A water-soluble supramolecular cup capsule based on molecular cup assembly, preparation method and application thereof

Abstract

The present invention relates to a water-soluble supramolecular cup capsule based on molecular cup assembly, a preparation method thereof and an application thereof. The water-soluble supramolecular cup capsule of the present invention has a structure in which a water-soluble 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1 has a functionalized deep-hole type resorcinol cup [4] aromatic hydrocarbon assembly unit H1. The present invention is based on water-soluble functionalized 2-hydroxybenzimidazole resorcinol cup [4] aromatic hydrocarbon, and utilizes the hydrophobic effect and the synergistic effect of dipolar non-covalent bonds to form a molecular capsule by dimerization self-assembly, which can be used to encapsulate amphiphilic or water-soluble amine guest molecules. The present invention develops a new method for simply and efficiently constructing water-soluble supramolecular capsules, and successfully applies it to the selective encapsulation of amine compounds, which provides a new idea for the construction of supramolecular capsules and is of great significance to the study of the behavior of small molecules in confined spaces.

Description

Technical Field

[0001] The present invention belongs to the field of supramolecular capsule design, construction and molecular recognition research in supramolecular chemistry, and relates to a water-soluble supramolecular capsule based on a functionalized resorcinol calix [4] aromatic molecular calix, a preparation method thereof and an application thereof. Background Art

[0002] Supramolecular capsules are formed by two or more molecules connected together by non-covalent reversible interactions between molecules and have a special closed cavity. Supramolecular capsules have potential application value in the fields of controlled drug release, catalysis, material science and biomedicine due to their unique spatial structure and molecular recognition properties. In particular, supramolecular capsules play an irreplaceable role in studying the special physical and chemical behaviors of guest molecules in confined spaces.

[0003] Self-assembly of modules containing cavities and pre-organized bonding sites is an effective method for constructing supramolecular capsules. In this regard, molecules of the calixarene family are the most widely used. Among them, resorcinol calix[4]arene, as an important subclass of the main molecule in calixarene, is a cyclic oligomer formed by bridging the resorcinol monomer with the methylene group through the ortho position of the phenolic hydroxyl group. It is shaped like a cup and has a cavity that can enclose guest molecules; and the size of the cavity can be adjusted by deepening the aromatic wall. Based on the efficient synthesis of the resorcinol calix[4]arene skeleton, chemists have developed efficient derivatization reactions on the calixarene skeleton, which can introduce functional bonding sites as needed. Studies have shown that the molecular cup body can dimerize and self-assemble to form supramolecular capsules through non-covalent bonding of the upper functional group, such as hydrogen bonding, halogen bonding, coordination, etc. In view of this, resorcinol calix[4]arene has become a good choice for constructing supramolecular capsules.

[0004] Since most of the life processes of organisms are carried out in water, the construction of water-soluble supramolecular capsules is very important for enzyme mimetic chemistry. Water-soluble supramolecular host molecules constructed by hydrogen bonds, metal coordination bonds and hydrophobic weak interactions have been widely reported, however, supramolecular capsules constructed by ion-dipole interactions are rarely reported. Summary of the invention

[0005] In order to solve the existing technical problems of supramolecular capsule construction, the purpose of the present invention is to overcome the shortcomings of the existing technology and provide a water-soluble supramolecular cup capsule based on molecular cup assembly, its preparation method and application. The water-soluble supramolecular cup capsule of the present invention is a water-soluble resorcinol calix [4] arene supramolecular capsule H1-H1 constructed by self-assembly based on non-covalent bond synergy, and is also a water-soluble functionalized 2-hydroxybenzimidazole resorcinol calix [4] arene. The present invention is based on water-soluble functionalized 2-hydroxybenzimidazole resorcinol calix [4] arene, and utilizes hydrophobic effect and dipole non-covalent bond synergy to form molecular capsules through dimerization self-assembly, which can be used to encapsulate amphiphilic or water-soluble amine guest molecules. The invention develops a new method for simply and efficiently constructing water-soluble supramolecular capsules, and successfully applies it to the selective encapsulation of amine compounds, which provides a new idea for the construction of supramolecular capsules and is of great significance to the study of small molecule behavior in confined space.

