Chiral surface-enhanced raman sensing material, and preparation method and application thereof

Abstract

The application belongs to the technical field of surface enhanced Raman sensing, and particularly relates to a chiral surface enhanced Raman sensing material, a preparation method and application thereof. The preparation method comprises the following steps: performing a coordination reaction on CxPh or a soluble alkali metal salt thereof and a zinc salt in an alcohol solvent under alkaline conditions to obtain a zinc coordination compound CxPhZn; dispersing or dissolving the CxPhZn in water or an alkaline aqueous solution to induce self-assembly of the CxPhZn to form a hydrogel, and obtaining a dry gel after drying the hydrogel, and the structure of the CxPh is as shown in the formula: wherein R is a C6-C12 alkyl group. The material can be used as a non-noble metal chiral SERS substrate and applied to enantiomer recognition of chiral small molecules such as glucose, amino acids and ibuprofen.

Description

Technical Field

[0001] This invention belongs to the field of surface-enhanced Raman sensing technology, specifically relating to a chiral surface-enhanced Raman sensing material, its preparation method, and its application. Background Technology

[0002] The statements herein provide only background information in relation to this invention and do not necessarily constitute prior art.

[0003] Surface-enhanced Raman scattering (SERS) technology can provide highly sensitive molecular vibrational fingerprint information, which has important applications in chemical analysis, biological detection, and drug analysis. Different enantiomers of chiral molecules may have similar physicochemical properties, but their biological activities or toxicities differ significantly. Chiral differentiation can avoid detection errors caused by enantiomer confusion.

[0004] However, reliable chiral differentiation has been difficult to achieve, especially in non-precious metal platforms dominated by chemical enhancement. Signal enhancement sites and enantioselective recognition sites are often difficult to couple in the same controllable structure, resulting in unclear structure-performance relationships. This usually requires the introduction of additional chiral modifiers or complex interface construction steps. It is difficult to balance structural stability, sensitivity, and enantioselectivity. Moreover, it generally relies on precious metal substrates such as gold and silver, which is costly. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the purpose of this invention is to provide a chiral surface-enhanced Raman sensing material, its preparation method, and its application.

[0006] To achieve the above objectives, the present invention is implemented through the following technical solution: In a first aspect, the present invention provides a method for preparing a chiral surface-enhanced Raman sensing material, comprising the following steps: The zinc coordination compound CxPhZn is obtained by coordinating CxPh or its soluble alkali metal salt with zinc salt in an alcohol solvent under alkaline conditions. CxPhZn is dispersed or dissolved in water or an alkaline aqueous solution. The obtained system is subjected to ultrasonic treatment, and after standing and self-assembling, a hydrogel is formed. After the hydrogel is dried, a dry gel is obtained. The structural formula for CxPh is: Wherein, R is a C6-C12 alkyl group.

[0007] Secondly, the present invention provides a chiral surface-enhanced Raman sensing material, which is prepared by the aforementioned preparation method.

[0008] Thirdly, the present invention provides the application of the chiral surface-enhanced Raman sensing material in the enantiomeric recognition of chiral small molecules.

[0009] The beneficial effects achieved by one or more embodiments of the present invention described above are as follows: This chiral surface-enhanced Raman sensing material is composed of chiral organic ligands CxPh and Zn. 2+ Coordination forms coordination building units, and further zinc-coordinated supramolecular dry gel materials are formed through hierarchical self-assembly via non-covalent interactions such as hydrogen bonds. This material can serve as a non-noble metal chiral SERS substrate. The resulting material contains both Zn-based active sites and rigid chiral pores formed by hierarchical self-assembly, and can be applied to the enantiomeric recognition and detection of chiral small molecules such as glucose, amino acids, and ibuprofen.

[0010] The chiral surface-enhanced Raman sensing material prepared by this invention forms a non-noble metal SERS platform, reducing the dependence on noble metal substrates. At the same time, it couples chiral recognition and signal enhancement into the same coordination-self-assembly system without the need for additional chiral modifiers or complex interface construction steps. Attached Figure Description

[0011] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0012] Figure 1 This is a photograph of the gel sample formed from the compound C8PhZn prepared in Example 1; Figure 2 These are transmission electron microscope (TEM) images (A) and scanning electron microscope (SEM) images (B) of the C8PhZn dry gel prepared in Example 1. Figure 3 The Fourier transform infrared (FTIR) spectra of the C8PhZn powder and C8PhZn dry gel prepared in Example 1 are shown. Figure 4 These are comparison images of the Raman spectra of C8PhZn materials before and after self-assembly prepared in Example 1; Figure 5 This is a comparison of the recognition performance of the C8PhZn material prepared in Example 1 for L / D-glucose enantiomers before and after self-assembly. Figure 6 This is a comparison of the recognition performance of the C8PhZn material prepared in Example 1 for L / D-proline enantiomers before and after self-assembly. Figure 7 It is the enantioselective SERS differentiation of L / D-histidine in C8PhZn before and after hierarchical self-assembly; Figure 8 This study focuses on the spectral differentiation and quantitative enantioselectivity analysis of R / S-ibuprofen before and after self-assembly. Detailed Implementation

