Artificial ion transport system and application of light-driven molecular motor with antibacterial and antitumor activities

Abstract

The present invention discloses an artificial ion transport system and application of a light-driven molecular motor with antibacterial and anti-tumor activity. The general structural formula of a light-driven molecular motor with a large steric olefin and unidirectional rotation is shown in any one of Formulas I to III: #imgabs0# The light-driven molecular motor with a multi-substituted large steric olefin provided by the present invention is a type of transporter molecule that can be inserted into a phospholipid bilayer membrane for light-controlled ion transmembrane transport, and has the advantages of controllable structure and easy derivatization. Transmembrane transport molecules can selectively transport ions across the membrane, and accelerate ion transmembrane transport by driving the motor movement through light, thereby realizing light-controlled and time-space precise gated ion transmembrane transport. In addition, the molecule can realize light-regulated ion transport on cell membranes and bacterial membranes, destroy the balance of ions inside and outside the cell to achieve excellent photosensitivity antibacterial and anti-tumor activity, and has good application prospects in the field of biomedicine.

Description

Technical Field

[0001] The invention belongs to the technical field of artificial ion transporters, and in particular relates to a light-gated artificial ion transport system with antibacterial and antitumor activities and its application in antibacterial and antitumor aspects. Background Art

[0002] Cells are the basic units of life activities. In order to maintain survival and promote metabolism, cells need to exchange nutrients and communicate information with the surrounding environment. Ion transporters are composed of special proteins produced by cells. They regulate the entry and exit of corresponding ions in cells alone or in aggregate and are embedded in the cell membrane, which is of great significance for realizing various cell functions. The transport of ions on the cell membrane is closely related to many life activities. Abnormal function of ion transporters can cause many diseases, such as cystic fibrosis, congenital myospasm, retinitis pigmentosa, etc. In order to explore the pathogenic mechanism of these diseases and discover specific therapeutic drugs, scientists began to analyze transporters and design artificially synthesized ion transporters to simulate the function of natural transporters, hoping to replace natural proteins with abnormal structure and function to achieve the treatment of related diseases.

[0003] Artificially synthesized ion transporters can exhibit their biological activity by inserting into the cell membrane and changing the ion concentration gradient inside and outside the cell. To date, several synthetic ion transporters have been shown to have antibacterial and anticancer effects (Saha T., atel. (2016) JAm Chem Soc., 138 (24): 7558-7567; Peters, AD, at el. (2020) Chem. Sci., 11 (27): 7023-7030). However, most reported artificial ion transporters have limited their practical therapeutic application value due to their relatively low ion transport activity and cell non-specificity. Therefore, the development of artificial ion transport systems that can efficiently transport ions on the cell membrane and selectively kill cancer cells and bacteria has aroused widespread interest among scientists. Although it is extremely challenging, it is urgent. In summary, it can be seen that the research and development of artificial transmembrane channels with multiple biological activities (such as antibacterial activity and anti-tumor cell activity) has broad application prospects in the biomedical field. Summary of the invention

[0004] The present invention is directed to the above problems. The first purpose is to provide a light-gated artificial ion transport system molecule, in particular a light-driven molecular motor of a multi-substituted bulky sterically hindered olefin. The motor molecule can be used for transmembrane transport of ions. Under light, the rotational motion of the molecular motor can significantly accelerate the transmembrane transport of ions and improve the molecular transport efficiency.

[0005] The second object of the present invention is to provide the application of the above-mentioned light-driven molecular motor, which has obvious light-controlled inhibition of the growth of bacteria and cancer cells and has good application prospects in biomedical fields such as antibacterial and anti-tumor.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0007] The first aspect of the present invention provides a light-driven molecular motor based on a large sterically hindered olefin, and the general structural formula I is shown below:

[0008]

[0009] Where X is N, O, S atom or CH 2 , CH 2 -CH 2 , CH 2 -CH 2 -CH 2 ;

[0010] Y is CH 2 , S, N, O, CH 2 -CH 2 , CH 2 -S, CH 2 -O, CH 2 -N-Boc;

[0011] Z is methyl, ethyl, propyl, isopropyl;

[0012] R 1 , R 2 is a linking group, each independently selected from any one of the following groups: hydrogen, a triazole substituent, an acetylene substituent, an ether bond substituent, an ester bond substituent, a carbonate bond substituent, a carbamate bond substituent, a mercaptoformate substituent or a phosphate bond substituent, an aryl group, a heteroaryl group, an alkyl group, an alkylene group, a modified alkyl group or a modified alkylene group, preferably an acetylene substituent;

[0013] R 3 , R 4 Selected from hydrogen, crown ether, aza crown ether, benzo crown ether, cyclodextrin, aryl-triazole derivatives, amide recognition groups, urea recognition groups.

[0014] Furthermore, in order to make the molecule have the function of ion transmembrane transport, R 3 , R 4 At least one of them is a group having ion recognition function.

[0015] Furthermore, the alkyl group is a saturated or unsaturated aliphatic straight chain or branched alkyl group having 1 to 30 carbon atoms; the alkylene group is a saturated or unsaturated aliphatic straight chain or branched alkylene group having 1 to 30 carbon atoms; the modified alkyl group is an alkyl group in which any carbon atom is selected from halogen atoms, -OH, -SH, -NO 2 , -CN, -CHO, -COOH, ester group, amide group, aryl group, arylene group, -CO-, -O-, -S-, -SO-, -SO 2 -, a group obtained by replacing at least one of a primary amine group, a secondary amine group, a tertiary amine group, a quaternary ammonium salt group, a saturated or unsaturated monocyclic or bicyclic cycloalkylene group, and a bridged aliphatic heterocycle, wherein the modified alkyl group has 1 to 30 atoms, and its carbon-carbon single bond can be arbitrarily replaced by a carbon-carbon double bond or a carbon-carbon triple bond;

[0016] The modified alkylene group is an alkylene group in which any carbon atom is selected from halogen atoms, -OH, -SH, -NO 2 , -CN, -CHO, -COOH, ester group, amide group, aryl group, arylene group, -CO-, -O-, -S-, -SO-, -SO 2 -, a group obtained by replacing at least one of a primary amine group, a secondary amine group, a tertiary amine group, a quaternary ammonium salt group, a saturated or unsaturated monocyclic or bicyclic cycloalkylene group, and a bridged aliphatic heterocycle, wherein the modified alkylene group has 1 to 30 atoms, and its carbon-carbon single bond can be arbitrarily replaced by a carbon-carbon double bond or a carbon-carbon triple bond;

[0017] Preferably, in the molecular formula of the light-driven molecular motor artificial ion transport system, the motor molecule is selected from one of the following structures: X is O, S atom or CH 2 ; R 3 , R 4 At the same time, a group having an ion recognition function is selected, and the groups are the same and are selected from crown ethers, azacrown ethers, benzocrown ethers, cyclodextrins, aryl-triazole derivatives, amide recognition groups, and urea recognition groups;

[0018] More preferably, the molecule of the light-driven molecular motor artificial ion transport system is one of the following structures I-1 to I-6:

[0019]

[0020]

[0021] Where X is O, S atom or CH 2 ;

[0022] Y is CH 2 , CH 2 -CH 2 , CH 2 -S, CH2 -O;

[0023] Z is methyl, ethyl, propyl, isopropyl;

[0024] m and n are both integers of 1-8, and t is an integer of 1-3.

[0025] The second aspect of the present invention provides a visible light-driven molecular motor based on a large sterically hindered olefin, and the general structural formula II is shown below:

[0026]

[0027] Where X is N, O, S atom or CH 2 , CH 2 -CH 2 , CH 2 -CH 2 -CH 2 ;

[0028] Y is CH 2 , S, N, O, CH 2 -CH 2 , CH 2 -S, CH 2 -O、CH 2 -N-Boc;

[0029] Z is methyl, ethyl, propyl, isopropyl;

[0030] R 1 , R 2 is a linking group, each independently selected from any one of the following groups: hydrogen, a triazole substituent, an acetylene substituent, an ether bond substituent, an ester bond substituent, a carbonate bond substituent, a carbamate bond substituent, a mercaptoformate substituent or a phosphate bond substituent, an aryl group, a heteroaryl group, an alkyl group, an alkylene group, a modified alkyl group or a modified alkylene group;

[0031] R 3 , R 4 Selected from hydrogen, crown ether, aza crown ether, benzo crown ether, cyclodextrin, aryl-triazole derivatives, amide recognition groups, urea recognition groups.

[0032] Furthermore, in order to make the molecule have the function of ion transmembrane transport, R 3 , R 4 At least one of them is a group having ion recognition function.

[0033] Furthermore, the alkyl group is a saturated or unsaturated aliphatic straight chain or branched alkyl group having 1 to 30 carbon atoms; the alkylene group is a saturated or unsaturated aliphatic straight chain or branched alkylene group having 1 to 30 carbon atoms; the modified alkyl group is an alkyl group in which any carbon atom is selected from halogen atoms, -OH, -SH, -NO 2 , -CN, -CHO, -COOH, ester group, amide group, aryl group, arylene group, -CO-, -O-, -S-, -SO-, -SO 2 -, a group obtained by replacing at least one of a primary amine group, a secondary amine group, a tertiary amine group, a quaternary ammonium salt group, a saturated or unsaturated monocyclic or bicyclic cycloalkylene group, and a bridged aliphatic heterocycle, wherein the modified alkyl group has 1 to 30 atoms, and its carbon-carbon single bond can be arbitrarily replaced by a carbon-carbon double bond or a carbon-carbon triple bond;

[0034] The modified alkylene group is an alkylene group in which any carbon atom is selected from halogen atoms, -OH, -SH, -NO 2 , -CN, -CHO, -COOH, ester group, amide group, aryl group, arylene group, -CO-, -O-, -S-, -SO-, -SO 2 -, a group obtained by replacing at least one of a primary amine group, a secondary amine group, a tertiary amine group, a quaternary ammonium salt group, a saturated or unsaturated monocyclic or bicyclic cycloalkylene group, and a bridged aliphatic heterocycle, wherein the modified alkylene group has 1 to 30 atoms, and its carbon-carbon single bond can be arbitrarily replaced by a carbon-carbon double bond or a carbon-carbon triple bond;

[0035] R 5 , R 6 , R 7 Each independently selected from any one of the following groups: hydrogen, hydroxyl, methoxy, alkyl, aryl, alkoxy, amino, substituted amino, ester, amide;

[0036] Preferably, in the molecular formula of the visible light driven molecular motor artificial ion transport system, the motor molecule is selected from one of the following structures: X is O, S atom or CH 2 ;

[0037] R 3 , R 4 At the same time, a group having an ion recognition function is selected, and the groups are the same and are selected from crown ethers, azacrown ethers, benzocrown ethers, cyclodextrins, aryl-triazole derivatives, amide recognition groups, and urea recognition groups;

[0038] More preferably, the molecule of the artificial ion transport system of the visible light driven molecular motor is any one of the following structures II-1 to II-6:

[0039]

[0040]

[0041] Where X is O, S atom or CH 2 ;

[0042] Y is CH 2 , CH 2 -CH 2 , CH 2 -S, CH 2 -O;

[0043] Z is methyl, ethyl, propyl, isopropyl;

[0044] m and n are both integers of 1-8, and t is an integer of 1-3;

[0045] R 5 , R 6 , R 7 Each is independently selected from any one of the following groups: hydroxyl, methoxy, alkyl, aryl, alkoxy, amino, substituted amino, ester, and amide.

[0046] The third aspect of the present invention provides a light-driven molecular motor based on a large sterically hindered olefin, and the general structural formula III is shown as follows:

[0047]

[0048] R 1 , R 2 Each independently selected from the following structures: a triazole substituent, an acetylene substituent, an ether bond substituent, an ester bond substituent, an amide bond substituent, a carbonate bond substituent, a carbamate bond substituent, a mercaptoformate substituent or a phosphate bond substituent, an alkyl group, an alkylene group, a modified alkyl group or a modified alkylene group;

[0049] R 3 , R 4 Selected from hydrogen, crown ether, aza crown ether, benzo crown ether, cyclodextrin, aryl-triazole derivatives, amide recognition groups, urea recognition groups.

[0050] Furthermore, in order to make the molecule have the function of ion transmembrane transport, R 3 , R 4 At least one of them is a group having ion recognition function.

