CN115650867B - Chiral rare earth supermolecule cage complex and preparation method and application thereof - Google Patents
Chiral rare earth supermolecule cage complex and preparation method and application thereof Download PDFInfo
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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
Technical Field
The invention belongs to the field of circular polarization luminescence sensors, and particularly relates to a chiral rare earth supermolecule cage complex, a preparation method and application thereof.
Background
Amino acids are important chiral molecules for maintaining human body function, and the precondition for their function in human body is that they carry target amino acids into cell membranes by using a t-RNA of a transfer ribonucleic acid with-OH on its structure as a recognition carrier. Therefore, realizing specific chiral recognition of amino acid has important significance for maintaining human health and exploring the recognition process of natural enzymes.
The metal-organic complex optical sensors for amino acid sensing reported so far are mainly focused on transition metal complex fluorescence sensors. Since the transition metal fluorescence sensor (ruthenium, iridium, platinum, rhenium and the like) does not have luminescence property, the luminescence property of the whole sensor can be regulated and controlled only by chemical modification of a ligand, so that the synthesis of the sensor is complicated, and when the transition metal fluorescence sensor is used for detecting chiral organic molecules of living bodies in an output mode, the fluorescence spectrum signal cannot be used for eliminating the background fluorescence of a system to be detected, so that the selectivity and the detection limit are reduced.
The mechanism of chiral amino acid sensing of the rare earth complex reported at present is mainly divided into the following three types: 1. amino acid molecules replace solvent molecules or ligands coordinated on chiral or achiral rare earth complexes, so that the composition and coordination environment of the rare earth complexes are changed; 2. the amino acid molecules utilize chiral configuration to disturb the coordination environment of the achiral rare earth complex, so that the coordination environment of the rare earth complex is changed; 3. the amino acid molecule forms hydrogen bond with the organic ligand to induce the coordination configuration of the rare earth complex to change. However, the former two sensing modes require that the ligand or coordination solvent molecules of the rare earth complex are easily replaced or the coordination environment is loose and easily influenced by other molecules so as to change, and in order to meet the conditions, the stability of the rare earth complex sensor is poor, which is extremely unfavorable for the practical application of the sensor. In addition, in the third sensing mode, only a small amount of hydrogen bonds are formed for sensing amino acids, and the interaction generated by the small amount of hydrogen bonds is weak, so that the detection sensitivity of the rare earth complex sensor is low.
Disclosure of Invention
The invention provides a chiral rare earth supermolecular cage complex, a preparation method and application thereof, and aims to solve the problems of poor stability and low detection sensitivity of chiral amino acid sensing of the existing rare earth complex.
The chiral rare earth supermolecule cage complex has the structural formula:
the structural general formula of the chiral rare earth supermolecular cage complex is Ln 4 L 4 Chiral rare earth ligand consisting of chiral ligand L and rare earth elementThe structural formula of the chiral ligand L is:
the preparation method of the chiral rare earth supermolecule cage complex comprises the following steps:
step one, synthesis of 3,3' -trimethoxytriphenylamine:
1g to 3g of meta-aminoanisole and 7g to 10g of 3-iodoanisole are weighed and dissolved in 150 mL to 250mL of toluene, and then 9g to 12g of copper powder, 2g to 4g of 18-crown ether-6 and 25 g to 35g K are added 2 CO 3 Heating and refluxing for reaction for 24 hours; monitoring the reaction progress by using thin layer chromatography, filtering after the reaction is finished, sequentially washing the obtained filtrate with dilute ammonia until the filtrate is colorless, repeatedly washing the filtrate with water, drying the filtrate with anhydrous sodium sulfate, removing excessive solvent by reduced pressure distillation to obtain a brown black crude product, and separating the brown black crude product by column chromatography to obtain 3,3' -trimethoxytriphenylamine; 3,3' -trimethoxytriphenylamine is a yellow oily liquid; filtration can remove copper powder, 18-crown-6 and K 2 CO 3 ；
Step two, synthesizing 3,3 '-trihydroxy-4, 4' -triacetyltrianiline:
3-6 g of 3,3' -trimethoxy triphenylamine is weighed and dissolved in 60-80 mL of dichloromethane to obtain solution A; weighing 10-12 g of anhydrous aluminum trichloride and 5-8 g of acetyl chloride, adding into 10-30 mL of dichloromethane, stirring until the aluminum trichloride is completely dissolved to obtain solution B, dropwise adding the solution B into the solution A under the ice bath condition, pouring the reaction solution into ice water after the reaction is complete, filtering to remove insoluble substances, separating a water layer, extracting with dichloromethane for 3 times, combining the dichloromethane extract with an organic layer, repeatedly washing with water to neutrality, drying with anhydrous sodium sulfate, filtering, steaming to remove dichloromethane solvent, obtaining a crude product, and separating the obtained crude product by column chromatography to obtain 3,3 '-trihydroxy-4, 4' -triacetyltrianiline as yellow solid powder;
step three, synthesis of 3,3 '- (2, 2-dimethyl-1, 3-dioxolane) -4,4' -triacetyltrianiline:
1-3 g of 3,3 '-trihydroxy-4, 4' -triacetyltrianiline is weighed and dissolved in 10-30 mL of acetonitrile, then 11-14 g of cesium carbonate is added, and the reaction solution is heated to 120 ℃ and continuously stirred for 0.5 hour; adding 8-12-g R-glycerolacetonide sulfonate and continuously heating and refluxing for 36 hours; monitoring the reaction progress by using thin layer chromatography, filtering to remove cesium carbonate after the reaction is finished, distilling under reduced pressure to remove acetonitrile solvent, and purifying by using column chromatography to obtain 3,3 '- (2, 2-dimethyl-1, 3-dioxolane) -4,4' -triacetyltrianiline as white solid;