[0006] In order to achieve the above object, the present invention adopts the following inventive concept:

[0007] The present invention uses a water-soluble deep-hole type resorcinol calix [4] aromatic hydrocarbon molecular calix macrocyclic body - 2-hydroxymethyl imidazolyl molecular calix body H1 as an assembly unit. This type of molecular calix body has an electron-rich deep hole hydrophobic cavity and a functional group modified with 2-hydroxymethyl benzimidazole on the upper edge, and exhibits good recognition performance for water-soluble molecules and large polar molecules. The present invention uses resorcinol calix [4] aromatic hydrocarbon as a skeleton, and successively deepens the aromatic wall, introduces 2-hydroxymethyl imidazolyl on the upper edge and water-soluble groups on the lower edge, thereby realizing the synthesis of functionalized water-soluble 2-hydroxymethyl benzimidazole molecular calix body H1. On this basis, the hydrophobic effect and the synergistic effect of dipole non-covalent bonds are used to carry out dimerization self-assembly to construct a water-soluble supramolecular capsule H1-H1. The hydrophobic cavity of the supramolecular capsule can combine with the alkyl chain of the guest molecule through hydrophobic interaction, and the four hydroxymethyl groups on the upper edge of the 2-hydroxymethylbenzimidazole molecular cup can undergo dipole interaction with the positively charged part of the guest center. The two synergistically promote the formation of the molecular capsule, thereby achieving selective inclusion of polar and water-soluble amine guest molecules.

[0008] According to the above inventive concept, the present invention adopts the following technical solution:

[0009] A water-soluble supramolecular cup capsule based on molecular cup assembly is a water-soluble 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1 based on deep-cavity water-soluble resorcinol calix[4]arene, and its structural formula is as follows:

[0010]

[0011] Preferably, the water-soluble supramolecular cup capsule of the present invention based on molecular cup assembly has two types of conformations of the molecular cup main body H1 as its constituent unit in water: when there is a guest, the 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1 has C 4v Symmetrical "vase" conformation; in the absence of an object, it adopts C 2v Symmetrical "kite" conformation and "kite dimer" conformation, and there is a dynamic balance between the two; water-soluble 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1 can be constructed by utilizing hydrophobic and dipole interactions.

[0012] Further preferably, the water-soluble supramolecular cup capsule based on molecular cup assembly of the present invention adopts a main compound H1 based on a deep-hole type water-soluble resorcinol cup [4] aromatic molecular cup-2-hydroxymethylimidazolyl molecular cup, wherein the main compound H1 has an electron-rich deep-hole hydrophobic cavity and a hydroxyl functional group modified at the upper edge; wherein the hydrophobic cavity is constructed by a bridging benzimidazole group, and the "wall" surrounded by benzene rings on all four sides provides a site for the occurrence of hydrophobic interaction; the hydroxymethyl functional group at the upper edge can be polarized to provide a dipole effect between the host and the guest, and the sodium carboxylate salt at the lower edge gives the main body solubility in aqueous solution; the hydrophobic effect is used to stabilize the vase conformation of the molecular cup, and the dipole effect is used to induce the two molecular cups in the vase conformation to approach each other to form a 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1.

[0013] A method for preparing a water-soluble supramolecular cup capsule based on molecular cup assembly according to the present invention comprises the following steps: the hydrophobic cavity of the supramolecular capsule can be combined with the alkyl chain of the guest molecule through hydrophobic interaction, and the four hydroxymethyl groups on the upper edge of the 2-hydroxymethylimidazolyl molecular cup can have a dipole interaction with the positive charge part of the guest center, and the two can synergistically promote the formation of the molecular capsule, thereby achieving selective inclusion of polar and water-soluble amine guest molecules, and preparing the 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1.

