Antibacterial polyurethane acrylate film material embedded with N-substituted benzisothiazolinone and alkenyl functionalized quaternary phosphonium salt

Abstract

The invention provides an antibacterial polyurethane acrylate film material embedded with N-substituted benzisothiazolinone and alkenyl functionalized quaternary phosphonium salt, and belongs to the field of organic antibacterial coatings. N-substituted alkenyl of benzisothiazolinone is functionalized, tri (4-methoxyphenyl) phosphine alkenyl is functionalized, and the antibacterial polyurethane acrylate film material is prepared. Double bonds are introduced into a benzisothiazolinone structural unit and a tri (4-methoxyphenyl) phosphine structural unit, N-substituted benzisothiazolinone (NIT) and tri (4-methoxyphenyl) (nonyl-8-ene-1-yl) phosphonium bromide (TPC9) are grafted into a polyurethane acrylate main chain at the same time, and by means of the remarkable antibacterial activity of the NIT and the TPC9 on escherichia coli and staphylococcus aureus, the polyurethane acrylate can be used for preparing the antibacterial polyurethane acrylate. A broad-spectrum antibacterial material is prepared, and a corresponding antibacterial coating can be used for modifying the surface of a base material.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic antibacterial polymer film materials, and particularly relates to an antibacterial polyurethane acrylate film material structure with benzisothiazolinone and quaternary phosphonium salt structural units grafted at different proportions, and a preparation method thereof. Background Art

[0002] Benzisothiazolinone is an isothiazolinone-type antimicrobial agent. Target proteins or glutathione within cells readily react with the N-S bond within the benzisothiazolinone molecular structure, breaking the N-S bond, opening the heterocyclic ring, and forming disulfides. These disulfides interfere with enzymatic processes, causing cell dysfunction and ultimately bacterial death. Benzisothiazolinone exhibits high antimicrobial activity. Quaternary phosphonium salts are organic cationic antimicrobial agents with strong antimicrobial activity. The cations within their molecular structure can adsorb onto bacterial cell walls through electrostatic interactions. The alkyl chains within their structure insert into and cleave the cell membrane, allowing bacterial substances to leak and leading to bacterial death. Tris(4-methoxyphenyl)phosphonium salts exhibit the highest antimicrobial activity and the broadest antimicrobial spectrum.

[0003] A search revealed a benzisothiazolinone compound used as a fungicide and its preparation method, with application number 20221065604. The method discloses a preparation method for benzisothiazolinone compounds. In the presence of p-toluenesulfonic acid, benzisothiazolinone reacts with fatty aldehydes and fatty alcohols to produce a series of N-substituted benzisothiazolinone derivatives with varying alkyl chain lengths, providing insights for the further development of new antimicrobial agents.

[0004] After searching, the application number is: 202410568555.X, which is a quaternary phosphonium salt modified polyacrylonitrile fiber antibacterial material. In the disclosed technology, under the action of potassium permanganate and benzoyl peroxide, methyltriphenylphosphonium bromide generates free radicals under the initiation of benzoyl peroxide, which react with the active groups of polyacrylonitrile fiber to form a quaternary phosphonium salt modified polyacrylonitrile fiber antibacterial coating. The coating has significant antibacterial effects on both Gram-negative and Gram-positive bacteria.

[0005] The preparation methods disclosed in the above patents do not involve covalently grafting benzisothiazolinone and quaternary phosphonium salt structural units onto the polyurethane acrylate backbone. In contrast, the present invention proposes a structure of an antibacterial polyurethane acrylate coating that is simultaneously grafted with benzisothiazolinone and quaternary phosphonium salt structural units, and a preparation method thereof. The prepared antibacterial film material not only has high-efficiency and broad-spectrum antibacterial properties, but also avoids the leakage of antibacterial small molecules, while expanding the scope of use of the antibacterial agent. Summary of the Invention

[0006] The present invention provides an antibacterial polyurethane acrylate film material embedded with N-substituted benzisothiazolinone and vinyl-functionalized quaternary phosphonium salt, which solves the problems in the prior art.