[0051] Preferably, R 3 , R 4 At the same time, a group having an ion recognition function is selected, and the groups are the same and are selected from crown ethers, azacrown ethers, benzocrown ethers, cyclodextrins, aryl-triazole derivatives, amide recognition groups, and urea recognition groups;

[0052] R 5 , R6 , R 7 and R 8 Each independently selected from any one of the following groups: hydrogen, methoxy, alkoxy, substituted amino, ester, alkyl, alkylene, modified alkyl or modified alkylene;

[0053] More preferably, the molecule of the light-driven molecular motor artificial ion transport system is any one of the following structures III-1 to III-5:

[0054]

[0055] Among them, R 5 , R 6 , R 7 and R 8 Each independently selected from any one of the following groups: hydrogen, methoxy, alkoxy, substituted amino, ester, alkyl, alkylene, modified alkyl or modified alkylene;

[0056] m and n are both integers of 1-8, and t is an integer of 1-3.

[0057] The fourth aspect of the present invention provides specific applications of the above-mentioned light-driven molecular motor: the first application is application in the preparation of anti-tumor drugs, and the second application is application in the preparation of antibacterial agents.

[0058] The light-driven molecular motor of the present invention has significant anti-tumor cell activity and the effect of inhibiting tumor cell growth under ultraviolet light, and can be used alone to prepare anti-tumor drugs, or combined or conjugated with other anti-tumor compounds for anti-tumor treatment.

[0059] Preferably, the tumors include cervical cancer, liver cancer, lung cancer, colorectal cancer, breast cancer, prostate cancer, hepatocellular carcinoma and leukemia. Through experiments, the light-driven molecular motor of the present invention has a significant inhibitory effect on human cervical cancer cells (HeLa), human liver cancer cells (HepG2), human lung cancer cells (A549), human colorectal cancer cells (HCT116), human breast cancer cells (MCF-7), human small lung cancer cells (NCI-H460), human prostate cells (PC-3), human liver cancer cells (SK-HEP-1) and human leukemia cells (K562).

[0060] In the second application, the light-driven molecular motor of the present invention has a broad-spectrum antibacterial property and has the ability to significantly reduce bacterial growth and proliferation under ultraviolet light, and can be combined or conjugated with other antibacterial drugs for antibacterial treatment.

[0061] Preferably, the pathogenic microorganisms include Gram-negative bacteria and Gram-positive bacteria, wherein Gram-negative bacteria include but are not limited to Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii; Gram-positive bacteria include but are not limited to Staphylococcus aureus.

[0062] The light-driven molecular motor of multi-substituted large steric olefin provided by the present invention is a type of transporter molecule that can be inserted into the phospholipid bilayer membrane for light-controlled ion transmembrane transport, and has the advantages of controllable structure and easy derivatization. The selective transport of ions is achieved by introducing ion-specific recognition groups; the light-gated transport of ions is achieved by light-regulated motor movement. These characteristics make the light-driven molecular motor of multi-substituted large steric olefin an ideal type of ion channel or carrier, and its application in molecular recognition, ion sensing, ion transport, antibacterial and anti-tumor has broad prospects.

[0063] Compared with the prior art, the technical solution of the present invention has the following advantages:

[0064] (1) The compound provided by the present invention has a light-driven motor structure of a large sterically hindered olefin, and has the advantages of controllable structure and easy derivatization; it can perform unidirectional rotation under the drive of light to promote the ion transport of molecules in phospholipid membranes; it can perform light-gated transport of ions through carriers and channel formation mechanisms; the carrier motor molecules can also achieve ion selective transport by modifying ion recognition groups, and has important application value in the fields of ion recognition, ion sensing and ion transport.

[0065] (2) The compounds provided by the present invention have significant anti-cancer activity; after irradiation with light, they can significantly increase anti-tumor cell activity and inhibit the growth of tumor cells by stimulating motor movement, showing excellent anti-tumor activity. They can be used alone to prepare anti-tumor agents, or combined or conjugated with other anti-tumor compounds for anti-tumor use; the compounds provided by the present invention have selectivity for cancer cells. Since the more permeable cell membrane properties of cancer cells are more conducive to the mechanical movement of light-driven motors, more effective ion transport occurs, and thus they have higher cytotoxicity to cancer cells.

[0066] (3) The compounds provided by the present invention have obvious and broad-spectrum antibacterial activity; after being irradiated with light, the antibacterial activity can be enhanced through the operation of the motor, and can be used as an antibacterial agent alone, or combined or conjugated with other antibacterial drugs for antibacterial treatment.

[0067] In summary, the compounds provided by the present invention have light-controlled antibacterial and anticancer activities, and can be further combined with the advantages of light's controllable time, space and dosage to achieve fixed-point, timed and positioned antibacterial and anticancer treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0068] Figure 1is the proliferation inhibition effect of the channel molecule A in Example 1 on cancer cells including human cervical cancer cells (HeLa), human liver cancer cells (HepG2), human lung cancer cells (A549), human breast cancer cells (MCF-7) and human prostate cancer cells (PC-3) under a) the condition of no ultraviolet light and b) the condition of ultraviolet light, wherein IC 50 It refers to the concentration of channel molecule A required when the ratio of apoptotic cells to total cells is equal to 50%. DETAILED DESCRIPTION

[0069] In order to more clearly illustrate the present invention, the above contents of the present invention are further described in detail by way of examples below. It should be understood by those skilled in the art that the contents specifically described below are illustrative rather than restrictive, and should not be used to limit the scope of protection of the present invention.

[0070] The experimental materials used in the examples of the present invention, unless otherwise specified, are all commercially available. The chemical reagents are all analytically pure and do not require further purification. The cells used in the present invention were purchased from the Cell Bank of the Chinese Academy of Sciences.

[0071] Example 1 Synthesis of molecule A of the light-driven molecular motor artificial ion transport system

[0072]

[0073] (1) Synthesis of Compound 1

[0074] AlCl 3 (10.4 g, 78 mmol) and methacryloyl chloride (3.8 mL, 39 mmol) in anhydrous dichloromethane (100 mL) were cooled to -78 °C, solid naphthalene was slowly added in batches, and the reaction was stirred at room temperature overnight. After the reaction was completed, the solution was poured into an ice-cold aqueous hydrochloric acid solution (1 M, 100 mL), and the resulting mixture was extracted with ether (100 mL). The organic layer was washed with anhydrous NaSO 4 The residue was dried, concentrated, and purified by silica gel column chromatography (petroleum ether: dichloromethane = 10:1) to obtain oily compound 1.

[0075] The physical parameters of compound 1 are: 1 HNMR (400MHz, CDCl 3), δ9.16(d,J=8.5Hz,1H),8.01(d,J=8.5Hz,1H),7.86(d,J=8.3Hz,1H),7.65(t,J=7.9Hz,1H),7.54(t,J =8.0Hz,1H),7.46(d,J=7.5Hz,1H),3.45(dd,J=6.8Hz,1H),2.80(m,J=7.0Hz,2H),1.37(d,J=6.8Hz,3H). 13 C NMR (150 MHz, CDCl 3 )δ209.01,153.91,134.60,132.78,130.98,130.93,129.81,129.54,128.40,127.95,127.79,40.67,38.23,15.56.HR-MS(ESI):calcd for C 14 H 12 O[M+H] + 197.0900, found 197.0902.

[0076] (2) Synthesis of Compound 2

[0077] Lawesson reagent (23.47 g, 58.09 mmol) was added to a toluene solution (30 mL) of compound 1 (1.90 g, 9.68 mmol), and the mixture was heated at 95°C for 3 h, and then the solvent was removed under vacuum. Purification by silica gel column chromatography (petroleum ether: dichloromethane = 10:1) gave a purple solid compound 2. Since the product was easily deteriorated, it was directly subjected to the next reaction without characterization.

[0078] (3) Synthesis of Compound 3

[0079] Br was added dropwise to a solution of 9-thioxanthone (5.0 g, 25 mmol) in acetic acid (50 mL). 2 (10 mL) and heated under reflux for 20 hours. After the reaction was complete, the mixture was cooled and poured into ice water. The precipitation was precipitated with saturated NaHCO 3 Solution, 20% NaHSO 3 The aqueous solution and water were washed successively, dried under vacuum, and recrystallized from toluene to obtain yellow solid compound 3.

[0080] The physical parameters of compound 3 are: 1 HNMR (400MHz, CDCl 3 ), δ7.47(d,J=8.4Hz,2H),7.74(d,J=8.4Hz,2H),8.74(s,2H). 13C NMR (150 MHz, CDCl 3 )δ180.02,138.60,138.42,134.51,134.13,130.86,130.60,129.35,129.47,128.19,128.02,121.14,121.15.HR-MS(ESI):calcd for C 13 H 6 Br 2 OS[M+H] + 368.8584, found 368.8580.

[0081] (4) Synthesis of Compound 4

[0082] To a toluene solution (100 mL) of compound 3 (4.0 g, 20 mmol) was added Lawesson's reagent (39.66 g, 98.09 mmol), the mixture was refluxed at 110° C. for 6 h, and then the solvent was removed under vacuum. The filtrate was slowly cooled, the solid was collected by filtration and dried under vacuum to obtain brown solid compound 4 without further purification.

[0083] The physical parameters of compound 4 are: 1 H NMR (400 MHz, CDCl 3 ): δ9.10(d,J=2.3Hz,2H),7.72(dd,J=8.6and 2.0Hz,2H),7.46(d,J=8.5Hz,2H). 13 C NMR (150 MHz, CDCl 3 )δ211.02,139.60,139.42,134.51,134.13,132.86,132.60,131.35,131.47,130.19,130.02,121.04,121.05.HR-MS:(EI)(m / z):[M]calcd for C 13 H 6 Br 2 S 2 :383.8300.Found:383.8301.

[0084] (5) Synthesis of Compound 5

[0085] Hydrazine hydrate (4.39 mL, 90.60 mmol) was added to an ethanol solution (35 mL) of compound 4 (3.50 g, 9.06 mmol), and the resulting mixture was refluxed for 20 min until the reaction solution turned green. The solvent was removed under vacuum. The compound 5 was purified by silica gel chromatography (dichloromethane) to obtain a light yellow solid.

[0086] The physical parameters of compound 5 are: 1 H NMR (400 MHz, CDCl 3 )δ8.18(d,J=2.0Hz,1H),7.93(d,J=2.1Hz,1H),7.46(dd,J=8.4,2.1Hz,1H),7.42–7.37(m,2H),7.20(d,J=8.4Hz,1H),5.98(s,2H). 13 C NMR (150 MHz, CDCl 3 )δ138.60,136.42,134.51,132.13,130.86,130.60,130.35,129.47,129.19,128.02,126.97,121.14,119.75.HR-MS(EI)(m / z):[M]calcd forC 13 H 8 N 2 SBr 2 ,383.8754,found 383.8762.

[0087] (6) Synthesis of Compound 6

[0088] Anhydrous sodium sulfate (6.59 g, 46.40 mmol) and manganese dioxide (8.07 g, 92.80 mmol) were added to compound 5 (2.97 g, 7.73 mmol) in anhydrous tetrahydrofuran solution (45 mL). The reaction was stirred at 0 ° C for 40 min. Then, the reaction solution was filtered with diatomaceous earth and washed with 20 mL of anhydrous tetrahydrofuran, and the filtrate was collected and immediately transferred to a Schlenk tube. Compound 2 (1.97 g, 9.28 mmol) was dissolved in 20 mL of anhydrous tetrahydrofuran and transferred to a Schlenk tube. The mixture was stirred at room temperature for 12 h, and then the solvent was removed under vacuum. Purification by silica gel column chromatography (petroleum ether: dichloromethane = 10: 1) gave compound 6 as a yellow solid.

[0089] The physical parameters of compound 6 are: 1 H NMR (400 MHz, CDCl 3)δ8.89(d,J=8.7Hz,1H),7.99(s,1H),7.83(s,1H),7.55(s,2H),7.37(d ,J=7.7Hz,2H),7.29(d,J=8.2Hz,1H),7.22(d,J=7.6Hz,1H),7.18(d,J=8 .0Hz,1H),6.84(d,J=8.1Hz,1H),6.77(d,J=8.3Hz,1H),3.43(dd,J=15.6,6.1Hz,1H),2.44(d,J=15.4Hz,1H),1.58(s,1H),1.12(d,J=6.6Hz,3H). 13 CNMR (150MHz, CDCl 3 )δ142.64,141.03,136.38,135.50,134.60,134.24,132.78,131.94,130.98,130.93,130.30,129.81,129.54,128.40,127.95 ,127.79,124.66,124.53,124.14,123.60,121.05,120.14,72.35,60.99,40.67,38.23,22.00.HR-MS(EI)(m / z):[M]calcdfor C 27 H 18 S 2 Br 2 ,565.9196,found565.9195.