step four, synthesizing a ligand L:
weighing 0.2-1.2 g of sodium methoxide and 1-6 g of ethyl trifluoroacetate, dissolving in 20-40 mL of ethylene glycol dimethyl ether, then adding 0.5-1.5 g of 3,3 '- (2, 2-dimethyl-1, 3-dioxolane) -4,4' -triacetyl triphenylamine, stirring at room temperature for reaction for 24 hours, after the reaction is completed, adjusting the pH to 2-3 by hydrochloric acid, filtering out yellow solid precipitate, washing with water for several times, and drying to obtain ligand L;
fifth, preparing rare earth supermolecule cage complex Ln 4 L 4 ：
Weighing 0.2-1.2 g of ligand L, adding the ligand L into 30-50 mL of methanol, adding 0.1-0.6 g of triethylamine, fully stirring until the ligand L is dissolved, and adding 0.2-0.6 mmol of rare earth chloride LnCl 3 ·6H 2 O, after the dripping is finished, reacting for 24 hours at room temperature, pouring the reaction solution into water to separate out yellow precipitate after the reaction is finished, and filtering and drying to obtain a complex;
the chiral rare earth supermolecule cage complex is used for detecting chiral amino acid, and the detection method is carried out according to the following steps:
1. mixing the chiral rare earth supermolecular cage complex with a solvent to obtain a chiral rare earth supermolecular cage complex solution, and detecting the circular polarization luminescence spectrum of the obtained chiral rare earth supermolecular cage complex solution under the excitation of 375nm light;
2. mixing the solution of the object to be detected with the chiral rare earth supermolecular cage complex solution in the first step, and detecting the circular polarization luminescence spectrum of the mixed solution under the excitation of 375nm light;
3. comparing the circular polarized light spectrum obtained in the second step with the circular polarized light spectrum of the chiral rare earth supermolecular cage complex obtained in the step 1, and obtaining a signal g through the circular polarized light spectrum lum The change of the value realizes qualitative detection, concentration detection and enantiomer composition detection of chiral amino acid;
the principle and beneficial effects of the invention are as follows:
1. the chiral rare earth supermolecular cage complex can realize high-selectivity, high-sensitivity and high-accuracy sensing of chiral amino acids. After the chiral rare earth supermolecular cage complex is used as a circularly polarized light-emitting probe and the chiral rare earth supermolecular cage complex and chiral amino acid are mixed in a solvent, the chiral rare earth supermolecular cage complex utilizes the chiral environment of the chiral rare earth supermolecular cage complex and a plurality of hydroxyl-OH groups favorable for forming a large number of hydrogen bonds, and forms an additive substance with asymmetric characteristics with the chiral amino acid through a large number of intermolecular hydrogen bonds, so that the sensor shows an asymmetric factor g on a circularly polarized light-emitting spectrum lum Change of value signal by detecting g of circularly polarized luminescence spectrum lum The qualitative detection, concentration detection and enantiomer composition detection of chiral amino acid can be realized through the value change.
2. The chiral rare earth complex has a tetrahedral cage structure, the eight-coordination environment is compact, and the chiral rare earth complex has strong structural stability, so that favorable conditions are provided for the practical application of the sensor. Meanwhile, when the chiral amino acid is sensed, the mechanism is that a large amount of hydrogen bonds are formed between ligands and the amino acid, and the synergistic effect is formed by the electrophilicity of diketone units in the ligands to nitrogen atoms on the amino acid, so that the sensing of the amino acid by the rare earth complex is realized, and the sensing of the amino acid by the rare earth complex has extremely high sensitivity and accuracy.
3. The chiral rare earth supermolecular cage complex has simple preparation route, low cost and easy acquisition of raw materials and synthetic reagents, and solves the problem of higher cost of chiral circular polarization luminescence sensors. The chiral rare earth supermolecular cage complex can sense chiral amino acid through a large number of hydrogen bonds, and realizes the chiral recognition process of simulating enzymes in a natural life body.
4. The chiral rare earth supermolecular cage complex has changeable signals, wherein the changeable signals are caused by the change of chiral configuration or chiral environment of chiral compounds when the chiral compounds are interfered by the outside, and the change may show the forms of signal enhancement, signal weakening, signal inversion or signal shape change on corresponding circular polarization luminescence spectrums. In general, two kinds of changes such as signal enhancement or quenching can only be generated on fluorescence or other detection spectrums by different chiral objects to be detected, which means that when two kinds of chiral objects to be detected can enhance fluorescence at the same time and the enhancement degree is smaller, the two kinds of objects to be detected cannot be distinguished. For the circular polarization luminescence spectrum detection technology, even if two chiral objects to be detected can enhance fluorescence at the same time, and the enhancement degree is similar, due to the difference of structures of the chiral objects to be detected, different changes are generated to chiral environments of chiral rare earth supermolecule cages, so that circular polarization luminescence spectrum signals are caused to show different change forms, and the objects to be detected are distinguished. When the chiral rare earth supermolecular cage complex is used in a detection system containing fluorescent small molecules, especially in a living body (the living body contains a large number of fluorescent small molecules), the emission of the fluorescent small molecules is usually in a short wavelength range, and the emission signal of the chiral rare earth supermolecular cage complex is in a long wavelength region of an emission spectrum, so that the interference of the fluorescent spectrum signal emitted by the small molecules on a detection result can be effectively avoided. Therefore, 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.
