WO2020113723A1 - 用于对手性化合物进行检测的基底材料 - Google Patents

用于对手性化合物进行检测的基底材料 Download PDF

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WO2020113723A1
WO2020113723A1 PCT/CN2018/124279 CN2018124279W WO2020113723A1 WO 2020113723 A1 WO2020113723 A1 WO 2020113723A1 CN 2018124279 W CN2018124279 W CN 2018124279W WO 2020113723 A1 WO2020113723 A1 WO 2020113723A1
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gold
base material
chiral
raman
fiber array
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French (fr)
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车顺爱
刘泽栖
段瑛滢
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Tongji University
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65—Raman scattering
    • G01N21/658—Raman scattering enhancement Raman, e.g. surface plasmons
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F9/00—Making metallic powder or suspensions thereof
    • B22F9/16—Making metallic powder or suspensions thereof using chemical processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F9/00—Making metallic powder or suspensions thereof
    • B22F9/16—Making metallic powder or suspensions thereof using chemical processes
    • B22F9/18—Making metallic powder or suspensions thereof using chemical processes with reduction of metal compounds
    • B22F9/24—Making metallic powder or suspensions thereof using chemical processes with reduction of metal compounds starting from liquid metal compounds, e.g. solutions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y40/00—Manufacture or treatment of nanostructures
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65—Raman scattering
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B5/00—Optical elements other than lenses

Definitions

  • the invention relates to a base material for detecting chiral compounds.
  • Chiral compounds refer to a class of compounds that have the same molecular structure but mirror each other in conformation.
  • a mirror image of a chiral compound usually has different characteristics, for example, thalidomide has two mirror image enantiomer configurations of S and R, in which the R type has a central sedative effect , S-type has a strong teratogenic effect. Therefore, in the R&D and production process involving chiral compounds, the distinction between enantiomers and content detection are crucial steps.
  • the analysis and detection methods of chiral compounds mainly include two types, that is, spectrum types and chromatography types.
  • Spectroscopic methods mostly use the optical rotation and circular dichroism of chiral compounds (that is, the characteristics of different interactions with left and right circularly polarized light that lead to deflection or increased ellipticity of the outgoing light), which cannot detect extinction Rotating system and molecules that do not contain chromophoric groups, and it is difficult to eliminate the interference of linearly polarized light generated in the process of switching left and right circularly polarized light.
  • Chromatography methods mainly rely on the interaction of chiral compounds in different conformations with column fixation for separation. However, chromatographic methods can be applied in a limited range, and cannot be used for compounds with too large molecular weight, too small molecular weight, or non-polarity. Perform separation.
  • Raman scattering refers to that when a certain frequency of laser light is irradiated onto the surface of a substance, the molecules in the substance absorb part of the energy, vibrate in different ways and degrees, and then scatter light at a lower frequency. The change in frequency depends on the scattering substance.
  • the "fingerprint spectrum" which is characterized and characterized as a characteristic, reflects the molecular structure of the substance, and the detection of unknown substances can be achieved by using this principle.
  • the chiral compounds that are enantiomers are the same in molecular structure, which cannot be distinguished by ordinary Raman spectrometers.
  • this type of ROA equipment needs to add an additional circularly polarized light filter component (to make the light generated by the light source become left and right circularly polarized light) in the ordinary Raman spectrometer or use a circularly polarized light detector (detect the left and right circularly polarized light separately ), so the cost of the instrument is high.
  • the method of detecting chiral compounds using ROA equipment still has the problems of low signal strength and susceptibility to false signal interference.
  • the inventors of the present invention conducted research on the Raman optical properties of chiral compounds and found that the chiral compounds have the following characteristics: when a surface plasmon resonance material with chirality is used as the base material for Raman scattering detection At this time, the intensity of Raman scattering of chiral compounds increases, and the degree of enhancement of Raman scattering of different enantiomers is different. Not only that, the inventors also found that the enhancement effect of chiral surface plasmon resonance materials on chiral compounds and the conformation ratio of chiral enantiomers are in line with the linear law, so according to the corresponding chiral compounds to be measured in Raman spectroscopy The characteristic peak intensity can be calculated to calculate its content ratio.
  • the inventor proposed a substrate material for the detection of chiral compounds, specifically using the following technical solutions:
  • the invention provides a base material for detecting chiral compounds, which is used in conjunction with a Raman spectrometer to detect chiral compounds, characterized in that the base material is a plasmon resonance material with chirality.
  • the substrate material for detecting chiral compounds provided by the present invention may also have such technical characteristics, in which both incident light and detection light of the Raman spectrometer are unpolarized light.
  • the base material for detecting chiral compounds provided by the present invention may also have such technical characteristics, wherein the base material is a micro-nano powder material or a micro-nano film material with a chiral structure composed of a metal or a metal oxide .
  • the substrate material for detecting chiral compounds provided by the present invention may also have such technical characteristics, wherein the metal is one or a combination of several of gold, silver, copper, and platinum.
  • the substrate material for detecting chiral compounds provided by the present invention may also have such technical characteristics, wherein the metal oxide is one of copper oxide, titanium oxide, zinc oxide, tin oxide, iron oxide, and cobalt oxide Or a combination of several.
  • the substrate material for detecting chiral compounds provided by the present invention may also have such technical characteristics, wherein the chiral structure is any one of a spiral fiber structure, a flower structure, a fan structure, and a propeller structure.
  • the base material for detecting chiral compounds provided by the present invention may also have such technical characteristics, wherein the spiral fiber structure is composed of a single-strand spiral or a double-strand spiral, and the diameter of the single-strand spiral and the double-strand spiral is 5 nm— 20nm, pitch 25nm-85nm.
  • the substrate material for chiral compound detection since the substrate material is a chiral plasmon resonance material, it can be used as a substrate material for Raman scattering detection to carry out specific Raman scattering of the chiral compound
  • Signal enhancement allows chiral compounds that are enantiomers to generate Raman scattering signals of different intensities, and the degree of enhancement of different enantiomers is different. Therefore, the intensity of the characteristic peak in the Raman spectrum can be calculated Its enantiomeric content ratio.
  • the detection of chiral compounds can be achieved by using the substrate material of the present invention combined with an ordinary Raman spectrometer, which has low cost, simple operation, small interference, accurate results, simple operation and wide application. advantage.
  • FIG. 1 is a low-power scanning electron microscope photograph of an L-shaped gold nanohelical fiber array according to Embodiment 1 of the present invention
  • Example 3 is a low-power transmission electron microscope photograph of an L-shaped gold nanohelical fiber array according to Example 1 of the present invention
  • Example 4 is a high-power transmission electron microscope photograph of an L-shaped gold nanohelical fiber array according to Example 1 of the present invention
  • FIG. 5 is a circular dichroism spectrum of the L-shaped gold nanohelical fiber array according to Embodiment 1 of the present invention.