[0014] Preferably, the method for preparing the water-soluble supramolecular calix capsule based on molecular calix assembly of the present invention comprises the following steps:

[0015] ⅰ. Using 0.01mmol molecular cup H1 as raw material, add at least 10mL of heavy water, ultrasonicate for at least 10 minutes until completely dissolved, and obtain the main solution for standby use;

[0016] ⅱ. 50 mmol of a polar or water-soluble guest is used as a raw material, to which at least 1 mL of heavy water is added, and ultrasonic treatment is performed for at least 10 minutes until the guest solution is completely dissolved, and the guest solution is set aside;

[0017] iii. In step i, 500 μL of the main solution is measured, and in step ii, at least 5 μL of the guest solution is measured. The main solution or the guest solution is mixed and ultrasonicated for at least 10 minutes until the mixture is uniformly mixed, thereby preparing 2-hydroxymethylbenzimidazole supramolecular capsules H1-H1.

[0018] Preferably, in step i, the preparation method of the deep-hole type water-soluble resorcinol calix[4]arene supramolecular capsule H1-H1 constituting the elementary molecular calix H1 is as follows:

[0019] Using resorcinol calix[4]arene as the skeleton, the synthesis of functionalized water-soluble 2-hydroxymethylimidazolyl molecular calix host H1 was achieved by deepening the aromatic wall, introducing 2-hydroxymethylimidazolyl groups on the upper edge and water-soluble groups on the lower edge.

[0020] Further preferably, in the step i, the preparation method of the deep-hole type water-soluble resorcinol calix[4]arene supramolecular capsule H1-H1 constituting the basic molecular calix H1 is as follows:

[0021] a. Using 0.23mmol of octaamino hydrochloride molecular cup with ester as raw material, adding at least 10 equivalents of glycolic acid thereto, and heating to not less than 105°C in hydrochloric acid with a concentration of not less than 4mol / L, reflux for at least 3 days; after the reaction is completed, the reaction solution is cooled to room temperature, then transferred to a 0°C ice bath, and ammonia water is added dropwise under stirring until no bubbles are generated, so that the pH of the mixed solution is 8±0.5, and then filtered and the filter cake is collected; the obtained filter cake is washed with deionized water at least 3 times, at least 10mL each time; finally, the filter cake is rinsed with at least 10mL of anhydrous ethanol and collected, and the obtained intermediate product is fully dried under vacuum;

[0022] b. Add the intermediate product prepared in step a to a round-bottom flask, add at least 15 mL of ethanol as a solvent, then add not less than 5 equivalents of solid sodium hydroxide relative to the amount of the intermediate product at room temperature, and terminate the reaction after vigorous stirring for at least 2 hours; the obtained reaction solution is filtered to separate the solid, and washed with anhydrous ethanol at least 3 times, at least 10 mL each time, and then the solid is collected and fully dried under vacuum to obtain the target product, a water-soluble 2-hydroxymethylimidazolyl molecular cup body H1.

[0023] Preferably, in step a, 0.23 mmol of ester-based octaamino hydrochloride molecular cup is used as a raw material, to which 10-25 equivalents of glycolic acid are added.

[0024] When the resorcinol calix[4]arene-derived supramolecular macrocyclic main compound of the present invention has the structure of a molecular calix main body H1, it can dimerize to form a supramolecular capsule H1-H1 by utilizing hydrophobic and dipole interactions, and can be used for the selective inclusion of amphiphilic molecules and water-soluble amine molecules.

[0025] An application of a water-soluble supramolecular cup capsule based on molecular cup assembly of the present invention, wherein the water-soluble 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1 based on deep-cavity water-soluble resorcinol cup [4] arene is applied as supramolecular catalytic process materials, biomimetic recognition materials and materials for preparing molecular reaction containers. The supramolecular capsule H1-H1 of the present invention has an electron-rich hydrophobic cavity, and recognizes large polarity and water-soluble amine molecules through the synergistic drive of hydrophobic action and dipole action. At the same time, this type of supramolecular capsule has potential applications in the fields of supramolecular catalysis, biomimetic recognition and molecular reaction containers.