Drawings
FIG. 1 is a circularly polarized luminescence signal g of the chiral rare earth supermolecular cage complex prepared in example 1 after interaction between tetrahydrofuran solution and L-glycine or D-glycine lum A graph of change in value;
FIG. 2 shows the preparation of chiral rare earth supermolecular cage complex of example 1 in tetrahydrofuran solution pair with different enantiomer compositions (L-glycerolMixtures of amino acids and D-glycine) and g of chiral amino acids of different concentrations lum Value change graph.
Detailed Description
The technical scheme of the invention is not limited to the specific embodiments listed below, and also comprises any reasonable combination of the specific embodiments.
The first embodiment is as follows: the chiral rare earth supermolecule cage complex of the embodiment has the structural formula:
the structural general formula of the chiral rare earth supermolecular cage complex is Ln 4 L 4 The chiral rare earth complex is composed of a chiral ligand L and rare earth elements, wherein the chiral ligand L has the structural formula:
the present embodiment has the following advantageous effects:
1. the chiral rare earth supermolecular cage complex can realize high-selectivity, high-sensitivity and high-accuracy sensing of chiral amino acids. After the chiral rare earth supermolecular cage complex is used as a circularly polarized light-emitting probe and the chiral rare earth supermolecular cage complex and chiral amino acid are mixed in a solvent, the chiral rare earth supermolecular cage complex utilizes the chiral environment of the chiral rare earth supermolecular cage complex and a plurality of hydroxyl-OH groups favorable for forming a large number of hydrogen bonds, and forms an additive substance with asymmetric characteristics with the chiral amino acid through a large number of intermolecular hydrogen bonds, so that the sensor shows an asymmetric factor g on a circularly polarized light-emitting spectrum lum Change of value signal by detecting g of circularly polarized luminescence spectrum lum The qualitative detection, concentration detection and enantiomer composition detection of chiral amino acid can be realized through the value change.
2. The chiral rare earth complex of the embodiment has a tetrahedral cage structure, the eight-coordination environment is compact, and the chiral rare earth complex has strong structural stability, so that favorable conditions are provided for the practical application of the sensor. Meanwhile, when the chiral amino acid is sensed, the mechanism is that a large amount of hydrogen bonds are formed between ligands and the amino acid, and the synergistic effect is formed by the electrophilicity of diketone units in the ligands to nitrogen atoms on the amino acid, so that the sensing of the amino acid by the rare earth complex is realized, and the sensing of the amino acid by the rare earth complex has extremely high sensitivity and accuracy.
3. The chiral rare earth supermolecular cage complex in the embodiment has changeable signals, wherein the changeable signals are caused by the change of chiral configuration or chiral environment of the chiral compound when the chiral compound is interfered by the outside, and the change may show the forms of signal enhancement, signal weakening, signal inversion or signal shape change on the corresponding circular polarization luminescence spectrum. In general, two kinds of changes such as signal enhancement or quenching can only be generated on fluorescence or other detection spectrums by different chiral objects to be detected, which means that when two kinds of chiral objects to be detected can enhance fluorescence at the same time and the enhancement degree is smaller, the two kinds of objects to be detected cannot be distinguished. For the circular polarization luminescence spectrum detection technology, even if two chiral objects to be detected can enhance fluorescence at the same time, and the enhancement degree is similar, due to the difference of structures of the chiral objects to be detected, different changes are generated to chiral environments of chiral rare earth supermolecule cages, so that circular polarization luminescence spectrum signals are caused to show different change forms, and the objects to be detected are distinguished. When the chiral rare earth supermolecular cage complex is used in a detection system containing fluorescent small molecules, especially in a living body (the living body contains a large number of fluorescent small molecules), the emission of the fluorescent small molecules is usually in a short wavelength range, and the emission signal of the chiral rare earth supermolecular cage complex in the embodiment is in a long wavelength region of an emission spectrum, so that the interference of the fluorescent spectrum signal emitted by the small molecules on a detection result can be effectively avoided. Therefore, the chiral rare earth supermolecular cage complex of the embodiment utilizes a circular polarization luminescence spectrum with changeable signals and capability of eliminating background interference for detection, and has more obvious advantages in detection sensitivity than the existing fluorescence spectrum detection technology.
The second embodiment is as follows: the first difference between this embodiment and the specific embodiment is that: 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 facilitates hydrogen bonding and has a relatively short chain length.
And a third specific embodiment: this embodiment differs from the first or second embodiment in that: the Ln is a lanthanide, and the lanthanide is Eu, yb, sm, gd or Tb.