[0007] The technical solution of the present invention is realized as follows: An antibacterial polyurethane acrylate film material embedded with N-substituted benzisothiazolinone and vinyl-functionalized quaternary phosphonium salt is an antibacterial polyurethane acrylate film material grafted with different proportions of benzisothiazolinone and quaternary phosphonium salt antibacterial units at the same time. The benzisothiazolinone structural unit refers to N-substituted benzisothiazolinone, and the quaternary phosphonium salt antibacterial unit refers to tris(4-methoxyphenyl)(non-8-en-1-yl)phosphonium bromide, which is grafted onto the main chain of polyurethane acrylate through carbon-carbon double bond free radical polymerization to obtain an antibacterial polyurethane acrylate film material;

[0008] The structural formula of the polymer is as follows:

[0009] Formula (1):

[0010]

[0011] Wherein R1:

[0012]

[0013] Wherein, the value range of M is 1-100; Is the main structure of the triol except H.

[0014] As a preferred embodiment, the polymer is composed of groups R1, blocks A, B, C, D, and E. The end of the three-branch structure of R1 is a double bond. The structures of R1 and blocks A, B, C, D, and E are as follows, wherein blocks D and E are respectively grafted with benzisothiazolinone and quaternary phosphonium salt structural units;

[0015] Wherein R1:

[0016]

[0017] Block A: Block B: [[ID=३८]]

[0018] Block C: Block D:

[0019] Block E:

[0020] As a preferred embodiment, the polymers corresponding to blocks A, B, C, D, and E are a, b, c, d, and e respectively, which can be adjusted according to the required degree of polymerization, and the value range is 2-50 or 25-45.

[0021] A method for preparing a polymer, comprising the following steps:

[0022] (1) Prepare the polymer corresponding to R1;

[0023] (2) Prepare a benzisothiazolinone derivative having the structure shown by monomer D corresponding to block D;

[0024] (3) Prepare a quaternary phosphonium salt having the structure shown by monomer E corresponding to block E;

[0025] (4) Add the R1 polymer, monomer D, monomer E, and the reactive diluent monomer A corresponding to block A, the reactive diluent monomer B corresponding to block B, and the reactive diluent monomer C corresponding to block C to a photoinitiator and mix to obtain a polyurethane acrylate prepolymer;

[0026] Wherein monomer A: Wherein monomer B:

[0027] Wherein monomer C: Wherein monomer D:

[0028] Wherein monomer E:

[0029] (5) The polyurethane acrylate prepolymer prepared in step (4) is cured by ultraviolet light to form a coating having antibacterial properties corresponding to formula (1).

[0030] As a preferred embodiment, the mass ratio range between the polyurethane polymer R1, the reactive diluent monomers (A + B + C), and the antibacterial small molecules (D + E) is 5:4.98:0.02 to 5:4.94:0.06; the sum of the masses of the reactive diluent monomers (A + B + C) and the antibacterial small molecules (D + E) is equal to the polyurethane polymer R1; wherein, the mass ratio of the reactive diluent monomers A, B, and C is 5:3:1.7 to 5:3:2; the mass ratio of the antibacterial small molecule benzisothiazolinone derivative and tris(4-methoxyphenyl(non-8-en-1-yl)phosphonium bromide) is 1:1, 1:2, 1:3, 2:3, 2:1, 3:1, 3:2.

[0031] An application of a polymer directly as an antibacterial film or antibacterial coating.

[0032] As a preferred embodiment, it is used to prepare an antibacterial film or antibacterial coating with bactericidal properties against Gram-positive bacteria and Gram-negative bacteria.

[0033] After adopting the above technical solution, the beneficial effects of the present invention are:

[0034] The polyurethane acrylate antibacterial coating with NIT:TPC9 = 3:1 (wt%) has the strongest antibacterial activity against Gram-positive and Gram-negative bacteria. The antibacterial coating prepared with the addition content of benzisothiazolinone derivative being 4.5 wt% and the addition content of tris(4-methoxyphenyl)(non-8-en-1-yl)phosphonium bromide being 1.5 wt% has an antibacterial property of 99.9% against Gram-positive bacteria and 96.8% against Gram-negative bacteria, making the antibacterial coating prepared in the present invention have a more excellent comprehensive antibacterial effect. Brief Description of the Drawings

[0035] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can be obtained based on these drawings.

