WO2021203746A1 - 手性分子ee值测量方法 - Google Patents

手性分子ee值测量方法 Download PDF

Info

Publication number
WO2021203746A1
WO2021203746A1 PCT/CN2020/139880 CN2020139880W WO2021203746A1 WO 2021203746 A1 WO2021203746 A1 WO 2021203746A1 CN 2020139880 W CN2020139880 W CN 2020139880W WO 2021203746 A1 WO2021203746 A1 WO 2021203746A1
Authority
WO
WIPO (PCT)
Prior art keywords
solution
chiral
value
host
measuring
Prior art date
Application number
PCT/CN2020/139880
Other languages
English (en)
French (fr)
Inventor
蒋伟
王力立
Original Assignee
南方科技大学
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 南方科技大学 filed Critical 南方科技大学
Publication of WO2021203746A1 publication Critical patent/WO2021203746A1/zh

Links

Classifications

    • 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
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/19—Dichroism
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/12—Circuits of general importance; Signal processing
    • G01N2201/122—Kinetic analysis; determining reaction rate
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/12—Circuits of general importance; Signal processing
    • G01N2201/129—Using chemometrical methods

Definitions

  • This application relates to the technical field of chemical property detection, in particular to a method for measuring the ee value of chiral molecules.
  • Chirality is a common phenomenon in nature (the term chirality means that an object cannot overlap with its mirror image, such as our hands, the left hand does not overlap with the mirror image of the right hand).
  • synthetic drugs, pesticides, food additives and other compounds also have chirality.
  • the enantiomers of chiral compounds have similar chemical and physical properties, but exhibit completely different drug and physiological activities. Due to the importance of chiral compounds in life sciences and pharmaceutical development, the synthesis of chiral compounds through asymmetric catalytic reactions has become a hot spot in chemistry research.
  • Enantiomeric excess value (abbreviation: ee value, enantiomeric Excess: Enantiomeric excess) is the evaluation criterion for the effect of asymmetric catalytic reaction. Therefore, the detection of ee value is very important in the screening of asymmetric catalytic conditions, that is to say, mastering the detection of ee value will directly affect whether Successfully synthesize chiral compounds through asymmetric catalytic reaction.
  • chromatography is mainly used to detect the ee value of chiral molecules. Although this method has high accuracy, the detection process is long and solvent-consuming, time-consuming, and high-cost, so that this method is not suitable for high-throughput screening of asymmetric catalytic conditions. And real-time monitoring of catalytic reactions.
  • the main purpose of this application is to propose a method for measuring the ee value of chiral molecules, which solves that the traditional method of detecting the ee value of chiral molecules is time-consuming and expensive, and is not suitable for high-throughput asymmetric catalytic condition screening and real-time monitoring technology problem.
  • this application proposes a method for measuring the ee value of a chiral molecule.
  • the method for measuring the ee value of a chiral molecule includes the following steps:
  • Adding a guest solution of a chiral molecule to be measured with a saturated concentration to the host solution to obtain a solution to be detected with a circular dichroism (abbreviation: CD, Circular Dichroism: circular dichroism) spectral signal saturated;
  • the first CD signal intensity value of the solution to be detected at a preset position of the CD spectrum is measured, and the first CD signal intensity value is substituted into a preset standard curve equation to calculate the ee value of the chiral molecule to be measured.
  • the method further includes:
  • step of drawing the preset standard curve equation based on the mixed solution and the standard guest solution with known ee value includes:
  • a standard curve is drawn using the ee value of the standard guest solution as the abscissa and the second CD signal intensity value as the ordinate to obtain the preset standard curve equation.
  • the preparation of the host solution, the chiral guest solution and the standard guest solution are all carried out in an aqueous solution.
  • the monochiral chiral guest solution includes R chiral chiral guest solution and S chiral chiral guest solution.
  • the predetermined host molecule is an amide molecular tube.
  • the first CD signal intensity value is substituted into a preset standard curve equation to calculate the chirality to be measured After the step of numerator ee value, it also includes:
  • the amide molecular tube is recovered from the solution to be tested, so as to prepare a new main body solution.
  • the step of recovering the amide molecular tube from the solution to be tested includes:
  • the pre-determined host molecules obtained by precipitation are ultrasonically cleaned and dried to complete the recovery of the amide molecular tube.
  • the concentration of the main body solution is between 0.01 mM and 0.1 mM.
  • the preset position is between 250 nm and 260 nm of the CD spectrum.
  • the method for measuring the ee value of chiral molecules proposed in this application is to prepare a host solution containing a preset host molecule; add a saturated concentration of the guest solution of the chiral molecule to be measured into the host solution to obtain CD signal saturation of the circular dichroism spectrum The solution to be detected; determine the first CD signal intensity value of the solution to be detected at a preset position of the CD spectrum, and substitute the first CD signal intensity value into the preset standard curve equation to calculate the chiral molecule to be measured Ee value.
  • the present application is based on the method of CD spectroscopy for determining the configuration of chiral molecules, adding a saturated concentration of the guest solution of the chiral molecule to be measured to a pre-prepared host solution containing a preset host molecule to form a solution to be detected with a saturated CD signal. Then the first CD signal intensity value of the solution to be tested at the preset position of the CD spectrum is determined, and the first CD signal intensity value is substituted into the preset standard curve equation drawn and calculated in advance, so as to calculate the to-be-measured The ee value of a chiral molecule.
  • This application realizes that the method of using CD spectroscopy to determine the configuration of chiral molecules is used to measure the ee value of chiral molecules. Compared with the traditional method of using chromatography to measure the ee value, this application uses CD spectroscopy to measure the ee value. Less solvents need to be detected, which reduces the cost of detection, and can detect the ee value of chiral molecules more quickly and easily, which is suitable for high-throughput screening of asymmetric catalytic conditions and real-time monitoring of catalytic reactions.
