CN115650867B - A kind of chiral rare earth supramolecular cage complex and its preparation method and application - Google Patents

Abstract

A chiral rare earth supermolecular cage complex and a preparation method and application thereof relate to a complex and a preparation method and application thereof. In order to solve the problems of poor stability and low sensitivity of the rare earth complex in chiral amino acid sensing. Preparation: synthesis of 3,3' -trimethoxytriphenylamine, 3', synthesis of 3' -trihydroxy-4, 4' -triacetyltrianiline, 3', synthesis of 3' - (2, 2-dimethyl-1, 3-dioxolane) -4,4' -triacetyltrianiline, synthesis of ligand L and preparation of rare earth supermolecular cage complex Ln ₄ L ₄ . The chiral rare earth supermolecular cage complex can realize high-selectivity, high-sensitivity and high-accuracy sensing of chiral amino acid compounds. The preparation route is simple and convenient, and the used raw materials and synthetic reagents are low in price and easy to obtain; the chiral rare earth supermolecular cage complex is detected by using a circular polarized light spectrum which has changeable signals and can exclude background interference, and has more obvious advantages in detection sensitivity than the existing fluorescence spectrum detection technology.

Description

A kind of chiral rare earth supramolecular cage complex and its preparation method and application

technical field

The invention belongs to the field of circularly polarized luminescent sensors, and in particular relates to a chiral rare earth supramolecular cage complex and its preparation method and application.

Background technique

As an important chiral molecule to maintain human body functions, amino acids must use transfer ribonucleic acid t-RNA with -OH in the structure as a recognition carrier to carry target amino acids into the cell membrane before they can function in the human body. Therefore, realizing the specific chiral recognition of amino acids is of great significance for maintaining human health and exploring the recognition process of natural enzymes.

The reported metal-organic complex optical sensors for amino acid sensing mainly focus on transition metal complex fluorescent sensors. Transition metal fluorescent sensors (ruthenium, iridium, platinum, rhenium, etc.) have no luminescent properties, so the luminescent properties of the entire sensor can only be adjusted by chemical modification of the ligand, which not only complicates the synthesis of the sensor , and when the fluorescence spectrum signal is used as the output method for the detection of chiral organic molecules in living organisms, the selectivity and detection limit will be reduced because the background fluorescence of the system to be detected cannot be eliminated.

The reported mechanism of chiral amino acid sensing by rare earth complexes is mainly divided into the following three types: 1. Amino acid molecules replace the solvent molecules or ligands coordinated on the chiral or achiral rare earth complexes, so that the rare earth complexes The composition and coordination environment change; 2. Amino acid molecules use their chiral configuration to disturb the coordination environment of achiral rare earth complexes, resulting in a change in the coordination environment of rare earth complexes; 3. Amino acid molecules interact with organic ligands Hydrogen bonds are formed between them to induce changes in the coordination configuration of rare earth complexes. However, the above-mentioned first two sensing methods require that the ligands or coordinating solvent molecules of rare earth complexes are easily substituted or the coordination environment is loose and easily affected by other molecules to change. In order to meet these conditions, this type of rare earth complex sensor The stability of the sensor is relatively poor, which is extremely unfavorable to the practical application of the sensor. In addition, in the above-mentioned third sensing method, the reported examples can only realize the formation of a small amount of hydrogen bonds for the sensing of amino acids. Due to the weak interaction caused by a small amount of hydrogen bonds, this kind of rare earth complex sensors detection sensitivity is low.

Contents of the invention

In order to solve the problems of poor stability and low detection sensitivity of the existing rare earth complexes in sensing chiral amino acids, the invention proposes a chiral rare earth supramolecular cage complex and its preparation method and application.

The structural formula of the chiral rare earth supramolecular cage complex of the present invention is:

The general structural formula of the chiral rare earth supramolecular cage complex is Ln ₄ L ₄ , which is a chiral rare earth complex composed of a chiral ligand L and a rare earth element, and the structural formula of the chiral ligand L is:

The preparation method of the above-mentioned chiral rare earth supramolecular cage complex is carried out according to the following steps:

Step 1, the synthesis of 3,3',3"-trimethoxytriphenylamine:

Weigh 1~3g m-aminoanisole and 7~10g 3-iodoanisole and dissolve in 150~250mL toluene, then add 9~12g copper powder, 2~4g 18-crown-6 and 25~35g K ₂ CO ₃ , heated to reflux for 24 hours; use thin-layer chromatography to monitor the reaction process, filter after the reaction is completed, and the obtained filtrate is washed with dilute ammonia water until it is colorless, washed repeatedly with water, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove excess solvent, to obtain a brownish black crude product, and then separated by column chromatography to obtain 3,3',3"-trimethoxytriphenylamine;3,3',3"-trimethoxytriphenylamine is a yellow oily liquid; filtration can remove copper powder, 18-crown-6 and K ₂ CO ₃ ;

Step 2. Synthesis of 3,3',3"-trihydroxy-4,4',4"-triacetyltriphenylamine:

Weigh 3-6g of 3,3',3"-trimethoxytriphenylamine and dissolve it in 60-80mL of dichloromethane to obtain solution A; weigh 10-12g of anhydrous aluminum trichloride and 5-8g of acetyl chloride and add to 10 ~30mL of dichloromethane, stirred until the aluminum chloride is completely dissolved to obtain solution B, under ice bath conditions, add solution B dropwise to solution A, after the reaction is complete, pour the reaction solution into ice water, filter to remove Insoluble matter, the water layer was separated and extracted 3 times with dichloromethane, the dichloromethane extract was combined with the organic layer, and washed with water repeatedly until neutral, dried over anhydrous sodium sulfate, filtered, dichloromethane solvent was evaporated, A crude product was obtained, and the obtained crude product was separated by column chromatography to obtain 3,3',3"-trihydroxy-4,4',4"-triacetyltriphenylamine as a yellow solid powder;

Step 3, Synthesis of 3,3',3"-(2,2-dimethyl-1,3-dioxolane)-4,4',4"-triacetyltriphenylamine:

Weigh 1~3g of 3,3',3"-trihydroxy-4,4',4"-triacetyltriphenylamine and dissolve it in 10~30mL of acetonitrile, then add 11~14g of cesium carbonate, and heat the reaction solution to Keep stirring at 120°C for 0.5 hours; add 8~12g of R-glyceryl acetonide sulfonate and continue to heat and reflux for 36 hours; use thin layer chromatography to monitor the reaction process, filter to remove cesium carbonate after the reaction is completed, and remove acetonitrile by distillation under reduced pressure Solvent, and then purified by column chromatography to obtain 3,3',3"-(2,2-dimethyl-1,3-dioxolane)-4,4',4"-triacetyltriphenylamine, as white solid;

Step 4, synthesis of ligand L:

Weigh 0.2-1.2g of sodium methoxide and 1-6g of ethyl trifluoroacetate and dissolve in 20-40mL of ethylene glycol dimethyl ether, then add 0.5-1.5g of 3,3',3"-(2,2-bis Methyl-1,3-dioxolane)-4,4',4"-triacetyltriphenylamine, stirred at room temperature for 24 hours, after the reaction was completed, adjusted the pH to 2-3 with hydrochloric acid, filtered the precipitated A yellow solid precipitated, washed several times with water and dried to obtain Ligand L;

Step 5. Preparation of Rare Earth Supramolecular Cage Complex Ln ₄ L ₄ :

Weigh 0.2-1.2g ligand L and add it to 30-50mL methanol, add 0.1-0.6g triethylamine, stir well until ligand L dissolves, then add 0.2-0.6mmol rare earth chloride LnCl ₃ 6H ₂ O, After the dropwise addition, react at room temperature for 24 hours. After the reaction is completed, the reaction solution is poured into water to precipitate a yellow precipitate, which is filtered and dried to obtain the complex;

The above-mentioned chiral rare earth supramolecular cage complex is used for the detection of chiral amino acids, and the detection method is carried out according to the following steps:

1. Mix the chiral rare earth supramolecular cage complex with a solvent to obtain a solution of the chiral rare earth supramolecular cage complex, and detect the circularly polarized luminescent spectrum of the obtained chiral rare earth supramolecular cage complex solution under light excitation of 375 nm ;

2. Mix the analyte solution with the chiral rare earth supramolecular cage complex solution in step 1, and detect the circularly polarized luminescent spectrum of the resulting mixed solution under light excitation of 375 nm;

3. Compare the circularly polarized luminescence spectrum obtained in step 2 with the circularly polarized luminescence spectrum of the chiral rare earth supramolecular cage complex obtained in step 1, and realize the qualitative change of the chiral amino acid by changing the g _lum value of the circularly polarized luminescence spectrum signal Detection, concentration detection and enantiomeric composition detection;

Principle of the present invention and beneficial effect are:

1. The chiral rare earth supramolecular cage complex of the present invention can realize high selectivity, high sensitivity and high accuracy sensing of chiral amino acids. Chiral rare earth supramolecular cage complexes are used as circularly polarized luminescent probes. After the chiral rare earth supramolecular cage complexes and chiral amino acids are mixed in a solvent, the chiral rare earth supramolecular cage complexes utilize their own chiral environment and facilitate Multiple hydroxyl-OH groups that form a large number of hydrogen bonds interact with chiral amino acids to form asymmetric adducts through a large number of intermolecular hydrogen bonds, which in turn causes the sensor to exhibit an asymmetric factor in the circularly polarized luminescence spectrum The change of the g _lum value signal can realize the qualitative detection, concentration detection and enantiomeric composition detection of the chiral amino acid by detecting the change of the g _lum value of the circularly polarized luminescence spectrum.

2. The chiral rare earth complex of the present invention has a tetrahedral cage structure, the eight-coordinated coordination environment is relatively compact, and has strong structural stability, which provides favorable conditions for the practical application of the sensor. At the same time, when sensing chiral amino acids, the mechanism is to form a large number of hydrogen bonds between the ligand and the amino acid and the electrophilicity of the diketone unit in the ligand to the nitrogen atom on the amino acid to form a synergistic effect on the amino acid. Sensing, so that the rare earth complexes have extremely high sensitivity and accuracy in the sensing of amino acids.

3. The preparation route of the chiral rare earth supramolecular cage complex of the present invention is simple, and the raw materials and synthetic reagents used are cheap and easy to obtain, which solves the problem of high cost of chiral circularly polarized light-emitting sensors. The chiral rare earth supramolecular cage complex of the invention can sense chiral amino acids through a large number of hydrogen bonds, and realizes the chiral recognition process of simulating enzymes in living organisms in nature.

