Preparation method of dimer alpha-cyclodextrin artificial transmembrane channel and application of dimer alpha-cyclodextrin artificial transmembrane channel in lithium ion purification

Abstract

The invention discloses a preparation method of a dimer alpha-cyclodextrin artificial transmembrane channel and application of the dimer alpha-cyclodextrin artificial transmembrane channel in lithium ion purification, and belongs to the field of organic chemistry. Alpha-cyclodextrin is used as a skeleton for modification, the organic nanotube is synthesized, the compound has a complete cylinder wall structure, and the interior of the tubular structure is modified with a multi-triazole group as a metal binding site. Nuclear magnetic titration experiments prove that the molecule has relatively strong binding capacity to lithium ions. In addition, a vesicle experiment proves that a target molecule can be successfully embedded into the membrane and can specifically transport lithium ions, and the transport efficiency of the target molecule is far higher than that of sodium and potassium ions. The designed lithium ion channel can efficiently and selectively mediate the transmembrane of the lithium ions, and a new thought and method are provided for efficient separation and extraction of the lithium ions.

Description

Technical Field

[0001] This invention relates to the field of organic chemistry, specifically to a method for preparing dimerized α-cyclodextrin artificial transmembrane channels and their application in lithium-ion purification. Background Technology

[0002] As a key element of modern energy technology, lithium ions have become a crucial resource for future development due to their irreplaceable role in energy, industry, and other fields. Therefore, the supply of lithium ions is vital for future development. Currently, lithium ion mining mainly relies on the extraction and purification of lithium ions from lithium carbonate ore, which is energy-intensive and global lithium reserves are limited. While seawater contains a vast amount of lithium, its concentration is low, and seawater lithium extraction efficiency is far lower than existing methods, resulting in high costs, enormous energy consumption, and environmental unfriendliness. Therefore, developing efficient, low-energy-consumption, and economically viable seawater lithium extraction methods is of great significance.

[0003] Natural ion channels are key proteins on the cell membrane regulating transmembrane ion transport, often exhibiting extremely high ion selectivity and mediating the transmembrane transport of single ions across lipid bilayers. This characteristic has attracted the attention of chemists. Chemists hope to use natural ion channel proteins as mimics to construct highly selective artificial ion channels through artificial systems, retaining the advantages of high efficiency and selectivity of natural ion channel proteins while overcoming their disadvantages such as structural instability and susceptibility to degradation. This would enable highly efficient and selective mediation of single-ion transmembrane transport in complex environments, achieving low-energy, high-efficiency ion enrichment and separation. Although some artificial ion channels have shown promising prospects in terms of high ion selectivity, due to the high dehydration energy of lithium ions, reports on artificial ion channels that can selectively mediate lithium ion transmembrane transport are still limited. Further industrial applications still face challenges such as complex synthesis steps, difficulties in structural modification, and low selectivity. Therefore, based on existing technologies, developing novel artificial ion channels that are easy to synthesize, have flexible structures that can be modified, and exhibit clear lithium-ion selectivity is of great value for promoting low-energy seawater lithium extraction and is also a technical problem that urgently needs to be solved in this field. Summary of the Invention

[0004] The technical problem solved by this invention is to provide an artificial transmembrane channel with lithium ion purification function and its preparation method. The dimerized α-cyclodextrin artificial transmembrane channel prepared by this method can be used for lithium ion purification.

[0005] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: a dimerized α-cyclodextrin artificial transmembrane channel, the general structural formula of which is: .

[0006] This invention also provides a method for preparing the aforementioned dimerized α-cyclodextrin artificial transmembrane channel, expressed by the following reaction equation: .

[0007] Furthermore, in the first step of the above technical solution, hexapropynyl-hexathioacetyl-α-cyclodextrin A is used as a raw material and reacted with compound B in CuI / DIPEA / DMF at 65°C to obtain compound 1a.

[0008] Furthermore, in the second step of the above technical solution, under nitrogen protection, compound 1a is used as a raw material to obtain compound 2 in a sodium methoxide / anhydrous methanol solution.

[0009] Furthermore, in the third step of the above technical solution, compound 2 is used as a raw material and reacted with trifluoroacetic acid in a dichloromethane solution at room temperature to obtain compound 3.

