Light-Induced Production of Reactive Oxygen Species by a Novel

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Research Article Cite This: ACS Appl. Mater. Interfaces 2019, 11, 26500−26506

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Light-Induced Production of Reactive Oxygen Species by a Novel Water-Soluble Benzophenone Derivative Containing Quaternary Ammonium Groups and Its Assembly on the Protein Fiber Surface Liu Hu,†,‡ Aiqin Hou,‡ Kongliang Xie,† and Aiqin Gao*,† †

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Key Lab of Science & Technology of Eco-textile, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology and ‡National Engineering Research Center for Dyeing and Finishing of Textiles, Donghua University, Shanghai 201620, P. R. China ABSTRACT: Developing an efficient antimicrobial surface has important significance in the field of advanced biomaterials. A novel water-soluble benzophenone tetracarboxylamine derivative containing two quaternary ammonium groups, 3,3′-[4,4′-carbonyl-diphthalimide-]-bis(N-benzyl-N,Ndimethyl-N-propyl-1-aminium)dichloride (BPTCA-N), as a photoactive antibacterial agent was designed and synthesized. The ability of BPTCA-N to generate reactive oxygen species (ROS) in solution was investigated by light-induced activity. Its antibacterial activity in a dark environment or UV exposure was tested on Staphylococcus aureus and Escherichia coli. The influences of different solvents and the pH values on the ability of BPTCAN to generate ROS were also discussed. BPTCA-N possessed high photoactivity and efficient ROS generation ability. The generation of hydroxyl radicals could be greatly affected by addition of other solvents and H+ or OH−. For the BPTCA-N solution at a concentration of 0.2 mmol/L, the reduction of S. aureus and E. coli could all reach 99.99%. The BPTCA-N compound was assembled onto wool protein fibers. The modified protein fabrics also showed excellent photoactivity and antibacterial property against S. aureus and E. coli. For the wool fabric modified with 30 g/L of BPTCA-N, the reduction of S. aureus could reach 99.91% and that of E. coli was 91.23%. BPTCA-N had the synergistic antibacterial effect of quaternary ammonium salt and benzophenones. It has potential application in the biomedical field as highly effective antimicrobial agent or antimicrobial biomaterial. KEYWORDS: benzophenone, quaternary ammonium salt, reactive oxygen species, antibacterial, protein surface

1. INTRODUCTION

Some advanced materials, such as noble-metal nanoparticles, inorganic quantum dots, and organic compounds, could generate ROS.14−16 Photoactive organic compounds, such as benzophenone, anthraquinone, and phthalocyanine derivatives, could effectively generate reactive oxygen species after absorbing ultraviolet light or visible light.17−19 These photoinduced ROS could provide strong and effective oxidative functions, and much attention has been paid to these functions induced by these photoactivated compounds in recent years.20−22 They have been employed in different applications including inactivating microorganisms, photodynamic therapy, and deoxidizing toxic compounds. Benzophenone and its derivatives have excellent photoactivity. 3,3′,4,4′-Benzophenone tetracarboxylic acid (BPTCA), a kind of benzophenone derivative, has been applied to offer excellent UV light-induced antimicrobial materials.23−26 Organic quaternary ammonium salt compounds, such as dodecyl dimethyl benzyl ammonium chloride (DDBAC), are widely used as antimicrobials in the clinic and used as

The resistance to microbials (bacterial, fungus, and viral) has become a global concern in the medical treatment. Reducing the usage of antibiotics in medicine is an effective way to solve this problem.1−3 So, developing new antimicrobials is very important. In recent years, few novel antimicrobials are being developed in advanced biomaterial field in vitro.4,5 One of the new ways to achieve clinical application is to use reactive oxygen species (ROS), which are derived from optically active compounds. ROS are highly reactive molecules containing oxygen atoms with short lifetime.6,7 They are produced during many chemical and biological processes. ROS include singlet oxygen (1O2), hydroxyl radical (•OH), hydroperoxyl radical (HOO•), superoxide radical (O2•−), and hydrogen peroxide (H2O2). ROS have effective antimicrobial property against viruses, bacteria, and fungi.8−10 They are directly antimicrobial and have rapid activity against all kinds of Gram-positive and Gram-negative bacteria, also containing multidrug-resistant strains. So, ROS play important roles in the prevention of infection, making them very applicable for chronic inflammatory conditions, such as chronic wounds, chronic bronchitis, and so on.4,5,11−13 © 2019 American Chemical Society