4. The signal of the chiral rare earth supramolecular cage complex of the present invention is changeable, and the signal change is due to the chiral configuration or chiral environment of the chiral compound will change when it is disturbed by the outside world. Polarized luminescence spectrum may appear in the form of signal enhancement, signal weakening, signal inversion or signal shape change. In general, different chiral analytes can only produce two kinds of changes in fluorescence or other detection spectra, such as signal enhancement or quenching, which means that when two chiral analytes can simultaneously enhance fluorescence , and the degree of enhancement is small, the two analytes cannot be distinguished. For the detection technology of circularly polarized luminescence spectroscopy, even if the two chiral analytes can enhance the fluorescence at the same time, and the degree of enhancement is similar, due to the difference in the structure of the chiral analyte, the chirality of the chiral rare earth supramolecular cage will be reduced. Different changes in the environment lead to different changes in the circularly polarized luminescence spectrum signal, thereby realizing the distinction of the object to be measured. When the chiral rare earth supramolecular cage complex of the present invention is used in a detection system containing fluorescent small molecules, especially in living bodies (living bodies contain a large number of fluorescent small molecules), the emission of small fluorescent molecules is usually located in the short wavelength range, while The emission signal of the chiral rare earth supramolecular cage complex of the invention is in the long wavelength region of the emission spectrum, which can effectively avoid the interference of the fluorescence spectrum signal emitted by the small molecule on the detection result. Therefore, the chiral rare earth supramolecular cage complex of the present invention is detected by circularly polarized luminescence spectrum with variable signal and background interference can be eliminated, which has obvious advantages in detection sensitivity compared with the existing fluorescence spectrum detection technology.

Description of drawings

Fig. 1 is the change diagram of the circularly polarized luminescent signal g _lum value of the complex after the tetrahydrofuran solution of the chiral rare earth supramolecular cage complex produced in Example 1 interacts with L-glycine or D-glycine;

Fig. 2 is the tetrahydrofuran solution of the chiral rare earth supramolecular cage complex prepared in Example 1 to the change of the g _lum value of chiral amino acids with different enantiomeric compositions (mixture of L-glycine and D-glycine) and different concentrations picture.

Detailed ways

The technical solution of the present invention is not limited to the specific embodiments listed below, but also includes any reasonable combination among the specific embodiments.

Specific embodiment 1: The structural formula of the chiral rare earth supramolecular cage complex in this embodiment is:

The general structural formula of the chiral rare earth supramolecular cage complex is Ln ₄ L ₄ , which is a chiral rare earth complex composed of a chiral ligand L and a rare earth element, and the structural formula of the chiral ligand L is:

This embodiment has the following beneficial effects:

1. The chiral rare earth supramolecular cage complex of this embodiment can realize high selectivity, high sensitivity and high accuracy sensing of chiral amino acids. Chiral rare earth supramolecular cage complexes are used as circularly polarized luminescent probes. After the chiral rare earth supramolecular cage complexes and chiral amino acids are mixed in a solvent, the chiral rare earth supramolecular cage complexes utilize their own chiral environment and facilitate Multiple hydroxyl-OH groups that form a large number of hydrogen bonds interact with chiral amino acids to form asymmetric adducts through a large number of intermolecular hydrogen bonds, which in turn causes the sensor to exhibit an asymmetric factor in the circularly polarized luminescence spectrum The change of the g _lum value signal can realize the qualitative detection, concentration detection and enantiomeric composition detection of the chiral amino acid by detecting the change of the g _lum value of the circularly polarized luminescence spectrum.

2. The chiral rare earth complex in this embodiment has a tetrahedral cage structure, the eight-coordinated coordination environment is relatively compact, and has strong structural stability, which provides favorable conditions for the practical application of the sensor. At the same time, when sensing chiral amino acids, the mechanism is to form a large number of hydrogen bonds between the ligand and the amino acid and the electrophilicity of the diketone unit in the ligand to the nitrogen atom on the amino acid to form a synergistic effect on the amino acid. Sensing, so that the rare earth complexes have extremely high sensitivity and accuracy in the sensing of amino acids.

3. The signal of the chiral rare earth supramolecular cage complex in this embodiment is variable, and the signal is variable because the chiral configuration or chiral environment of the chiral compound will change when it is disturbed by the outside world. The forms that may appear on the circularly polarized luminescence spectrum include signal enhancement, signal weakening, signal inversion, or signal shape change. In general, different chiral analytes can only produce two kinds of changes in fluorescence or other detection spectra, such as signal enhancement or quenching, which means that when two chiral analytes can simultaneously enhance fluorescence , and the degree of enhancement is small, the two analytes cannot be distinguished. For the detection technology of circularly polarized luminescence spectroscopy, even if the two chiral analytes can enhance the fluorescence at the same time, and the degree of enhancement is similar, due to the difference in the structure of the chiral analyte, the chirality of the chiral rare earth supramolecular cage will be reduced. Different changes in the environment lead to different changes in the circularly polarized luminescence spectrum signal, thereby realizing the distinction of the object to be measured. When the chiral rare earth supramolecular cage complex of this embodiment is used in a detection system containing fluorescent small molecules, especially in living bodies (living bodies contain a large number of fluorescent small molecules), the emission of small fluorescent molecules is usually in the short wavelength range. However, the emission signal of the chiral rare earth supramolecular cage complex in this embodiment is in the long-wavelength region of the emission spectrum, which can effectively avoid the interference of the fluorescence spectrum signal emitted by the small molecule on the detection result. Therefore, the chiral rare earth supramolecular cage complex in this embodiment is detected by circularly polarized luminescence spectrum with variable signal and background interference can be eliminated, which has obvious advantages in detection sensitivity compared with the existing fluorescence spectrum detection technology.