[0010] .

[0011] Furthermore, in the first step of the above technical solution, hexapropynyl-hexathioacetyl-α-cyclodextrin A is used as a raw material and reacted with compound C or D in CuI / DIPEA in acetone solution at 65°C to obtain compound 4a or 5a.

[0012] Furthermore, in the second step of the above technical solution, compound 4a or 5a is used as a raw material and reacted with sodium methoxide in a methanol solution at room temperature to obtain compound 4 or 5.

[0013] This invention also provides the application of the aforementioned dimerized α-cyclodextrin artificial transmembrane channel in lithium ion purification. Attached Figure Description

[0014] Figure 1 The NMR titration spectrum of compound 4a bound to lithium ions in Example 4 is shown. Figure 2 This is a graph showing the selectivity of compound 3 as an artificial transmembrane channel for anions in Example 5; Figure 3 This is a graph showing the selectivity of compound 4 as an artificial transmembrane channel for cations in Example 6. Detailed Implementation

[0015] The following examples further illustrate the above-described content of the present invention, but it should not be construed as limiting the scope of the subject matter of the present invention to the following examples. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Example 1

[0016] Preparation of compounds 2 and 3: , Compound 1 (300 mg, 0.19 mmol) was dissolved in ultra-dry DMF, and N,N-diisopropylethylamine (DIPEA, 60 µL) and cuprous iodide (CuI, 20 mg) were added. The reaction mixture was stirred at 65 °C for 12 h. After the reaction was completed, the solvent was removed under vacuum, the residue was dissolved in dichloromethane, washed with water and brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography using dichloromethane:methanol (15:1) as the eluent to give the desired white solid product 1a. 1 H NMR (400 MHz, CDCl3): δ 7.80 (s, 6H), 5.15 (s, 12H), 4.98 (d, J = 12Hz, 6H), 4.88-4.79(m,12H), 4.57-4.53(m, 18H), 3.97(q, J = 8.0 Hz, 12H), 3.84 (t, J = 4.0 Hz, 12H),3.55-3.48 (m, 24H), 3.29-3.24 (m, 24H), 2.32(s, 18H), 1.43 (s, 54H). HRMS:calcd for C 120 H 192 N 24 O 48 S6[M+Na] 2+ : 1488.0731, found 1488.0841.

[0017] , Under nitrogen protection, compound 1a (250 mg, 0.336 mmol) was dissolved in 1.5 M sodium methoxide / anhydrous methanol solution (0.5 mL) in ultradry methanol (3 mL). After stirring, 6 mL of deionized water was added to the reaction system, and the mixture was stirred vigorously in air for 48 h. The residue was purified by reverse-phase high-pressure extraction after adding an appropriate amount of acetonitrile. The eluent was A(H2O):B(CH3CN), with a linear gradient of B (50%-65%, 10 min, 65%-75%, 15 min, 75%-95%, 5 min). The flow rate was 30.0 mL / min. Lyophilization gave white product 2, with a yield of 5%. 1 H NMR (400 MHz, CDCl3): δ 7.80 (s, 12H), 5.15 (s, 12H), 4.98 (d, J= 12Hz, 12H), 4.88- 4.79(m, 24H), 4.57-4.53(m, 36H), 3.97(q, J = 8.0Hz, 24H), 3.84 (t, J = 4.0 Hz, 24H), 3.55-3.48(m, 48H), 3.29-3.24(m, 48H),1.43(s, 108H). HR MS: calcd for C 216 H 348 N 48 O 84 S 12 [M+Na] 3+ :1805.0261, found1805.0348.

[0018] , Compound 2 (100 mg, 0.18 mmol) was dissolved in dichloromethane (5 mL), and trifluoroacetic acid (5 mL) was added. The reaction was carried out at room temperature for 3 hours. After the reaction was completed, the dichloromethane was removed by concentration under reduced pressure. A suitable amount of deionized water was added to the residue to form a homogeneous solution, and then the aqueous solution was transferred to a lyophilizer for freeze drying to obtain compound 3 as a white powder, with a yield of 59%. 1 H NMR (400 MHz, D2O): δ 8.11 (s, 12H), 5.05 (d, J = 4.0 Hz, 12H), 4.83 (s, 24H), 4.66 (t, J = 8.0 Hz, 24H), 3.99-3.86 (m, 49H), 3.68 (t, J = 8.0 Hz, 24H),3.5-3.51 (m, 24H), 3.50- 3.38(m, 24H), 3.13 (t, J = 12.0 Hz, 24H), 1.16(d, J =16.0 Hz, 12H). HRMS: calcd for C 156 H 252 N 48 O 60 S 12 [M+H] 3+ :1381.8347, found1381.8431. Example 2

