Synthesis and Antifungal Activities of Amphiphilic PDMS-b

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Synthesis and antifungal activities of amphiphilic PDMSb-QPDMAEMA copolymers on Rhizoctonia solani Yaling Lin, Weiqiang Zhong, Chenyun Dong, Chang Zhang, Xixiang Feng, and Anqiang Zhang ACS Appl. Bio Mater., Just Accepted Manuscript • DOI: 10.1021/acsabm.8b00545 • Publication Date (Web): 16 Nov 2018 Downloaded from http://pubs.acs.org on November 19, 2018

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Antifungal mechanism of PDMS-b-QPDMAEMA against R. solani sclerotia 216x194mm (300 x 300 DPI)

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Synthesis and antifungal activities of amphiphilic PDMS-b-QPDMAEMA copolymers on Rhizoctonia solani Yaling Lin a, *, Weiqiang Zhong b, Chenyun Dong a, Chang Zhang b, Xixiang Feng b, Anqiang Zhang b, * a. College of Materials and Energy, South China Agricultural University, 483 Wushan Rd., Guangzhou 510642, Guangdong, China

b. School of Materials Science and Engineering, South China University of Technology, 381 Wushan Rd., Guangzhou 510641, Guangdong, China * Corresponding authors: Y. Lin, Email: [email protected]; A. Zhang, Email: [email protected] KEYWORDS: PDMS-b-QPDMAEMA copolymers, hydrophobic-hydrophilic balance, adsorption, permeation, R. solani sclerotia ABSTRACT Cationic polymers are prospective fungicidal agents for inhibiting plant diseases because of the controllability of their structure and properties. This study investigates the effect of the hydrophobic-hydrophilic balance on the antifungal activities of antimicrobial polymers against phytopathogenic fungi (Rhizoctonia solani Kühn AG-1(IA)),

the

pathogen

of

rice

sheath

blight

1


(RShB).

A

series

of

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polydimethylsiloxane-polymethacrylate block copolymers containing quaternary ammonium salts (PDMS-b-QPDMAEMA, labeled as SnQm, n and m represent one thousandth of the molecular weight of PDMS and QPDMAEMA chain respectively.) were synthesized via anionic ring-opening polymerization and atom transfer radical polymerization (ATRP). The abilities of the quaternary ammonium salts to adsorb onto the surface of R. solani sclerotia and permeate the R. solani sclerotia were investigated based on static water contact angles and fluorescence labeling. The results indicated that the moderately hydrophobic PDMS chain helped stabilize the attachment of the hydrophilic QPDMAEMA chain and then help it penetrate the R.

solani sclerotia. Its antifungal properties toward R. solani were characterized by determining its minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) and the inhibition rate of R. solani sclerotia germination. The hydrophobic PDMS chains had a significant influence on the antifungal activities of amphiphilic SnQm against R. solani sclerotia. This work highlights the prospective application of amphiphilic antimicrobial polymers as antifungal agents for inhibiting plant diseases.

2



Page 4 of 38

1. INTRODUCTION Fungal disease is the main risk to the agricultural development throughout the world, and the loss caused by fungal disease each year is substantial. Rice sheath blight (Rhizoctonia solani) is a devastating disease in intense and high-input rice production systems, which account for most of the global consumption of rice fungicide.1 R. solani can grow into sclerotia when the environmental are unfavourable for their survival. R. solani sclerotia have a well-defined layer of living cells in the center surrounded by an outer layer of empty cells.2 The living cells in the center can grow outward again to form mycelium and infect the host when the environment is suitable for their development. There are studies that shown extreme temperature and humidity cannot completely inhibited the germination of sclerotia, and 27.5 percent of sclerotia still germinated over 11 years.3 However, most existing pesticides are small molecules, such as hydrophilic validamycin and hydrophobic thiophanate-methyl, and they are easily washed away, which makes them inefficient as antifungal agents. Therefore, existing pesticides lack the ability to permeate into the sclerotia and are used to kill the mycelium rather than the sclerotia. Although the

R. solani mycelium could be killed by spraying high levels of pesticides regularly, the R. solani can form sclerotia and germinate next year. Due to the complicated structure of sclerotia, the traditional pesticides cannot achieve the purpose of killing the R. solani completely. However, the fungi can develop resistance to the pesticides because of the heavy use of pesticides. The components of fungi cell wall, which included chitin, glucans and so on, are more complicated than bacteria cell wall. 3


4, 5

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And they are more resistant to antifungal agents as compared to Gram-negative and Gram-positive bacteria due to the structural difference in their cell membranes.6 In order to properly solve the problem of drug resistance, alternative antifungal strategies and materials have attracted much of people's interest and attention. The use of the photodynamic therapy (PDT) silver nanoparticles

14

6-8,

cationic polymers

9-12,

zinc oxide

13

and

for fungal infection therapy are promising approach and

materials. Cationic polymers possess potent broad-spectrum antimicrobial activity by interact with the microbial membrane 15-18 and do not elicit antimicrobial resistance. 9, 19