[0090] (7) Synthesis of Compound 7

[0091] Trimethylphosphite (5 mL, 42.4 mmol) was added to a 50 mL pressure bottle of compound 6 (2.0 g, 3.6 mmol) and the mixture was stirred at 130 ° C for 12 h. After the reaction, the mixture was cooled to room temperature, poured into methanol (50 mL), and the precipitate was filtered and washed with methanol (15 mL). Purification by silica gel column chromatography (petroleum ether: dichloromethane = 10: 1) gave yellow solid compound 7.

[0092] (8) Synthesis of Compound 8

[0093] Compound 7 (1.50 g, 1.4 mmol), tris(dibenzylideneacetone)dipalladium (51.2 mg, 0.06 mmol) in chloroform were added, CuI (10.80 mg, 0.06 mmol), triphenylphosphine (52.6 mg, 0.28 mmol) and 4-(tert-butyldimethylsilyloxy)-1-butyne (2.88 ml, 14.0 mmol). Triethylamine (14 mL) was added and the mixture was stirred at 70°C overnight. The resulting mixture was washed with saturated NH 4 The organic layer was washed three times with anhydrous NaSO 4 The residue was dried, concentrated, and purified by silica gel column chromatography (petroleum ether: dichloromethane = 10:3) to obtain compound 8 as a yellow solid.

[0094] The physical parameters of compound 8 are: 1 HNMR (400MHz, CDCl 3 )δ7.79(d,J=1.7Hz,1H),7.75(d,J=8.2Hz,1H),7.70(d,J=8.2Hz,1H),7.50(dd,J 1 =8.0,J 2 =0.4Hz,1H),7.47(dt,J 1 =8.0,J 2 =0.4Hz,1H),7.44(d,J=8.2Hz,1H),7.26(dd,J 1 =8.1,J 2 =1.8,1H),7.19(ddd,J 1 =8.1,J 2 =5.7,J 3 =2.2Hz,1H),7.03(dd,J 1 =8.1,J 2 =1.8Hz,1H),6.87–6.78(m,2H),6.73(dd,J 1 =1.8,J 2 =0.5Hz,1H),4.24(p,J=6.7Hz,1H),3.86(t,J=6.9Hz,2H),3.64(dd,J 1 =15.4,J 2=6.2Hz,1H),3.56(td,J=7.2,1.1Hz,2H),2.67(t,J=6.9Hz,2H),2.63(d,J=15.4Hz,1H),2.34(t,J=7.1Hz,2H) ,0.94(d,J=0.4Hz,9H),0.84(d,J=0.4Hz,9H),0.78(d,J=6.8Hz,3H),0.13(s,6H),-0.02(s,3H),-0.03(s,3H). 13 C NMR (150 MHz, CDCl 3 )δ147.00,146.11,139.96,137.72,135.37,134.85,134.70,133.11,131.55,130.77,130 .43,129.38,129.19,128.78,127.91,127.62,127.30,127.16,125.94,124.90,124.41,12 3.69,122.09,122.04,88.02,87.07,81.35,80.68,61.92,61.76,39.77,37.94,25.96,25 .89,23.99,23.68,19.53,18.44,18.32,5.15,5.16,5.27,5.28.HR-MS(EI)m / zcalculated for[M+H] + Calculate for C 47 H 57 O 2 SSi 2 741.3612, found 741.3610.

[0095] (9) Synthesis of Compound 9

[0096] TBAF (3.66 mL, 3.66 mmol, 2.0 M THF solution) was added dropwise to a THF solution of compound 8 (1.09 g, 1.46 mmol), and the mixture was stirred at room temperature for 1.5 hours. The mixture was poured into water (50 mL) and filtered, the solid was collected, washed with water (20 mL×2), and dried under vacuum to obtain compound 9 as a light yellow solid, which was directly used in the next step.

[0097] (10) Synthesis of Compound 10

[0098] 4-Toluenesulfonyl chloride (2.0 g, 10.5 mmol) and DMAP (catalytic amount) were added to a dichloromethane solution of compound 9 (1.07 g, 2.1 mmol). Triethylamine (1.45 mL, 10.5 mmol) was added under ice bath conditions. The reaction was continued for 18 hours, and the resulting yellow solution was washed three times with water (40 mL). The organic phase was washed with anhydrous NaSO 4 The residue was dried, concentrated, and purified by silica gel column chromatography (petroleum ether: dichloromethane = 10:2) to obtain compound 10 as a light yellow solid.

[0099] The physical parameters of compound 10 are: 1 H NMR (600 MHz, CDCl 3 )δ7.83(d,J=8.3Hz,2H),7.78–7.74(m,2H),7.72-7.67(m,3H),7.50(d,J=8.0Hz,1H),7.47(d,J=8.0Hz,1H),7.44(d,J=8.2Hz,1 H),7.31(d,J=8.0Hz,2H),7.27-7.25(m,2H),7.20-7.18(td,J=8.3,1.6Hz,2H),6.97(dd,J=8.1,1.8Hz,1H),6.81(td,J=7.5,6.6 ,1.3Hz,1H),6.77(d,J=8.2Hz,1H),6.66(d,J=1.7Hz,1H),4.27–4.17(m,3H),3.92(td,J=7.3,1.6Hz,2H),3.66(dd,J=15.4,6.1 Hz,1H),2.83(t,J=7.0Hz,2H),2.65(d,J=15.4Hz,1H),2.48(t,J=7.3Hz,2H),2.391(s,3H),2.388(s,3H),0.79(d,J=6.8Hz,3H). 13 C NMR (150 MHz, CDCl 3)δ147.38,146.18,144.98,144.83,139.87,137.67,135.93,135.43,134.50,S15133.10,1 32.95,132.89,131.63,130.85,130.58,129.91,129.84,129.40,129.24,128.69,127.97,1 27.90,127.66,127.32,126.72,125.83,124.89,124.41,123.72,121.27,121.24,84.59,8 3.58,82.47,81.78,67.69,67.49,39.75,37.87,21.63,20.55,20.16,19.55.HR-MS(EI)m / z calcd for[M+H] + C 49 H 41 O 6 S 3 821.2060, found 821.2062.

[0100] (11) Synthesis of Compound 11

[0101] To a solution of compound 11 (0.36 g, 0.44 mmol) in DMF (15 mL) was added NaN 3 (0.06 g, 0.88 mmol), and the mixture was stirred at 80 °C overnight. After cooling to room temperature, the mixture was added with dichloromethane and then washed with water (30 mL × 3). The organic phase was washed with anhydrous NaSO 4 The residue was dried and concentrated to obtain compound 11 as a pale yellow solid.

[0102] The physical parameters of compound 11 are: 1 H NMR (600 MHz, CDCl 3)δ7.81(d,J=1.6Hz,1H),7.76(d,J=8.1Hz,1H),7.71(d,J=8.1Hz,1H),7.51(d,J=8.0Hz,1H),7.48(d,J=8.0Hz,1H),7.43(d, J=8.1Hz,1H),7.27(dd,J=8.0,1.7Hz,1H),7.20(ddd,J=8.0,6.4,1.4Hz,1H),7.05(dd,J=8.1,1.8Hz,1H),6.83(ddd,J=7.9, 6.5,1.3Hz,1H),6.81–6.77(m,1H),6.73(d,J=1.7Hz,1H),4.23(p,J=6.8Hz,1H),3.64(dd,J=15.3,6.2Hz,1H),3.51(t,J=6. 8Hz, 2H), 3.21 (t, J = 6.9Hz, 2H), 2.76 (t, J = 6.7Hz, 2H), 2.63 (d, J = 15.4Hz, 1H), 2.41 (t, J = 6.9Hz, 2H), 0.79 (d, J = 6.8Hz, 3H). 13 C NMR (150 MHz, CDCl 3 )147.28,146.14,139.87,137.70,135.84,135.29,134.61,133.12,131. 64,130.84,130.44,129.35,129.16,128.73,127.87,127.67,127.33,126 .85,125.91,124.90,124.38,123.69,121.45,121.43,86.51,85.58,82.3 5,81.62,49.92,49.69,39.72,37.87,20.84,20.39,19.55.HR-MS(EI)m / z Calculation for [M+Na] + C 35 H 26 N 6 SNa 585.1832, found 585.1835.

[0103] (12) Synthesis of Compound 12

[0104] 4-Dimethylaminopyridine (DMAP, 0.17 g, 1.45 mmol) was added to a dichloromethane solution (50 mL) of 4-carboxybenzo-18-crown-6 (1.03 g, 2.89 mmol) and 9-decyn-1-ol (0.87 g, 5.78 mmol). The mixture was stirred at 0°C for 10 min and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI, 0.54 g, 2.89 mmol) was added. The reaction solution was stirred at room temperature for 36 hours, the solvent was evaporated under reduced pressure, 100 mL of ethyl acetate was added to dissolve the product, the organic phase was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated by rotary evaporation, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:4) to obtain white solid compound 12.

[0105] The physical parameters of compound 12 are: 1 H NMR (400 MHz, CDCl 3 )δ7.65(dd,J=8.4,1.9Hz,1H),7.54(d,J=1.9Hz,1H),6.86(d,J=8.5Hz,1H),4. 27(t,J=6.7Hz,2H),4.23–4.18(m,4H),3.94(td,J=7.2,4.5Hz,4H),3.80–3.75 (m,4H),3.72(dd,J=5.4,2.6Hz,4H),3.69(s,4H),2.18(td,J=7.1,2.6Hz,2H), 1.94(t,J=2.6Hz,1H),1.80–1.70(m,2H),1.58–1.47(m,2H),1.46–1.31(m,8H). 13 C NMR (150 MHz, CDCl 3 )δ166.56,153.08,148.45,123.94,123.35,114.75,112.33,84.84,71.11,71.08,70.96,70.89,70.86,70.82,69. 65,69.53,69.31,69.04,68.26,65.05,29.27,29.11,28.87,28.77,28.55,26.12,18.51.HR-MS(ESI)(m / z):[M+Na] + Calculate for C 27 H 40 O 8 Na,515.2621,found 515.2624.

[0106] (13) Synthesis of Compound A

[0107] A mixture containing 11 (50.00 mg, 0.089 mmol), 12 (96.00 mg, 0.20 mmol), CuSO 4 ·5H 2 A 10 mL sealed tube containing 1,2-dichloromethane (2.22 mg, 0.0089 mmol) and sodium ascorbate (5.28 mg, 0.027 mmol) was sealed with a rubber seal. A mixture of dichloromethane (1.5 mL) and water (1.5 mL) was added to the tube, and the sealed tube was stirred at room temperature for 12 hours, extracted three times with dichloromethane (10 mL), and the organic phase was collected and concentrated in vacuo. Yellow solid compound A was obtained by preparative liquid chromatography (HPLC). HPLC purification: the column was gradient eluted with acetonitrile and aqueous solution (60-100%) within 10 minutes.