[0036] Figure 1 1H NMR spectrum of the antibacterial small molecule NIT prepared in the present invention;

[0037] Figure 2 13C NMR spectrum of the antibacterial small molecule NIT prepared in the present invention;

[0038] Figure 3 1H NMR spectrum of the antibacterial small molecule TPC9 prepared in the present invention;

[0039] Figure 4 13C NMR spectrum of the antibacterial small molecule TPC9 prepared in the present invention;

[0040] Figure 5 Attenuated total reflection infrared spectra of the PUA, PUA-NIT-6wt%, PUA-TPC9-6wt%, PUA-(NIT-TPC9(3:1))-2wt%, PUA-(NIT-TPC9(3:1))-4wt%, PUA-(NIT-TPC9(3:1))-6wt% coatings prepared in the present invention;

[0041] Figure 6 Thermogravimetric stability test charts (TGA) of the PUA, PUA-NIT-6wt%, PUA-TPC9-6wt%, PUA-(NIT-TPC9(3:1))-2wt%, PUA-(NIT-TPC9(3:1))-4wt%, PUA-(NIT-TPC9(3:1))-6wt% coatings prepared in the present invention;

[0042] Figure 7Full thermodynamic stability test diagrams (DTG) of the PUA, PUA-NIT-6wt%, PUA-TPC9-6wt%, PUA-(NIT-TPC9(3:1))-2wt%, PUA-(NIT-TPC9(3:1))-4wt%, and PUA-(NIT-TPC9(3:1))-6wt% coatings prepared according to the present invention;

[0043] Figure 8 Antibacterial zone test diagrams of the PUA-(NIT-TPC9(1:1))-6wt%, PUA-(NIT-TPC9(1:2))-6wt%, PUA-(NIT-TPC9(1:3))-6wt%, PUA-(NIT-TPC9(2:3))-6wt%, PUA-(NIT-TPC9(2:1))-6wt%, PUA-(NIT-TPC9(3:1))-6wt%, and PUA-(NIT-TPC9(3:2))-6wt% coatings prepared according to the present invention;

[0044] Figure 9 Bacterial plate counting method test diagrams of the PUA, PUA-(NIT-TPC9(1:1))-4wt%, PUA-(NIT-TPC9(1:2))-4wt%, PUA-(NIT-TPC9(1:3))-4wt%, PUA-(NIT-TPC9(2:3))-4wt%, PUA-(NIT-TPC9(2:1))-4wt%, PUA-(NIT-TPC9(3:1))-4wt%, PUA-(NIT-TPC9(3:2))-4wt%, PUA-NIT-4wt%, PUA-TPC9-4wt%, PUA-(NIT-TPC9(3:1))-2wt%, and PUA-(NIT-TPC9(3:1))-6wt% coatings prepared according to the present invention;

[0045] Figure 10 For the PUA, PUA-(NIT-TPC9(3:1))-2wt%, PUA-(NIT-TPC9(3:1))-4wt%, and PUA-(NIT-TPC9(3:1))-6wt% coatings prepared according to the present invention BacLightTM bacterial cell viability diagrams. Detailed implementation manners

[0046] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0047] An antibacterial polyurethane acrylate film material embedded with N-substituted benzisothiazolinone and alkenyl-functionalized quaternary phosphonium salts, and an antibacterial polyurethane acrylate coating grafted with different proportions of benzisothiazolinone and quaternary phosphonium salt structural units;

[0048] One of the structural formulas is as follows:

[0049] Formula (1)

[0050]

[0051] Wherein R1 is:

[0052] Formula (2) [[ID=ID=19]]

[0053]

