A natural tetrapeptide-based MOF material and a preparation method thereof

Abstract

The application provides a natural tetrapeptide-based MOF material and a preparation method thereof. The natural tetrapeptide-based MOF material is assembled by a tetrapeptide, amino-glycine-histidine-glycine-glycine-carboxyl (GHGG) as a ligand and a divalent copper ion, and is abbreviated as Cu-GHGG, wherein the molar ratio of the ligand to the divalent copper ion is 1:1. The Cu-GHGG prepared by the application is a layered crystal, and the crystallization solvent is filled between layers during crystallization. After the crystallization solvent is removed by heating, the material still maintains crystallinity. The material after removal of the solvent can adsorb water molecules in the air by itself when placed in humid air.

Description

Technical Field

[0001] This invention belongs to the field of peptide-based MOF material preparation, specifically relating to a natural tetrapeptide-based MOF material and its preparation method. Background Technology

[0002] Natural proteins utilize conformational variations in their peptide chains to perform complex biological functions, making them essential for life activities. Various metal ions also participate in protein behavior, working in conjunction with the flexible structure of peptide chains to achieve various life processes, including recognition, transport, and catalysis. However, in artificial metal-organic hybrid materials, especially metal-organic frameworks (MOFs), large-scale structural changes achieved through conformational changes in organic components are rare. This is because the flexibility of organic components in traditional MOFs is far less than that of peptides. Although some flexible peptide-based MOFs (p-MOFs) have been studied, their development is limited by the number of amino acids; currently, the developed peptide ligands are no more than three amino acids in length.

[0003] Peptides exhibit strong coordination abilities with metals, but the longest peptides reported to form continuous framework crystals are no more than three amino acids in length. This is because long-chain peptide structures provide too many coordination sites, resulting in a metal ion coordinating with only one peptide molecule, thus preventing the formation of a network structure. The previously reported tetrapeptide-metal complex (Cu-DAHK) exemplifies this. Therefore, obtaining tetrapeptide-metal complexes that form continuous framework crystals is challenging, requiring meticulous peptide screening and precise control and optimization of crystallization parameters. Summary of the Invention

[0004] The purpose of this invention is to provide a natural tetrapeptide-based MOF material. This natural tetrapeptide-based MOF material possesses a stable framework structure under high temperature and desolvation conditions. In addition to flexible channels with guest responses similar to its homologs, it also exhibits hydrogen bonding based on water molecules participating in the crystallization process. This is analogous to the interaction between proteins and water molecules in the physiological environment. Therefore, dehydrated p-MOFs can utilize water molecules in the air to rebuild hydrogen bonds and achieve water collection. Flexible long-chain peptide-metal frameworks provide a pathway for mimicking protein behavior and even constructing artificial proteins.

[0005] The natural tetrapeptide-based MOF material provided by this invention is assembled from tetrapeptide-amino-glycine-histidine-glycine-glycine-carboxyl (GHGG) as a ligand and divalent copper ions, abbreviated as Cu-GHGG, wherein the molar ratio of the ligand to the divalent copper ions is 1:1.

[0006] The Cu-GHGG is a layered crystal. During crystallization, the spaces between the layers are filled with a crystallization solvent. After the crystallization solvent is removed, it has a stable framework structure.

[0007] The above-mentioned natural tetrapeptide-based MOF material was prepared by a method including the following steps: A deep blue mixture was obtained by mixing copper salt with an aqueous solution of amino-glycine-histidine-glycine-glycine-carboxylic acid hydrochloride (GHGG). The pH was adjusted to 6.0-6.5 by adding alkali, and a light green solution was obtained by adding DMF. A light blue solution was obtained by adding deionized water. The resulting solution was heated at 85-95°C for 8-12 hours, allowed to cool naturally, and then placed in a container at 4°C for 14-21 days for growth. Blue crystals were obtained at the bottom of the container, which is Cu-GHGG containing the crystallization solvent.