  • Example 6 is a Raman spectrum diagram of the mixture of R-limonene and S-limonene detected by the L-shaped gold nanohelical fiber array of Example 1 of the present invention
  • Example 7 is a linear fit diagram of the intensity of Raman characteristic peak and the percentage of enantiomeric content obtained by the Raman scattering detection of the mixture of R-limonene and S-limonene using the L-shaped gold nanohelical fiber array of Example 1 of the present invention ;
  • FIG. 8 is a Raman spectrum diagram for detecting a mixture of L-cyclohexylglycine and D-cyclohexylglycine using the L-shaped gold nanohelical fiber array of Example 1 of the present invention
  • FIG. 9 is a graph showing the Raman characteristic peak intensity and the percentage of enantiomeric content obtained by Raman scattering detection of a mixture of L-cyclohexylglycine and D-cyclohexylglycine using the L-shaped gold nanohelical fiber array of Example 1 of the present invention Linear fit graph;
  • Example 10 is a Raman spectrum diagram of a mixture of L-phenylglycine and D-phenylglycine using the L-shaped gold nanohelical fiber array of Example 1 of the present invention
  • FIG. 11 is a graph showing the Raman characteristic peak intensity and enantiomeric content percentage obtained by Raman scattering detection of a mixture of L-phenylglycine and D-phenylglycine using the L-shaped gold nanohelical fiber array of Example 1 of the present invention Linear fit graph;
  • Example 12 is a low-power scanning electron microscope photograph of an L-shaped gold nanohelical fiber array with an amount of 4.45 mM 4-mercaptobenzoic acid in Example 2 of the present invention
  • Example 13 is a high-magnification scanning electron microscope photograph of an L-shaped gold nanohelical fiber array with a 4-mercaptobenzoic acid dosage of 3.45 mM according to Example 2 of the present invention
  • Example 15 is a high-power scanning electron microscope photograph of an L-shaped gold nanohelical fiber array with a 4-mercaptobenzoic acid dosage of 4.14 mM according to Example 2 of the present invention
  • Example 16 is a low-power scanning electron microscope photograph of an L-shaped gold nanohelical fiber array with an amount of 4-mercaptobenzoic acid of 2.76 mM in Example 2 of the present invention
  • Example 17 is a high-power scanning electron microscope photograph of an L-shaped gold nanohelical fiber array with an amount of 4-mercaptobenzoic acid of 2.76 mM in Example 2 of the present invention
  • 21 is a comparative example of the present invention using a common Raman spectrometer and a substrate material without chirality to detect limonene Raman spectrum chart;
  • Fig. 22 is a spectrogram of detection of pinene using ROA equipment.
  • an L-shaped gold nanospiral fiber array is used as a base material.
  • the L-shaped gold nanohelical fiber array is a membrane material, which is prepared by a method of induced growth, and specifically includes the following steps:
  • Step S1 the clean silicon substrate is placed in a mixed solution containing concentrated sulfuric acid and hydrogen peroxide, hydrophilized, heated at 60°C for 2 hours, and sonicated for half an hour, then the substrate is taken out and washed three times with deionized water;
  • step S2 the hydrophilicized substrate is placed in a 5 mM aminosilylation reagent, and left to stand for 2 hours for amination, and then the substrate is taken out and washed three times with deionized water;
  • Step S3 Put the aminated substrate in the gold seed solution and soak for 2 hours to load the gold seed on the surface of the substrate;
  • Step S4 the gold-loaded substrate is placed in a solution containing 3.45 mM chiral inducer (N-acetyl-L-cysteine or N-acetyl-D-cysteine), 2.76 mM 4- Mercaptobenzoic acid, 8.62 mM chloroauric acid, 20.69 mM ascorbic acid solution, react for 15 minutes, take out, wash three times with ethanol, dry to obtain chiral gold nanospiral fiber array.
  • 3.45 mM chiral inducer N-acetyl-L-cysteine or N-acetyl-D-cysteine
  • 4- Mercaptobenzoic acid 8.62 mM chloroauric acid
  • 20.69 mM ascorbic acid solution react for 15 minutes, take out, wash three times with ethanol, dry to obtain chiral gold nanospiral fiber array.
  • step S5 cyclic voltammetry is used to remove the residual organic matter in the chiral gold nanohelical fiber array.
  • N-acetyl-L-cysteine and N-acetyl-D-cysteine were used to prepare L-shaped (left-handed) gold nanohelical fiber array and R Type (right-handed) gold nanospiral fiber array.
  • FIG. 1 is a low-power scanning electron microscope photograph of an L-shaped gold nanohelical fiber array according to Embodiment 1 of the present invention
  • FIG. 2 is a high-power scanning electron microscope photograph of an L-shaped gold nanospiral fiber array according to Embodiment 1 of the present invention
  • FIG. 3 is the present invention
  • FIG. 4 is a high-power transmission electron microscope photograph of the L-shaped gold nanospiral fiber array of Embodiment 1 of the present invention.
  • FIGS. 1 to 4 are electron micrographs of the L-shaped gold nanohelical fiber array.
  • the appearance of the R-shaped gold nanohelical fiber array in the electron micrograph is similar to that of FIGS. 1 to 4 and will not be listed here.
  • the above-mentioned gold nanohelical fiber array is composed of neatly arranged single-strand gold spiral fibers, and each gold spiral fiber has a diameter of about 10 nm. It is estimated that the pitch of each gold spiral fiber is about 50nm.
  • FIG. 5 is a circular dichroism spectrum of the L-shaped gold nanohelical fiber array according to Embodiment 1 of the present invention.
  • L-Au NHWs are L-shaped gold nanospiral fiber arrays
  • R-Au NHWs are R-shaped gold nanospiral fiber arrays.
  • the L-shaped gold nanospiral fiber array and the R-shaped gold nanospiral fiber array have obvious circular dichroism, indicating that the two have opposite chirality.
  • the above-mentioned L-shaped gold nanospiral fiber array is used as a base material, and a chiral compound is detected in combination with a Raman spectrometer. That is, the test sample of the chiral compound is formulated into a solution with an appropriate concentration, and the solution is added dropwise to the L-shaped gold nanohelical fiber array on the silicon substrate, and then the silicon substrate is placed at the sample cell of the Raman spectrometer for Raman scattering detection.
  • FIG. 6 is a Raman spectrum diagram for detecting a mixture of R-limonene and S-limonene by using the L-shaped gold nanohelical fiber array of Example 1 of the present invention.
  • -100% is a sample containing only R-limonene
  • 100% is a sample containing only S-limonene
  • -50% is a sample with a content ratio of R-limonene to S-limonene of 75:25
  • 0% It is a sample with an R-limonene to S-limonene content ratio of 50:50
  • 50% is a R-limonene to S-limonene content ratio of 25:75.
  • Example 7 is a linear simulation of the intensity of the Raman characteristic peak and the percentage of the chiral enantiomer content obtained by the Raman scattering detection of the mixture of R-limonene and S-limonene using the L-shaped gold nanohelical fiber array of Example 1 of the present invention Picture.
  • the abscissa is the percentage of chiral enantiomer content (ee value)
  • the ordinate is the intensity of Raman characteristic peak.