The specific embodiment IV is as follows: the preparation method of the chiral rare earth supermolecular cage complex in the embodiment is carried out according to the following steps:
step one, synthesis of 3,3' -trimethoxytriphenylamine:
1g to 3g of meta-aminoanisole and 7g to 10g of 3-iodoanisole are weighed and dissolved in 150 mL to 250mL of toluene, and then 9g to 12g of copper powder, 2g to 4g of 18-crown ether-6 and 25 g to 35g K are added 2 CO 3 Heating and refluxing for reaction for 24 hours; monitoring the reaction progress by using thin layer chromatography, filtering after the reaction is finished, sequentially washing the obtained filtrate with dilute ammonia until the filtrate is colorless, repeatedly washing the filtrate with water, drying the filtrate with anhydrous sodium sulfate, removing excessive solvent by reduced pressure distillation to obtain a brown black crude product, and separating the brown black crude product by column chromatography to obtain 3,3' -trimethoxytriphenylamine; 3,3' -trimethoxytriphenylamine is a yellow oily liquid; filtration can remove copper powder, 18-crown-6 and K 2 CO 3 ；
Step two, synthesizing 3,3 '-trihydroxy-4, 4' -triacetyltrianiline:
3-6 g of 3,3' -trimethoxy triphenylamine is weighed and dissolved in 60-80 mL of dichloromethane to obtain solution A; weighing 10-12 g of anhydrous aluminum trichloride and 5-8 g of acetyl chloride, adding into 10-30 mL of dichloromethane, stirring until the aluminum trichloride is completely dissolved to obtain solution B, dropwise adding the solution B into the solution A under the ice bath condition, pouring the reaction solution into ice water after the reaction is complete, filtering to remove insoluble substances, separating a water layer, extracting with dichloromethane for 3 times, combining the dichloromethane extract with an organic layer, repeatedly washing with water to neutrality, drying with anhydrous sodium sulfate, filtering, steaming to remove dichloromethane solvent, obtaining a crude product, and separating the obtained crude product by column chromatography to obtain 3,3 '-trihydroxy-4, 4' -triacetyltrianiline as yellow solid powder;
step three, synthesis of 3,3 '- (2, 2-dimethyl-1, 3-dioxolane) -4,4' -triacetyltrianiline:
1-3 g of 3,3 '-trihydroxy-4, 4' -triacetyltrianiline is weighed and dissolved in 10-30 mL of acetonitrile, then 11-14 g of cesium carbonate is added, and the reaction solution is heated to 120 ℃ and continuously stirred for 0.5 hour; adding 8-12-g R-glycerolacetonide sulfonate and continuously heating and refluxing for 36 hours; monitoring the reaction progress by using thin layer chromatography, filtering to remove cesium carbonate after the reaction is finished, distilling under reduced pressure to remove acetonitrile solvent, and purifying by using column chromatography to obtain 3,3 '- (2, 2-dimethyl-1, 3-dioxolane) -4,4' -triacetyltrianiline as white solid;
step four, synthesizing a ligand L:
weighing 0.2-1.2 g of sodium methoxide and 1-6 g of ethyl trifluoroacetate, dissolving in 20-40 mL of ethylene glycol dimethyl ether, then adding 0.5-1.5 g of 3,3 '- (2, 2-dimethyl-1, 3-dioxolane) -4,4' -triacetyl triphenylamine, stirring at room temperature for reaction for 24 hours, after the reaction is completed, adjusting the pH to 2-3 by hydrochloric acid, filtering out yellow solid precipitate, washing with water for several times, and drying to obtain ligand L;
fifth, preparing rare earth supermolecule cage complex Ln 4 L 4 ：
Weighing 0.2-1.2 g of ligand L, adding the ligand L into 30-50 mL of methanol, adding 0.1-0.6 g of triethylamine, fully stirring until the ligand L is dissolved, and adding 0.2-0.6 mmol of rare earth chloride LnCl 3 ·6H 2 O, after the dripping is finished, reacting for 24 hours at room temperature, pouring the reaction liquid into water to separate out yellow precipitate after the reaction is finished, and filtering and drying to obtain the complex.
1. The chiral rare earth supermolecular cage complex prepared by the embodiment can realize high-selectivity, high-sensitivity and high-accuracy sensing of chiral amino acid. Chiral rare earth supermolecular cage complex is used as circular polarized light emitting probe, and after chiral rare earth supermolecular cage complex and chiral amino acid are mixed in solvent, the chiral rare earth supermolecular cage complex utilizes its own chiral environmentMultiple hydroxyl-OH groups favorable for forming a large number of hydrogen bonds, and chiral amino acid form an addition object with asymmetric characteristics through a large number of intermolecular hydrogen bonds, so that the sensor shows an asymmetric factor g on a circular polarized luminescence spectrum lum Change of value signal by detecting g of circularly polarized luminescence spectrum lum The qualitative detection, concentration detection and enantiomer composition detection of chiral amino acid can be realized through the value change.
2. The chiral rare earth complex prepared by the embodiment has a tetrahedral cage structure, the eight-coordination environment is compact, and the chiral rare earth complex has strong structural stability, so that favorable conditions are provided for the practical application of the sensor. Meanwhile, when the chiral amino acid is sensed, the mechanism is that a large amount of hydrogen bonds are formed between ligands and the amino acid, and the synergistic effect is formed by the electrophilicity of diketone units in the ligands to nitrogen atoms on the amino acid, so that the sensing of the amino acid by the rare earth complex is realized, and the sensing of the amino acid by the rare earth complex has extremely high sensitivity and accuracy.