[0026] Preferably, the water-soluble 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1 based on deep-cavity water-soluble resorcinol calix[4]arene is used to identify amphiphilic molecules and water-soluble molecules including alkylamines, quaternary ammonium salts and triethylenediamine compounds. The supramolecular capsule H1-H1 derived from resorcinol calix[4]arene of the present invention has a large hydrophobic space, and promotes the selective recognition of amphiphilic molecules and water-soluble polar molecules through the synergistic effect of its own deep-cavity hydrophobic cavity and the 2-hydroxymethylimidazolyl group on the upper edge. The supramolecular capsule H1-H1 derived from resorcinol calix[4]arene is used to identify amphiphilic and water-soluble amine molecules.

[0027] Preferably, the water-soluble 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1 based on deep-cavity water-soluble resorcinol calix [4] arene is used for the selective inclusion of polar and water-soluble amine guest molecules. Based on the water-soluble deep-cavity molecular cup main body H1, the present invention utilizes the hydrophobic effect and the synergistic effect of dipole non-covalent bonds to self-assemble to form a molecular capsule, and realizes the selective inclusion of ammonia guest molecules.

[0028] Compared with the prior art, the present invention has the following obvious outstanding substantive features and significant advantages:

[0029] 1. The synthetic route for constructing the primitive 2-hydroxymethylbenzimidazole molecular cup of the present invention is simple in process, the raw materials are readily available, the reaction conditions are mild, the yield is high, and the repeatability is good;

[0030] 2. The water-soluble 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1 of the present invention has a novel structure and a simple and efficient construction method. The novel water-soluble functionalized raphyl calix [4] aromatic molecular cup is used as the assembly unit, the vase conformation of the molecular cup is stabilized by hydrophobic effect, and the two molecular cups in vase conformation are induced to approach each other by dipole effect, and the two synergistically drive the construction of the 2-hydroxymethylbenzimidazole supramolecular capsule;

[0031] 3. The supramolecular capsule H1-H1 of the present invention synergistically promotes the selective inclusion of polar and water-soluble amine guests through the deep hydrophobic inner cavity and the 2-hydroxymethyl functional group on the upper edge. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0033] Figure 1 This is the H NMR spectrum of the molecular cup H1 in Example 1 of the present invention (600 MHz, DMSO-d6:D2O=1:9, v / vmL, 298K).

[0034] Figure 2 This is the NMR carbon spectrum (151 MHz, DMSO-d6, 298 K) of the molecular cup H1 in Example 1 of the present invention.

[0035] Figure 3 This is a high-resolution mass spectrum of the molecular cup H1 in Example 1 of the present invention.

[0036] Figure 4 Schematic diagram of the construction method of supramolecular capsule H1-H1 in Example 1 of the present invention.

[0037] Figure 5 Schematic diagram of supramolecular capsule H1-H1 constructed by quaternary ammonium salt and amine compound in Example 1 of the present invention.

[0038] Figure 6 This is the H1-H1 nuclear magnetic resonance hydrogen spectrum of the supramolecular capsule constructed by quaternary ammonium salt and amine compounds in Example 1 of the present invention.

[0039] Figure 7 Schematic diagram of supramolecular capsule H1-H1 constructed with dialkyl-substituted triethylenediamines according to Example 1 of the present invention.

[0040] Figure 8 This is the H1-H1 nuclear magnetic resonance hydrogen spectrum of the supramolecular capsule constructed by dialkyl-substituted triethylenediamines of the present invention.

[0041] Fig. 9 This is a CPK model diagram of the supramolecular capsule H1-H1 constructed with quaternary ammonium salt and amine compounds in Example 1 of the present invention.

[0042] Fig.10 This is a CPK model diagram of the supramolecular capsule H1-H1 constructed by dialkyl-substituted triethylene amines in Example 1 of the present invention.