Therefore, cationic polymers are potential fungicidal agents for controlling plant

diseases. Compared to R. solani mycelium, the structure of R. solani sclerotia is much more complicated. Only antifungal agents with the ability to penetrate the outer layer of sclerotia can kill the R. solani. However, most of the existing pesticides are hydrophilic small molecules that can easily run off in soil. Unlike traditional pesticides and cationic small molecules, amphiphilic cationic polymers have the necessary adsorption

ability,

permeation

ability

and

relatively

low

toxicity

to

the

environment.20-22 In

our

previous

methacrylamide)

studies,

containing

a

series

quaternary

of

poly(N,N-dimethylamine

ammonium

salts

propyl

(QPDMAPMA),

QP(DMAPMA-co-BA) and QP(DMAPMA-co-EMA) were synthesized, and the antifungal activities toward R. solani mycelium were improved by adding hydrophobic acrylate monomers (BA or EMA).23 Then the backbone of quaternary ammonium salts were replaced with polysiloxane (PDMS) which was more hydrophobic and

4



benzyldimethylaminopropyl

chloride

grafted

polysiloxane

Page 6 of 38

(PDMS-g-BC)

were

synthesized, and the antifungal activities toward R. solani mycelium were further improved.

24

In addition, QPDMAEMA homopolymer which have hydrophobic

polymethacrylate backbone with different molecular weights were synthesized and the optimal antifungal activities toward R. solani mycelium were achieved when the molecular weights of QPDMAEMA was lower than 5 kDa.25 Additionally, we find that polymeric quaternary ammonium salts, including QPDMAPMA and PDMS-g-BC, showed a special mechanism for causing the lipid peroxidation of the R. solani mycelium cell membrane and this mechanism was not observed with small molecule quaternary ammonium salts, such as DDBAC.26,

27

However, most of the research focused on the antifungal

prosperities against R. solani mycelium, while the studies on antifungal agents against R. solani sclerotia were scarce. It is important to inhibit the germination of R. solani sclerotia which can interrupt the life cycle of R. solani and make it possible to control R. solani fundamentally. In this study, we synthesized a series of polydimethylsiloxane-polymethacrylate block copolymers containing quaternary ammonium salts (PDMS-b-QPDMAEMA, labeled as SnQm, n and m represent one thousandth of the molecular weight of PDMS and QPDMAEMA chain, respectively) via anionic ring-opening polymerization and atom transfer radical polymerization (ATRP). The hydrophilic quaternary ammonium salts chain of SnQm provides the antifungal activity, and the amphipathy allows adsorption and permeation. To explore the relationship between the antifungal activity against R. solani sclerotia and the hydrophobic-hydrophilic balance

5


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of amphiphilic polymeric quaternary ammonium salts, we systematically assessed the adsorption ability, permeation ability and inhibition effect to R. solani sclerotia germination using SnQm with various hydrophobic PDMS chain lengths. Additionally, a small molecule quaternary ammonium salt (DDBAC) and the hydrophilic poly quaternary ammonium salt QPDMAPMA for comparison, which highlighted the adsorption ability and the relatively low environmental toxicity of amphiphilic SnQm. In order to directly observe the distribution of quaternary ammonium salt in R. solani sclerotia, the fluorescein had been grafted onto S5Q5, QPDMAPMA and DDBAC.

2. EXPERIMENTAL SECTION 2.1 Sample Preparation 2.1.1 Materials Hexamethylcyclotrisiloxane (D3) was supplied by Xin-mingtai Chemicals Co., Ltd. (Wuhan, China). Dimethylvinylchlorosilane (97%), 2,2'-azobis(2-methylpropionitrile) (AIBN,

98%),

2-mercaptoethano

(99%),

2,2-dimethoxy-2-phenylacetophenone

(DMPA, 98%), ethyl 2-bromoisobutyrate (EtBriB, 98%), α-bromoisobutyryl bromide (BIBB, 98%), triethylamine (99%), 2-(dimethylamino)ethyl methacrylate (DMAEMA, 99%), N,N,N',N'',N''-pentamethyldiethylenetriamine (PMDETA, 98%) and copper(I) bromide (CuBr, 99%), N,N-dimethylamine propyl methacrylamide (DMAPMA, 99%), fluorescein (90%), chloroacetyl chloride (98%), N,N-dimethyldodecylamine (98%) and benzyldimethyldodecylammonium chloride (DDBAC, 99%) were purchased from Macklin (Shanghai, China). Benzyl chloride (BC, 99%) and n-butyl lithium (n-BuLi) 6



Page 8 of 38

were purchased from Aladdin (Shanghai, China). Agar was supplied by MYM Biological Technology Company (Shanghai, China). Kunming mice (weight range 18 22 g, provided by Southern Medical University, China) were used to evaluate the acute oral toxicity characteristics of the materials under study. All of the animal experiments were completed with the approval of the Animal Research Ethics Committee of the South China Agricultural University. During the study, all the mice had access to food and water ad libitum. 2.1.2 Characterization The characterizations were shown in the Supporting Information (Part S-1). 2.1.3 Synthesis of QPDMAEMA (S0Q5) QPDMAEMA (labeled as S0Q5) was synthesized via our previously published procedures (approximately 70% yield and 96% conversion),

25

as shown in Scheme

1, and the molecule weight of QPDMAEMA was designed as 5 kDa. 2.1.4 Synthesis of PDMS-b-QPDMAEMA (SnQm) The synthesis procedure for PDMS-b-QPDMAEMA (labeled as SnQm) block copolymers was shown in Scheme 1.

