A Multi-Substituted Ferrocene-Cu + Chiral materials, preparation methods and their applications in electrochemical chiral recognition
By introducing Cu+ into the polysubstituted ferrocene, a ternary complex with D-type amino acids is formed, and the configuration difference is used to identify amino acid enantiomers, the problem of limited recognition ability in the prior art is solved, and efficient amino acid enantiomer recognition is achieved.
Patent Information
- Application Number
- CN202211412169.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2022-11-11
- Publication Date
- 2025-04-11
- Estimated Expiration
- 2042-11-11
AI Technical Summary
The prior art is difficult to efficiently identify and separate enantiomers of amino acids, especially in electrochemical chiral recognition, with limited recognition capabilities.
By introducing Cu+, polysubstituted ferrocene (such as Taniaphos) forms a ternary complex with Cu+ and D-type amino acids, and the identification of amino acid enantiomers is achieved using configuration differences.
It realizes efficient recognition of amino acid enantiomers, enhances the chiral recognition ability of multi-substituted ferrocene, and especially significantly improves the recognition efficiency in electrochemical chiral recognition.
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Figure CN115894574B_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of chiral materials, and specifically relates to a multi-substituted ferrocene-Cu + Chiral materials, preparation methods and their applications in electrochemical chiral recognition. Technical Background
[0002] Chiral recognition is of great significance for catalysis and drug synthesis. Chirality refers to the property that the mirror images of isomers do not overlap, which plays an important role in the framework of food and life sciences. Therefore, the study of chiral substances has attracted much attention in recent years. In addition, efficient identification and detection of chiral isomers is of great significance in the fields of medicine and pharmaceuticals. Chiral amino acids are widely used in pharmaceuticals, food, cosmetics, agriculture and other industries.
[0003] Tryptophan (Trp) is not only one of the essential amino acids for the human body, but also a basic component of protein and an important precursor for the synthesis of auxin in organisms. L-Tryptophan (L-Trp) plays a significant role in organisms and helps control people's emotions. Lack of L-Trp may lead to some diseases and is widely used in the food and pharmaceutical industries. D-Tryptophan (D-Trp) is a non-protein amino acid. Although it does not participate in the metabolism of living systems, D-Trp is often used to synthesize immunosuppressants and anticancer drugs. Therefore, exploring a simple, efficient and practical method for identifying amino acid enantiomers is of great significance to pharmaceutics and biochemistry.
[0004] Electrochemical methods have attracted more and more attention in recent years due to their advantages such as easy operation, low cost, high efficiency and strong recognition ability. The construction of electrochemical chiral interfaces is a hot topic in the research of electrochemical sensors.
[0005] (2R)-1-[(S)-α-(dimethylamino)-2-(diphenylphosphino)benzyl]-2-diphenylphosphinoferrocene (Taniaphos) is a common multi-substituted ferrocene, often used as a catalyst for asymmetric synthesis. Since the benzene ring on the substituent of Taniaphos can rotate, it is considered to be a chiral diphosphine ligand ferrocene. Therefore, various amino acid enantiomers can be separated by adjusting its stereochemical structure. Taniaphos, Cu + D-amino acids can form ternary complexes to enhance the chirality of Taniaphos, and electrochemical recognition based on Taniaphos has received little attention. Inspired by this, we prepared multi-substituted ferrocene-Cu + (Taniaphos-Cu + ) chiral materials, providing a good chiral interface for molecular recognition. Summary of the invention
[0006] In view of the problems existing in the above-mentioned prior art, the object of the present invention is to design and provide a multi-substituted ferrocene-Cu + Chiral materials, preparation methods and applications in electrochemical chiral recognition. The substituents on the multi-substituted ferrocene containing phenylphosphino groups, wherein the P atom is used to react with Cu + The present invention prepares multi-substituted ferrocene (such as Taniaphos)-Cu + Chiral interface for electrochemical chiral recognition of amino acid enantiomers. + Introduced into polysubstituted ferrocene, making polysubstituted ferrocene (such as Taniaphos), Cu + , D-amino acids form ternary complexes, while L-amino acids cannot form ternary complexes with polysubstituted ferrocene (such as Taniaphos) and Cu due to their different configurations. + The formation of a ternary complex enables the recognition of amino acid enantiomers. + The introduction of not only makes multi-substituted ferrocene (such as Taniaphos), D-amino acids and Cu + The formation of a ternary complex also enhances the chiral recognition ability of multi-substituted ferrocenes (such as Taniaphos).