[0043] Fig.11 The supramolecular capsule H1-H1 of the preferred embodiment of the present invention is constructed with the basic 2-hydroxymethylbenzimidazole molecular cup H1 conformation. DETAILED DESCRIPTION

[0044] The present invention will be further described in detail below in conjunction with specific embodiments. It should be noted that the specific embodiments are intended to explain the present invention rather than to limit it. The preferred embodiments of the present invention are described in detail as follows:

[0045] Embodiment 1:

[0046] In this embodiment, on the basis of the resorcinol calix [4] aromatic hydrocarbon skeleton, the novel water-soluble 2-hydroxymethyl imidazolyl functionalized supramolecular capsule H1-H1 is constructed by deepening the aromatic wall, introducing the 2-hydroxymethyl imidazolyl group on the upper edge and the sodium salt of the carboxylic acid on the lower edge. The strategy for constructing supramolecular capsules in this embodiment is as follows: the hydrophobic cavity of the molecular cup body can combine with the alkyl chain of the guest molecule through hydrophobic interaction, and the hydroxymethyl functional group on the upper edge of the molecular cup body can interact with the positive charge part of the guest center by dipole, and the two synergistically promote the formation of the molecular capsule, thereby achieving selective inclusion of polar and water-soluble amine guest molecules. The novel water-soluble functionalized 2-hydroxymethyl benzimidazole supramolecular capsules H1-H1 can be used to identify amphiphilic molecules and water-soluble molecules including alkylamines, quaternary ammonium salts and triethylenediamine compounds.

[0047]

[0048] The design and construction of the building block molecular cup H1 of the supramolecular capsule H1-H1: the hydrophobic cavity is constructed by the bridging benzimidazole group, and the electron-rich aromatic wall provides the site for the hydrophobic interaction; the hydroxymethyl functional group on the upper edge provides the dipole interaction site between the host and the guest, and the sodium carboxylate salt on the lower edge gives the host water solubility. The structural formula of the molecular cup H1 is as follows:

[0049]

[0050] In this embodiment, the preparation method of the building block molecular calix H1 of the water-soluble 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1 uses the ester-based octaamino hydrochloride molecular calix S1 as the starting reaction raw material, and obtains the corresponding target compound molecular calix H1 through two steps of acid-ammonia cyclocondensation and acid-base neutralization. The synthesis route is as follows:

[0051]

[0052] In this embodiment, the preparation method of the water-soluble resorcinol calix[4]arene molecular calix H1 specifically includes the following synthesis steps:

[0053] a. The ester-based octaamino hydrochloride molecular calix compound S1 (300 mg, 0.23 mmol, 1 eq) and glycolic acid (436 mg, 5.75 mmol, 25 eq) were placed in a 50 mL flask, and 25 mL of 4 mol / L hydrochloric acid was added. A condenser was installed and heated to 105 ° C for reflux for 72 hours under nitrogen protection; after the reaction was completed, it was cooled to room temperature, and the reaction solution was transferred to an ice bath at 0 ° C, and ammonia water was added dropwise under the ice bath to adjust the pH to 8; filtered, the filter cake was washed 3 times with 15 mL of deionized water, and then quickly rinsed once with 10 mL of anhydrous ethanol, the solid was collected and dried under vacuum to obtain compound S2, which was a brown solid of 225 mg with a yield of 85%;

[0054] b. The product S2 (200 mg, 0.15 mmol, 1 eq) prepared in step a was placed in a 25 mL round-bottom flask, followed by the addition of 10 mL of anhydrous ethanol and sodium hydroxide (32 mg, 0.78 mmol, 5 eq), and stirred at room temperature for 2 hours. After the reaction stopped, it was directly filtered and washed three times with 10 mL of anhydrous ethanol. The solid was collected and fully dried under vacuum to obtain the water-soluble molecular cup H1, a building block of the supramolecular capsule H1-H1, as a khaki solid of 184 mg with a yield of 86%.

[0055] In this example, the intermediate product S2 was characterized by NMR and mass spectrometry. 1 HNMR(400MHz,DMSO-d6:D2O=9:1,v / v mL,δppm)δ8.13(s,8H),7.96(s,4H),7.70(s,4H),5.56(t,J=8.2Hz,4H),4.68(s,8H),2.54(m,8H),2.20(t,J=7.1Hz,8H). 13 C NMR (151MHz, DMSO-d6, δppm): 174.5, 156.6, 156.0, 151.0, 135.4, 129.1, 125.3, 117.5, 109.8, 33.3, 32.5, 27.3.ESI-HRMS: Calcd.forchemical formula C 72 H 55 N8O 20 :1351.3611,found 1351.3525.[MH] - .

