CN108689943B

CN108689943B - Ruthenium-containing supramolecular compound and preparation method and application thereof

Info

Publication number: CN108689943B
Application number: CN201810562990.6A
Authority: CN
Inventors: 曹昌盛; 史延慧; 赵义波
Original assignee: Jiangsu Normal University
Current assignee: Jiangsu Normal University
Priority date: 2018-06-04
Filing date: 2018-06-04
Publication date: 2021-07-30
Anticipated expiration: 2038-06-04
Also published as: CN108689943A; CN112940276A

Abstract

A ruthenium-containing supramolecular compound, a preparation method and application thereof, and relates to a novel ruthenium-containing supramolecular compound, a preparation method and application thereof, a novel benzimidazole ligand and a preparation method thereof. The benzimidazole ligand of the invention has low toxicity, is a novel benzimidazole ligand, and has far lower toxicity than pyridine ligands. The ruthenium-containing supramolecular compound disclosed by the invention is a novel ruthenium-containing supramolecular compound, and has a good inhibition effect on human lung cancer cell lines HCT-116 and A549.

Description

Ruthenium-containing supramolecular compound and preparation method and application thereof

Technical Field

The embodiment belongs to the field of organic chemical synthesis, and particularly relates to a ruthenium-containing supramolecular compound and a preparation method and application thereof.

Background

A full tumor refers to a lump formed by abnormal proliferation of cells of local tissues under the action of various tumorigenic factors. Tumors can be classified into benign tumors and malignant tumors, and malignant tumors (also called cancers) can destroy the structure and function of tissues and organs, cause hemorrhagic necrosis and infection of the tissues and organs, and finally, patients can die due to exhaustion of the organ function. The ruthenium-based compound has good anticancer activity, and an important class of the ruthenium-based compound is arene ruthenium (II) supermolecule self-assembly anticancer compound constructed by coordination bond driving.

Suss-Fink synthesized the first arene ruthenium (II) supramolecular coordination compound in 1997. An arene ruthenium (II) acceptor is a partially encapsulated ruthenium-based coordination compound that has a structure similar to a piano stool (also known as a molecular clip), and is two ruthenium (II) ions connected by a bridging ligand, leaving one coordinatable site on each metal ion. The aromatic ruthenium (II) acceptor and ligands with different angles or different types are used for obtaining the polynuclear supermolecule self-assembly compound with a two-dimensional or three-dimensional structure by a self-assembly means. Most of the anticancer p-cymene ruthenium self-assembly compounds in the prior art mostly adopt double-headed pyridine or carboxylic acid ligands.

Disclosure of Invention

The invention aims to provide a novel ruthenium-containing supramolecular compound, a preparation method and application thereof.

It is another object of the present invention to provide a novel benzimidazole ligand.

In order to achieve the purpose, the technical scheme of the invention is as follows:

a benzimidazole ligand having the structure shown in formula I:

wherein R is n-C₄H₉O or n-C₈H₁₇O。

The invention also provides a preparation method of the benzimidazole ligand in the technical scheme, which comprises the following steps:

(1) dropwise adding dilute nitric acid and fuming nitric acid into an acetic acid solution of 1, 2-dialkoxybenzene for nitration reaction to obtain a nitration product, wherein the 1, 2-dialkoxybenzene is 1, 2-dibutoxybenzene or 1, 2-dioctyloxybenzene;

(2) mixing the nitration product obtained in the step (1), a Pd/C catalyst, absolute ethyl alcohol and hydrazine hydrate to perform a reduction reaction to obtain a reduction product;

(3) mixing the reduction product obtained in the step (2) with formic acid to perform cyclization reaction to obtain an imidazole ring, so as to obtain a benzimidazole derivative, wherein the benzimidazole derivative is 5, 6-dibutoxybenzimidazole or 5, 6-dioctyloxybenzimidazole;

(4) and (4) mixing the benzimidazole derivative obtained in the step (3), p-bromobenzene, potassium carbonate, copper oxide and N, N-dimethylformamide to perform Ullmann reaction to obtain the benzimidazole ligand with the structure shown in the formula I.

The invention also provides a ruthenium-containing supramolecular compound which has a structure shown in a formula II:

wherein A is a compound having a structure represented by formula A1, A2, or A3:

l is a compound having the structure shown in formula L1, L2, L4 or formula I:

wherein R is n-C₄H₉O or n-C₈H₁₇O。

The invention also provides a ruthenium-containing supramolecular compound having a structure shown in formula III:

l is a compound having the structure shown in formula L3:

the embodiment also provides a preparation method of the ruthenium-containing supramolecular compound in the technical scheme, which comprises the following steps: and mixing the compound A, the compound L and a polar organic solvent to perform coordination-driven self-assembly reaction to obtain the ruthenium-containing supramolecular compound.

Preferably, the time of the coordination-driven self-assembly reaction is 24-48 h.

Preferably, the coordination-driven self-assembly reaction further comprises: removing the polar organic solvent in the coordination-driven self-assembly reaction product, and adding diethyl ether for centrifugal treatment.

Preferably, the rotation speed of the centrifugal treatment is 2900rpm, and the time of the centrifugal treatment is 10 min.

Preferably, the polar organic solvent comprises dichloromethane and/or methanol.

The embodiment also provides the application of the ruthenium-containing supramolecular compound in the technical scheme in the preparation of anti-cancer drugs.

Compared with the prior art, the invention has the beneficial effects that: the benzimidazole ligand of the invention has low toxicity, is a novel benzimidazole ligand, and has far lower toxicity than pyridine ligands. The ruthenium-containing supramolecular compound disclosed by the invention is a novel ruthenium-containing supramolecular compound, and has a good inhibition effect on human lung cancer cell lines HCT-116 and A549.

Drawings

FIG. 1 shows L5 prepared in example 13 of the present invention¹H-NMR spectrum;

FIG. 2 shows L5 prepared in example 13 of the present invention¹³A C-NMR spectrum;

FIG. 3 shows L6 prepared in example 16 of the present invention¹H-NMR spectrum;

FIG. 4 shows L6 prepared in example 16 of the present invention¹³C-NMR spectrum.

The specific implementation mode is as follows:

the present invention provides benzimidazole ligands having the structure shown in formula I:

wherein R is n-C₄H₉O or n-C₈H₁₇O。

In the present invention, the structure of the benzimidazole ligand having the structure shown in formula I is as follows:

The method comprises the step of dropwise adding dilute nitric acid and fuming nitric acid into an acetic acid solution of 1, 2-dialkoxybenzene for nitration reaction to obtain a nitration product, wherein the 1, 2-dialkoxybenzene is 1, 2-dibutoxybenzene or 1, 2-dioctyloxybenzene. In the present invention, the nitric acid and fuming nitric acid are preferably mixed and then added dropwise. In the present invention, the dropping is preferably performed using a constant pressure dropping funnel. In the present invention, the dropwise addition is preferably carried out in an ice bath, the temperature of which is preferably 0 ℃.

In the present invention, the amount ratio of the dilute nitric acid, fuming nitric acid, 1, 2-dialkoxybenzene and acetic acid is preferably 3.5 mL: 30mL of: 18.0 mol: 40 mL.

In the invention, the temperature of the nitration reaction is preferably room temperature, no additional heating or cooling is needed, the time of the nitration reaction is preferably 3-5 h, more preferably 4h, and the time of the nitration reaction is calculated when the reaction system reaches the room temperature after the dropwise addition is finished. In the present invention, it is preferable that the ice bath is removed after the completion of the dropwise addition so that the reaction system reaches the temperature of the nitration reaction.

The source of the 1, 2-dialkoxybenzene is not particularly limited by the invention, and the 1, 2-dialkoxybenzene is prepared by a preparation method well known by a person skilled in the art, and concretely comprises the steps of mixing catechol with N, N-dimethylformamide, slowly adding anhydrous potassium carbonate, then adding bromoalkane, carrying out nucleophilic substitution reaction at 90 ℃ for 18h, extracting with water/ethyl acetate, combining organic phases, washing with NaOH aqueous solution for three times, then washing with saturated salt water for three times, drying with anhydrous sodium sulfate, and spin-drying the solvent with a rotary evaporator to obtain the 1, 2-dialkoxybenzene. In the invention, the brominated alkane is n-butyl bromide or n-octane bromide.