[0007] In order to achieve the above object, the present invention adopts the following technical solutions:
[0008] In one aspect, the present invention provides a polysubstituted ferrocene-Cu + Chiral materials, the polysubstituted ferrocene-Cu + The chiral materials are multi-substituted ferrocene, Cu + The binary complex formed.
[0009] The multi-substituted ferrocene-Cu + The chiral material, wherein the polysubstituted ferrocene is a polysubstituted ferrocene containing a phenylphosphine group on the substituent, and preferably the polysubstituted ferrocene is (2R)-1-[(S)-α-(dimethylamino)-2-(diphenylphosphino)benzyl]-2-diphenylphosphinoferrocene, (Rp)-1-[(R)-α-(dimethylamino)-2-(di-p-tolylphosphino)benzyl]-2-di-p-tolylphosphinoferrocene.
[0010] The present invention provides a multi-substituted ferrocene-Cu + The method for preparing a chiral material is characterized by comprising the following steps:
[0011] Weigh the monovalent copper ion complex and polysubstituted ferrocene, add 1,2-dichloroethane, and after they are completely dissolved, transfer to a 100 mL volumetric flask, make up to volume, shake well, and let stand to obtain polysubstituted ferrocene-Cu +Solution.
[0012] The multi-substituted ferrocene-Cu + A method for preparing a chiral material, wherein the monovalent copper ion complex comprises tetraacetonitrile copper (I) hexafluorophosphate, the mass ratio of the monovalent copper ion complex to polysubstituted ferrocene is 36-40:67-71 mg; the mass and volume ratio of the monovalent copper ion complex to 1,2-dichloroethane is 36-40 mg:8-12 mL.
[0013] The multi-substituted ferrocene-Cu + The preparation method of chiral material comprises the following standing conditions: temperature 2-6°C, time 10-14h.
[0014] In a second aspect, the present invention provides an electrode capable of identifying electroactive amino acid enantiomers, wherein the surface of the electrode capable of identifying electroactive amino acid enantiomers contains the multi-substituted ferrocene-Cu + Chiral materials.
[0015] The present invention provides a method for preparing an electrode capable of identifying electroactive amino acid enantiomers, comprising the following steps:
[0016] Weigh polysubstituted ferrocene-Cu + Chiral materials are evenly dropped on the electrode surface and dried to obtain multi-substituted ferrocene-Cu + Chiral material modified electrodes.
[0017] In the preparation method, the electrode is a glassy carbon electrode.
[0018] In a third aspect, the present invention provides the use of the electrode in identifying electroactive amino acid enantiomers.
[0019] The application is characterized in that the electroactive amino acid enantiomers include tryptophan, cysteine and tyrosine.
[0020] Compared with the prior art, the present invention has the following beneficial effects:
[0021] The chiral material of the present invention is obtained by introducing Cu + , so that the polysubstituted ferrocene containing phenylphosphine, Cu + , D-amino acids form ternary complexes, while L-amino acids cannot form ternary complexes with polysubstituted ferrocene and Cu due to their different configurations. + The formation of a ternary complex enables the recognition of amino acid enantiomers. + The introduction of not only makes multi-substituted ferrocene, D-amino acid and Cu + The formation of a ternary complex also enhances the chiral recognition ability of multi-substituted ferrocenes such as Taniaphos. BRIEF DESCRIPTION OF THE DRAWINGS
[0022] Figure 1 is the Taniaphos-Cu in Example 1 + Scanning electron microscope image of
[0023] Figure 2 [(CH3CN)4Cu]PF6, Taniaphos and Taniaphos-Cu in Example 1 + Fourier transform infrared spectrum of
[0024] Figure 3 The bare glassy carbon electrode (GCE), [(CH3CN)4Cu]PF6 / GCE, Taniaphos / GCE and Taniaphos-Cu in Example 2 + / GCE in the presence of 5 mM [Fe(CN)6] 4- / 3- Cyclic voltammogram in 0.1M KCl solution;
[0025] Figure 4 The bare glassy carbon electrode (GCE), [(CH3CN)4Cu]PF6 / GCE, Taniaphos / GCE and Taniaphos-Cu in Example 2 + / GCE in the presence of 5 mM [Fe(CN)6] 4- / 3- Electrochemical impedance spectroscopy in 0.1M KCl solution;
[0026] Figure 5 The Taniaphos-Cu prepared in Example 3 + / Differential pulse voltammogram of GCE recognition of Trp enantiomers;
[0027] Figure 6 The Taniaphos-Cu prepared in Example 4 + / Differential pulse voltammogram of GCE recognition of cysteine enantiomers;
[0028] Figure 7 The Taniaphos-Cu prepared in Example 4 + / Differential pulse voltammogram of GCE recognition of tyrosine enantiomers;
[0029] Figure 8 The differential pulse voltammogram of Taniaphos / GCE prepared in Comparative Example 1 recognizing Trp enantiomers;
[0030] Fig. 9 This is a scanning electron microscope image of Taniaphos prepared in Comparative Example 1. DETAILED DESCRIPTION
[0031] The present invention will be further described below in conjunction with the accompanying drawings and embodiments. The following embodiments are intended to illustrate the present invention rather than to further limit the present invention.