[0056] In this embodiment, see Figure 1-Figure 3 The molecular cup H1 was characterized by NMR and mass spectrometry. 1H NMR(600MHz,D2O:DMSO-d6=9:1,v / v mL,δppm)δ7.91(s,8H),7.82(s,4H),7.68(s,4H),5.69(t,J=8.3Hz,4H),4.71(s,8H),2.66(d,J=7.8Hz,8H),2.24(t,J=7.3Hz,8H). 13 C NMR (151MHz, D2O:DMSO-d6=9:1, v / v mL, δppm)181.8,157.3,155.7,148.4,135.7,135.5,124.4,116.9,109.6,35.8,33.4,28.3.ESI-HRMS:Calcd.for chemical formula C 72 H 55 N8O 20 :1351.3611,found1351.3525.[M-4Na+3H] - .

[0057] In this embodiment, based on the construction method of the water-soluble functionalized deep-hole resorcinol calix [4] aromatic molecular calix, a novel water-soluble 2-hydroxymethyl imidazole-based supramolecular capsule H1-H1 is prepared using the water-soluble molecular calix H1 as the assembly unit; the construction scheme is as follows: Figure 4 shown.

[0058] The preparation method of the water-soluble supramolecular cup capsule based on molecular cup assembly in this embodiment comprises the following steps:

[0059] Take molecular cup H1 (14.40 mg, 10.00 μmol) and add it to a 25 mL sample bottle, add 10 mL of heavy water, and ultrasonicate for 10 minutes until it is completely dissolved to obtain a clear and transparent light yellow heavy water solution with a concentration of 1 mmol / L, i.e., the main solution, which is reserved for later use;

[0060] Take 50 mmol of a polar or water-soluble guest as a raw material, add at least 1 mL of heavy water thereto, and ultrasonicate for 10 minutes until it is completely dissolved, and prepare a heavy water solution with a concentration of 50 mmol / L to obtain a guest solution for later use;

[0061] 500 μL of the host solution and 5 μL of the guest solution were measured, and the host solution or the guest solution was mixed and ultrasonicated for at least 10 minutes until the mixture was uniform, thereby preparing the 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1.

[0062] In this embodiment, the host H1 and the polar or water-soluble guest in the above two solutions are mixed at a molar ratio of 2:1 to prepare 2-hydroxymethylbenzimidazole supramolecular capsules H1-H1.

[0063] Host-guest NMR data analysis:

[0064] 500 μL of the molecular cup H1 solution prepared in the above embodiment was added to the NMR tube, and then 10 μL of a 50 mmol / L heavy aqueous solution of polar molecules or water-soluble molecules was added to the NMR tube. After the solutions were mixed, the 298K NMR hydrogen spectrum was measured on a Bruker AVANCE III HD 600M machine, and the spectral width of the scan was set to 25, the center to 5, and the number of scans to 64 times.

[0065] The chemical shift change is calculated by subtracting the NMR signal of the complexed guest from the NMR signal of the guest in the natural free state. The formula is: Δδ = δ boundguest –δ freeguest .

[0066] A new type of water-soluble supramolecular capsule H1-H1 was constructed based on the synergistic self-assembly driven by hydrophobic effect and dipole interaction. Figure 4 shown.

[0067] The supramolecular capsule H1-H1 based on water-soluble functionalized deep-cavity resorcinol calix[4]arene molecular calix is ​​used for the selective inclusion of water-soluble and amphiphilic amine compounds. Figure 5 shown.