Specific embodiment 2: The difference between this embodiment and specific embodiment 1 is that the R' is R-1,2-propanediol, L-menthol, (S)-(+)-2-phenylglycinol, (1S,2R)-2-amino-1,2-diphenylethanol, D-aminopropanol, etc. R' is a chiral group that is conducive to the formation of hydrogen bonds, and the chain length is relatively short.

Embodiment 3: This embodiment is different from Embodiment 1 or Embodiment 2 in that: the Ln is a lanthanide, and the lanthanide is Eu, Yb, Sm, Gd or Tb.

Specific embodiment four: The preparation method of the chiral rare earth supramolecular cage complex in this embodiment is carried out according to the following steps:

Step 1, the synthesis of 3,3',3"-trimethoxytriphenylamine:

Weigh 1~3g m-aminoanisole and 7~10g 3-iodoanisole and dissolve in 150~250mL toluene, then add 9~12g copper powder, 2~4g 18-crown-6 and 25~35g K ₂ CO ₃ , heated to reflux for 24 hours; use thin-layer chromatography to monitor the reaction process, filter after the reaction is completed, and the obtained filtrate is washed with dilute ammonia water until it is colorless, washed repeatedly with water, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove excess solvent, to obtain a brownish black crude product, and then separated by column chromatography to obtain 3,3',3"-trimethoxytriphenylamine;3,3',3"-trimethoxytriphenylamine is a yellow oily liquid; filtration can remove copper powder, 18-crown-6 and K ₂ CO ₃ ;

Step 2. Synthesis of 3,3',3"-trihydroxy-4,4',4"-triacetyltriphenylamine:

Weigh 3-6g of 3,3',3"-trimethoxytriphenylamine and dissolve it in 60-80mL of dichloromethane to obtain solution A; weigh 10-12g of anhydrous aluminum trichloride and 5-8g of acetyl chloride and add to 10 ~30mL of dichloromethane, stirred until the aluminum chloride is completely dissolved to obtain solution B, under ice bath conditions, add solution B dropwise to solution A, after the reaction is complete, pour the reaction solution into ice water, filter to remove Insoluble matter, the water layer was separated and extracted 3 times with dichloromethane, the dichloromethane extract was combined with the organic layer, and washed with water repeatedly until neutral, dried over anhydrous sodium sulfate, filtered, dichloromethane solvent was evaporated, A crude product was obtained, and the obtained crude product was separated by column chromatography to obtain 3,3',3"-trihydroxy-4,4',4"-triacetyltriphenylamine as a yellow solid powder;

Step 3, Synthesis of 3,3',3"-(2,2-dimethyl-1,3-dioxolane)-4,4',4"-triacetyltriphenylamine:

Weigh 1~3g of 3,3',3"-trihydroxy-4,4',4"-triacetyltriphenylamine and dissolve it in 10~30mL of acetonitrile, then add 11~14g of cesium carbonate, and heat the reaction solution to Keep stirring at 120°C for 0.5 hours; add 8~12g of R-glyceryl acetonide sulfonate and continue to heat and reflux for 36 hours; use thin layer chromatography to monitor the reaction process, filter to remove cesium carbonate after the reaction is completed, and remove acetonitrile by distillation under reduced pressure Solvent, and then purified by column chromatography to obtain 3,3',3"-(2,2-dimethyl-1,3-dioxolane)-4,4',4"-triacetyltriphenylamine, as white solid;

Step 4, synthesis of ligand L:

Weigh 0.2-1.2g of sodium methoxide and 1-6g of ethyl trifluoroacetate and dissolve in 20-40mL of ethylene glycol dimethyl ether, then add 0.5-1.5g of 3,3',3"-(2,2-bis Methyl-1,3-dioxolane)-4,4',4"-triacetyltriphenylamine, stirred at room temperature for 24 hours, after the reaction was completed, adjusted the pH to 2-3 with hydrochloric acid, filtered the precipitated A yellow solid precipitated, washed several times with water and dried to obtain Ligand L;

Step 5. Preparation of Rare Earth Supramolecular Cage Complex Ln ₄ L ₄ :

Weigh 0.2-1.2g ligand L and add it to 30-50mL methanol, add 0.1-0.6g triethylamine, stir well until ligand L dissolves, then add 0.2-0.6mmol rare earth chloride LnCl ₃ 6H ₂ O, After the dropwise addition, the reaction was carried out at room temperature for 24 hours. After the reaction was completed, the reaction solution was poured into water to precipitate a yellow precipitate, which was filtered and dried to obtain the complex.

1. The chiral rare earth supramolecular cage complex prepared in this embodiment can realize high selectivity, high sensitivity and high accuracy sensing of chiral amino acids. Chiral rare earth supramolecular cage complexes are used as circularly polarized luminescent probes. After the chiral rare earth supramolecular cage complexes and chiral amino acids are mixed in a solvent, the chiral rare earth supramolecular cage complexes utilize their own chiral environment and facilitate Multiple hydroxyl-OH groups that form a large number of hydrogen bonds interact with chiral amino acids to form asymmetric adducts through a large number of intermolecular hydrogen bonds, which in turn causes the sensor to exhibit an asymmetric factor in the circularly polarized luminescence spectrum The change of the g _lum value signal can realize the qualitative detection, concentration detection and enantiomeric composition detection of the chiral amino acid by detecting the change of the g _lum value of the circularly polarized luminescence spectrum.