In the present invention, the volume ratio of water to ethyl acetate in the water/ethyl acetate is preferably 1: 0.2-1: 0.5.

after the nitration reaction is finished, the reaction solution obtained by the nitration reaction is preferably mixed with an ice-water mixture, filtered, washed, refluxed with absolute ethyl alcohol, cooled, separated out and filtered again to obtain a nitration product. The specific operations of the ice-water mixture, the water and the absolute ethyl alcohol, the suction filtration, the alcohol reflux, the cooling precipitation and the re-suction filtration are not particularly limited, and the method well known by the technical personnel in the field can be adopted.

In the present invention, the nitrated product has a structure represented by the following formula:

wherein R is n-C₄H₉O-or n-C₈H₁₇O-。

After a nitration product is obtained, the nitration product, the Pd/C catalyst, the absolute ethyl alcohol and the hydrazine hydrate are mixed to carry out reduction reaction, and a reduction product is obtained. In the present invention, the amount ratio of the nitrated product, the Pd/C catalyst, the anhydrous ethanol and the hydrazine hydrate is preferably 12.8 mol: 90 mg: 40mL of: 6.3 mL.

In the present invention, the temperature of the reduction reaction is preferably 80 ℃, and the time of the reduction reaction is preferably 12 hours. The source of the catalyst is not particularly limited in the present invention, and a Pd/C catalyst known to those skilled in the art may be used.

In the present invention, before the reduction reaction, it is preferable to further include evacuating and changing nitrogen gas. In the present invention, the number of times of the evacuation ventilation is preferably 3 times. In the present invention, the pressure of the nitrogen gas is preferably atmospheric pressure.

After the reduction reaction is completed, the reaction solution obtained by the reduction reaction is preferably cooled to room temperature, and then is subjected to diatomite and spin-drying to obtain a reduction product. In the present invention, the cooling to room temperature is preferably natural cooling. In the present invention, the diatomaceous earth is used for removing solid by-products such as Pd/C catalyst generated in the reduction reaction. In the present invention, the spin-drying of the solvent is preferably carried out in a rotary evaporator.

In the present invention, the structure of the reduction product is represented by the following formula:

after obtaining the reduction product, mixing the reduction product with formic acid to perform cyclization reaction to obtain an imidazole ring, thereby obtaining the benzimidazole derivative, wherein the benzimidazole derivative is 5, 6-dibutoxybenzoimidazole or 5, 6-dioctyloxybenzimidazole. In the present invention, the amount ratio of the reduction product to formic acid is preferably 12.8 mol: 50 mL.

In the present invention, before the cyclization reaction to form imidazole ring, it is preferable to further include evacuating and changing nitrogen gas. In the present invention, the number of times of the evacuation ventilation is preferably 3 times. In the present invention, the pressure of the nitrogen gas is preferably atmospheric pressure.

In the present invention, the time for the cyclization reaction to form the imidazole ring is preferably 12 hours.

After the reaction to form imidazole ring is completed, the present invention also preferably removes formic acid from the reaction solution obtained by the reaction to form imidazole ring, adjusts the pH value to be neutral, extracts with ethyl acetate, washes with water, washes with saturated saline, spin-dries the solvent, washes with ether, and filters in order to obtain the benzimidazole derivative. In the present invention, the formic acid is preferably removed by distillation under reduced pressure. In the present invention, the reagent for adjusting the pH is preferably ammonia or a saturated sodium carbonate solution. The amount of ethyl acetate, water, saturated brine and diethyl ether used in the present invention is not particularly limited, and may be those known to those skilled in the art.

After obtaining the benzimidazole derivative, mixing the benzimidazole derivative, p-bromobenzene, potassium carbonate, copper oxide and N, N-dimethylformamide to perform Ullmann reaction to obtain the benzimidazole ligand with the structure shown in the formula I. In the present invention, the benzimidazole derivative, p-bromobenzene, potassium carbonate, copper oxide and N, N-dimethylformamide are preferably used in a ratio of 122.4 mmol: 50.4 mmol: 124.8 mmol: 6.0 mmol: 60 mL.

In the present invention, the temperature of the Ullmann reaction is preferably 150 ℃, and the reagent of the Ullmann reaction is preferably 48 h.

In the present invention, it is preferable that the Ullmann reaction is performed before the Ullmann reaction is performed by replacing nitrogen with vacuum. In the present invention, the number of times of evacuating and replacing nitrogen gas is preferably 3 times. In the present invention, the pressure of the nitrogen gas is preferably atmospheric pressure.

After the Ullmann reaction is finished, the invention also preferably comprises the steps of sequentially passing reaction liquid of the Ullmann reaction through diatomite, dichloromethane washing, water washing, saturated salt water washing, anhydrous sodium sulfate drying, spin-drying a solvent, pentane washing, filtering and column chromatography to obtain the benzimidazole ligand with the structure shown in the formula I. The amounts of the diatomaceous earth, methylene chloride, water, saturated saline solution, anhydrous sodium sulfate and pentane used in the present invention are not particularly limited, and may be those well known to those skilled in the art. In the invention, the eluent used for the column chromatography is ethyl acetate.

The present invention also provides ruthenium-containing supramolecular compounds having the structure shown in formula II:

l is a compound having the structure shown in formula L1, L2, L4 or formula I:

wherein R is n-C₄H₉O-or n-C₈H₁₇O-。

The present invention also provides ruthenium-containing supramolecular compounds having the structure shown in formula III:

l is a compound having the structure shown in formula L3:

in the invention, A and L are connected through coordination bonds, the cation part is a rectangular or triangular prism formed by A and L, and the anion part is trifluoromethanesulfonate.

The invention also provides a preparation method of the ruthenium-containing supramolecular compound in the technical scheme, which comprises the following steps: and mixing the compound A, the compound L and a polar organic solvent to perform coordination-driven self-assembly reaction to obtain the ruthenium-containing supramolecular compound.

In the present invention, when L is a compound having a structure represented by formula L1, L2, L4 or formula I, the molar ratio of a to L is 1:1, and when L is a compound having a structure represented by formula L3, the molar ratio of a to L is 3: 2.

The source of the A is not particularly limited in the invention, and the A can be prepared by a preparation method well known to those skilled in the art, specifically, the A comprises the following steps:

a1 was prepared by dissolving dichlorobis (4-methylisopropylphenyl) ruthenium (II) and oxamine in a mixed solvent of methanol/chloroform (V: V ═ 1:1), vacuum-pumping the mixture to displace nitrogen, refluxing the reaction, cooling the reaction system to room temperature, drying the solvent using a rotary evaporator, dissolving the residue in dichloromethane, and filtering. The filtrate was spin-dried to give a pale yellow solid. And dissolving the obtained solid and silver trifluoromethanesulfonate equivalent in methanol, stirring for 2-4 h at room temperature, separating out white AgCl precipitate, filtering by using kieselguhr, washing for three times by using methanol to obtain filtrate, rotating the filtrate to be slightly dry, adding diethyl ether to separate out yellow solid, centrifuging (2500r/min) for 10min, removing supernatant to obtain a target product, and then drying in vacuum.

A2 is prepared by placing dichlorobis (4-methylisopropylphenyl) ruthenium (II), 2, 5-dihydroxy-1, 4-benzoquinone and sodium acetate in an eggplant-shaped flask, adding 25mL of ethanol, evacuating to replace nitrogen, and refluxing under vigorous stirring for 24 h. When the reaction system is cooled to room temperature, centrifuging (2500r/min) for 10min, discarding the supernatant to obtain a dark red solid, and washing twice with ethanol, acetone and diethyl ether respectively. Dissolving the solid and silver trifluoromethanesulfonate in methanol, stirring at room temperature for 2-4 h to separate out white AgCl precipitate, then filtering with diatomite to obtain a filtrate, rotating the filtrate to be slightly dry, adding ether, and separating out a dark red solid. Centrifuging (2500r/min) for 10min to obtain the target product, and then drying in vacuum.

The preparation method of A3 comprises the following steps: adding dichlorobis (4-methyl isopropylphenyl) ruthenium (II), nerchinaberry root and sodium acetate into a pear-shaped bottle, adding ethanol, and refluxing for 24h under vigorous stirring. And (3) cooling the reaction system to room temperature, centrifuging (2500r/min) for 10min, discarding the supernatant, and washing the solid twice with ethanol, acetone and diethyl ether respectively to obtain a brown solid. Dissolving the solid and silver trifluoromethanesulfonate in methanol, stirring at room temperature for 2-4 h to separate out white AgCl precipitate, then filtering with diatomite to obtain a filtrate, rotating the filtrate to be slightly dry, adding ether, and separating out a green solid. Centrifuging (2500r/min) for 10min to obtain the target product, and then drying in vacuum.