[0019] Preparation of compound 4: , Compound 1 (500 mg, 0.32 mmol) and 840 mg (4.86 mmol) of ethyl azidomethyl carbonate were dissolved in acetone. NN-diisopropylethylamine (DIPEA, 60 µL) and cuprous iodide (CuI, 20 mg) were added, and the mixture was stirred at 65 °C for 8 h. After the reaction was complete, the solvent was removed under vacuum, and the remaining solid was dissolved in dichloromethane, washed with deionized water and saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The product was then mixed with silica gel and separated by column chromatography in a dichloromethane-methanol (DCM: CH3OH = 15:1) solvent system, finally yielding a white solid compound 4a in 82% yield. 1 H NMR (400 MHz, D2O) δ 8.11(s, 12H), 5.05 (d, J = 4.0 Hz, 12H), 4.83 (s, 24H), 4.66 (t, J = 8.0 Hz, 24H),3.99-3.86 (m, 49H), 3.68 (t, J = 8.0 Hz, 24H), 3.58-3.51 (m, 24H), 3.50-3.38(m, 24H), 3.13 (t, J =12.0 Hz, 24H), 1.16(d, J =16.0 Hz, 12H). HRMS: calcd forC 102 H 150 N 18 O 48 S6[M+Na] 2+ : 1316.8996, found1316.9091.

[0020] , Under nitrogen protection, 400 mg (0.15 mmol) of compound 4a was dissolved in 5 mL of ultra-dry methanol. After dissolution, 1.5 mL of sodium methoxide solution was added, and the mixture was stirred at room temperature for 8 h. Then, 5 mL of deionized water (H2O) was added, and the mixture was stirred for 72 h. After the reaction was complete, 1 M HCl was added to acidify until a white precipitate formed. After centrifugation, the residue was washed with acetone solution to obtain a white precipitate. The precipitate was purified by reverse high-pressure extraction using an acetonitrile:water ratio of 1:1 eluent with A (H2O) and B (CH3CN) as eluents. The linear gradient was B (5%-25%, 15 min, 25%-35%, 15 min, 35%-50%, 5 min, 50%-60%, 5 min) at a flow rate of 30.0 mL / min to obtain compound 4. 1 H NMR (400 MHz, DMSO): δ 12.60 (s, 12H), 8.11 (s, 12H), 4.95 (s, 12H), 4.80 (d, J = 4.0 Hz, 36H), 4.55 (t, J = 8.0 Hz, 48H), 4.02 (s, 36H), 3.88 (t, J = 8.0 Hz, 60H), HRMS: calcd for C 156 H 216 N 36 O 84 S 12 [M+H] 3+ : 1441.3534, found 1441.3525. Example 3

[0021] Preparation of compound 5: , Under nitrogen protection, compound 1 (450 mg, 0.29 mmol) and 754 mg (4.36 mmol) of azidomethylperacetate were dissolved in acetone. NN-diisopropylethylamine (DIPEA, 60 µL) and cuprous iodide (CuI, 70 mg) were added, and the reaction mixture was stirred at 65 °C for 8 h. After the reaction was complete, the solvent was removed under vacuum, and the residue was dissolved in dichloromethane, washed with deionized water and saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The resulting product was mixed with silica gel and separated by column chromatography in a dichloromethane-methanol (DCM:CH3OH = 15:1) solvent system to give compound 5a in 80% yield. 1H NMR (400 MHz, CDCl3): δ 7.80 (s, 6H), 5.01-4.88 (m, 12H), 4.79(d, J = 16 Hz, 6H), 4.60-4.54 (m,18H), 4.18 (t, J = 8.0Hz, 12H), 4.08 (t, J = 16.0Hz, 6H), 3.96 (t, J = 24.0Hz, 6H), 3.88 (t, J = 12 Hz, 12H), 3.64 (t, J = 8.0Hz, 12H), 3.52-3.50 (m, 6H), 3.23-3.15(m, 12H), 2.31(s, 18H), 2.05(s, 12H). HRMS: calcd for C 102 H 150 N 18 O 48 S6[M+Na] 2+ : 1317.9029, found 1317.9419.