Received: May 7, 2019 Accepted: June 26, 2019 Published: June 26, 2019 26500

DOI: 10.1021/acsami.9b07992 ACS Appl. Mater. Interfaces 2019, 11, 26500−26506

Research Article

ACS Applied Materials & Interfaces antimicrobial finishing agents in protein fiber or nylon fiber.27−29 They can inactivate microorganisms by disturbing their cytoplasmic membrane. To develop new antibacterial materials with high efficiency and synergism, a novel watersoluble benzophenone tetracarboxylamine derivative, 3,3′[4,4′-carbonyl-diphthalimide-]-bis(N-benzyl-N,N-dimethyl-Npropyl-1-aminium)dichloride (BPTCA-N), was designed, containing two active groups, a photoactive benzophenone group, and quaternary ammonium salt groups. The formation of hydroxyl radical and singlet oxygen of the compound is analyzed. Its antibacterial activities were investigated. BPTCAN was assembled onto protein fibers by electrostatic attraction. The photoactivity and antibacterial property against Staphylococcus aureus and Escherichia coli of the assembled protein fabrics were also studied.

[(Dimethylamino)propyl]-4,4′-carbonyldiphthalimide was obtained (white solid, 3.45 g, yield 90%) with mp of 156−158 °C; FT-IR v (cm−1): 2962.2, 2937.4 and 2857.8 (−CH2 and −CH3), 1707.0 (C− CO), 1657.16 (N−CO); 1H NMR δ ppm (DMSO-d6): 8.18 (d, Ar−H, 2H), 8.16 (d, Ar−H, 2H), 8.07 (s, Ar−H, 2H), 3.65 (t, −N− CH2−, 4H), 2.27 (t, −N−CH2−, 4H), 2.11 (s, −CH3, 12H), 1.74 (m, −CH2−, 4H). 13C NMR δ ppm (CDCl3): 193.08 (1C, CO), 167.15 (2C, OC−N), 167.13 (2C, N−CO), 141.46 (2C, C of Ar), 135.48 (2C, C of Ar), 135.35 (2C, C of Ar), 132.56 (2C, C of Ar), 124.14 (2C, C of Ar), 123.66 (2C, C of Ar), 56.94 (2C, CH2− N), 45.35 (4C, −CH3), 36.78 (2C, −CH2−N), 26.43 (2C, −CH2−). Benzyl chloride (1.30 g, 10 mmol) was added to 30 mL of the acetone solution of N,N-bis[(dimethylamino)propyl]-4,4′-carbonyldiphthalimide (2.00 g, 5 mmol). The mixture was reacted at 50 °C for 7 h. After that, the formed precipitate was collected by filtration, washed with acetone, and vacuum-dried. A white solid was obtained (3.08 g, yield 94%) with mp of 226−228 °C; FT-IR v (cm−1): 3054.8 (CH), 2970.6, 2951.5, and 2839.9 (−CH2 and −CH3), 1708.2 (C−CO), 1658.5 (N−CO); 1H NMR δ ppm (DMSO-d6): 8.21 (d, Ar−H, 2H), 8.14 (d, Ar−H, 2H), 8.08 (s, Ar− H, 2H), 7.55−7.46 (m, Ar−H, 10H), 4.54 (s, −N+−CH2−, 4H), 3.72 (t, −N−CH2−, 4H), 3.40 (t, −N+−CH2−, 4H), 2.96 (s, −CH3, 12H), 2.25−2.11 (m, −CH2, 4H). 13C NMR δ ppm (D2O): 194.70 (1C, CO), 168.54 (2C, OC−N), 168.41 (2C, N−CO), 141.09 (2C, C of Ar), 136.57 (2C, C of Ar), 134.69 (2C, C of Ar), 132.66 (4C, C of Ar), 131.44 (2C, C of Ar), 130.73 (2C, C of Ar), 129.07 (4C, C of Ar), 126.94 (2C, C of Ar), 124.16 (2C, C of Ar), 123.91 (2C, C of Ar), 67.98 (2C, CH2−Ar), 60.67 (2C, CH2−N), 50.11(4C, N−CH3), 34.97(2C, N−CH2), 21.76 (2C, −CH2−). 2.3. Assembly of BPTCA-N on the Wool Protein Fiber. The synthesized BPTCA-N was dissolved in deionized water with the pH value 9.5 in a certain concentration (1, 5, 10, 20, and 30 g/L). The wool fabrics were impregnated respectively in the BPTCA-N solutions at a liquor ratio of 1:10 and oscillated at 90 °C for 40 min in a XDS motor dyeing machine (L-12/24C, XDS Motor Co, China). At last, the assembled wool fabrics were rinsed under deionized water and then dried at room temperature. The sample treated without BPTCAN served as a control sample. 2.4. Detection of Hydroxyl Radicals. The •OH generation by the BPTCA and BPTCA-N solutions (0, 1, 5, 10, 15, and 25 mmol/ L) in the phosphate buffer solution (PBS) (0.01 M, pH 7.4) was detected by a photometric method.30 p-NDA served as the •OH scavenger, whereas the formation of other ROS was considered to be ineffective during the p-NDA bleaching process. Although p-NDA undergoes absorption under UVA irradiation (365 nm), the literature31 has reported that it does not generate any ROS. The contents of hydroxyl radicals were calculated using eqs 1 and 2.