3. The chiral rare earth supermolecular cage complex of the embodiment has simple preparation route, low price and easy obtainment of raw materials and synthetic reagents, and solves the problem of higher cost of chiral circular polarization luminescence sensors. The chiral rare earth supermolecular cage complex can sense chiral amino acid through a large number of hydrogen bonds, and realizes the chiral recognition process of simulating enzymes in natural life bodies.
4. The chiral rare earth supermolecular cage complex prepared by the embodiment has changeable signals, wherein the changeable signals are caused by the change of chiral configuration or chiral environment of the chiral compound when the chiral compound is interfered by the outside, and the change may show the forms of signal enhancement, signal weakening, signal inversion or signal shape change on the corresponding circular polarization luminescence spectrum. In general, two kinds of changes such as signal enhancement or quenching can only be generated on fluorescence or other detection spectrums by different chiral objects to be detected, which means that when two kinds of chiral objects to be detected can enhance fluorescence at the same time and the enhancement degree is smaller, the two kinds of objects to be detected cannot be distinguished. For the circular polarization luminescence spectrum detection technology, even if two chiral objects to be detected can enhance fluorescence at the same time, and the enhancement degree is similar, due to the difference of structures of the chiral objects to be detected, different changes are generated to chiral environments of chiral rare earth supermolecule cages, so that circular polarization luminescence spectrum signals are caused to show different change forms, and the objects to be detected are distinguished. When the chiral rare earth supermolecular cage complex is used in a detection system containing fluorescent small molecules, especially in a living body (the living body contains a large number of fluorescent small molecules), the emission of the fluorescent small molecules is usually in a short wavelength range, and the emission signal of the chiral rare earth supermolecular cage complex in the embodiment is in a long wavelength region of an emission spectrum, so that the interference of the fluorescent spectrum signal emitted by the small molecules on a detection result can be effectively avoided. Therefore, the chiral rare earth supermolecular cage complex of the embodiment utilizes a circular polarization luminescence spectrum with changeable signals and capability of eliminating background interference for detection, and has more obvious advantages in detection sensitivity than the existing fluorescence spectrum detection technology.
Fifth embodiment: the fourth difference between this embodiment and the third embodiment is that: step five, wherein Ln is Eu, yb, sm, gd or Tb.
Specific embodiment six: the chiral rare earth supermolecular cage complex is used for detecting chiral amino acid.
Seventh embodiment: the sixth embodiment differs from the first embodiment in that: the method for detecting chiral amino acid by using the chiral rare earth supermolecular cage complex comprises the following steps:
1. mixing the chiral rare earth supermolecular cage complex with a solvent to obtain a chiral rare earth supermolecular cage complex solution, and detecting the circular polarization luminescence spectrum of the obtained chiral rare earth supermolecular cage complex solution under the excitation of 375nm light;
2. mixing the solution of the object to be detected with the chiral rare earth supermolecular cage complex solution in the first step, and detecting the circular polarization luminescence spectrum of the mixed solution under the excitation of 375nm light;
the object to be detected is chiral amino acid; such as one or more of L-glycine, D-glycine, L-alanine, D-alanine;
3. comparing the circular polarized light spectrum obtained in the second step with the circular polarized light spectrum of the chiral rare earth supermolecular cage complex obtained in the step 1, and obtaining a signal g through the circular polarized light spectrum lum The change of the value realizes qualitative detection, concentration detection and enantiomer composition detection of chiral amino acid.
1. The chiral rare earth supermolecular cage complex can realize high-selectivity, high-sensitivity and high-accuracy sensing of chiral amino acids. After the chiral rare earth supermolecular cage complex is used as a circularly polarized light-emitting probe and the chiral rare earth supermolecular cage complex and chiral amino acid are mixed in a solvent, the chiral rare earth supermolecular cage complex utilizes the chiral environment of the chiral rare earth supermolecular cage complex and a plurality of hydroxyl-OH groups favorable for forming a large number of hydrogen bonds, and forms an additive substance with asymmetric characteristics with the chiral amino acid through a large number of intermolecular hydrogen bonds, so that the sensor shows an asymmetric factor g on a circularly polarized light-emitting spectrum lum Change of value signal by detecting g of circularly polarized luminescence spectrum lum The qualitative detection, concentration detection and enantiomer composition detection of chiral amino acid can be realized through the value change.
2. The chiral rare earth complex of the embodiment has a tetrahedral cage structure, the eight-coordination environment is compact, and the chiral rare earth complex has strong structural stability, so that favorable conditions are provided for the practical application of the sensor. Meanwhile, when the chiral amino acid is sensed, the mechanism is that a large amount of hydrogen bonds are formed between ligands and the amino acid, and the synergistic effect is formed by the electrophilicity of diketone units in the ligands to nitrogen atoms on the amino acid, so that the sensing of the amino acid by the rare earth complex is realized, and the sensing of the amino acid by the rare earth complex has extremely high sensitivity and accuracy.
