A nitrogen mustard synergistic strontium ion antibacterial fabric and its preparation method and use

Abstract

The present invention discloses a nitrogen mustard-synergistic strontium ion antibacterial fabric, as well as its preparation method and use. An azo drug, 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide, is prepared using dopamine hydrochloride and N-phenyldiethanolamine. The drug is then coordinated with strontium ions on fabric fibers through in-situ growth to form nanoparticles. Upon contact with bacteria, the functionally coated fabric releases nitrogen mustard within the bacterial environment, forming a strong electrophilic alkylating agent within the cells. This covalently binds to electron-rich groups in DNA, RNA, and some enzymes, deactivating them and killing the bacteria. Furthermore, a large amount of strontium ions slowly released from the antibacterial fabric can be adsorbed on the surface of bacterial cell membranes, causing a voltage difference between the inside and outside of the cell membranes, weakening and rupturing the cell membranes. The strontium ions then enter the cells and hinder their formation and metabolism, thereby achieving a synergistic antibacterial effect.

Description

Technical Field

[0001] The invention belongs to the technical field of antibacterial fabrics, and particularly relates to the preparation and application of antibacterial fabrics using nitrogen mustard in conjunction with strontium ions. Background Art

[0002] Textiles are inherently porous, ideal breeding grounds for bacteria and fungi. Furthermore, the presence of dandruff and sweat on clothing creates a warm, humid environment that is particularly conducive to the growth of microorganisms. The growth and proliferation of microorganisms not only damages the fabric itself but also affects the wearer's comfort. In severe cases, they can lead to skin diseases and even cancer.

[0003] Not only does the high consumer demand for clothing provide a market guarantee for antimicrobial fabrics, but the future market for antimicrobial fibers is also expected to be even broader, with applications such as outdoor products, filter membranes, textile accessories, and medical textiles. For these reasons, research into antimicrobial fabrics to inhibit the growth and reproduction of bacteria on fabrics is essential.

[0004] Metal ion sterilization technology is a classic and effective antimicrobial technique. Metal ions adsorbed on microbial surfaces disrupt cell membranes and enter the cell interior, interfering with cellular metabolism or inhibiting enzyme activity, disrupting various cellular mechanisms, and ultimately leading to apoptosis. Currently, commonly used metal ions for antimicrobial applications include silver, copper, and zinc. However, these ions face numerous challenges in their practical application as antimicrobial agents. For example, silver is a heavy metal ion, and its metabolic processes may pose safety risks to organisms. Furthermore, copper ions are inherently colored and can stain fabrics, making them unsuitable for widespread use. Studies have shown that zinc ions have poor antimicrobial efficacy, often requiring high concentrations to achieve optimal antimicrobial efficacy, limiting their widespread use. Therefore, the search for highly effective antimicrobial ions with excellent biosafety and cost-effectiveness is of great practical significance. Recent research indicates that strontium, as an alkaline earth metal, has broad application prospects, exhibiting anticancer, antioxidant, and immune-enhancing properties. Strontium-containing composite materials also exhibit certain antimicrobial properties. Therefore, incorporating strontium ions into fabric coatings can not only ensure biosafety but also achieve antimicrobial effects. In the present invention, in order to improve the antibacterial effect of the fabric coating containing strontium ions, the antibacterial functions of the ions and nitrogen mustard are combined, and an antibacterial functional fabric with nitrogen mustard and strontium ions is formed by in situ growth, which can provide an effective and feasible solution for the development of new and efficient antibacterial fabrics. Summary of the Invention

[0005] The purpose of the present invention is to provide a preparation and application of antibacterial functional fabric with nitrogen mustard and strontium ions. Through the ingenious design of the antibacterial fabric, the bactericidal effect of strontium ions and the antibacterial effect of nitrogen mustard are simultaneously effective, providing a potential solution for fabric antibacterial.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] An antibacterial functional fabric with nitrogen mustard and strontium ions is prepared by the following steps:

[0008] Step 1, N-phenyldiethanolamine and phosphorus oxychloride are reacted to synthesize the compound N,N-di(2-chloroethyl)aniline (i.e., NMB);

[0009] Step 2: N,N-di(2-chloroethyl)aniline and p-aminobenzoic acid are reacted to synthesize 4-(4-(di(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid (i.e., NMC);

[0010] Step 3, the compound 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid is reacted with dopamine hydrochloride to generate 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide (i.e., NMCDA);

[0011] In step 4, 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide is coordinated with strontium chloride on the fabric fiber to form nanoparticles through in situ growth.

[0012] In step 3, dopamine hydrochloride, the compound 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid, 0-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate, and N,N-diisopropylethylamine are mixed and dissolved in N,N-dimethylformamide and reacted under magnetic stirring.