  • the chiral compound limonene when the chiral compound limonene is detected using an L-shaped gold nanohelical fiber array, its Raman signal intensity is proportional to the ratio of chiral enantiomers in the sample. That is to say, when two samples of limonene with unknown isomer content need to be detected, the L-shaped gold nanohelical fiber array of this embodiment is used as the base material for Raman scattering detection, and then the detection result is compared with the standard product By comparing the formed linear fitting graphs, the content ratio of S-limonene and R-limonene in the sample to be tested can be calculated.
  • This embodiment uses the same L-shaped gold nanohelical fiber array as the first embodiment to detect cyclohexylglycine.
  • the preparation method of the L-shaped gold nanohelical fiber array is also the same as that of the first embodiment, and will not be repeated here. .
  • FIG. 8 is a Raman spectrum diagram for detecting a mixture of L-cyclohexylglycine and D-cyclohexylglycine using the L-shaped gold nanohelical fiber array of Example 1 of the present invention.
  • -100% is a sample containing only L-cyclohexylglycine
  • 100% is a sample containing only D-cyclohexylglycine
  • -50% is the content ratio of L-cyclohexylglycine to D-cyclohexylglycine is
  • 75:25 samples 0% is a sample with a 50:50 ratio of L-cyclohexylglycine and D-cyclohexylglycine
  • 50% is a 25:25 ratio with L-cyclohexylglycine and D-cyclohexylglycine: 75 samples.
  • FIG. 9 is a Raman characteristic peak intensity and chiral enantiomeric content obtained by Raman scattering detection of a mixture of L-cyclohexylglycine and D-cyclohexylglycine using the L-shaped gold nanohelical fiber array of Example 1 of the present invention Linear fit graph of percentages.
  • the abscissa is the percentage of chiral enantiomer content (ee value)
  • the ordinate is the intensity of Raman characteristic peak.
  • the intensity of its Raman characteristic peak was proportional to the percentage of the chiral enantiomer in the sample relationship. That is to say, when it is necessary to detect two samples of cyclohexylglycine with unknown isomer content, the L-shaped gold nanohelical fiber array of this embodiment is used as a base material for Raman scattering detection, and then the detection results are compared with By comparing the linear fitting graphs formed by the standard products, the content ratio of D-cyclohexylglycine and L-cyclohexylglycine in the test sample can be calculated.
  • the inventors also used the gold nanohelical fiber array of Example 1 as the base material, combined with a Raman spectrometer to detect a variety of other chiral compounds, and found that this detection method can achieve the content ratio detection of different conformations.
  • FIG. 10 is a Raman spectrum diagram of a mixture of L-phenylglycine and D-phenylglycine using the L-shaped gold nanohelical fiber array of Embodiment 1 of the present invention
  • FIG. 11 is a L of the first embodiment of the present invention.
  • Table 1 Chiral compounds verified to be able to detect the content ratio by the combination of gold nanohelical fiber array and Raman spectrometer
  • the chiral compounds that can be detected by the ratio of the gold nanohelical fiber array and the Raman spectrometer are close to one hundred pairs, and these chiral compounds have different characteristics.
  • Table 1 it can be seen that according to the number of chiral centers, single-chiral center compounds and multi-chiral center compounds are included in Table 1; by polar classification, polar compounds and non-polar compounds are included in Table 1; in addition, in Table 1 It also contains many different kinds of chiral compounds such as chromophore molecules, non-chromophore molecules, macromolecules, small molecules and biological molecules. It can be seen that as long as the compound has Raman scattering properties, the enantiomeric content ratio can be detected by combining the gold nanohelical fiber array and the Raman spectrometer.
  • a total of three gold nanospiral fiber arrays were prepared in this embodiment.
  • the preparation process of the three kinds of gold nanohelical fiber arrays is the same as that in the first embodiment, but the conditions are different. The details are as follows:
  • step S4 the amount of 4-mercaptobenzoic acid in step S4 is changed to 3.45mM;
  • step S4 the amount of 4-mercaptobenzoic acid in step S4 is changed to 4.14mM
  • step S4 the dosage of N-acetyl L-cysteine in step S4 is changed to 2.76 mM.
  • FIG. 12 is a low-power scanning electron microscope photograph of an L-shaped gold nanohelical fiber array with an amount of 4-mercaptobenzoic acid of 3.45 mM in Example 2 of the present invention
  • FIG. 13 is an amount of 4-mercaptobenzoic acid in Example 2 of the present invention with an amount of 3.45 High magnification scanning electron micrograph of mM L-shaped gold nanohelical fiber array.
  • each gold spiral fiber is about 12 nm
  • the pitch of each gold spiral fiber is about 60 nm.
  • FIG. 14 is a low-power scanning electron microscope photograph of an L-shaped gold nanohelical fiber array with a 4-mercaptobenzoic acid dosage of 4.14 mM in Example 2 of the present invention
  • FIG. 15 is a 4-mercaptobenzoic acid dosage of 4.14 in Example 2 of the present invention High magnification scanning electron micrograph of mM L-shaped gold nanohelical fiber array.
  • each gold spiral fiber As shown in FIGS. 14 and 15, when the amount of 4-mercaptobenzoic acid is 4.14mM, the diameter of each gold spiral fiber is about 15nm, and the pitch of each gold spiral fiber is about 75nm.
  • FIG. 16 is a low-magnification scanning electron microscope photograph of an L-shaped gold nanohelical fiber array with an amount of 2.76 mM 4-mercaptobenzoic acid in Example 2 of the present invention
  • FIG. 17 is an amount of 4-mercaptobenzoic acid in Example 2 of the present invention with an amount of 2.76 High magnification scanning electron micrograph of mM L-shaped gold nanohelical fiber array.
  • each gold spiral fiber is about 7 nm, and the pitch of each gold spiral fiber is about 35 nm.
  • the above three types of gold nanohelical fiber arrays can all exhibit the same characteristics as the gold nanohelical fiber arrays of Example 1. That is to say, the gold nanospiral fiber arrays obtained under different preparation conditions can be used as a substrate material in conjunction with a Raman spectrometer, so as to achieve the detection of the enantiomeric content ratio of chiral compounds of different conformations in the sample to be tested.
  • this example prepared a gold-silver nanospiral fiber array and used the gold-silver nanospiral fiber array as a base material for Raman scattering Test test.
  • the first four steps of the method for preparing the gold-silver nanospiral fiber array are the same as steps S1 to S4 of the embodiment.
  • the difference is that after step S4, a silver attachment step is also performed, as follows:
  • the gold nanohelical fiber array obtained in step S4 is placed in a solution containing 5 mM silver nitrate and 10 mM ascorbic acid, left to react for 5 minutes, taken out, washed with ethanol three times, and dried to obtain a chiral gold-silver nanohelical fiber array.