  • FIG. 1 is a schematic flowchart of an embodiment of a method for measuring ee value of a chiral molecule according to the present application
  • FIG. 2 is a schematic flowchart of another embodiment of a method for measuring ee value of a chiral molecule according to the present application
  • FIG. 3 is a schematic flowchart of another embodiment of a method for measuring ee value of a chiral molecule according to the present application
  • Figure 4 (1a) is a schematic diagram of the structure of a preset host molecule in an embodiment of a method for measuring the ee value of a chiral molecule according to the present application;
  • Figure 4 (1b) is a schematic diagram of the stereoisomers of the preset host molecule in an embodiment of a method for measuring the ee value of a chiral molecule according to the present application;
  • Fig. 5 is a schematic diagram of a representative structure of a detectable part of a chiral molecule in an embodiment of a method for measuring the ee value of a chiral molecule of the present application.
  • This application proposes a method for measuring the ee value of chiral molecules.
  • FIG. 1 is a schematic flow chart of the first embodiment of the method for measuring the ee value of chiral molecules according to the present application.
  • the embodiment of the application provides an embodiment of the method for measuring the ee value of a chiral molecule. Steps shown or described.
  • step S100 a host solution containing preset host molecules is prepared.
  • the preparation of the host solution is carried out in an aqueous solution to reduce the cost of detecting the ee value of chiral molecules; in addition, in this embodiment, the preset host molecule is as shown in Figure 4 (1a)
  • the amide molecular tube with the structure shown in Figure 4 (1a) can be selected as required.
  • a host solution with a preset concentration of a preset host molecule is prepared.
  • the preset concentration is the concentration of the prepared body solution, and the concentration is between 0.01 mM (millimolar) and 0.1 mM, such as 0.01 mM, 0.02 mM, 0.03 mM, 0.04 mM , 0.05 mM, 0.06 mM, 0.07 mM, 0.08 mM, 0.09 mM or 0.1 mM.
  • the structure shown in Figure 4 (1a) or the amide molecular tube of the stereoisomer shown in Figure 4 (1b) is used to prepare the main solution, which can be based on the hydrophobic effect and hydrogen bond recognition of the amide molecular tube.
  • Organic small molecules in the solution so that the main solution prepared by the amide molecular tube can be used to realize chiral epoxy, chiral alcohol, chiral amine, chiral imine, chiral ester, chiral ether (Figure 5 in turn Shown from left to right is the representative structure of each chiral molecule, including but not limited to these types of chiral molecules) and other molecules' ee value detection, which improves the versatility of optical measurement of ee value of chiral molecules.
  • the chiral molecule ee value measurement method of the present application further includes:
  • step S400 a single chiral chiral guest solution is added to the host solution to obtain a mixed solution saturated with a CD signal.
  • the chiral guest solution of single chirality includes the chiral guest solution of R chirality and the chiral guest solution of S chirality, wherein R chirality and S chirality respectively correspond to chiral molecules.
  • R chirality and S chirality respectively correspond to chiral molecules.
  • Two standard configurations ie, for example, the right hand and left hand of a human hand, R corresponds to the right and S corresponds to the left).
  • the pre-prepared R-chiral or S-chiral chiral guest solution is added one by one to obtain a mixed solution saturated with the CD signal.
  • the chiral guest solution of R chiral that is also prepared in the aqueous solution is added one by one to form the host solution and the chiral guest of R chiral.
  • the mixed solution of the solution in the process of adding the R chiral chiral guest solution successively, continue to perform CD detection on the formed mixed solution until the strongest CD signal is detected (that is, the CD signal is saturated, no longer added When the R chiral chiral guest solution is enhanced), stop adding the R chiral chiral guest solution to obtain a mixed solution of the host solution saturated with the CD signal and the R chiral chiral guest solution.
  • the signal intensity through circular dichroism can be achieved.
  • the positive and negative of the sum signal can be used to simultaneously detect the absolute chirality (R chirality or S chirality) and ee value of the chiral molecular target to be measured.
  • step S500 based on the mixed solution and a standard guest solution with a known ee value, the preset standard curve equation is drawn.
  • the pre-prepared R-chiral or S-chiral chiral guest solution is added one by one to obtain a mixed solution saturated with the CD signal.
  • the standard guest solution of a chiral molecule with known ee value is added to the mixed solution successively, and a standard curve identifying the ee value of the chiral molecule is drawn based on the continuously monitored CD signal of the mixed solution after adding the standard guest solution.
  • the preset standard curve equation used to calculate the ee value of chiral molecules is obtained.
  • step S500 includes:
  • Step S501 detecting the saturation concentration of the CD signal of the mixed solution, and adding a standard guest solution with a known ee value at the saturation concentration to the host solution;
  • Step S502 reading the second CD signal intensity value of the host solution after adding the standard guest solution at the preset position of the CD spectrum
  • step S503 a standard curve is drawn using the ee value of the standard guest solution as the abscissa and the second CD signal intensity value as the ordinate to obtain the preset standard curve equation.
  • the preset position is any position between 250 nm (nanometer) and 260 nm on the CD spectrum, for example, at 255 nm.
  • the detection of the R-chiral chiral guest solution in a prepared host solution with a concentration of 0.05 mM successively adds the R-chiral chiral guest solution in a mixed solution saturated with the CD signal.
  • Saturated concentration according to the saturated concentration, prepare a standard guest solution of the R chiral molecule 1-phenylethanol with an ee value of +100% in the aqueous solution, and then, also add this preparation to the prepared host solution with a concentration of 0.05 mM
  • step S200 a guest solution of a chiral molecule to be measured with a saturated concentration is added to the host solution to obtain a solution to be detected saturated with a CD signal of the circular dichroism spectrum.
  • the guest solution of the chiral molecule to be measured with a saturated concentration is added to obtain the solution to be detected with a saturated CD signal.
  • the chiral guest solution of R chiral is successively added to obtain a mixed solution with saturated CD signal, the chirality of R chirality The saturation concentration of the guest solution.