The sources of the L1, L2, L3 and L4 in the present invention are not particularly limited, and may be commercially available products known to those skilled in the art or prepared by methods known to those skilled in the art, specifically, such as:

the preparation method of L1 comprises mixing 1, 4-p-bromobenzene, imidazole and potassium carbonate N, N-dimethylformamide, displacing nitrogen three times, and reacting at 150 deg.C for 48 h. And (3) passing the crude product through diatomite, washing with dichloromethane, combining organic phases, then adding water for washing for three times, washing with saturated saline solution for three times, drying with anhydrous sodium sulfate, spin-drying the solvent with a rotary evaporator to obtain a solid, washing with pentane, filtering with a distributed funnel to obtain a yellow solid, and performing column chromatography (EA) on the crude product to obtain a white solid, namely the target product.

The preparation method of L2 comprises mixing 1, 3-m-bromobenzene, imidazole, potassium carbonate and N, N-dimethylformamide, displacing nitrogen three times, and reacting at 150 deg.C for 48 h. And (3) passing the crude product through diatomite, washing with dichloromethane, combining organic phases, then adding water for washing for three times, washing with saturated saline solution for three times, drying with anhydrous sodium sulfate, spin-drying the solvent with a rotary evaporator to obtain a solid, washing with pentane, filtering with a distributed funnel to obtain a yellow solid, and performing column chromatography (EA) on the crude product to obtain a white solid, namely the target product.

The preparation method of L3 comprises mixing m-tribromobenzene, imidazole, potassium carbonate and N, N-dimethylformamide, displacing nitrogen for three times, and reacting at 150 deg.C for 48 h. And (3) passing the crude product through diatomite, washing with dichloromethane, combining organic phases, then adding water for washing for three times, washing with saturated saline solution for three times, drying with anhydrous sodium sulfate, spin-drying the solvent with a rotary evaporator to obtain a solid, washing with pentane, filtering with a distributed funnel to obtain a yellow solid, and performing column chromatography (EA) on the crude product to obtain a white solid, namely the target product.

The preparation method of L4 comprises mixing 1, 3-m-bromobenzene, benzimidazole, potassium carbonate and DMSO, displacing nitrogen three times, and reacting at 150 deg.C for 48 h. The crude product was passed through celite, washed with dichloromethane and then extracted with dichloromethane/water, the organic phases were combined, dried over anhydrous sodium sulphate, washed with pentane after drying of the solvent and filtered to give a yellow solid, and the crude product was subjected to column chromatography (EA) to give a white solid.

In the invention, the time of the coordination-driven self-assembly reaction is preferably 24-48 h, and the temperature of the coordination-driven self-assembly reaction is preferably room temperature, so that additional heating or cooling is not required.

In the present invention, the coordination-driven self-assembly reaction preferably further comprises: removing the polar organic solvent in the coordination-driven self-assembly reaction product, and adding diethyl ether for centrifugal treatment. The method for removing the polar organic solvent is not particularly limited in the present invention, and a method known to those skilled in the art, specifically, a purge, may be used. The invention has no special limit on the dosage of the ether, and can separate out the ruthenium-containing supramolecular compound.

In the present invention, the rotation speed of the centrifugation is preferably 2900rpm, and the time of the centrifugation is preferably 10 min. After obtaining the centrifuged product, the present invention preferably further comprises washing the centrifuged product with diethyl ether as well. The amount of ether and the number of times of centrifugation are not particularly limited in the present invention, and any method known to those skilled in the art may be used.

In the present invention, the polar organic solvent preferably includes CD₃One or more of OD, DCM and methanol (MeOH), more preferably mixture of DCM and methanol, CD₃A mixture of OD and DCM. In the present invention, the volume ratio of DCM to methanol in the mixture of DCM and methanol is preferably 1:1, and the CD is preferably₃CD in mixture of OD and DCM₃The volume ratio of OD to DCM is preferably 1: 1.

The invention also provides the application of the ruthenium-containing supramolecular compound in the technical scheme in the preparation of anti-cancer drugs.

In the invention, the ruthenium-containing supramolecular compound can be prepared into various pharmaceutical dosage forms (including tablets, capsules, sprays, effervescent tablets, ointments and injections) for use.

In the present invention, the cancer cell preferably includes HCT-116 (human colon cancer cell) or A549 (human lung cancer cell).

In the present invention, the effective dose of the ruthenium-containing supramolecular compound is preferably 0.37 to 50 μm.

The ruthenium-containing supramolecular compounds, methods for preparing and using the same, and benzimidazole ligands and methods for preparing the same provided by the present invention are described in detail below with reference to the examples, but they should not be construed as limiting the scope of the present invention.

Example 1

Preparation of A1, dichlorobis (4-methylisopropylphenyl) ruthenium (II) (306.2mg,0.5mmol) and oxamine (62.1mg,0.5mmol) were taken up in a 100mL eggplant-shaped flask, dissolved in 30mL of a methanol/chloroform (V: V ═ 1:1) mixed solvent, the nitrogen was replaced by vacuum evacuation, the reaction was refluxed for 6h, the reaction system was cooled to room temperature, the solvent was dried by spin drying using a rotary evaporator, the residue was dissolved in dichloromethane, and filtered. The filtrate was spin-dried to give a pale yellow solid. Dissolving the obtained solid and silver trifluoromethanesulfonate equivalent in methanol, stirring at room temperature for 2h to separate out white AgCl precipitate, then filtering with diatomite to obtain filtrate, turning the filtrate to be slightly dry, and adding ether to separate out yellow solid. Centrifuging (2500r/min) for 10min, discarding supernatant to obtain target product, and vacuum drying.

Preparation of L1: 24.6g (105mmol) of 1, 4-p-bromobenzene, 17.5g (205mmol) of imidazole and 36.0g (260mmol) of potassium carbonate were weighed out in a 200mL eggplant-shaped bottle, and 100mL of N, N-dimethylformamide was added thereto, and nitrogen gas was replaced three times to react at 150 ℃ for 48 hours. Washing the crude product with diatomite and dichloromethane, combining organic phases, then adding water for three times, washing with saturated saline solution for three times, drying with anhydrous sodium sulfate, spin-drying the solvent with a rotary evaporator to obtain a solid, washing with pentane, filtering with a distributed funnel to obtain a yellow solid, and performing column chromatography (developing solvent: ethyl acetate) on the crude product to obtain a white solid, namely the target product.

Ligand L1(2.1mg,0.01mmol) and metal acceptor A1(8.6mg,0.01mmol) were accurately weighed into a 8mL catalytic vial, dissolved with methanol, self-assembled by coordination driven stirring at room temperature for 24h, the solvent was blown to 0.2mL and ether was added to precipitate a solid, centrifuged for 10min with a centrifuge (2900R/min), the supernatant was discarded, and washed once with ether to give a metal rectangular ruthenium-containing supramolecular compound R1.

Characterization of the metallic rectangular ruthenium-containing supramolecular compound R1:

¹H NMR(400MHz,CD₃OD+DMSO-d₆V/V＝5/1)δ8.57(s,4H,H_2-imidazole),7.94(s,4H,H_5-imidazole),7.71(s,8H,Ph),6.85(s,4H,H_4-imidazole),6.21(d,J＝6.4Hz,8H,Ph_p-cymene),6.03(d,J＝6.4Hz,8H,Ph_p-cymene),3.10–3.00(m,4H,CH),2.46(s,12H,CH₃),1.57(d,J＝6.9Hz,24H,CH(CH₃)₂)；

¹³C NMR(100MHz,CD₃OD+DMSO-d₆V/V＝5/1):δ172.3,139.0,135.8,130.7,130.1,127.4,123.5,122.6,121.0,120.4,102.2,99.2,83.9,81.7,32.3,22.8,18.5；

MS(ESI):m/z calcd for[R1-2OTf]²⁺:918.05；found:917.96；elemental analysis:calcd(％)for C₇₂H₇₆N₈O₂₀F₁₂S₄Ru₄:C 40.52,H 3.59,N 5.25；found:C 40.55,H 3.57,N 5.49。

example 2

Preparation of A2 dichloro-bis (4-methylisopropylphenyl) ruthenium (II) (138.7mg,0.30mmol),2, 5-dihydroxy-1, 4-benzoquinone (42.0mg,0.30mmol) and sodium acetate (29.5mg, 0.36mmol) were placed in a 100mL eggplant-shaped flask, 25mL of ethanol were added, nitrogen was replaced by vacuum, and reflux was carried out for 24h with vigorous stirring. When the reaction system is cooled to room temperature, centrifuging (2500r/min) for 10min, discarding the supernatant to obtain a dark red solid, and washing twice with ethanol, acetone and diethyl ether respectively. The solid and silver triflate were dissolved in methanol, stirred at room temperature for 4h to precipitate a white AgCl precipitate, which was then filtered through celite to give a filtrate which was spun to slightly dry, and ether was added to precipitate a dark red solid. Centrifuging (2500r/min) for 10min to obtain the target product, and then drying in vacuum.