[0108] The physical parameters of compound A are: 1 H NMR (600 MHz, CDCl 3 )δ7.76(d,J=8.2Hz,1H),7.75(s,1H),7.71(d,J=8.1Hz,1H),7.64(dd,J=8.4,1.8Hz,2H ),7.53(s,1H),7.53(s,1H),7.51(d,J=8.0Hz,1H),7.49(d,J=8.1Hz,1H),7.45(d,J=8. 2Hz,1H),7.42(s,1H),7.21(d,J=6.9Hz,2H),7.04(s,1H),7.00(dd,J=8.0,1.5Hz,1H), 6.85(s,1H),6.84(s,1H),6.82(d,J=7.6Hz,1H),6.78(d,J=8.5Hz,1H),6.69(d,J=1.3Hz ,1H),4.58(t,J=6.9Hz,2H),4.31(dt,J=13.4,6.7Hz,1H),4.28–4.21(m,6H),4.21–4.1 8(m,8H),3.95–3.91(m,8H),3.76(dd,J=8.6,3.8Hz,8H),3.71(dd,J=9.1,5.0Hz,8H),3. 68(s,8H),3.67–3.64(m,1H),3.04(t,J=6.9Hz,2H),2.72(t,J=7.7Hz,2H),2.70–2.65( m,3H),2.65–2.62(m,2H),1.74–1.63(m,8H),1.40–1.30(m,16H),0.79(d,J=6.8Hz,3H). 13 C NMR (150 MHz, CDCl 3)δ166.58,152.92,148.50,148.33,148.19,147.56,146.40,139.93,137.75,136.12,135.66,134.65,133.22,131.67,130.88,130.66,12 9.50,129.37,128.84,128.00,127.87,127.54,126.84,126.10,125. 04,124.54,123.97,123.87,123.26,121.30,121.26,121.12,121.08, 114.33,112.05,85.94,85.21,83.12,82.45,70.96,70.93,70.85,70 .79,70.72,70.69,69.52,69.40,69.05,68.84,65.05,48.90,48.78, 39.87,37.99,29.67,29.60,29.43,29.37,29.31,29.28,28.86,26.15,26.11,25.79,25.72,21.91,21.69,19.69.HR-MS(ESI)(m / z):[M+H] + Calculate for C 89 H 107 N 6 O 16 S,1548.7498,found 1548.7491.

[0109] Example 2 Synthesis of molecule B of the light-driven molecular motor artificial ion transport system

[0110]

[0111] (1) The synthesis method of compound 1-9 refers to compound 1-9 in Example 1.

[0112] (2) Synthesis of Compound 10

[0113] Isothiocyanate (2.92 mmol) was added to dichloromethane of 4-(4-aminophenyl)butyric acid (0.50 g, 2.92 mmol), stirred overnight at room temperature, dried by rotation, and recrystallized (dichloromethane: petroleum ether = 1:1) to obtain white solid compound 10. The physical parameters of compound 10 are: 1 H NMR (400 MHz, CDCl 3)δ11.93(s,1H),9.32(s,1H),7.86(s,1H),7.55–7.21(m,2H),7.06(dt,J=7. 5,1.0Hz,2H),3.04(s,3H),2.53(t,J=1.0Hz,2H),2.26(m,2H),1.76(m,2H). 13 C NMR (100 MHz, CDCl 3 )δ181.45,177.33,139.32,134.58,127.69,117.53,34.33,33.50,30.05,26.63.LR-MS(ESI)(m / z):[M] + Calculate for C 12 H 16 N 2 O 2 S,252.09,found 252.09.

[0114] (3) Synthesis of Compound B

[0115] 4-Dimethylaminopyridine (DMAP, catalytic amount) was added to a dichloromethane solution (50 mL) of compound 9 (0.1 g, 2.89 mmol) and compound 10 (0.09 g, 5.78 mmol). The reaction mixture was stirred at 0°C for 10 min and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI, 0.03 g, 2.89 mmol) was added. Then, the reaction solution was stirred at room temperature for 36 hours, spin-dried, 100 mL of ethyl acetate was added to dissolve the product, the organic phase was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, spin-dried, and purified by preparative liquid chromatography (HPLC) to obtain a yellow solid compound B. Wherein, HPLC purification: the column was eluted with a gradient of acetonitrile and aqueous solution (60-100%) within 10 minutes.

[0116] The physical parameters of compound B are: 1 H NMR (400 MHz, CDCl 3)δ9.73(s,2H),7.90(s,1H),7.82–7.75(m,4H),7.51–7.43(m,4H),7.43–7.35(m,7H) ,7.30(s,1H),7.14(s,1H),7.07(dt,J=7.6,1.1Hz,4H),4.24(d,J=12.5Hz,2H),4.17 (d,J=12.4Hz,2H),3.58(s,1H),3.54(s,1H),3.03(d,J=4.4Hz,7H),3.00(s,1H),2.9 2(d,J=12.4Hz,2H),2.62–2.51(m,4H),2.39–2.29(m,5H),1.72(s,4H),1.01(s,3H). 13 C NMR (100 MHz, CDCl 3 )δ=180.40,173.64,140.87,138.91,134.90,132.82,131.49,129.10,128.70 ,127.66,127.50,127.09,126.15,125.83,125.67,125.50,125.01,124.91,12 3.70,122.44,121.68,121.07,120.30,118.52,117.33,94.23,80.37,62.46,5 0.26,41.17,33.98,33.24,30.67,25.84,23.08,15.56.LR-MS(ESI)(m / z):[M] + Calculate for C 59 H 56 N 4 O 4 S 4 ,1012.32,found 1012.32.

[0117] Example 3 Synthesis of molecule C of the light-driven molecular motor artificial ion transport system

[0118]

[0119] (1) The synthesis method of compound 1-9 refers to compound 1-9 in Example 1.

[0120] (2) Synthesis of Compound 10

[0121] 2-(tert-Butyloxycarbonylamino)ethyl bromide (7.1 g, 10 mmol) and potassium carbonate (4.4 g, 10 mmol) were added to a solution of 3,5-dibromophenol (4.0 g, 5 mmol) in acetonitrile (100 mL), and the mixture was stirred at 80°C overnight. The reaction solution was then dried by spin-drying, the residue was dissolved in ethyl acetate and then washed three times with saturated brine, the organic phase was dried over anhydrous sodium sulfate, and dried by spin-drying under reduced pressure, and the crude product was further purified by column chromatography to obtain yellow liquid compound 10.

[0122] The physical parameters of compound 10 are: 1 H NMR (400 MHz, CDCl 3 )δ7.24(s,1H),6.97(s,2H),5.06(s,1H),3.98(t,J=4.9Hz,2H),3.51(d,J=4.7Hz,2H),1.45(s,9H); 13 C NMR (100 MHz, CDCl 3 )159.70,155.78,126.74,123.13,116.92,79.65,67.78,39.87,28.37; LR-MS(ESI-TOF)(m / z):[M+Na] + Calcd.For C 13 H 17 Br 2 NO 3 Na:415.95.Found:415.94.

[0123] (3) Synthesis of Compound 11

[0124] Compound 10 (3.6 g, 2.76 mmol), Pd(PPh 3 ) 2 Cl 2 (0.3 g, 0.16 mmol), PPh 3 (47.1mg, 0.06mmol) and CuI (34.2mg, 0.06mmol) were dispersed in 25mL dry piperidine in a 100mL sealed tube and deoxygenated three times. After stirring for 5min, trimethylethynylsilane (5.4mL, 13.15mmol) was added with a syringe, and then the reaction solution was reacted at 60℃ for 72 hours. Dichloromethane was poured into the reaction solution, and then washed with saturated ammonium chloride, 10% hydrochloric acid aqueous solution and saturated salt water respectively. The organic phase was collected and anhydrous Na 2 SO 4 The crude product was further purified by column chromatography to obtain compound 11.

[0125] The physical parameters of compound 11 are:1 H NMR (400 MHz, CDCl 3 )δ7.24(s,1H),6.97(s,2H),5.06(s,1H),3.98(t,J=4.9Hz,2H),3.51(d,J=4.7Hz,2H),1.45(s,9H),0.25(s,18H); 13 C NMR (100 MHz, CDCl 3 )δ159.70,155.78,126.74,123.13,116.92,79.65,67.78,39.87,28.37,3.4; LR-MS(ESI-TOF)(m / z):[M+H] + Calcd.For C 23 H 35 NO 3 Si 2 :430.22.Found:430.20.

[0126] (4) Synthesis of Compound 12

[0127] Compound 11 (2.00 g, 4.40 mmol), TBAF (6.90 g, 26.50 mmol), and THF (40 mL) were added to a 100 mL round-bottom flask, stirred and reacted at room temperature, and the reaction progress was monitored by thin layer chromatography. After the reaction was complete, the reaction solution was spin-dried, dichloromethane was added, washed with water, and the organic phase was collected, dried, and concentrated. The crude product was further purified by column chromatography to obtain a white solid 12.

[0128] The physical parameters of compound 12 are: 1 H NMR (400 MHz, CDCl 3 )δ7.21(s,1H),6.99(s,2H),5.06(s,1H),3.93(t,J=6.5Hz,2H),3.60-3.54(m,2H),3.05(s,2H),1.45(s,9H); 13 C NMR (100 MHz, CDCl 3 )δ159.70,155.78,126.74,123.13,116.92,79.65,67.78,39.87,28.37; LR-MS(ESI-TOF)(m / z):[M]Calcd.For C 17 H 19 NO 3 :285.14.Found:285.14.

[0129] (5) Synthesis of Compound 13

[0130] 3-Aminophenol (1.63 g, 14.96 mmol) was dissolved in 45 mL of 2M HCl aqueous solution, and sodium nitrite (1.23 g, 18.00 mmol) aqueous solution was added dropwise under ice bath while stirring. The reaction solution was then stirred at room temperature for 30 minutes, and sodium azide (1.46 g, 22.50 mmol) aqueous solution was added dropwise. The resulting dark red reaction solution was continued to react at room temperature for 2 hours. The reaction solution was extracted with ethyl acetate, and then 0.1 M HCl (26 mL), saturated NH 4 The organic phase was collected, dried over anhydrous magnesium sulfate, and rotary evaporated. The crude product was then purified by column chromatography to obtain red oily liquid 13.

[0131] The physical parameters of compound 13 are: 1 H NMR (400 MHz, CDCl 3 )δ7.18(t,J=8.1Hz,1H),6.61(ddd,J=12.4,7.9,2.2Hz,2H),6.52(t,J=2.3Hz,1H),4.15(q,J=7.1Hz,1H); 13 C NMR (100 MHz, CDCl 3 )δ156.6,141.4,130.7112.1,111.6,105.3.LR-MS(ESI)(m / z):[M+Na] + calcdfor C 6 H 5 N 3 ONa,158.03,found 158.03.

[0132] (6) Synthesis of Compound 14

[0133] The synthesis of compound 14 was based on the synthesis of compound 10.

[0134] The physical parameters of compound 14 are: 1 HNMR (400MHz, CDCl 3)δ7.23(t,J=8.2Hz,1H),6.67(dd,J=8.3,2.4Hz,1H),6.62(dd,J=7.8,2.1Hz,1H),6.54(s,1H),3.94(t,J=6.5Hz,2H),3.67(s,2H),3. 65(dd,J=5.7,3.4Hz,10H),3.47(t,J=6.7Hz,3H),3.38(s,3H),1.77(dt,J=8.3,6.4Hz,2H),1.62(p,J=6.9Hz,2H),1.52-1.36(m,4H); 13 C NMR (100 MHz, CDCl 3 )δ160.5,141,1,130.3,111.1,105.4,71.9,70.6,70.5,70.0,68.0,59.0,29.5,29.1,25.8; LR-MS(ESI-TOF):Calcd.For C 19 H 31 N 3 O 5 Na[M+Na] + :404.22.Found:404.20.

[0135] (7) Synthesis of Compound 15

[0136] The mixture was charged with 14 (1.2 g, 8.90 mmol), 12 (2.0 g, 2.00 mmol), CuSO 4 ·5H 2 O (0.78 g, 8.90 mmol) and sodium ascorbate (1.9 g, 2.70 mmol) were placed in a 100 mL round-bottom flask, and tetrahydrofuran: water (2 / 1, 50 mL) was added and stirred at 60°C for 3 hours. The solvent was evaporated under reduced pressure, and the crude product was purified by column chromatography to obtain a yellow solid product 15.

[0137] The physical parameters of compound 15 are: 1 HNMR (400MHz, CDCl 3)δ8.48(s,2H),7.75–7.68(m,3H),7.52(t,J=7.4Hz,2H),7.08(d,J=2.1Hz,2H),7.01–6.92(m,4H),5.76(s,1H),4.17–4.04(m,6H),3.89–3 .74(m,16H),3.70(dd,J=12.5,4.9Hz,4H),3.54(d,J=4.7Hz,8H),3.43(s,2H),3.27(s,6H),1.77(s,4H),1.54–1.44(m,12H),1.42(s,9H). 13 C NMR (100 MHz, CDCl 3 )δ157.15,156.15,155.91,148.12,142.11,130.93,130.07,125.47,122.35,121.08,114.45,113.15,107.33,79.42,72.0 8,71.09,70.62,69.25,69.21,68.80,68.48,59.11,43.10,29.82,29.64,28.31,26.20,25.76.HR-MS(ESI-TOF):Calcd.For C 55 H 81 N 7 O 3 Na[M+Na] + :1070.5905.Found:1070.5908.