  • the guest solution of the chiral molecule to be measured is added to the host solution of mM to obtain the solution to be detected in which the CD signal is saturated.
  • the guest solution of the chiral molecule to be measured is also pre-prepared based on the aqueous solution.
  • the host solution containing the preset host molecule, the chiral guest solution with a single chirality, the standard guest solution with known ee value, and the guest solution of the chiral molecule to be measured are all prepared in an aqueous solution. Therefore, this application uses water as the detection solvent. Compared with the traditionally used non-aqueous solvents, this application is not only green and environmentally friendly, but also reduces the cost of detection.
  • the guest solution of the chiral molecule to be measured is added to the host solution with the preset concentration of the preset host molecule to prepare the solution to be detected saturated with CD signal, After the solution is fully mixed, the incubation time of the solution to be tested can be kept no more than 1 minute, or, after the solution to be tested is fully mixed, the CD signal intensity value at the preset position can be directly measured for the calculation of the measured solution The ee value of a chiral molecule.
  • Step S300 Determine the first CD signal intensity value of the solution to be detected at the preset position of the CD spectrum, and substitute the first CD signal intensity value into the preset standard curve equation to calculate the ee of the chiral molecule to be measured. value.
  • the solution to be detected for detecting the ee value of the chiral molecule to be measured is prepared, based on the CD spectrum of the solution to be detected, the first CD signal intensity value of the solution to be detected at the preset position of the CD spectrum is measured, and then The first CD signal intensity value is directly substituted into the preset standard curve equation calculated in advance and used to calculate the ee value of the chiral molecule, and the ee value of the chiral molecule to be measured is calculated.
  • the chiral molecule to be measured is 1-phenylethanol
  • a guest solution of unknown 1-phenylethanol ee value prepared in an aqueous solution is successively added to the mixed solution saturated with the CD signal to
  • the CD signal intensity of the solution to be tested also at 255nm Value (the average value of the CD signal intensity value at 255nm of the 3 times CD spectrum)
  • the value of the standard guest solution of 1-phenylethanol, taking the ee value of the standard guest solution of 1-phenylethanol added as the abscissa, on the CD spectrum of the mixed solution after adding the standard guest solution of 1-phenylethanol, 255nm Draw the standard curve with the CD signal
  • a host solution with a preset concentration of a preset host molecule with the structure shown in FIG. 4 and stereoisomers in an aqueous solution In the host solution, add the pre-prepared R-chiral or S-chiral chiral guest solution to saturate the CD signal of the mixed solution to obtain the saturation concentration of the chiral guest solution; based on this data in the preset concentration of the host solution A standard guest solution of a chiral molecule with a known ee value of saturated concentration is added to the standard guest solution, and a standard curve identifying the ee value of the chiral molecule is drawn based on the detected CD signal of the mixed solution after adding the standard guest solution, so as Calculate the preset standard curve equation for calculating the ee value of the chiral molecule; add the saturated concentration of the guest solution of the chiral molecule to be measured to the prepared host solution with the preset concentration of the host molecule to obtain The solution to be detected with saturated CD signal; based on the CD
  • the application of the chiral molecule ee value measurement method of the present application to real-time monitoring of the process of asymmetric catalytic reaction may specifically be:
  • the application of the chiral molecule ee value measurement method of the present application to the process of monitoring the racemization reaction may specifically be:
  • the application of the chiral molecule ee value measurement method of the present application to the determination of the optical purity of chiral drugs may specifically be as follows:
  • the chiral drug is formulated into an aqueous solution and then added to the main body solution, and the CD signal value of the system is measured. Substitute the signal intensity value at 255 nm into the standard curve equation to calculate the optical purity of the chiral drug.
  • the method for measuring the ee value of a chiral molecule of the present application further includes:
  • step S600 the amide molecular tube is recovered from the solution to be tested, so as to prepare a new main body solution.
  • the first CD signal intensity value of the solution to be detected at a preset position is measured, and then the first CD signal intensity value is substituted into the preset standard curve equation calculated in advance to calculate After the ee value of the chiral molecule to be measured, the pH of the solution to be tested is adjusted to recover the preset host molecule from the solution to be tested for preparing a new host solution, which realizes the recovery and reuse of the host molecule used.
  • step S600 includes:
  • Step S601 adjusting the pH value of the solution to be tested for precipitation to obtain the amide molecular tube
  • step S602 the amide molecular tube obtained by the precipitation is ultrasonically cleaned and dried to complete the recovery of the amide molecular tube.
  • the first CD signal intensity value of the solution to be detected at the preset position of the CD spectrum is measured, and then the first CD signal intensity value is substituted into the pre-calculated prediction.
  • the standard curve equation after calculating the ee value of the chiral molecule to be measured, add hydrochloric acid to adjust the solution to the solution to be tested (the solution after the ee value of the chiral molecule has been measured) until the pH value of the solution is Adjust to about 1, so that the amide molecular tube in the solution to be tested is precipitated under acidic conditions, and then the precipitated amide molecular tube is filtered and recovered, and dichloromethane is added to the recovered amide molecular tube for ultrasound Wash, repeat washing twice and then dry to obtain a pure amide molecular tube for subsequent repeated preparation of the main solution.
  • the first CD signal intensity value of the solution to be detected at a preset position is measured, and then the first CD signal intensity value is substituted into the preset standard calculated in advance.
  • the pH of the solution to be tested is adjusted to recover the amide molecular tube from the solution to be tested for the preparation of a new host solution, which realizes the control of the amide molecular tube used. Recycling and reuse further reduce the cost of testing.