The preparation of L1 was the same as in example 1.

Ligand L1(2.1mg,0.01mmol) and metal acceptor A2(9.1mg,0.01mmol) were accurately weighed into a 8mL catalytic vial, dissolved with methanol, stirred at room temperature for 24h, solvent was blown to 0.2mL and diethyl ether was added, centrifuged using a centrifuge (2500R/min) for 10min, the supernatant was discarded, and washed once with diethyl ether to give a metallic rectangular ruthenium-containing supramolecular compound R2.

Performing structural characterization on the metal rectangular ruthenium-containing supramolecular compound R2:

¹H NMR(400MHz,CD₃OD)δ8.46(s,4H,H_2-imidazole),7.68(s,4H,H_5-imidazole),7.62(s,8H,Ph),6.76(s,4H,H_4-imidazole),6.04(d,J＝6.2Hz,8H,Ph_p-cymene),5.83(d,J＝6.2Hz,8H,Ph_p-cymene),5.79(s,4H,H_dobq),2.95–2.78(m,4H,CH),2.23(s,12H,CH₃),1.35(d,J＝6.9Hz,24H,CH(CH₃)₂)；

¹³C NMR(100MHz,CD₃OD)δ185.4,139.9,136.8,131.0,123.7,121.2,104.1,102.6,100.3,85.0,82.3,32.6,22.6,18.4；

MS(ESI):m/z calcd for[R2-2OTf]²⁺:968.57；found:968.95；elemental analysis:calcd(％)for C₈₀H₈₀N₈O₂₀F₁₂S₄Ru₄:C 43.01,H 3.61,N 5.02；found:C 42.77,H 3.60,N 5.14。

example 3

The preparation method of A3 comprises the following steps: dichlorobis (4-methylisopropylphenyl) ruthenium (II) (145.0mg,0.24mmol), naphthazarin (45.6mg,0.23mmol) and sodium acetate (38.4mg,0.47mmol) were taken and added to a 100mL pear-shaped flask, 25mL ethanol was added, and reflux was carried out for 24h with vigorous stirring. And (3) cooling the reaction system to room temperature, centrifuging (2500r/min) for 10min, discarding the supernatant, and washing the solid twice with ethanol, acetone and diethyl ether respectively to obtain a brown solid. Dissolving the solid and silver trifluoromethanesulfonate in methanol, stirring at room temperature for 3h to precipitate white AgCl, then filtering with diatomite to obtain a filtrate, and adding ether to precipitate a green solid. Centrifuging (2500r/min) for 10min to obtain the target product, and then drying in vacuum.

The preparation of L1 was the same as in example 1.

Ligand L1(2.1mg,0.01mmol) and metal acceptor A3(9.6mg,0.01mmol) were weighed into a 8mL catalytic vial, dissolved with methanol, stirred at room temperature for 24h, solvent was blown to 0.2mL and diethyl ether was added, centrifuged using a centrifuge (2500R/min) for 10min, the supernatant was discarded and washed once with diethyl ether to give a metallic rectangular ruthenium-containing supramolecular compound R3.

Performing structural characterization on the metal rectangular ruthenium-containing supramolecular compound R3:

¹H NMR(400MHz,CD₃OD)δ8.39(s,4H,CH_2-imidazole),7.58(s,8H,Ph),7.56(s,4H,H_5-imidazole),7.16(s,8H,H_donq),6.97(s,4H,H_4-imidazole),5.82(d,J＝6.0Hz,8H,Ph_p-cymene),5.60(d,J＝6.1Hz,8H,Ph_p-cymene),2.85–2.74(m,4H,CH),2.11(s,12H,CH₃),1.30(d,J＝6.9Hz,24H,CH(CH₃)₂)；

¹³C NMR(100MHz,CD₃OD)δ172.3,138.6,138.4,136.8,130.7,123.6,121.1,112.7,104.1,101.3,86.0,82.9,32.0,22.5,17.6；

MS(ESI):m/z calcd for[R3-2OTf]²⁺:1018.58；found:1018.93；elemental analysis:calcd(％)for C₈₈H₈₄N₈O₂₀F₁₂S₄Ru₄:C 45.28,H 3.63,N 4.80；found:C 45.16,H 3.68,N 4.80。

example 4

Preparation of L2: 24.6g (105mmol) of 1, 3-m-bromobenzene, 17.5g (205mmol) of imidazole and 36.0g (260mmol) of potassium carbonate were weighed out in a 200mL eggplant-shaped bottle, and 100mL of N, N-dimethylformamide was added thereto, and nitrogen was replaced three times to react at 150 ℃ for 48 hours. Washing the crude product with diatomite and dichloromethane, combining organic phases, then adding water for three times, washing with saturated saline solution for three times, drying with anhydrous sodium sulfate, spin-drying the solvent with a rotary evaporator to obtain a solid, washing with pentane, filtering with a distributed funnel to obtain a yellow solid, and performing column chromatography (developing solvent: ethyl acetate) on the crude product to obtain a white solid, namely the target product.

The preparation of a1 was the same as in example 1.

Ligand L2(2.1mg,0.01mmol) and metal acceptor A1(8.6mg,0.01mmol) were accurately weighed into a 8mL catalytic vial, dissolved with methanol, stirred at room temperature for 24h, solvent was blown to 0.2mL and diethyl ether was added, centrifuged using a centrifuge (2500R/min) for 10min, the supernatant was discarded and washed once with diethyl ether to give a metallic rectangular ruthenium-containing supramolecular compound R4.

Performing structural characterization on the metal rectangular ruthenium-containing supramolecular compound R4:

¹H NMR(400MHz,CD₃OD)δ8.35(s,4H,H_2-imidazole),7.74(s,4H,H_5-imidazole),7.47–7.35(m,8H,Ph),6.64(s,4H,H_4-imidazole),5.98(d,J＝6.2Hz,8H,Ph_p-cymene),5.83(d,J＝6.2Hz,8H,Ph_p-cymene),2.92–2.76(m,4H,CH),2.26(s,12H,CH₃),1.37(d,J＝6.9Hz,24H,CH(CH₃)₂)；

¹³C NMR(100MHz,CD₃OD)δ172.4,139.1,137.7,133.3,130.8,121.2,120.8,112.5,102.7,99.2,83.7,81.9,32.5,22.6,18.2；

MS(ESI):m/z calcd for[R4-2OTf]²⁺:918.05；found:917.96；elemental analysis:calcd(％)for C₇₂H₇₆N₈O₂₀F₁₂S₄Ru₄:C 40.52,H 3.59,N 5.25；found:C 40.53,H 3.50,N 5.19。

example 5

The preparation of a2 was the same as in example 2 and L2 was the same as in example 4.

Ligand L2(2.1mg,0.01mmol) and metal acceptor A2(9.1mg,0.01mmol) were accurately weighed into a 8mL catalytic vial, dissolved with methanol, stirred at room temperature for 24h, solvent was blown to 0.2mL and diethyl ether was added, centrifuged using a centrifuge (2500R/min) for 10min, the supernatant was discarded, and washed once with diethyl ether to give a metallic rectangular ruthenium-containing supramolecular compound R5.

Performing structural characterization on the metal rectangular ruthenium-containing supramolecular compound R5:

¹H NMR(400MHz,CD₃OD)δ8.47(s,4H,H_2-imidazole),7.66(s,4H,H_5-imidazole),7.65–7.61(m,2H,Ph),7.51–7.39(m,6H,Ph),6.75(s,4H,H_4-imidazole),6.04(d,J＝6.2Hz,8H,Ph_p-cymene),5.85(d,J＝6.3Hz,12H,Ph_p-cymene),5.83(s,4H,H_dobq),2.92–2.78(m,4H,CH),2.24(s,12H,CH₃),1.34(d,J＝6.9Hz,24H,CH(CH₃)₂)；

¹³C NMR(100MHz,CD₃OD)δ185.3,140.0,138.1,132.9,131.0,121.7,121.3,114.9,104.1,102.6,100.4,85.0,82.3,32.6,22.6,18.4；

MS(ESI):m/z calcd for[R5-2OTf]²⁺:968.56；found:968.10；elemental analysis:calcd(％)for C₈₀H₈₀N₈O₂₀F₁₂S₄Ru₄:C 43.01,H 3.61,N 5.02；found:C 42.91,H 3.50,N 5.09。

example 6

The preparation of a3 was the same as in example 3 and L2 was the same as in example 4.