7


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Scheme 1. Synthesis route of QPDMAPMA, S0Q5 and SnQm.

PDMS-Vi was synthesized via anionicring-opening polymerization. The D3 was dissolved in THF in a 200 mL Schlenk flask. The reaction system was subjected to three freeze-pump-thaw cycles and filled with nitrogen. Then, n-BuLi was injected to the mixture, and the reaction mixture was stirred at 0 °C for 24 h and quenched by dimethylvinylchlorosilane. PDMS-OH

was

synthesized

via

thiol-ene

8


click

reaction.

PDMS-Vi,


2-mercaptoethano and DMPA were dissolved in THF solvent. The reaction mixture was exposed to 365 nm UV with stirring for 30 min. The resulting polymer was dissolved with methanol. PDMS-Br was synthesized via esterify reaction. The polymerization was carried out in a two-necked flask with a constant-pressure dropping funnel and a nitrogen outlet. PDMS-OH and triethylamine were dissolved in THF solvent and stirred in a 0 °C bath. BIBB was dissolved in THF solvent and dripping slowly. Then, the reaction mixture was stirred at 0 °C for 1 h followed by stirring at room temperature for 24 h under nitrogen. The resulting polymer was dissolved with methanol. PDMS-b-PDMAEMA was polymerized via our previously published procedures, and PDMS-Br is used as initiator to replace EtBriB (approximately 70% yield and 90% to 97% conversion).25 The products were named PDMS-n-b-PDMAEMA (n was one thousandth of the molecular weight of PDMS). SnQm was synthesized from PDMS-b-PDMAEMA and BC and refer to our previously published procedures (approximately 90% yield). 25 2.1.5 Synthesis of QPDMAPMA PDMAPMA was synthesized via radical polymerization. 10.0 g of DMAPMA (58.7 mmol) was dissolved in 25 g of methylbenzene solvent in a three-necked flask with a stirrer, a condense pipe and a constant-pressure dropping funnel. And then 0.2 g of AIBN (1.2 mmol) was added into the three-necked flask. The reaction mixture was stirred at 65 °C for 12 h under nitrogen. QPDMAPMA was synthesized from PDMAPMA and BC and refer to our previously 9


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published procedures. 25 2.1.6 Synthesis of fluorescence labels The synthesis procedure for S5Q5-FL, DDBAC-FL and QPDMAPMA-FL was shown in Scheme 2. FL-Cl was synthesized via esterify reaction. 0.7 g of fluorescein (2 mmol) was dissolved in 150 ml of acetone in the three-necked flask with a stirrer, a condense pipe and a nitrogen inlet. 0.2 g of chloroacetyl chloride (2 mmol) was dissolved in 30 ml of acetone and dripping slowly. Then, the reaction mixture was stirred at room temperature for 7 h under nitrogen. The solid product was obtained by filtration. S5Q5-FL

was

synthesized

via

quaternization

reaction.

1.13

g

of

PDMS-5-b-PDMAEMA and 0.12 g of FL-Cl were dissolved in 120 ml of ethyl alcohol in the three-necked flask with a stirrer, a condense pipe and a nitrogen inlet. Then, the reaction mixture was stirred at 70 °C for 24 h under a nitrogen atmosphere, after which 0.29 g of BC was added and the reaction was continued for 12 h. The products were precipitated and washed with diethyl ether three times. DDBAC-FL

was

synthesized

via

quaternization

reaction.

1.06

g

of

N,N-dimethyldodecylamine and 2.03 g of FL-Cl were dissolved in 120 ml of ethyl alcohol in the three-necked flask with a stirrer, a condense pipe and a nitrogen inlet. Then, the reaction mixture was stirred at 70 °C for 24 h under a nitrogen atmosphere. The products were precipitated and washed with diethyl ether three times.

10



Scheme 2. Synthetic route to S5Q5-FL, DDBAC-FL and QPDMAPMA-FL. QPDMAPMA-FL was synthesized via quaternization reaction. 1.43 g of PDMAPMA and 0.10 g of FL-Cl were dissolved in 120 ml of ethyl alcohol in the three-necked flask with a stirrer, a condense pipe and a nitrogen inlet. Then, the reaction mixture was stirred at 70 °C for 24 h under a nitrogen atmosphere, after which 1.03 g of BC was added and the reaction was continued for 12 h. The products were precipitated and washed with diethyl ether three times. 2.2 Adsorption tests. The capacities of SnQm, PDMAPMA and DDBAC to adsorb on

11


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the surface of R. solani sclerotia were tested using static water contact angles values. 1 g/L aqueous solutions of SnQm, PDMAPMA and DDBAC were prepared. The R.