  • FIG. 18 is a Raman spectrum diagram of detecting a mixture of R-limonene and S-limonene using the gold-silver nanospiral fiber array of Embodiment 3 of the present invention
  • FIG. 19 is a gold-silver nanospiral using Embodiment 3 of the present invention The linear array of the intensity of Raman characteristic peak and the percentage of chiral enantiomer content obtained by the fiber array on the mixture of R-limonene and S-limonene by Raman scattering detection.
  • the Raman signal intensity is also proportional to the ratio of chiral enantiomers in the sample.
  • the gold-silver nanohelical fiber array can also be used as a base material in conjunction with a Raman spectrometer to achieve the detection of the enantiomeric content ratio of chiral compounds of different conformations in the sample to be tested.
  • the inventor also used ordinary plasmon resonance material and ordinary Raman spectrometer to detect the two limonenes in the first embodiment.
  • FIG. 20 is a Raman spectrum chart of a comparative example of the present invention for detecting limonene using a common Raman spectrometer.
  • FIG. 21 is a Raman spectrum chart of a comparative example of the present invention for detecting limonene using a common Raman spectrometer and a substrate material without chirality.
  • an ordinary Raman spectrometer and a plasmon resonance material without chirality in this comparative example, gold nanoparticles are used, the gold nanoparticles are plasmon resonance materials, but do not have a chiral structure.
  • the characteristic peak intensity of each limonene sample is stronger overall, but the Raman spectra of the five kinds are also the same, indicating that the combination of ordinary Raman spectrometers without chirality Plasmon resonance materials can well achieve qualitative and quantitative, but can not distinguish the enantiomers, and can not detect the content ratio of different conformations.
  • Example 1 By comparing Example 1 with Comparative Example 1, it can be seen that when using the chiral plasmon resonance material of the present invention as a base material and a Raman spectrometer to detect limonene, limonene samples with different ee values show different characteristic peaks Strength, while ordinary base materials do not have this characteristic.
  • the inventors speculate that the reason for this phenomenon may be that the electromagnetic field generated by the chiral gold nanohelical fiber array under the detection light irradiation also has chiral characteristics, which can specifically enhance a certain chiral conformation.
  • the Raman signal (for example, the L-shaped gold nanohelical fiber array has a stronger enhancement effect on the S-limonene molecule) but hardly enhances another chiral conformation.
  • Example 2 and Example 3 1.
  • the base material of the gold nanohelical fiber array of the present invention can detect hundreds of chiral compounds; 2. Even if other types of Plasmon resonance materials, the detection method of the present invention can also realize the detection of chiral compounds; 3. Chiral plasmon resonance materials prepared under different conditions and different morphologies (such as different diameters and different screw pitches) can realize hand Sex compound detection.
  • the substrate material is a chiral plasmon resonance material
