An amide molecular cage and its preparation method and application

Abstract

The present application relates to the field of organic synthesis technology, and specifically discloses an amide molecular cage and its preparation method and application. The amide molecular cage has the following structure: wherein R is independently selected from ‑H, ‑XR 1 ;X is O or ‑CH2‑;R 1 Each occurrence is independently selected from a straight-chain alkane having 1 to 10 carbon atoms, an alkoxy group, a terminal alkenyl group, a terminal alkynyl group, an ester group, a carboxylate substituent, an ammonium salt substituent, a sulfonate substituent, a phosphate substituent, a pyridinium cation substituent, or an imidazolium cation substituent. The amide molecular cage in the present application has a good cavity structure and can adapt to the shape of the anion through conformational regulation, thereby achieving efficient recognition of anions of various shapes. In addition, by changing the tail chain functional group, the derivatization of the molecular cage with different functional group tail chains is achieved.

Description

Technical Field

[0001] The present application relates to the technical field of organic synthesis, and in particular to an amide molecular cage and a preparation method and application thereof. Background Art

[0002] With the development of economy and technology, anion research has become increasingly important in fields such as medicine, life sciences, environmental protection, agricultural production, and industrial catalysis. For example, negative ions have unique physiological and biochemical functions in the body, effectively preventing dental caries and osteoporosis in the elderly. Measuring chloride ion concentration in the body is particularly important for those with alveolar fibrosis. DNA, which carries genetic information, is often a polyanion. Many enzymes that play a key role in metabolism are also anions. Phosphate anions play a vital role in energy storage, information processing, and transmission in organisms. Furthermore, polluting anions are closely related to river eutrophication (phosphate) and carcinogenesis (silicate). Therefore, anion recognition technology and the design and synthesis of anion receptors are of paramount importance.

[0003] However, designing anion receptors faces more challenges than designing cation receptors. Because anions usually have a larger radius and smaller charge density than cations with the same number of electrons, their electrostatic interactions with receptors are weaker. At the same time, the geometric shapes of anions are diverse, and the receptor structure needs to be highly complementary to achieve efficient recognition of specific anions. In the development of anion recognition, a series of non-cyclic or monocyclic hosts have been reported at home and abroad to achieve the recognition of anions, but in general, the bonding strength is average. Compared with chain and macrocyclic host molecules, cage molecules with three-dimensional spatial structures can more completely encapsulate guests and embed more bonding sites, with better host-guest bonding properties, becoming ideal anion receptors. At present, many amide molecular cages have been reported for anions (such as Cl - Br - 、CH3COO - While some of these compounds have shown strong affinity, their synthesis methods are complex, have harsh reaction conditions, unstable intermediates, and are difficult to derivatize. Therefore, the existing technology needs to be improved. Summary of the Invention

[0004] In view of the above-mentioned deficiencies in the prior art, the purpose of this application is to provide an amide molecular cage and its preparation method and application, aiming to solve the problems of the existing amide molecular cage synthesis steps being complex, the reaction conditions being harsh, the intermediates being unstable, and the derivatization development being difficult.

[0005] The technical solution of this application is as follows:

[0006] In a first aspect of the present application, an amide molecular cage is provided, wherein the amide molecular cage has the following structure:

[0007]

[0008] Wherein, R is independently selected from -H, -XR 1 ; X is O or -CH2-; R 1 Each occurrence is independently selected from a straight-chain alkane having 1 to 10 C atoms, an alkoxy group, a terminal alkenyl group, a terminal alkynyl group, an ester group, a carboxylate substituent, an ammonium salt substituent, a sulfonate substituent, a phosphate substituent, a pyridinium cation substituent or an imidazolium cation substituent.

[0009] Alternatively, R is an alkoxy group having 1 to 10 C atoms or a triazole substituent having 20 to 30 C atoms.

[0010] Optionally, R is selected from one of the following structures:

[0011] -OC8H 17 、-OC8H 15 、 Indicates the junction site.

[0012] In a second aspect of the present application, a method for preparing the above-mentioned amide molecular cage is provided, comprising the steps of:

[0013] 2,4,6-triethylbenzene-1,3,5-trimethylamine trihydrochloride, active carboxylate, reaction solvent and organic base are mixed and reacted under an inert atmosphere. The post-reaction system is purified to obtain the amide molecular cage.