Ligand L2(2.1mg,0.01mmol) and metal acceptor A3(9.6mg,0.01mol) were accurately weighed into a 8mL catalytic vial, dissolved with methanol, stirred at room temperature for 24h, solvent was blown to 0.2mL and diethyl ether was added, centrifuged using a centrifuge (2900R/min) for 10min, the supernatant was discarded, and washed once with diethyl ether to give a metallic rectangular ruthenium-containing supramolecular compound R6.

Performing structural characterization on the metal rectangular ruthenium-containing supramolecular compound R6:

¹H NMR(400MHz,CD₃OD)δ8.44(s,4H,H_2-imidazole),7.61(s,2H,Ph),7.56(s,4H,H_5-imidazole),7.53–7.39(m,4H,Ph),7.19(s,8H,H_donq),6.89(s,4H,H_4-imidazole),5.86(d,J＝6.2Hz,8H,Ph_p-cymene),5.62(d,J＝6.2Hz,8H,Ph_p-cymene),2.90–2.74(m,4H,CH),2.13(d,J＝4.6Hz,12H,CH₃),1.40–1.26(m,24H,CH(CH₃)₂)；

¹³C NMR(100MHz,CD₃OD)δ172.3,139.1,138.5,138.4,132.8,130.7,123.4,121.6,121.0,120.2,114.5,112.8,104.0,101.4,86.1(2),82.8,32.1,22.5,17.6；

MS(ESI):m/z calcd for[R4-2OTf]²⁺:1018.59；found:1018.96；elemental analysis:calcd(％)for C₈₈H₈₄N₈O₂₀F₁₂S₄Ru₄:C 45.28,H 3.63,N 4.80；found:C 45.03,H 3.62,N 4.73。

example 7

Preparation of L3M-tribromobenzene 24.6g (105mmol), 17.5g (205mmol) imidazole and 36.0g (260mmol) potassium carbonate were weighed into a 200mL eggplant-shaped bottle, 100mL of N, N-dimethylformamide was added thereto, nitrogen gas was replaced three times, and the mixture was reacted at 150 ℃ for 48 hours. Washing the crude product with diatomite and dichloromethane, combining organic phases, then adding water for three times, washing with saturated saline solution for three times, drying with anhydrous sodium sulfate, spin-drying the solvent with a rotary evaporator to obtain a solid, washing with pentane, filtering with a distributed funnel to obtain a yellow solid, and performing column chromatography (developing solvent: ethyl acetate) on the crude product to obtain a white solid, namely the target product.

The preparation of a1 was the same as in example 1.

Ligand L3(2.8mg,0.010mmol) was accurately weighed into a 8mL catalytic vial with metal acceptor a1(12.9mg,0.015mmol dissolved with DCM/MeOH (v: v ═ 1:1), stirred at room temperature for 24h, solvent was blown to 0.2mL and ether was added, centrifuged using a centrifuge (2900R/min) for 10min, the supernatant discarded and washed once with ether to give the metalprism ruthenium-containing supramolecular compound R7.

Performing structural characterization on the metal triangular prism ruthenium-containing supramolecular compound R7:

¹H NMR(400MHz,CD₃OD:DMSO-d₆v:v＝1:1):δ8.51(s,6H,H_2-imidazole),8.03(s,6H,H_5-imidazole),7.79(s,6H,Ph),6.78(s,6H,H_4-imidazloe),6.1(d,J＝5.7Hz,12H,H_p-cymene),5.92(d,J＝5.9Hz,12H,H_p-cymene),2.99–2.85(m,6H,CH),2.33(s,18H,CH₃),1.44(d,J＝6.9Hz,36H,CH(CH₃)₂)；

¹³C NMR(400MHz,CD₃OD:DMSO-d₆v:v＝1:1):δ＝172.50,139.66,139.06,131.10,123.37,121.37,121.38,120.19,102.84,99.41,83.71,32.45,22.65,18.26；

MS(ESI):m/z calcd for[R7-2OTf]²⁺:1412.53；found:1412.34；elemental analysis:calcd(％)for C₁₀₂H₁₀₈N₁₂O₃₀F₁₈S₆Ru₆:C 39.23,H 3.49,N 5.38；found:C 39.66,H 3.38,N5.33。

example 8

The preparation of a2 was the same as in example 2 and L3 was the same as in example 7.

Ligand L3(2.8mg,0.010mmol) and metal acceptor a2(13.6mg,0.015mmol) were accurately weighed into a 8mL catalytic vial, dissolved with DCM/MeOH (v/v ═ 1:1), stirred at room temperature for 24h, the solvent was blown to 0.2mL and diethyl ether was added, centrifuged using a centrifuge (2900R/min) for 10min, the supernatant was discarded and washed once with diethyl ether to give the ruthenium-containing supramolecular compound R8.

Performing structural characterization on the metal triangular prism ruthenium-containing supramolecular compound R8:

¹H NMR(400MHz,CD₃OD):δ8.86(s,6H,H_2-imidazole),7.89(s,6H,H_5-imidazole),7.81(s,6H,Ph),6.74(s,6H,H_4-imidazole),6.08(d,J＝6.2Hz,12H,H_p-cymene),5.85(d,J＝6.2Hz,12H,H_p-cymene),5.9(s,6H,H_dobq),2.94–2.82(m,6H,CH),2.25(s,18H,CH₃),1.36(d,J＝6.9Hz,36H,CH(CH₃)₂)；

¹³C NMR(100MHz,CD₃OD):δ＝185.3,140.0,139.1,130.7,121.2,120.1,111.8,104.2,102.7,100.8,85.0,82.1,32.6,22.6,18.4；

MS(ESI):m/z calcd for[R8-2OTf]²⁺:1487.55；found:1488.13；elemental analysis:calcd(％)for C₁₁₄H₁₁₄N₁₂O₃₀F₁₈S₆Ru₆:C 41.83,H 3.51,N 5.14；found:C 41.31,H 3.47,N4.93。

example 9

The preparation of a3 was the same as in example 3 and L3 was the same as in example 7.

Ligand L3(2.8mg,0.010mmol) and metal acceptor A3(14.4mg,0.015mmol) were accurately weighed into a 8mL catalytic vial, dissolved using DCM/CD3OD (v/v ═ 1:1), stirred at room temperature for 24h, solvent was blown to 0.2mL, ether was added, centrifuged using a centrifuge (2900R/min) for 10min, the supernatant was discarded, and washed once with ether to give the ruthenium-containing supramolecular compound R9.

Performing structural characterization on the metal triangular prism ruthenium-containing supramolecular compound R9:

¹H NMR(400MHz,CD₃OD):δ8.74(s,6H,H_2-imidazole),7.76(s,6H,H_5-imidazole),7.74(s,6H,Ph),7.25(s,12H,H_donq),6.90(s,6H,H_4-imidazole),5.89(d,J＝5.9Hz,12H,H_p-cymene),5.67(d,J＝5.9Hz,12H,H_p-cymene),2.87–2.76(m,6H,CH),2.14(s,18H,CH₃),1.32(d,J＝6.9Hz,36H,CH(CH₃)₂)；

¹³C NMR(100MHz,CD₃OD):δ＝170.7,137.8,137.7,137.1,128.8,121.9,119.3,118.8,111.2,109.7,102.5,100.5,85.0,81.1,30.7,21.2,16.3；

MS(ESI):m/z calcd for[R7-2OTf]²⁺:1562.58；found:1562.28；elemental analysis:calcd(％)for C₁₂₆H₁₂₀N₁₂O₃₀F₁₈S₆Ru₆:C 44.21,H 3.53,N 4.91；found:C 44.71,H 3.59,N4.73。

example 10

Preparation of L4 9.8g (42mmol) of 1, 3-m-bromobenzene, 12.1g (102mmol) of benzimidazole and 14.3g (104mmol) of potassium carbonate were weighed out in a 200mL eggplant-shaped bottle, 100mL of DMSO was added thereto, nitrogen gas was replaced three times, and the mixture was reacted at 150 ℃ for 48 hours. The crude product was passed through celite, washed with dichloromethane and then extracted with dichloromethane/water, the organic phases were combined, dried over anhydrous sodium sulphate, washed with pentane after drying of the solvent and filtered to give a yellow solid, and the crude product was subjected to column chromatography (EA) to give a white solid.