  • it can more or less specifically enhance the Raman signal of the chiral compound, so it can also be combined with Raman Spectrometer to detect the ratio of enantiomeric content of chiral compounds.
  • the base material of the present invention can be used in conjunction with an ordinary Raman spectrometer to detect chiral compounds, compared with the detection methods of chiral compounds in the prior art, the base material of the present invention is combined with a Raman spectrometer
  • the detection method has the advantages of low cost, simple operation, low interference, accurate results, simple operation and wide application.
  • the plasmon resonance material with chirality is a gold nanospiral fiber array and a gold-silver nanospiral fiber array.
  • the chiral plasmon resonance material may also be other kinds of chiral plasmon resonance material, including micro-nano material powder or micro Nano film material.
  • the metal may be one or a combination of gold, silver, copper, platinum, and the metal oxide may be one or more of copper oxide, titanium oxide, zinc oxide, tin oxide, iron oxide, cobalt oxide or Several kinds of compositions; in addition to the nano-helical fiber structure (that is, the spiral fiber structure) of the embodiment, the chiral structure may also be a flower-shaped structure, a fan-shaped structure, a propeller-shaped structure, or the like. These materials are all chiral plasmon resonance materials, which can generate an electromagnetic field with chiral characteristics under the detection light irradiation to specifically enhance the Raman signal of a certain chiral conformation, so they can achieve the Detection.

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Abstract

一种用于对手性化合物进行检测的基底材料，与拉曼光谱仪配合使用从而对手性化合物进行检测，其特征在于：其中，基底材料为具有手性的表面等离子体共振材料。所述的基底材料能够对手性化合物进行特异性的拉曼散射信号增强，并且其对不同对映体的增强程度不同，因此，通过拉曼光谱中的特征峰强度即可推算得出其对映体含量比例。与现有技术中的检测手段相比，采用所述的基底材料结合拉曼光谱仪即可实现手性化合物的检测，具有成本低、操作简单、干扰小、结果准确、操作简单且应用广泛等优点。

Description

用于对手性化合物进行检测的基底材料 技术领域
本发明涉及一种用于对手性化合物进行检测的基底材料。
背景技术
手性化合物是指分子结构相同，但构象上互为镜像的一类化合物。在医药化工领域中，互为镜像的一对手性化合物之间通常具有不同的特性，例如，沙利度胺具有S和R两种互为镜像的对映体构象，其中R型具有中枢镇静作用，S型却具有强烈的致畸作用。因此，在涉及手性化合物的研发生产过程中，对映体之间的区分及含量检测是至关重要的步骤。
现有技术中，手性化合物的分析检测方法主要包括两类，即光谱类和色谱类。光谱类的方法多利用手性化合物的旋光性和圆二色性(即，分别与左右圆偏振光发生不同的相互作用导致出射光发生偏转或椭圆度增加的特性)实现，其无法检测外消旋体系和不含有发色基团的分子，且难以消除左右圆偏振光切换过程中所产生的线偏振光的干扰。色谱类方法主要依赖于色谱柱固定相对不同构象手性化合物的相互作用不同而进行分离，然而，色谱类方法能够应用的范围有限，对分子量过大、分子量过小或没有极性的化合物等无法进行分离。
拉曼散射是指一定频率的激光照射到物质表面时，物质中的分子吸收了部分能量，发生不同方式和程度的振动，然后散射出较低频率的光，其频率的变化决定于散射物质的特性并表现为特征的“指纹光谱”，反映出物质的分子结构，利用该原理即可实现未知物质的检测。然而，互为对映体的手性化合物在分子结构上是相同的，普通的拉曼光谱仪无法对其进行区分。
现有技术中出现了一种通过采用圆偏振光源或圆偏振光检测器让拉曼光谱仪实现手性化合物检测的设备(即拉曼光学活性设备，简称ROA设备)，其对蒎烯这种手性化合物的检测结果如图22所示。从图22中可以看出，当样品中含有蒎烯的两种对映体且两种对映体含量不同时，ROA检测的特征峰强度有明显区别，因此能够得出不同构象手性化合物的含量比例。然而，这类ROA设备需要在普通的拉曼光谱仪中额外增设圆偏振光过滤组件(让光源产生的光分别成为左右圆偏振光)或使用圆偏振光检测器(分别检测出射的左右圆偏振光)，因此仪器成本高。另外，利用ROA设备进行手性化合物检测的方法仍然存在信号强度低、易受假信号干扰等问题。
发明内容
为解决上述问题，本发明的发明人针对手性化合物的拉曼光学特性进行了研究，发现手性化合物具有如下特性：当采用具有手性的表面等离子体共振材料作为拉曼散射检测的基 底材料时，手性化合物的拉曼散射强度增加，且对不同对映异构体的拉曼散射增强程度不同。不仅如此，发明人还发现，具有手性的表面等离子体共振材料对手性化合物的增强作用与手性对映体的构象比例符合线性规律，因此根据拉曼光谱中待测手性化合物所对应的特征峰强度即可推算得出其含量比例。
基于上述发现，发明人提出了一种用于对手性化合物进行检测的基底材料，具体采用了如下技术方案：
本发明提供了一种用于对手性化合物进行检测的基底材料，用于与拉曼光谱仪配合使用从而对手性化合物进行检测，其特征在于：其中，基底材料为具有手性的等离子体共振材料。
本发明提供的用于对手性化合物进行检测的基底材料，还可以具有这样的技术特征，其中，拉曼光谱仪的入射光和检测光均为非偏振光。
本发明提供的用于对手性化合物进行检测的基底材料，还可以具有这样的技术特征，其中，基底材料为由金属或金属氧化物构成的具有手性结构的微纳米粉末材料或微纳米膜材料。
本发明提供的用于对手性化合物进行检测的基底材料，还可以具有这样的技术特征，其中，金属为金、银、铜、铂中的一种或几种的组合物。
本发明提供的用于对手性化合物进行检测的基底材料，还可以具有这样的技术特征，其中，金属氧化物为氧化铜、氧化钛、氧化锌、氧化锡、氧化铁、氧化钴中的一种或几种的组合物。