[0008] In the above method, the copper salt can be at least one of copper chloride and copper acetate, specifically CuCl2·2H2O; The molar ratio of copper ions in the copper salt to GHG in the aqueous solution of amino-glycine-histidine-glycine-glycine-carboxylic acid hydrochloride (GHGG) can be 1:1 to 1:1.5; specifically, it can be 1:1. The copper salt is added in the form of an aqueous solution of copper salt; The volume ratio of the copper salt aqueous solution to the amino-glycine-histidine-glycine-glycine-carboxylic acid hydrochloride (GHGG) aqueous solution can be specifically 0.3:1; The alkali is a 1M NaOH aqueous solution, and the amount (volume) of the alkali added is 1 / 8 of the volume of the GHGG aqueous solution; The volume ratio of DMF, deionized water and GHGG aqueous solution can be (9-11):(0.9-1.1):1, specifically 10:1:1.

[0009] The amount of DMF and subsequent deionized water added affects the crystallization rate and yield, with a ratio of 10:1:1 yielding the best results.

[0010] The method further includes collecting blue crystals, heating, and obtaining desolvated Cu-GHGG, wherein the heating is performed at 120°C for 3 hours or more (specifically, 3 hours) or at 100°C in a vacuum and held for 3 hours or more (specifically, 3 hours).

[0011] The application of the desolventized Cu-GHGG prepared by the above method in the adsorption of water molecules in air also falls within the scope of protection of this invention.

[0012] The application of the desolventized Cu-GHGG prepared by the above method in the fields of gas separation and storage, antibacterial, anticancer, and laccase-like catalysis is also within the scope of protection of this invention.

[0013] Previously reported similar ligands are amino-glycine-histidine-carboxyl (GH) and amino-glycine-histidine-glycine-carboxyl (GHG), and framework materials (Cu-GH and Cu-GHG) formed by their coordination with divalent copper ions have also been reported. However, Cu-GH, Cu-GHG, and Cu-GHGG have significantly different structures and properties. Cu-GH is composed of one-dimensional crystal fibers, has a close-packed structure, very low porosity, and is unresponsive to water vapor in the air. Cu-GHG has a three-dimensional network structure with large pores. During crystallization, the pores are filled with a crystallization solvent. When the crystallization solvent is removed, the crystal framework collapses, loses its crystal structure, and is irreversible; it is also unresponsive to water vapor in the air. The Cu-GHGG prepared in this invention is a layered crystal, with the crystallization solvent filling the spaces between the layers during crystallization. After removing the crystallization solvent by heating, the material retains its crystallinity. The solvent-removed material, when placed in humid air, can adsorb water molecules from the air on its own.

[0014] This invention uses glycine-containing peptides to prepare p-MOF because: (1) In p-MOF formed by short peptides (dipeptides, tripeptides) and metals, the amino acid side chains will cause greater steric hindrance due to the short peptide chain length. Therefore, the use of glycine (GX, GHX, etc.) in part or all of glycine (GG) can alleviate the steric pressure during the crystallization process. (2) In p-MOFs formed by longer peptides (tetrapeptides) and metals, the coordination activity of the side chains easily leads to the formation of 1:1 complex molecules between the peptide and the metal ion. In addition, the side chains of some amino acids generate more interactions, such as intermolecular hydrogen bonds and π-π interactions. These interactions may affect the framework formation dominated by coordination interactions during crystallization, leading to unpredictability in the framework structure. Therefore, using glycine as an inert side-chain amino acid in the construction of p-MOFs can avoid this situation.

[0015] Based on this, we constructed a tetrapeptide (GHGG) using glycine and histidine, and successfully synthesized the first tetrapeptide MOF. We also discovered that it possesses excellent structural stability and can specifically adsorb water molecules from the air, thus achieving air-based water collection. Attached Figure Description

[0016] Figure 1 The diagrams show the crystal structures of Cu-peptides. Specifically, a represents the crystal structure of Cu-GH, b represents the crystal structure of Cu-GHG, c represents the monolayer crystal structure of Cu-GHGG, d represents the layered crystal stacking of Cu-GHGG, e represents the coordination environment of copper ions in Cu-GHGG, f represents the coordination environment of peptides in Cu-GHGG, g represents the distribution of interlayer hydrogen bonds in Cu-GHGG, and h represents the hydrogen bond formation between the crystallization solvent and ligand groups in Cu-GHGG.