The preparation of a1 was the same as in example 1.

Ligand L4(3.1mg,0.01mmol) and metal acceptor A1(8.6mg,0.01mmol) were weighed into a 8mL catalytic vial, dissolved with methanol, stirred at room temperature for 24h, solvent was blown to 0.2mL and diethyl ether was added, centrifuged using a centrifuge (2900R/min) for 10min, the supernatant was discarded and washed once with diethyl ether to give a metallic rectangular ruthenium-containing supramolecular compound R10.

Performing structural characterization on the metal rectangular ruthenium-containing supramolecular compound R10:

¹H NMR(400MHz,CD₃OD):δ＝8.59(s,4H,H_2-imidazole),7.72(d,J＝8.2Hz,4H,H_7-imidazole),7.64–7.58(m,2H,Ph),7.54(d,J＝8.5Hz,4H,H_4-imidazole),7.37(t,J＝7.8Hz,6H,Ph),7.32(d,J＝8.3Hz,4H,H_5-imidazole),7.12(t,J＝7.7Hz,4H,H_6-imidazole),6.11(d,J＝5.5Hz,4H,Ph_p-cymene),5.98(d,J＝5.6Hz,4H,Ph_p-cymene),5.92(d,J＝5.7Hz,4H,Ph_p-cymene),5.88(d,J＝5.5Hz,4H,Ph_p-cymene),2.99–2.82(m,4H,CH),2.13(s,12H,CH₃),1.40(dd,J＝30.9,6.7Hz,24H,CH(CH₃)₂)；

¹³C NMR(100MHz,CD₃OD):δ＝185.3,140.0,139.1,130.6,123.3,121.2,111.8,104.2,102.7,100.7,85.0,82.1,32.6,22.6,18.4；

MS(ESI):m/z calcd for[R10-2OTf]²⁺:1018.58；found:1018.49；elemental analysis:calcd(％)for C₈₈H₈₄N₈O₂₀F₁₂S₄Ru₄:C 45.28,H 3.63,N 4.80；found:C 44.53,H 3.60,N 4.93。

example 11

The preparation of a2 was the same as in example 2 and L4 was the same as in example 10.

Ligand L4(3.1mg,0.01mmol) and metal acceptor A2(9.1mg,0.01mmol) were accurately weighed into a 8mL catalytic vial, dissolved with methanol, stirred at room temperature for 24h, the solvent was blown to about 0.2mL and diethyl ether was added, centrifuged using a centrifuge (2900R/min) for 10min, the supernatant was discarded, and washed once with diethyl ether to give a metallic rectangular ruthenium-containing supramolecular compound R11.

Performing structural characterization on the metal rectangular ruthenium-containing supramolecular compound R11:

¹H NMR(400MHz,CD₃OD):δ＝8.75(s,4H,H_2-imidazole),7.90–7.79(m,4H,H_7-imidazole),7.77–7.70(s,2H,Ph),7.61(d,J＝8.3Hz,4H,H_4-imidazole),7.58–7.45(m,6H,Ph),7.33(t,J＝7.8Hz,4H,H_5-imidazole),7.04(s,4H,H_6-imidazole),6.14(d,J＝6.4Hz,8H,Ph_p-cymene),5.91(d,J＝6.2Hz,8H,Ph_p-cymene),5.71(s,4H,H_dobq),2.96–2.82(m,4H,CH),2.13(s,12H,CH₃),1.34(d,J＝6.9Hz,24H,CH(CH₃)₂)；

¹³C NMR(100MHz,CD₃OD):δ＝185.1,146.3,141.3,137.3,133.3,126.9,126.4,125.5,123.4,120.2,119.5,113.1,105.6,102.3,100.4,84.5,82.3,32.7,22.6,18.6；

MS(ESI):m/z calcd for[R11-2OTf]²⁺:1068.63；found:1068.48；elemental analysis:calcd(％)for C₉₆H₈₈N₈O₂₀F₁₂S₄Ru₄:C 47.37,H 3.64,N 4.60；found:C 47.00,H 3.59,N 4.64。

example 12

The preparation of a3 was the same as in example 3 and L4 was the same as in example 10.

Ligand L4(3.1mg,0.01mmol) and metal acceptor A3(9.9mg,0.01mmol) were accurately weighed into a 8mL catalytic vial, dissolved with methanol, stirred at room temperature for 24h, the solvent was blown to about 0.2mL and diethyl ether was added, centrifuged using a centrifuge (2900R/min) for 10min, the supernatant was discarded, and washed once with diethyl ether to give a metallic rectangular ruthenium-containing supramolecular compound R12.

Performing structural characterization on the metal rectangular ruthenium-containing supramolecular compound R12:

¹H NMR(400MHz,CD₃OD):δ＝8.66(s,4H,H_2-imidazole),7.86(t,J＝8.1Hz,2H,Ph),7.80(d,J＝8.3Hz,4H,H_7-imidazole),7.64(s,2H,Ph),7.40(d,J＝8.4Hz,4H,H_4-imidazole),7.37–7.28(m,4H,Ph),7.25(t,J＝7.8Hz,4H,H_{5-benzimidazole}),7.13(s,8H,H_donq),6.69(s,4H,H_6-imidazole),5.93(d,J＝6.0Hz,8H,Ph_p-cymene),5.67(d,J＝6.0Hz,8H,Ph_p-cymene),2.91–2.80(m,4H,CH),2.01(s,12H,CH₃),1.29(d,J＝6.9Hz,24H,CH(CH₃)₂)；

¹³C NMR(100MHz,CD₃OD):δ＝172.0,145.0,141.8,138.3,137.4,133.6,132.9,126.4,126.1,124.9,119.6,118.2,113.0,112.6,105.1,101.3,85.6,83.1,32.1,22.6,18.0；

MS(ESI):m/z calcd for[R12-2OTf]²⁺:1118.62；found:1118.49；elemental analysis:calcd(％)for C₁₀₄H₉₂N₈O₂₀F₁₂S₄Ru₄:C 49.29,H 3.66,N 4.42；found:C 49.01,H4.40,N 4.28。

example 13

Preparation of L5: catechol (4.4g,40mmol) was weighed out, 50mL of N, N-dimethylformamide was added and stirred to dissolve, anhydrous potassium carbonate (23.2g,168mmol) was slowly added, 9.4mL, 12.1g,88mmol, ρ ═ 1.28g/mL (25 ℃) N-bromo-butane was added after stirring for 30min to undergo nucleophilic substitution reaction at 90 ℃ for 18h, extraction was performed with water/ethyl acetate, the organic phases were combined, washed three times with aqueous NaOH solution and then three times with saturated brine, dried over anhydrous sodium sulfate, and the solvent was dried by rotary evaporator to give 1, 2-dibutoxybenzene. 1, 2-dibutoxybenzene (4.0g, 18.0mmol) was dissolved in 40mL of acetic acid, stirred under ice bath to cool the reaction system to 0 ℃ and 3.5mL of nitric acid and 30mL of fuming nitric acid were measured, and after mixing uniformly, the mixture was slowly dropped into the system by a constant pressure dropping funnel, and the reaction solution was always kept at about 0 ℃. After the dropwise addition, removing the ice bath, returning the reaction temperature to room temperature, stirring for 4 hours to carry out nitration reaction, pouring into an ice-water mixture after the reaction is finished, separating out yellow solid, carrying out suction filtration after ice blocks are melted, and washing with a large amount of water. Collecting solid, adding 80mL of absolute ethyl alcohol, refluxing for 0.5h, slowly cooling after yellow solid is completely dissolved, separating out yellow crystals, performing suction filtration again, collecting solid, weighing nitration product (4.0g,12.8mmol) and Pd/C catalyst (90mg) in a 100mL eggplant-shaped bottle, and adding 40mL of absolute ethyl alcohol for dissolving. Vacuumizing and ventilating for 3 times, quickly adding 6.3mL of hydrazine hydrate into a reaction system, reacting at 80 ℃ overnight to generate a reduction reaction, cooling the reaction system to room temperature, quickly passing through diatomite to remove solid byproducts generated in the reaction, suspending a solvent by using a rotary evaporator to obtain a yellow solid, adding 50mL of formic acid, vacuumizing and ventilating, refluxing, performing cyclization and imidazole reaction overnight, then performing reduced pressure distillation to remove most of the formic acid, using ammonia water, adjusting the reaction pH value to be neutral by using a saturated sodium carbonate solution, extracting by using ethyl acetate, combining organic phases, washing for three times by using saturated saline, suspending the solvent by using the rotary evaporator, adding ether to wash, and filtering by using a funnel cloth to obtain the 5, 6-dibutoxybenzimidazole. P-bromobenzene (11.8g,50.4mmol), 5, 6-dibutoxybenzimidazole (32.1g,122.4mmol), potassium carbonate (17.2g,124.8mmol) and copper oxide (0.5g,6.0mmol) were weighed into a 200mL eggplant-shaped bottle, 60mL of N, N-dimethylformamide was added thereto, nitrogen gas was replaced three times, and Ullmann reaction was carried out at 150 ℃ for 48 hours. And (3) passing the crude product through diatomite, washing with dichloromethane, combining organic phases, then adding water for washing for three times, washing with saturated saline solution for three times, drying with anhydrous sodium sulfate, spin-drying the solvent with a rotary evaporator to obtain a solid, washing with pentane, filtering with a distributed funnel to obtain a white solid, and performing column chromatography (ethyl acetate) on the crude product to obtain the white solid, namely the target product.