[0014] Optionally, the structure of the active carboxylate is as follows:

[0015]

[0016] Wherein, R is independently selected from -H, -XR 1 ; X is O or -CH2-; R 1 Each occurrence is independently selected from a straight-chain alkane having 1 to 10 C atoms, an alkoxy group, a terminal alkenyl group, a terminal alkynyl group, an ester group, a carboxylate substituent, an ammonium salt substituent, a sulfonate substituent, a phosphate substituent, a pyridinium cation substituent or an imidazolium cation substituent.

[0017] Optionally, R is selected from one of the following structures:

[0018] -OC8H 17 、-OC8H 15 、 Indicates the attachment site.

[0019] Optionally, the reaction temperature is 15-25° C., and the reaction time is 24-48 h.

[0020] Optionally, the purification treatment includes rotary evaporation and column chromatography purification, the column chromatography purification method is thin layer chromatography, and the volume ratio of dichloromethane to tetrahydrofuran in the solvent of the thin layer chromatography is 4:1.

[0021] The third aspect of the present application provides an application of the above-mentioned amide molecular cage in anion recognition, wherein the anion includes at least one of chloride ion, bromide ion, nitrate ion, fluoroborate ion, hexafluorophosphate ion, and thiocyanate ion.

[0022] In a fourth aspect of the present application, there is provided a use of the above-mentioned amide molecular cage in the recognition of polar organic molecules, wherein the polar organic molecules include at least one of amino alcohol compounds, aspartic acid, and adenosine triphosphate.

[0023] Compared with the existing technology, this application has the following advantages:

[0024] The amide molecular cage in this application has a good cavity structure, and the NH bonds in the amide bonds are highly pre-organized and all point to the inside of the cavity, which can serve as hydrogen bond donors, while the aromatic CH bonds adjacent to the carboxyl group point to the inside of the molecular cage, which can form CH-group interactions with the guest and anions, thereby enhancing the host-guest bond strength. The amide molecular cage in this application has a larger hydrophobic cavity and can adapt to the shape of the anion through conformational regulation. In addition, the amide molecular cage in this application realizes the derivative expansion of molecular cages with different functional group tail chains through the change of the tail chain functional group, so as to be applied to different usage scenarios.

[0025] The amide cage synthesis method described in this application introduces reactive carboxylates with different side chain groups as side arms, using 2,4,6-triethylbenzene-1,3,5-trimethylamine as a lid. This cage is then closed in a single step at room temperature via an amidation reaction. This synthesis method features simple steps, mild reaction conditions, and allows for the derivatization of tail-chain molecular cages with different functional groups, enabling efficient recognition of anions of various shapes using the molecular cage. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following briefly introduces the drawings required for describing the embodiments.

[0027] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of MC-1 provided in the examples of this application;

[0028] Figure 2This is the hydrogen nuclear magnetic resonance spectrum of MC-2 provided in the examples of this application;

[0029] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of MC-3 provided in the examples of this application;

[0030] Figure 4 This is the hydrogen nuclear magnetic resonance spectrum of MC-4 provided in the examples of this application;

[0031] Figure 5 MC-1 and Cl provided in the examples of this application - ITC titration diagram in tetrahydrofuran;

[0032] Figure 6 MC-2 and Cl provided in the examples of this application - ITC titration diagram in dichloroethane;

[0033] Figure 7 This is the ITC titration diagram of MC-4 and G1 in water provided in the examples of this application. DETAILED DESCRIPTION

[0034] To make the purpose, technical solutions and advantages of this application clearer, the technical solutions in the embodiments of this application will be clearly and completely described below in conjunction with the drawings and embodiments of this application. Obviously, the described embodiments are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments of this application, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of this application. In the absence of conflict, the features in the following embodiments and embodiments can be combined with each other.

[0035] It should be noted that if there are descriptions involving "first", "second", etc. in the implementation of this application, the descriptions such as "first", "second", etc. are only used for descriptive purposes and cannot be understood as indicating or suggesting their relative importance and implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of such features. In addition, the technical solutions between the various embodiments can be combined with each other, but they must be based on the fact that ordinary technicians in this field can implement them. When the combination of technical solutions is contradictory or cannot be implemented, it should be deemed that such a combination of technical solutions does not exist and is not within the scope of protection required by this application.