Landscapes

  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

一种手性分子ee值测量方法，步骤包括：配制含有预设主体分子的主体溶液（S100）；在主体溶液中加入饱和浓度的待测量手性分子的客体溶液，得到CD信号饱和的待检测溶液（S200）；测定待检测溶液在CD光谱预设位置的第一CD信号强度值，将第一CD信号强度值代入预设标准曲线方程，以计算待测量手性分子的ee值（S300）。

Description

手性分子ee值测量方法
本申请要求：2020年4月9日申请的、申请号为202010278361.8、名称为“手性分子ee值测量方法”的中国专利申请的优先权，在此将其引入作为参考。
技术领域
本申请涉及化学性质检测技术领域，尤其涉及一种手性分子ee值测量方法。
 背景技术
手性是大自然界中普遍存在的一种现象（手性一词指一个物体不能与其镜像相重合，如我们的双手，左手与互成镜像的右手不重合）。除了自然存在的，人工合成的药物、农药、食品添加剂等化合物也具有手性。手性化合物对映异构体的化学、物理性质相近，但是表现出截然不同的药物和生理活性。由于手性化合物在生命科学和医药开发等方面的重要意义，通过不对称催化反应合成手性化合物已成为了化学研究的热点。
对映体过量值（简称：ee值，enantiomeric excess：对映体过量）是不对称催化反应效果的评价标准，因此，ee值的检测在不对称催化条件筛选中至关重要，也就是说，掌握好对ee值的检测将直接影响能否成功通过不对称催化反应合成手性化合物。传统主要采用色谱法来对手性分子ee值进行检测，虽然该方法准确率高，但是检测过程漫长且耗费溶剂，耗时长、成本高，以致该方法不适用于高通量的不对称催化条件筛选和催化反应的实时监控。
上述内容仅用于辅助理解本申请的技术方案，并不代表承认上述内容是现有技术。
 技术解决方案
本申请的主要目的是提出一种手性分子ee值测量方法，解决传统检测手性分子ee值的方式耗时长、成本高，不适用于高通量的不对称催化条件筛选和实时监控的技术问题。
为实现上述目的，本申请提出一种手性分子ee值测量方法，所述手性分子ee值测量方法，包括如下步骤：
配制含有预设主体分子的主体溶液；
在所述主体溶液中加入饱和浓度的待测量手性分子的客体溶液，得到圆二色(简称：CD，Circular Dichroism:圆二色) 光谱信号饱和的待检测溶液；
测定所述待检测溶液在CD光谱预设位置的第一CD信号强度值，将所述第一CD信号强度值代入预设标准曲线方程，以计算所述待测量手性分子的ee值。
进一步地，在所述配制含有预设主体分子的主体溶液的步骤之后，还包括：
在所述主体溶液中加入单一手性的手性客体溶液，得到CD信号饱和的混合溶液；
基于所述混合溶液和已知ee值的标准客体溶液，绘制所述预设标准曲线方程。
进一步地，所述基于所述混合溶液和已知ee值的标准客体溶液，绘制所述预设标准曲线方程的步骤，包括：
检测所述混合溶液CD信号的饱和浓度，并在所述主体溶液中加入所述饱和浓度下已知ee值的标准客体溶液；
读取加入所述标准客体溶液后的主体溶液在CD光谱所述预设位置的第二CD信号强度值；
以所述标准客体溶液的ee值为横坐标，所述第二CD信号强度值为纵坐标绘制标准曲线，以得到所述预设标准曲线方程。
进一步地，所述主体溶液、所述手性客体溶液和所述标准客体溶液的配制，均在水溶液中进行。
进一步地，所述单一手性的手性客体溶液包括R手性的手性客体溶液和S手性的手性客体溶液。
进一步地，所述预设主体分子为酰胺分子管。
进一步地，在所述测定所述待检测溶液在CD光谱预设位置的第一CD信号强度值，将所述第一CD信号强度值代入预设标准曲线方程，以计算所述待测量手性分子的ee值的步骤之后，还包括：
从所述待检测溶液中回收所述酰胺分子管，以用于配制新的所述主体溶液。
进一步地，所述从所述待检测溶液中回收所述酰胺分子管的步骤，包括：
调节所述待检测溶液的pH值以沉淀得到所述酰胺分子管；
对沉淀得到的所述预设主体分子进行超声清洗和干燥处理以完成对所述酰胺分子管的回收。
进一步地，所述主体溶液的浓度处于0.01 mM至0.1 mM之间。
进一步地，所述预设位置处于所述CD光谱的250 nm至260nm之间。
本申请提出的手性分子ee值测量方法，通过配制含有预设主体分子的主体溶液；在所述主体溶液中加入饱和浓度的待测量手性分子的客体溶液，得到圆二色光谱CD信号饱和的待检测溶液；测定所述待检测溶液在CD光谱预设位置的第一CD信号强度值，将所述第一CD信号强度值代入预设标准曲线方程，以计算所述待测量手性分子的ee值。
本申请基于CD光谱测定手性分子构型的方法，在预先配制的含有预设主体分子的主体溶液中加入饱和浓度的待测量手性分子的客体溶液，以形成CD信号饱和的待检测溶液，然后测定出该待检测溶液在CD光谱预设位置处的第一CD信号强度值，并将该第一CD信号强度值代入预先绘制计算的预设标准曲线方程中，从而计算得出该待测量手性分子的ee值。
本申请实现了，利用CD光谱测定手性分子构型的方法来对手性分子的ee值进行测量，相比于传统采用色谱法进行测量的方式，本申请利用CD光谱来测量ee值的方式所需检测溶剂更少，减少了检测成本，且能够更加快速、简便的检测出手性分子的ee值，得以适用于高通量的不对称催化条件筛选和催化反应的实时监控。
 附图说明
图1是本申请一种手性分子ee值测量方法一实施例的流程示意图；
图2是本申请一种手性分子ee值测量方法另一实施例流程示意图；
图3是本申请一种手性分子ee值测量方法又一实施例流程示意图；
图4（1a）是本申请一种手性分子ee值测量方法一实施例中预设主体分子的结构示意图；
图4（1b）是本申请一种手性分子ee值测量方法一实施例中预设主体分子的立体异构体示意图；
图5是本申请一种手性分子ee值测量方法一实施例中可检测部分手性分子代表性结构示意图。
本申请目的的实现、功能特点及优点将结合实施例，参照附图做进一步说明。
 本发明的实施方式
下面将结合本申请实施例，对本申请实施例中的技术方案进行清楚、完整地描述，应当理解，此处所描述的具体实施例仅仅用以解释本申请，仅仅是本申请的一部分实施例，而不是全部的实施例。基于本申请中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本申请保护的范围。
另外，各个实施例之间的技术方案可以相互结合，但是必须是以本领域普通技术人员能够实现为基础，当技术方案的结合出现相互矛盾或无法实现时应当认为这种技术方案的结合不存在，也不在本申请要求的保护范围之内。
本申请提出一种手性分子ee值测量方法。
请参照图1，图1为本申请手性分子ee值测量方法第一实施例的流程示意图。
本申请实施例提供了手性分子ee值测量方法的实施例，需要说明的是，虽然在流程图中示出了逻辑顺序，但是在某些情况下，可以以不同于此处的顺序执行所示出或描述的步骤。
本实施例手性分子ee值测量方法包括：