[0138] (8) Synthesis of Compound 16

[0139] To a solution of compound 15 (0.92 g, 1.95 mmol) in dichloromethane (25 mL) was added trifluoroacetic acid (2.5 mL), and the resulting solution was stirred at room temperature for 1 hour. After the solvent was removed in vacuo, compound 16 was obtained.

[0140] (9) Synthesis of Compound C

[0141] Compound 9 (1.07g, 2.0mmol), DMAP (catalytic amount) and TEA (0.87mL, 6.0mmol) were added dropwise in anhydrous dichloromethane solution of p-nitrophenyl chloroformate (0.93g, 4.4mmol). The reaction was continued for 4 hours, and the obtained yellow solution was spin-dried and concentrated, and the compound was purified by silica gel chromatography (ethyl acetate) to obtain a light yellow solid. The obtained compound was further dissolved in anhydrous dichloromethane, compound 16 (1.1g, 1.1mmol) and TEA (0.44mL, 3.0mmol) were added, and the reaction was continued for 12 hours, and the solvent was spin-dried, and the compound C was purified by silica gel chromatography (ethyl acetate) to obtain a light yellow solid.

[0142] The physical parameters of compound C are: 1 H NMR (400 MHz, CDCl 3 )δ8.48(s,4H),7.83(d,J=19.7Hz,2H),7.75–7.68(m,7H),7.56–7.42(m,8H),7.30(dt,J=7.3,1.0 Hz,2H),7.17(d,J=10.6Hz,2H),7.08(d,J=2.1Hz,4H),7.01–6.92(m,9H),5.71(s,2H),4.21–4.02 (m,17H),3.89–3.74(m,34H),3.70(dd,J=12.5,4.9Hz,8H),3.58–3.48(m,16H),3.42(s,4H),3.27 (s,12H),2.91(s,5H),1.77(d,J=0.8Hz,8H),1.57–1.46(m,19H),1.46–1.40(m,6H),1.13(s,3H). 13 C NMR (100 MHz, CDCl 3)δ157.15,156.65,156.51,153.97,147.83,143.98,135.21,134.35,134.04,131.32,130.93,130.15,128.37,12 7.38,127.17,126.48,126.42,126.19,125.47,125.02,124.21,123.80,123.45,123.30,123.09,121.21,119.45, 116.89,114.45,113.78,113.33,107.33,94.23,81.42,72.13,72.02,71.32,70.69,69.77,69.37,69.25,68.80, 68.50,64.60,59.31,43.10,40.53,36.83,29.84,29.50,26.82,26.45,23.08,13.77.HR-MS(ESI-TOF):Calcd.For C 138 H 172 N 14 O 27

[0143] [M] + :2457.2503.Found:2457.2503.

[0144] Example 4 Synthesis of Molecule D of the Artificial Ion Transport System Driven by Visible Light

[0145]

[0146] (1) The synthesis method of compound 1-8 refers to compound 1-8 in Example 1.

[0147] The physical parameters of compound 8 are: 1 H NMR (400 MHz, CDCl 3 )δ11.71(s,2H),7.76(s,1H),7.60(d,J=1.9Hz,2H),7.57–7.45(m,5H),7.31(s,1H),7.14(s,1H),6.91(s,1H),3.83(s,3 H),2.91(d,J=13.0Hz,1H),2.88–2.81(m,2H),2.66(s,4H),2.14(s,4H),1.61(d,J=0.8Hz,4H),1.50(s,4H),1.07(s,3H). 13 C NMR (100 MHz, CDCl 3)δ=174.42,152.59,135.89,135.49,134.46,133.27,128.27,127.22,126.80,126.00,125.73,125.22,125.02,124.76,124.72,123.1 5,123.12,120.30,118.52,108.95,94.23,81.42,55.94,46.32,37.67,32.99,27.75,27.53,24.75,18.17.LR-MS(ESI-TOF):Calcd.For C 42 H 38 O 6 [M] + :638.27.Found:638.27.

[0148] (2) Synthesis of Compound 9

[0149] Dissolve tetraethylene glycol (4 mL, 23 mmol) in dichloromethane, add triethylamine (25 mL) in an ice bath, dropwise add dichloromethane solution (50 mL) containing p-toluenesulfonyl chloride (12 g, 64 mmol), and react at room temperature for 4 hours. Then spin dry the reaction solvent, add dichloromethane and water to extract three times. Collect the organic phase, and use 240 mL of 2 mol / L hydrochloric acid aqueous solution, 5% NaHCO 3 The collected organic phase was washed with anhydrous Na 2 SO 4 The residue was dried, evaporated under reduced pressure, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain compound 9.

[0150] The physical parameters of compound 9 are: 1 HNMR (400MHz, CDCl 3 )δ: 2.45 (s, 6H), 3.57 (s, 8H), 3.68 (t, J = 4.7Hz, 4H), 4.16 (t, J = 4.7Hz, 4H), 7.35 (d, J = 8.2Hz, 4H), 7.80 (d, J = 8.2Hz, 4H). 13 CNMR (100MHz, CDCl 3 )δ:144.8,133.0,129.8,128.0,70.7,70.5,69.3,68.7,21.6.LR-MS(ESI-TOF):Calcd.For C 22 H 30 O 9 S 2 [M]+ :502.1.Found:502.1.

[0151] (3) Synthesis of Compound 10

[0152] K 2 CO 3 (7.05 g, 50.00 mmol) was added to a solution of p-hydroxybenzonitrile (2.24 g, 18.80 mmol) and compound 9 (4.64 g, 9.25 mmol) in acetonitrile (260 mL), and the resulting mixture was heated to reflux for 3 days. The solid portion was filtered off from the reaction solution, and the resulting filtrate was directly spin-dried and purified by silica gel column chromatography (dichloromethane: ethyl acetate = 9:1) to obtain a white solid 10.

[0153] The physical parameters of compound 10 are: 1 HNMR (400MHz, CDCl 3 )δ:7.62-7.53(m,4H),7.00-6.92(m,4H),4.20-4.13(m,4H),3.90-3.83(m,4H),3.77-3.64(m,8H). 13 C NMR (100 MHz, CDCl 3 )δ:162.08,133.97,119.17,115.32,104.17,70.91,70.66,69.44,67.76.LR-MS(ESI-TOF):Calcd.For C 22 H 24 N 2 O 5 Na[M+Na] + :419.2.Found:419.3.

[0154] (4) Synthesis of Compound 11

[0155] 1M LiAlH 4 A THF solution (75 mL, 75 mmol) of compound 10 (4.72 g, 15.83 mmol) in an ice bath was added dropwise to the THF solution (70 mL). The reaction solution was stirred until it turned yellow and heated to reflux for 4 hours. The reaction solution was cooled to room temperature and 2.88 mL of H 2 O, 2.88 mL 15% aqueous NaOH and 8.58 mL HO 2 O. The aluminum salt after the reaction was then filtered off, and the collected filtrate was concentrated under reduced pressure to obtain a white solid 11.

[0156] The physical parameters of compound 11 are: 1H NMR (400 MHz, CDCl 3 )δ:7.23-7.16(m,4H),6.89-6.84(m,4H),4.10(dd,J=5.7,4.1Hz,4H),3.84(dd,J=5.8,4.0Hz,4H),3.75-3.65(m,8H). 13 CNMR (100MHz, CDCl 3 )δ:157.74,135.52,128.27,114.69,70.82,70.67,69.76,67.48,45.81.LR-MS(ESI-TOF):Calcd.For C 22 H 33 N 2 O 5 [M+H] + :405.2.Found:405.2.

[0157] (5) Synthesis of Compound 12

[0158] Anhydrous potassium carbonate (37.70g, 273.20mmol), 4-hydroxy-2,6-dicarboxylpyridine (10.00g, 54.64mmol), benzyl bromide (20.82mL, 174.85mmol) and acetone (250mL) were added to a 500mL two-necked flask, and the reaction was refluxed at 70°C for 12 hours under argon protection. After the reaction was completed, the reaction solution was cooled to room temperature, filtered with suction, and the filtrate was spin-dried and dissolved in dichloromethane again. The dichloromethane solution was washed with 350mL5% potassium hydroxide aqueous solution, 200mL saturated salt water, and then the organic solvent collected by anhydrous sodium sulfate drying was spin-dried, and a light yellow solid compound 12 was obtained by purification by silica gel chromatography (petroleum ether: ethyl acetate = 9: 1).

[0159] The physical parameters of compound 12 are: 1 H NMR (400 MHz, CDCl 3 )δ:7.84(s,2H),7.47-7.45(m,5H),7.42-7.29(m,10H),5.43(s,4H),5.17(s,2H). 13 C NMR (100 MHz, CDCl 3 )δ:166.52,164.39,150.04,135.04,130.28,124.56,114.81,69.25.LR-MS(ESI-TOF):Calcd.For C 28 H 23 NO 5 Na[M+Na]+ :476.1.Found:476.4.

[0160] (6) Synthesis of Compound 13

[0161] KOH (2.45 g, 43.71 mmol) was added to a solution of ethanol (200 mL) containing compound 12 (2.48 g, 5.46 mmol), and the reaction solution was heated to reflux and stirred overnight. After the reaction was completed, the reaction solution was cooled to room temperature, and then the reaction solution was filtered, the filter cake was washed with ethanol, and the obtained filter cake was dissolved in 100 mL of water again. Trifluoroacetic acid was added dropwise to the solution until a white solid was completely precipitated. The white solid was collected by suction filtration and dried to obtain a white solid product 13.

[0162] The physical parameters of compound 13 are: 1 HNMR (400MHz, CDCl 3 )δ:7.77(s,2H),7.58-7.28(m,5H),5.41(s,2H). 13 CNMR (100MHz, CDCl 3 )δ:164.3,162.1,150.2,135.9,129.0,128.7,128.3,113.6,70.8.LR-MS(ESI-TOF):Calcd.For C 14 H 11 NO 5 K[M+K] + :312.0.Found:312.0.

[0163] (7) Synthesis of Compound 14

[0164] A dichloromethane solution (240 mL) containing compound 13 (5.25 g, 13.03 mmol) and triethylamine (3.3 mL) was added to a dichloromethane solution (24 mL) of 4-hydroxybenzyl-2,6-dicarboxylic acid pyridine chloride (3.58 g, 13.08 mmol) under ice bath conditions. The entire process was operated under anhydrous conditions. The reaction solution was stirred for 12 hours, and then the solvent was removed by rotary evaporation. The crude product was purified by silica gel chromatography (dichloromethane: methanol = 96:4) to obtain a white solid compound 14.

[0165] The physical parameters of compound 14 are: 1 H NMR (400 MHz, CDCl 3)δ:7.99(s,2H),7.89(s,2H),7.50-7.32(m,5H),7.11(d,J=8.5Hz,4H),6.76(d,J=8.4Hz,4H),5.2 8(s,2H),4.56(d,J=5.5Hz,4H),4.08(dd,J=5.8,3.5Hz,4H),3.94-3.84(m,4H),3.77-3.64(m,8H). 13 C NMR (100 MHz, CDCl 3 )δ:163.13,158.28,150.65,135.15,129.90,128.84,128.57,127.77,114.72,1 11.64,77.23,70.90,70.63,69.66,67.64,43.00.LR-MS(ESI-TOF):Calcd.ForC 36 H 39 N 3 O 8 Na[M+Na] + :664.3.Found:664.4.

[0166] (8) Synthesis of Compound 15

[0167] Compound 14 (0.64 g, 1.00 mmol) was dissolved in a mixed solvent of methanol (15 mL) and dichloromethane (15 mL), and then Pd / C (10%, 0.05 g) was added. The reaction solution was stirred at room temperature for 15 hours under a hydrogen pressure of 70 atm, the palladium carbon catalyst was filtered off, and the mixture was rinsed with tetrahydrofuran. The filtrate was dried to obtain compound 15 as a white solid.

