Phenylalanine-tryptophan dipeptide skeleton mesoporous silicon material as well as preparation method and application thereof
By synthesizing phenylalanine-tryptophan dipeptide mesoporous silicon material, the problem of unstable efficacy of chloramphenicol in the existing technology is solved, efficient adsorption and stability improvement are achieved, and new materials are provided for applications in multiple fields.
Patent Information
- Application Number
- CN202510083896.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-17
- Publication Date
- 2025-04-29
AI Technical Summary
In the prior art, chloramphenicol has good fat solubility, poor water solubility, and is easily affected by the external environment, resulting in a decrease in drug efficacy and lack of effective carriers and controlled release methods.
The mesoporous silicon material with phenylalanine-tryptophan dipeptide skeleton is used as a carrier, and the phenylalanyl tryptophan dipeptide silicone precursor is mixed with tetraethyl orthosilicate, and then reacted in water bath and crystallized at high temperature to obtain a mesoporous silicon material with a high specific surface area and adjustable pore size, which is used to effectively adsorb chloramphenicol.
It has achieved efficient adsorption of chloramphenicol, with an adsorption amount of up to 90mg/g, which reduces the impact of the external environment on chloramphenicol, improves the stability of chloramphenicol, and provides potential applications for environmental purification, drug controlled release, anti-aging and sun protection, and chemical sensing.
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Abstract
Description
Technical Field
[0001] The invention relates to the field of environment and chemical technology, and in particular to the synthesis and application of a phenylalanine-tryptophan dipeptide skeleton mesoporous silicon material. Background Art
[0002] Chloramphenicol is a broad-spectrum antibacterial agent, commonly used in the treatment of eye infections, but it has good lipid solubility and poor water solubility, and is easily affected by the external environment during use, which reduces the efficacy. To this end, various technologies are used to solve these problems. With the development of nanotechnology, nanomaterials as carriers to load drugs and control release have become one of the effective means to improve application stability and improve drug efficacy. Organic skeleton mesoporous silica materials, as a type of nanomaterial, are often used in drug adsorption and controlled release research. It forms an organic disilicon precursor through functional molecules and introduces it into the silicon wall of the mesoporous material. It can effectively control the content of functional components, maintain the high specific surface area, large pore volume, easy functionalization of the pore wall and adjustable pore size of the mesoporous material, and has attracted much attention.
[0003] Therefore, the phenylalanine-tryptophan dipeptide skeleton mesoporous silica material for effective adsorption of chloramphenicol has certain research significance and is expected to become one of the drug carriers and expand its application space. Summary of the invention
[0004] The invention provides a preparation method of a phenylalanine-tryptophan dipeptide skeleton mesoporous silicon material for effectively adsorbing chloramphenicol, so as to solve the defects in the prior art.
[0005] In order to achieve the above object, the present invention adopts the following technical scheme.
[0006] Phenylalanyltryptophan dipeptide organosilicon precursor of structural formula (I):
[0007]
[0008] A method for preparing a phenylalanyltryptophan dipeptide organosilicon precursor (I), comprising:
[0009]
[0010] In the step of preparing compound I from compound III and compound V, the coupling reagent is o-benzotriazole-N,N,N',N'-tetramethyluronium tetrafluoroboric acid, and the organic base is triethylamine or N,N-diisopropylethylamine; in the step of preparing compound VII from compound VI, the strong base is sodium hydroxide or potassium hydroxide; in the step of preparing compound VIII from compound VII, the activating reagents are 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide, and the organic base is triethylamine or N,N-diisopropylethylamine; in the step of preparing compound I from compound IX, the organic base is triethylamine or N,N-diisopropylethylamine.
[0011] A method for preparing a phenylalanine-tryptophan dipeptide skeleton mesoporous silicon material comprises the following steps:
[0012] S1: Phenylalanyltryptophan dipeptide organosilicon precursor (I) and tetraethyl orthosilicate are mixed in proportion, and added dropwise to a mixed solution of template, deionized water, and sodium chloride hydrochloric acid, reacted in a water bath, crystallized at high temperature, and then filtered, washed with water, and dried;
[0013] S2: removing the template in a mixed solvent of anhydrous ethanol and hydrochloric acid, drying, and obtaining a phenylalanine-tryptophan dipeptide skeleton mesoporous silica material.