步骤S100，配制含有预设主体分子的主体溶液。
需要说明的是，本实施例中，主体溶液的配制在水溶液中进行，以减少手性分子ee值的检测成本；此外，本实施例中，预设主体分子为如图4（1a）所示结构的酰胺分子管，或者为如图4（1b）所示的酰胺分子管的立体异构体，针对不同的手性分子可根据需要选择如图4（1a）所示结构的酰胺分子管来配制主体溶液，或者选择如图4（1b）所示立体异构体的酰胺分子管来配制主体溶液。
在水溶液中，配制含有预设主体分子的预设浓度的主体溶液。
需要说明的是，本实施例中，预设浓度为配制完成的主体溶液的浓度，该浓度介于0.01 mM（毫摩尔）至0.1 mM之间，例如0.01 mM，0.02 mM，0.03 mM，0.04 mM，0.05 mM，0.06 mM，0.07 mM，0.08 mM，0.09 mM或0.1 mM。
具体地，例如，取0.56 mg如图4（1a）或者图4（1b）所示结构的酰胺分子管加入到10 mL容量瓶中，并加二次超纯水进行溶解以配制成浓度为0.05 mM的主体溶液，用于后续的手性分子ee值测量。
在本实施例中，选用如图4（1a）所示结构或者图4（1b）所示立体异构体的酰胺分子管来配制主体溶液，可基于该酰胺分子管的疏水作用和氢键识别溶液当中的有机小分子，从而，通过该酰胺分子管配制的主体溶液可用于实现对手性环氧、手性醇、手性胺、手性亚胺、手性酯、手性醚（图5依次从左至右所示为该各手性分子的代表性结构，包括但不限于这几类手性分子）等分子的ee值检测，提高了手性分子ee值光学测量的通用性。
进一步地，请参照图2，在本申请手性分子ee值测量方法的另一个实施例中，在上述步骤S100之后，本申请手性分子ee值测量方法还包括：
步骤S400，在所述主体溶液中加入单一手性的手性客体溶液，得到CD信号饱和的混合溶液。
需要说明的是，本实施例中，单一手性的手性客体溶液包括R手性的手性客体溶液和S手性的手性客体溶液，其中R手性和S手性分别对应手性分子的两种标准构型（即例如人手的右手和左手，R对应右、S对应左）。
在配制好的含有预设主体分子的预设浓度的主体溶液中，逐量加入预先配制的R手性或者为S手性的手性客体溶液，以得到CD信号饱和的混合溶液。
具体地，例如，在配制好的浓度为0.05 mM的主体溶液中，逐次加入，预先同样在水溶液当中配制好的R手性的手性客体溶液，以形成主体溶液与R手性的手性客体溶液的混合溶液，在逐次加入该R手性的手性客体溶液的过程中，持续对所形成的混合溶液进行CD检测，直到检测到CD信号最强（即CD信号处于饱和，不再随加入R手性的手性客体溶液而增强）时，停止继续加入该R手性的手性客体溶液，从而得到CD信号饱和的主体溶液与R手性的手性客体溶液的混合溶液。
在本实施例中，通过在主体溶液中加入单一手性（R手性或者为S手性）的手性客体溶液，来配制得到CD信号饱和的混合溶液，可以实现通过圆二色谱的信号强度和信号的正负性，来同时检测待测量手性分子目标物的绝对手性（R手性或者为S手性）和ee值。
步骤S500，基于所述混合溶液和已知ee值的标准客体溶液，绘制所述预设标准曲线方程。
在配制好的含有预设主体分子的预设浓度的主体溶液中，逐量加入预先配制的R手性或者为S手性的手性客体溶液，以得到CD信号饱和的混合溶液之后，基于在该混合溶液中逐次加入已知ee值的手性分子的标准客体溶液，并根据持续监测到的加入该标准客体溶液后混合溶液的CD信号，来绘制标识该手性分子ee值的标准曲线，从而求出用于计算手性分子ee值的预设标准曲线方程。
进一步地，步骤S500，包括：
步骤S501，检测所述混合溶液CD信号的饱和浓度，并在所述主体溶液中加入所述饱和浓度下已知ee值的标准客体溶液；
步骤S502，读取加入所述标准客体溶液后的主体溶液在CD光谱所述预设位置的第二CD信号强度值；
步骤S503，以所述标准客体溶液的ee值为横坐标，所述第二CD信号强度值为纵坐标绘制标准曲线，以得到所述预设标准曲线方程。
需要说明的是，在本实施例中，在使用已知ee值的标准客体溶液来绘制标准曲线，从而求算计算手性分子ee值的预设标准曲线方程的过程中，所使用标准客体溶液均需满足CD信号饱和的要求。
需要说明的是，本实施例中，预设位置为CD光谱上250 nm（纳米）至260nm之间的任意一个位置，例如255nm处。
具体地，例如，检测通过在配制好的浓度为0.05 mM的主体溶液中，逐次加入R手性的手性客体溶液，而得到CD信号饱和的混合溶液中，R手性的手性客体溶液的饱和浓度，按照该饱和浓度在水溶液当中配制ee值为+100%的R手性分子1-苯乙醇的标准客体溶液，然后，同样在配制好的浓度为0.05 mM的主体溶液中，加入该配制好的1-苯乙醇的标准客体溶液，以所加入1-苯乙醇的标准客体溶液的ee值为横坐标，以加入该1-苯乙醇的标准客体溶液后的混合溶液的CD光谱上，255nm处的CD信号强度值为纵坐标绘制标准曲线，并得到标准曲线方程y=0.145x-0.443，其中，y为CD信号强度，x为ee值大小。
进一步地，提出用于求算预设标准曲线方程的优选实施例：
配制不同ee值的高浓度手性分子的标准客体溶液，加入到0.05 mM的主体溶液中混匀，使该标准客体溶液的浓度达到CD饱和浓度之后，测定不同ee值的标准客体溶液诱导主体溶液产生的CD光谱。CD光谱的扫描区间为240nm至400 nm，共扫描3次，对光谱进行平均处理。以ee值为横坐标，并选取CD光谱255 nm处的信号强度值为纵坐标作CD标准曲线，得到相应的标准方程。
步骤S200，在所述主体溶液中加入饱和浓度的待测量手性分子的客体溶液，得到圆二色光谱CD信号饱和的待检测溶液。
在配制好的含有预设主体分子的预设浓度的主体溶液中，加入饱和浓度的待测量手性分子的客体溶液，以得到CD信号饱和的待检测溶液。
具体地，例如，按照检测到的在配制好的浓度为0.05 mM的主体溶液中，逐次加入R手性的手性客体溶液，而得到CD信号饱和的混合溶液过程中，R手性的手性客体溶液的饱和浓度，预先在水溶液当中配制一定饱和浓度的待测量手性分子的客体溶液（未知ee值），然后，在配制好的浓度为0.05 mM的主体溶液中，加入该待测量手性分子的客体溶液，从而得到CD信号处于饱和的待检测溶液。
需要说明的是，本实施例中，待测量手性分子的客体溶液同样是基于水溶液预先配制得到的。
在本实施例中，含有预设主体分子的主体溶液、单一手性的手性客体溶液、已知ee值的标准客体溶液以及待测量手性分子的客体溶液，均是在水溶液当中配制得到的，从而，本申请以水作为检测溶剂，相比传统使用的非水溶剂，本申请不仅绿色环保，也降低了检测成本。
进一步地，在另一个实施例中，在向含有预设主体分子的预设浓度的主体溶液中加入待测量手性分子的客体溶液，以配制得到CD信号饱和的待检测溶液时，在待检测溶液充分混匀之后，可保持待检测溶液的孵育时间不大于1分钟，或者，在待检测溶液充分混匀之后，即可直接进行预设位置处CD信号强度值的测定以用于计算待测量手性分子的ee值。如此，通过在配制用于检测待测量手性分子的ee值的待检测溶液时，仅需混合溶液与待测量手性分子的客体溶液充分混匀之后，保持极短的孵育时间或者无需等待孵育，即可进行待测量手性分子的ee值的测量计算，实现了ee值的快速测量，确保了本申请检测手性分子ee值测量方法，得以适用于高通量的不对称催化条件筛选和催化反应的实时监控。
