Nickel complex of N-acetyl-D-phenylalanine, preparation method and application thereof

Abstract

The present invention discloses a nickel coordination polymer with N-acetyl-D-phenylalanine as the main ligand, and its chemical formula is {[Ni(D-acphe)2(4,4'-bipy)(H2O)2]} n , wherein D-acphe ‑ represents that N-acetyl-D-phenylalanine has lost a carboxyl hydrogen atom and carries a unit negative charge; 4,4'-bipy represents 4,4'-bipyridine. The chiral amino acid derivative complex of the present invention has good stability, and the preparation method is simple, the conditions are mild, the price is low, the period is short, and the yield is high. The complex can identify tryptophan enantiomers by cyclic voltammetry. Under certain experimental conditions, the complex has good enantioselectivity for tryptophan enantiomers and is expected to become an electrochemical sensor for distinguishing tryptophan enantiomers.

Description

Technical Field

[0001] The present invention relates to a chiral amino acid derivative complex, and more particularly to a nickel coordination polymer with N-acetyl-D-phenylalanine as the main ligand, belonging to the technical field of material chemistry. Background Art

[0002] Chirality is one of the basic properties of nature. Most of the molecules that make up living organisms are asymmetric chiral molecules, and these macromolecules have important physiological functions in living organisms. Amino acids, as a common chiral compound, are widely used in several industries closely related to human life and health, such as medicine, food, health products, and feed. In addition, different configurations of chiral amino acids involve different sources, metabolic pathways, biological activities, and toxicities, and play different indicative roles in the diagnosis of various diseases. Therefore, the recognition of chiral amino acids plays a key role in chemical biology and pharmacology. L-tryptophan (L-Trp) is widely used in the food and chemical industries, while D-tryptophan (D-Trp) is identified as a precursor for the synthesis of anticancer drugs and immunosuppressants. Therefore, developing effective methods to recognize Trp enantiomers has practical significance in biological and pharmaceutical systems. So far, researchers have developed various analytical methods such as chromatography and spectroscopy to achieve sensitive detection of amino acid enantiomers. In 2019, the research group of Yuanyuan Cui constructed a chiral metal-organic framework [Zn2(L-Phe)2(bpe)2] using the chiral ligand L-phenylalanine (L-Phe). n(bpe = 1,2-bis(4-pyridyl)ethylene). In the absence of a chiral shift reagent, the chiral recognition mechanism of Zn-MOF was investigated using CCP MAS nuclear magnetic resonance (NMR) spectroscopy. (Ma X.; Zhang Y.; Gao Y.; Li X.L.; Wang C.J.; Yuan H.; Yu J.; Zhang S.S.; Cui Y.Y. Chem. Commun., 2020, 56(7), 1034 - 1037.) In 2021, the Xian-Ming Zhang research group constructed a homochiral two-dimensional MOF using the chiral ligand 5,5'-((1R,2R)-cyclohexanedicarbonylbis-(azadimethyl))dibenzoic acid, 4,4'-bipyridine, and a Zn salt, and obtained 2D HMOF-3 nanosheets that could effectively recognize a variety of amino acids as a fluorescence sensor through solvent-assisted sonication. (Zhao Y.W.; Guo L.E.; Zhang F.Q.; Yao J.; Zhang X.M. ACS Appl. Nano Mater., 2021, 13(17), 20821 - 20829.) In 2022, the Carol Hua research group synthesized a chiral coordination polymer [Zn3((S)-L1)(tma)2(DMF)3]·2DMF ((S)-1) (H3tma = trimesic acid) using the 1,1′-binaphthol (BINOL)-derived ligand 4,4′-bipyridyl-2,2′-diethoxy-1,1′-dinaphthalene (S-L1), which could be used as an effective chiral sensor for a series of chiral analytes. (Thoonen H.; Tay H.M.; Hua C. Chem. Commun., 2022, 58(28), 4512 - 4515.). In 2022, the De-Ming Kong research group designed and synthesized a pair of chiral enantiomeric ligands (2R,3R)-dibenzyl-2,3-bis(isonicetyloxy)succinate ((R,R)-L) and (2S,3S)-dibenzyl-2,3-bis(isonicetyloxy)succinate ((S,S)-L) to construct 7 complexes, among which the complex {[Cu((R,R)-L)Br2(THF)]·CH3CN} nIt can be used as a circular dichroism spectroscopic probe to monitor the configuration and concentration of L / D-cysteine in aqueous media according to the ligand exchange mechanism. (Li Z.Y., Yuan B., Wang H.X., He T.S., Lan Y.L, Wang S.Y., Zhu L.N., Kong D.M., Li X.Z. Chem. Asian J., 2022, 17(11), e202200263.). These spectroscopic and chromatographic methods are costly, time-consuming, and require specialized experimental equipment or technicians. Electrochemical methods, on the other hand, are characterized by high sensitivity and stability, relative simplicity, and rapid response, and can be used to identify chiral enantiomers. Currently, electrodes modified with cyclodextrins, biomaterials, mesoporous materials, chiral ionic liquids, etc. are mostly used in electrochemical detection techniques to identify amino acid enantiomers, but reports on electrochemical chiral recognition based on chiral metal-organic frameworks are still very limited and further development and improvement are still needed. In 2023, the research group of Yan Huang proposed a homochiral metal-organic framework Cu-TBPBe, which has good enantioselectivity and sensitivity for the electrochemical recognition of L-tryptophan (Trp). The L-to-D ratio of the differential pulse voltammetry (DPV) current reached 53, which is much higher than the values reported in previous electrochemical sensors (Huang Y, Wang Y Y, An R, Gao E Q, Yue Q. ACS Sens. 2023, 8(2), 774-783.).