[0168] The physical parameters of compound 15 are: 1 H NMR (400 MHz, DMSO-d 6 )δ:11.44(s,1H),9.69(t,J=6.3Hz,2H),7.58(s,2H),7.21(d,J=8.3Hz,4H),6.89(d,J=8. 4Hz, 4H), 4.54 (d, J = 6.4Hz, 4H), 4.09-3.96 (m, 4H), 3.78-3.67 (m, 4H), 3.58-3.48 (m, 8H). 13 C NMR (100 MHz, DMSO-d 6)δ:163.03,157.38,150.72,131.20,128.11,114.20,111.45,69.89,68.83,67.16,40.97.LR-MS(ESI-TOF):Calcd.For C 29 H 33 N 3 O 8 Na[M+Na] + :574.2.Found:574.6.

[0169] (9) Synthesis of Compound 16

[0170] To a solution of compound 15 (5.28 g, 9.58 mmol) and tert-butyl N-(2-bromoethyl)carbamate (3.84 g, 17.25 mmol) in DMF (300 mL) was added K 2 CO 3 (7.05 g, 50.05 mmol) and a catalytic amount of KI (0.004 g), and then the reaction mixture was heated to 90 ° C for 2 days. The K in the solution was filtered off. 2 CO 3 The filtrate was dried in spun-drying mode, and the crude product was purified by column chromatography (dichloromethane:methanol=100:2) to obtain compound 16 as a white solid.

[0171] The physical parameters of compound 16 are: 1 HNMR (400 MHz, DMSO-d 6 )δ7.68(s,2H),7.20(d,J=8.3Hz,4H),6.88(d,J=8.7Hz,4H),4.56(d,J=6.3Hz,5H),4.22 (t,J=5.4Hz,2H),4.08-3.97(m,4H),3.75-3.67(m,4H),3.60-3.47(m,8H),1.37(s,9H). 13 C NMR (100 MHz, CDCl 3 )δ:167.32,163.60,162.55,157.93,130.26,128.70,114.25,111.26,70.81,70. 63,69.65,68.05,67.41,42.75,39.71,36.49,28.44.LR-MS(ESI-TOF):Calcd.For C 36 H 46 N 4 O 10 Na[M+Na] +:717.3.Found:717.5.

[0172] (10) Synthesis of Compound 17

[0173] Compound 16 (0.33 g, 0.48 mmol) was dissolved in 13 mL of dichloromethane and 3 mL of trifluoroacetic acid, and stirred at room temperature for 40 min. Then 10 mL of ethyl acetate was added and the mixture was evaporated until the excess trifluoroacetic acid and other solvents were dried to obtain compound 17.

[0174] The physical parameters of compound 17 are: 1 H NMR (400 MHz, DMSO-d 6 )δ:9.76(t,J=6.3Hz,2H),7.76(s,2H),7.27-7.14(m,4H),6.95-6.81(m,4H),4.56(d,J=6.3Hz,4H),4 .44(t,J=5.0Hz,2H),4.08-3.96(m,4H),3.75-3.66(m,4H),3.59-3.47(m,8H),3.31(q,J=5.4Hz,2H). 13 CNMR (100MHz, DMSO-d 6 )δ:166.57,162.69,157.43,150.91,131.10,128.17,114.22,110.56,69.90,68.83,67.17,65.17,41.08,38.05.LR-MS(ESI-TOF):Calcd.For C 31 H 38 N 4 O 8 [M] + :594.2.Found:594.5.

[0175] (11) Synthesis of Compound D

[0176] A DCM solution containing compound 8 (0.39 g, 0.60 mmol) was added to a dichloromethane solution containing condensing agent PyBop (0.47 g, 0.90 mmol) and triethylamine (0.50 mL, 2.70 mmol). The reaction mixture was stirred for 5 min, and then a DCM solution (5 mL) containing compound 17 (0.35 g, 0.60 mmol) was added. The reaction mixture was stirred at room temperature overnight. Ice water was poured to quench the reaction solution, and DCM was extracted three times. The collected organic phase was successively treated with 1 mol / L Na 2 CO 3(5×5mL), washed with saturated brine (2×5mL), dried over anhydrous sodium sulfate. The organic solvent was dried and column chromatography was used

[0177] (dichloromethane:methanol=98:2) to obtain a light yellow solid D.

[0178] The physical parameters of compound D are: 1 HNMR (400MHz, CDCl 3 )δ7.76(s,1H),7.66(s,2H),7.63(d,J=2.1Hz,2H),7.52(d,J=1.8Hz,1H),7.52– 7.49(m,2H),7.39(s,1H),7.37(s,1H),7.33–7.29(m,6H),7.23–7.21(m,3H),7.2 0(q,J=1.3Hz,2H),7.18(s,2H),7.06(s,1H),6.89(s,1H),6.85(d,J=0.8Hz,4H) ,6.83(d,J=1.6Hz,2H),6.80(d,J=1.6Hz,2H),6.79(d,J=1.6Hz,2H),4.40–4.37( m,4H),4.30(s,2H),4.25(s,4H),4.22(s,4H),4.11(s,4H),3.88(d,J=2.8Hz,7H ),3.81(s,4H),3.69(s,4H),3.67(d,J=1.3Hz,2H),3.64(d,J=1.4Hz,2H),3.56(s ,16H),3.41(d,J=2.0Hz,4H),2.91(d,J=13.0Hz,1H),2.85(d,J=13.0Hz,1H),2.7 6(s,1H),2.53(s,4H),2.15(s,4H),1.64(s,4H),1.61–1.50(m,4H),1.01(s,3H). 13 C NMR (100 MHz, CDCl 3)δ=172.60,161.62,155.75,155.69,152.59,140.30,137.59,137.17,135.22,134.92,134.50,131.61,13 0.70,129.37,128.90,128.45,128.31,128.27,127.21,126.90,126.38,126.25,124.91,123.80,122.80,1 22.44,114.90,114.60,112.07,108.74,103.00,94.23,81.42,70.76,70.56,69.84,68.27,68.02,55.91,4 8.10,46.33,46.31,44.84,42.54,37.67,36.30,27.75,27.30,25.00,17.58.LR-MS(ESI-TOF):Calcd.ForC 104 H 114 N 8 O 18 [M] + :1762.83.Found:1762.83.

[0179] Example 5 Synthesis of Molecule E of the Artificial Ion Transport System Driven by Visible Light Molecular Motor

[0180]

[0181] (1) The synthesis method of compound 1-8 refers to compound 1-8 in Example 1.

[0182] The physical parameters of compound 8 are: 1 H NMR (400 MHz, CDCl 3 )δ7.80(s,1H),7.69(s,1H),7.64(dd,J=7.5,1.8Hz,2H),7.60(d,J=2.1Hz,2H) ,7.54(d,J=7.3Hz,2H),7.46(s,1H),7.37(s,1H),6.98(s,1H),4.47(t,J=5.4Hz ,2H),3.51(qd,J=12.5,5.7Hz,4H),2.88(s,6H),2.87–2.83(m,2H),2.66(d,J=1 3.0Hz,1H),2.59(s,4H),1.75–1.65(m,4H),1.58(d,J=3.9Hz,4H),1.03(s,3H). 13 C NMR (100 MHz, CDCl 3)δ141.22,134.75,133.29,132.23,131.50,128.63,128.58,127.75,127.50,127.24,126.00,125.71,124.86,124.45,123.19,12 2.44,120.30,118.52,116.64,94.23,83.00,62.05,42.93,42.80,37.67,30.50,25.54,23.62,18.17.LR-MS(ESI-TOF):Calcd.For C 41 H 41 NO 2 S[M] + :611.29.Found:611.29.

[0183] (2) Synthesis of Compound 10

[0184] The synthesis method of compound 10 refers to compound 12 in Example 1.

[0185] The physical parameters of compound 10 are: 1 H NMR (400 MHz, CDCl 3 )δ7.81–7.74(m,2H),7.63(dd,J=7.5,1.8Hz,1H),7.42(d,J=1.9Hz,1H),7.34(dq,J=7.8,1.1Hz,2H),7.01(d,J=7.5Hz,1H),4.28(s,2H ),4.17(d,J=11.9Hz,4H),3.79(d,J=11.4Hz,4H),3.65(s,2H),3.56(d,J=1.3Hz,8H),2.43(t,J=1.0Hz,3H),1.95(s,2H),1.89(s,2H). 13 C NMR (100 MHz, CDCl 3 )δ165.81,152.44,148.39,144.70,135.78,129.80,127.93,124.37,122.42,113.87,112.12,70 .84,69.87,69.80,69.50,69.17,68.54,65.92,29.11,27.62,21.62.LR-MS(ESI-TOF):Calcd.For C 26 H 34 O 10 S[M] + :538.19.Found:538.19.

[0186] (3) Synthesis of Compound E

[0187] To a dichloromethane solution containing compound 8 (0.40 g, 0.90 mmol), triethylamine (0.27 mL, 2.70 mmol) and DMAP (catalytic amount) was added a DCM solution of compound 10 (0.77 g, 1.98 mmol), and the reaction was stirred at room temperature overnight. The organic solvent was dried and purified by column chromatography (dichloromethane: methanol = 100: 2) to obtain a light yellow solid compound E.

[0188] The physical parameters of compound E are: 1 H NMR (400 MHz, CDCl 3 )δ7.80(s,1H),7.65(dd,J=7.4,2.0Hz,4H),7.58(s,1H),7.52(dd,J=7.4,1.9H z,2H),7.41–7.30(m,5H),7.28(s,1H),7.01–6.95(m,3H),4.28(s,4H),4.17(d ,J=4.9Hz,8H),3.81(s,4H),3.69(s,4H),3.59–3.48(m,24H),2.90(d,J=15.3H z,8H),2.76(s,1H),2.48(s,4H),1.80(s,4H),1.76–1.66(m,12H),1.01(s,3H). 13 C NMR (100 MHz, CDCl 3 )δ165.80,149.39,145.98,141.79,133.96,132.40,131.61,131.50,130.70,128.27,128.2 0,127.50,127.14,126.92,126.72,126.00,125.50,125.45,123.23,122.80,122.62,122.4 4,116.93,114.80,114.16,94.23,81.42,72.02,71.51,71.24,70.58,69.84,69.61,66.00, 42.17,41.65,37.67,29.88,29.11,29.03,26.28,23.70,17.58.LR-MS(ESI-TOF):Calcd.For C 79 H 93 NO 16 S[M] + :1343.62.Found:1343.62.

[0189] Example 6 Synthesis of the Light-Driven Molecular Motor Artificial Ion Transport System Molecule F

[0190]

[0191] (1) The synthesis method of compound 1-8 refers to compound 1-8 in Example 1.

[0192] The physical parameters of compound 8 are: 1 H NMR (400 MHz, CDCl 3 )δ7.85(s,1H),7.82(s,1H),7.75(s,1H),7.70(d,J=2.1Hz,2H),7.57(dd,J=7.5,2.1Hz,2H),7.42(s,1H),7.35(s,1H),7.21(d,J=7.3 Hz,2H),7.14(s,1H),3.03(s,4H),2.75(d,J=13.0Hz,1H),2.71(s,4H),2.66(d,J=13.2Hz,1H),2.42(s,1H),2.10(s,2H),0.90(s,9H). 13 C NMR (100 MHz, CDCl 3 )δ152.69,137.63,133.82,133.65,133.47,133.42,129.39,128.53,127.41,127.31,126.48,125.60,125.54,125.44, 123.40,122.60,120.99,110.93,93.20,83.91,49.80,34.72,32.80,27.53,27.11,26.72.LR-MS(ESI-TOF):Calcd.For C 38 H 34 OS 2 [M] + :570.21.Found:570.21.

[0193] (2) Synthesis of Compound F

[0194] DMAP (catalytic amount) was added to a dichloromethane solution (50 mL) of compound 9 (0.78 g, 2.4 mmol) and compound 8 (0.52 g, 1.2 mmol). The mixture was stirred at 0°C for 10 min and EDC (0.35 g, 2.4 mmol) was added. The reaction solution was stirred at room temperature for 36 hours, the solvent was evaporated under reduced pressure, 100 mL of ethyl acetate was added to dissolve the product, the organic phase was washed with 100 mL of saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated by rotary evaporation. The white solid compound F was purified by silica gel column chromatography (methanol: dichloromethane = 3:100).