[0017] Figure 2 The figures show the characterization of the desolventization and gas adsorption processes of Cu-peptide complex crystals. a) Powder X-ray diffraction pattern of Cu-GHGG during vacuum heating and desolventization; b) Powder X-ray diffraction pattern of Cu-GH during vacuum heating and desolventization; c) Powder X-ray diffraction pattern of Cu-GHG during vacuum heating and desolventization; d) Figure showing the isothermal adsorption-desorption of Cu-GHGG by water vapor at 298 K; e) Curve showing the relationship between adsorption amount and temperature versus time during the isothermal adsorption-desorption of Cu-GHGG by water vapor at 25°C; f) Figure showing the isothermal adsorption-desorption of nitrogen at 77 K. Detailed Implementation

[0018] The present invention will now be described in further detail with reference to specific embodiments. The given embodiments are merely illustrative of the invention and not intended to limit its scope. The embodiments provided below can serve as a guide for further improvements by those skilled in the art and do not constitute a limitation on the invention in any way.

[0019] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Unless otherwise specified, the materials and reagents used in the following examples are commercially available.

[0020] In the following examples, copper chloride was a product of Beijing Chemical Plant, copper acetate was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., DMF was from Tianjin Concord Technology Co., Ltd., and deionized water was prepared by a laboratory pure water system, model ELGA-Purelab Ultra.

[0021] All peptides used in the following examples were purchased from Beijing Keyifeng Biotechnology Development Co., Ltd.

[0022] Example 1: Preparation of natural tetrapeptide MOF (Cu-GHGG) 0.3 mL of CuCl₂·2H₂O aqueous solution (0.336 M) was added to 1 mL of amino-glycine-histidine-glycine-glycine-carboxylic acid hydrochloride (GHGG) aqueous solution (0.1 M), and the mixture immediately turned deep blue. Then, 1 M NaOH aqueous solution was added to adjust the pH to 6.5, with a volume of 1 / 8 of the GHGG aqueous solution. Next, 10 mL of DMF was added, and the solution turned light green. Afterward, 1 mL of deionized water was added, and the solution turned light blue. The mixture was heated at 85°C for 10 hours, and then grown at 4°C for 2 weeks, during which blue crystals were observed forming at the bottom.

[0023] Figure 1The diagrams show the crystal structures of Cu-peptides. Specifically, a represents the crystal structure of Cu-GH, b represents the crystal structure of Cu-GHG, c represents the monolayer crystal structure of the prepared Cu-GHGG, d represents the layered crystal packing diagram of the prepared Cu-GHGG, e represents the coordination environment of copper ions in the prepared Cu-GHGG, f represents the coordination environment of peptides in the prepared Cu-GHGG, g represents the interlayer hydrogen bond distribution of the prepared Cu-GHGG, and h represents the hydrogen bond formation between the crystallization solvent and ligand groups in the prepared Cu-GHGG.

[0024] Cu-GH was prepared by the following steps: 0.3 mL of CuCl2·2H2O aqueous solution (0.336 M) was added to 1 mL of amino-glycine-histidine-carboxylic acid hydrochloride (GH) aqueous solution (0.1 M), and the mixture immediately turned deep blue. Then, 10 mL of DMF was added, and the solution turned light green. Subsequently, 1 mL of deionized water was added, and the solution turned light blue. The mixed solution was heated at 85°C for 10 hours, and then grown at 4°C for 1 week, during which blue crystals were observed to form at the bottom.

[0025] Cu-GHG was prepared by the following steps: 0.09 mmol of amino-glycine-histidine-glycine-carboxytrifluoroacetate (GHG) and 14.67 mg of copper acetate monohydrate (Cu(OAc)₂·H₂O) were dissolved in 1 mL of deionized water. 1 M NaOH was added dropwise to this mixture until the pH reached 5.5, with a volume ratio of approximately 5:1 between the mixture and NaOH. After filtering the mixture, 1 mL of ethanol was added, followed by acetonitrile, while shaking dropwise until a fine blue precipitate appeared in the solution. The amount of acetonitrile used was approximately 2 mL. Then, 5 mg of GHG powder was added until the blue precipitate dissolved. The mixture was then transferred to 4 °C, and after one day, purple crystals formed at the bottom of the flask.

[0026] The collected blue crystals are descaled by removing the crystallization solvent at high temperature to obtain desolvated Cu-GHGG crystals. Specifically, the filtered and collected Cu-GHGG crystals are washed three times with DMF, and then heated at 120°C for 3 hours, or heated in a vacuum to 100°C and held for more than 3 hours to obtain desolvated Cu-GHGG crystals.