[0003] In addition, the ligand N-acetyl-D-phenylalanine is not only inexpensive and readily available but also has groups such as carboxyl, carbonyl, and imino groups that are conducive to coordination. The participation of the carboxyl group in coordination can enable the complex to form strong metal-carboxylic acid bonds, thereby making the framework of the complex more stable and reducing the solvation effect. It is an excellent ligand for the synthesis of chiral complexes. Summary of the Invention

[0004] The object of the present invention is to provide a nickel complex of N-acetyl-D-phenylalanine.

[0005] The object of the present invention also lies in providing a preparation method of a nickel complex of N-acetyl-D-phenylalanine.

[0006] The third object of the present invention is to provide an application of a nickel complex of N-acetyl-D-phenylalanine in the electrochemical recognition of amino acid enantiomers.

[0007] To achieve the object of the present invention, the present invention adopts the following technical solution: A nickel complex of N-acetyl-D-phenylalanine, with the chemical formula {[Ni(D-acphe)2(4,4’-bipy)(H2O)2]} n , where D-acphe -It represents that N-acetyl-D-phenylalanine has lost a carboxyl hydrogen atom and carries a unit negative charge; 4,4'-bipy represents 4,4'-bipyridine, and D-acphe - The structural formula and the metal nickel coordination mode are as follows:

[0008]

[0009] A preparation method of a nickel complex of N-acetyl-D-phenylalanine according to the present invention comprises the following steps:

[0010] (1) Accurately weigh Ni(CH3COO)2·4H2O and D-Hacphe, place them in a beaker, add distilled water, stir until they are completely dissolved, then drop the ethanol solution containing 4,4'-bipy into the above solution, continue stirring for no less than 5 minutes, and then adjust the mixed solution to pH = 5.0 - 5.5 with NaOH solution, preferably pH is 5.1.

[0011] The molar ratio of the reactants nickel acetate tetrahydrate (Ni(CH3COO)2·4H2O), N-acetyl-D-phenylalanine (D-Hacphe) and 4,4'-bipyridine (4,4'-bipy) is 2:2:1.

[0012] (2) Filter the mixed solution obtained in step (1), let the filtrate stand at room temperature, and after slow evaporation, light blue columnar crystals grow out after at least 15 days, obtaining a chiral amino acid derivative complex, that is, a nickel complex of N-acetyl-D-phenylalanine with electrochemical recognition function.

[0013] The chiral amino acid derivative complex of the present invention has an electrochemical recognition function and can be used to recognize Trp enantiomers.