[0068] H NMR spectrum analysis of the host-guest complex of supramolecular capsule H1-H1 with quaternary ammonium salts and amine molecules: The supramolecular capsule H1-H1 has an electron-rich hydrophobic cavity, which can fully utilize the long alkyl chain part of the hydrophobic effect to encapsulate the guest in aqueous solution. The upper edge of the supramolecular capsule H1-H1 has a hydroxymethyl functional group that is easily polarized, which can recognize positively charged guests through dipole interactions. From the hydrogen spectrum of the host-guest complex of supramolecular capsule H1-H1 with amine and quaternary ammonium salt molecules, it can be found that the long alkyl chains of amine and quaternary ammonium salt molecules penetrate deep into the interior of the molecular capsule due to the hydrophobic effect and are strongly shielded. The chemical shift change value (Δδ) of the terminal methyl group reaches -5.16ppm. The substituents on the positively charged nitrogen atom are surrounded by the hydroxymethyl group of the molecular capsule, and the host and guest are combined through the synergistic effect of hydrophobic and dipole effects. Figure 6 shown.

[0069] The supramolecular capsule H1-H1 based on resorcinol calix[4]arene molecular calix was used for the selective inclusion of water-soluble triethylenediamine compounds. Figure 7 shown.

[0070] H NMR spectrum analysis of the host-guest complex of supramolecular capsule H1-H1 and dialkyl-substituted triethylenediamine molecules: supramolecular capsule H1-H1 has an electron-rich hydrophobic cavity, which can encapsulate the hydrophobic alkyl chain of the guest in aqueous solution by hydrophobic interaction. The upper edge of supramolecular capsule H1-H1 has polar hydroxymethyl groups, which are easily polarized and encapsulate the triethylenediamine ring with double positive charges through dipole interactions. From the H NMR spectrum of the host-guest complex of supramolecular capsule H1-H1 and dialkyl-substituted triethylenediamine molecules, it can be found that the long alkyl chain of dialkyl triethylenediamine molecules penetrates deep into the interior of the molecular capsule due to the hydrophobic effect and is strongly shielded, and the chemical shift change value (Δδ) of the terminal methyl group reaches -5.17ppm. The triethylenediamine ring containing double positive charge is surrounded by the hydroxymethyl group of the supramolecular capsule H1-H1 and moves slightly to the low field region (Δδ = 0.07-0.22 ppm). The host and the guest combine through the synergistic effect of hydrophobic interaction and dipole interaction to form a host-guest complex. Figure 8 shown.

[0071] The synergistic effect of H1-H1 hydrophobic interaction and dipole interaction in supramolecular capsules drives the CPK model of amine and quaternary ammonium salt molecules. Fig. 9 shown.

[0072] The CPK model of supramolecular capsules driven by the synergistic H1-H1 hydrophobic and dipole interactions for encapsulating dialkyl-substituted triethylenediamine molecules. Fig.10 shown.

[0073] When the water-soluble 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1 of the preferred embodiment of the present invention has the structure of the functionalized deep-hole type resorcinol calix [4] aromatic hydrocarbon assembly unit H1, the water-soluble supramolecular capsule has an electron-rich deep-hole hydrophobic cavity and a hydroxyl functional group modified at the upper edge; wherein the hydrophobic cavity is constructed by the bridging benzimidazole group, and the electron-rich aromatic wall provides a hydrophobic interaction site; the hydroxymethyl functional group at the upper edge provides a dipole interaction site between the host and the guest, and the sodium carboxylate at the lower edge gives the main body water solubility. The molecular cup main body H1 has two conformations C in water. 4v Symmetrical "vase" conformation and C 2v Symmetrical "kite" conformation, and there is a dynamic balance between the two. The present invention uses hydrophobic effect to stabilize the vase conformation of the molecular cup, and uses the dipole effect to induce the two molecular cups in the vase conformation to approach each other. The two synergistically drive the construction of 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1, such as Fig.11 shown.

[0074] Finally, it should be noted that the above is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, researchers in this field can still modify the research schemes recorded in the aforementioned embodiments, or make equivalent replacements for parts of them. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention. Although the above describes the specific implementation methods of the present invention, it is not a limitation on the protection scope of the present invention. Researchers in the relevant field should understand that on the basis of the technical solution of the present invention, various modifications or deformations that researchers in this field can make without creative work are still within the protection scope of the present invention.