2. The chiral rare earth complex prepared in this embodiment has a tetrahedral cage structure, and the eight-coordinated coordination environment is relatively compact and has strong structural stability, which provides favorable conditions for the practical application of the sensor. At the same time, when sensing chiral amino acids, the mechanism is to form a large number of hydrogen bonds between the ligand and the amino acid and the electrophilicity of the diketone unit in the ligand to the nitrogen atom on the amino acid to form a synergistic effect on the amino acid. Sensing, so that the rare earth complexes have extremely high sensitivity and accuracy in the sensing of amino acids.

3. The preparation route of the chiral rare earth supramolecular cage complex described in this embodiment is simple, and the raw materials and synthetic reagents used are cheap and easy to obtain, which solves the problem of high cost of chiral circularly polarized light-emitting sensors. The chiral rare earth supramolecular cage complex described in this embodiment can sense chiral amino acids through a large number of hydrogen bonds, and realizes the chiral recognition process that simulates enzymes in living organisms in nature.

4. The signal of the chiral rare earth supramolecular cage complex prepared in this embodiment is variable, and the signal is variable because the chiral configuration or chiral environment of the chiral compound will change when it is disturbed by the outside world. Corresponding forms of circularly polarized luminescence spectrum may show signal enhancement, signal weakening, signal inversion or signal shape change. In general, different chiral analytes can only produce two kinds of changes in fluorescence or other detection spectra, such as signal enhancement or quenching, which means that when two chiral analytes can simultaneously enhance fluorescence , and the degree of enhancement is small, the two analytes cannot be distinguished. For the detection technology of circularly polarized luminescence spectroscopy, even if the two chiral analytes can enhance the fluorescence at the same time, and the degree of enhancement is similar, due to the difference in the structure of the chiral analyte, the chirality of the chiral rare earth supramolecular cage will be reduced. Different changes in the environment lead to different changes in the circularly polarized luminescence spectrum signal, thereby realizing the distinction of the object to be measured. When the chiral rare earth supramolecular cage complex of this embodiment is used in a detection system containing fluorescent small molecules, especially in living bodies (living bodies contain a large number of fluorescent small molecules), the emission of small fluorescent molecules is usually in the short wavelength range. However, the emission signal of the chiral rare earth supramolecular cage complex in this embodiment is in the long-wavelength region of the emission spectrum, which can effectively avoid the interference of the fluorescence spectrum signal emitted by the small molecule on the detection result. Therefore, the chiral rare earth supramolecular cage complex in this embodiment is detected by circularly polarized luminescence spectrum with variable signal and background interference can be eliminated, which has obvious advantages in detection sensitivity compared with the existing fluorescence spectrum detection technology.

Embodiment 5: This embodiment is different from Embodiment 4 in that: Ln in Step 5 is Eu, Yb, Sm, Gd or Tb.

Embodiment 6: In this embodiment, the chiral rare earth supramolecular cage complex is used for the detection of chiral amino acids.

Embodiment 7: The difference between this embodiment and Embodiment 6 is that the method of using chiral rare earth supramolecular cage complexes for the detection of chiral amino acids is carried out according to the following steps:

1. Mix the chiral rare earth supramolecular cage complex with a solvent to obtain a solution of the chiral rare earth supramolecular cage complex, and detect the circularly polarized luminescent spectrum of the obtained chiral rare earth supramolecular cage complex solution under light excitation of 375 nm ;

2. Mix the analyte solution with the chiral rare earth supramolecular cage complex solution in step 1, and detect the circularly polarized luminescent spectrum of the resulting mixed solution under light excitation of 375 nm;

The analyte is a chiral amino acid; for example, one or more of L-glycine, D-glycine, L-alanine, and D-alanine;

3. Compare the circularly polarized luminescence spectrum obtained in step 2 with the circularly polarized luminescence spectrum of the chiral rare earth supramolecular cage complex obtained in step 1, and realize the qualitative change of the chiral amino acid by changing the g _lum value of the circularly polarized luminescence spectrum signal detection, concentration detection and enantiomeric composition detection.

1. The chiral rare earth supramolecular cage complex of this embodiment can realize high selectivity, high sensitivity and high accuracy sensing of chiral amino acids. Chiral rare earth supramolecular cage complexes are used as circularly polarized luminescent probes. After the chiral rare earth supramolecular cage complexes and chiral amino acids are mixed in a solvent, the chiral rare earth supramolecular cage complexes utilize their own chiral environment and facilitate Multiple hydroxyl-OH groups that form a large number of hydrogen bonds interact with chiral amino acids to form asymmetric adducts through a large number of intermolecular hydrogen bonds, which in turn causes the sensor to exhibit an asymmetric factor in the circularly polarized luminescence spectrum The change of the g _lum value signal can realize the qualitative detection, concentration detection and enantiomeric composition detection of the chiral amino acid by detecting the change of the g _lum value of the circularly polarized luminescence spectrum.

2. The chiral rare earth complex in this embodiment has a tetrahedral cage structure, the eight-coordinated coordination environment is relatively compact, and has strong structural stability, which provides favorable conditions for the practical application of the sensor. At the same time, when sensing chiral amino acids, the mechanism is to form a large number of hydrogen bonds between the ligand and the amino acid and the electrophilicity of the diketone unit in the ligand to the nitrogen atom on the amino acid to form a synergistic effect on the amino acid. Sensing, so that the rare earth complexes have extremely high sensitivity and accuracy in the sensing of amino acids.