Characterization of L5 from example 13 is shown in FIG. 1¹HNMR spectrogram, FIG. 2 is¹³As can be seen from FIGS. 1 to 2, the obtained L5 has the structure shown in the figure.

The preparation of a1 was the same as in example 1.

Ligand L5(6.0mg,0.01mmol) and metal acceptor A1(8.6mg,0.01mmol) were accurately weighed into a 8mL catalytic vial, dissolved with methanol, stirred at room temperature for 24h, solvent was blown to 0.2mL and diethyl ether was added, centrifuged using a centrifuge (2900R/min) for 10min, the supernatant was discarded and washed once with diethyl ether to give a metallic rectangular ruthenium-containing supramolecular compound R13.

Performing structural characterization on the metal rectangular ruthenium-containing supramolecular compound R13:

¹H NMR(400MHz,CD₃OD)major conformational isomer:δ＝8.32(s,4H,H_2-imidazole),7.56(s,8H,Ph),6.99(s,4H,H_7-imidazole),6.71(s,4H,H_4-imidazole),5.98–5.91(m,8H,Ph_p-cymene),5.78–5.72(m,8H,Ph_p-cymene),4.24–4.10(m,8H,H_1-butyl),3.98(t,J＝6.3Hz,8H,H_1-butyl),2.92–2.82(m,4H,CH),2.20(s,12H,CH₃),1.99–1.85(m,16H,H_2-butyl),1.73–1.59(m,16H,H_3-butyl),1.41(d,J＝6.9Hz,12H,CH(CH₃)₂),1.36(d,J＝6.9Hz,12H,CH(CH₃)₂),1.12(t,J＝7.4Hz,12H,CH₂CH₃),1.06(t,J＝7.4Hz,12H,CH₂CH₃)；

¹³C NMR(100MHz,CD₃OD):δ＝173.2,171.9,151.3,149.9,143.1,135.4,135.3,126.9,126.2,103.6,102.4,98.7,95.5,83.2,82.9,82.4,82.0,70.8,70.5,32.8,32.7(2),22.8,22.5,20.6,20.5,18.4,14.5(2)；

MS(ESI):m/z calcd for[R13-2OTf]²⁺:1306.81；found:1306.62；elemental analysis:calcd(％)for C₁₂₀H₁₄₈N₈O₂₈F₁₂S₄Ru₄:C 49.51,H 5.12,N 3.85；found:C 49.22,H 5.13,N 3.75。

example 14

The preparation of a2 was the same as in example 2 and L5 was the same as in example 13.

Ligand L5(6.0mg,0.01mmol) and metal acceptor A2(9.1mg,0.01mmol) were accurately weighed into a 8mL catalytic vial, dissolved with methanol, stirred at room temperature for 24h, solvent was blown to 0.2mL and diethyl ether was added, centrifuged using a centrifuge (2900R/min) for 10min, the supernatant was discarded and washed once with diethyl ether to give a metallic rectangular ruthenium-containing supramolecular compound R14.

Performing structural characterization on the metal rectangular ruthenium-containing supramolecular compound R14:

¹H NMR(400MHz,CD₃OD)major conformational isomer:δ＝8.36(s,4H,H_2-imidazole),7.72(s,8H,Ph),7.07(s,4H,H_7-imidazole),7.00(s,8H,H_4-imidazole),6.14–6.06(m,8H,Ph_p-cymene),5.85(m,8H,Ph_p-cymene),5.62(s,4H,H_dobq),4.04–3.97(m,8H,H_1-butyl),3.96–3.88(m,8H,H_1-butyl),3.01–2.85(m,4H,CH),2.15(s,12H,CH₃),1.84–1.70(m,16H,H_2-butyl),1.60–1.45(m,16H,H_3-butyl),1.36(d,J＝6.9Hz,24H,CH(CH₃)₂),0.98(t,24H,J＝6.1Hz,CH₂CH₃)；

¹³C NMR(100MHz,CD₃CN):δ＝185.2,150.3,149.4,143.3,135.7,135.3,127.4,127.3,123.7,120.5,104.8,103.1,102.1,101.7,99.4,96.4,83.9,82.6,82.3,70.1,32.4,31.9,22.7,22.4,20.0(2),18.7,14.7；

MS(ESI):m/z calcd for[R14-2OTf]²⁺:1356.83；found:1356.66；elemental analysis:calcd(％)for C₁₂₈H₁₅₂N₈O₂₈F₁₂S₄Ru₄:C 51.06,H 5.09,N 3.72；found:C 50.98,H 5.11,N 3.75。

example 15

The preparation of a3 was the same as in example 3 and L5 was the same as in example 13.

Ligand L5(6.0mg,0.01mmol) and metal acceptor A3(9.9mg,0.01mmol) were accurately weighed into a 8mL catalytic vial, dissolved with methanol, stirred at room temperature for 24h, the solvent was blown to about 0.2mL and diethyl ether was added, centrifuged using a centrifuge (2900R/min) for 10min, the supernatant was discarded, and washed once with diethyl ether to give a metallic rectangular ruthenium-containing supramolecular compound R15.

Performing structural characterization on the metal rectangular ruthenium-containing supramolecular compound R15:

¹H NMR(400MHz,CD₃CN)major conformational isomer:δ＝8.05(s,4H,H_2-imidazole),7.63(s,8H,Ph),7.20(s,4H,H_7-imidazole),7.08(s,8H,H_dobq),6.86(s,4H,H_4-imidazole),5.79–5.70(m,8H,Ph_p-cymene),5.56(d,J＝6.1Hz,8H,Ph_p-cymene),4.15–4.04(m,8H,H_1-butyl),3.96–3.86(m,8H,H_1-butyl),2.93–2.80(m,4H,CH),2.08(s,12H,CH₃),1.86–1.75(m,8H,H_2-butyl),1.74–1.61(m,8H,H_2-butyl),1.57–1.50(m,8H,H_3-butyl),1.48–1.36(m,8H,H_3-butyl),1.31(d,J＝7.1Hz,24H,CH(CH₃)₂),1.10(t,J＝7.0Hz,12H,CH₂CH₃),1.00(t,J＝7.4Hz,12H,CH₂CH₃)；

¹³C NMR(100MHz,CD₃CN):δ＝172.5,170.6,149.9,149.2,142.7,138.3,138.1,135.7,135.3,127.6,127.1,123.7,120.5,112.4,104.5,101.9,100.4,96.2,84.9,83.6,83.3,70.0,32.0,31.9,31.7,22.7,22.3,20.0,17.8,14.2(2)；

MS(ESI):m/z calcd for[R13-2OTf]²⁺:1406.86；found:1406.64.elemental analysis:calcd(％)for C₁₃₆H₁₅₆N₈O₂₈F₁₂Ru₄S₄:C 52.50,H 5.05N 3.60；found:C 52.43,H 5.10,N 3.50。

example 16

The preparation of L6 is similar to that of L5 in example 13, except that n-bromo-n-octane is used instead of n-bromo-n-butane.

Characterization of the L6 obtained in the examples, FIG. 3¹HNMR spectrogram, FIG. 4 is¹³The C NMR spectrum of the product is shown in FIGS. 3-4, and the obtained L6 has the structure shown in the specification.

The preparation of a1 was the same as in example 1.