[0036] Molecular cages are a class of three-dimensional organic or inorganic molecules with unique internal cavities, widely used in fields such as chemistry, materials science, and biomedical research. Molecular cages can be synthesized through a variety of strategies, including self-assembly and chemical bonding. They exhibit significant confinement and stability in catalytic reactions and can also serve as carriers for nanoscale drug delivery. They are highly flexible and functional material systems with broad application prospects. However, existing molecular cages suffer from complex procedures, harsh reaction conditions, unstable intermediates, and difficulty in derivatization.

[0037] Based on this, the first aspect of the embodiments of the present application provides an amide molecular cage having the structure shown below:

[0038]

[0039] Wherein, R is independently selected from -H, -XR 1 ; X is O or -CH2-; R 1 Each occurrence is independently selected from a straight-chain alkane having 1 to 10 C atoms, an alkoxy group, a terminal alkenyl group, a terminal alkynyl group, an ester group, a carboxylate substituent, an ammonium salt substituent, a sulfonate substituent, a phosphate substituent, a pyridinium cation substituent or an imidazolium cation substituent.

[0040] The amide molecular cages in the embodiments of this application have a well-defined cavity structure. The NH bonds in the amide bonds are highly pre-organized and all point toward the interior of the cavity, acting as hydrogen bond donors. The aromatic CH bonds adjacent to the carboxyl group point toward the interior of the molecular cage, forming CH-group-anion interactions with the guest, thereby enhancing the host-guest bond strength. The amide molecular cages of this application have a relatively large hydrophobic cavity that can adapt to the shapes of different anions through conformational adjustment.

[0041] In some embodiments, R is selected from an alkoxy group having 1 to 10 C atoms or a triazole substituent having 20 to 30 C atoms.

[0042] Furthermore, R is selected from one of the following structures:

[0043] -OC8H 17 、-OC8H 15 、 -OC8H 15 It can be:

[0044] in, Indicates the attachment site.

[0045] The amide molecular cage in this application introduces different side arms (R groups) through active carboxylates with the same side chain groups to achieve the derivatization and expansion of molecular cages with different functional group tail chains, and utilizes the molecular cage to achieve efficient recognition of anions of various shapes for application in different usage scenarios.

[0046] A second aspect of the embodiments of the present application provides a method for preparing the amide molecular cage in the embodiments of the present application, comprising the steps of:

[0047] 2,4,6-triethylbenzene-1,3,5-trimethylamine trihydrochloride, an active carboxylate, a reaction solvent, and an organic base are mixed and reacted under an inert atmosphere. The post-reaction system is purified to obtain the amide molecular cage. The inert atmosphere gas may be nitrogen, argon, helium, or the like.

[0048] In some embodiments, the reaction solvent is selected from tetrahydrofuran (THF), N,N-dimethylformamide (DMF), 1,3-dimethyl-2-imidazolidinone (DMI), 1,4-dioxane, N-methylpyrrolidone (NMP), hexamethylphosphoric triamide (HMPA) or dimethyl sulfoxide (DMSO).

[0049] In some embodiments, the organic base is selected from N,N-diisopropylethylamine (DIPEA), triethylamine, tetramethylethylenediamine, pentamethyldiethylenetriamine, or 4-dimethylaminopyridine (DMAP). During the reaction, the organic base activates 2,4,6-triethylbenzene-1,3,5-trimethylamine trihydrochloride, removing the hydrochloric acid proton in 2,4,6-triethylbenzene-1,3,5-trimethylamine trihydrochloride to react the amino group with the active carboxylate, completing the cage process.

[0050] Specifically, the preparation method of the amide molecular cage includes the steps of:

[0051] S1. Mix 2,4,6-triethylbenzene-1,3,5-trimethylamine trihydrochloride, active carboxylate, a reaction solvent and an organic base, and react under an argon atmosphere to obtain a reaction product.

[0052] In some embodiments, the molar ratio of 2,4,6-triethylbenzene-1,3,5-trimethylamine trihydrochloride to the active carboxylate is 1:1.5. This ratio ensures the synthesis of the amide molecular cage without excess raw materials, reduces the formation of impurities after the reaction, and avoids cost issues caused by waste.

[0053] In some embodiments, the reaction temperature is 15-25° C., for example, the reaction temperature is 15° C., 16° C., 17° C., 18° C., 19° C., 20° C., 21° C., 22° C., 23° C., 24° C., or 25° C. The reaction time is 24-48 h, for example, the reaction time is 24 h, 28 h, 32 h, 36 h, 40 h, 44 h, or 48 h.

