Co-120-D catalytic luminol-hydrogen peroxide reaction in Example 1, regulated by quinine and quinidine, is shown, where L represents quinine and D represents quinidine. The corresponding k values ​​are recorded in Table 1.

[0089] Table 1. k values ​​of Co-120-L and Co-120-D regulating chiral drugs

[0090]

[0091] from Figures 11-16 As shown in Table 1, there are significant differences in the k values ​​of Co-120-L and Co-120-D for L-penicillamine / D-penicillamine, L-methyldopa / D-methyldopa, or quinine / quinidine. By detecting the k value using the method provided in this example, rapid identification of L-penicillamine / D-penicillamine, L-methyldopa / D-methyldopa, or quinine / quinidine can be achieved.

[0092] Application Comparative Example 1

[0093] In this example, Co-120-L and Co-120-D prepared in Example 1 are used as chiral guests for the identification of chiral drugs chiral alanine, chiral cysteine, chiral phenylalanine, chiral threonine, chiral glutamic acid, chiral histidine, chiral carvone, chiral 2-pentanol, chiral 2-amino-1-pentanol, and chiral benzotetraimidazole. The specific steps are as follows:

[0094] The Co-120-L and Co-120-D prepared in Example 1 were filled into the interior of a chemiluminescent reaction cell. A peristaltic pump provided power to inject luminol solution (1.0 × 10⁻⁶) into the system piping. -5 (mol / L). Record the equilibrium baseline signal and turn off the peristaltic pump. Chiral drug with H2O2 (1.0×10 mol / L). -4 A quantitative circulation (10 μL) of luminol / L solution was filled. The peristaltic pump was started, and luminol was mixed with the hydrogen peroxide solution of the chiral drug. The luminol carried the hydrogen peroxide solution of the chiral drug into the chemiluminescence reaction cell, where it circulated and contacted the catalyst, triggering a multi-stage chemiluminescence signal.

[0095] The corresponding k values ​​are recorded in Tables 2 and 3.

[0096] Table 2. k values ​​(n=3) for the dynamic reaction detection of chiral alanine, chiral cysteine, chiral carvone, chiral 2-pentanol, chiral 2-amino-1-pentanol, chiral benzotetraimidazole, chiral phenylalanine, chiral threonine, chiral glutamic acid, and chiral histidine based on Co-120-L catalysis.

[0097] Chiral molecules k value RSD / % Chiral molecules k value RSD / % L-alanine 9.0 3.2 D-alanine 9.1 4.3 L-cysteine 11.2 5.0 D-cysteine 10.6 4.6 L-phenylalanine 12.4 4.5 D-phenylalanine 12.9 4.2 L-threonine 11.6 4.0 D-Threonine 11.9 3.5 L-glutamic acid 13.9 4.4 D-glutamic acid 14.1 3.7 L-histidine 14.1 2.4 D-histidine 14.5 4.1 (R)-(+)-carvone 12.3 3.7 (S)-(+)-carvone 12.0 3.5 (R)-2-pentanol 13.9 4.4 (S)-2-pentanol 13.5 4.3 (R)-2-amino-1-pentanol 10.2 4.9 (S)-2-amino-1-pentanol 10.5 3.8 (-)-Benztetraimidazole 12.8 4.2 (+)-Benztetraimidazole 12.5 3.2

[0098] Table 3. k values ​​(n=3) for the dynamic reaction detection of chiral alanine, chiral cysteine, chiral carvone, chiral 2-pentanol, chiral 2-amino-1-pentanol, chiral benzotetraimidazole, chiral phenylalanine, chiral threonine, chiral glutamic acid, and chiral histidine based on Co-120-D catalysis.

[0099]

[0100]

[0101] As shown in Tables 2 and 3, the k values ​​of these chiral molecules are not significantly different, and the dynamic reactions catalyzed by Co-120-L and Co-120-D cannot distinguish them. The luminol-hydrogen peroxide reactions catalyzed by Co-120-L and Co-120-D are more effective in differentiating L-penicillamine / D-penicillamine, L-methyldopa / D-methyldopa, or quinine / quinyl.

[0102] Application Example 3

[0103] This example applies the Co-120-L and Co-120-D prepared in Example 1 to the detection of chiral drug concentrations in biological samples. The specific steps are as follows:

[0104] Add 100 μL of biological sample (serum or urine sample) and 900 μL of ammonium acetate buffer solution (0.01 mol / L, pH = 5.12) to a 1.5 mL centrifuge tube, vortex for 5 min, centrifuge for 15 min (4℃, 12000 r / min), transfer 800 μL of the supernatant to another numbered centrifuge tube, incubate at -20℃ for 30 min, centrifuge again at 4℃, 12000 r / min for 5 min, and after centrifugation, transfer all the supernatant and filter it through a 0.25 μm filter membrane.