Ligand L6(8.2mg,0.01mmol) and metal acceptor A1(8.6mg,0.01mmol) were accurately weighed into a 8mL catalytic vial, dissolved with methanol, stirred at room temperature for 24h, solvent was blown to 0.2mL and diethyl ether was added, centrifuged using a centrifuge (2900R/min) for 10min, the supernatant was discarded and washed once with diethyl ether to give a metallic rectangular ruthenium-containing supramolecular compound R16.

Characterization of the metallic rectangular ruthenium-containing supramolecular compound R16:

¹H NMR(400MHz,CD₃OD):δ＝8.31(s,4H,H_2-imidazole),7.55(s,8H,Ph),6.98(s,4H,H_7-imidazole),6.70(s,4H,H_4-imidazole),5.97–5.89(m,8H,Ph_p-cymene),5.74(d,J＝6.3Hz,8H,Ph_p-cymene),4.02–3.83(m,16H,H_1-nonyl),2.92–2.80(m,4H,CH),2.19(s,12H,CH₃),1.99–1.85(m,16H,H_2-nonyl),1.74–1.56(m,16H,H_3-nonyl),1.50–1.32(m,88H,H_{4,5,6,7-nonyl},CH(CH₃)₂),1.01–0.91(m,24H,CH₂CH₃)；

¹³C NMR(100MHz,CD₃OD):δ＝151.4,149.9,143.0,135.4,135.3,126.9,126.2,103.7,102.5,98.7,95.5,83.2,82.9,82.4,82.0,71.1,70.8,33.3,33.2,32.7,31.0(2),30.9,30.8,30.7,27.6,27.5,23.9(2),22.8,22.5,18.4,14.6(2)；

MS(ESI):m/z calcd for[R17-2OTf]²⁺:1531.06；found:1530.81；elemental analysis:calcd(％)for C₁₅₂H₂₁₂N₈O₂₈F₁₂Ru₄S₄:C 54.34,H 6.36,N 3.34；found:C 54.04,H 6.34,N 3.26。

example 17

The preparation of a2 was the same as in example 2 and L6 was the same as in example 16.

Ligand L6(8.2mg,0.01mmol) and metal acceptor A2(9.1mg,0.01mmol) were accurately weighed into a 8mL catalytic vial, dissolved with methanol, stirred at room temperature for 24h, solvent was blown to 0.2mL and diethyl ether was added, centrifuged using a centrifuge (2900R/min) for 10min, the supernatant was discarded and washed once with diethyl ether to give a metallic rectangular ruthenium-containing supramolecular compound R17.

Performing structural characterization on the metal rectangular ruthenium-containing supramolecular compound R17:

¹H NMR(400MHz,CD₃OD)major conformational isomer:δ＝8.37(s 4H,H_2-imidazole),7.79(s,8H,Ph),7.04(s,4H,H_7-imidazole),6.94(s,4H,H_4-imidazole),6.10(s,8H,Ph_phenyl),5.87(d,J＝8.0Hz,8H,Ph_p-cymene),5.60(s,4H,H_dobq),4.16–4.03(m,8H,H_1-nonyl),4.03–3.96(m,8H,H_1-nonyl),3.00–2.86(m,4H,CH),2.16(s,12H,CH₃),1.91–1.81(m,8H,H_2-nonyl),1.81–1.73(m,8H,H_2-nonyl),1.62–1.53(m,8H,H_3-nonyl),1.53–1.46(m,8H,H_3-nonyl),1.44–1.20(m,88H,H_{4,5,6,7,8-nonyl,}CH(CH₃)₂),0.97–0.81(m,24H,CH₂CH₃)；

¹³C NMR(100MHz,CD₃CN):δ＝185.2,184.7,150.3,149.4,143.1,135.6,135.2,127.5,125.8,104.7,103.0,102.1,101.7,99.4,96.4,84.1,83.9,82.7,82.2,70.2,66.3,32.7,32.4,30.3,30.2,30.1,29.9,26.9(2),26.8,23.5,22.7,22.4,18.7,14.5；

MS(ESI):m/z calcd for[R16-2OTf]²⁺:1581.08；found:1581.84；elemental analysis:calcd(％)for C₁₆₀H₂₁₆N₈O₂₈F₁₂S₄Ru₄:C 55.45,H 6.29,N 3.24；found:C 54.94,H 6.24,N 3.20。

application example

MTT experiments are carried out on the ruthenium-containing supramolecular compounds R1-17 prepared in the embodiment of the invention, unassembled ligands and acceptors to verify whether the compounds have anticancer activity. Frozen cancer cells HCT-116 (human colon cancer cells) and A549 (human lung cancer cells) are taken and placed in a water bath kettle, and then are recovered at 37 ℃. HCT-116 cells were cultured in DMEM medium, and A549 cells were cultured in F-12K medium. All media used were supplemented with 10% heat-extinguished Fetal Bovine Serum (FBS) and 1% penicillin-streptomycin solution. Cancer cells cultured at 37 deg.C and containing CO₂5% cell culture box. The growth of the cells was observed daily using a microscope and the experiment was started after passage 3 for both cancer cells.

Ruthenium-containing supramolecular compounds R1-17 and contrast drugs adriamycin and cisplatin are respectively dissolved in DMSO to prepare 5 mg/mL^-1The stock solution was stored in a freezer at-20 ℃ for further use. The cancer cell suspension was transferred to a 96-well plate using a pipette, and the number of cells per well was controlled to 0.5X 10⁴～1.0×10⁴In each well plate, the plate was pre-incubated in an incubator for 12/24h, the drug stock was added to the medium and diluted in a gradient, and then the drug-containing medium (DMSO concentration in the medium) was used<0.5%) was substituted for the original culture medium in the well plate, and the reaction time of the cells with the drug was 48 hours.

After the reaction was completed, MTT was added to Phosphate Buffer (PBS) at pH 7.2 and filtered through a 0.22M microporous filter (care should be taken to avoid light during preparation). 20L of MTT solution was added to each well and incubated in an incubator for 4 hours. After the reaction, the solution in the well plate was removed, 100L DMSO was added to each well, the well plate was placed on a shaker and shaken for 30min, and then absorbance (λ. about.492 nm) was measured using a microplate reader, and the percentage of viable cells was calculated from the ratio of the absorbance of the cells after the drug action to that of the negative control group. Finally, IC was determined by fitting a linear regression function to the log percent viable cells versus drug concentration₅₀The results are shown in table 1, and the ruthenium-containing supramolecular compounds R3, R6, R9 and R12 were somewhat more effective.

TABLE 1 IC₅₀Test results

Survival rate ═ 100% (control a value-treatment well a value)/(control a value-blank a value) × (control a value-treatment well a value) × (control a value-blank a value)

Inhibition rate (1-survival rate) × 100%

lgIC₅₀＝Xm-I(P-(3-Pm-Pn)/4)

Xm is lg maximum dose;

lg (maximum dose/adjacent dose);

p: sum of positive reaction rates;

pm: the maximum positive reaction rate;

pn: minimal positive reaction rate.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims

1. A benzimidazole ligand, characterized by the structural formula (i):

wherein R is n-C₄H₉O or n-C₈H₁₇O。

2. The method of synthesizing a benzimidazole ligand according to claim 1, comprising the steps of:

(4) and (4) mixing the benzimidazole derivative obtained in the step (3), bromobenzene, potassium carbonate, copper oxide and N, N-dimethylformamide to perform Ullmann reaction to obtain a benzimidazole ligand.

3. The ruthenium-containing supramolecular compound is characterized in that the structural formula is shown as the following formula (II),

wherein A is a compound having a structure represented by the following formula A1, A2 or A3,

l is a compound of the formula (I) as defined in claim 1.

4. A process for the preparation of ruthenium-containing supramolecular compounds as claimed in claim 3, characterized in that it comprises the steps of: and mixing the compound A, the compound L and a polar organic solvent to perform coordination-driven self-assembly reaction to obtain the ruthenium-containing supramolecular compound.

5. The method according to claim 4, wherein the polar organic solvent is dichloromethane and/or methanol.

6. The preparation method according to claim 4, wherein the time for the coordination-driven self-assembly reaction is 24-48 h.

7. The method of claim 4, wherein the coordination-driven self-assembly reaction post-treatment process comprises: removing the polar organic solvent in the coordination-driven self-assembly reaction product, and adding diethyl ether for centrifugal treatment.

8. The method according to claim 7, wherein the rotation speed of the centrifugation is 2900rpm, and the time of the centrifugation is 10 min.

9. Use of the ruthenium-containing supramolecular compounds as claimed in claim 3 for the preparation of anticancer drugs.