[0013] It should be noted that the following detailed description is illustrative and intended to provide further explanation of the invention. Unless otherwise specified, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0014] To address the technical problems mentioned in the background art, the present invention provides a method for preparing a chiral surface-enhanced Raman sensing material, comprising the following steps: The zinc coordination compound CxPhZn is obtained by coordinating CxPh or its soluble alkali metal salt with zinc salt in an alcohol solvent under alkaline conditions. CxPhZn is dispersed or dissolved in water or an alkaline aqueous solution, the obtained system is subjected to ultrasonic treatment, and allowed to stand and self-assemble to form a hydrogel. After the hydrogel is dried, a dry gel is obtained. The structural formula for CxPh is: Wherein, R is a C6-C12 alkyl group.

[0015] Taking the representative ligand C8Ph as an example, the inventors discovered through experiments that it is difficult for it to form a stable hydrogel on its own; when combined with Zn... 2+ After coordination, a stable gel network is formed. Zn 2+ Coordination can significantly enhance self-assembly capabilities, enabling the system to form a stable, thermally reversible hydrogel network.

[0016] In the preparation of the hydrogel, ultrasonic treatment was employed. The high-frequency mechanical vibration of ultrasound promoted the uniform dispersion and dissolution of CxPhZn molecules in water, while the cavitation effect broke up the initial aggregation between molecules, providing a uniform reaction environment for subsequent self-assembly. In addition, ultrasonic energy could help open weak intermolecular interactions (such as van der Waals forces), promote the exposure of active sites of CxPhZn molecules, and accelerate the initiation of the self-assembly process.

[0017] Standing is a crucial step in hydrogel formation, providing a stable self-assembly environment for CxPhZn molecules. During standing, molecules gradually arrange themselves in an orderly manner through non-covalent interactions such as hydrogen bonds, hydrophobic interactions, and π-π stacking interactions, forming a three-dimensional network structure.

[0018] The chirality of the dry gel originates from the molecular structure of the chiral ligand CxPh, which contains a chiral center (S configuration) in its interaction with Zn. 2+After coordination to form CxPhZn, chirality is retained in the supramolecular assembly through coordination bonds and non-covalent interactions (such as hydrogen bonds and π-π stacking), ultimately forming a three-dimensional network structure with a chiral microenvironment in the dry gel.

[0019] During the drying process of the hydrogel, water evaporation further enhances intermolecular interactions, forming rigid chiral pores with a relatively stable structure. These chiral pores selectively confine the size and chirality of the analyte molecules. Enantiomers with chiral matches to the pores can enter the pores more stably, enhancing adsorption through steric hindrance and multi-point interactions, thus increasing the SERS signal intensity. Conversely, mismatched enantiomers are difficult to bind stably due to steric repulsion, resulting in a significant decrease in the SERS signal intensity.

[0020] Zn in dry gel 2+ Not only a coordination center, but also a core site for SERS chemical enhancement, Zn 2+ It can form coordination bonds with the analyte molecule, bringing the molecule closer to the substrate and promoting charge transfer. Zn 2+ The d orbitals of the molecule form energy level coupling with the π orbitals of the analyte, increasing the size of the Raman scattering cross section and enhancing the SERS signal. Rigid chiral pores and Zn 2+ Active sites synergistically enhance the sensitivity and selectivity of enantiomer recognition.

[0021] CxPhZn forms a hierarchical fiber network structure through self-assembly. After drying, it retains a high specific surface area and abundant active sites, which increases the contact area with the target molecules and improves the adsorption efficiency.

[0022] In some embodiments, the ( S The preparation method of 2-amino-3-(4-alkoxyphenyl)propionic acid CxPh is as follows: N -tert-Butyloxycarbonyl- L - A mixture of tyrosine methyl ester, haloalkanes, and potassium carbonate is subjected to an alkylation reaction in a rare gas atmosphere to produce... N -tert-Butyloxycarbonyl- O -alkyl- L -Tyrosine methyl ester; Will N -tert-Butyloxycarbonyl- O -alkyl- L -Tyrosine methyl ester was removed using trifluoroacetic acid. N -tert-butylcarbonyl protecting group, yielding O -alkyl- L -Tyrosine methyl ester; Will O -alkyl- L -Tyrosine methyl ester is obtained by hydrolysis ( S)-2-amino-3-(4-alkoxyphenyl)propionic acid CxPh.

[0023] Taking 1-bromooctane as an example, the reaction route for preparing C8Ph is as follows: .

[0024] N -tert-Butyloxycarbonyl- L In the mixed alkylation reaction of tyrosine methyl ester, 1-bromooctane, and potassium carbonate, potassium carbonate provides a basic environment, causing the phenolic hydroxyl group to deprotonate and generate a phenoxide anion (nucleophile). This phenoxide then undergoes a nucleophilic substitution reaction with 1-bromooctane, introducing an octyl chain onto the oxygen atom of the phenolic hydroxyl group, resulting in... N -tert-Butyloxycarbonyl- O -Sinki- L -Tyrosine methyl esters, through alkylation, extend the hydrophobic chain of the molecule, providing a structural basis for subsequent self-assembly.