solani sclerotia were immersed in the 1 g/L SnQm, PDMAPMA and DDBAC solutions for 1 h respectively. Then, the R. solani sclerotia were gently washed with ultrapure water and dried for 4 d at room temperature. The static water contact angles of R. solani sclerotia before and after immersing were measured, and all the experiments were repeated for five times. 2.3 Fluorescence labeling. The R. solani sclerotia were immersed in 10 g/L solutions of S5Q5-FL, DDBAC-FL and QPDMAPMA-FL at 8 °C for 7 d. The R. solani sclerotia and their cross sections were observed under a stereomicroscope using white light and 365 nm ultraviolet, respectively. 2.4 Determination of the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). The MIC and MFC were evaluated according to the literature.23, 24 2.5 Inhibition effect on sclerotia germination. The R. solani sclerotia were immersed in solutions of SnQm and DDBAC and QPDMAPMA at concentrations of 5 × MIC, 10 × MIC, 15 × MIC and 20 × MIC at 8 °C for 35 d. Forty R. solani sclerotia were randomly chosen every 7 d. Then, polymer solutions at concentrations of 50 × MIC, 100 × MIC, 150 × MIC and 200 × MIC were prepared, and the samples were dissolved in PD. The polymer solution (5 mL) and 45 mL of potato dextrose agar (PDA) were added into the 90 mm Petri dishes. Then, the R. solani sclerotia were

12



transferred to the Petri dishes and incubated at 28 °C for 24 h. The percentages of ungerminated R. solani sclerotia were analyzed. Then, the ungerminated R. solani sclerotia were cut into four pieces and transferred to another set of Petri dishes with polymer solutions at the same concentrations as before and incubated at 28 °C for 48 h. The number of R. solani sclerotia that were still ungerminated was analyzed. 2.6 Toxicity tests. The laboratory animals included insect (silkworm) and mammal (Kunming mice) models. The biotoxicity of DDBAC, QPDMAPMA and SnQm were evaluated based on their median lethal concentration (LC50) and median lethal dose (LD50) for silkworm and Kunming mice, according to GB/T 31270.11-2014 (for LC50) and GB/T 21826-2008 (for LD50), respectively. Deveined mulberry leaves (1.0 g) were immersed in 10 mL of quaternary ammonium salt solutions at five different concentrations for 10 s and then dried. Deionized water was added instead of the quaternary ammonium salts solutions as a control. Twenty silkworms were fed the mulberry leaves in Petri dishes (diameter of 90 mm) at each concentration. The number of deaths and poisoning symptoms in the silkworms were observed and recorded over 96 h. The experiment was repeated three times. The LC50 values were calculated using SPSS software. Five experimental mice, which were fasted for 4~6 h before the test, were fed doses of the drug of 5000 mg/kg by intragastric administration. The LD50 is higher than 5000 mg/kg if more than three experimental mice survive for more than 48 h. Otherwise, an up-down procedure (UDP) would be used to complete the test. The doses of the quaternary ammonium salts were 1.75 mg/kg, 5.5 mg/kg, 17.5 mg/kg, 13


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55 mg/kg, 175 mg/kg, 555 mg/kg, 2000 mg/kg and 5000 mg/kg. The first experimental mice were fed a dose of 2000 mg/kg. The next experimental mouse was fed a dose one level lower if the first experimental mice died in 48 h. The next experimental mouse was fed a dose one level higher if the previous experimental mice survived more than 48 h. In addition, the survival of the first experimental mice was monitored at 14 d. These steps were repeated until three experimental mice died at the same concentration. The LD50 values were calculated using AOT425 software.

3. RESULTS AND DISCUSSION 3.1 Design and synthesis of S0Q5, SnQm and QPDMAPMA. Since PDMS possess good hydrophobicity, thus PDMS chain segments were used as hydrophobic segment and synthetized via anionic ring-opening polymerization. DMAEMA with multiple functional groups could be polymerized and then quaternized with halohydrocarbons to prepare antibacterial materials.28 And compare with short linear haloalkanes, when halogenated reagents were benzyl chloride, the antifungal activities of cationic polymers were better according to our previous studies.23 The antimicrobial activity of cationic polymers is associated with various factors, such as the nature of the charge, the hydrophobic groups, the balance of cationic to hydrophobic moieties, and the polymer composition and length.29-33 And the antimicrobial activity of cationic amphiphilic polymers is provided by both the hydrophilic cationic and hydrophobic moieties.

34-36

As hydrophobic moieties, benzyl

14



Page 16 of 38

can well interact with the inner hydrophobic core of the fungi membrane leading to a disruption in integrity and subsequent cell death. As for PDMS-n-b-PDMAEMA, the molecular weights of PDMS chain were designed as 2 kDa to 10 kDa and the molecular weights of PDMAEMA chain were designed as 2.7 kDa. The hydrophobicity of SnQm and its ability to form micelles would increase as the length of the hydrophobic PDMS chains increased. And the molecular weights of PDMS-Vi, PDMAEMA, PDMS-n-b-PDMAEMA and PDMAPMA are shown in Table S2 and Figure S1. The FT-IR and 1H NMR spectroscopies of the products were shown in the Supporting Information. 3.2 Design and synthesis of S5Q5-FL, DDBAC-FL and QPDMAPMA-FL. To further explore the mechanism of the inhibition of germination by polymeric quaternary ammonium salts on R. solani sclerotia, we replaced a few of the benzyl groups of DDBAC, QPDMAPMA and S5Q5 with fluorescent groups. As shown in Figure S9, the Φ-H proton signals of fluorescein shifted from 6.55 and 6.70 to 6.54 and 6.69 ppm respectively after quaternization reaction, which indicated that the fluorescein had been grafted onto the quaternary ammonium salts and there have not free FL-Cl is left in the product after purification. And there were approximately one fluorescein molecules attached per S5Q5-FL chain and one fluorescein molecules attached every three QPDMAPMA-FL chain according to

1H

NMR. The UV-Vis and

photoluminescence (PL) spectra of DDBAC-FL, QPDMAPMA-FL and S5Q5-FL are shown in Figure 1.