2. EXPERIMENTAL METHOD 2.1. Materials and Instruments. 3,3′,4,4′-Benzophenone tetracarboxylic dianhydride (BPTCD) and p-nitrosodimethylaniline (p-NDA) were obtained from Sun Chemical Technology Co., Ltd. (Shanghai, China). N,N-Dimethyl-1,3-propanediamine, benzyl chloride, and other chemicals were obtained from Sinopharm Chemical Reagent Co., Ltd. (Shanghai, China). All of these chemicals were used with no further purification. Wool fabric was obtained from Shandong Ruyi Woolen Garment Group Co., Ltd. (Jining, China). UV−visible absorption spectra were recorded with a U-3310 spectrophotometer (Hitachi Co., Ltd, Japan). Fourier transform infrared (FT-IR) spectra were recorded on Perkin Elmer Spectrum Two (Perkin Elmer Co., Ltd). 1H NMR spectra were recorded by Bruker Avance 400 (Bruker Co., Ltd, Switzerland) using DMSO-d6 as a solvent. 13C NMR spectra were recorded with Bruker Avance 600 (Bruker Co., Ltd, Switzerland) using D2O and CDCl3 as solvents. 2.2. Synthesis of BPTCA-N. The synthesis of 3,3′-[4,4′-carbonyldiphthalimide-]-bis(N-benzyl-N,N-dimethyl-N-propyl-1-aminium)dichloride was carried out, and the reaction process is shown in Scheme 1. Nine millimolar of BPTCD and 19 mmol of N,N-dimethyl-1,3propanediamine were added to 30 mL of acetic acid. The mixture was stirred and refluxed for 6 h. Then, the product was concentrated under reduced pressure. The crude product was purified by methanol recrystallization. The precipitate was dried under vacuum. N,N-