[0054] In some embodiments, the structure of the active carboxylate is as follows:

[0055]

[0056] Wherein, R is independently selected from -H, -XR 1 ; X is O or -CH2-; R 1 Each occurrence is independently selected from a straight-chain alkane having 1 to 10 C atoms, an alkoxy group, a terminal alkenyl group, a terminal alkynyl group, an ester group, a carboxylate substituent, an ammonium salt substituent, a sulfonate substituent, a phosphate substituent, a pyridinium cation substituent or an imidazolium cation substituent.

[0057] Furthermore, R is selected from one of the following structures:

[0058] -OC8H 17 、-OC8H 15 、 -OC8H 15 It can be:

[0059] in, Indicates the attachment site.

[0060] In some embodiments, step S1 may be: under argon, 2,4,6-triethylbenzene-1,3,5-trimethylamine trihydrochloride (1.00 g, 2.80 mmol, 2 equiv.), active carboxylate (4.20 mmol, 3 equiv.), deionized water (70 mL) and tetrahydrofuran (THF, 300 mL) are added to a 500 mL two-necked flask, and a THF solution (60 mL) of N,N-diisopropylethylamine (DIPEA, 1.45 g, 11.2 mmol, 8 equiv.) is slowly added to the two-necked flask through a syringe pump, and the reaction is carried out at room temperature for 36 h.

[0061] In dilute solution and under mild reaction conditions, an amide molecular cage with multiple hydrogen-bonding recognition sites was synthesized in a single step via an amidation reaction using an active ester and 2,4,6-triethylbenzene-1,3,5-trimethylamine trihydrochloride. Compared to previously reported methods, this novel approach features mild reaction conditions, a simple procedure, and high yields. Furthermore, by regulating the type of active carboxylate side chain, the derivatization of the molecular cage with different functional group tails was achieved.

[0062] S2. The reaction product was subjected to rotary evaporation and extracted with dichloromethane to obtain a combined organic phase.

[0063] The rotary evaporation process can be performed using, but is not limited to, a rotary evaporator or a self-assembled device. Those skilled in the art can make a selection based on actual conditions. The rotary evaporation process can be performed under reduced pressure using a rotary flask to increase the evaporation area, thereby improving the efficiency of distillation and achieving the purpose of separation and purification. The reaction product is subjected to rotary evaporation to remove THF from the reaction product. The number of dichloromethane extractions can be 1, 2, or 3 times, with the goal of fully dissolving the target component in the reaction product in dichloromethane.

[0064] S3. Purify the combined organic phases using column chromatography to obtain the amide molecular cage.

[0065] In some embodiments, the column chromatography purification is thin layer chromatography, wherein the volume ratio of dichloromethane to tetrahydrofuran (CH2Cl2:THF) in the thin layer chromatography solvent is 4:1.

[0066] The amide molecular cage prepared by this preparation method has good host-guest chemical properties, and the prepared amide molecular cage has a large hydrophobic cavity that can adapt to the shape of the anion through conformational regulation.

[0067] A third aspect of the present invention provides an application of the amide molecular cage in the present invention in anion recognition, wherein the anion comprises at least one of chloride ion, bromide ion, nitrate ion, fluoroborate ion, hexafluorophosphate ion, and thiocyanate ion.

[0068] The amide molecular cage in the embodiment of the present application realizes the derivatization and expansion of the molecular cage with different functional group tail chains by changing the side chain groups, so as to be applied to anion recognition.

[0069] In a fourth aspect of the embodiments of the present application, there is provided an application of the amide molecular cage in the embodiments of the present application in the recognition of polar organic molecules, wherein the polar organic molecules include at least one of amino alcohol compounds, aspartic acid, and adenosine triphosphate.

[0070] The amide molecular cage in the embodiment of the present application realizes the derivatization and expansion of the molecular cage with different functional group tail chains by changing the side chain groups, so as to be applied to the recognition of polar organic molecules.

[0071] The following is further described by way of specific examples. Unless otherwise specified, the materials used in the following examples can all be purchased.