[0054] The preparation method of the antibacterial polyurethane acrylate coating grafted with different proportions of benzisothiazolinone and quaternary phosphonium salt structural units includes but is not limited to the following steps:

[0055] (1) Prepare the R1 polymer, the structure of which is shown in Formula (2);

[0056] (2) Prepare the benzisothiazolinone derivative with the structure shown in monomer D;

[0057] (3) Prepare the quaternary phosphonium salt with the structure shown in monomer E;

[0058] (4) Add the R1 polymer, monomer D, monomer E, and the active diluent monomer A corresponding to block A, the active diluent monomer B corresponding to block B, and the active diluent monomer C corresponding to block C (monomers A, B, and C are all purchased from Anyaji Chemical Company), and mix with a photoinitiator to obtain a polyurethane acrylate prepolymer;

[0059] Monomer A: Monomer B:

[0060] Monomer C: Monomer D:

[0061] Monomer E:

[0062] (5) The polyurethane acrylate prepolymer prepared in step (4) forms a coating with antibacterial properties after ultraviolet curing.

[0063] Furthermore, the mass ratio range of the polyurethane polymer R1, the reactive diluent monomers (A + B + C), and the antibacterial small molecules (D + E) is 5:4.98:0.02 to 5:4.94:0.06; among them, the mass ratio of the reactive diluent monomers A, B, and C is 5:3:1.7 to 5:3:2, preferably 5:3:2; the mass ratio of the antibacterial small molecules benzisothiazolinone derivative and tris(4-methoxyphenyl)(non-8-en-1-yl)phosphonium bromide is 1:1, 1:2, 1:3, 2:3, 2:1, 3:1, 3:2.

[0064] Example 1

[0065] Weigh 8.4 mmol (1.87 g) of isophorone diisocyanate (IPDI) and add it to a 50 mL three-necked flask. Slowly add 4.2 mmol (12.58 g) of polyether polyol HSH330N and 0.006 eq (0.03 g) of the catalyst dibutyltin dilaurate (DBTDL) through a constant pressure dropping funnel, and mechanically stir at 35 °C for 2 h. After the reaction is complete, slowly add 4.5 mmol (0.52 g) of hydroxyethyl acrylate (HEA) through the constant pressure dropping funnel, and continue to react for 40 min to obtain the polymer R1.

[0066] Add 15 g of the above polymer R1 to 15 g of the reactive diluent (monofunctional isobornyl methacrylate i.e. A: 1,6-hexanediol diacrylate i.e. B: trimethylolpropane triacrylate i.e. C = 5:3:2), and mechanically stir at 35 °C for 40 min to obtain a pale white transparent viscous polyurethane acrylate prepolymer.

[0067] Take 0.92 g of the polyurethane acrylate prepolymer solution, 15 mg of tris(4-methoxyphenyl)(non-8-en-1-yl)phosphonium bromide, 45 mg of the benzisothiazolinone derivative (NIT), add 0.02 eq (0.02 g) of the photoinitiator 2-hydroxy-2-methylphenylpropanone (HMPP), stir well to obtain a transparent liquid mixture, then evenly apply it to a silica gel plate, cover the surface with a transparent glass sheet, and cure it under ultraviolet light irradiation to obtain a coating with antibacterial properties PUA-(NIT-TPC9(3:1))-6 wt%, and the same is true for other mass ratios.

[0068] According to the method of Example 1, by changing the total content of benzisothiazolinone derivative and tris(4-methoxyphenyl)(non-8-en-1-yl)phosphonium bromide, a series of polyurethane acrylate antibacterial coatings grafted with different proportions of benzisothiazolinone structural units and quaternary phosphonium salt structural units are prepared, and named PUA-(NIT-TPC9(n1:n2))-xwt%, where xwt% is the total added mass of benzisothiazolinone structural units and quaternary phosphonium salt structural units in the main chain. When NIT:TPC9 = 3:1, xwt% is set to 2wt%, 4wt%, 6wt% here; the corresponding antibacterial coatings prepared are PUA-(NIT-TPC9(3:1))-2wt%, PUA-(NIT-TPC9(3:1))-4wt%, PUA-(NIT-TPC9(3:1))-6wt% and the blank control PUA coating.