[0022] , Under nitrogen protection, 300 mg (0.15 mmol) of compound 5a was dissolved in 5 mL of ultra-dry methanol. After dissolution, 1.5 mL of sodium methoxide solution was added, and the mixture was stirred at room temperature for 5 h. Then, 5 mL of deionized water (H2O) was added, followed by 1.5 mL of sodium methoxide, and the mixture was stirred for 72 h. The system was lyophilized and purified by reverse high pressure elution. A linear gradient elution was performed using H2O (phase A) and acetonitrile (phase B) as mobile phases: B (5%-20%, 5 min, 20%-30%, 20 min, 30%-50%, 10 min, 50%-60%, 5 min, 60%-95%, 5 min), at a flow rate of 30.0 mL / min, to obtain compound 5. 1 H NMR (400 MHz, DMSO-d6): δ 8.09 (s, 12H), 4.95 (s, 12H), 4.80 (s, 24H), 4.62 (s, 12H), 4.52(t, J = 12.0Hz, 24H), 3.80 (t, J = 12.0Hz, 60H), 3.45(d, J= 4.0Hz, 36H), 3.41(d, J = 4.0Hz, 60H). HRMS: calcd for C 156 H 240 N 36 O 72 S 12 [M+Na] 3+ : 1470.7528, found1470.7579. Example 4

[0023] The ability of the molecule to transport Li+ ions across the membrane was verified by nuclear magnetic resonance titration experiments, as well as the binding ratio with lithium ions was verified.

[0024] Compound 4a was selected as the host molecule, and LiPF6 (lithium hexafluorophosphate) as the guest molecule for the experiment. Ten groups of compounds 4a with different concentrations were prepared and loaded into NMR tubes. The concentration of the guest molecule LiPF6 in the NMR tubes was gradually increased, and the NMR tubes were placed at 25°C for two hours to allow compounds 4a and LiPF6 to fully react. ¹H NMR measurements were then performed. Example 5

[0025] Cyclodextrin derivatives can selectively transport anions during the process of mediating ion transmembrane transport.

[0026] 1. Preparation of biomimetic cells (large monolayer vesicles (LUVs)): Weigh 20 mg of EYPC and dissolve it in chloroform (CHCl3, 5.0 mL) to form a homogeneous solution. Transfer the solution to a rotary evaporator and evaporate to dryness at 40 °C. After removing the chloroform, a homogeneous lipid film forms on the inner wall of the container. Subsequently, the obtained lipid film is placed in a high vacuum environment for continuous drying for 6 hours to completely remove residual solvent. A buffer solution containing HPTS (2 mL, HEPES, 10 mM) and NaM (M = Cl) is then added. - , Br - SO4 2- , ClO - Mix 100 mM, pH = 7) to obtain a mixed solution. Maintain a constant temperature using a vortex mixer for 1.5 h. After rapid freezing with liquid nitrogen for 1.5 min, thaw the frozen solution in water at 40°C, repeating this freeze-thaw cycle 10 times. Extrude the suspension through a polycarbonate membrane (0.2 μm) 9 times. Place the resulting solution in a dialysis bag (MWCO = 14000) for dialyzing three times using the prepared buffer solution, at intervals of 1 h, 1 h, and 8 h, to remove unencapsulated HPTS.

[0027] 2. Fluorescence test: HEPES buffer solution (2.0 mL, 10 mM HEPES, 100 mM NaNO3, pH = 8.0) and the prepared LUVs suspension were placed in a fluorescence cuvette. Compound 3 and DMSO solution (9 μL) were added to the cuvette. The fluorescence intensity at 510 nm was continuously monitored over 480 s, with an excitation wavelength of 460 nm. After 6 min of detection, 10 µL of vesicle quencher (X-100) was added to the cuvette. The cuvette was vigorously shaken to rupture the vesicles until the fluorescence intensity (I∞) no longer changed. The data were normalized. The specificity of compound 3 for anions was obtained.