[0014] The specific method for using the prepared nickel complex of N-acetyl-D-phenylalanine for electrochemical recognition of chiral Trp enantiomers is as follows:

[0015] (1) Electrochemical tests are carried out in a three-electrode system. The auxiliary electrode and the reference electrode are a platinum wire electrode and an Ag / AgCl electrode respectively. The working electrode is modified by mixing the crystal and carbon powder (the total mass is 20 mg, and they are mixed and modified in the ratios of 1:1, 1:1.5, 1:3, 1:4 respectively), and the electrochemical impedance of the electrodes with different mixing ratios is tested. Select the crystal mixture (1:3) with lower electrochemical impedance for further electrochemical performance tests;

[0016] (2) In the test range of -1.0V - 1.2V, the cyclic voltammetry method is used to study the electrochemical oxidation-reduction performance of the complex. And observe whether there is a linear relationship between the scanning speed and the peak current;

[0017] (3) The cyclic voltammetry (CV) curves of the glassy carbon electrode modified with the complex and the bare electrode were respectively tested in Na2SO4 electrolyte and Na2SO4 solution containing 0.5 mmol·L -1 of D-Trp and L-Trp, proving that Trp enantiomers can be chiral recognized under the chiral microenvironment provided by the complex.

[0018] (4) Cyclic voltammetry was used to optimize the experimental conditions for the recognition of Trp enantiomers. First, the optimal pH for the recognition efficiency of Trp by the glassy carbon electrode modified with the complex was explored. The cyclic voltammetry curves of the modified electrode in D-Trp or L-Trp solutions at pH values of 4, 5, 6, and 7 were respectively tested, and the peak potential difference PD of the reduction peak (PD = Ep L - Ep D ) was calculated and a bar graph was made. At the optimal pH, the cyclic voltammetry curves of the modified electrode and a series of different concentrations of D-Trp or L-Trp were respectively tested to explore the influence of concentration on the recognition efficiency.

[0019] (5) The selectivity of the electrochemical chiral recognition of the complex was studied. Cys (cysteine) and Tyr (tyrosine) enantiomers were used to study the enantioselectivity of the chiral interface of the complex, and their cyclic voltammetry curves were recorded using CV technology under the same conditions.

[0020] The present invention has the following beneficial effects:

[0021] 1. The preparation method of the complex is simple, the reaction conditions are mild, and the raw materials are cheap and easily available;

[0022] 2. The product is in a pure phase, and the main framework of the complex still exists stably when heated to 214.2 °C under a nitrogen atmosphere;

[0023] 3. The complex can rapidly and simply recognize Trp enantiomers. Description of the Drawings

[0024] Figure 1 It is the coordination environment of a chiral amino acid derivative metal nickel organic complex with electrochemical recognition function.

[0025] Figure 2 It is the one-dimensional linear structure of a chiral amino acid derivative metal nickel organic complex with electrochemical recognition function.

[0026] Figure 3 It is the two-dimensional layered structure of a chiral amino acid derivative metal nickel organic complex with electrochemical recognition function.

[0027] Figure 4 It is the three-dimensional supramolecular structure of a chiral amino acid derivative metal nickel organic complex with electrochemical recognition function.

[0028] Figure 5 The single crystal data simulation of a metal nickel organic complex of a chiral amino acid derivative with electrochemical recognition function and the X-ray powder (PXRD) diffraction pattern of the sample.

[0029] Figure 6 The thermogravimetric (TG) curve of a metal nickel organic complex of a chiral amino acid derivative with electrochemical recognition function.

[0030] Figure 7 The infrared (IR) spectrum of a metal nickel organic complex of a chiral amino acid derivative with electrochemical recognition function.

[0031] Figure 8 The electrochemical impedance diagram of a metal nickel organic complex of a chiral amino acid derivative with electrochemical recognition function.

[0032] Figure 9 The cyclic voltammogram of a metal nickel organic complex of a chiral amino acid derivative with electrochemical recognition function and the linear relationship between different scan rates and peak current (I-I').

[0033] Figure 10 The CV curves of a modified electrode and a bare electrode of a metal nickel organic complex of a chiral amino acid derivative with electrochemical recognition function for recognizing Trp enantiomers.