本发明提供的用于对手性化合物进行检测的基底材料，还可以具有这样的技术特征，其中，手性结构为螺旋纤维结构、花形结构、扇形结构、螺旋桨形结构中的任意一种。
本发明提供的用于对手性化合物进行检测的基底材料，还可以具有这样的技术特征，其中，螺旋纤维结构由单股螺旋或双股螺旋构成，单股螺旋及双股螺旋的直径为5nm–20nm，螺距为25nm–85nm。
发明作用与效果
根据本发明提供的用于对手性化合物进行检测的基底材料，由于该基底材料是具有手性的等离子体共振材料，能够作为拉曼散射检测时的基底材料对手性化合物进行特异性的拉曼散射信号增强，让互为对映体的手性化合物产生强度不同的拉曼散射信号，并且其对不同对映体的增强程度不同，因此，通过拉曼光谱中的特征峰强度即可推算得出其对映体含量比例。与现有技术中的检测手段相比，采用本发明的基底材料结合普通拉曼光谱仪即可实现手性化合物的检测，具有成本低、操作简单、干扰小、结果准确、操作简单且应用广泛等优点。
附图说明
图1是本发明实施例一的L型金纳米螺旋纤维阵列的低倍扫描电镜照片；
图2是本发明实施例一的L型金纳米螺旋纤维阵列的高倍扫描电镜照片；
图3是本发明实施例一的L型金纳米螺旋纤维阵列的低倍透射电镜照片；
图4是本发明实施例一的L型金纳米螺旋纤维阵列的高倍透射电镜照片；
图5是本发明实施例一的L型金纳米螺旋纤维阵列的圆二色光谱；
图6是采用本发明实施例一的L型金纳米螺旋纤维阵列对R-柠檬烯和S-柠檬烯的混合物进行检测的拉曼光谱图；
图7是采用本发明实施例一的L型金纳米螺旋纤维阵列对R-柠檬烯和S-柠檬烯的混合物进行拉曼散射检测得到的拉曼特征峰强度与对映体含量百分比的线性拟合图；
图8是采用本发明实施例一的L型金纳米螺旋纤维阵列对L-环己基甘氨酸和D-环己基甘氨酸的混合物进行检测的拉曼光谱图；
图9是采用本发明实施例一的L型金纳米螺旋纤维阵列对L-环己基甘氨酸和D-环己基甘氨酸的混合物进行拉曼散射检测得到的拉曼特征峰强度与对映体含量百分比的线性拟合图；
图10是采用本发明实施例一的L型金纳米螺旋纤维阵列对L-苯基甘氨酸和D-苯基甘氨酸的混合物的拉曼光谱图；
图11是采用本发明实施例一的L型金纳米螺旋纤维阵列对L-苯基甘氨酸和D-苯基甘氨酸的混合物进行拉曼散射检测得到的拉曼特征峰强度与对映体含量百分比的线性拟合图；
图12是本发明实施例二的4-巯基苯甲酸用量为3.45mM的L型金纳米螺旋纤维阵列的低倍扫描电镜照片；
图13是本发明实施例二的4-巯基苯甲酸用量为3.45mM的L型金纳米螺旋纤维阵列的高倍扫描电镜照片；
图14是本发明实施例二的4-巯基苯甲酸用量为4.14mM的L型金纳米螺旋纤维阵列的低倍扫描电镜照片；
图15是本发明实施例二的4-巯基苯甲酸用量为4.14mM的L型金纳米螺旋纤维阵列的高倍扫描电镜照片；
图16是本发明实施例二的4-巯基苯甲酸用量为2.76mM的L型金纳米螺旋纤维阵列的低倍扫描电镜照片；
图17是本发明实施例二的4-巯基苯甲酸用量为2.76mM的L型金纳米螺旋纤维阵列的高倍扫描电镜照片；
图18是采用本发明实施例三的金-银纳米螺旋纤维阵列对R-柠檬烯和S-柠檬烯的混合物进行检测的拉曼光谱图；
图19是采用本发明实施例三的金-银纳米螺旋纤维阵列对R-柠檬烯和S-柠檬烯的混合物进 行拉曼散射检测得到的拉曼特征峰强度与手性对映体含量百分比的线性拟合图；
图20是本发明比较例的采用普通拉曼光谱仪对柠檬烯进行检测的拉曼光谱图；
图21是本发明比较例的采用普通拉曼光谱仪以及不具有手性的基底材料对柠檬烯进行检测的拉曼光谱图；
图22是采用ROA设备对蒎烯进行检测的光谱图。
具体实施方式
以下结合附图来说明本发明的具体实施方式。
<实施例一>
本实施例采用L型金纳米螺旋纤维阵列作为基底材料。该L型金纳米螺旋纤维阵列为一种膜材料，采用诱导生长的方法制备，具体包括如下步骤：
步骤S1，将干净的硅基板置于含有浓硫酸、过氧化氢的混合溶液中，亲水化，60℃加热2小时，并超声半小时，然后取出基板，去离子水洗涤三次；
步骤S2，将亲水化的基板放入5mM氨基硅烷化试剂中，静置2小时从而进行氨基化，然后取出基板，去离子水洗涤三次；
步骤S3，将氨基化的基板放入金种溶液中，浸泡2小时，将金种负载到基板表面；
步骤S4，将负载金种的基板置于含有3.45mM的手性诱导剂(N-乙酰-L-半胱氨酸或N-乙酰-D-半胱氨酸)溶液中，2.76mM的4-巯基苯甲酸，8.62mM的氯金酸，20.69mM的抗坏血酸溶液中，反应15分钟，取出，乙醇洗三次，干燥后得手性金纳米螺旋纤维阵列。
步骤S5，采用循环伏安法去除手性金纳米螺旋纤维阵列中残留的有机物。
本实施例中，分别采用N-乙酰-L-半胱氨酸以及N-乙酰-D-半胱氨酸这两种手性诱导剂制备了L型(左手型)金纳米螺旋纤维阵列和R型(右手型)金纳米螺旋纤维阵列。
图1是本发明实施例一的L型金纳米螺旋纤维阵列的低倍扫描电镜照片，图2是本发明实施例一的L型金纳米螺旋纤维阵列的高倍扫描电镜照片，图3是本发明实施例一的L型金纳米螺旋纤维阵列的低倍透射电镜照片，图4是本发明实施例一的L型金纳米螺旋纤维阵列的高倍透射电镜照片。
上述图1-图4均为L型金纳米螺旋纤维阵列的电镜照片，R型金纳米螺旋纤维阵列在电镜照片中呈现的外观与图1-图4近似，在此不再列出。
从图1-图4可以看出，上述金纳米螺旋纤维阵列由整齐排列的单股金螺旋纤维构成，每根金螺旋纤维的直径约为10nm。经推算，每根金螺旋纤维的螺距约为50nm。
图5是本发明实施例一的L型金纳米螺旋纤维阵列的圆二色光谱。图5中，L-Au NHWs为L型金纳米螺旋纤维阵列，R-Au NHWs为R型金纳米螺旋纤维阵列。
如图5所示，L型金纳米螺旋纤维阵列和R型金纳米螺旋纤维阵列具有明显的圆二色性， 说明二者具有相反的手性。
本实施例中，为了说明金纳米螺旋纤维阵列的作用，采用上述L型金纳米螺旋纤维阵列作为基底材料，结合拉曼光谱仪对手性化合物进行检测。即，将手性化合物的待测样品配制成浓度适当的溶液，将该溶液滴加至硅基板上的L型金纳米螺旋纤维阵列处，然后将硅基板放置于拉曼光谱仪的样品池处进行拉曼散射检测。
图6是采用本发明实施例一的L型金纳米螺旋纤维阵列对R-柠檬烯和S-柠檬烯的混合物进行检测的拉曼光谱图。
图6中，-100％是仅含有R-柠檬烯的样品，100％是仅含有S-柠檬烯的样品，-50％是R-柠檬烯与S-柠檬烯的含量比为75:25的样品，0％是R-柠檬烯与S-柠檬烯的含量比为50:50的样品，50％是R-柠檬烯与S-柠檬烯的含量比为25:75的样品。
图7是采用本发明实施例一的L型金纳米螺旋纤维阵列对R-柠檬烯和S-柠檬烯的混合物进行拉曼散射检测得到的拉曼特征峰强度与手性对映体含量百分比的线性拟合图。图7中，横坐标为手性对映体含量百分比(ee值)，纵坐标为拉曼特征峰强度。
如图6和图7所示，当采用L型金纳米螺旋纤维阵列对柠檬烯这种手性化合物进行检测时，其拉曼信号强度与样品中的手性对映体比例呈正比关系。也就是说，当需要对两种异构体含量未知的柠檬烯样品进行检测时，将本实施例的L型金纳米螺旋纤维阵列作为基底材料进行拉曼散射检测，然后将其检测结果与标准品所形成的线性拟合图进行对比，即可计算得到待测样品中S-柠檬烯和R-柠檬烯的含量比例。
<实施例二>
本实施例采用与实施例一相同的L型金纳米螺旋纤维阵列作为基底材料对环己基甘氨酸进行检测，该L型金纳米螺旋纤维阵列的制备方法也与实施例一相同，在此不再赘述。
图8是采用本发明实施例一的L型金纳米螺旋纤维阵列对L-环己基甘氨酸和D-环己基甘氨酸的混合物进行检测的拉曼光谱图。
图8中，-100％是仅含有L-环己基甘氨酸的样品，100％是仅含有D-环己基甘氨酸的样品，-50％是L-环己基甘氨酸与D-环己基甘氨酸的含量比为75:25的样品，0％是L-环己基甘氨酸与D-环己基甘氨酸的含量比为50:50的样品，50％是L-环己基甘氨酸与D-环己基甘氨酸的含量比为25:75的样品。
图9是采用本发明实施例一的L型金纳米螺旋纤维阵列对L-环己基甘氨酸和D-环己基甘氨酸的混合物进行拉曼散射检测得到的拉曼特征峰强度与手性对映体含量百分比的线性拟合图。图9中，横坐标为手性对映体含量百分比(ee值)，纵坐标为拉曼特征峰强度。