[0014] The amount of phenylalanyltryptophan dipeptide organosilicon precursor (I) in the sum of phenylalanyltryptophan dipeptide organosilicon precursor (I) and tetraethyl orthosilicate is 5%-20%.
[0015] The temperature of the water bath in step S1 is 40°C-60°C, the reaction time in the water bath is 24-36h, and the temperature of high temperature crystallization is 100°C-110°C.
[0016] In step S2, the template agent is a triblock copolymer of polyethylene oxide-polypropylene oxide-polyethylene oxide. The concentration of hydrochloric acid is 2M.
[0017] A phenylalanine-tryptophan dipeptide skeleton mesoporous silicon material is prepared by any of the above-mentioned preparation methods.
[0018] Finally, the present application also provides an application of the above-mentioned phenylalanine-tryptophan dipeptide skeleton mesoporous silicon material in the adsorption of chloramphenicol, which can effectively adsorb chloramphenicol with an adsorption amount of up to 90 mg / g, and also reduces the impact of the external environment on chloramphenicol, thereby improving the stability of chloramphenicol.
[0019] The phenylalanine-tryptophan dipeptide organic mesoporous silica material obtained by the present invention has a greatly improved adsorption capacity for chloramphenicol. Because there are multiple active groups in its pores, it has potential applications in the fields of environmental purification, drug controlled release, anti-aging and sun protection, and chemical sensing.
[0020] The raw materials in the preparation steps described in the present invention are simple and easy to obtain, the synthesis process is simple and the material components are adjustable, so different proportions of different functional molecules can be designed according to specific uses to obtain mesoporous silicon materials with diverse properties. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for describing the embodiments are briefly introduced below.
[0022] Figure 1 This is a diagram showing the results of the measurement of the nuclear magnetic resonance hydrogen spectrum of the phenylalanyltryptophan organosilicon precursor;
[0023] Figure 2 This is the X-ray diffraction (XRD) pattern of the mesoporous silica material containing 5% phenylalanine-tryptophan dipeptide skeleton;
[0024] Figure 3 The nitrogen adsorption-desorption curve and pore size distribution diagram of the mesoporous silicon material containing 5% phenylalanine-tryptophan dipeptide skeleton;
[0025] Figure 4 This is the X-ray diffraction (XRD) pattern of the mesoporous silica material containing 10% phenylalanine-tryptophan dipeptide skeleton;
[0026] Figure 5 The nitrogen adsorption-desorption curve and pore size distribution diagram of the mesoporous silicon material containing 10% phenylalanine-tryptophan dipeptide skeleton;
[0027] Figure 6 This is the X-ray diffraction (XRD) pattern of mesoporous silica material containing 15% phenylalanine-tryptophan dipeptide skeleton;
[0028] Figure 7 The nitrogen adsorption-desorption curve and pore size distribution diagram of the mesoporous silicon material containing 15% phenylalanine-tryptophan dipeptide skeleton;
[0029] Figure 8 This is the X-ray diffraction (XRD) pattern of the mesoporous silica material containing 20% phenylalanine-tryptophan dipeptide skeleton;
[0030] Fig. 9 The nitrogen adsorption-desorption curve and pore size distribution diagram of the mesoporous silicon material containing 20% phenylalanine-tryptophan dipeptide skeleton;
[0031] Fig.10 This is the synthetic route of phenylalanine-tryptophan dipeptide skeleton mesoporous silica material. DETAILED DESCRIPTION
[0032] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0033] Example 1: Preparation of 5% phenylalanine-tryptophan dipeptide skeleton mesoporous silica material
[0034] (1) Synthesis of N-tert-butoxycarbonylphenylalanine and tryptophan methyl ester hydrochloride:
[0035]
[0036] 2 g of sodium hydroxide and 3.3 g of phenylalanine were added to a flask, followed by 50 mL of deionized water to dissolve; 4.8 g of di-tert-butyl dicarbonate was dissolved in 50 mL of tetrahydrofuran and slowly added dropwise to the flask under ice bath conditions. Stir at room temperature for 12 h. The solvent was removed by vacuum distillation, the pH value of the aqueous phase was adjusted to 2 with hydrochloric acid, the aqueous phase was extracted three times with ethyl acetate, and the solvent was removed under reduced pressure to obtain 5 g of white oily N-tert-butyloxycarbonylphenylalanine (Compound III).