[0027] Desolventized Cu-GHGG morphology images are unavailable because electron beam scanning during testing would damage the sample morphology. Evidence of preserved crystallinity is visible. Figure 2 In the case of a, after heating to 120°C, there are still obvious XRD diffraction peaks, which can be regarded as a crystalline material with good crystallinity.

[0028] Characterization of adsorbed water molecules is shown in [reference needed]. Figure 2In the figure, d, e, and f represent the adsorption effects of water molecules and nitrogen gas, respectively. It can be seen that the material has a very low adsorption capacity for nitrogen gas, but a very high adsorption capacity for water molecules.

[0029] The flexibility of Cu-GHGG crystal materials can be improved from Figure 2 From a, Figure 2 Figure a shows the in-situ XRD pattern of Cu-GHGG during the vacuum heating process. It can be seen that during the solvent removal process, the structure of Cu-GHGG transforms from a crystalline to an amorphous state, and then back to a crystalline state, demonstrating the flexibility of the structure. The amorphous state data are as follows: Figure 2 The sixth data line from the bottom up in the middle is line a.

[0030] The present invention has been described in detail above. Those skilled in the art will recognize that the invention can be practiced in a wide range of ways with equivalent parameters, concentrations, and conditions without departing from its spirit and scope, and without requiring unnecessary experiments. While specific embodiments have been provided, it should be understood that further modifications can be made to the invention. In summary, according to the principles of the invention, this application is intended to include any changes, uses, or improvements to the invention, including changes made using conventional techniques known in the art that depart from the scope disclosed herein.

Claims

1. A natural tetrapeptide-based MOF material, assembled from tetrapeptide-amino-glycine-histidine-glycine-glycine-carboxyl (GHGG) ligands and divalent copper ions, abbreviated as Cu-GHGG. in, The molar ratio of the ligand to the divalent copper ion is 1:

1.

2. The natural tetrapeptide-based MOF material according to claim 2, characterized in that, The Cu-GHGG is a layered crystal. During crystallization, the spaces between the layers are filled with a crystallization solvent. After the crystallization solvent is removed, it has a stable framework structure.

3. A method for preparing the natural tetrapeptide-based MOF material according to claim 1 or 2, comprising the following steps: mixing copper salt with an aqueous solution of amino-glycine-histidine-glycine-glycine-carboxylic acid hydrochloride to obtain a deep blue mixture; adjusting the pH to 6.0-6.5 with alkali; adding DMF to obtain a light green solution; adding deionized water to obtain a light blue solution; heating the obtained solution at 85-95°C for 8-12 hours; allowing it to cool naturally; and then incubating it at 4°C for 14-21 days to obtain blue crystals at the bottom of the container, i.e., Cu-GHGG containing the crystallization solvent.

4. The method according to claim 3, characterized in that, The copper salt is at least one of copper chloride and copper acetate; The molar ratio of copper ions in the copper salt to GHGG in the aqueous solution of amino-glycine-histidine-glycine-glycine-carboxylic acid hydrochloride (GHGG) is 1:1 to 1:1.

5.

5. The method according to claim 3, characterized in that, The copper salt is added in the form of an aqueous solution of copper salt; The volume ratio of the copper salt aqueous solution to the amino-glycine-histidine-glycine-glycine-carboxylic acid hydrochloride (GHGG) aqueous solution is 0.3:1; The alkali is a 1M NaOH aqueous solution, and the amount (volume) of the alkali added is 1 / 8 of the volume of the GHGG aqueous solution.

6. The method according to claim 3, characterized in that, The volume ratios of DMF, deionized water, and GHGG aqueous solution are (9-11): (0.9-1.1): 1, respectively.

7. The method according to claim 3, characterized in that, The method further includes collecting blue crystals, heating, and obtaining desolvated Cu-GHGG, wherein the heating is performed at 120°C for 3 hours or more, or at 100°C in a vacuum and held for 3 hours or more.

8. Desolventized Cu-GHGG prepared by the method of claim 7.

9. The application of the desolventized Cu-GHGG of claim 8 in the adsorption of water molecules in air.

10. The application of the desolventized Cu-GHGG of claim 8 in the fields of gas separation and storage, antibacterial, anticancer, and laccase-like catalysis.

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