[0025] Remove N - In the reaction of the tert-butyl carbonyl protecting group N The -tert-butyloxycarbonyl (Boc) protecting group undergoes a deprotection reaction under acidic conditions, releasing a free amino group to yield... O -Sinki- L -Tyrosine methyl ester. The amino protecting group is removed, preparing it for subsequent reaction with Zn. 2+ The coordination reaction provides the active site.

[0026] Under alkaline conditions, the ester group undergoes hydrolysis, converting the ester bond into a free carboxylic acid, ultimately yielding ( S 2-amino-3-(4-octyloxyphenyl)propionic acid, with the introduction of a carboxyl functional group, together with the amino group, constitutes Zn. 2+ The coordination site.

[0027] In some embodiments, the alkyl group in the haloalkane is selected from C6-C12 alkyl groups, preferably n-hexyl, n-octyl, n-decyl or n-dodecyl, more preferably n-octyl, and even more preferably, the haloalkane is 1-bromooctane.

[0028] In some embodiments, during the alkylation reaction N -tert-Butyloxycarbonyl- L The mass ratio of tyrosine methyl ester, haloalkanes, and potassium carbonate is 2-5:1-3:1-3.

[0029] Preferably, the alkylation reaction is carried out at a temperature of 20-35 °C for 10-20 h.

[0030] In some embodiments, removal N- tert-butyl carbonyl protecting group, N -tert-Butyloxycarbonyl- O -Sinki- L - After mixing tyrosine methyl ester with dichloromethane, the mixture is cooled to -5 to 5 °C, and trifluoroacetic acid is added under nitrogen protection. The reaction is continued for 0.5 to 1.5 h, and then the temperature is raised to 20 to 35 °C to continue the reaction for 2 to 5 h.

[0031] Preferably, after the reaction is complete, a saturated sodium bicarbonate aqueous solution is added to the reaction solution for quenching.

[0032] Trifluoroacetic acid (TFA) is a strong acid. Its quenching can be achieved by neutralizing residual TFA with the weak alkalinity of sodium bicarbonate, adjusting the system pH to neutral or weakly alkaline, and avoiding adverse effects on the product. O -Sinki- L -Tyrosine methyl esters cause damage; neutralizing acids can completely terminate the deprotection reaction and prevent excess TFA from continuing to react with the product in side reactions.

[0033] In some embodiments, during the hydrolysis reaction, O -Sinki- L - Tyrosine methyl ester and tetrahydrofuran were mixed in a solvent of water and then subjected to alkaline hydrolysis at a temperature of 20-35 °C for 2-4 h.

[0034] O -Sinki- L -Tyrosine methyl ester exhibits some hydrophobicity and low solubility in pure water. THF, as a polar organic solvent, can effectively dissolve the organic substrate, forming a miscible system with water. This ensures uniform substrate dispersion and avoids uneven reaction or byproduct formation due to excessively high local concentrations. The hydrolysis reaction requires alkaline conditions, with the aqueous phase providing the dissociation environment for the base. The addition of THF can adjust the solvent polarity, promoting the reaction of the ester group (-COOCH3) with OH-. - The increased contact probability accelerates ester bond breakage and promotes hydrolysis.

[0035] Preferably, the alkali used in the alkaline hydrolysis is one or more of sodium hydroxide, lithium hydroxide, potassium hydroxide, and cesium hydroxide.

[0036] Preferably, after alkaline hydrolysis and neutralization, the solvent is removed, and the residue is washed with a mixture of ethyl acetate and n-hexane, wherein the volume ratio of ethyl acetate to n-hexane is 2-4:5-8, preferably 3-4:7-8.

[0037] Ethyl acetate is moderately polar, while n-hexane is nonpolar. By mixing ethyl acetate and n-hexane in a certain ratio, different types of impurities can be washed simultaneously. The target product C8Ph, due to the presence of amino and carboxyl groups in its molecule, is highly polar and has low solubility in the mixed solvent. Therefore, it can be retained in the solid residue through filtration, reducing the loss of the target product.

[0038] A further preferred embodiment involves adding a mixture of ethyl acetate and water to the washed solid, wherein the volume ratio of ethyl acetate to water is 25-35:2-4. After stirring, the mixture is allowed to stand and separate into layers. The water layer is then removed, and the ethyl acetate is removed to obtain CxPh.

[0039] The main component of the washed solid is the target product CxPh, which contains amino and carboxyl groups and has a certain degree of polarity. Adding a mixture of ethyl acetate (a moderately polar organic solvent) and water allows the ethyl acetate phase to dissolve CxPh, while the aqueous phase dissolves residual water-soluble impurities in the solid, thus purifying CxPh.

[0040] In some embodiments, the apparent pH of the coordination reaction is 8-12, preferably 9-11.

[0041] In some embodiments, the alcohol solvent for the coordination reaction is one or more of methanol, ethanol, n-propanol, and isopropanol, preferably methanol.