[0069] Test characterization and antibacterial performance test

[0070] (1) 1H NMR and 13C NMR tests

[0071] The preparation of antibacterial small molecules NIT and TPC9 in the examples was detected by nuclear magnetic resonance. The test results of 1H NMR and 13C NMR are as Figure 1-4 shown, where the solvents were selected as CDCl3 and DMSO-d6; it can be obtained from the spectral analysis that the antibacterial small molecules NIT and TPC9 were successfully prepared.

[0072] (2) Attenuated total reflection infrared (FT-IR) test

[0073] The prepared antibacterial coatings in the examples were tested by attenuated total reflection infrared. The test results are as Figure 5 shown; for the polyurethane added with antibacterial agents, the antibacterial coatings showed a bending vibration absorption peak of ortho-disubstituted benzene of NIT at 743 cm-1; a bending vibration absorption peak of para-disubstituted benzene at 834 cm-1; no stretching vibration absorption peak of carbon-carbon double bond (C=C) in compounds NIT and TPC9 was observed at 1630 cm-1; the stretching vibration absorption peak of -NCO group of IPDI near 2270 cm-1 disappeared. It can be obtained from the spectral analysis that the prepared antibacterial coatings were completely cured and NIT and TPC9 were embedded in the main chain.

[0074] (3) Thermodynamic stability tests (TGA, DTG)

[0075] The prepared antibacterial coatings in the examples were tested for thermodynamic stability. The test results are as Figure 6-7 shown; the coating began to degrade significantly at 310 °C, showing good thermal stability. Adding a small amount of antibacterial agents NIT and TPC9 had little effect on the overall thermal stability of the coating.

[0076] (4) Antibacterial performance test

[0077] The antibacterial coatings prepared in the examples were subjected to inhibition zone test, plate counting method test and BacLightTM bacterial cell viability test.

[0078] In the inhibition zone test, the bacterial solution (Gram-negative bacterium Escherichia coli) was diluted to 109 CFU·mL-1. 100 μL of the diluted bacterial solution was spread on a culture dish. Before the test, the coating film was sterilized under ultraviolet light for 30 min, cut into small squares, and placed on the culture dish coated with the bacterial solution, and cultured at 37 °C for 24 h, and whether an inhibition zone was generated was observed. The test results are as Figure 8 shown. The results show that no inhibition zone was generated in the coating film, indicating that this coating is a contact-type antibacterial material, and NIT and TPC9 are completely embedded in the polyurethane main chain.

[0079] In the plate counting method test, the bacterial solutions (corresponding to E. coli and S. aureus respectively) were diluted to 109 CFU·mL-1. The sterilized small square coating film was placed in the bacterial solution and cultured at 37 °C for 3 h. The coating film was taken out, slowly rinsed with PBS on the surface, placed in a PBS solution and ultrasonically vibrated. 100 μL of the vibrated liquid was spread on a solid culture dish and cultured at 37 °C for 24 h. The colonies on the culture dish were observed, and the coating film without adding antibacterial agent was used as a blank control. The test results are as Figure 9 shown. When NIT:TPC9 = 3:1 (wt%), the antibacterial effect of the series of coating films is the best. When the total added mass is 6 wt%, the antibacterial rate against S. aureus reaches 99.9%, and the antibacterial rate against E. coli reaches 96.8%. It shows that the prepared coating film has high-efficiency and broad-spectrum antibacterial properties.

[0080] Taking E. coli as an example, the coating film was subjected to BacLightTM bacterial cell viability test. The bacterial solution was diluted to 109 CFU·mL-1. The sterilized small square coating film was placed in the bacterial solution and cultured at 37 °C for 3 h. The coating film was taken out, and the surface was slowly rinsed with PBS. The coating film was stained with PI and SYTO-9 under light avoidance and cultured at 37 °C for 15 min, and then rinsed with PBS, and the fluorescence state of the bacteria was observed with a confocal microscope. The test results are as Figure 10 shown. When the total added mass is 6 wt%, almost all the figures observed under the microscope are red, indicating that the antibacterial performance of the coating is excellent.