Scheme 1. Synthesis Route of BPTCA-N

ΔC = C0 − Ct

(1)

bleaching rate of p‐NDA = ΔC / C0

(2)

where C0 is the p-NDA concentration before UV exposure and Ct is the p-NDA concentration after the exposure. The generation of hydroxyl radicals of the assembled fabrics was determined according to the method we have reported before.32 The influence of acidic or alkaline medium (pH value: 4.8, 7.4, and 8.9) on the •OH production of BPTCA-N (1.0 mmol/L) was analyzed. For the preparation of solutions with different pH values, first, Na2HPO4·12H2O (71.6 g) was dissolved in 1000 mL of water to prepare 0.2 M Na2HPO4 solution and NaH2PO4·2H2O (31.2 g) was dissolved in 1000 mL of water to prepare 0.2 M NaH2PO4 solution. Eighty-one milliliters of the Na2HPO4 solution and 19 mL of the NaH2PO4 solution were mixed to prepare 0.2 M PBS with the pH value of 7.4. A 0.01 M PBS with a pH value of 7.4 was obtained by diluting 0.2 M PBS for 20 times. HCl (0.1 M) or NaOH (0.1 M) was used to adjust the PBS (pH = 7.4) to obtain the PBS of pH 4.9 or 8.9, respectively. 2.5. Antibacterial Activities. The antibacterial activities of the agents in solution were measured by a minimum inhibitory 26501

DOI: 10.1021/acsami.9b07992 ACS Appl. Mater. Interfaces 2019, 11, 26500−26506

Research Article

ACS Applied Materials & Interfaces

generate •OH was determined by the bleaching rate of p-NDA. The bleaching rates of p-NDA under different concentrations (0, 1, 5, 10, 15, and 25 mmol/L) of BPTCA or BPTCA-N solution are shown in Figure 2. With increasing concentration of BPTCA or BPTCA-N, the bleaching rate of p-NDA increased. Compared with that of the BPTCA solution, the bleaching rate of BPTCA-N was obviously higher. BPTCA-N exhibited excellent light activity for the generation of ROS. As mentioned in the literature,33 1O2 could react with Lhistidine to form an intermediate that can oxidize p-NDA. Thus, the photobleaching rates of p-NDA with the addition of L-histidine could be used to confirm the photoinduced generation of 1O2. Figure 3a,b shows the bleaching rates of p-NDA with different exposure times upon the addition of 0 or 1.0 mmol/L L-histidine to the system (1.0 mmol/L BPTCA or BPTCA-N). It can be observed that the bleaching rate of pNDA in the system with L-histidine was far higher than that of the system without L-histidine, and there was a consistent growth of bleaching rate as time extended to 90 min. This result demonstrated the formation of 1O2 through the photoexcitation process. A comparison of panels a and b of Figure 3 shows that BPTCA-N exhibits better photoactivity. Excellent generation of hydroxyl radicals in BPTCA-N is attributed to its chemical structure. Comparing the structure of BPTCA and BPTCA-N, we observe that the latter has a larger conjugate system, which is beneficial to the stability of lightinduced free radicals. The generation of ROS in BPTCA-N could be explained by the mechanism shown in Scheme 2. The photosensitive benzophenone derivative can be excited to the singlet state and then move to its triplet state through intersystem crossing (ISC) under ultraviolet light. The triplet state intermediate could be quenched by oxygen and 1O2 was produced, or a hydrogen atom could be abstracted from another molecule to form the radical of the benzophenone derivatives. With continuous exposure to light, a series of ROS could be produced through several reactions between the benzophenone radical and oxygen. 3.2. Production of ROS in BPTCA-N Solution. An interesting phenomenon was observed in the study of the formation process of ROS. The formation of ROS was affected by addition of other solvents or the pH value of the system. The effect of different compounds, isopropanol and DMSO, on the generation of hydroxyl radicals in BPTCA-N was further discussed in detail. The amounts of hydroxyl radicals generated in an aqueous solution containing isopropanol or DMSO were measured, and the results are shown in Figure 4a. The bleaching rate of p-NDA could be obviously increased with the addition of isopropanol (10 vol %) and reach 100% after 90 min, which was far higher than that of BPTCA-N only in the water solution. Isopropanol may act as a hydrogen donor in this system. 34 BPTCA-N may extract hydrogen from isopropanol to form more BPTCA-N radicals, and the formed BPTCA-N radicals could react with oxygen to form ROS. With DMSO (10 vol %), the bleaching of p-NDA was not obviously affected during the first 20 min. However, there was a significant growth in the bleaching rate after 30−60 min of irradiation. This may be attributed to the formation of excited triplet benzophenone derivatives during the reaction of benzophenone derivatives and DMSO, which is beneficial to the generation of ROS.35 It can also be obtained from Figure 4a that the production of hydroxyl radicals tended to be stable after illumination for 60 min. Further, the amount of •OH