3. The signal of the chiral rare earth supramolecular cage complex in this embodiment is variable, and the signal is variable because the chiral configuration or chiral environment of the chiral compound will change when it is disturbed by the outside world. The forms that may appear on the circularly polarized luminescence spectrum include signal enhancement, signal weakening, signal inversion, or signal shape change. In general, different chiral analytes can only produce two kinds of changes in fluorescence or other detection spectra, such as signal enhancement or quenching, which means that when two chiral analytes can simultaneously enhance fluorescence , and the degree of enhancement is small, the two analytes cannot be distinguished. For the detection technology of circularly polarized luminescence spectroscopy, even if the two chiral analytes can enhance the fluorescence at the same time, and the degree of enhancement is similar, due to the difference in the structure of the chiral analyte, the chirality of the chiral rare earth supramolecular cage will be reduced. Different changes in the environment lead to different changes in the circularly polarized luminescence spectrum signal, thereby realizing the distinction of the object to be measured. When the chiral rare earth supramolecular cage complex of this embodiment is used in a detection system containing fluorescent small molecules, especially in living bodies (living bodies contain a large number of fluorescent small molecules), the emission of small fluorescent molecules is usually in the short wavelength range. However, the emission signal of the chiral rare earth supramolecular cage complex in this embodiment is in the long-wavelength region of the emission spectrum, which can effectively avoid the interference of the fluorescence spectrum signal emitted by the small molecule on the detection result. Therefore, the chiral rare earth supramolecular cage complex in this embodiment is detected by circularly polarized luminescence spectrum with variable signal and background interference can be eliminated, which has obvious advantages in detection sensitivity compared with the existing fluorescence spectrum detection technology.

Embodiment 8: The difference between this embodiment and Embodiment 7 is that the solvent described in step 1 and step 2 is tetrahydrofuran, acetonitrile, methanol or ethanol.

Embodiment 9: This embodiment differs from Embodiment 7 in that: the concentration of the chiral rare earth supramolecular cage complex solution in step 1 is 1×10 ^-6 ~1×10 ^-3 M.

Embodiment 10: This embodiment differs from Embodiment 7 in that: the concentration of the analyte solution in step 2 is 1×10 ^-3 ~ 2×10 ^-1 M; the analyte in the analyte solution The molar ratio of the test object to the chiral rare earth supramolecular cage complex is (0.01-10):1.

Example 1

The preparation method _of the chiral rare earth supramolecular cage complex _Ln4L4 in this embodiment is carried out according to the following steps:

Step 1: Synthesis of 3,3',3"-trimethoxytriphenylamine:

Weigh m-aminoanisole (1.85g, 15.00mmol) and 3-iodoanisole (8.07g, 34.50mmol) dissolved in 200mL toluene, copper powder (9.45g, 150.00mmol), 18-crown ether- 6 (2.38g, 0.90mmol) and K ₂ CO ₃ (31.16g, 22.58mmol) were added to the above solution, and heated to reflux for 24 hours; the reaction progress was monitored by thin-layer chromatography, and the catalyst was removed by filtration after the reaction was completed, and the obtained filtrate was sequentially : Washed with dilute ammonia until colorless, washed repeatedly with water, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove excess solvent to obtain a brown-black crude product, which was then separated by column chromatography to obtain 3,3',3"-trimethoxytri Aniline (4.00 g, yield: 80%); 3,3',3"-trimethoxytriphenylamine as a yellow oily liquid.

Step 2: Synthesis of 3,3',3"-trihydroxy-4,4',4"-triacetyltriphenylamine:

Weigh 3,3',3"-trimethoxytriphenylamine (4.00g, 11.90mmol) and dissolve it in 70mL of dichloromethane, then weigh anhydrous aluminum trichloride (11.15g, 83.58mmol) and acetyl chloride (6.56 g, 83.58mmol) was added to 20mL of dichloromethane, stirred until the aluminum chloride was completely dissolved, and the solution was slowly added dropwise to 3,3',3"-trimethoxytriphenylamine di in methyl chloride solution. After the reaction is complete, pour the reaction solution into ice water, filter to remove insoluble matter, separate the water layer and extract it with dichloromethane for 3 times, combine the dichloromethane extract with the organic layer, and wash repeatedly with water until neutral and anhydrous. Drying over sodium sulfate, filtering, and distilling off the dichloromethane solvent to obtain a crude product, the resulting crude product was separated by column chromatography to obtain 3,3',3"-trihydroxy-4,4',4"-triacetyltriphenylamine ( 2.50 g, yield: 85%), as a yellow solid powder.

Step 3: Synthesis of 3,3',3"-(2,2-dimethyl-1,3-dioxolane)-4,4',4"-triacetyltriphenylamine:

Weigh 3,3',3"-trihydroxy-4,4',4"-triacetyltriphenylamine (2.00g, 4.70mmol) and dissolve it in 20mL of acetonitrile, then weigh cesium carbonate (13.90g, 42.90mmol ) was added to the above-mentioned acetonitrile solution, and the reaction solution was heated to 120° C. and kept stirring for 0.5 hours. R-glyceryl acetonide sulfonate (9.00 g, 42.90 mmol) was added to the reaction system and heated to reflux for 36 hours. Use thin-layer chromatography to monitor the reaction process. After the reaction is completed, cesium carbonate is removed by filtration, and the acetonitrile solvent is removed by distillation under reduced pressure, and then purified by column chromatography to obtain 3,3',3"-(2,2-dimethyl-1,3- Dioxolane)-4,4',4"-triacetyltriphenylamine (1.00 g, yield: 78%), as a white solid.