[0037]
[0038] 8.17 g of tryptophan was added to a flask, followed by 100 mL of ice-cold methanol. 9 mL of thionyl chloride was added dropwise to the flask under ice bath conditions. After the addition was completed, the reaction system was heated to reflux at 80 ° C for 5 h, the solvent was distilled off under reduced pressure, and the excess thionyl chloride was removed with dichloromethane. After drying, 8 g of white solid tryptophan methyl ester hydrochloride (Compound V) was obtained.
[0039] (2) Synthesis of phenylalanyltryptophan-ethylenediamine hydrochloride:
[0040]
[0041] 5.3 g of N-tert-butoxycarbonylphenylalanine and 100 mL of tetrahydrofuran were added to a flask, and 7.68 g of o-benzotriazole-N, N, N', N'-tetramethyluronium tetrafluoroborate and 8.5 mL of triethylamine were added under ice bath conditions and stirred for 30 min, and then 5.08 g of tryptophan methyl ester hydrochloride was added and stirred at room temperature for 3 h. After the reaction was completed, it was purified by column chromatography with the eluent being PE: EA = 1: 2 to obtain 5 g of white solid N-tert-butoxycarbonylphenylalanyltryptophan methyl ester.
[0042]
[0043] The mixture was added to a round-bottomed flask, and 50 mL of 1 M NaOH solution and 50 mL of tetrahydrofuran were added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the solvent was removed by distillation under reduced pressure, the pH value was adjusted to 2 with 1 M hydrochloric acid, the aqueous phase was extracted with ethyl acetate, and the mixture was combined and distilled under reduced pressure, and 4.2 g of N-tert-butyloxycarbonylphenylalanyltryptophan as a white solid was obtained after drying.
[0044]
[0045] Add N-tert-butoxycarbonylphenylalanyltryptophan and 50 mL of tetrahydrofuran into a flask, add 2.14 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 1.28 g of N-hydroxysuccinimide under ice bath conditions and stir for 1 h, then stir at room temperature for 5 h, add 1.5 g of N-tert-butoxycarbonylethylenediamine and excess triethylamine, and continue stirring for 1 h.
[0046] Compound VIII was purified by column chromatography using an eluent of PE:EA in a ratio of 1:1.
[0047]
[0048] 3.5 g of the above compound VIII was added into a round-bottom flask, and after adding 50 mL of methanol, 5 mL of acetyl chloride was slowly added dropwise, stirred at room temperature for 2 h, and distilled under reduced pressure and dried to obtain 2.5 g of brown oily phenylalanyltryptophan-ethylenediamine hydrochloride.
[0049] (3) Synthesis of phenylalanyltryptophan dipeptide organosilicon precursor:
[0050]
[0051] Dissolve phenylalanyltryptophan-ethylenediamine hydrochloride (2.5 g) in 60 mL of anhydrous tetrahydrofuran, add excess triethylamine to adjust the pH to alkaline, then add 3 g of 3-isocyanate propyltriethoxysilane (IPTES), and stir the reaction at room temperature for 5 h. After the reaction is completed, distill under reduced pressure, and finally wash with anhydrous n-hexane to remove impurities, filter and dry to obtain a brown solid phenylalanyltryptophan dipeptide organosilicon precursor. Nuclear magnetic resonance determination: 1H NMR (400MHz, DMSO-d6): δ=10.81 (s, 1H, NH), 8.06 (d, J=8.1Hz, 1H, NH), 7.94 (s, 1H, NH), 7.57 (d, J=7.9Hz, 1H, Ar-H), 7.32 (d, J=8.0Hz, 1H, Ar-H) , 7.19 (dt, J=13.7, 6.8Hz, 3H, Ar-H, NH), 7.12 (dd, J=5.5, 2.3Hz, 3H, Ar-H), 7.05 (t, J=7.5Hz, 1H, Ar-H), 6.97 (t, J=7.4Hz, 1H, Ar-H), 6.15 (t, J=5 .7Hz, 1H, NH), 6.05-5.91 (m, 2H, NH), 5.86 (s, 1H, NH), 4.45 (q, J=7.5Hz, 1H, CH), 4.33 (t, J=6.9Hz, 1H, CH), 3.76-3.69 (m, 12H, CH), 3.07 (q, J=7.2 Hz, 8H, CH), 2.92 (dd, J=12.9, 6.1Hz, 5H, CH), 1.38 (p, J=8.9, 8.4Hz, 4H, CH), 1.13 (td, J=7.0, 1.9Hz, 18H, CH), 0.50 (dt, J=11.8, 4.7Hz, 4H, CH) (such as Figure 1 ).