[0013] The molar ratio of the compound 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid, dopamine hydrochloride, 0-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate and N,N-diisopropylethylamine is 8:10:9:12.

[0014] In step 4, the molar concentration ratio of the compound 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenethyl)benzamide solution and the strontium chloride solution is 2:3.

[0015] The invention discloses an application of a fabric coating having antibacterial functions of nitrogen mustard and strontium ions in the preparation of antibacterial fabrics.

[0016] Application of the above antibacterial fabric.

[0017] The invention uses dopamine hydrochloride and N-phenyldiethanolamine to prepare an azo drug 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide, which is coordinated with strontium ions on textile fibers to form nanoparticles through in-situ growth.

[0018] The antibacterial fabric of the present invention can release nitrogen mustard in bacteria, forming a strong electrophilic alkylating agent in the cells, which will covalently bind to the electron-rich groups in DNA, RNA and some enzymes, causing them to lose their activity; on the other hand, a large amount of strontium ions in the antibacterial fabric will be adsorbed on the surface of the bacterial cell membrane, causing the voltage difference between the inside and outside of the cell membrane to change, weakening the cell membrane and creating holes, which will enter the cell and hinder the cell's formation and metabolism.

[0019] The antibacterial fabric of the present invention has simple synthesis steps and low cost, and is therefore suitable for large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The synthetic chemical equation for 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide in Example 1 is shown in FIG.

[0021] Figure 2 This is the hydrogen spectrum of 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenethyl)benzamide.

[0022] Figure 3 This is the SEM image of the nanoparticles grown in situ on the fabric in Example 1.

[0023] Figure 4 This is the ultraviolet spectrum of 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenethyl)benzamide in Example 1.

[0024] Figure 5 This is the infrared spectrum of 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenethyl)benzamide of Example 1.

[0025] Figure 6 This is a graph showing the antibacterial performance of the antibacterial fabric of Example 1. DETAILED DESCRIPTION

[0026] To illustrate the structural features, technical means, and achieved objectives and effects of the present invention in detail, the following is a detailed description in conjunction with the embodiments and accompanying drawings.

[0027] The invention provides an antibacterial functional fabric with nitrogen mustard and strontium ions.

[0028] Specifically, the nitrogen mustard synergistic antibacterial fabric is prepared by coordinating strontium ions with the catechol structure in 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide through an in situ growth method to form nanoparticles on the fabric fibers.

[0029] The preparation method of the antibacterial fabric comprises the following steps:

[0030] Step 1: N-phenyldiethanolamine and phosphorus oxychloride are reacted to synthesize the compound N,N-di(2-chloroethyl)aniline

[0031] Place 2 g of N-phenyldiethanolamine in a round-bottom flask, cool in an ice-water bath, and slowly add 4.5 ml of phosphorus oxychloride (POCl3). Stir magnetically until uniform. Then, transfer the round-bottom flask to 110°C and reflux for 1 hour. Add 15 ml of saturated brine and 15 ml of ethyl acetate to the reaction solution. Separate the liquid, retaining the organic phase. Purify the resulting compound, N,N-di(2-chloroethyl)aniline, by column chromatography.

[0032] Step 2: Synthesize 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid by reacting N,N-bis(2-chloroethyl)aniline with p-aminobenzoic acid.

[0033] Dissolve 0.6 g of p-aminobenzoic acid and 0.4 g of sodium nitrite in 10 ml of deionized water, add 1.4 ml of concentrated hydrochloric acid, and stir for 20 minutes. Dissolve 1 gram of the compound N,N-bis(2-chloroethyl)aniline from Step 1 in 30 ml of anhydrous ethanol, and after uniform dissolution, add the mixture to the aqueous solution and stir for 2 hours. After the reaction is complete, filter the orange-red solid and purify it by recrystallization to obtain the compound 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid.

[0034] Step 3: The compound 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid is reacted with dopamine hydrochloride to generate 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide;

[0035] 189 mg of dopamine hydrochloride, 300 mg of the compound 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid, 342 mg of 0-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), and 205 μL of N,N-diisopropylethylamine (DIPEA) were dissolved in 9 mL of N,N-dimethylformamide (DMF) and magnetically stirred for 24 hours. After the reaction, 25 mL of deionized water was added, the mixture was shaken, and then extracted with 25 mL of ethyl acetate (EA). The organic phase was retained and purified by column chromatography. After drying, an orange-red solid of 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide was obtained.

[0036] Step 4: Coordinate 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide with strontium chloride on the fabric fiber to form nanoparticles through in situ growth.