步骤S300，测定所述待检测溶液在CD光谱预设位置的第一CD信号强度值，将所述第一CD信号强度值代入预设标准曲线方程，以计算所述待测量手性分子的ee值。
在配制得到用于检测待测量手性分子的ee值的待检测溶液之后，基于该待检测溶液的CD光谱，测定该待检测溶液的在CD光谱预设位置的第一CD信号强度值，然后将该第一CD信号强度值直接代入预先求算得出，用于计算手性分子ee值的预设标准曲线方程中，计算该待测量手性分子的ee值。
具体地，例如，待测量手性分子为1-苯乙醇，则在将预先在水溶液当中配制好的未知1-苯乙醇ee值的客体溶液，逐次加入至该CD信号饱和的混合溶液当中，以制备得到检测1-苯乙醇的ee值，且CD信号饱和的待检测溶液之后，基于测定该待检测溶液的CD光谱（测定3次），选取该待检测溶液的同样在255nm处的CD信号强度值（3次CD光谱255nm处的CD信号强度值的平均值），然后，将该255nm处的CD信号强度值，作为“y”代入至预先根据在CD信号饱和的混合溶液当中加入已知ee值的1-苯乙醇的标准客体溶液，以所加入1-苯乙醇的标准客体溶液的ee值为横坐标，以加入该1-苯乙醇的标准客体溶液后的混合溶液的CD光谱上，255nm处的CD信号强度值为纵坐标绘制标准曲线，求算得到的标准曲线方程y=0.145x-0.443中，从而计算得出待测量手性分子1-苯乙醇在不对称催化反应中的ee值。
本实施例中，通过在水溶液中，配制含有如图4所示结构和立体异构体的预设主体分子的预设浓度的主体溶液；在配制好的含有预设主体分子的预设浓度的主体溶液中，加入预先配制的R手性或者为S手性的手性客体溶液，使混合溶液的CD信号饱和，以得到手性客体溶液的饱和浓度；基于此数据在预设浓度的主体溶液中分别加入饱和浓度的已知ee值的手性分子的标准客体溶液，并根据检测到的加入该标准客体溶液后混合溶液的CD信号，来绘制标识该手性分子ee值的标准曲线，从而求出用于计算手性分子ee值的预设标准曲线方程；在配制好的含有预设主体分子的预设浓度的主体溶液中，加入饱和浓度的待测量手性分子的客体溶液，以得到CD信号饱和的待检测溶液；基于该待检测溶液的CD光谱，选取该待检测溶液的在预设位置的第一CD信号强度值，然后将该第一CD信号强度值直接代入预先求算得出，用于计算手性分子ee值的预设标准曲线方程中，计算该待测量手性分子的ee值。
实现了，利用圆二色光谱测定手性分子构型的方法来对手性分子的ee值进行测量，相比于传统采用色谱法进行测量的方式，本申请能够更加快速、简便的检测出手性分子的ee值，从而得以适用于高通量的不对称催化条件筛选和催化反应的实时监控。
进一步地，在另一个实施例中，本申请手性分子ee值测量方法应用于实时监控不对称催化反应的过程具体可以为：
在圆二色谱样品池中加入浓度为1 mM的R-乙酸-1-苯乙醇酯和0.05 mM的大环主体，随后加入终浓度为100 mM的氢氧化钠溶液。将样品池置于圆二色谱仪中，对样品255 nm处的CD信号进行实时测试。R-乙酸-1-苯乙醇酯在碱性条件下水解生成手性R-1-苯乙醇，CD信号发生变化。通过对CD信号的监控可以实现对不对称催化反应的实时监控。
进一步地，在另一个实施例中，本申请手性分子ee值测量方法应用于监控外消旋化反应的过程具体可以为：
在50mL的圆底烧瓶中加入25 mL浓度为80 mM的R-1-苯乙醇水溶液，向该水溶液中加入0.5 g Amberlyst-15（一种酸性催化剂），65℃加热回流并快速搅拌。每隔一段时间，取25 L溶液与2 mL 0.05 mM的主体溶液混合后测CD光谱3次，待取平均后将255 nm处的CD信号强度值代入标准曲线方程计算ee值，实现外消旋化进程的实时监控。
进一步地，在另一个实施例中，本申请手性分子ee值测量方法应用于手性药物光学纯度测定的过程具体可以为：
将手性药物配制成水溶液后加入到主体溶液中，测定体系的CD信号值。将255 nm处的信号强度值代入到标准曲线方程，计算手性药物的光学纯度。
进一步地，基于上述手性分子ee值测量方法第一实施例，提出本申请手性分子ee值测量方法的第二实施例。
请参照图3，本实施例中，在上述步骤S300之后，本申请手性分子ee值测量方法还包括：
步骤S600，从所述待检测溶液中回收所述酰胺分子管，以用于配制新的所述主体溶液。
在基于待检测溶液的CD光谱，测定该待检测溶液的在预设位置的第一CD信号强度值，然后将该第一CD信号强度值代入预先求算得出的预设标准曲线方程中，计算该待测量手性分子的ee值之后，基于调节待检测溶液的酸碱度以从该待检测溶液中回收预设主体分子用于配制新的主体溶液，实现了对所使用主体分子的回收重复利用。
进一步地，步骤S600，包括：
步骤S601，调节所述待检测溶液的pH值以沉淀得到所述酰胺分子管；
步骤S602，对沉淀得到的所述酰胺分子管进行超声清洗和干燥处理以完成对所述酰胺分子管的回收。
具体地，例如，在基于待检测溶液的CD光谱，测定该待检测溶液的在CD光谱预设位置的第一CD信号强度值，然后将该第一CD信号强度值代入预先求算得出的预设标准曲线方程中，计算该待测量手性分子的ee值之后，向该待检测溶液（已经进行手性分子的ee值测量之后的溶液）中加入盐酸调节溶液，直至该溶液的pH值被调节至1左右，从而使该待检测溶液中的酰胺分子管在酸性条件下沉淀出来，然后，对沉淀出来的酰胺分子管进行过滤回收，并在回收的酰胺分子管中加入二氯甲烷进行超声清洗，重复清洗两遍之后干燥得到纯的酰胺分子管留待后续重复配制主体溶液。
本实施例中，在基于待检测溶液的CD光谱，测定该待检测溶液的在预设位置的第一CD信号强度值，然后将该第一CD信号强度值代入预先求算得出的预设标准曲线方程中，计算该待测量手性分子的ee值之后，基于调节待检测溶液的酸碱度以从该待检测溶液中回收酰胺分子管用于配制新的主体溶液，实现了对所使用酰胺分子管的回收重复利用，更进一步地降低了检测成本。
需要说明的是，在本文中，术语“包括”、“包含”或者其任何其他变体意在涵盖非排他性的包含，从而使得包括一系列要素的过程、方法、物品或者系统不仅包括那些要素，而且还包括没有明确列出的其他要素，或者是还包括为这种过程、方法、物品或者系统所固有的要素。在没有更多限制的情况下，由语句“包括一个……”限定的要素，并不排除在包括该要素的过程、方法、物品或者系统中还存在另外的相同要素。
上述本申请实施例序号仅仅为了描述，不代表实施例的优劣。
以上仅为本申请的优选实施例，并非因此限制本申请的专利范围，凡是利用本申请说明书及附图内容所作的等效结构或等效流程变换，或直接或间接运用在其他相关的技术领域，均同理包括在本申请的专利保护范围内。