[0052] (4) Add 2.0g of the template agent polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer (P123), 60.0g of hydrochloric acid (2M) and 15.0g of deionized water into a 250mL beaker, stir at room temperature until dissolved, and then add 9.36g of NaCl. After dissolution, transfer the beaker to a 40°C water bath. According to the percentage of phenylalanyl tryptophan dipeptide organosilicon precursor to the total silicon source (the sum of phenylalanyl tryptophan dipeptide organosilicon precursor and tetraethyl orthosilicate) of 5%, slowly add phenylalanyl tryptophan dipeptide organosilicon precursor and tetraethyl orthosilicate dissolved in 1mL of methanol into the system, and stir continuously for 24h. Then transfer the solution in the beaker to a high-pressure hydrothermal reactor and place it in an oven at 100°C for crystallization for 24h. After crystallization, the material was washed with deionized water and ethanol, dried at 60°C overnight, and placed in a Soxhlet extractor, extracted with anhydrous ethanol and hydrochloric acid (50:1) for 48 hours to remove the template, and dried at room temperature.
[0053] (5) Figure 2 It can be seen that there are three strong diffraction peaks at 0.84, 1.46 and 1.68, which are d 100 d 110 and d 200The crystal plane diffraction peaks indicate that the material has an ordered two-dimensional hexagonal mesoporous structure.
[0054] (6) Figure 3 The nitrogen adsorption-desorption curve and pore size distribution diagram in the sample indicate that the sample belongs to type IV, with a sudden jump between P / P0 of 0.6 and 0.8, and the hysteresis loop is of type H1, indicating the presence of mesoporous capillary condensation. From the pore size distribution diagram, it can be seen that the mesopore size is about 4.3 nm.
[0055] (7) 0.1 g of a mesoporous silica material containing 5% phenylalanine-tryptophan dipeptide skeleton was added to a conical flask, and a certain concentration of chloramphenicol ethanol solution was added. The mixture was stirred at room temperature for 24 h, then filtered and dried at room temperature. The adsorption amount was determined by a UV-visible spectrophotometer to be 83 mg / g.
[0056] Example 2: Preparation of 10% phenylalanine-tryptophan dipeptide skeleton mesoporous silica material
[0057] The steps (1), (2), and (3) of this implementation are the same as those of Example 1.
[0058] (4) This step is basically the same as step (4) of Example 1, except that the amount of phenylalanyl tryptophan dipeptide organosilicon precursor added to the total silicon source (the sum of phenylalanyl tryptophan dipeptide organosilicon precursor and tetraethyl orthosilicate) is 10%.
[0059] (5) Figure 4 It can be seen that there are three diffraction peaks at 0.84, 1.46 and 1.68, which are d 100 d 110 and d 200 The crystal plane diffraction peak shows that the material has an ordered two-dimensional hexagonal mesoporous structure, but the strength is significantly weakened.
[0060] (6) Figure 5 The nitrogen adsorption-desorption curve and pore size distribution diagram in the sample show that it belongs to type IV, with a sudden jump between P / P0 of 0.5-0.8, and the hysteresis loop is an H1 type hysteresis loop, and there is mesoporous capillary condensation. From the pore size distribution diagram, it can be seen that the mesopore size is about 3.9nm.
[0061] (7) This step is basically the same as step (7) of Example 1, except that the adsorption amount is 90 mg / g.
[0062] Example 3: Preparation of 15% phenylalanine-tryptophan dipeptide skeleton mesoporous silica material
[0063] The steps (1), (2), and (3) of this implementation are the same as those of Example 1.
[0064] (4) This step is basically the same as step (4) of Example 1, except that the amount of phenylalanyl tryptophan dipeptide organosilicon precursor added to the total silicon source (the sum of phenylalanyl tryptophan dipeptide organosilicon precursor and tetraethyl orthosilicate) is 15%.
[0065] (5) Figure 6 It can be seen that at 0.88 d 100 Diffraction peak, and d 110 and d 200 The crystal plane diffraction peak is not obvious, indicating that the material has a mesoporous structure.
[0066] (6) Figure 7 The nitrogen adsorption-desorption curve and pore size distribution diagram in the sample show that it belongs to type IV, with a sudden jump between P / P0 of 0.5-0.8, and the hysteresis loop is an H1 type hysteresis loop, and there is mesoporous capillary condensation. From the pore size distribution diagram, it can be seen that the mesopore size is about 3.5nm.