15


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Figure 1. UV-Vis and PL spectra of (A) DDBAC-FL, (B) QPDMAPMA-FL and (C) S5Q5-FL. 3.3 Micellar conformation of S0Q5 and SnQm in water. The CMC values of S0Q5 and SnQm were measured via the electrical conductivity method. Figure 2 shows the CMC values of S0Q5 and SnQm. The test results indicated that the CMC values of SnQm with long polysiloxane chains are lower than the other SnQm samples with shorter polysiloxane chains. The CMC of amphiphilic polymers is negatively correlated with the hydrophobicity. The hydrophobicity of SnQm and its ability to form micelles increased as the length of the hydrophobic chains increased.

16



Figure 2. CMC values of S0Q5 and SnQm. The zeta potentials and intensity particle size distributions of SnQm are shown in Figures 3 and 4. The zeta potential of S0Q5 was lower than 40, which meant it easily to aggregate into large vesicle.. At the same time, the zeta potentials of SnQm were higher than 60, which meant that the micelles formed by SnQm were very stable. Additionally, SnQm, with longer hydrophobic chains, formed smaller particles than the samples with shorter hydrophobic chains. The hydrophobic-hydrophilic balance of an amphiphilic polymer is closely associated with the aggregation morphology of the amphiphilic polymer in water. As shown in Figure 5, TEM analysis of the micellar conformations of S0Q5 and SnQm exhibit that the particle sizes of S0Q5 were larger than other samples, which corresponded to the results of the particle sizes distributions tests. In conclusion, SnQm has a lower CMC, higher zeta potential and smaller particle sizes compared to S0Q5, which is due to its increased amphipathy. In addition, the amphipathy of SnQm provides the adsorption and permeation abilities required to kill R. solani sclerotia.

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Figure 3. Zeta potentials of S0Q5 and SnQm.

Figure 4. Particle size distributions of S0Q5 and SnQm.

18



Figure 5. Transmission electron microscopy micrographs of (A) S0Q5, (B) S2Q5, (C) S3Q5, (D) S4Q5, (E) S5Q5, (F) S8Q5 and (G) S10Q5. 3.4 Adsorption tests. The capacities of SxQm, PDMAPMA and DDBAC to adsorb on the surface of R. solani sclerotia were tested using static water contact angles values. Surfactants tend to congregate and form a monolayer with hydrophobic chain toward surface and hydrophilic chain toward water by absorbing onto the hydrophobic surface in water, which lead to the decrease of hydrophobicity of the surface. The R.

solani sclerotia which have hydrophobic surface were immersed in the quaternary ammonium salts solutions, and then the amphiphilic quaternary ammonium salts congregated and absorbed onto the surface of R. solani sclerotia which lead to the decrease of static water contact angles values. The R. solani sclerotia were gently washed with ultrapure water after immersing and ensure the adsorption of amphiphilic quaternary ammonium salts was stable. The decrement of the static water contact angles represented the adsorption capacity of quaternary ammonium salts on the surface of R. solani sclerotia. As shown in Figure 6, the change in the 19


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static water contact angles is nonmonotonic, which means that the adsorption capacity of SnQm does not have a linear relationship with the length of the hydrophobic chains. On the one hand, hydrophobic chains enhance the adsorption ability of amphiphilic SnQm copolymers on R. solani sclerotia. On the other hand, the long hydrophobic chains spread out on the R. solani sclerotia surface and occupy a large number of adsorption sites, which leads to lower adsorption capacities for polymers with long hydrophobic chains (SnQm). Therefore, the maximum adsorption capacity is achieved when the length of the hydrophobic chains is appropriate.

Figure 6. Static water contact angles values for R. solani sclerotia (A) before and (B) after immersing in the solutions of S0Q5, S2Q5, S3Q5, S4Q5, S5Q5, S8Q5, S10Q5, QPDMAPMA and DDBAC. 3.5 Fluorescence labeling. The R. solani sclerotia were immersed in the S5Q5-FL,