[0032] The chiral Taniaphos-Cu + The modified electrode recognizes amino acid enantiomers as follows:
[0033] R D / L =I D / I L
[0034] In the formula, R D / L represents the oxidation peak current ratio of amino acid enantiomers, I D and I L Represent the oxidation peak currents of D-amino acids and L-amino acids, respectively.
[0035] Example 1: Preparation of Taniaphos-Cu + Chiral Materials
[0036] Preparation of Taniaphos-Cu + Chiral material, comprising the following steps:
[0037] Preparation of Taniaphos-Cu + Solution: Weigh 37.72 mg of tetraacetonitrile copper hexafluorophosphate (I) and 68.7 mg of (2R)-1-[(S)-α-(dimethylamino)-2-(diphenylphosphino)benzyl]-2-diphenylphosphinoferrocene in a beaker, add 10 mL of 1,2-dichloroethane, and after the solid is completely dissolved, transfer the solution to a 100 mL volumetric flask, make up to volume, shake well, and stand at 4 ° C for 12 h to obtain Taniaphos-Cu + Solution, namely Taniaphos-Cu + Chiral materials.
[0038] like Figure 1 Taniaphos-Cu + Scanning electron microscope image. It can be seen that Taniaphos-Cu + It has an irregular block structure.
[0039] Fourier transform infrared spectroscopy was used to characterize [(CH3CN)4Cu]PF6, Taniaphos and Taniaphos-Cu + The results are as follows Figure 2 [(CH3CN)4Cu]PF6 at 829cm –1 and 559cm –1There are two strong peaks at 1651 cm-1, which are attributed to the stretching vibration of PF. –1 The characteristic peaks are attributed to the stretching vibration of C=C in cyclopentadiene. + In the spectrum of –1 characteristic peak, and at 840cm –1 A new characteristic peak appeared at , which was attributed to the formation of Cu-P coordination bond, proving that Taniaphos-Cu + Successful synthesis of chiral materials.
[0040] Example 2: Preparation of Taniaphos-Cu + Modified Electrode
[0041] Preparation of Taniaphos-Cu + Modifying the electrode, comprising the following steps:
[0042] Use a pipette to transfer 5 μL of the prepared Taniaphos-Cu + The solution was dropped onto the surface of the glassy carbon electrode and dried in a fume hood to obtain Taniaphos-Cu + Modified electrode.
[0043] The cyclic voltammetry and electrochemical impedance spectroscopy were used to investigate the effects of bare GCE, [(CH3CN)4Cu]PF6 / GCE, Taniaphos / GCE, and Taniaphos-Cu + / GCE in the presence of 5 mM [Fe(CN)6] 4- / 3- Electrochemical behavior in 0.1M KCl solution. Figure 3 As shown, bare GCE exhibits a pair of obvious redox peaks, which are attributed to [Fe(CN)6] 3- and [Fe(CN)6] 4- When [(CH3CN)4Cu]PF6 was modified to GCE, the peak current decreased, which was attributed to the poor conductivity of the complex. When Taniaphos was modified to the GCE surface, the peak current decreased sharply, which may be attributed to the fact that the dicyclopentadiene of Taniaphos carries two units of negative charge, which is different from [Fe(CN)6] 4- / 3- There is a strong electrostatic repulsion between ion pairs. + After that, the redox peak current almost completely disappeared, which is attributed to the Cu + The charge transfer resistance (R) of different electrodes is shown in Table 1. ct) is shown in Figure 4 , showing the following trend: R ct (GCE) <R ct ([(CH3CN)4Cu]PF6 / GCE) <R ct (Taniaphos / GCE) <R ct (Taniaphos-Cu + / GCE), and this trend is consistent with the results of cyclic voltammogram.