[0072] Example 1

[0073] Under argon, a 500 mL two-necked flask was charged with 2,4,6-triethylbenzene-1,3,5-trimethylamine trihydrochloride (1.00 g, 2.80 mmol, 2 equiv.), an active carboxylate (4.20 mmol, 3 equiv.), deionized water (70 mL), and THF (300 mL). A THF solution (60 mL) of DIPEA (1.45 g, 11.2 mmol, 8 equiv.) was slowly added to the two-necked flask via a syringe pump. The mixture was allowed to react at room temperature for 36 h. After the reaction, the THF was removed by rotary evaporation and extracted three times with dichloromethane to obtain a combined organic phase. The combined organic phase was purified by column chromatography (CH2Cl2:THF = 4:1) to obtain the target product MC-1. Its synthetic route is as follows:

[0074]

[0075] MC-1: (white solid, yield 28%). Its nuclear magnetic resonance detection results are as follows Figure 1 As shown. Among them, 1 H NMR(500MHz,THF-d8)δ8.16(dd,J=8.0,1.5Hz,6H),7.89(s,3H),7.59(t,J=8.0Hz,3H) ,7.15(br,6H),4.66(d,J=5.0Hz,12H),2.80(q,J=7.5Hz,12H),1.25(t,J=7.5Hz,18H).

[0076] Example 2

[0077] Under argon, a 500 mL two-necked flask was charged with 2,4,6-triethylbenzene-1,3,5-trimethylamine trihydrochloride (1.00 g, 2.80 mmol, 2 equiv.), an active carboxylate (4.20 mmol, 3 equiv.), deionized water (70 mL), and THF (300 mL). A THF solution (60 mL) of DIPEA (1.45 g, 11.2 mmol, 8 equiv.) was slowly added to the two-necked flask via a syringe pump. The mixture was allowed to react at room temperature for 36 h. After the reaction, the THF was removed by rotary evaporation, and the mixture was extracted three times with dichloromethane to obtain a combined organic phase. The combined organic phase was purified by column chromatography (CH2Cl2:THF = 4:1) to obtain the target product MC-2. Its synthetic route is as follows:

[0078]

[0079] MC-2: (white solid, yield 36%). Its nuclear magnetic resonance detection results are as follows Figure 2 As shown. Among them, 1 H NMR (500MHz, CDCl3) δ7.81(d,J=1.5Hz,6H),6.97(t,J=1.5Hz,3H),5.92(t,J=4.5Hz,6H),4.69(d,J=4.5Hz,12H),4.10(t,J=6.5Hz,6 H), 2.69 (q, J = 7.0Hz, 12H), 1.87-1.80 (m, 6H), 1.52-1.45 (m, 6H), 1.32 (t, J = 7.5Hz, 18H), 1.38-1.26 (m, 24H), 0.91 (t, J = 7.0Hz, 9H).

[0080] Example 3

[0081] Under argon, a 500 mL two-necked flask was charged with 2,4,6-triethylbenzene-1,3,5-trimethylamine trihydrochloride (1.00 g, 2.80 mmol, 2 equiv.), an active carboxylate (4.20 mmol, 3 equiv.), deionized water (70 mL), and THF (300 mL). A THF solution of DIPEA (1.45 g, 11.2 mmol, 8 equiv.) (60 mL) was slowly added to the flask via a syringe pump. The mixture was allowed to react at room temperature for 36 h. After the reaction, the THF was removed by rotary evaporation, and the mixture was extracted three times with dichloromethane to obtain a combined organic phase. The combined organic phase was purified by column chromatography (CH2Cl2:THF = 4:1) to obtain the target product MC-3. Its synthetic route is as follows:

[0082]

[0083] MC-3: (white solid, yield 35%). Its nuclear magnetic resonance detection results are as follows Figure 3 As shown. Among them, 1 H NMR (500MHz, CDCl3) δ7.79(d,J=1.5Hz,6H),6.95(t,J=1.5Hz,3H),5.89(t,J=4.5Hz,6H),5.86-5.76(m,3H),5.08-4.88(m,6H),4.67(d,J=4 .5Hz,12H),4.08(t,J=6.5Hz,6H),2.67(q,J=7.5Hz,12H),2.09-2.04(m,6H),1.88-1.74(m,6H),1.51-1.36(m,18H),1.29(t,J=7.5Hz,18H).