20



DDBAC-FL and QPDMAPMA-FL solutions at 8 °C. Lower temperatures can inhibit the germination of sclerotia and prevent the interference of the mycelium. To observe the adsorption and permeation, R. solani sclerotia were randomly chosen after 7 d of immersing and observed under a stereomicroscope using white light and 365 nm ultraviolet (as shown in Figure 7). As a small-molecule quaternary ammonium salt, it is difficult for DDBAC-FL to stably adsorb on the surface of R. solani sclerotia. However, a large amount of green fluorescence can be observed in the inside of sclerotia, which meant that the DDBAC-FL permeated into the sclerotia. In addition, the fluorescence in the sclerotia section was reduced by washing. Although small-molecule quaternary ammonium salts can easily diffuse through the cell walls of the outer layer of empty cells, it is difficult for DDBAC-FL to stably adsorb on the surface of R. solani sclerotia, and it can easily run off into the soil. In addition, as for QPDMAPMA-FL, green fluorescence cannot be observed either on the surface or inside the R. solani sclerotia. The backbone of QPDMAPMA was polymethacrylamide, which was more hydrophilic than QPDMAEMA and PDMS-b-QPDMAEMA. This result shows that the abilities of the hydrophilic polymeric quaternary ammonium salts to absorb and permeate into the R. solani sclerotia are weak. As for amphiphilic S5Q5-FL, green fluorescence can clearly be observed on the surface of R. solani sclerotia and inside the sclerotia. In addition, the intensity of the fluorescence on the sclerotia section was not reduced by washing. S5Q5-FL can stably attach to the surface of R. solani sclerotia because its long hydrophobic

21


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chains spread out on the surface of the sclerotia. The strong amphipathy allows S5Q5-FL to stably attach to the surface of R. solani sclerotia and then permeate the

R. solani sclerotia. Traditional antifungal agents, as the hydrophilic or hydrophobic small molecular,are easily run off in soil. The adsorption of S5Q5-FL, which is strongly amphipathic, on R. solani sclerotia persisted and was stable. Therefore, compared to traditional antimicrobial agents, amphiphilic S5Q5-FL has prolonged lifetimes.

22



Figure 7. Stereoscopic photographs of R. solani sclerotia after immersing in the solutions of (A) DDBAC-FL, (B) QPDMAPMA-FL and (C) S5Q5-FL (using white light and 365 nm ultraviolet, respectively). 3.6 Antifungal activity against R. solani. The MIC and MFC of DDBAC, QPDMAPMA and SnQm against R. solani mycelium are shown in Figure 8. 23


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As forcationic bactericide, the ability to diffuse through the cell wall could be inhibited by increasing the molecular weight and the ability to disrupt the cytoplasmic membrane could be enhanced by increasing the molecular weight..37,

38

Therefore,

the molecular weight and ability to aggregate of the quaternary ammonium salts have a great influence on their antimicrobial activity. As shown in Figure 8, the MIC and MFC values of QPDMAPMA are higher than those of DDBAC and SnQm, which meant that the antifungal activity of QPDMAPMA against R. solani mycelium was lower than those of DDBAC and SnQm. It is reasonable to assume that the hydrophilic QPDMAPMA chains are in a stretched conformation in aqueous solutions. Thus, QPDMAPMA lacked the ability to diffuse through the cell wall. As amphiphilic quaternary ammonium salts, DDBAC and SnQm can form micelles, which lead to the aggregation of charge. In addition, as a small molecule, DDBAC can easily diffuse through the cell wall of R. solani mycelium. Thus, BC and SnQm exhibited good antifungal activities against R. solani mycelium. Notably, SnQm with various PDMS chain lengths exhibited rather similar antifungal activities. Although PDMS chains can enhance adsorption abilities, the ability of diffuse through the cell wall might be weakened by increases in molecular weight. In addition, the micellar conformations of SnQm with different PDMS chain lengths are similar.

24



Figure 8. MIC and MFC values of DDBAC, QPDMAPMA and SnQm against R.

solani. However, the addition of hydrophobic PDMS chains is particularly important for the inhibition R. solani sclerotia germination. The isolation of outer layer, which is composed of empty cells, the antifungal agent must possess the abilities of adsorption and permeation. As shown in Figure 9, SnQm in low concentrations (5 × MIC and 10 × MIC) exhibited moderate inhibitions on R. solani sclerotia germination, while DDBAC demonstrated weaker activity at similar concentrations. It was reasonable to assume that the strong amphipathy allows SnQm to stably attach and accumulate on the surface of R. solani sclerotia and then permeate into the R. solani sclerotia. As a hydrophilic polymeric quaternary ammonium salt, QPDMAPMA in high concentrations (15 × MIC and 20 × MIC) exhibited a moderate ability to inhibit R.

solani sclerotia germination. It is difficult for QPDMAPMA to attach to the surface of R. solani sclerotia and diffuse through the outer layer of sclerotia. For SnQm with different polysiloxane chain lengths, the optimal antifungal activity against R. solani sclerotia was gained when the molecular weight of the 25


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polysiloxane chain segments was 5 × 103. The abilities to adsorb and permeat the sclerotia are enhanced by increasing the length of the polysiloxane chain segments. However, the long hydrophobic chains spread out on the surface of the sclerotia and occupy a large number of adsorption sites, which lead to the low adsorption capacity of SnQm with long polysiloxane chains lengths. In addition, the water solubility of polymerized quaternary ammonium salts is another key factor influencing their antibacterial activity.28, 39 Long polysiloxane chains may reduce the water solubility of SnQm, reducing its antifungal activity against R. solani sclerotia of SnQm. Compared with S0Q5, although the antifungal activity of SnQm against R. solani mycelium was not improved, SnQm with an appropriate polysiloxane chain length exhibited effective antifungal activity against R. solani sclerotia. Therefore, SnQm is suitable for application in the slack season.