[0044] Example 3: Taniaphos-Cu + Electrochemical Recognition of Trp Enantiomers by Modified Electrode
[0045] Taniaphos-Cu + The modified electrode is a three-electrode system with the working electrode as the electrode. The prepared Taniaphos-Cu + The modified electrodes were placed in 20 mL of 0.1 M phosphate buffer solution with a pH of 7.0 containing 1 mM L-Trp and D-Trp, respectively, and allowed to stand for 10 s. The differential pulse voltammetry test was performed in the potential range of 0.5 to 1.1 V. The oxidation peak current ratio (I D-Trp / I L-Trp ) to evaluate the chiral recognition efficiency.
[0046] Taniaphos-Cu + The differential pulse voltammogram of the modified electrode recognizing Trp enantiomers is shown in Figure 5 , I D-Trp / I L-Trp- is 2.45. It can be seen that the introduction of Cu + Later, Taniaphos, Cu + , D-Trp form a ternary complex, resulting in more D-Trp being enriched on the electrode surface to produce a larger oxidation peak current; while L-Trp cannot react with Taniaphos and Cu due to its configuration difference + A ternary complex is formed, thereby achieving recognition of Trp enantiomers.
[0047] Example 4: Taniaphos-Cu + Electrochemical recognition of cysteine enantiomers and tyrosine enantiomers using modified electrodes
[0048] The differential pulse voltammetry method was used to study the Taniaphos-Cu prepared in Example 1. + Modified electrode for recognition of cysteine (Cys) and tyrosine (Tyr) enantiomers. Taniaphos-Cu +The differential pulse voltammogram of the modified electrode recognizing cysteine enantiomers is shown in Figure 6 , I D-Cys / I L-Cys- is 1.31; Taniaphos-Cu + The differential pulse voltammogram of the modified electrode recognizing tyrosine enantiomers is shown in Figure 7 , I D-Tyr / I L-Tyr- is 1.71. This indicates that Taniaphos-Cu + The modified electrode has good chiral recognition effect on other electroactive amino acid enantiomers such as cysteine and tyrosine.
[0049] Embodiment 5:
[0050] (1) Preparation of Taniaphos-Cu + Solution chiral materials: Weigh 36 mg of tetraacetonitrile copper hexafluorophosphate (I) and 67 mg of (2R)-1-[(S)-α-(dimethylamino)-2-(diphenylphosphino)benzyl]-2-diphenylphosphinoferrocene in a beaker, add 8 mL of 1,2-dichloroethane, and after the solid is completely dissolved, transfer the solution to a 100 mL volumetric flask, make up to volume, shake well, and let stand at 2°C for 10 h to obtain Taniaphos-Cu + Solution.
[0051] (2) Preparation of Taniaphos-Cu + Modified electrode: Use a pipette to transfer 5 μL of the prepared Taniaphos-Cu + The solution was dropped onto the surface of the glassy carbon electrode and dried in a fume hood to obtain Taniaphos-Cu + Modified electrode.
[0052] Embodiment 6:
[0053] (1) Preparation of Taniaphos-Cu + Solution: Weigh 40 mg of tetraacetonitrile copper hexafluorophosphate (I) and 71 mg of (2R)-1-[(S)-α-(dimethylamino)-2-(diphenylphosphino)benzyl]-2-diphenylphosphinoferrocene in a beaker, add 12 mL of 1,2-dichloroethane, and after the solid is completely dissolved, transfer the solution to a 100 mL volumetric flask, make up to volume, shake well, and let stand at 6 ° C for 14 h to obtain Taniaphos-Cu + Solution.
[0054] (2) Preparation of Taniaphos-Cu + Modified electrode: Use a pipette to transfer 5 μL of the prepared Taniaphos-Cu +The solution was dropped onto the surface of the glassy carbon electrode and dried in a fume hood to obtain Taniaphos-Cu + Modified electrode.
[0055] Comparative Example 1:
[0056] Preparation of Taniaphos modified electrode for electrochemical recognition of Trp enantiomers includes the following steps:
[0057] (1) Preparation of Taniaphos solution: Weigh 68.7 mg of (2R)-1-[(S)-α-(dimethylamino)-2-(diphenylphosphino)benzyl]-2-diphenylphosphinoferrocene into a beaker, add 10 mL of 1,2-dichloroethane, and after the orange-yellow solid is completely dissolved, transfer the solution to a 100 mL volumetric flask, make up to volume, shake well, and let stand at 4°C for 12 h to obtain a Taniaphos solution.