[0042] In some embodiments, the coordination reaction is carried out at a temperature of 55-70 °C for a time of 1-5 h.

[0043] Preferably, the coordination reaction is carried out at a temperature of 55-65 °C for 2-4 h.

[0044] In some embodiments, the zinc salt is one or more of zinc chloride, zinc bromide, zinc iodide, zinc acetate, zinc nitrate, and zinc trifluoromethanesulfonate.

[0045] In some embodiments, after the coordination reaction is complete, the solvent is removed, ethyl acetate is added to the residue to form a heterogeneous phase, and after washing with water, ethyl acetate is removed to obtain CxPhZn.

[0046] In some embodiments, CxPhZn is dispersed or dissolved in water or an alkaline aqueous solution, wherein the concentration of CxPhZn is 0.05-0.2 mmol / mL and the concentration of the alkali is 0.5-1 M.

[0047] Preferably, the ultrasonic treatment time is 3-10 min, the standing time is 5-15 min, a hydrogel is formed, the hydrogel is spread in a container, and after drying, a dry gel is obtained.

[0048] More preferably, the drying method is natural air drying, depressurized drying, or freeze drying.

[0049] Secondly, the present invention provides a chiral surface-enhanced Raman sensing material, which is prepared by the aforementioned preparation method.

[0050] Thirdly, the present invention provides the application of the chiral surface-enhanced Raman sensing material in the enantiomeric recognition of chiral small molecules, wherein the chiral small molecules are selected from at least one of glucose, amino acids, and ibuprofen.

[0051] The present invention will be further described below with reference to the embodiments.

[0052] Example 1 The synthetic route for C8Ph is shown below: ; The preparation method of C8Ph includes the following steps: (1) N -tert-Butyloxycarbonyl- O -Sinki- L Preparation of tyrosine methyl ester (compound 1): Add to the reaction flask equipped with a magnetic stir bar N -tert-Butyloxycarbonyl- L -Tyrosine methyl ester (Boc-Tyr-OMe) 2.40 g (8.13 mmol) and N , N 42 mL of dimethylformamide (DMF) was dissolved by stirring, followed by the addition of 2.10 mL (12.20 mmol) of 1-bromooctane and 1.68 g (12.20 mmol) of potassium carbonate. The mixture was stirred at room temperature for 16 h under nitrogen protection.

[0053] After the reaction was complete, the reaction solution was poured into 80 mL of water and extracted with ethyl acetate (3 × 100 mL). The combined organic phases were washed with saturated brine (3 × 100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography using ethyl acetate / 40-60 °C petroleum ether = 1:9 (v / v) as the eluent. The target fraction was collected and concentrated under reduced pressure to give compound 1 as 3.00 g of a white solid, 91% yield, with a melting point of 58-59 °C.

[0054] (2) O -Sinki- L Preparation of tyrosine methyl ester (compound 2): 1.22 g (2.99 mmol) of compound 1 and 15 mL of dichloromethane were added to a reaction flask equipped with a magnetic stirrer. The mixture was cooled to 0 °C, and 3.45 mL (45 mmol) of trifluoroacetic acid was slowly added dropwise under nitrogen protection. After the addition was complete, the mixture was stirred at 0 °C for 1 h, and then heated to room temperature and stirred for another 3 h.

[0055] After the reaction was complete, the reaction solution was carefully poured into 200 mL of saturated sodium bicarbonate aqueous solution for quenching. After standing and separating the layers, the organic phase was collected and washed with saturated brine (3 × 100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product compound 2. This crude product was used directly in the next reaction without further purification.

[0056] (3) S Preparation of 2-amino-3-(4-octyloxyphenyl)propionic acid (compound 3, C8Ph): Compound 2,615 mg (2.0 mmol) and 8 mL of tetrahydrofuran / water (1:1, v / v) mixed solvent were added to a reaction flask equipped with a magnetic stir bar. Lithium hydroxide monohydrate 168 mg (4.0 mmol) was added with stirring, and the reaction was stirred at room temperature for 3 h.

[0057] After the reaction was complete, the system was adjusted to pH 7 with 1 M hydrochloric acid, and then the solvent was removed under reduced pressure. The resulting residue was washed with ethyl acetate / n-hexane = 3 / 7 (v / v) (3 × 20 mL). Subsequently, 30 mL of ethyl acetate and 3 mL of water were added to the solid, and the mixture was stirred for 10 min. After standing and separating the layers, the aqueous layer was carefully removed. The ethyl acetate phase was concentrated under reduced pressure to give 505 mg of compound 3 (C8Ph) as a white solid, in 86% yield, with a melting point of 180–181 °C.

[0058] (4) double [( S Preparation of 2-amino-3-(4-octoxyphenyl)propionyloxy]zinc (C8PhZn): 147 mg (0.5 mmol) of compound 3 (C8Ph), 40 mg (1.0 mmol) of sodium hydroxide, and 2 mL of methanol were added to a reaction flask equipped with a magnetic stirrer, and the mixture was stirred at 60 °C for 1 h. Subsequently, 34 mg (0.25 mmol) of zinc chloride was dissolved in 1 mL of methanol and slowly added dropwise to the above reaction system, and the mixture was stirred at 60 °C for another 3 h.