3. The chiral rare earth supermolecular cage complex in the embodiment has changeable signals, wherein the changeable signals are caused by the change of chiral configuration or chiral environment of the chiral compound when the chiral compound is interfered by the outside, and the change may show the forms of signal enhancement, signal weakening, signal inversion or signal shape change on the corresponding circular polarization luminescence spectrum. In general, two kinds of changes such as signal enhancement or quenching can only be generated on fluorescence or other detection spectrums by different chiral objects to be detected, which means that when two kinds of chiral objects to be detected can enhance fluorescence at the same time and the enhancement degree is smaller, the two kinds of objects to be detected cannot be distinguished. For the circular polarization luminescence spectrum detection technology, even if two chiral objects to be detected can enhance fluorescence at the same time, and the enhancement degree is similar, due to the difference of structures of the chiral objects to be detected, different changes are generated to chiral environments of chiral rare earth supermolecule cages, so that circular polarization luminescence spectrum signals are caused to show different change forms, and the objects to be detected are distinguished. When the chiral rare earth supermolecular cage complex is used in a detection system containing fluorescent small molecules, especially in a living body (the living body contains a large number of fluorescent small molecules), the emission of the fluorescent small molecules is usually in a short wavelength range, and the emission signal of the chiral rare earth supermolecular cage complex in the embodiment is in a long wavelength region of an emission spectrum, so that the interference of the fluorescent spectrum signal emitted by the small molecules on a detection result can be effectively avoided. Therefore, the chiral rare earth supermolecular cage complex of the embodiment utilizes a circular polarization luminescence spectrum with changeable signals and capability of eliminating background interference for detection, and has more obvious advantages in detection sensitivity than the existing fluorescence spectrum detection technology.
Eighth embodiment: the present embodiment is different from the seventh embodiment in that: the solvent in the first step and the second step is tetrahydrofuran, acetonitrile, methanol or ethanol.
Detailed description nine: the present embodiment is different from the seventh embodiment in that: step one the concentration of the solution of the chiral rare earth supermolecular cage complex is 1 multiplied by 10 -6 ～1×10 -3 M。
Detailed description ten: the present embodiment is different from the seventh embodiment in that: step two, the concentration of the solution of the object to be detected is 1 multiplied by 10 -3 ～2×10 -1 M; the molar ratio of the object to be detected in the object solution to be detected to the chiral rare earth supermolecular cage complex is (0.01-10): 1.
Example 1
Chiral of this exampleRare earth supermolecular cage complex Ln 4 L 4 The preparation method of the catalyst comprises the following steps:
step one: synthesis of 3,3',3 "-trimethoxytriphenylamine:
meta-aminoanisole (1.85 g,15.00 mmol) and 3-iodoanisole (8.07 g,34.50 mmol) were weighed into 200mL toluene, and copper powder (9.45 g,150.00 mmol), 18-crown-6 (2.38 g,0.90 mmol) and K were added 2 CO 3 (31.16 g,22.58 mmol) was added to the above solution and heated under reflux for 24 hours; monitoring the reaction progress by thin layer chromatography, filtering to remove the catalyst after the reaction is completed, and sequentially carrying out the following steps of: washing with dilute ammonia water until colorless, repeatedly washing with water, drying with anhydrous sodium sulfate, removing excessive solvent by reduced pressure distillation to obtain brown-black crude product, and separating by column chromatography to obtain 3,3' -trimethoxytriphenylamine (4.00 g, yield: 80%); 3,3' -trimethoxytriphenylamine was a yellow oily liquid.
Step two: synthesis of 3,3',3 "-trihydroxy-4, 4',4" -triacetyltrianiline:
3,3',3 "-trimethoxytriphenylamine (4.00 g,11.90 mmol) was weighed and dissolved in 70mL of dichloromethane, then anhydrous aluminum trichloride (11.15 g,83.58 mmol) and acetyl chloride (6.56 g,83.58 mmol) were weighed and added to 20mL of dichloromethane, stirred until the aluminum trichloride was completely dissolved, and the solution was slowly added dropwise to a dichloromethane solution of 3,3',3" -trimethoxytriphenylamine under ice bath conditions. After the reaction was completed, the reaction solution was poured into ice water, insoluble matters were removed by filtration, an aqueous layer was separated and extracted 3 times with methylene chloride, the methylene chloride extract was combined with the organic layer, and repeatedly washed with water to neutrality, dried over anhydrous sodium sulfate, filtered, and the methylene chloride solvent was distilled off to obtain a crude product, and the obtained crude product was separated by column chromatography to obtain 3,3',3 "-trihydroxy-4, 4',4" -triacetyltrianiline (2.50 g, yield: 85%) as a yellow solid powder.
Step three: synthesis of 3,3',3"- (2, 2-dimethyl-1, 3-dioxolane) -4,4',4" -triacetyltrianiline:
3,3',3 "-trihydroxy-4, 4',4" -triacetyltrianiline (2.00 g,4.70 mmol) was weighed into 20mL acetonitrile, cesium carbonate (13.90 g,42.90 mmol) was then weighed into the acetonitrile solution, and the reaction solution was heated to 120℃and stirred continuously for 0.5 hours. R-glycerolacetonide sulfonate (9.00 g,42.90 mmol) was added to the reaction system and heated under reflux for 36 hours. The progress of the reaction was monitored by thin layer chromatography, cesium carbonate was removed by filtration after completion of the reaction, acetonitrile solvent was distilled off under reduced pressure, and 3,3',3"- (2, 2-dimethyl-1, 3-dioxolane) -4,4',4" -triacetyltrianiline (1.00 g, yield: 78%) was obtained as a white solid by purification by column chromatography.