[0034] Figure 11 The CV curves of a metal nickel organic complex of a chiral amino acid derivative with electrochemical recognition function for recognizing Trp enantiomers at different pH values and the peak potential difference PD for comparing the recognition of Trp enantiomers at different pH values.

[0035] Figure 12 The CV curves of a metal nickel organic complex of a chiral amino acid derivative with electrochemical recognition function for recognizing Trp enantiomers in the concentration range of 0.5 mM - 2.5 mM; the CV curves of a metal nickel organic complex of a chiral amino acid derivative with electrochemical recognition function for recognizing Trp enantiomers in the concentration range of 0.5 mM - 2.5 mM; the linear fitting curves of the peak potential responses of D-Trp and L-Trp at different concentrations (the inserted figures in the upper left and lower right are the CV curves of D-Trp and L-Trp at different concentrations); and the peak potential difference PD for comparing the recognition of Trp enantiomers at different concentrations.

[0036] Figure 13 The CV curves of a metal nickel organic complex of a chiral amino acid derivative with electrochemical recognition function for recognizing Trp, Cys, and Tyr enantiomers. Detailed implementation mode

[0037] The following examples are used to illustrate the present invention.

[0038] Example 1

[0039] A chiral amino acid derivative nickel organic complex with electrochemical recognition function, and its chemical formula is {[Ni(D-acphe)2(4,4’-bipy)(H2O)2]} n , where D-acphe - represents that N-acetyl-D-phenylalanine has lost a carboxyl hydrogen atom and carries a unit negative charge; 4,4’-bipy represents 4,4’-bipyridine, and the structural formula of D-acphe - is as follows:

[0040]

[0041] Structural description: A chiral amino acid derivative nickel organic complex with electrochemical recognition function, and its chemical formula is {[Ni(D-acphe)2(4,4’-bipy)(H2O)2]} n , where D-acphe - represents that N-acetyl-D-phenylalanine has lost a carboxyl hydrogen atom and carries a unit negative charge; 4,4’-bipy represents 4,4’-bipyridine.

[0042] Single crystal structure analysis and characterization were carried out on the chiral amino acid derivative nickel organic complex with electrochemical recognition function to determine its unit cell and spatial structure. The crystal belongs to the monoclinic system, the P212121 chiral space group, and is a 1D layered structure. The structural unit of the complex consists of a Ni(II) cation, two D-acphe - anionic chiral ligands, a 4,4'-bipy molecule, and two coordinated water molecules, as shown in the appendix Figure 1 . The coordination mode of the central metal Ni(II) is NiO4N2: O1 and O4 come from two D-acphe - ligands; N5 and N7 come from two 4,4'-bipy ligands respectively; O13 and O14 come from two coordinated water molecules, showing a distorted octahedral configuration. The two pyridine nitrogen atoms of the 4,4'-bipy ligand molecule bridge adjacent central metal Ni(II), forming a 1D straight chain structure along the c-axis direction, as shown in the appendix Figure 2 . The chiral D-acphe - ligands on both sides of the metal Ni(II) participate in coordination in a monodentate mode using the carboxyl O. In the complex, the hydrogen bond interaction between the carboxyl oxygen atom of the D-acphe - ligand and the coordinated water molecule, D-acphe -Under the hydrogen bond interaction between the carboxyl oxygen atom and the imino nitrogen atom of the ligand, a 2D layered structure is formed on the ac plane and stacked in the ABAB form in the b direction, as shown in the appendix Figure 3 shown. The 2D layers are further connected by the hydrogen bonds between the carboxyl oxygen atom of the D-acphe - ligand and the coordinated water oxygen atom, enabling the complex to finally expand into a 3D supramolecular structure, as shown in the appendix Figure 4 shown.

[0043] As shown in the appendix Figure 5 shown, the X-ray powder diffraction pattern indicates that the chiral amino acid derivative nickel metal complex with electrochemical recognition function is in the pure phase. As shown in the appendix Figure 6 shown, the thermogravimetric analysis shows that the chiral amino acid derivative nickel metal complex with electrochemical recognition function has good thermal stability.