[0084] Example 4

[0085] Under argon, a 500 mL two-necked flask was charged with 2,4,6-triethylbenzene-1,3,5-trimethylamine trihydrochloride (1.00 g, 2.80 mmol, 2 equiv.), an active carboxylate (4.20 mmol, 3 equiv.), deionized water (70 mL), and THF (300 mL). A THF solution of DIPEA (1.45 g, 11.2 mmol, 8 equiv.) (60 mL) was slowly added to the flask via a syringe pump. The mixture was allowed to react at room temperature for 36 h. After completion of the reaction, the THF was removed by rotary evaporation, and the reaction solution was extracted three times with dichloromethane to obtain a combined organic phase. The combined organic phase was purified by column chromatography (CH2Cl2:THF = 4:1) to obtain the intermediate product MC-click. The intermediate product MC-click (80 mg, 30 μmol) and dichloromethane (30 mL) were added to a 100 mL eggplant-shaped flask, and 5 mL of trifluoroacetic acid was added under ice bath conditions. The reaction was then allowed to react at room temperature for 8 hours. After the reaction was completed, the organic solvent was removed, and the product was precipitated by adding water and filtered to obtain a white solid. The dried solid (61 mg, 28.4 μmol) was dissolved in 1 mL of sodium hydroxide solution (1.14 mg, 28.4 μmol) and dried using a freeze dryer to obtain the target product MC-4. Its synthesis route is as follows:

[0086]

[0087] MC-4: (white solid, yield 20%). Its nuclear magnetic resonance detection results are as follows Figure 4 As shown. Among them, 1H NMR(500MHz,D2O)δ8.25(s,3H),7.73(d,J=1.5Hz,3H),7.72(d,J=1.5Hz,6H),5.43(s,6H),4.59(s,12H), 3.90(s,18H),3.54(t,J=7.0Hz,18H),2.65-2.57(m,12H),2.26(t,J=7.0Hz,18H),1.14(t,J=7.5Hz,18H).

[0088] Test Example 1

[0089] The amide molecular cage MC-1 prepared in Example 1 was used to identify anions. The isothermal titration calorimeter was used to measure the reaction of the amide molecular cage MC-1 prepared in Example 1 with Cl in tetrahydrofuran. - Br - 、NO3 - and BF4 - The bonding constant (Ka) of MC-1 and Cl was determined using the TANANO ITC LV isothermal titration calorimeter with tetrahydrofuran as solvent and a temperature of 25°C. - The results of ITC titration in tetrahydrofuran are as follows Figure 5 As shown, MC-1 reacts with Cl in tetrahydrofuran. - Br - 、NO3 - and BF4 - The test results of the bonding constants are shown in Table 1:

[0090] Table 1. Bonding constants of MC-1 with anions in tetrahydrofuran

[0091]

[0092]

[0093] The data in Table 1 show that MC-1 shows obvious size selectivity in the recognition of anions. For smaller anions, such as Cl - Br - 、NO3 - , showing extremely strong bonding ability, the bonding constant can reach 10 7 M -1 , while for larger anions, such as BF4 - , the bond constant dropped significantly by 3 orders of magnitude.

[0094] Test Example 2

[0095] The amide molecular cage MC-2 prepared in Example 2 was used to recognize anions. The bonding constants (Ka) of the amide molecular cage MC-2 prepared in Example 2 with anions of various shapes in dichloroethane were measured using an isothermal titration calorimeter. The isothermal titration calorimeter model was: TA Nano ITC LV; solvent: dichloroethane; temperature: 25°C. - The results of ITC titration in dichloroethane are as follows Figure 6 As shown, the test results of the bonding constants of MC-2 with anions of various shapes in dichloroethane are shown in Table 2:

[0096] Table 2. Bonding constants of MC-2 with anions in dichloroethane

[0097] object <![CDATA[Bonding constant (K a / M -1 )]]> <![CDATA[Cl - ]]> <![CDATA[(1.2±0.3)×10 7 ]]> <![CDATA[Br - ]]> <![CDATA[(3.0±0.3)×10 6 ]]> <![CDATA[SCN - ]]> <![CDATA[(5.4±1.3)×10 6 ]]> <![CDATA[NO3 - ]]> <![CDATA[(4.0±0.4)×10 7 ]]> <![CDATA[BF4 - ]]> <![CDATA[(2.1±0.1)×10 5 ]]> <![CDATA[PF6 - ]]> <![CDATA[(6.9±0.9)×10 3 ]]>

[0098] The data in Table 2 show that the anion binding of MC-2 is similar to that of MC-1, and the recognition of anions shows obvious size selectivity. For smaller anions, such as spherical, planar triangular, and linear anions, it shows extremely strong bonding ability, and the bonding constant can reach 10 7 M -1 For larger tetrahedral anions, such as BF4 - , the bonding constant decreases by 3 orders of magnitude, while for larger octahedral anions, such as PF6 - , the bonding constant dropped by 4 orders of magnitude.