Step 4: Synthesis of Ligand L:

Weigh sodium methoxide (0.57g, 10.63mmol) and ethyl trifluoroacetate (1.49g, 10.63mmol) and dissolve in 30mL DME (ethylene glycol dimethyl ether), then add 3,3',3"-(2, 2-Dimethyl-1,3-dioxolane)-4,4',4"-triacetyltriphenylamine (0.9g, 1.18mmol), stirred at room temperature for 24 hours, after the reaction was completed, washed with hydrochloric acid Adjust the pH to 2-3, filter the precipitated yellow solid, wash with water several times and dry to obtain Ligand L (0.91 g, yield: 85%).

Step 5: Preparation of Rare Earth Supramolecular Cage Complex Ln ₄ L ₄ :

Weigh ligand L (0.30g, 0.31mmol) and add it to 40mL methanol, add triethylamine (0.13g, 1.30mmol), stir well until ligand L dissolves, add rare earth chloride EuCl ₃ 6H ₂ O (0.31 mmol); after the dropwise addition, react at room temperature for 24 hours. After the reaction is completed, the reaction solution is poured into water to precipitate a yellow precipitate, which is filtered and dried to obtain the target complex.

Eu ₄ L ₄ was characterized by X-ray single crystal diffraction, and the specific results are shown in Table 1; the data in Table 1 shows that the target product Eu ₄ L ₄ was obtained in this example.

Table 1. Crystallographic parameters of Eu ₄ L ₄

Interaction of the chiral rare earth supramolecular cage complex prepared in Example 1 with L-glycine or D-glycine in THF solution. The concentration of the chiral rare earth supramolecular cage complex is 1×10 ^-4 mol/L, the concentrations of L-glycine and D-glycine are respectively 0.16mol/L, and the asymmetry factor g of the chiral rare earth supramolecular cage complex is detected The change of _lum value, the result is shown in Figure 1. It can be seen from FIG. 1 that the maximum value of the asymmetry factor of the chiral rare earth supramolecular cage complex in Example 1 is located at 591 nm. In Figure 1, it can be seen that analytes with different chiral configurations are gradually added to the chiral rare earth supramolecular cage complexes, and the two chiral analytes cause different signals of the chiral rare earth supramolecular cage complexes. The (S,S)-analyte enhanced the signal of the chiral rare earth supramolecular cage complex, while the (R,R)-analyte reversed the signal of the chiral rare earth supramolecular cage complex, After the signal is inverted, continue to increase the amount of the DUT, and the signal after the inversion will also show a small signal enhancement. Therefore, the chiral configuration of the unknown analyte can be judged by the different forms and degrees of changes in the circularly polarized luminescent spectrum signals of the chiral rare earth supramolecular cage complexes produced by the analyte with two chiral configurations.

Fig. 2 is the concentration of the analyte (mixture of L-glycine and D-glycine) with different enantiomeric compositions of the chiral rare earth supramolecular cage complex measured in THF solution and the chiral rare earth supramolecular The graph of the relationship between the g _lum values of the circularly polarized luminescence signals of the cage complexes. The percentage in Figure 2 represents the enantiomeric excess ratio of the same amino acid with two different configurations mixed. A positive number represents a large amount of L-configuration amino acid content, and a negative number represents a large amount of D-configuration amino acid content. 0% means that the amino acids in each configuration account for 50%, canceling each other out. Figure 2 shows the changes in the circularly polarized luminescence spectrum signal of the chiral rare earth supramolecular cage complex after two identical amino acids with different configurations are mixed in different proportions. In fact, the same chiral substance in two configurations will form a racemate after mixing in equal proportions, which means that the opposite chirality of the two configurations is canceled, and there will be no difference in the circularly polarized luminescence spectrum. Any signal is consistent with the performance of non-chiral substances on the circularly polarized luminescence spectrum. In the present invention, after two same amino acids with different configurations are mixed in different proportions, except for the case where equal amounts are mixed to form a racemate, the remaining cases are called enantiomeric excess, that is to say, a certain amino acid in the mixture A chiral species has a higher content than another chiral species. The analytes with different enantiomeric excess ratios produce different changes in the circularly polarized luminescent spectrum signal of the chiral rare earth supramolecular cage complex.

Claims (8)

1. A chiral rare earth supramolecular cage complex, characterized in that: the structural formula of the chiral rare earth supramolecular cage complex is:

The general structural formula of the chiral rare earth supramolecular cage complex is Ln ₄ L ₄ , which is a chiral rare earth complex composed of a chiral ligand L and a rare earth element, and the structural formula of the chiral ligand L is:

In the structural formula, R' is R-1,2-dihydroxypropan-3-yl; The Ln is Eu. 2. the preparation method of chiral rare earth supramolecular cage complex as claimed in claim 1 is characterized in that: the preparation method of chiral rare earth supramolecular cage complex is carried out according to the following steps: Step 1, the synthesis of 3,3',3"-trimethoxytriphenylamine: Weigh 1~3g m-aminoanisole and 7~10g 3-iodoanisole and dissolve in 150~250mL toluene, then add 9~12g copper powder, 2~4g 18-crown-6 and 25~35g K ₂ CO ₃ , heated to reflux for 24 hours; use thin-layer chromatography to monitor the reaction process, filter after the reaction is completed, and the obtained filtrate is washed with dilute ammonia water until it is colorless, washed repeatedly with water, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove excess Solvent to obtain a brown-black crude product, and then separated by column chromatography to obtain 3,3',3"-trimethoxytriphenylamine;3,3',3"-trimethoxytriphenylamine is a yellow oily liquid; Step 2. Synthesis of 3,3',3"-trihydroxy-4,4',4"-triacetyltriphenylamine: Weigh 3-6g of 3,3',3"-trimethoxytriphenylamine and dissolve it in 60-80mL of dichloromethane to obtain solution A; weigh 10-12g of anhydrous aluminum trichloride and 5-8g of acetyl chloride and add to 10 ~30mL of dichloromethane, stirred until the aluminum chloride is completely dissolved to obtain solution B, under ice bath conditions, add solution B dropwise to solution A, after the reaction is complete, pour the reaction solution into ice water, filter to remove Insoluble matter, the water layer was separated and extracted 3 times with dichloromethane, the dichloromethane extract was combined with the organic layer, and washed with water repeatedly until neutral, dried over anhydrous sodium sulfate, filtered, dichloromethane solvent was evaporated, A crude product was obtained, and the obtained crude product was separated by column chromatography to obtain 3,3',3"-trihydroxy-4,4',4"-triacetyltriphenylamine as a yellow solid powder; Step 3, 3,3', 3"-tris(2,3-glycerol acetonidyl)-4,4', 4"-triacetyl triphenylamine synthesis: Weigh 1~3g of 3,3',3"-trihydroxy-4,4',4"-triacetyltriphenylamine and dissolve it in 10~30mL of acetonitrile, then add 11~14g of cesium carbonate, and heat the reaction solution to Keep stirring at 120°C for 0.5 hours; add 8~12g of R-glyceryl acetonide sulfonate and continue to heat and reflux for 36 hours; use thin layer chromatography to monitor the reaction process, filter to remove cesium carbonate after the reaction is completed, and remove acetonitrile by distillation under reduced pressure Solvent, and then purified by column chromatography to obtain 3,3′,3″-tris(2,3-glycerolacetonyl)-4,4′,4″-triacetyltriphenylamine as a white solid; Step 4, synthesis of ligand L: Weigh 0.2-1.2g of sodium methoxide and 1-6g of ethyl trifluoroacetate and dissolve in 20-40mL of ethylene glycol dimethyl ether, then add 0.5-1.5g of 3,3′,3″-tris(2,3- Glycerol acetonidyl)-4,4′,4″-triacetyltriphenylamine, stirred and reacted at room temperature for 24 hours, after the reaction was completed, adjusted the pH to 2-3 with hydrochloric acid, filtered the precipitated yellow solid precipitate, washed several times with water After drying, ligand L is obtained; Step 5. Preparation of Rare Earth Supramolecular Cage Complex Ln ₄ L ₄ : Weigh 0.2~1.2g ligand L and add it to 30~50mL methanol, add 0.1~0.6g triethylamine, stir well until ligand L dissolves, then add 0.2~0.6mmol LnCl ₃ 6H ₂ O, dropwise Then react at room temperature for 24 hours. After the reaction is completed, the reaction solution is poured into water to precipitate a yellow precipitate, which is filtered and dried to obtain the complex. 3. The preparation method of the chiral rare earth supramolecular cage complex according to claim 2, characterized in that: the Ln in step 5 is Eu. 4. The application of the chiral rare earth supramolecular cage complex as claimed in claim 1, characterized in that: the chiral rare earth supramolecular cage complex is used for the detection of chiral amino acids for non-disease diagnosis and treatment purposes. 5. application according to claim 4, is characterized in that: utilize chiral rare earth supramolecular cage complex to be used for the method for the detection of chiral amino acid to carry out according to the following steps: 1. Mix the chiral rare earth supramolecular cage complex with a solvent to obtain a solution of the chiral rare earth supramolecular cage complex, and detect the circularly polarized luminescent spectrum of the obtained chiral rare earth supramolecular cage complex solution under light excitation of 375 nm ; 2. Mix the analyte solution with the chiral rare earth supramolecular cage complex solution in step 1, and detect the circularly polarized luminescent spectrum of the resulting mixed solution under light excitation of 375 nm; 3. Compare the circularly polarized luminescence spectrum obtained in step 2 with the circularly polarized luminescence spectrum obtained in step 1, and realize the qualitative detection, concentration detection and enantiomeric composition of chiral amino acids through the change of the g _lum value of the circularly polarized luminescence spectrum signal detection. 6. The application according to claim 5, characterized in that: the solvent in step 1 is tetrahydrofuran, acetonitrile, methanol or ethanol. 7. The application according to claim 5, wherein the concentration of the solution of the chiral rare earth supramolecular cage complex in step 1 is 1×10 ^-6 ~1×10 ^-3 M. 8. The application according to claim 5, characterized in that: the concentration of the analyte solution in step 2 is 1×10 ^-3 ~ 2×10 ^-1 M; the analyte in the analyte solution The molar ratio to the chiral rare earth supramolecular cage complex in the chiral rare earth supramolecular cage complex solution is (0.01˜10):1.

Images