如图8和图9所示，当采用L型金纳米螺旋纤维阵列对环己基甘氨酸这种手性化合物进行检测时，其拉曼特征峰强度与样品中的手性对映体含量百分比呈正比关系。也就是说， 当需要对两种异构体含量未知的环己基甘氨酸样品进行检测时，将本实施例的L型金纳米螺旋纤维阵列作为基底材料进行拉曼散射检测，然后将其检测结果与标准品所形成的线性拟合图进行对比，即可计算得到待测样品中D-环己基甘氨酸和L-环己基甘氨酸的含量比例。
另外，发明人还采用实施例一的金纳米螺旋纤维阵列为基底材料，配合拉曼光谱仪对其他多种手性化合物进行了检测，发现这种检测方法都能够实现不同构象的含量比例检测。
例如，图10是采用本发明实施例一的L型金纳米螺旋纤维阵列对L-苯基甘氨酸和D-苯基甘氨酸的混合物的拉曼光谱图，图11是采用本发明实施例一的L型金纳米螺旋纤维阵列对L-苯基甘氨酸和D-苯基甘氨酸的混合物进行拉曼散射检测得到的拉曼特征峰强度与手性对映体含量百分比的线性拟合图。
如图10及图11所示，当采用L型金纳米螺旋纤维阵列对苯基甘氨酸这种手性化合物进行检测时，其拉曼特征峰强度与样品中的手性对映体含量百分比呈正比关系。
经验证，其他多种常见手性化合物均能够通过实施例一的金纳米螺旋纤维阵列结合拉曼光谱仪进行含量比例检测，并且其ee值和特征峰强度均呈现正比关系。发明人验证过的手性化合物如下表1所示：
表1经验证能够通过金纳米螺旋纤维阵列结合拉曼光谱仪进行含量比例检测的手性化合物
Figure PCTCN2018124279-appb-000001
Figure PCTCN2018124279-appb-000002
Figure PCTCN2018124279-appb-000003
Figure PCTCN2018124279-appb-000004
根据表1可知，能够通过金纳米螺旋纤维阵列结合拉曼光谱仪进行对映体含量比例检测的手性化合物接近百对，并且这些手性化合物特性各异。例如，以手性中心数量分类，表1中包含了单手性中心化合物和多手性中心化合物；以极性分类，表1中包含了极性化合物和非极性化合物；另外，表1中还包含了有发色基团分子、无发色基团分子、大分子、小分子和生物分子等多种不同种类的手性化合物。可见，只要是具有拉曼散射特性的化合物，均可通过金纳米螺旋纤维阵列结合拉曼光谱仪来进行对映体含量比例检测。
<实施例三>
本实施例中，为验证不同制备条件对金纳米螺旋纤维阵列的影响，采用不同条件制备得到不同的金纳米螺旋纤维阵列，并采用这些金纳米螺旋纤维阵列作为基底材料分别进行拉曼散射检测试验。
本实施例一共制备了三种金纳米螺旋纤维阵列，该三种的制备过程与实施例一相同，但条件有所不同，具体如下：
第一种：步骤S4中的4-巯基苯甲酸用量改为3.45mM；
第二种：步骤S4中的4-巯基苯甲酸用量改为4.14mM；
第三种：步骤S4中的N-乙酰L-半胱氨酸用量改为2.76mM。
图12是本发明实施例二的4-巯基苯甲酸用量为3.45mM的L型金纳米螺旋纤维阵列的低倍扫描电镜照片，图13是本发明实施例二的4-巯基苯甲酸用量为3.45mM的L型金纳米螺旋纤维阵列的高倍扫描电镜照片。
如图12及图13所示，当4-巯基苯甲酸用量为3.45mM时，每根金螺旋纤维的直径约为12nm，同时每根金螺旋纤维的螺距约为60nm。
图14是本发明实施例二的4-巯基苯甲酸用量为4.14mM的L型金纳米螺旋纤维阵列的低倍扫描电镜照片，图15是本发明实施例二的4-巯基苯甲酸用量为4.14mM的L型金纳米螺旋纤维阵列的高倍扫描电镜照片。
如图14及图15所示，当4-巯基苯甲酸用量为4.14mM时，每根金螺旋纤维的直径约为15nm，同时每根金螺旋纤维的螺距约为75nm。
图16是本发明实施例二的4-巯基苯甲酸用量为2.76mM的L型金纳米螺旋纤维阵列的低倍扫描电镜照片，图17是本发明实施例二的4-巯基苯甲酸用量为2.76mM的L型金纳米螺旋纤维阵列的高倍扫描电镜照片。
如图16及图17所示，当4-巯基苯甲酸用量为2.76mM时，每根金螺旋纤维的直径约为7nm，同时每根金螺旋纤维的螺距约为35nm。
经拉曼散射检测试验，上述三种金纳米螺旋纤维阵列均能够表现出与实施例一的金纳米螺旋纤维阵列相同的特性。也就是说，不同制备条件得到的金纳米螺旋纤维阵列均可作为基底材料与拉曼光谱仪配合使用，从而实现待测样品中不同构象手性化合物的对映体含量比例检测。
<实施例四>
为验证其他种类的金属纳米螺旋纤维阵列是否也可用于进行手性化合物检测，本实施例制备了金-银纳米螺旋纤维阵列并采用该金-银纳米螺旋纤维阵列作为基底材料进行了拉曼散射检测试验。
本实施例中，金-银纳米螺旋纤维阵列的制备方法前四个步骤与实施例的步骤S1-步骤S4相同。不同之处在于，在步骤S4后还进行了银的附着步骤，具体如下：
将步骤S4得到的金纳米螺旋纤维阵列放入含有5mM的硝酸银、10mM抗坏血酸的溶液中，静置反应5分钟，取出，乙醇洗三次，干燥后得手性金-银纳米螺旋纤维阵列。
图18是采用本发明实施例三的金-银纳米螺旋纤维阵列对R-柠檬烯和S-柠檬烯的混合物进行检测的拉曼光谱图，图19是采用本发明实施例三的金-银纳米螺旋纤维阵列对R-柠檬烯和S-柠檬烯的混合物进行拉曼散射检测得到的拉曼特征峰强度与手性对映体含量百分比的线性拟合图。
如图18和图19所示，当采用金-银纳米螺旋纤维阵列对柠檬烯进行检测时，其拉曼信号强度与样品中的手性对映体比例也呈正比关系。也就是说，金-银纳米螺旋纤维阵列也可以作为基底材料与拉曼光谱仪配合使用，从而实现待测样品中不同构象手性化合物的对映体含量比例检测。
<比较例>
为说明本发明的具有手性的等离子体共振材料的作用效果，发明人还采用普通等离子体共振材料及普通拉曼光谱仪对实施例一中的两种柠檬烯进行了检测。
图20是本发明比较例的采用普通拉曼光谱仪对柠檬烯进行检测的拉曼光谱图。
如图20所示，采用普通拉曼光谱仪(不使用基底材料)对总含量相同但ee值不同的五个柠檬烯样品进行检测时，各个柠檬烯样品特征峰强度完全相同，说明普通拉曼光谱仪能够对柠檬烯样品进行定性(通过特征峰位移)和定量(通过特征峰强度)，但无法区分对映体，也就无法实现不同构象的含量比例检测。另外，从图20可以看出，不使用基底材料时，拉曼光谱中的特征峰强度较低，因此还存在信号弱、定性和定量较为困难的问题。
图21是本发明比较例的采用普通拉曼光谱仪以及不具有手性的基底材料对柠檬烯进行检测的拉曼光谱图。
如图21所示，采用普通拉曼光谱仪以及不具有手性的等离子体共振材料(本比较例采用了金纳米颗粒，该金纳米颗粒为等离子体共振材料，但不具有手性结构)对总含量相同但ee值不同的五个柠檬烯样品进行检测时，各个柠檬烯样品特征峰强度整体较强，但这五种的拉曼图谱也是完全相同的，说明普通拉曼光谱仪结合不具有手性的通常等离子体共振材料能够很好地实现定性和定量，但无法区分对映体，无法实现不同构象的含量比例检测。
实施例作用与效果
从上述实施例中可以看出，当采用具有手性的等离子体共振材料作为基底材料对手性化合物进行拉曼散射检测时，其对手性化合物不同对映体的拉曼信号增强作用有明显区别，这样的区别反映到光谱图上就使得不同对映体的特征峰强度有明显差异。因此，通过拉曼光谱中的特征峰强度即可推算得出其含量比例。
将实施例一与比较例一对比可以看出，采用本发明的具有手性的等离子体共振材料作为基底材料配合拉曼光谱仪对柠檬烯进行检测时，不同ee值的柠檬烯样品表现出不同的特征峰强度，而普通基底材料则不具有这种特性。发明人推测，这种现象发生的原因可能是具有手性的金纳米螺旋纤维阵列在检测光照射下产生的电磁场也具有类似于手性的特性，可以特异性地增强某一种手性构象的拉曼信号(例如，L型金纳米螺旋纤维阵列对S-柠檬烯分子增强作用更强)而对另一种手性构象则几乎不具增强作用。
另外，从实施例二及实施例三可以得出如下结果：1、本发明的金纳米螺旋纤维阵列这种基底材料能够对上百种手性化合物实现检测；2、即使更换其他种类的具有手性的等离子体共振材料，本发明的检测方法也能够实现手性化合物的检测；3、不同条件制备得到的不同形貌(例如不同直径、不同螺距)的手性等离子体共振材料均能够实现手性化合物检测。