[0059] After the reaction was complete, the mixture was cooled to room temperature and the solvent was removed by vacuum distillation. 10 mL of ethyl acetate was added to the residue to form a heterogeneous system. The mixture was washed with water (2 × 1 mL), and the aqueous layer was removed. The ethyl acetate phase was then concentrated under reduced pressure to give 154 mg of C8PhZn as a white solid with a yield of 95% and a melting point of 191-192 °C.

[0060] The preparation methods for C8PhZn gel and dry gel are as follows: C8PhZn was prepared into an aqueous solution with a concentration of 0.1 mmol / mL. When C8PhZn has poor solubility or dispersibility in water, 1 M NaOH solution can be used instead of water as a solvent. The resulting solution was sonicated for 5 min and then allowed to stand for 10 min to form a gel. The resulting gel was then spread evenly in a petri dish and allowed to air dry naturally to obtain a dry gel.

[0061] Structural and performance testing: Morphological characterization: The fiber network structure was observed using transmission electron microscopy (TEM) and scanning electron microscopy (SEM); Elemental composition: Elemental composition and distribution were analyzed using energy-dispersive X-ray spectroscopy (EDS). Rheological testing: Dynamic rheological testing was conducted using a rheometer at 25 °C. Thermal analysis: Differential scanning calorimetry (DSC) was used to characterize the thermal response behavior; Spectral characterization: Fourier transform infrared (FTIR) spectroscopy (400-4000 cm⁻¹) was used. -1 Raman spectroscopy and SERS spectroscopy were used to characterize the structure and response before and after self-assembly.

[0062] The SERS test conditions are as follows: Conventional Raman spectroscopy measurements use a 633 nm He-Ne laser; SERS spectroscopy uses a 785 nm near-infrared laser to reduce sample fluorescence and photothermal damage; Employs an 1800 grooves / mm grating and a 50× long working distance objective lens (NA=0.75); Each SERS spectrum was integrated for 10 seconds, and the results were accumulated three times and averaged to ensure the statistical representativeness of the data.

[0063] The host molecule (C8PhZn) and guest molecules (L / D-proline, L / D-histidine, L / D-glucose, and S / R-ibuprofen) were separately ground into fine powders using an agate mortar. Subsequently, the host and guest molecules were mixed at a precise 1:1 mass ratio and homogenized by further grinding. The resulting mixture was then pressed into self-supporting tablets (18 mm in diameter and approximately 1 mm thick) under uniaxial pressure of 5–8 MPa. All Raman tests were performed at room temperature (298 K) using a 521 cm⁻¹ silicon wafer prior to data acquisition. -1 The spectral lines are used to calibrate the instrument.

[0064] The test results are shown in Table 1.

[0065] Table 1. SERS test results of different analytes

[0066] Note: DI = (I L I D ) / (I L + I D (glucose and amino acids); DI = (I S I R ) / (I S + I R (ibuprofen).

[0067] Analysis of the experimental results shows that the chiral surface-enhanced Raman sensing material prepared in this invention exhibits significant substrate-dependent chiral recognition characteristics. The enhanced chiral recognition of glucose is particularly pronounced: the DI in the powder state is +0.839, which increases to +0.938 after hierarchical self-assembly to form a dry gel, and the L / D intensity ratio increases from 11.45 to 31.12. This indicates that the chiral microenvironment formed by hierarchical self-assembly helps improve the selective recognition ability of glucose enantiomers.

[0068] In contrast, for proline and histidine, which differ in molecular size and coordination geometry, the distinguishing ability before and after self-assembly shows different trends due to the differences between them and the chiral microenvironment after self-assembly. This substrate dependence indicates that the dry gel platform exhibits differentiated responses to different chiral molecules, which is beneficial for the recognition and detection of chiral small molecules.

[0069] Figure 1 This is a photograph of the gel sample formed from the compound C8PhZn prepared in Example 1; Figure 2 These are TEM and SEM images of the C8PhZn dry gel prepared in Example 1; Figure 3This is the FTIR spectrum of C8PhZn and its dry gel prepared in Example 1; 3500-3200 cm⁻¹ -1 1700-1350cm -1 and 900-750 cm -1 The changes in band shifts and intensities within the region reflect the alteration of the local chemical environment during the self-assembly of functional groups to form supramolecular networks.

[0070] Figure 4 These are Raman spectra comparisons of the C8PhZn material samples before and after self-assembly prepared in Example 1, with excitation wavelengths of 633 nm and 785 nm, respectively; (a) Raman / SERS comparison spectra of C8PhZn in its original (before self-assembly) state and self-assembled dry gel state recorded under 633 nm excitation condition; (b) Raman / SERS comparison spectra of C8PhZn in its original (before self-assembly) state and self-assembled dry gel state recorded under 785 nm excitation condition. Compared with the original sample, the dry gel exhibits a significantly higher signal intensity, which is consistent with the formation of densely packed fiber connection nodes in the porous supramolecular network and the enhanced coupling between the analyte and the framework.