concentration (MIC) according to the AATCC 100 standard.33 One milliliters of 105−106 colony-forming units (CFU)/mL of S. aureus (ATCC-6538) or E. coli (ATCC-8099) suspension was added into 9 mL of phosphate-buffered saline (PBS) with different concentrations of BPTCA or BPTCA-N, respectively. After 60 min of exposure to UV light or dark, 0.1 mL of the resultant solution was diluted by sterilized deionized water to 10, 102, 103, and 104 CFU/mL in series and incubated on an agar plate for 18 h for S. aureus and 10 h for E. coli at 37 °C. The same testing procedure was used for the PBS solution with no BPTCA or BPTCA-N (control sample). The bacterial reduction rate was calculated according to eq 3 on the basis of the numbers of colony-forming units

reduction of bacteria (%) = (B − A)/ B × 100

(3)

where B and A are the number of colony-forming units of control (without agents) and the samples, respectively. The light-induced antibacterial activities of the assembled wool samples against S. aureus or E. coli were evaluated according to the testing method we have reported before.32

3. RESULTS AND DISCUSSION 3.1. Photoactivity of BPTCA-N and Its Production of ROS. In general, derivatives of diphenylketone have strong

Figure 1. UV−vis absorption spectrum of BPTCA-N (1.0 mmol/L in deionized water).

Figure 2. Generation of hydroxyl radicals in BPTCA and BPTCA-N in different concentrations (UV exposure time: 60 min).

ultraviolet absorption in the UV range. The UV−vis spectrum of the BPTCA-N aqueous solution is given in Figure 1. This indicates that BPTCA-N has a strong absorption in the UV region. BPTCA-N was synthesized by BPTCD. BPTCD was dissolved in water at 70−80 °C under agitation to completely hydrolyze to BPTCA. BPTCA is also a good water-soluble photoactive compound. In this paper, the photoactivity of BPTCA-N was compared with that of BPTCA. Their ability to 26502

DOI: 10.1021/acsami.9b07992 ACS Appl. Mater. Interfaces 2019, 11, 26500−26506

Research Article

ACS Applied Materials & Interfaces

Figure 3. Generation of •OH and 1O2 by (a) 1.0 mM BPTCA and (b) 1.0 mM BPTCA-N.

Scheme 2. Mechanism Responsible for the Photoactivity of Benzophenone Derivatives

The influence of acidic or alkaline medium (pH value 4.8, 7.4, and 8.9) on the production of hydroxyl radicals in BPTCA-N (1.0 mmol/L) was studied and is shown in Figure 5a. With the UV exposure time increasing from 0 to 90 min, the amount of •OH generated obviously increases during the first 20 min, as shown in Figure 5a. The amount of hydroxyl radicals produced in the acid or alkaline system was more than that produced in the neutral condition in the same exposure time. It indicates that the presence of H+ or OH− could promote the formation of hydroxyl radicals. H+ or OH− may

generated by different concentrations of BPTCA-N (0, 1, 5, 10, 15, and 25 mmol/L) exposed in UV light for 60 min in the different solutions were measured, and the results are shown in Figure 4b. With increasing concentration of BPTCA-N, the contents of produced •OH increased. The addition of isopropanol sharply increased the photobleaching rate; all pNDA could be oxidized by the formed •OH when the BPTCAN concentration reached 5 mmol/L. The production of hydroxyl radicals could also be obviously promoted by DMSO with the concentration of BPTCA-N. 26503

DOI: 10.1021/acsami.9b07992 ACS Appl. Mater. Interfaces 2019, 11, 26500−26506

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ACS Applied Materials & Interfaces

Figure 4. Effects of different organic compounds on the production of hydroxyl radical in BPTCA-N: (a) exposure time effect (BPTCA-N concentration: 1.0 mmol/L) and (b) concentration effect.