[0044] A preparation method of a chiral amino acid derivative nickel metal organic complex with electrochemical recognition function includes the following steps:

[0045] (1) Accurately weigh 0.1 mmol of Ni(CH3COO)2·4H2O and 0.1 mmol of D-Hacphe into a 50 mL small beaker, add 10 mL of distilled water, stir until it is completely dissolved, and then add 5 mL of ethanol solution containing 0.05 mmol of 4,4'-bipy dropwise to the above solution. After continuing to stir for at least 5 minutes, use 1 mol·L -1 NaOH solution to adjust the mixed solution to pH = 5 - 5.5, and the optimal pH is 5.1;

[0046] (2) Filter the mixed solution in step (1), let the filtrate stand at room temperature, and after slow evaporation, light blue columnar crystals grow out after 15 days, or it is called a chiral amino acid derivative nickel metal organic complex with electrochemical recognition function. Elemental analysis C 32 H 36 N4NiO8 (Mr = 663.36), theoretical values (%) : C, 57.94; H, 5.47; N, 8.44; experimental values (%) : C, 57.39; H, 5.58; N, 8.47. The main peaks of the infrared spectrum IR (KBr, cm -1 ) ν: 3255(s), 3078(m), 1649(m), 1589(s), 1490(s), 1289(m), 1207(m), 1121(m), 1061(m), 1005(w), 990(w), 956(w), 821(s), 695(s), 632(m), 549(m). As shown in the appendix Figure 7 shown.

[0047] A chiral amino acid derivative nickel complex with electrochemical recognition function is used to recognize Trp enantiomers. The specific method is as follows:

[0048] Electrochemical tests were carried out in a three-electrode system. The auxiliary electrode and the reference electrode were a platinum wire electrode and an Ag / AgCl electrode respectively. The working electrode was modified by mixing crystals and carbon powder (with a total mass of 20 mg, and modified with mixing ratios of 1:1, 1:1.5, 1:3, and 1:4 respectively). First, the electrochemical impedance of electrodes with different mixing ratios was tested, and the crystal mixture with lower electrochemical impedance (ratio of 1:3) was selected for the next electrochemical performance test, as shown in the appendix Figure 8 as shown

[0049] In the test range of -1.0 V - 1.2 V, cyclic voltammetry was used to study the electrochemical redox performance of the complex, as shown in the appendix Figure 9 as shown. The peak potentials of the complex were located at 0.559 V (II) / 0.387 V (II'), which can be attributed to the redox process of Ni(II) / Ni(III). It can be seen that the increase in the scanning rate was accompanied by the enhancement of the peak current, the appearance of the peak shape became gradually obvious, and there was a good linear relationship between the two, indicating that the redox reversibility of the complex was good

[0050] The CV curves of the glassy carbon electrode modified with the complex and the bare electrode were respectively tested in Na2SO4 electrolyte and Na2SO4 solution containing 0.5 mmol·L -1 of D-Trp and L-Trp, as shown in the appendix Figure 10 as shown. In the test range, the bare electrode GCE showed low and overlapping currents for Trp enantiomers, and no obvious redox peaks appeared. However, due to the good electrochemical activity and excellent electron transfer promotion characteristics of the complex, a larger current appeared on the complex-modified electrode, and a potential response to tryptophan enantiomers (PD = 134 mV) was made. By comparing with the peak potential of the reduction peak in the blank sample, the response of the electrode to L-Trp was more significant, and the peak potential shift was greater. The above phenomena indicate that Trp enantiomers can be chiral recognized under the chiral microenvironment provided by the complex

[0051] Cyclic voltammetry was used to optimize the experimental conditions for recognizing Trp enantiomers. First, the optimal pH for the recognition efficiency of Trp by the glassy carbon electrode modified with the complex was explored. The cyclic voltammograms of the modified electrode in D / L-Trp solutions at pH 4, 5, 6, and 7 were respectively tested, and the peak potential difference PD of the reduction peak was calculated (PD = Ep L - Ep D ) and a bar chart was made. As shown in the appendix Figure 11As shown, the maximum recognition efficiency (PD = 134 mV) was obtained at pH = 5. Therefore, in this experiment, we selected pH = 5 as the optimal pH value for chiral recognition.