[0067] (7) This step is basically the same as step (7) of Example 1, except that the adsorption amount is 87 mg / g.
[0068] Example 4: Preparation of 20% phenylalanine-tryptophan dipeptide skeleton mesoporous silica material
[0069] The steps (1), (2), and (3) of this implementation are the same as those of Example 1.
[0070] (4) This step is basically the same as step (4) of Example 1, except that the amount of phenylalanyl tryptophan dipeptide organosilicon precursor added to the total silicon source (the sum of phenylalanyl tryptophan dipeptide organosilicon precursor and tetraethyl orthosilicate) is 20%.
[0071] (5) Figure 8 It can be seen that at 0.88 d 100 Diffraction peak, and d 110 and d 200 The crystal plane diffraction peak is not obvious, but the intensity is weakened, indicating that the material has a mesoporous structure.
[0072] (6) Fig. 9 The nitrogen adsorption-desorption curve and pore size distribution diagram in the sample show that it belongs to type IV, with a sudden jump between P / P0 of 0.4-1.0, and the hysteresis loop is an H1 type hysteresis loop, and there is mesoporous capillary condensation. From the pore size distribution diagram, it can be seen that the mesopore size is about 3.1nm.
[0073] (7) This step is basically the same as step (7) of Example 1, except that the adsorption amount is 85 mg / g.
[0074] Fig.10 This is a preparation route for phenylalanine-tryptophan dipeptide skeleton mesoporous materials.
[0075] It can be seen from the X-ray diffraction diagrams of the above four examples that the ordered structure and orderliness of the material decrease with the increase of the dipeptide organosilicon content, but the material still has a mesoporous structure. It can be seen from the nitrogen adsorption-desorption isotherm that the specific surface area, pore volume and pore size of the material all show a decreasing trend with the increase of the dipeptide organosilicon content.
[0076] The above is only a preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.
Claims
1. Phenylalanyltryptophan dipeptide organosilicon precursor of structural formula (I):
2. A method for preparing the phenylalanyltryptophan dipeptide organosilicon precursor (I) according to claim 1, characterized in that: include:
3. The preparation method according to claim 2, characterized in that: In the step of preparing compound I from compound III and compound V, the coupling reagent is o-benzotriazole-N,N,N',N'-tetramethyluronium tetrafluoroboric acid, and the organic base is triethylamine or N,N-diisopropylethylamine; in the step of preparing compound VII from compound VI, the strong base is sodium hydroxide or potassium hydroxide; in the step of preparing compound VIII from compound VII, the activating reagents are 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide, and the organic base is triethylamine or N,N-diisopropylethylamine; in the step of preparing compound I from compound IX, the organic base is triethylamine or N,N-diisopropylethylamine.
4. A method for preparing a phenylalanine-tryptophan dipeptide skeleton mesoporous silicon material, characterized in that: The steps include: S1: Phenylalanyltryptophan dipeptide organosilicon precursor (I) and tetraethyl orthosilicate are mixed in proportion, and added dropwise to a mixed solution of template, deionized water, and sodium chloride hydrochloric acid, reacted in a water bath, crystallized at high temperature, and then filtered, washed with water, and dried; S2: removing the template in a mixed solvent of anhydrous ethanol and hydrochloric acid, drying, and obtaining a phenylalanine-tryptophan dipeptide skeleton mesoporous silica material.
5. The preparation method according to claim 4, characterized in that: The amount of the phenylalanyltryptophan dipeptide organosilicon precursor (I) accounts for 5%-20% of the sum of the phenylalanyltryptophan dipeptide organosilicon precursor (I) and tetraethyl orthosilicate.
6. The preparation method according to claim 4, characterized in that: The temperature of the water bath in step S1 is 40°C-60°C, the reaction time in the water bath is 24-36h, and the temperature of high temperature crystallization is 100°C-110°C.
7. The preparation method according to claim 4, characterized in that: The template agent is a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer.
8. The preparation method according to claim 4, characterized in that: The concentration of hydrochloric acid is 2M.
9. A phenylalanine-tryptophan dipeptide skeleton mesoporous silica material, characterized in that: The invention is prepared by the preparation method described in any one of claims 4 to 8.
10. Use of the phenylalanine-tryptophan dipeptide skeleton mesoporous silica material according to claim 9 in adsorbing chloramphenicol.