[0071] Figure 5 This is a comparison of the recognition performance of the C8PhZn material prepared in Example 1 for L / D-glucose enantiomers before and after self-assembly. The enantioselective SERS differentiation of L-glucose and D-glucose by C8PhZn before and after hierarchical self-assembly is shown. The SERS spectra of L / D-glucose collected in the original C8PhZn powder state (before self-assembly) and the self-assembled dry gel state are also presented. In the powder state, the two enantiomers show only slight spectral differences, indicating limited chiral discrimination ability in the disordered assembly state. After the formation of the dry gel, significant differentiation appears at the characteristic bands, consistent with the formation of a confined chiral microenvironment locked by self-assembly; this microenvironment enhances enantioselective interactions, thereby achieving reliable differentiation of glucose enantiomers.

[0072] Figure 6This is a comparison of the recognition performance of the C8PhZn material prepared in Example 1 for L / D-proline enantiomers before and after self-assembly. The enantioselectivity SERS distinguishing of L / D-proline by C8PhZn before and after hierarchical self-assembly is shown. The SERS spectra of L / D-proline collected in the original C8PhZn powder state (before self-assembly) and the self-assembled dry gel state are presented, along with the corresponding quantitative enantioselectivity indices (e.g., DI value and characteristic peak intensity ratio). The results show that proline exhibits some enantioselectivity in the powder state, while its enantioselectivity is weakened in the dry gel state, showing only weak distinguishing ability. Unlike glucose, the enantioselectivity of proline did not further increase after self-assembly, indicating that the enantioselectivity of this system is significantly substrate-dependent, possibly related to differences in size, polarity, and binding geometry between the analyte and the assembly-locked chiral pocket.

[0073] Figure 7 This paper presents the enantioselective SERS differentiation of L / D-histidine by C8PhZn before and after hierarchical self-assembly. SERS spectra of L / D-histidine collected in the original C8PhZn powder state (before self-assembly) and the self-assembled dry gel state are shown, along with the corresponding quantitative enantioselectivity indices (e.g., DI value and characteristic peak intensity ratio). Histidine enantiomeric differences are significantly reduced in the dry gel state, exhibiting only weak distinguishing ability. Unlike glucose, histidine enantiomeric differences are reduced after self-assembly, indicating that the enantioselectivity of this system is significantly substrate-dependent, possibly related to differences in size, polarity, and binding geometry between the analyte and the self-assembled locked chiral pocket.

[0074] Figure 8 This is a schematic diagram illustrating the spectral differentiation and quantitative enantioselectivity analysis of R / S-ibuprofen before and after self-assembly. It shows the SERS spectral responses and corresponding DI values ​​of R-ibuprofen and S-ibuprofen in both C8PhZn powder and self-assembled dry gel states. The platform exhibits a consistent preference for R-ibuprofen in both states, and the increased absolute value of DI after self-assembly further indicates that the supramolecular dry gel structure enhances the chiral differentiation ability for larger drug-like molecules.

[0075] Example 2 Preparation of C8PhZn dry gels under different gelation conditions: The C8PhZn prepared in Example 1 was used as the host molecule. An aqueous solution of C8PhZn with a concentration of 0.15 mmol / mL was prepared; when the solubility or dispersibility of C8PhZn in water is poor, 1 M NaOH solution can be used instead of water as the solvent. The resulting solution was sonicated for 10 min and then allowed to stand for 15 min to form a gel. The resulting gel was then spread evenly in a petri dish and allowed to air dry naturally to obtain a dry gel.

[0076] This embodiment shows that when the C8PhZn concentration is increased to 0.15 mmol / mL, and the ultrasonic treatment time and standing time are appropriately extended, a gel can still be formed and a dry gel can be obtained. This indicates that the system described in this invention has good operability and repeatability within a certain concentration range and assembly time range.

[0077] Example 3 Preparation method of C6PhZn: C6 series compounds were prepared using the same method as in Example 1. The difference was that 1-bromohexane was used instead of 1-bromooctane in step (1), while the other raw material types, feed ratios, and reaction steps remained basically the same, yielding the corresponding compounds. O -Jiji- L -Tyrosine intermediate, further hydrolyzed to obtain C6Ph. Subsequently, using the same coordination method as step (4) of Example 1, C6Ph reacts with zinc salt to obtain the corresponding zinc coordination compound C6PhZn.

[0078] The obtained C6PhZn can be further prepared into gels and dry gels according to the method described in Example 2, and applied to surface-enhanced Raman recognition of chiral small molecules.

[0079] Example 4 Preparation method of C7PhZn: C7 series compounds were prepared using the same method as in Example 1. The difference was that 1-bromoheptane was used instead of 1-bromooctane in step (1), while the other raw material types, feed ratios, and reaction steps remained basically the same, yielding the corresponding compounds. O -Gengji- L -Tyrosine intermediate, further hydrolyzed to obtain C7Ph. Subsequently, using the same coordination method as step (4) of Example 1, C7Ph reacts with zinc salt to obtain the corresponding zinc coordination compound C7PhZn.

