Method for recognizing excessive chiral enantiomers

Abstract

The invention discloses a method for identifying chiral enantiomeric excess, which is characterized in that a helical polymer P3HT-PPI is used as a gas sensitive active layer to construct a detector so as to detect the chiral enantiomeric excess. The configuration content in the mixed configuration chiral enantiomer is detected by utilizing the difference interaction between different configurations of a chiral object to be detected and the structure of a chiral detection object, and the mixed configuration chiral enantiomer can be applied to the fields of drug inferior quality identification, medical diagnosis and the like, has good cycling stability, is simple in manufacturing method, is easy to integrate, and can be widely applied to the fields of drug inferior quality identification, medical diagnosis and the like. Good application prospects are realized.

Description

Technical Field

[0001] This invention belongs to the field of gas detector technology, specifically relating to a method for identifying an excess of chiral enantiomers. Background Technology

[0002] The core background of research on chiral enantiomer excess (ee value) stems from the prevalence and importance of chirality in the life sciences and materials science world. Many organic molecules, especially drugs, pesticides, fragrances, and bioactive molecules, exist as mirror-image isomers (enantiomers), much like left and right hands that cannot be perfectly superimposed. The "thalidomide tragedy" of the mid-20th century shocked the world, its root cause being the drastically different pharmacological and teratogenic activities of the R and S enantiomers. This profoundly revealed that the biological activities, toxicities, and metabolic pathways of chiral enantiomers can be vastly different. Since then, the development of single-enantiomer drugs has become mainstream, and regulatory agencies have imposed strict requirements on the purity of drug enantiomers. At the same time, organic synthetic chemists are dedicated to developing efficient and highly selective asymmetric catalytic synthesis methods to directly prepare single-chiral molecules. Whether ensuring drug safety and efficacy (avoiding ineffective or toxic isomers) or evaluating and optimizing the efficiency of asymmetric synthesis reactions (a core indicator for measuring enantioselectivity), accurately determining the excess of the target enantiomer relative to its mirror image in the product (i.e., the ee value) has become an indispensable key link and technical requirement in fields such as chemistry, pharmacy, biology, and materials science. Research on accurate, rapid, and sensitive detection methods for the ee value is the cornerstone supporting the development of these fields.

[0003] However, since the physicochemical properties of enantiomers are mostly very similar, especially for nonpolar chiral substances like limonene, which lack polar functional groups, the interaction between enantiomers is weak, making separation impossible using liquid chromatography columns. Summary of the Invention

[0004] To address the shortcomings of the existing technology, this invention provides a method for identifying excess chiral enantiomers. This invention utilizes the interaction between the different configurations of the chiral analyte and the structural differences of the chiral detector to detect the (R / S) configuration content in chiral substances.

[0005] The method for identifying chiral enantiomer excess of the present invention uses the helical polymer P3HT-PPI as the gas-sensitive active layer to construct a detector, thereby realizing the detection of chiral enantiomer excess.

[0006] The helical polymer P3HT-PPI used as the gas-sensitive active layer is either pure L-configuration or pure D-configuration P3HT-PPI.

[0007] The detector includes a substrate and a gas-sensitive active layer disposed on the substrate, wherein a positive electrode and a negative electrode are disposed on the gas-sensitive active layer.

[0008] The substrate is obtained by CYTOP modification of a highly doped silicon wafer with a SiO2 layer.

[0009] The structure of the helical polymer P3HT-PPI is as follows: Figure 2 As shown.

[0010] Furthermore, the detector equipped with the gas-sensitive active layer is placed in a volatile chiral gas enantiomer atmosphere, and the chiral enantiomer excess (ee value) is obtained by detecting the current response value of the volatile chiral enantiomer.

[0011] The chiral enantiomers are selected from R,S configuration chiral limonene, R,S configuration chiral carvone, R,S configuration chiral phenylethylamine, or R,S configuration chiral phenylethanol. The structures are as follows: Figure 3 , Figure 7 As shown.

[0012] Chiral enantiomer excess (ee value) can be calculated by comparing the current response values ​​of volatile chiral enantiomers with those of pure R-configuration or pure S-configuration chiral enantiomers. The specific relationship is R... V = (R S -R1) / (R1-R R ).

[0013] Among them, R V R is the volume ratio of the R-configuration chiral enantiomer to the S-configuration chiral enantiomer in the mixed-configuration chiral enantiomer, R1 is the device response value of the mixed-configuration chiral enantiomer, R R and R S These are the device response values ​​for the chiral enantiomers with pure R and pure S configurations, respectively; R1, R R and R S The tests were conducted at the saturation concentrations of the corresponding volatile gases, and the saturation concentrations of the volatile gases of the mixed configuration chiral enantiomers were equal to the saturation concentrations of the volatile gases of their pure R and pure S configuration chiral enantiomers.