Step four: synthesis of ligand L:
sodium methoxide (0.57 g,10.63 mmol) and ethyl trifluoroacetate (1.49 g,10.63 mmol) were weighed into 30mL DME (ethylene glycol dimethyl ether), then 3,3 '- (2, 2-dimethyl-1, 3-dioxolane) -4,4' -triacetyltrianiline (0.9 g,1.18 mmol) was added, the reaction was stirred at room temperature for 24 hours, after the reaction was completed, the pH was adjusted to 2-3 with hydrochloric acid, the precipitated yellow solid was filtered, washed with water and dried to obtain ligand L (0.91 g, yield: 85%).
Step five: preparation of rare earth supermolecular cage Complex Ln 4 L 4 ：
Ligand L (0.30 g,0.31 mmol) was weighed into 40mL of methanol, triethylamine (0.13 g,1.30 mmol) was added, stirred thoroughly until ligand L dissolved, rare earth chloride EuCl was added 3 ·6H 2 O (0.31 mmol); and (3) reacting for 24 hours at room temperature after the dripping is finished, pouring the reaction solution into water to separate out yellow precipitate after the reaction is finished, and filtering and drying to obtain the target complex.
For Eu 4 L 4 X-ray single crystal diffraction characterization is carried out, and specific results are shown in table 1; the data in Table 1 show that the present example gives the target product Eu 4 L 4 。
TABLE 1 Eu 4 L 4 Is of the crystallographic parameters of (a)
Interaction of the chiral rare earth supermolecular cage complex prepared in example 1 with L-glycine or D-glycine in THF solution.The concentration of the chiral rare earth supermolecular cage complex is 1 multiplied by 10 -4 The concentrations of mol/L, L-glycine and D-glycine are respectively 0.16mol/L, and the asymmetry factor g of the chiral rare earth supermolecular cage complex is detected lum The result of the change in value is shown in fig. 1. As can be seen from FIG. 1, the maximum value of the asymmetry factor of the chiral rare earth supermolecular cage complex of example 1 is located at 591nm. In fig. 1, it can be seen that the to-be-detected objects with different chiral configurations are gradually added into the chiral rare earth supermolecular cage complex, the two chiral to-be-detected objects enable signals of the chiral rare earth supermolecular cage complex to change differently, (S, S) -to-be-detected objects enable signals of the chiral rare earth supermolecular cage complex to be enhanced, and the (R, R) -to-be-detected objects enable signals of the chiral rare earth supermolecular cage complex to be inverted, after the signals are inverted, the amount of the to-be-detected objects is continuously increased, and small-amplitude signal enhancement can also occur for the inverted signals. Therefore, the chiral configuration of the unknown object to be detected can be judged through different change forms and change degrees generated by the circular polarized light spectrum signals of the chiral rare earth supermolecular cage complex of the object to be detected with two chiral configurations.
FIG. 2 shows the concentration of the test substance (mixture of L-glycine and D-glycine) having different enantiomeric compositions and the circular polarized luminescence signal g of the chiral rare earth supermolecular cage complex of example 1, as measured in THF solution lum A graph of the relationship between values. In FIG. 2, the percentages represent the ratio of enantiomeric excess after mixing two identical amino acids of different configurations, the positive number represents the substantial amount of amino acid in the L configuration and the negative number represents the substantial amount of amino acid in the D configuration. 0% represents 50% of each amino acid configuration, which cancel each other out. FIG. 2 shows the change in the circular polarized luminescence spectrum signal of chiral rare earth supermolecular cage complex after two identical amino acids of different configurations are mixed in different proportions. In fact, the same chiral substance in both configurations forms racemates after being mixed in equal proportions, meaning that the opposite chiralities of the two configurations are counteracted, and no signal is generated on the circular polarized light emission spectrum, which is consistent with the appearance of the substance without chiralities on the circular polarized light emission spectrum. In the present invention, two identical amino acids with different configurations are used inAfter mixing in different proportions, the racemate is formed by removing equal amounts of the mixture, and the remaining conditions are referred to as enantiomeric excess, i.e., the mixture contains a higher amount of one chiral species than another chiral species. The changes generated by the circular polarized luminescence spectrum signals of chiral rare earth supermolecular cage complexes of the objects to be detected with different enantiomeric excess ratios are different.
Claims (8)
1. A chiral rare earth supermolecule cage complex is characterized in that: the chiral rare earth supermolecular cage complex has the structural formula:
the structural general formula of the chiral rare earth supermolecular cage complex is Ln 4 L 4 The chiral rare earth complex is composed of a chiral ligand L and rare earth elements, wherein the chiral ligand L has the structural formula:
r' in the structural formula is R-1, 2-dihydroxypropyl-3-yl;
and Ln is Eu.