[0052] At the optimal pH, the effect of a series of concentrations on the recognition effect was further investigated. As the concentrations of D-Trp and L-Trp increased, the reduction peak potential was dependent on the concentration and showed a linear relationship in the range of 0.5 mM - 2.5 mM, as shown in the appendix. Figure 12 The linear equations for D-Trp and L-Trp were E(V) = 0.023c - 0.4 (R 2 = 0.92) and E(V) = 0.073c - 0.55 (R 2 = 0.99), respectively. The chiral recognition efficiency of the complex modified electrode gradually decreased with the increase in concentration, and the recognition effect was not obvious when the concentration of tryptophan enantiomers exceeded 2.0 mM. Therefore, in this chiral recognition experiment, 0.5 mM was the optimal concentration of tryptophan isomers.

[0053] In addition, the selectivity of the complex electrochemical chiral recognition was also studied. Cys (cysteine) and Tyr (tyrosine) enantiomers were used to study the enantioselectivity of the chiral interface of the complex, and their cyclic voltammograms were recorded using the CV technique under the same conditions. As shown in the appendix. Figure 13 The recognition efficiency of Trp was much greater than that of Tyr and Cys, indicating that the complex had high chiral specificity for tryptophan enantiomers. The test results confirmed that the complex modified electrode had good enantioselectivity.

[0054] The above results confirmed that the chiral amino acid derivative complex of the present invention had an electrochemical recognition function, could recognize Trp enantiomers using CV, showed good enantioselectivity for tryptophan enantiomers under optimized experimental conditions, and was expected to become an electrochemical sensor for distinguishing tryptophan enantiomers.

[0055] It should be specifically noted that the technical solution of the present invention has been pilot-tested. After the pilot test was completed, user usage research was carried out on a small scale. The research results showed that the user satisfaction was relatively high. Currently, preparations have been made for the transformation and application of the results. At the same time, research on intellectual property risk early warning has also been carried out.

Claims

1. A nickel complex of N-acetyl-D-phenylalanine with the chemical formula {[Ni(D-acphe)2(4,4’-bipy)(H2O)2]} n , wherein D-acphe - represents that one carboxyl hydrogen atom of N-acetyl-D-phenylalanine is removed, carrying a unit of negative charge; 4,4'-bipy represents 4,4'-bipyridine, and the - structural formula of D-acphe and its coordination mode with nickel metal are as follows: 。 2. The nickel complex according to claim 1, wherein The complex forms a 1D linear chain structure in the c-axis direction through the bridging of 4,4'-bipyridine molecules, and finally further expands into a 3D supramolecular structure under the action of hydrogen bonds.

3. A method for preparing a nickel complex as claimed in claim 1 or 2, characterized in that It includes the following steps: (1) Accurately weigh Ni(CH3COO)2·4H2O and D-Hacphe in a 50 mL small beaker, add 10 mL of distilled water, stir until completely dissolved, then drop 5 mL of ethanol solution containing 4,4-bipy into the above solution, continue stirring for no less than 5 minutes, and adjust the mixed solution to pH = 5 - 5.5 with NaOH solution; (2) Filter the mixed solution obtained in step (1), let the filtrate stand at room temperature, and grow light blue columnar crystals after slow evaporation for at least 15 days to obtain a chiral amino acid derivative nickel organic complex with electrochemical recognition function.

4. The preparation method of the nickel complex according to claim 3, characterized in that The molar ratio of the reactants Ni(CH3COO)2·4H2O, D-Hacphe to 4,4'-bipy is 2:2:

1.

5. The preparation method of the nickel complex according to claim 3, characterized in that Adjust the mixed solution to pH 5.1 with NaOH solution.

6. The preparation method of the nickel complex according to claim 3, characterized in that The concentration of the NaOH solution is 1 mol·L -1 .

7. The preparation method of the nickel complex according to claim 3, characterized in that, The stirring and mixing time of the ethanol solution is more than 5 minutes.

8. The preparation method of the nickel complex according to claim 3, characterized in that, The preparation time of the nickel complex is more than 15 days.

9. Use of a nickel complex as described in claim 1 or 2, characterized in that It is used for the electrochemical recognition of tryptophan enantiomers.

10. Use of the nickel complex according to claim 9, characterized in that Cyclic voltammetry is used to study the enantioselectivity of the chiral interface of the complex.

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