Claims (17)

  1. 一种手性分子对映体过量ee值测量方法，其中，所述手性分子ee值测量方法，包括如下步骤：
    配制含有预设主体分子的主体溶液；
    在所述主体溶液中加入饱和浓度的待测量手性分子的客体溶液，得到圆二色光谱CD信号饱和的待检测溶液；
    测定所述待检测溶液在CD光谱预设位置的第一CD信号强度值，将所述第一CD信号强度值代入预设标准曲线方程，以计算所述待测量手性分子的ee值。
  2. 如权利要求1所述的手性分子ee值测量方法，其中，在所述配制含有预设主体分子的主体溶液的步骤之后，还包括：
    在所述主体溶液中加入单一手性的手性客体溶液，得到CD信号饱和的混合溶液；
    基于所述混合溶液和已知ee值的标准客体溶液，绘制所述预设标准曲线方程。
  3. 如权利要求2所述的手性分子ee值测量方法，其中，所述基于所述混合溶液和已知ee值的标准客体溶液，绘制所述预设标准曲线方程的步骤，包括：
    检测所述混合溶液CD信号的饱和浓度，并在所述主体溶液中加入所述饱和浓度下已知ee值的标准客体溶液；
    读取加入所述标准客体溶液后的主体溶液在CD光谱所述预设位置的第二CD信号强度值；
    以所述标准客体溶液的ee值为横坐标，所述第二CD信号强度值为纵坐标绘制标准曲线，以得到所述预设标准曲线方程。
  4. 如权利要求2所述的手性分子ee值测量方法，其中，所述主体溶液、所述手性客体溶液和所述标准客体溶液的配制，均在水溶液中进行。
  5. 如权利要求2所述的手性分子ee值测量方法，其中，所述单一手性的手性客体溶液包括R手性的手性客体溶液和S手性的手性客体溶液。
  6. 如权利要求1至3任一项所述的手性分子ee值测量方法，其中，所述预设主体分子为酰胺分子管。
  7. 如权利要求1至3任一项所述的手性分子ee值测量方法，其中，所述预设主体分子为酰胺分子管的立体异构体。
  8. 如权利要求6所述的手性分子ee值测量方法，其中，在所述测定所述待检测溶液在CD光谱预设位置的第一CD信号强度值，将所述第一CD信号强度值代入预设标准曲线方程，以计算所述待测量手性分子的ee值的步骤之后，还包括：
    从所述待检测溶液中回收所述酰胺分子管，以用于配制新的所述主体溶液。
  9. 如权利要求8所述的手性分子ee值测量方法，其中，所述从所述待检测溶液中回收所述酰胺分子管的步骤，包括：
    调节所述待检测溶液的pH值以沉淀得到所述酰胺分子管；
    对沉淀得到的所述酰胺分子管进行超声清洗和干燥处理以完成对所述酰胺分子管的回收。
  10. 如权利要求1所述的手性分子ee值测量方法，其中，所述主体溶液的浓度处于0.01 mM至0.1 mM之间。
  11. 如权利要求1所述的手性分子ee值测量方法，其中，所述预设位置处于所述CD光谱的250 nm至260nm之间。
  12. 如权利要求11所述的手性分子ee值测量方法，其中，所述预设位置为255nm。
  13. 如权利要求1所述的手性分子ee值测量方法，其中，
    配制含有预设主体分子的主体溶液的浓度介于0.01 mM至0.1 mM之间。
  14. 如权利要求13所述的手性分子ee值测量方法，其中，
    配制含有预设主体分子的主体溶液的浓度为0.05 mM。
  15. 如权利要求1所述的手性分子ee值测量方法，其中，所述在所述主体溶液中加入饱和浓度的待测量手性分子的客体溶液，得到圆二色光谱CD信号饱和的待检测溶液的步骤之后，所述测量方法进一步包括：
    在待检测溶液充分混匀之后，保持待检测溶液的孵育时间不大于1分钟。
  16. 如权利要求1所述的手性分子ee值测量方法，其中，所述在所述主体溶液中加入饱和浓度的待测量手性分子的客体溶液，得到圆二色光谱CD信号饱和的待检测溶液的步骤之后，所述测量方法进一步包括：
    直接进行预设位置处CD信号强度值的测定。
  17. 如权利要求1-16所述的手性分子ee值测量方法，其中，所述手性分子可以是：手性环氧、手性醇、手性胺、手性亚胺、手性酯、或者手性醚。
PCT/CN2020/139880 2020-04-09 2020-12-28 手性分子ee值测量方法 WO2021203746A1 (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202010278361.8A CN111398181A (zh) 2020-04-09 2020-04-09 手性分子ee值测量方法
CN202010278361.8 2020-04-09

Publications (1)

Publication Number Publication Date
WO2021203746A1 true WO2021203746A1 (zh) 2021-10-14

Family

ID=71436939

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2020/139880 WO2021203746A1 (zh) 2020-04-09 2020-12-28 手性分子ee值测量方法