[0080] The obtained C7PhZn can be further prepared into gels and dry gels according to the method described in Example 2, and applied to surface-enhanced Raman recognition of chiral small molecules.

[0081] Example 5 Preparation method of C9PhZn: C9 series compounds were prepared using the same method as in Example 1. The difference was that 1-bromononane was used instead of 1-bromooctane in step (1), while the other raw material types, feed ratios, and reaction steps remained basically the same, yielding the corresponding compounds. O -Renji- L -Tyrosine intermediate, further hydrolyzed to obtain C9Ph. Subsequently, using the same coordination method as step (4) of Example 1, C9Ph reacts with zinc salt to obtain the corresponding zinc coordination compound C9PhZn.

[0082] The obtained C9PhZn can be further prepared into gels and dry gels according to the method described in Example 2, and applied to surface-enhanced Raman recognition of chiral small molecules.

[0083] Example 6 Preparation method of C10PhZn: C10 series compounds were prepared using the same method as in Example 1. The difference was that 1-bromodecane was used instead of 1-bromooctane in step (1), while the other raw material types, feed ratios, and reaction steps remained basically the same, yielding the corresponding compounds. O -Kelium- L -Tyrosine intermediate, further hydrolyzed to obtain C10Ph. Subsequently, using the same coordination method as step (4) of Example 1, C10Ph reacts with zinc salt to obtain the corresponding zinc coordination compound C10PhZn.

[0084] The obtained C10PhZn can be further prepared into gels and dry gels according to the method described in Example 2, and applied to surface-enhanced Raman recognition of chiral small molecules.

[0085] Example 7 Preparation method of C11PhZn: C11 series compounds were prepared using the same method as in Example 1. The difference was that 1-bromoundecane was used instead of 1-bromooctane in step (1), while the other raw material types, feed ratios, and reaction steps remained basically the same, yielding the corresponding compounds. O -undecyl- L -Tyrosine intermediate, further hydrolyzed to obtain C11Ph. Subsequently, using the same coordination method as step (4) of Example 1, C11Ph reacts with zinc salt to obtain the corresponding zinc coordination compound C11PhZn.

[0086] The obtained C11PhZn can be further prepared into gels and dry gels according to the method described in Example 2, and applied to surface-enhanced Raman recognition of chiral small molecules.

[0087] Example 8 Preparation method of C12PhZn: C12 series compounds were prepared using the same method as in Example 1. The difference was that 1-bromododecane was used instead of 1-bromooctane in step (1), while the other raw material types, feed ratios, and reaction steps remained basically the same, yielding the corresponding compounds. O -Dodecyl- L -Tyrosine intermediate, further hydrolyzed to obtain C12Ph. Subsequently, using the same coordination method as step (4) of Example 1, C12Ph reacts with zinc salt to obtain the corresponding zinc coordination compound C12PhZn.

[0088] The obtained C12PhZn can be further prepared into gels and dry gels according to the method described in Example 2, and applied to surface-enhanced Raman recognition of chiral small molecules.

[0089] Comparative Example 1 SERS recognition of L / D-glucose by raw C8PhZn powder The raw C8PhZn powder prepared in Example 1 was used as a control sample. The raw powder was mixed with L-glucose or D-glucose at a 1:1 mass ratio, thoroughly ground in an agate mortar, and then pressed into self-supporting tablets (18 mm in diameter and approximately 1 mm thick) under a uniaxial pressure of 5-8 MPa. The testing conditions were the same as in Example 1.

[0090] Test results show that the original C8PhZn powder has a certain ability to distinguish L / D-glucose, with preferred characteristic peak intensities of 4664.89 au and 407.57 au, corresponding to a DI value of +0.839 and an L / D intensity ratio of 11.45. Compared with the recognition results in the dry gel state in Example 1, the DI value and intensity ratio of the original powder are both lower, indicating that the chiral recognition ability of the sample without hierarchical self-assembly is relatively weak. This further demonstrates that the dry gelation process described in this invention helps to form a more stable and effective chiral recognition microenvironment.

[0091] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for preparing a chiral surface-enhanced Raman sensing material, characterized in that: Includes the following steps: The zinc coordination compound CxPhZn is obtained by coordinating CxPh or its soluble alkali metal salt with zinc salt in an alcohol solvent under alkaline conditions. CxPhZn is dispersed or dissolved in water or an alkaline aqueous solution to induce self-assembly and form a hydrogel. The hydrogel is dried to obtain a dry gel. The structural formula for CxPh is: Wherein, R is a C6-C12 alkyl group.