Figure 5. Effects of pH value on the production of hydroxyl radical in BPTCA-N: (a) exposure time effect (BPTCA-N concentration: 1.0 mmol/L) and (b) concentration effect (exposure time: 60 min).

Figure 6. Reduction of bacteria in BPTCA-N and BPTCA solution of different concentrations: (a) S. aureus and (b) E. coli.

Scheme 3. Assembly of BPTCA-N on the Wool Protein Surface

Figure 7. Generation of hydroxyl radicals of the assembled wool fibers with different concentrations of BPTCA-N.

lead to the formation of benzophenone radical. Figure 5b shows the amounts of hydroxyl radicals generated by different concentrations of the BPTCA-N solution (0, 1, 5, 10, 15, and 25 mmol/L) in UVA light for 60 min. It also demonstrates that more hydroxyl radicals were produced at any BPTCA-N concentration in acid or alkaline system. The photoactivity of

BPTCA-N was greatly enhanced by the hydrogen donor, H+, and OH−. As discussed above, BPTCA-N had better photoactivity than BPTCA. Varied light-induced activities 26504

DOI: 10.1021/acsami.9b07992 ACS Appl. Mater. Interfaces 2019, 11, 26500−26506

Research Article

ACS Applied Materials & Interfaces Table 1. Light-Induced Antibacterial Activity of the Assembled Wool Fabric BPTCA-N (g/L) reduction rate of bacteria (%)

S. aureus E. coli

0

1

5

10

20

30

20.12 11.28

34.68 29.28

54.21 44.31

60.16 57.23

88.57 73.45

99.91 91.23

could lead to different antibacterial activities. Human body is prone to sweating, which is conducive to the growth of bacteria. Sweat is usually acidic or alkaline (for diabetics); thus, this novel antimicrobial is appropriate to be applied in antibacterial textiles. 3.3. Antibacterial Activity of BPTCA-N in Water Solution. The antibacterial properties (S. aureus and E. coli) of the BPTCA-N and BPTCA solutions in dark condition or UVA exposure were measured by a minimum inhibitory concentration (MIC) according to the AATCC 100 standard. Figure 6 shows the light-induced antibacterial properties of BPTCA-N and BPTCA at different concentrations. The results showed that both BPTCA and BPTCA-N had light-induced antibacterial activities. The reduction of both types of bacteria increased with the increasing concentrations of BPTCA-N and BPTCA. BPTCA-N offered better antibacterial performance than BPTCA. When the BPTCA-N concentration was only 0.2 mmol/L, the reduction of bacteria count could reach 99.99% for both S. aureus and E. coli under UV exposure. The reduction of S. aureus and E. coli at the BPTCA concentration of 0.2 mmol/L under UV exposure reached 67.01 and 72.77%, respectively. So, BPTCA-N exhibited efficient antibacterial activity. Meantime, BPTCA-N also exhibited higher antibacterial activity in dark condition, and the reduction of bacteria for S. aureus and E. coli at BPTCA-N 0.2 mmol/L reached 60.23 and 72.52%, respectively. Under the same condition, the reduction of bacteria for S. aureus and E. coli for BPTCA was only 29.36 and 20.68%, respectively. Two active groups in the chemical molecule, quaternary ammonium group and benzophenone group, had effective synergistic antibacterial properties. Quaternary ammonium salt with a positive charge could be adsorbed onto the bacterial cell wall due to its negative charge, and the lipid side chain of the quaternary ammonium salt can be inserted into the bacterial cell membrane, which results in the destruction of the membrane and the death of the bacteria. Large amounts of reactive oxygen species produced with light exposure have strong oxidation to protein of bacteria. Thus, BPTCA-N has efficient antibacterial activity than that of BPTCA. 3.4. Generation of Hydroxyl Radicals and Antibacterial Activities of Assembled Protein Fibers with BPTCAN. An increase in infectious diseases caused by bacteria has become a major health problem in recent decade. Efficient antimicrobials are assembled on suitable fiber surfaces to obtain biomaterials for use in antimicrobial gauze, absorbable sewing threads, or tissue engineering materials. Wool protein fibers are composed of amino acids, which contain amino and carboxylic groups. Under alkaline condition, the protein fiber surface possesses a lot of carboxylate anionic groups. The molecule of BPTCA-N has positive charges, which can be assembled onto the wool protein surface. Scheme 3 shows the assembly process of BPTCA-N on the wool protein surface. The wool fabrics were assembled with BPTCA-N under different concentrations (0, 1, 5, 10, 20, 30 g/L). The amount of BPTCA-N on wool fibers increased with the increasing concentration of BPTCA-N. The production of hydroxyl