Country Status (2)

Country Link
CN (1) CN111398181A (zh)
WO (1) WO2021203746A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117607123A (zh) * 2023-12-04 2024-02-27 海南大学 一种分辨低浓度手性物质对映体的方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111398181A (zh) * 2020-04-09 2020-07-10 南方科技大学 手性分子ee值测量方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109705036A (zh) * 2018-12-10 2019-05-03 五邑大学 含氟喹啉酰胺折叠体、制备方法及手性识别方法和应用
CN110297044A (zh) * 2018-03-21 2019-10-01 中国医学科学院药物研究所 一种识别氨基酸及肽类化合物绝对构型和光学纯度的方法
WO2020056012A1 (en) * 2018-09-11 2020-03-19 Georgetown University Quantitative auxiliary-free chirality sensing with a metal probe
CN111398181A (zh) * 2020-04-09 2020-07-10 南方科技大学 手性分子ee值测量方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110297044A (zh) * 2018-03-21 2019-10-01 中国医学科学院药物研究所 一种识别氨基酸及肽类化合物绝对构型和光学纯度的方法
WO2020056012A1 (en) * 2018-09-11 2020-03-19 Georgetown University Quantitative auxiliary-free chirality sensing with a metal probe
CN109705036A (zh) * 2018-12-10 2019-05-03 五邑大学 含氟喹啉酰胺折叠体、制备方法及手性识别方法和应用
CN111398181A (zh) * 2020-04-09 2020-07-10 南方科技大学 手性分子ee值测量方法

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHEN XUAN-XUAN, JIANG YUN-BAO, ANSLYN ERIC V.: "A racemate-rules effect supramolecular polymer for ee determination of malic acid in the high ee region", CHEMICAL COMMUNICATIONS, ROYAL SOCIETY OF CHEMISTRY, UK, vol. 52, no. 85, 1 January 2016 (2016-01-01), UK , pages 12669 - 12671, XP055856842, ISSN: 1359-7345, DOI: 10.1039/C6CC06716F *
JO HYUN HWA, LIN CHUNG-YON, ANSLYN ERIC V.: "Rapid Optical Methods for Enantiomeric Excess Analysis: From Enantioselective Indicator Displacement Assays to Exciton-Coupled Circular Dichroism", ACCOUNTS OF CHEMICAL RESEARCH, ACS , WASHINGTON , DC, US, vol. 47, no. 7, 15 July 2014 (2014-07-15), US , pages 2212 - 2221, XP055856840, ISSN: 0001-4842, DOI: 10.1021/ar500147x *
LIN CHUNG-YON, GIULIANO MICHAEL W., ELLIS BRYAN D., MILLER SCOTT J., ANSLYN ERIC V.: "From substituent effects to applications: enhancing the optical response of a four-component assembly for reporting ee values", CHEMICAL SCIENCE, ROYAL SOCIETY OF CHEMISTRY, UNITED KINGDOM, vol. 7, no. 7, 1 January 2016 (2016-01-01), United Kingdom , pages 4085 - 4090, XP055856841, ISSN: 2041-6520, DOI: 10.1039/C5SC04629G *
WANG LI-LI, CHEN ZHAO, LIU WEI-ER, KE HUA, WANG SHENG-HUA, JIANG WEI: "Molecular Recognition and Chirality Sensing of Epoxides in Water Using Endo -Functionalized Molecular Tubes", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, vol. 139, no. 25, 28 June 2017 (2017-06-28), pages 8436 - 8439, XP055856839, ISSN: 0002-7863, DOI: 10.1021/jacs.7b05021 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117607123A (zh) * 2023-12-04 2024-02-27 海南大学 一种分辨低浓度手性物质对映体的方法
CN117607123B (zh) * 2023-12-04 2024-05-03 海南大学 一种分辨低浓度手性物质对映体的方法

Also Published As

Publication number Publication date
CN111398181A (zh) 2020-07-10

Similar Documents

Publication Publication Date Title
WO2021203746A1 (zh) 手性分子ee值测量方法
CN110172337B (zh) 一种苯并噻唑衍生物荧光探针及其制备方法和应用
Wei et al. A two-step responsive colorimetric probe for fast detection of formaldehyde in weakly acidic environment
CN108003869B (zh) 一种高灵敏检测次氯酸根的荧光探针及其合成方法与应用
CN106833628B (zh) 表面修饰的碳纳米点的制备方法和作为荧光探针检测Cu2+及谷胱甘肽的应用
CN109575042B (zh) 一种具有螺吡喃特性的手性荧光探针及其制备方法和应用
CN110156688B (zh) 一种靶向内质网检测极性的荧光探针及其应用
CN111349070B (zh) 一种用于检测生物细胞粘度的近红外荧光分子探针及其制备方法和应用
CN107417671A (zh) 一种含喹啉取代的香豆素衍生物及其制备方法和在比率型pH荧光探针上的应用
CN111289425A (zh) 基于荧光标记流式单分子计数的蛋白质含量计量基准方法
CN112142639B (zh) 一种基于醛基的手性氨基酸识别探针及其制备方法和应用
Prabodh et al. Fluorescence detected circular dichroism (FDCD) for supramolecular host–guest complexes
CN105527277B (zh) 一种雌酮分子印迹电化学发光传感器的制备方法及应用
CN110092771A (zh) 一种用于人血清白蛋白检测的荧光探针及其制备方法、荧光试剂盒
CN111349101B (zh) 一种对生物细胞粘度响应的Turn-on型荧光分子探针及其制备方法和应用
CN105622540A (zh) 一种co探针及其制备方法和应用
CN110845320B (zh) 一种联萘醛手性荧光探针及其制备方法和应用
CN111040465A (zh) 一种双模态检测二氧化硫的近红外荧光探针及其制备方法和用途
TWI824243B (zh) 一種胜肽拓印導電聚合物及其用途
CN108896523B (zh) 一种荧光增强型检测次氯酸根的方法和应用
CN114621210A (zh) 一种新型检测l-半胱氨酸荧光分子探针的制备方法及应用
CN115825057B (zh) 一种喹啉羧酸酯类有机杂环小分子的应用
CN115745936B (zh) 一种荧光化合物及其制备方法和作为荧光探针的应用
CN114920776B (zh) 一种甲醛荧光探针及其制备方法和应用
CN114716360A (zh) 一种用于检测酸性pH变化的比色/光谱双模式荧光传感器的制备及应用

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20929695

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20929695

Country of ref document: EP

Kind code of ref document: A1