26



Figure 9. The inhibition rate of germination by (A) S0Q5, (B) S2Q5, (C) S3Q5, (D) S4Q5, (E) S5Q5, (F) S8Q5, (G) S10Q5, (H) DDBAC and (I) QPDMAPMA against R. solani sclerotia. 3.7 Toxicity tests. The environmental toxicity affects the usage of antifungal agents in agriculture. Only the antifungal agents have low toxicity to humans, mammals and even insects can the antifungal agents were used in agriculture. The toxicity to insects (silkworm) and mammals (Kunming mice) was systematically assessed. The hydrophobic moieties of amphiphilic quaternary ammonium salts can interact with the inner hydrophobic core of the bacterial membrane, which leads to

27


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the improving of the antimicrobial activity.15, 16 However, the hydrophobic segments will also increase the cytotoxicity of the quaternary ammonium salts and it is important to find the hydrophobic-hydrophilic balance which influence the antimicrobial activity and cytotoxicity.40 As a hydrophilic poly quaternary ammonium salt, QPDMAPMA show nontoxic to silkworms and Kunming mice (As shown in Table 1). However, excessive hydrophobicity also leads to the low antimicrobial activity of QPDMAPMA. S0Q5 and SnQm are nontoxic or nearly nontoxic while DDBAC exhibited low toxicity to silkworms and Kunming mice. Unlike small-molecule quaternary ammonium salts, polymeric quaternary ammonium salts have a relatively low environmental toxicity. Although the MIC and MFC test show that the small-molecule quaternary ammonium salts is superior compared to the quaternary ammonium salts polymers, the higher toxicity to mammals and insects did not allow small-molecule quaternary ammonium salts be used in agriculture. Table 1. Toxicity of S0Q5, SnQm, DDBAC and QPDMAPMA to silkworm and Kunming mice. LC50 (mg/L)

LD50 (mg/kg)

Silkworm

Kunming mice

S0Q5

˃ 2000

2000

S2Q5

˃ 2000

5000

S3Q5

˃ 2000

3162

S4Q5

˃ 2000

5000

Samples

28



S5Q5

˃ 2000

5000

S8Q5

˃ 2000

5000

S10Q5

˃ 2000

5000

QPDMAPMA

˃ 2000

˃ 5000

DDBAC

1150

555

4. CONCLUSIONS In this paper, QPDMAPMA, S0Q5 and SnQm with tunable hydrophobic PDMS chain lengths were synthetized to determine the relationship between their antifungal activities toward R. solani and the hydrophobic-hydrophilic balance. The optimal antifungal activity against R. solani sclerotia was achieved with PDMS chains of the appropriate length. The results indicated that the moderately hydrophobic PDMS blocks help stabilize the attachment of the hydrophilic quaternary ammonium salts chain and then help it penetrate the R. solani sclerotia. In addition, unlike small-molecule quaternary ammonium salts, polymeric quaternary ammonium salts have a relatively low environmental toxicity. The research for the antifungal activities of SnQm with different hydrophobic PDMS chain lengths can be guidance of the design of antifungal polymers for controlling plant diseases.

ACKNOWLEDGMENTS This work was supported by the Science and Technology Program of Guangzhou, China, under grants 201704020084, 201803020015; the National

29


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Natural Science Foundation of China under grant 31772202; and the Science and Technology Planning Project of Guangdong Province, China under grant 2016A020210105.

ASSOCIATED CONTENT Supporting Information Available: Characterization data of products, conductivity plots of the determination of CMC for S0Q5 and SnQm, and photographs of the MIC and MFC tests. REFERENCES (1)

Wu, W.; Liao, Y.; Shah, F.; Nie, L.; Peng, S.; Cui, K.; Huang, J. Plant Growth Suppression Due to Sheath Blight and the Associated Yield Reduction under Double Rice-cropping System in Central China. Field Crops Res. 2013, 144, 268–280.

(2)

Hashiba, T.; Mogi, S. Developmental Changes in Sclerotia of Rice Sheath Blight Fungus. Phytopathology 1975, 65, 159–162.

(3)

Peng, S.; Zeng, S.; Zhang, Z. Rice Sheath Blight and Its Prevention. Shanghai

scientific & technical publishers 1986, 53–54. (4)

Bowman, S. M.; Free, S. J. The Structure and Synthesis of the Fungal Cell Wall.

BioEssays 2006, 28, 799–808. (5)

Adams, D. J. Fungal Cell Wall Chitinases and Glucanases. Microbiology 2004,

150, 2029–2035. (6)

Xing, C,; Yang, G.; Liu, L.; Yang, Q.; Lv, F.; Wang, S. Conjugated Polymers for 30



Light-activated Antifungal Activity. Small 2012, 8, 524–529. (7)

Lambrechts, S. A. G.; Aalders, M. C. G.; Van Marle, J. Mechanistic Study of the Photodynamic Inactivation of Candida albicans by a Cationic Porphyrin.

Antimicrob. Agents Chemother. 2005, 49, 2026–2034. (8)

Kim, J. R.; Michielsen, S. Photodynamic Antifungal Activities of Nanostructured Fabrics Grafted with Rose Bengal and Phloxine B Against Aspergillus fumigatus.