[0195] The physical parameters of compound F are: 1 H NMR (400 MHz, CDCl 3 )δ7.85(s,1H),7.81(s,1H),7.64–7.54(m,5H),7.42(s,2H),7.30–7.22(m,3H),7.13(d,J=7.3Hz,2H) ,7.05(s,6H),6.66(s,2H),4.29(s,2H),4.05(s,4H),3.96(s,4H),3.86(d,J=7.5Hz,8H),3.33(s,4H), 2.96–2.89(m,3H),2.82(s,1H),2.75(d,J=12.4Hz,2H),2.50(s,4H),2.46(s,1H),1.90(d,J=12.2Hz,2 H),1.84(d,J=12.5Hz,2H),1.74–1.64(m,4H),1.42–1.25(m,12H),1.25(d,J=1.6Hz,4H),0.89(s,9H). 13 C NMR (100 MHz, CDCl 3 )δ196.05,171.36,171.06,171.03,170.92,153.74,135.32,134.25,132.82,131.84,1 30.97,128.20,127.50,127.41,127.31,125.92,125.60,125.55,124.96,123.79,123.7 5,120.05,117.46,94.23,81.85,53.26,49.80,44.54,43.40,37.86,36.65,32.10,30.7 7,29.54,29.46,29.16,28.98,27.41,25.68,23.98,23.96.LR-MS(ESI-TOF):Calcd.For C 74 H 88N 10 O 13 S 2 [M] + :1388.60.Found:1388.60.

[0196] Example 7 Synthesis of the molecule G of the light-driven molecular motor artificial ion transport system

[0197]

[0198] (1) Synthesis of Compound 2

[0199] p-Nitroaniline (235.0 mg, 1.7 mmol), compound 1 (1.62 g, 5.1 mmol), cuprous iodide (129.0 mg, 0.681 mmol) and Cs 2 CO 3 (4.26 g, 13.1 mmol) was added to a dry Schlenk tube, anhydrous DMF (6 mL) was added and the mixture was heated to 130 ° C. The reaction was stopped after 3 days under an argon atmosphere. After cooling to room temperature, the crude mixture was filtered through celite and the solvent was evaporated under reduced pressure. Compound 2 was obtained by recrystallization from a water / methanol mixture (8:2, 100 mL).

[0200] The physical parameters of compound 2 are: 1 H NMR (400 MHz, CDCl 3 )δ7.47–7.43(m,2H),7.33(dd,J=7.5,2.1Hz,2H),7.27–7.20(m,4H),6.88(d,J=7.5Hz,2 H), 4.17 (d, J = 5.5Hz, 8H), 3.80 (s, 2H), 3.74 (s, 6H), 3.56 (d, J = 2.9Hz, 16H), 2.28 (s, 3H). 13 C NMR (100 MHz, CDCl 3 )δ169.41,150.40,148.23,148.08,143.35,142.59,121.16,119.96,117.10,116. 02,106.70,71.00,70.08,69.90,69.50,69.17,20.89.LR-MS(ESI-TOF):Calcd.For C 36 H 45 NO 12 [M] + :683.29.Found:683.29.

[0201] (2) Synthesis of Compound 3

[0202] Compound 1 (1.5 g, 4.2 mmol) was added to a 50% sodium hydroxide methanol solution (30 mL), and the reaction was continued for 6 h. The solvent was removed by vortexing, and dichloromethane was added to dissolve the mixture. The mixture was washed with saturated brine (2×100 mL). The collected organic phase was dried over anhydrous sodium sulfate, and the solvent was dried by vortexing to obtain compound 3.

[0203] The physical parameters of compound 3 are: 1 H NMR (400 MHz, CDCl 3 )δ9.30(s,1H),7.33(dd,J=7.5,2.1Hz,2H),7.25–7.18(m,4H),6.90–6.78(m, 4H), 4.17 (d, J = 5.5Hz, 8H), 3.80 (s, 2H), 3.74 (s, 6H), 3.56 (d, J = 2.9Hz, 16H). 13 C NMR (100 MHz, CDCl 3 )δ157.34,148.08,147.80,143.15,140.62,122.12,120.05,116.20,115.24,106.96,71.00,70.08,69.90,69.50,69.17.LR-MS(ESI-TOF):Calcd.For C 34 H 43 NO 11 [M] + :641.28.Found:641.28.

[0204] (3) Synthesis of Compound 4

[0205] Compound 3 (1.50 g, 3.0 mmol) and Cs 2 CO 3 (2.29 g, 10.5 mmol) in acetonitrile (100 mL), 1,9-dibromononane (0.74 g, 3.3 mmol) was added, and the mixture was heated to 90 ° C. The reaction was stopped after 12 h under argon atmosphere. After cooling to room temperature, the crude mixture was filtered through diatomaceous earth, and the solvent was evaporated under reduced pressure. Compound 2 was purified by column chromatography (dichloromethane: methanol = 100: 4) to obtain compound 2.

[0206] The physical parameters of compound 4 are: 1 H NMR (400 MHz, CDCl 3)δ7.33(dd,J=7.5,2.1Hz,2H),7.24–7.18(m,4H),6.93–6.82(m,4H),4.17(d,J=2.9Hz,8H),4.04(s,2H),3.80 (s,2H),3.74(s,6H),3.61–3.54(m,18H),2.03(s,2H),1.77(s,2H),1.47(d,J=3.9Hz,4H),1.34–1.25(m,6H). 13 CNMR (100MHz, CDCl 3 )δ157.85,148.23,148.08,142.59,141.12,121.49,117.29,115.55,114.60,106.51,71.23,70.55,69.99, 69.87,69.54,68.80,33.87,32.32,30.39,29.66,29.48,29.03,28.15,26.10.LR-MS(ESI-TOF):Calcd.For C 43 H 60 BrNO 11 [M] + :845.33.Found:845.33.

[0207] (4) Synthesis of Compound 6: Refer to Compound 9 in Example 1

[0208] The physical parameters of compound 6 are: 1 H NMR (400 MHz, CDCl 3 )δ9.16(s,2H),6.86(q,J=0.9Hz,2H),2.64(s,4H),2.48–2.42(m,8H),2.20(s,6H),1.02(s,6H). 13 C NMR (100 MHz, CDCl 3 )δ156.22,140.65,138.88,127.96,121.81,121.31,114.10,43.72,36.90,20.20,18.60,11.44.LR-MS(ESI-TOF):Calcd.For C 24 H 28 O 2 [M] + :348.21.Found:348.21.

[0209] (5) Synthesis of Compound G

[0210] Compound 6 (0.50 g, 1.0 mmol) and Cs 2 CO 3 Compound 4 (2.67 g, 2.2 mmol) was added to a solution of 1.4 g, 3.0 mmol) in acetonitrile (100 mL), and the mixture was heated to 90 ° C. The reaction was stopped after 12 h under an argon atmosphere. After cooling to room temperature, the crude mixture was filtered through diatomaceous earth, and the solvent was evaporated under reduced pressure. Compound G was obtained by purification by column chromatography (dichloromethane: methanol = 100: 4).

[0211] The physical parameters of compound G are: 1 H NMR (400 MHz, CDCl 3 )δ7.33(dd,J=7.5,2.1Hz,4H),7.27–7.19(m,8H),6.93–6.87(m,4H),6.87–6.80(m,6H),4 .19–4.14(m,16H),4.05(dd,J=5.6,1.7Hz,8H),3.80(d,J=11.1Hz,16H),3.57(d,J=5.7Hz ,32H),2.91(s,2H),2.77(s,2H),2.41(s,2H),2.27(d,J=0.8Hz,6H),2.22(s,6H),1.76(d ,J=6.2Hz,8H),1.50–1.40(m,8H),1.37–1.30(m,8H),1.29(d,J=1.3Hz,4H),1.03(s,6H). 13 C NMR (100 MHz, CDCl 3 )δ157.41,157.05,148.23,147.85,144.70,143.40,139.50,137.31,13 1.90,124.60,121.57,120.71,117.48,116.34,114.91,113.60,106.71 ,71.23,70.56,70.20,69.99,69.87,69.65,68.80,40.50,37.40,29.64,29.43,29.38,29.07,19.45,17.32,12.00.LR-MS(ESI-TOF):Calcd.For C 110 H 146 N 2 O 24 [M] + :1879.03.Found:1879.03.

[0212] Example 8: Synthesis of Molecular H in an Artificial Ion Transport System Using a Light-Driven Molecular Motor

[0213]

[0214] The synthesis of compound H was similar to that of compound B in Example 2.

[0215] The physical parameters of compound H are: 1 H NMR (400 MHz, CDCl 3 )δ8.82(s,2H),8.11(s,2H),7.84(s,1H),7.73(s,1H),7.64(s,1H),7.48–7.43(m,4H),7.38(dt,J=7. 8,1.0Hz,2H),7.28(s,1H),7.23–7.18(m,5H),7.08–6.99(m,5H),6.80(s,2H),4.37(s,1H),4.27–4.14 (m,5H),3.82(s,6H),3.32(d,J=12.4Hz,2H),3.23(d,J=12.4Hz,2H),3.01(d,J=12.4Hz,2H),2.92(d,J =12.4Hz,2H),2.86(s,1H),2.32–2.19(m,4H),1.55–1.46(m,6H),1.42(d,J=12.5Hz,2H),0.95(s,9H). 13 C NMR (100 MHz, CDCl 3 )δ173.56,157.38,156.50,154.74,142.21,137.38,131.77,130.75,129.10,128.60,128 .27,127.82,127.49,126.55,126.00,125.87,125.21,124.91,122.44,122.23,121.95,1 21.21,117.12,115.48,114.29,108.78,100.81,100.73,94.23,81.42,70.90,62.46,56. 68,49.68,42.41,37.09,34.08,28.37,27.52,24.78,23.08.HR-MS(ESI-TOF):Calcd.For C 68 H 68 N 6 O 7 S[M] + :1112.4900.Found:1112.4903.

[0216] Example 9 Synthesis of Light-Driven Molecular Motor Artificial Ion Transport System Molecule I

[0217]

[0218] The synthesis method of compound I is similar to that of compound B in Example 2.

[0219] The physical parameters of compound I are: 1 H NMR (400 MHz, CDCl 3 )δ9.73(s,2H),7.85(s,1H),7.77(t,J=4.9Hz,4H),7.52–7.44(m,3H),7.42–7.33(m,6H),7.28–7. 16(m,8H),4.23(d,J=12.4Hz,2H),4.16(d,J=12.4Hz,2H),3.77(t,J=0.9Hz,2H),3.37(s,1H),3.2 5(s,1H),3.03(d,J=4.4Hz,7H),3.00(s,1H),2.92(d,J=12.4Hz,2H),2.61(t,J=1.0Hz,4H),2.31( s,1H),2.22(s,4H),1.79–1.68(m,2H),1.65(s,4H),1.50(s,4H),1.32–1.21(m,16H),0.88(s,3H). 13 C NMR (100 MHz, CDCl 3 )δ180.40,173.60,139.28,135.12,134.90,131.93,131.82,131.77,131.00,128.73,128.20, 127.47,127.13,126.91,126.61,126.42,125.55,125.50,124.96,123.45,123.41,122.65,12 2.39,120.87,118.48,116.66,94.23,82.51,62.46,40.75,37.48,36.00,34.15,33.98,30.68 ,30.67,29.48,29.32,29.18,29.11,25.27,23.20,21.84,11.77.HR-MS(ESI-TOF):Calcd.For C 71 H 80 N 4 O 4 S 3 [M] + :1148.5300.Found:1148.5302.

[0220] Example 10 Synthesis of the Light-Driven Molecular Motor Artificial Ion Transport System Molecule J

[0221]

[0222] The synthesis method of compound J is as follows:

[0223] The physical parameters of compound J are: 1 H NMR (400 MHz, CDCl 3 )δ8.11(s,2H),7.81(d,J=4.9Hz,2H),7.76(s,1H),7.63(dd,J=7.5,1.8Hz,2H),7.49(dd,J=7.5,2.1Hz,2H),7.42(d d,J=10.5,1.9Hz,4H),7.24(s,1H),7.20–7.12(m,4H),7.02(d,J=7.5Hz,2H),4.41(s,4H),4.29(s,4H),4.17(d,J=4 .9Hz,8H),3.95(t,J=1.0Hz,2H),3.81(s,4H),3.64(s,2H),3.57(d,J=5.5Hz,26H),3.15(s,4H),3.00(d,J=13.0Hz, 1H),2.67–2.56(m,4H),2.53–2.46(m,2H),1.78–1.68(m,4H),1.61(d,J=2.6Hz,4H),1.56–1.45(m,4H),0.93(s,9H). 13 C NMR (100 MHz, CDCl 3 )δ165.79,149.39,147.21,144.91,135.21,134.04,133.43,133.10,133.00,132.82,128.37,127.41 ,127.36,127.31,126.13,125.55,125.48,125.45,124.96,124.50,123.93,123.79,123.66,123.45,1 22.62,120.64,118.57,114.80,114.16,93.20,81.53,71.24,70.93,70.60,69.84,69.61,66.00,47.7 3,46.13,36.83,36.54,36.23,32.83,30.78,29.08,28.21,27.41,27.23.HR-MS(ESI-TOF):Calcd.For C 87 H 102 N6 O 16 [M] + :1486.7400.Found:1486.7400.