[0099] Test Example 3

[0100] The amide cage MC-4 prepared in Example 4 was used to identify hydrophilic polar organic molecules in aqueous phase. The bonding constants (Ka) of MC-4 with various organic small molecules in water were determined using isothermal titration calorimetry. The isothermal titration calorimeter was a Malvern MicroCal PEAQ-ITC Automated instrument, using ultrapure water as the solvent and a temperature of 25°C. The organic small molecules are listed in Table 3 below:

[0101] Table 3. Hydrophilic polar organic molecules

[0102]

[0103] The test data is shown in Table 4:

[0104] Table 4. Bonding constants of MC-4 with hydrophilic polar organic molecules in water

[0105]

[0106]

[0107] The data in Table 4 show that MC-4 has a high affinity for a variety of hydrophilic polar organic molecules in water, and the bonding constant for amino alcohol compounds G1 and G2 is as high as 10 5 M -1 The bonding constant of the insecticide trichlorophenol G4 and phosphate G5 also reached 10 5 M -1 In addition, MC-4 also has a binding capacity of 10 for aspartic acid and ATP. 4 M -1 .

[0108] Combining Examples 1-4 and Test Examples 1 and 2, it can be seen that the amide molecular cage preparation method in the examples of this application uses an active ester and 2,4,6-triethylbenzene-1,3,5-trimethylamine trihydrochloride in a dilute solution under mild reaction conditions to synthesize an internally modified molecular cage with multiple hydrogen bond recognition sites through a one-step amidation reaction. Compared with previously reported methods, this method is relatively novel, with mild reaction conditions, simple steps, and high yield. By regulating the type of active carboxylate side chain, the derivatization of molecular cages with different functional group tail chains is achieved.

[0109] At the same time, the amide molecular cages in the examples of this application have good host-guest chemical properties. MC-1 prepared in Example 1 and MC-2 prepared in Example 2 exhibit high affinity and significant size selectivity for anions in organic solvents, with a binding constant of 10 for size-matched anions. 7 M -1 , can be used in biomedicine (such as anion transmembrane transport), supramolecular catalysis, polymer materials, etc., and has broad application prospects. The water-soluble derivatized amide molecular cage MC-4 prepared in Example 4 shows good affinity for hydrophilic polar organic molecules, and the bonding constant for amino alcohol compounds can reach 10 5 M -1 The bonding constant for aspartic acid and ATP also reaches 10 4 M -1 , can selectively identify neutral molecules, polar molecules and organic pollutants in water, and also has broad application prospects.

[0110] In summary, the amide molecular cage in this application has a good cavity structure. The NH bonds in the amide bond are highly pre-organized and all point to the inside of the cavity, which can act as hydrogen bond donors. The aromatic CH bonds adjacent to the carboxyl group point to the inside of the molecular cage and can form CH-anion interactions with the guest, thereby enhancing the host-guest bonding strength. The amide molecular cage in this application has a relatively large hydrophobic cavity and can adapt to the shape of the anion through conformational adjustment. In addition, the amide molecular cage in this application realizes the derivatization and expansion of molecular cages with different functional group tail chains through changes in the tail chain functional groups, so as to be applied to different usage scenarios. The amide molecular cage synthesis method in this application, by introducing active carboxylates with different side chain groups as side arms, using 2,4,6-triethylbenzene-1,3,5-trimethylamine as the lid, closes the cage in one step at room temperature through an amidation reaction, and forms an amide molecular cage. This synthesis method has simple steps, mild reaction conditions, and realizes the derivatization of molecular cages with different functional group tail chains, using molecular cages to achieve efficient recognition of anions of various shapes.

[0111] It should be understood that the application of this application is not limited to the above examples. For ordinary technicians in this field, they can make improvements or changes based on the above description. All these improvements and changes should fall within the scope of protection of the claims attached to this application.

Claims

1. An amide molecular cage, characterized in that: The amide molecular cage has the structure shown below: Among them, the structural formula of R is: ; " ” indicates the attachment site.

2. Use of the amide molecular cage according to claim 1 in the recognition of polar organic molecules; The polar organic molecule is at least one of amino alcohol compounds, aspartic acid, and adenosine triphosphate.

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