[0037] Dissolve 25 mg of NMCDA in 2 ml of DMF, shake well, and add 8 ml of methanol, which is recorded as liquid A. Dissolve 10 mg of strontium chloride in 10 ml of aqueous solution, which is recorded as liquid B. Soak the cut cloth in liquid A and liquid B for 30 minutes respectively, repeat five times, take out the soaked cloth, and place it in an oven to dry.

[0038] The dopamine hydrochloride, N-phenyldiethanolamine, phosphorus oxychloride, ethyl acetate, p-aminobenzoic acid, sodium nitrite, concentrated hydrochloric acid, anhydrous ethanol, p-aminophenol, 0-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate, N,N-diisopropylethylamine, N,N-dimethylformamide and strontium chloride are all commonly used chemical raw materials for preparation and can be directly ordered from the reagent website.

[0039] The antibacterial fabric with nitrogen mustard and strontium ions exhibits dual antibacterial effects. The large amount of strontium ions in the antibacterial fabric adsorbs onto the surface of bacterial cell membranes, rupturing the outer membrane. Once the nanoparticles penetrate the ruptured cell membranes and enter the bacteria, the strontium ions hinder cellular metabolism and inactivate important enzymes. Simultaneously, the nitrogen mustard in the nanoparticles alkylates DNA, RNA, and enzymes within the cells, hindering bacterial growth and ultimately killing them.

[0040] It is understood that the dual antibacterial properties of nitrogen mustard and strontium ions in the antibacterial fabric can significantly reduce bacterial growth on the fabric. Furthermore, the antibacterial fabric of the present invention is synthesized from inexpensive raw materials and has a simple preparation process, making it easy to mass-produce.

[0041] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific examples, but should not be construed as limiting the present invention. Without departing from the spirit and substance of the present invention, modifications or substitutions made to the inventive method, steps or conditions are intended to fall within the scope of the present invention. Experimental methods and reagents for which specific conditions are not specified in the examples are based on conventional conditions in the art. Example 1

[0042] (1) N-phenyldiethanolamine and phosphorus oxychloride are used to synthesize the compound N,N-di(2-chloroethyl)aniline

[0043] Place 2 g of N-phenyldiethanolamine in a round-bottom flask and cool in an ice-water bath. Slowly add 4.5 ml of phosphorus oxychloride and stir magnetically. Then, transfer the flask to 110°C and reflux for 1 hour. Add 15 ml of saturated brine and 15 ml of ethyl acetate to the solution, separate the layers, and retain the organic phase. Purify the mixture using column chromatography to obtain the compound N,N-di(2-chloroethyl)aniline.

[0044] (2) Compound N,N-di(2-chloroethyl)aniline and p-aminobenzoic acid are used to synthesize 4-(4-(di(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid

[0045] Dissolve 0.6 g of p-aminobenzoic acid and 0.4 g of sodium nitrite in 10 ml of deionized water, add 1.4 ml of concentrated hydrochloric acid, and stir for 20 minutes. Dissolve 1 gram of the compound N,N-bis(2-chloroethyl)aniline from Step 1 in 30 ml of anhydrous ethanol, and after uniform dissolution, add the mixture to the aqueous solution and stir for 2 hours. After the reaction is complete, filter the orange-red solid and purify it by recrystallization to obtain the compound 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid.

[0046] (3) reacting the compound 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid with dopamine hydrochloride to generate 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide;

[0047] 189 mg of dopamine hydrochloride, 300 mg of the compound 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid, 342 mg of 0-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), and 205 μL of N,N-diisopropylethylamine (DIPEA) were dissolved in 9 mL of N,N-dimethylformamide (DMF) and magnetically stirred for 24 hours. After the reaction, 25 mL of deionized water was added, the mixture was shaken, and then extracted with 25 mL of ethyl acetate (EA). The organic phase was retained and purified by column chromatography. After drying, an orange-red solid of 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide was obtained.

[0048] (4) 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide was coordinated with strontium chloride on textile fibers to form nanoparticles by in situ growth.

[0049] Dissolve 25 mg of 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide in 2 ml of DMF, shake well, and add 8 ml of methanol (this solution is referred to as Liquid A). Dissolve 10 mg of strontium chloride in 10 ml of aqueous solution (this solution is referred to as Liquid B). Soak the cut fabric in Liquid A and Liquid B, respectively, for 30 minutes each. Repeat this process five times, remove the soaked fabric, and dry it in an oven.

[0050] Figure 1 、 Figure 2 They are respectively the synthesis equation and hydrogen spectrum of 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenethyl)benzamide in the examples.