[0224] Example 11 Synthesis of the molecule K of the light-driven molecular motor artificial ion transport system

[0225]

[0226] The synthesis method of compound K is as follows:

[0227] The physical parameters of compound K are: 1 H NMR (400 MHz, CDCl 3 )δ9.73(s,2H),7.87(s,1H),7.78(d,J=7.5Hz,3H),7.71(s,1H),7.58(dd,J=7.4,1.9Hz,2H) ,7.44–7.36(m,7H),7.28(s,1H),7.16–7.11(m,3H),7.07(dt,J=7.6,1.1Hz,4H),4.24(d,J=1 2.5Hz,2H),4.17(d,J=12.4Hz,2H),3.57(s,1H),3.07(s,1H),3.03(d,J=4.4Hz,7H),3.00(s, 1H), 2.92 (d, J = 12.4Hz, 2H), 2.62–2.51 (m, 4H), 2.39–2.29 (m, 5H), 1.72 (s, 4H), 1.00 (s, 3H). 13 C NMR (100 MHz, CDCl 3 )δ180.40,173.64,154.91,153.74,140.87,138.91,136.03,134.49,132.82,1 31.09,128.70,127.50,127.23,127.09,125.83,125.67,125.01,123.75,123.2 0,123.17,121.68,121.65,121.04,117.33,116.35,94.23,81.42,62.46,53.03 ,49.35,33.98,33.24,30.67,25.84,23.08,17.06.HR-MS(ESI-TOF):Calcd.For C 59 H 56 N 4 O 5 S 3 [M] +:996.3400.Found:996.3401.

[0228] Example 12 Synthesis of molecule L of the light-driven molecular motor artificial ion transport system

[0229]

[0230] The synthesis method of compound L is as follows:

[0231] The physical parameters of compound L are: 1 H NMR (400 MHz, CDCl 3 )δ7.86(s,1H),7.68–7.55(m,5H),7.53–7.46(m,3H),7.32(d,J=1.9Hz, 2H),7.28(s,1H),7.16–7.07(m,3H),7.01–6.94(m,3H),4.27(d,J=13.0H z,5H),4.20–4.14(m,9H),3.81(s,4H),3.69(s,4H),3.59–3.48(m,24H), 3.05(s,1H),2.38(s,4H),1.80(s,4H),1.76–1.66(m,12H),1.12(s,3H). 13 C NMR (100 MHz, CDCl 3 )δ165.80,155.70,154.49,149.39,145.98,135.86,131.32,131.29,130.71,128.20,127 .88,127.22,126.77,126.40,126.14,125.45,123.75,122.62,120.05,119.14,117.63,11 5.48,114.80,114.16,110.75,94.23,81.85,76.86,72.02,71.51,71.24,70.58,69.84,69 .61,66.00,43.37,29.88,29.11,29.03,26.07,23.70,16.14.HR-MS(ESI-TOF):Calcd.For C 77 H 88 O 18 [M] + :1300.6000.Found:1300.6001.

[0232] Example 13 Determination of anti-tumor activity of artificial transmembrane channel molecules based on light-driven motors

[0233] Test method: CCK-8 method was used to determine the proliferation inhibition effect of channel molecule (AL) on human cervical cancer cells (HeLa), human liver cancer cells (HepG2), human lung cancer cells (A549), human breast cancer cells (MCF-7) and human prostate cancer cells (PC-3). In addition, in order to test the selectivity of cancer cells, cytotoxicity tests were also performed on normal cells including mouse embryonic fibroblasts (NIH3T3), human umbilical vein endothelial cells (HUVEC) and mouse fibroblasts (L929). The specific test process is as follows:

[0234] (1) The above tumor cell lines were prepared into single cell suspensions using the corresponding complete culture medium. The concentration of the single cell suspension was 5000 cells / mL. 200 μL of the cell suspension was inoculated into a 96-well culture plate and placed in a CO 2 Incubator (37°C, 5% CO 2 , 95% air) for 24 h; human cervical cancer cells (HeLa), human liver cancer cells (HepG2), mouse embryonic fibroblasts (NIH3T3), human umbilical vein endothelial cells (HUVEC) and mouse fibroblasts (L929) were cultured in DMEM high glucose medium (containing 10% newborn calf serum, 1% double antibody); human prostate cancer cells (PC-3) and human lung cancer cells (A549) were cultured in 1640 medium (containing 10% newborn calf serum, 1% double antibody); human breast cancer cells (MCF-7) were cultured in MEM medium (containing 10% newborn calf serum, 1% double antibody).

[0235] (2) Dissolve the compound in DMSO and prepare a series of solutions with concentrations of 0.10, 0.25, 0.50, 1.00, 2.00 and 5.00 μM (final concentration, 0.1% DMSO) in culture medium. Remove the culture medium and add the culture medium containing the compound for 16 h.

[0236] For light manipulation, cells were first co-cultured with channel molecules for 12 h and then illuminated for 5 min (UV: 365 nm LED light or Vis: 405 nm LED light, 5 mW cm -2 , a safe dose without cytotoxicity) and co-cultured for another 4 h.

[0237] (3) After 16 hours of culture, the culture medium was removed and replaced with fresh culture medium, and then 10 μL of CCK-8 (Cell Counting Kits-8) reagent was added to each well of cells. After incubation at 37°C for 1.5 hours, the absorbance at 450 nm was measured using a Biotek multifunctional microplate reader. Cell viability was expressed as the ratio of the number of live cells after treatment to the number of live cells without treatment. The data are the average of at least four experiments. Among them, the presence of 0.1% DMSO and the applied light irradiation had no cytotoxicity to all selected cells.

[0238] (4) Test results: As shown in Table 1, the channel molecules of the present invention exhibited a certain degree of inhibitory effect on various tumor cells. 50 >10.3μM, for normal cells, IC 50 >15.3μM; Under UV light, IC 50 <0.83μM, normal cells HUVEC (IC 50 2.70±0.09μM), L929 cells (IC 50 5.60±0.15μM), NIH3T3 cells (IC 50 is 4.40±0.10μM).

[0239] Table 1. Channel molecule cytotoxicity test data.

[0240]

[0241]

[0242] In general, channel molecules have the following advantages: 1) they have certain anti-cancer activity without light exposure; 2) they show high anti-tumor activity under ultraviolet light, and have obvious effects of killing tumor cells and inhibiting tumor cell growth; 3) they have higher cytotoxicity to cancer cells than normal cells, and can selectively target and kill cancer cells. Therefore, the present invention has important application value in the research and development of anti-cancer.

[0243] Example 14 Antibacterial activity test of artificial transmembrane channel molecules based on light-driven motors

[0244] Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli were used as the research objects and as bacterial strains for antibacterial experiments. The newly purchased strains were inoculated into TSB or LB culture medium, placed in a 37°C constant temperature shaker (150RPM), and cultured overnight. The strains were inoculated onto a blood agar plate with an inoculation loop and cultured for 24 hours. If there was a hemolysis zone on the culture plate, the strain could be used normally. The revived strains were inoculated into liquid culture medium and cultured in a 37°C constant temperature shaker (150RPM). Every 1 hour, 1 mL of culture medium was taken to determine the OD of the bacterial solution. 600 Take 2 mL of bacterial culture in the exponential growth phase and centrifuge at 4°C (3000 RPM) for 10 minutes. Remove the supernatant and wash three times with sterile PBS. 6 The bacterial solution with CFU / mL is ready for use. The bacterial concentration is determined by the standard curve.

[0245] Antimicrobial activity assay

[0246] Bacterial co-culture test: Take 200 μL of bacterial solution onto TSA agar plate, spread evenly, add different concentration gradients of channel molecules, and culture in a biochemical incubator at 37°C for 18-24 hours. Count after the culture. For light operation, first co-culture the bacteria with the channel molecules for 12 hours, then illuminate for 5 minutes (UV: 365nm LED light or Vis: 405nm LED light, 5mW cm -2 , a safe dose without toxicity), and then co-culture for 6-12 hours. The lowest sample concentration at which no bacterial growth is observed is its minimum inhibitory concentration (MIC). At the same time, a blank control without any sample and a solvent control with DMSO (﹤5%) added are set up.

[0247] The test results are shown in Table 2. The compounds of the present invention exhibit a certain degree of inhibitory effect on Staphylococcus aureus and Escherichia coli. In general, the present invention has important potential application value in the research and development of drugs against Gram-positive bacteria such as Staphylococcus aureus and Gram-negative bacteria such as Escherichia coli.

[0248] Table 2 Antibacterial activity test of channel molecules

[0249]

[0250]

[0251] Comparative Example 1

[0252] To further demonstrate the excellent anti-cancer performance of the artificial transmembrane channel molecule of the light-driven motor of the present invention, a horizontal comparison was made between the compound A prepared in Example 1 and the commercial anticancer drug doxorubicin. The results are shown in Table 3.

[0253]

[0254] Table 3 Comparison of channel molecules and doxorubicin cancer cell toxicity test

[0255]

[0256] As shown in Table 3, the toxicity of the synthesized channel molecule A before illumination is lower than that of doxorubicin, but after illumination, the cytotoxicity is greatly increased, and the anticancer activity is higher than that of the commercial anticancer drug molecule doxorubicin.

[0257] Comparative Example 2

[0258] In order to further demonstrate the excellent antibacterial properties of the artificial transmembrane channel molecules of the light-driven motor of the present invention, a horizontal comparison was made between the compound E prepared in Example 5 and the reference molecule chitosan.

[0259]

[0260] Table 4 Antibacterial activity test of channel molecule E and chitosan

[0261]

[0262] As shown in Table 4, the MIC of chitosan for Staphylococcus aureus is 95.7 μg mL -1 ; For E. coli, the MIC is 120.4 μg mL -1 Compared with the channel molecule E prepared in Example 5 of the present invention, the antibacterial performance is poor.

[0263] The above is only a preferred embodiment of the present invention, and does not limit the present invention in any form. Although the present invention has been disclosed as a preferred embodiment, it is not used to limit the present invention. Any technician familiar with this patent can make some changes or modify the technical contents suggested above into equivalent embodiments without departing from the scope of the technical solution of the present invention. However, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the solution of the present invention.

Claims

1. A light-driven molecular motor based on a large sterically hindered olefin. It is characterized in that The structure is selected from any one of the following: Where X is O, S or CH 2 ; Y 2 CH 2 -CH 2 CH 2 -S、CH 2 -O Z is methyl, ethyl, propyl, isopropyl; m and n are both integers of 1-8, and t is an integer of 1-3; R 5 , R 6 , R 7 Each is independently selected from any one of the following groups: hydrogen, hydroxyl, amino.

2. A light-driven molecular motor based on a large sterically hindered olefin. It is characterized in that The structure is selected from any one of the following: Among them, R 5 , R 6 , R 7 and R 8 Each independently selected from any one of the following groups: hydrogen, methoxy, methyl; m and n are both integers of 1-8, and t is an integer of 1-3.

3. Use of the light-driven molecular motor based on large sterically hindered olefins according to claim 1 or 2 in the preparation of anti-tumor drugs, It is characterized in that The tumor is selected from cervical cancer, liver cancer, lung cancer, breast cancer or prostate cancer.

4. Use of the light-driven molecular motor based on large sterically hindered olefins according to claim 1 or 2 in the preparation of anti-pathogenic microbial preparations, It is characterized in that The pathogenic microorganism is selected from Gram-negative bacteria or Gram-positive bacteria.

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