2. The method for preparing the chiral surface-enhanced Raman sensing material according to claim 1, characterized in that: The method for inducing self-assembly is as follows: the obtained system is subjected to ultrasonic treatment, and then allowed to stand to self-assemble into a hydrogel; preferably, the ultrasonic treatment time is 3-10 min and the standing time is 5-15 min; more preferably, the formed hydrogel is spread flat in a container and air-dried naturally to obtain a dry gel. Alternatively, when CxPhZn is dispersed or dissolved in water or an alkaline aqueous solution, the concentration of CxPhZn is 0.05-0.2 mmol / mL; the concentration of the alkali is 0.5-1 M. Or, the ( S The preparation method of 2-amino-3-(4-alkoxyphenyl)propionic acid CxPh is as follows: N -tert-Butyloxycarbonyl- L - A mixture of tyrosine methyl ester, haloalkanes, and potassium carbonate is subjected to an alkylation reaction in a rare gas atmosphere to produce... N -tert-Butyloxycarbonyl- O -alkyl- L -Tyrosine methyl ester; Will N -tert-Butyloxycarbonyl- O -alkyl- L -Tyrosine methyl ester was removed using trifluoroacetic acid. N -tert-butylcarbonyl protecting group, yielding O -alkyl- L -Tyrosine methyl ester; Will O -alkyl- L -Tyrosine methyl ester is prepared by hydrolysis ( S )-2-amino-3-(4-alkoxyphenyl)propionic acid CxPh; Alternatively, the alkyl group in the haloalkane is selected from C6-C12 straight-chain alkyl groups; Preferably, the haloalkane is selected from 1-bromohexane, 1-bromoheptane, 1-bromooctane, 1-bromononane, 1-bromodecane, 1-bromoundecane, or 1-bromododecane.

3. The method for preparing the chiral surface-enhanced Raman sensing material according to claim 2, characterized in that: In the alkylation reaction N -tert-Butyloxycarbonyl- L - The mass ratio of tyrosine methyl ester, haloalkanes and potassium carbonate is 2-5:1-3:1-3; the alkylation reaction temperature is 20-35 °C and the time is 10-20 h; Or, remove N - tert-butyl carbonyl protecting group, N -tert-Butyloxycarbonyl- O -alkyl- L - After mixing tyrosine methyl ester with dichloromethane, the mixture is cooled to -5 to 5 °C, and trifluoroacetic acid is added under a rare gas atmosphere. The reaction is continued for 0.5 to 1.5 h, and then the temperature is raised to 20 to 35 °C to continue the reaction for 2 to 5 h.

4. The method for preparing the chiral surface-enhanced Raman sensing material according to claim 2, characterized in that: During the hydrolysis reaction, O -alkyl- L - Tyrosine methyl ester, tetrahydrofuran, and water were mixed in a mixed solvent and then subjected to alkaline hydrolysis at a temperature of 20-35 °C for 2-4 h. Preferably, the alkali used in the alkaline hydrolysis is one or more of sodium hydroxide, lithium hydroxide, potassium hydroxide, and cesium hydroxide; Preferably, after the alkaline hydrolysis and neutralization are completed, a purification step is further included: removing the solvent, washing the residue with a mixture of ethyl acetate and n-hexane, wherein the volume ratio of ethyl acetate to n-hexane is 2-4:5-8; preferably, adding a mixture of ethyl acetate and water to the washed solid, wherein the volume ratio of ethyl acetate to water is 25-35:2-4, stirring and allowing it to stand to separate into layers, removing the water layer, and removing the ethyl acetate to obtain CxPh.

5. The method for preparing the chiral surface-enhanced Raman sensing material according to claim 1, characterized in that: The apparent pH of the coordination reaction is 8-12; preferably, the alcohol solvent for the coordination reaction is selected from one or more of methanol, ethanol, n-propanol or isopropanol, more preferably methanol; preferably, the temperature of the coordination reaction is 55-70 °C and the time is 1-5 h; preferably, the zinc salt is one or more of zinc chloride, zinc bromide, zinc iodide, zinc acetate, zinc nitrate or zinc trifluoromethanesulfonate.

6. The method for preparing the chiral surface-enhanced Raman sensing material according to any one of claims 1-5, characterized in that: After the coordination reaction was completed, the solvent was removed, ethyl acetate was added to the residue to form a heterogeneous phase, and the residue was washed with water to remove the ethyl acetate, yielding CxPhZn.

7. A chiral surface-enhanced Raman sensing material, characterized in that: It is prepared by the preparation method according to any one of claims 1-6.

8. The chiral surface-enhanced Raman sensing material according to claim 7, characterized in that: The chiral surface-enhanced Raman sensing material is a zinc-coordinated supramolecular dry gel; The zinc coordination supramolecular dry gel is formed by the self-assembly of the zinc coordination compound CxPhZn; wherein CxPhZn is a chiral organic ligand CxPh and Zn. 2+ Compounds formed through coordination; wherein, the structural formula of CxPh is: Wherein, R is a C6-C12 alkyl group.

9. The application of the chiral surface-enhanced Raman sensing material according to claim 7 or 8 in the enantiomeric recognition of chiral small molecules.

10. The application according to claim 9, characterized in that: The chiral small molecule is selected from chiral sugars, chiral amino acids, or chiral drugs; preferably, the chiral small molecule is glucose, histidine, proline, or ibuprofen.

Images