Claims

1. A water-soluble supramolecular cup capsule based on molecular cup assembly, characterized in that: The invention is a water-soluble 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1 based on deep-hole water-soluble resorcinol calix[4]arene in the presence of a compound selected from alkylamines, quaternary ammonium salts and triethylenediamine as a guest, and its structural formula is as follows:

2. A method for preparing a water-soluble supramolecular cup capsule based on molecular cup assembly according to claim 1, characterized in that: The steps include: ⅰ. Using 0.01mmol molecular calix main compound H1 as raw material, add at least 10mL of heavy water thereto, and ultrasonicate for at least 10 minutes until completely dissolved to obtain a main solution for standby use; the structural formula of the molecular calix main compound H1 is: ⅱ. To 50 mmol of a polar or water-soluble guest as a raw material, add at least 1 mL of heavy water, and ultrasonicate for at least 10 minutes until completely dissolved to obtain a guest solution for later use; iii. Measure 500 μL of the main solution obtained in step ⅰ, measure at least 5 μL of the guest solution obtained in step ⅱ, mix the main solution and the guest solution and ultrasonicate for at least 10 minutes until the mixture is uniform, and 2-hydroxymethylbenzimidazole supramolecular capsules H1-H1 can be prepared.

3. The method for preparing a water-soluble supramolecular cup capsule based on molecular cup assembly according to claim 2, characterized in that: In the step i, the functionalized water-soluble 2-hydroxymethylimidazolyl molecular cup main compound H1 is synthesized by using resorcinol calix [4]arene as the skeleton, sequentially deepening the aromatic wall, introducing the 2-hydroxymethylimidazolyl group at the upper edge and the water-soluble group at the lower edge. The preparation method of the deep-hole type water-soluble resorcinol calix [4]arene supramolecular capsule H1-H1 constituent unit molecular cup main compound H1 is as follows: a. Using 0.23mmol of octaamino hydrochloride molecular cup with ester as raw material, adding at least 10 equivalents of glycolic acid thereto, and heating to not less than 105°C in hydrochloric acid with a concentration of not less than 4mol / L, reflux for at least 3 days; after the reaction is completed, the reaction solution is cooled to room temperature, then transferred to a 0°C ice bath, and ammonia water is added dropwise under stirring until no bubbles are generated, so that the pH of the mixed solution is 8±0.5, and then filtered and the filter cake is collected; the obtained filter cake is washed with deionized water at least 3 times, at least 10mL each time; finally, the filter cake is rinsed with at least 10mL of anhydrous ethanol and collected, and the obtained intermediate product is fully dried under vacuum; the structural formula S1 of the octaamino hydrochloride molecular cup with ester is: b. Add the intermediate product prepared in step a to a round-bottom flask, add at least 15 mL of ethanol as a solvent, then add not less than 5 equivalents of solid sodium hydroxide relative to the amount of the intermediate product at room temperature, and terminate the reaction after vigorous stirring for at least 2 hours; the obtained reaction solution is filtered to separate the solid, and washed with anhydrous ethanol at least 3 times, at least 10 mL each time, and then the solid is collected and fully dried under vacuum to obtain the target product, a water-soluble 2-hydroxymethylimidazolyl molecular cup main compound H1.

4. An application of the water-soluble supramolecular cup capsule based on molecular cup assembly according to claim 1, characterized in that: The water-soluble 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1 based on deep-cavity water-soluble resorcinol calix[4]arene is applied to supramolecular catalytic process materials, bionic recognition materials and materials for preparing molecular reaction containers.

5. The use of the water-soluble supramolecular cup capsule based on molecular cup assembly according to claim 4, characterized in that: The water-soluble 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1 based on deep-cavity water-soluble resorcinol calix[4]arene is used to identify amphiphilic molecules and water-soluble molecules including alkylamines, quaternary ammonium salts and triethylenediamine compounds.

6. The use of the water-soluble supramolecular cup capsule based on molecular cup assembly according to claim 4, characterized in that: The water-soluble 2-hydroxymethylbenzimidazole supramolecular capsule H1-H1 based on deep-cavity water-soluble resorcinol calix[4]arene is used for the selective inclusion of polar and water-soluble amine guest molecules.

Images