[0058] (2) Preparation of Taniaphos modified electrode: Use a pipette to take 5 μL of the prepared Taniaphos solution and apply it on the surface of the glassy carbon electrode. After drying in a fume hood, the Taniaphos modified electrode is obtained.
[0059] (3) Electrochemical identification of Trp enantiomers: A three-electrode system with a Taniaphos modified electrode as the working electrode was used to electrochemically identify Trp enantiomers by differential pulse voltammetry. The prepared Taniaphos modified electrodes were placed in 20 mL of 0.1 M pH 7.0 phosphate buffer solution containing 1 mM L-Trp and D-Trp, respectively, and allowed to stand for 10 s. The differential pulse voltammetry test was performed in the potential range of 0.5 to 1.1 V. The oxidation peak current ratio (I D-Trp / I L-Trp ) to evaluate the chiral recognition efficiency.
[0060] The differential pulse voltammogram of Trp enantiomers recognized by Taniaphos modified electrode is shown in Figure 8 , I D-Trp / I L-Trp is 1.83. This indicates that the Taniaphos modified electrode has a certain recognition ability for tryptophan enantiomers, but the chiral recognition ability is not strong. + After introduction, Taniaphos, D-Trp and Cu + The formation of a ternary complex enhances the chiral recognition ability of Taniaphos. Tryptophan enantiomers in Taniaphos-Cu + The oxidation peak current ratio on the modified electrode can reach 2.45.
[0061] Fig. 9 This is a scanning electron microscope image of Taniaphos. Figure 1 Taniaphos-Cu + The morphologies vary greatly, presenting a three-dimensional structure in the shape of a flower cluster.
[0062] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.
Claims
1. An electrode for identifying electroactive amino acid enantiomers, characterized in that: The surface modification of the electrode for recognizing electroactive amino acid enantiomers is multi-substituted ferrocene-Cu + Chiral materials; The polysubstituted ferrocene-Cu + The chiral material is a binary complex formed by the reaction of multi-substituted ferrocene and monovalent copper ion complex; The polysubstituted ferrocene is (2R)-1-[(S)-α-(dimethylamino)-2-(diphenylphosphino)benzyl]-2-diphenylphosphinoferrocene or (Rp)-1-[(R)-α-(dimethylamino)-2-(di-p-tolylphosphino)benzyl]-2-di-p-tolylphosphinoferrocene; The monovalent copper ion complex is tetraacetonitrile copper (I) hexafluorophosphate; The amino acid is tryptophan, cysteine or tyrosine.
2. An electrode for recognizing electroactive amino acid enantiomers as claimed in claim 1, characterized in that: The polysubstituted ferrocene-Cu + The method for preparing the chiral material comprises the following steps: Weigh the monovalent copper ion complex and polysubstituted ferrocene, add 1,2-dichloroethane, and after they are completely dissolved, transfer to a 100 mL volumetric flask, make up to volume, shake well, and let stand to obtain polysubstituted ferrocene-Cu + Solution.
3. An electrode for recognizing electroactive amino acid enantiomers as claimed in claim 2, characterized in that: The mass ratio of the monovalent copper ion complex to the polysubstituted ferrocene is 36-40 mg:67-71 mg; the mass-to-volume ratio of the monovalent copper ion complex to 1,2-dichloroethane is 36-40 mg:8-12 mL.
4. An electrode for recognizing electroactive amino acid enantiomers as claimed in claim 2, characterized in that: The standing conditions are: temperature 2-6°C, time 10-14h.
5. A method for preparing an electrode for recognizing electroactive amino acid enantiomers according to any one of claims 1 to 4, characterized in that: The following steps are involved: Weigh polysubstituted ferrocene-Cu + The chiral material is evenly dropped on the electrode surface and dried to obtain multi-substituted ferrocene-Cu + Chiral material modified electrodes.
6. The preparation method according to claim 5, characterized in that: The electrode is a glassy carbon electrode.
7. Use of the electrode according to any one of claims 1 to 4 in identifying electroactive amino acid enantiomers, characterized in that: The electroactive amino acid enantiomers are tryptophan, cysteine and tyrosine.