radicals in modified wool fabrics with different concentrations of BPTCA-N after 60 min of UV exposure was measured (shown in Figure 7). This indicates that the production of • OH increased with the increasing BPTCA-N concentration. This result demonstrates that the modified protein surface with BPTCA-N possessed the photoinduced activities and could generate ROS. The antibacterial activities induced by UV light of the assembled wool fabrics were evaluated against S. aureus and E. coli as listed in Table 1. Wool fabric itself (control sample) had certain antibacterial performance. All assembled samples with BPTCA-N had photoinduced antibacterial properties. When the wool sample was assembled with 30 g/L BPTCA-N solution, the reduction rate of S. aureus could reach 99.91% and that of E. coli was 91.23%. The wool protein surface assembled with BPTCA-N had excellent antibacterial activities. Because of the biocompatibility of protein fiber, it has potential application as highly effective antimicrobial biomaterials, such as hemostatic gauze, surgical sewing thread, and other biomaterials.

4. CONCLUSIONS A novel water-soluble antibacterial, BPTCA-N, was designed and synthesized, which contained a benzophenone group and two quaternary ammonium groups. The BPTCA-N exhibited good optical activity and excellent ability for the generation of ROS. The formation of ROS was obviously affected by addition of isopropanol, DMSO, and pH values of the system. BPTCA-N had efficient antibacterial activity. When the BPTCA-N concentration was only 0.2 mmol/L, the reduction of both S. aureus and E. coli could reach 99.99% under UV exposure. The quaternary ammonium groups and benzophenone group in the molecule had effective synergistic antibacterial property. BPTCA-N could be applied to assemble wool protein surface. The assembled protein fabrics also showed excellent photoactivity and antibacterial activity against S. aureus and E. coli, the reduction of which could reach 99.91 and 91.23%, respectively. BPTCA-N and its assembled materials have potential applications in the biomedical field or antimicrobial biomaterials.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Phone: +86 21 6779 2271. ORCID

Aiqin Hou: 0000-0002-5311-2431 Kongliang Xie: 0000-0002-4676-3762 Aiqin Gao: 0000-0001-8470-7895 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the Natural Science Foundation of Shanghai (No. 18ZR1400800), the Fundamental Research Funds for the Central Universities and Graduate Student Innovation Fund of Donghua University (CUSF-DH-D26505

DOI: 10.1021/acsami.9b07992 ACS Appl. Mater. Interfaces 2019, 11, 26500−26506

Research Article

ACS Applied Materials & Interfaces

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2019063), and China Postdoctoral Science Foundation (2019M651327).

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DOI: 10.1021/acsami.9b07992 ACS Appl. Mater. Interfaces 2019, 11, 26500−26506