[0081] The above are only the preferred embodiments of the present invention, and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. An antibacterial polyurethane acrylate film material embedded with N-substituted benzisothiazolinone and alkenyl-functionalized quaternary phosphonium salts, characterized in that, An antibacterial polyurethane acrylate film material grafted with different proportions of benzisothiazolinone and quaternary phosphonium salt antibacterial units simultaneously. The benzisothiazolinone structural unit refers to N-substituted benzisothiazolinone, and the quaternary phosphonium salt antibacterial unit refers to tris(4-methoxyphenyl)(non-8-en-1-yl)phosphonium bromide, which is grafted onto the polyurethane acrylate main chain through carbon-carbon double bond free radical polymerization to obtain an antibacterial polyurethane acrylate film material; The structural formula of the polymer is as follows: Formula (1): Where R1: Among them, the value range of M is 1 - 100; is the main structure of the triol except for H.

2. An antibacterial polyurethane acrylate film material incorporating N-substituted benzisothiazolinone and alkenyl-functionalized quaternary phosphonium salt according to claim 1, characterized in that, The polymer is composed of group R1 and blocks A, B, C, D, and E. The three-branch structure end of R1 is a double bond. The structures of R1 and blocks A, B, C, D, and E are as follows, where blocks D and E are grafted with benzisothiazolinone and quaternary phosphonium salt structural units respectively; Where R1: Block A: Block B: Block C: Block D: Block E:

3. An antibacterial polyurethane acrylate film material incorporating N-substituted benzisothiazolinone and alkenyl-functionalized quaternary phosphonium salts according to claim 2, characterized in that, The polymers corresponding to blocks A, B, C, D, and E are a, b, c, d, and e respectively, which can be adjusted according to the required degree of polymerization, and the value range is 2 to 50 or 25 to 45.

4. A method for preparing a polymer according to any one of claims 1, 2 or 3, characterized in that It includes the following steps: (1) Prepare the polymer corresponding to R1; (2) Prepare the benzisothiazolinone derivative with the structure shown by monomer D corresponding to block D; (3) Prepare the quaternary phosphonium salt with the structure shown by monomer E corresponding to block E; (4) Add the R1 polymer, monomer D, monomer E, and the reactive diluent monomer A corresponding to block A, the reactive diluent monomer B corresponding to block B, and the reactive diluent monomer C corresponding to block C, and add a photoinitiator and mix to obtain a polyurethane acrylate prepolymer; Among them, monomer A: Among them, monomer B: Among them, monomer C: Among them, monomer D: Among them, monomer E: (5) The polyurethane acrylate prepolymer prepared in step (4) is cured by ultraviolet light to form a coating with antibacterial properties corresponding to formula (1).

5. The preparation method of a polymer according to claim 4, characterized in that, The mass ratio range between the polyurethane polymer R1, the reactive diluent monomers (A + B + C), and the antibacterial small molecules (D + E) is 5:4.98:0.02 to 5:4.94:0.06; the sum of the masses of the reactive diluent monomers (A + B + C) and the antibacterial small molecules (D + E) is equal to the polyurethane polymer R1; among them, the mass ratio of the reactive diluent monomers A, B, and C is 5:3:1.7 to 5:3:2; the mass ratio of the antibacterial small molecule benzisothiazolinone derivative and tris(4-methoxyphenyl(non-8-en-1-yl)phosphonium bromide) is 1:1, 1:2, 1:3, 2:3, 2:1, 3:1, 3:

2.

6. Application of the polymer according to claim 1 or 2 or 3 directly as an antibacterial film or antibacterial coating.

7. Use of the polymer antibacterial film or antibacterial coating according to claim 6, characterized in that, For preparing an antibacterial film or antibacterial coating with bactericidal properties against Gram-positive bacteria and Gram-negative bacteria.

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