[0028] . Example 6

[0029] Cyclodextrin derivatives exhibit lithium-ion selectivity in mediating transmembrane ion transport.

[0030] 1. Preparation of biomimetic cells (large monolayer vesicles (LUVs)): 20 mg of EYPC was dissolved in chloroform (CHCl3, 5.0 mL) to form a homogeneous solution. This solution was transferred to a rotary evaporator and evaporated at 40°C to remove the chloroform, resulting in a homogeneous lipid film on the inner wall of the container. The resulting lipid film was then dried under high vacuum for 6 hours to completely remove residual solvent. After drying, 1 mL of a HEPES buffer solution containing 0.1 mM HPTS (10 mM HEPES, 100 mM NaCl, pH = 7.0) was added to a 25 mL round-bottom flask and vortexed for 2 hours. A milky white lipid suspension was obtained. This suspension was then subjected to twelve freeze-thaw cycles, each cycle consisting of rapid freezing in liquid nitrogen followed by thawing in a warm water bath. The treated suspension was then repeatedly extruded nine times through a 0.2 μm pore size polycarbonate membrane to obtain a preliminary vesicle suspension. Finally, using a dialysis bag with a molecular weight cutoff of 14,000, the dialysis bag was placed in 300 mL of pH 7 HEPES buffer solution and dialyzed four times to produce a vesicle suspension ([lipid] = 13.3 mM).

[0031] 2. Fluorescence test: Draw 2 mL of NaCl buffer solution (HEPES (10 mM)) into a quartz cuvette using a syringe, and pipette 100 µL of MCl (100 mM, M = Li) into the cuvette. + Na + , K + Rb + or Cs+ A suspension of LUVs (pH = 7.0) was prepared in a quartz cuvette. At 0.5 min, 3 µL of DMSO solution was added to the cuvette to prepare compound 4, and the fluorescence intensity (It) at 510 nm (excitation wavelength 460 nm) was continuously monitored. 10 µL of X-100 (Triton) aqueous solution was added with gentle agitation. The data were normalized after the fluorescence intensity (It) ceased to change. This revealed that compound 4 exhibited cation-specific selectivity.

[0032] .

[0033] The above embodiments describe the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the present invention. Various changes and modifications can be made to the present invention without departing from its principles, and all such changes and modifications fall within the scope of protection of the present invention.

Claims

1. A dimeric a-cyclodextrin artificial transmembrane channel, characterized in that, The structural general formula is: 。 2. The method for synthesizing the dimerized α-cyclodextrin artificial transmembrane channel as described in claim 1, characterized in that, The method comprises the following steps: Method A: ， Method B: 。 3. The method of claim 1, wherein the synthetic method of a dimeric a-cyclodextrin artificial transmembrane channel is characterized by: Method A first step, hexa-propargyl-hexathioacetyl-α-cyclodextrin A as raw material, with compound B in CuI / DIPEA / DMF 65 DEG C, compound 1a is obtained.

4. The method of claim 1, wherein the synthetic method of a dimeric a-cyclodextrin artificial transmembrane channel is characterized by: Method A second step, under nitrogen protection, compound 1a as raw material, in sodium methoxide / anhydrous methanol solution, compound 2 is obtained.

5. The method of claim 1, wherein the synthetic method of a dimeric a-cyclodextrin artificial transmembrane channel is characterized by: Method A third step, compound 2 as raw material, with trifluoroacetic acid in dichloromethane solution, room temperature, compound 3 is obtained.

6. The method of claim 1, wherein the synthetic method of a dimeric a-cyclodextrin artificial transmembrane channel is characterized by: Method B first step, hexa-propargyl-hexathioacetyl-α-cyclodextrin A as raw material, with compound C or D in CuI / DIPEA in acetone solution 65 DEG C, compound 4a or 5a is obtained.

7. The method for synthesizing the dimerized α-cyclodextrin artificial transmembrane channel according to claim 1, characterized in that: Method B second step, compound 4a or 5a as raw material, with sodium methoxide in methanol solution, room temperature, compound 4 or 5 is obtained.

8. The application of the dimeric α-cyclodextrin artificial transmembrane channel in the purification of lithium ions according to claim 1.

Images