结合上述检测原理方面的推断可以得知，只要基底材料是具有手性的等离子体共振材料，其都能够或多或少地对手性化合物的拉曼信号进行特异性增强，因而也能够结合拉曼光谱仪来实现手性化合物的对映体含量比例检测。由于本发明的这种基底材料与普通的拉曼光谱仪配合使用就可以对手性化合物进行检测，因此，与现有技术中的手性化合物检测手段相比，采用本发明的基底材料结合拉曼光谱仪进行检测的方法具有成本低、操作简单、干扰小、结果准确、操作简单且应用广泛等优点。
上述实施例仅用于举例说明本发明的具体实施方式，而本发明的用于对手性化合物进行检测的基底材料不限于上述实施例所描述的范围。
实施例中，具有手性的等离子体共振材料为金纳米螺旋纤维阵列和金-银纳米螺旋纤维阵列。然而，在本发明中，具有手性的等离子体共振材料还可以是其他种类的具有手性的等离子体共振材料，包括由金属或金属氧化物构成的具有手性结构的微纳米材料粉末或微纳米膜材料。其中，金属可以是金、银、铜、铂中的一种或几种的组合物，金属氧化物可以是氧 化铜、氧化钛、氧化锌、氧化锡、氧化铁、氧化钴中的一种或几种的组合物；手性结构除了实施例的纳米螺旋纤维结构(即螺旋纤维结构)以外，还可以是花形结构、扇形结构、螺旋桨形结构等结构。这些材料均是具有手性的等离子体共振材料，能够在检测光照射下产生具有手性特性的电磁场而特异性地增强某一种手性构象的拉曼信号，因此均能够实现手性化合物的检测。

Claims (7)

  1. 一种用于对手性化合物进行检测的基底材料，用于与拉曼光谱仪配合使用从而对所述手性化合物进行检测，其特征在于：
    其中，所述基底材料为具有手性的等离子体共振材料。
  2. 根据权利要求1所述的用于对手性化合物进行检测的基底材料，其特征在于：
    其中，所述拉曼光谱仪的入射光和检测光均为非偏振光。
  3. 根据权利要求1所述的用于对手性化合物进行检测的基底材料，其特征在于：
    其中，所述基底材料为由金属或金属氧化物构成的具有手性结构的微纳米粉末材料或微纳米膜材料。
  4. 根据权利要求3所述的用于对手性化合物进行检测的基底材料，其特征在于：
    其中，所述金属为金、银、铜、铂中的一种或几种的组合物。
  5. 根据权利要求3所述的用于对手性化合物进行检测的基底材料，其特征在于：
    其中，所述金属氧化物为氧化铜、氧化钛、氧化锌、氧化锡、氧化铁、氧化钴中的一种或几种的组合物。
  6. 根据权利要求3-5中任一项所述的用于对手性化合物进行检测的基底材料，其特征在于：
    其中，所述手性结构为螺旋纤维结构、花形结构、扇形结构、螺旋桨形结构中的任意一种。
  7. 根据权利要求6所述的用于对手性化合物进行检测的基底材料，其特征在于：
    其中，所述螺旋纤维结构由单股螺旋或双股螺旋构成，
    所述单股螺旋及所述双股螺旋的直径为5nm–20nm，螺距为25nm–85nm。
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113588626A (zh) * 2021-08-24 2021-11-02 上海师范大学 一种苯丙氨酸对映体的拉曼光谱检测方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118561886B (zh) * 2024-05-16 2025-11-28 海南大学 一种识别手性葡萄糖的荧光探针的制备及检测方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007134446A1 (en) * 2006-05-23 2007-11-29 The University Of Western Ontario High-throughput screening of enantiomeric excess (ee)
CN101695756A (zh) * 2009-11-02 2010-04-21 中国科学院长春应用化学研究所 一种在聚电解质多层膜中制备金银合金纳米粒子的方法
CN101776604A (zh) * 2010-01-26 2010-07-14 中国科学院光电技术研究所 一种增强分子拉曼散射的基底制作方法
CN101865841A (zh) * 2010-06-28 2010-10-20 北京航空航天大学 一种高灵敏度表面等离子体共振传感器
CN105259157A (zh) * 2015-11-06 2016-01-20 合肥学院 一种热点可见的表面增强拉曼散射基底、制备方法及利用该基底检测分子的方法

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003029790A1 (en) * 2001-10-01 2003-04-10 Georgia Tech Research Corporation High-throughput chiral detector and methods for using same
US7191070B2 (en) * 2003-12-03 2007-03-13 Baylor University Methods for determining enantiomeric purity
CN102864493B (zh) * 2012-10-12 2015-03-18 江南大学 一种基于有机小分子盐的金纳米棒手性自组装材料的制备方法
CN103896846B (zh) * 2014-03-05 2016-05-25 上海师范大学 一种以壳聚糖修饰的金纳米通道膜分离组氨酸对映体的方法及其检测方法
CN106053810A (zh) * 2016-05-10 2016-10-26 江南大学 一种基于手性纳米组装体的循环肿瘤细胞检测新方法
CN106086793B (zh) * 2016-07-01 2018-09-04 陕西师范大学 一种二维手性金属-介质纳米结构及其制备方法
JP7066703B2 (ja) * 2016-10-26 2022-05-13 ユニバーシティ オブ バージニア パテント ファウンデーション キラル分析用のキャビティエンハンスト・フーリエ変換分光法
CN107036971B (zh) * 2016-11-14 2019-06-25 四川大学 手性传感元件、设备，手性表征方法，浓度表征方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007134446A1 (en) * 2006-05-23 2007-11-29 The University Of Western Ontario High-throughput screening of enantiomeric excess (ee)
CN101695756A (zh) * 2009-11-02 2010-04-21 中国科学院长春应用化学研究所 一种在聚电解质多层膜中制备金银合金纳米粒子的方法
CN101776604A (zh) * 2010-01-26 2010-07-14 中国科学院光电技术研究所 一种增强分子拉曼散射的基底制作方法
CN101865841A (zh) * 2010-06-28 2010-10-20 北京航空航天大学 一种高灵敏度表面等离子体共振传感器
CN105259157A (zh) * 2015-11-06 2016-01-20 合肥学院 一种热点可见的表面增强拉曼散射基底、制备方法及利用该基底检测分子的方法

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113588626A (zh) * 2021-08-24 2021-11-02 上海师范大学 一种苯丙氨酸对映体的拉曼光谱检测方法
CN113588626B (zh) * 2021-08-24 2024-05-24 上海师范大学 一种苯丙氨酸对映体的拉曼光谱检测方法

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