2. The method for preparing chiral rare earth supermolecular cage complex according to claim 1, which is characterized in that: the preparation method of the chiral rare earth supermolecular cage complex comprises the following steps:
step one, synthesis of 3,3' -trimethoxytriphenylamine:
1g to 3g of meta-aminoanisole and 7g to 10g of 3-iodoanisole are weighed and dissolved in 150 mL to 250mL of toluene, and then 9g to 12g of copper powder, 2g to 4g of 18-crown ether-6 and 25 g to 35g K are added 2 CO 3 Heating and refluxing for reaction for 24 hours; monitoring the reaction progress by thin layer chromatography, filtering after the reaction is completed, sequentially washing the obtained filtrate with dilute ammonia to colorless, repeatedly washing with water, and anhydrous sulfuric acidDrying sodium, distilling under reduced pressure to remove excessive solvent to obtain brown black crude product, and separating by column chromatography to obtain 3,3' -trimethoxytriphenylamine; 3,3' -trimethoxytriphenylamine is a yellow oily liquid;
step two, synthesizing 3,3 '-trihydroxy-4, 4' -triacetyltrianiline:
3-6 g of 3,3' -trimethoxy triphenylamine is weighed and dissolved in 60-80 mL of dichloromethane to obtain solution A; weighing 10-12 g of anhydrous aluminum trichloride and 5-8 g of acetyl chloride, adding into 10-30 mL of dichloromethane, stirring until the aluminum trichloride is completely dissolved to obtain solution B, dropwise adding the solution B into the solution A under the ice bath condition, pouring the reaction solution into ice water after the reaction is complete, filtering to remove insoluble substances, separating a water layer, extracting with dichloromethane for 3 times, combining the dichloromethane extract with an organic layer, repeatedly washing with water to neutrality, drying with anhydrous sodium sulfate, filtering, steaming to remove dichloromethane solvent, obtaining a crude product, and separating the obtained crude product by column chromatography to obtain 3,3 '-trihydroxy-4, 4' -triacetyltrianiline as yellow solid powder;
step three, synthesis of 3,3',3 "-tris (2, 3-glycerylacetone) -4,4',4" -triacetyltrianiline:
1-3 g of 3,3 '-trihydroxy-4, 4' -triacetyltrianiline is weighed and dissolved in 10-30 mL of acetonitrile, then 11-14 g of cesium carbonate is added, and the reaction solution is heated to 120 ℃ and continuously stirred for 0.5 hour; adding 8-12-g R-glycerolacetonide sulfonate and continuously heating and refluxing for 36 hours; monitoring the reaction progress by using thin layer chromatography, filtering to remove cesium carbonate after the reaction is finished, distilling under reduced pressure to remove acetonitrile solvent, and purifying by using column chromatography to obtain 3,3 '-tris (2, 3-glycerolacetonide) -4,4' -triacetyltrianiline as white solid;
step four, synthesizing a ligand L:
weighing 0.2-1.2 g of sodium methoxide and 1-6 g of ethyl trifluoroacetate, dissolving in 20-40 mL of ethylene glycol dimethyl ether, then adding 0.5-1.5 g of 3,3 '-tris (2, 3-glycerylacetonyl) -4,4' -triacetyltrianiline, stirring at room temperature for reaction for 24 hours, adjusting the pH to 2-3 by using hydrochloric acid after the reaction is completed, filtering out yellow solid precipitate, washing for several times, and drying to obtain ligand L;
fifth, preparing rare earth supermolecule cage complex Ln 4 L 4 ：
Weighing 0.2-1.2 g of ligand L, adding the ligand L into 30-50 mL of methanol, adding 0.1-0.6 g of triethylamine, fully stirring until the ligand L is dissolved, and then adding 0.2-0.6 mmol of LnCl 3 ·6H 2 O, after the dripping is finished, reacting for 24 hours at room temperature, pouring the reaction liquid into water to separate out yellow precipitate after the reaction is finished, and filtering and drying to obtain the complex.
3. The method for preparing chiral rare earth supermolecular cage complex according to claim 2, which is characterized in that: and step five, the Ln is Eu.
4. The use of a chiral rare earth supermolecular cage complex according to claim 1, characterized in that: the chiral rare earth supermolecular cage complex is used for detecting chiral amino acid for diagnosis and treatment of non-diseases.
5. The use according to claim 4, characterized in that: the method for detecting chiral amino acid by using the chiral rare earth supermolecular cage complex comprises the following steps:
1. mixing the chiral rare earth supermolecular cage complex with a solvent to obtain a chiral rare earth supermolecular cage complex solution, and detecting the circular polarization luminescence spectrum of the obtained chiral rare earth supermolecular cage complex solution under the excitation of 375nm light;
2. mixing the solution of the object to be detected with the chiral rare earth supermolecular cage complex solution in the first step, and detecting the circular polarization luminescence spectrum of the mixed solution under the excitation of 375nm light;
3. comparing the circularly polarized light emission spectrum obtained in the second step with the circularly polarized light emission spectrum obtained in the first step, and transmitting a circularly polarized light emission spectrum signal g lum The change of the value realizes qualitative detection, concentration detection and enantiomer composition detection of chiral amino acid.
6. The use according to claim 5, characterized in that: in the first step, the solvent is tetrahydrofuran, acetonitrile, methanol or ethanol.
7. The use according to claim 5, characterized in that: step one the concentration of the solution of the chiral rare earth supermolecular cage complex is 1 multiplied by 10 -6 ～1×10 -3 M。
8. The use according to claim 5, characterized in that: step two, the concentration of the solution of the object to be detected is 1 multiplied by 10 -3 ～2×10 -1 M; the molar ratio of the object to be detected in the object solution to the chiral rare earth supermolecular cage complex in the chiral rare earth supermolecular cage complex solution is (0.01-10): 1.
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