[0105] A series of concentrations of chiral penicillamine (L-penicillamine and D-penicillamine) solutions were added to biological samples such as urine and serum. Co-120-L and Co-120-D were then packed into the interior of the chemiluminescent reaction cell. A peristaltic pump provided power to inject luminol solution (1.0 × 10⁻⁶) into the system tubing. -5 (mol / L). Record the equilibrium baseline signal and turn off the peristaltic pump. Biological sample with H2O2 (1.0 × 10⁻⁶ mol / L). -4 A quantitative circulation (10 μL) of luminol / L solution was filled. The peristaltic pump was started, and luminol was mixed with the hydrogen peroxide solution of the sample. The luminol carried the hydrogen peroxide solution of the biological sample into the chemiluminescence reaction cell, where it circulated and contacted the catalyst, triggering a multi-stage chemiluminescence signal.

[0106] Figure 17 The graph shows the relationship between the amount of L-penicillamine added and the k value in urine samples under Co-120-L catalysis. Figure 18 The graph shows the relationship between the amount of D-penicillamine added and the k value in urine samples under Co-120-L catalysis. Figure 19 The graph shows the relationship between the amount of L-penicillamine added and the k value in urine samples under Co-120-D catalysis. Figure 20 The graph shows the relationship between the amount of D-penicillamine added and the k value in urine samples under Co-120-D catalysis. Figure 21 The graph shows the relationship between the amount of L-penicillamine added and the k value in serum samples under Co-120-L catalysis. Figure 22 The graph shows the relationship between the amount of D-penicillamine added and the k value in serum samples under Co-120-L catalysis. Figure 23 The graph shows the relationship between the amount of L-penicillamine added and the k value in serum samples under Co-120-D catalysis. Figure 24 This is a graph showing the relationship between the amount of D-penicillamine added and the k value in serum samples under Co-120-D catalysis. Figures 17-24 It is known that the amount of chiral penicillamine added to biological samples is linearly related to the k value. Therefore, by using the multi-level signal of luminol-hydrogen peroxide catalyzed by the chiral MOF of this invention to obtain the k value, rapid detection of chiral penicillamine concentration in biological samples can be achieved.

[0107] The chiral metal-organic framework (chiral MOF) of this invention exhibits stable physicochemical properties and possesses advantages such as inexpensive raw materials, mild preparation conditions, no need for organic solvents, environmental friendliness, and the ability to be prepared in large quantities. The chiral MOF catalyzes the luminol-hydrogen peroxide reaction, generating multi-level signals in a cyclic chemiluminescence system. Furthermore, using the carbonyl group in chiral tartaric acid as a chiral recognition site, the chiral MOF can selectively recognize polar chiral drugs, particularly achieving rapid recognition of L-penicillamine / D-penicillamine, L-methyldopa / D-methyldopa, or quinine / quinidine. Simultaneously, the chiral MOF can also be used to detect the concentration of chiral drugs in biological samples. Therefore, the chiral MOF provided by this invention has significant application prospects in drug analysis and drug metabolism.

Claims

1. The application of a chiral metal-organic framework compound in recognizing chiral drugs, characterized in that, The chiral metal-organic framework compound comprises a central metal, organic ligand I, and organic ligand II; the central metal is cobalt, organic ligand I is bipyridine, and organic ligand II is chiral tartaric acid, wherein the tartaric acid comprises... L Tartaric acid or D -tartaric acid; The crystal cell parameters of the chiral metal-organic framework compound are as follows: a =6.600Å, b =14.223Å, c =19.095Å, α =90 , β =90 , γ =90 ;or a =6.591Å, b =14.212Å, c =19.087Å, α =90 , β =90 , γ =90 ; The chiral drug includes L -Penicillamine / D -Penicillamine, L -Methyldopa / D At least one of methyldopa or quinine / quinidine.

2. The application according to claim 1, characterized in that, The cobalt is divalent cobalt; the bipyridine includes 2'2-bipyridine, 4'4-bipyridine, or a combination thereof.

3. The application according to claim 1, characterized in that, The chiral metal-organic framework compound is prepared by a method comprising the following steps: taking an aqueous mixture containing cobalt salt, bipyridine and chiral tartaric acid, and subjecting it to a hydrothermal reaction to obtain the chiral metal-organic framework compound.

4. The application according to claim 3, characterized in that, The molar ratio of the cobalt salt, bipyridine, and chiral tartaric acid is 1:(1~1.5):(1~1.5).

5. The application according to claim 3, characterized in that, The hydrothermal reaction temperature is 100~140℃; the hydrothermal reaction time is 50~62h.

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