[0014] Taking limonene as an example, R V R is the volume ratio of (R)-limonene to (S)-limonene, R1 is the device response value of the mixed configuration limonene gas, and R R and R S These are the device response values ​​under limonene gas in pure R and pure S configurations, respectively.

[0015] At the same time, it is not difficult to find that the degree of change is related to the ability of chiral molecules to distinguish chiral limonene. The higher the degree of distinction, the greater the difference in current for pure R or pure S configuration limonene, and the more obvious the change in current for mixed configuration limonene.

[0016] The presence of an electrical current response from the gas-sensitive active layer to chiral molecules does not necessarily indicate its ability to detect the ee value of chiral enantiomers. The response must also exhibit significant differences, which are represented in this paper by the g-value. A low g-value does not necessarily indicate a differentiated response. If the resolution of the response is too low, errors cannot be eliminated, and thus an accurate ee value cannot be obtained. This invention uses the helical polymer P3HT-PPI as the gas-sensitive active layer, enabling precise identification of enantiomer excesses such as limonene through intermolecular interactions. The identification process only requires the device to come into contact with the volatile gas, avoiding contamination of the analyte. Furthermore, it achieves the conversion of chemical signals to electrical signals, facilitating more visual analysis of the detection process and greatly reducing equipment dependence.

[0017] Compared with existing technologies, the beneficial effects of this invention are reflected in:

[0018] 1. The device of the present invention has a simple device structure and a simple fabrication process, which provides a technical basis for realizing the integration and commercialization of the device.

[0019] 2. The chiral detector of the present invention outputs an electrical signal, which can be monitored in real time and has a fast detection speed. Furthermore, it can detect enantiomer excess by changing the configuration content of non-pure enantiomers and comparing the electrical signals. Attached Figure Description

[0020] Figure 1 This is a schematic diagram of the chiral detector of the present invention. Reference numerals in the diagram: 1. Substrate; 2. Gas-sensitive active layer; 3. Positive electrode; 4. Negative electrode.

[0021] Figure 2 The structural formulas are those of the helical polymers P3HT-PPI(L) and P3HT-PPI(D).

[0022] Figure 3 The structural formula is that of chiral limonene.

[0023] Figure 4 This is the current-voltage curve of Example 1 of the present invention under chiral limonene gas. Here, "Initial" refers to the current-voltage curve of the device in air, and "(R)-limonene" and "(S)-limonene" refer to the current-voltage curves of the device in "(R)-limonene" or "(S)-limonene" atmospheres, respectively.

[0024] Figure 5 The curve showing the difference in the discrimination of chiral limonene as a function of voltage is shown in Example 1 of the present invention.

[0025] Figure 6 The curves showing the change of current over time under different purities of limonene enantiomers under appropriate voltage conditions in Embodiment 1 of the present invention are shown.

[0026] Figure 7 The structural formulas are those of chiral carvone, chiral phenylethylamine, and chiral phenylethanol.

[0027] Figure 8 This is a curve showing the change of current over time under different chiral gases at the same voltage in Embodiment 2 of the present invention. Detailed Implementation

[0028] The embodiments of the present invention are described in detail below. These embodiments are implemented based on the technical solution of the present invention, and provide detailed implementation methods and specific operation processes. However, the scope of protection of the present invention is not limited to the following embodiments.

[0029] Example 1:

[0030] like Figure 1 As shown, this embodiment provides a detector for identifying an excess of chiral enantiomers. It comprises a gas-sensitive active layer 2 disposed on a substrate 1, and a positive electrode 3 and a negative electrode 4 disposed on the gas-sensitive active layer 2. Specifically, in this embodiment: the gas-sensitive active layer is P3HT-PPI(D); the substrate is a CYTOP-modified SiO2 / Si wafer; and the positive and negative electrodes are Au electrodes.

[0031] Take a highly doped silicon wafer with a SiO2 layer on its surface, clean it sequentially with piranha solution and deionized water, then dry it with nitrogen gas flow, spin-coat CYTOP as a modification layer on its surface at 3000 rpm for 40 s, and then place it on a 180℃ hot stage for heating and curing for 15 min to obtain the substrate.