[0051] 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenethyl)benzamide: orange-red solid, 1 H-NMR (400 MHz, DMSO) δ: 8.79 (s, 1H, NH), δ: 8.66 (t, 2H, OH), δ: 7.97 (d, 2H, ArH), δ: 7.83 (d, 4H, ArH), δ: 6.98 (d, 2H, ArH), δ: 6.6 3 (d, 2H, ArH), δ: 6.50 (d, 1H, ArH), δ: 3.88 (d, 4H, CH2), δ: 3.80 (d, 4H, CH2), δ: 3.37 (t, 2H, CH2), δ: 2.67 (d, 2H, CH2).

[0052] Performance testing:

[0053] Morphology determination of nanoparticles on antibacterial fabrics

[0054] Figure 3 This is the SEM image of the nanoparticles grown in situ on the fabric fibers in Example 1.

[0055] Determination of properties of 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide

[0056] pass Figure 4 The UV absorption spectrum of 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenethyl)benzamide shows that the absorption peak at 225 nm is the characteristic peak of the benzene ring structure in 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenethyl)benzamide, the absorption peak at 280 nm is the characteristic peak of the nitrogen mustard structure in 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenethyl)benzamide, and the absorption peak at 450 nm is the characteristic peak of the azo (-N=N-) structure in 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenethyl)benzamide.

[0057] pass Figure 5 The infrared spectrum of 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide can be analyzed at 855cm -1 The peak at 749 cm is the characteristic peak of the para-substituted structure of the benzene ring. -1 The peak at 719 cm is the characteristic peak of the ortho-substituted structure of the benzene ring. -1 The characteristic peak of C-Cl is 1510 cm -1 The peaks are characteristic of azo structure.

[0058] 3. Antibacterial Activity Determination

[0059] The antibacterial fabric in Example 1 was prepared and recorded as the fabric+NMCDAC group.

[0060] Preparation of fabrics attached with the compound 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenethyl)benzamide, denoted as the fabric+NMCDA group: 25 mg of 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenethyl)benzamide was dissolved in 2 ml of DMF, shaken, and then 8 ml of methanol was added. The cut fabrics were soaked in the solution for 30 minutes. This process was repeated five times. The soaked fabrics were removed and dried in an oven.

[0061] pass Figure 6 It can be seen that ordinary fabrics have no antibacterial ability. The fabric + NMCDA group can inhibit the growth of some bacteria because of the presence of nitrogen mustard structure; the fabric + NMCDAC group can effectively inhibit the growth of bacteria. This is because compared with the fabric + NMCDA group, the fabric + NMCDAC not only has the antibacterial effect of nitrogen mustard, but the rich strontium ions in it can also inhibit the growth of bacteria. The synergistic effect of the two greatly enhances the antibacterial effect of the fabric.

Claims

1. A fabric coating with nitrogen mustard and strontium ion antibacterial function, characterized by: Prepared by the following steps: Step 1, synthesizing the compound N,N-di(2-chloroethyl)aniline by reacting N-phenyldiethanolamine with phosphorus oxychloride; Step 2, synthesizing 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid by reacting N,N-bis(2-chloroethyl)aniline with p-aminobenzoic acid; Step 3, the compound 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid is reacted with dopamine hydrochloride to generate 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide; Step 4, by in situ growth, 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide is coordinated with strontium chloride on the fabric fiber to form nanoparticles; In step 3, dopamine hydrochloride, the compound 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid, 0-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate, and N,N-diisopropylethylamine are mixed and dissolved in N,N-dimethylformamide and reacted under magnetic stirring.

2. The textile coating with nitrogen mustard and strontium ion antibacterial function according to claim 1, characterized in that: The molar ratio of the compound 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid, dopamine hydrochloride, 0-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate and N,N-diisopropylethylamine is 8:10:9:

12.

3. The textile coating with nitrogen mustard and strontium ion antibacterial function according to claim 1, characterized in that: In 4, the molar concentration ratio of the compound 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenethyl)benzamide solution and the strontium chloride solution is 2:

3.

4. A method for preparing a fabric coating having antibacterial properties synergistically with strontium ions as claimed in claim 1, characterized in that: The following steps are involved: Step 1, synthesizing the compound N,N-di(2-chloroethyl)aniline by reacting N-phenyldiethanolamine with phosphorus oxychloride; Step 2, synthesizing 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid by reacting N,N-bis(2-chloroethyl)aniline with p-aminobenzoic acid; Step 3, the compound 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)benzoic acid is reacted with dopamine hydrochloride to generate 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide; In step 4, 4-(4-(bis(2-chloroethyl)amino)phenyl)diazenyl)-N-(3,4-dihydroxyphenylethyl)benzamide is coordinated with strontium chloride on the fabric fiber to form nanoparticles through in situ growth.

5. Use of the textile coating comprising the nitrogen mustard and strontium ion antibacterial function according to claim 1 in the preparation of antibacterial textiles.

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