[0032] PMMA was dissolved in dichlorobenzene at a concentration of 0.1 mg / mL, and P3HT-PPI(D) was dissolved in dichlorobenzene at a concentration of 5 mg / mL. The PMMA solution and semiconductor solution were mixed at a volume ratio of 2:1, and heated with shaking for 1 h. In a glove box, the mixture was spin-coated onto a cleaned Si wafer at 2000 rpm for 60 s. It was then dried overnight in a vacuum oven without heating to remove the solvent. The film was then transferred to a CYTOP-coated substrate using KOH solution, and the PMMA on the surface was washed off with acetone. It was then dried overnight in a vacuum oven without heating to remove residual solvent. Subsequently, Au was thermally evaporated onto the gas-sensitive active layer through a shadow mask to form a patterned electrode with a thickness of 50 nm, wherein the length and width of the channel were 4500 μm and 40 μm, respectively.

[0033] The chiral detector in this embodiment can determine the configuration content of a mixed gas by measuring the difference in current changes under different purities of limonene enantiomers.

[0034] like Figure 4 As shown, we tested the current-voltage curves of the detector of Embodiment 1 of the present invention in air and in S-configuration limonene and R-configuration limonene gases. Figure 5 As shown, we define the chiral gas discrimination effect of the device based on the current asymmetry factor g in the circularly polarized light detector, specifically, g = 2×(R S -R R ) / (R S +R R ), where R R and R S These are the device response values ​​under pure (R) and pure (S) limonene gas, respectively. We then selected the voltage value with the highest discriminative power for subsequent testing.

[0035] like Figure 6 As shown, the current increase is essentially linear with the increase in the content of S-configured limonene. Therefore, we can use this relationship for further analysis to determine the enantiomeric excess (ee value) of chiral substances in the mixed liquid. The quantification of enantiomers can be calculated by comparing the response value of the mixed gas with the response value of pure (R / S)-limonene. Specifically, the relationship is R... V = (R S -R1) / (R1-R R ), where R V R is the volume ratio of (R)-limonene to (S)-limonene, R1 is the device response value of the mixed configuration gas, and R R and R S These are the device response values ​​under pure (R) and pure (S) limonene gas, respectively.

[0036] Example 2:

[0037] The device fabrication process is the same as in Example 1, except that P3HT-PPI(D) is replaced with P3HT-PPI(L) for the semiconductor material. Since they are chiral enantiomers, their electrical properties should be essentially the same. Therefore, we used the voltage from Example 1 for subsequent experiments. The chiral detector in this example can identify other chiral liquids, including chiral carvone, chiral phenylethylamine, and chiral phenylethanol (structural formula as shown). Figure 7 As shown in the figure, we can also determine the configuration content of the gas mixture by the change in current under enantiomers of different purities.

[0038] like Figure 8As shown, we measured different chiral gases of varying purities. We observed that as the proportion of the R configuration gradually increases, its electrical response rises linearly. We can also use this relationship to perform qualitative and quantitative analysis of the configuration ratio. Furthermore, it is readily apparent that the degree of change is related to the chiral molecules' ability to distinguish chiral gases. Higher distinguishability results in greater current differences for pure R or pure S configuration limonene, and more significant current changes for mixed configuration chiral gases. Therefore, this invention provides an effective method for the over-detection of chiral enantiomers.

[0039] The above description is merely an exemplary embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for identifying chiral enantiomer excess, characterized in that: A detector was constructed using the helical polymer P3HT-PPI as the gas-sensitive active layer to achieve the detection of chiral enantiomer excess.

2. The method according to claim 1, characterized in that: The helical polymer P3HT-PPI used as the gas-sensitive active layer is either pure L-configuration or pure D-configuration P3HT-PPI.

3. The method according to claim 1, characterized in that: The detector includes a substrate and a gas-sensitive active layer disposed on the substrate, wherein a positive electrode and a negative electrode are respectively disposed on the gas-sensitive active layer.

4. The method according to claim 3, characterized in that: The substrate is obtained by CYTOP modification of a highly doped silicon wafer with a SiO2 layer.

5. The method according to claim 1, characterized in that: The detector equipped with the gas-sensitive active layer is placed in a volatile chiral enantiomer atmosphere. The chiral enantiomer excess is obtained by detecting the current response value of the volatile chiral enantiomer, specifically the relationship R. V = (R S -R1) / (R1-R R ); Among them, R V R is the volume ratio of the R-configuration chiral enantiomer to the S-configuration chiral enantiomer in the mixed-configuration chiral enantiomer, R1 is the device response value of the mixed-configuration chiral enantiomer, R R and R S These are the device response values ​​for the chiral enantiomers with pure R and pure S configurations, respectively; R1, R R and R S The detection was performed at the saturation concentration of the corresponding volatile gases.

6. The method according to claim 5, characterized in that: The chiral enantiomers are selected from chiral limonene with R,S configuration, chiral carvone with R,S configuration, chiral phenylethylamine with R,S configuration, or chiral phenylethanol with R,S configuration.

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