J. Appl. Polym. Sci. 2015, 132. (9)

Choi, H.; Kim, K. J.; Lee, D. G. Antifungal Activity of the Cationic Antimicrobial Polymer-polyhexamethylene Guanidine Hydrochloride and Its Mode of Action.

Fungal Biol. 2017, 121, 53–60. (10) Li, R.; Guo, Z.; Jiang, P. Synthesis, Characterization, and Antifungal Activity of Novel Quaternary Chitosan Derivatives. Carbohydr. Res. 2010, 34, 1896–1900. (11) Tan, W.; Li, Q.; Dong, F.; Chen, Q.; Guo, Z. Preparation and Characterization of Novel Cationic Chitosan Derivatives Bearing Quaternary Ammonium and Phosphonium Salts and Assessment of Their Antifungal Properties. Molecules 2017, 22, 1438. (12) Tan, W.; Zhang, J.; Luan, F.; Wei, L.; Chen, Y.; Dong, F.; Li, Q.; Guo, Z. Design, Synthesis of Novel Chitosan Derivatives Bearing Quaternary Phosphonium Salts and Evaluation of Antifungal Activity. Int. J. Biol. Macromol. 2017, 102, 704–711. (13) Vlad, S.; Tanase, C.; Macocinsschi, D.; Ciobanu, C.; Balaes, T.; Filip, D.; Gostin, I. N.; Gradinaru, L. M. Antifungal Behaviour of Polyurethane Membranes with

31


Page 32 of 38

Page 33 of 38 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Zinc Oxide Nanoparticles. Dig. J. Nanomater. Bios. 2012, 7, 51–58. (14) Rzayev, Z. M. O.; Erdönmez, D.; Erkan, K.; Şimsekş, M.; Bunyatova, U. Functional Copolymer/Organo-MMT Nanoarchitectures. XXII. Fabrication and Characterization of Antifungal and Antibacterial Poly (vinyl alcohol-co-vinyl acetate/ODA-MMT/AgNPs Nanofibers and Nanocoatings by E-spinning and C-spinning Methods. Int. J. Polym. Mater. Polym. Biomater. 2015, 64, 267–278. (15) Sovadinova, I.; Palermo, E. F.; Urban, M.; Mpiga, P.; Caputo, Kroda, G. A.; K. Activity

and

Mechanism

of

Antimicrobial

Peptide-mimetic

Amphiphilic

Polymethacrylate Derivatives. Polymers 2011, 3, 1512–1532. (16) Paslay, L. C.; Abel, B. A.; Brown, T. D.; Koul, V.; Choudhary, V.; McCormick, C. L.; Morgan, S. E. Antimicrobial Poly(methacrylamide) Derivatives Prepared via Aqueous RAFT Polymerization Exhibit Biocidal Efficiency Dependent upon Cation Structure. Biomacromolecules 2012, 13, 2472–2482. (17) Lenoir, S.; Pagnoulle, C.; Galleni, M.; Compere, P.; Jerome, R..; Detrembleur, C. Polyolefin Matrixes with Permanent Antibacterial Activity: Preparation, Antibacterial

Activity,

and

Action

Mode

of

the

Active

Species.

Biomacromolecules 2006, 7, 2291–2296. (18) Huang, J.; Koepsel, R. R.; Murata, H.; Wu, W.; Lee, S. B.; Kowalewski, T.; Russell, A. J.; Matyjaszewski, K. Nonleaching Antibacterial Glass Surfaces via “Grafting onto”: the Effect of the Number of Quaternary Ammonium Groups on Biocidal Activity. Langmuir, 2008, 24, 6785–6795. (19) Luo, W.; Venkataraman, S.; Zhong, G.; Ding, B.; Tan, J. P.K.; Xu, L.; Fan, w.;

32



Page 34 of 38

Yang, Y. Y. Antimicrobial Polymers as Therapeutics for Treatment of Multidrugresistant Klebsiella pneumoniae Lung Infection. Acta Biomater. 2018,

78, 78-88. (20) Chen, C. Z.; Beck-Tan, N. C.; Dhurjati, P.; Van Dyk, T. K.; LaRossa, R. A.; Cooper, S. L. Quaternary Ammonium Functionalized Poly(propylene imine) Dendrimers

as

Effective

Antimicrobials:

Structure-activity

Studies.

Biomacromolecules 2000, 1, 473–480. (21) Kenawy, E. R.; Worley, S. D.; Broughton, R. The Chemistry and Applications of Antimicrobial Polymers: a State-of-the-art Review. Biomacromolecules 2007, 8, 1359–1384. (22) Timofeeva, L.; Kleshcheva, N. Antimicrobial Polymers: Mechanism of Action, Factors of Activity, and Applications. Appl. Microbiol. Biotechnol. 2011, 89, 475–492. (23) Zhang, A.; Liu, Q.; Lei, Y.; Hong, S.; Lin, Y. Synthesis and Antimicrobial Activities of Acrylamide Polymers Containing Quaternary Ammonium Salts on Bacteria and Phytopathogenic Fungi. React. Funct. Polym. 2015, 88, 39–46. (24) Lin, Y.; Liu, Q.; Cheng, L.; Lei, Y.; Zhang, A. Synthesis and Antimicrobial Activities of Polysiloxane-containing Quaternary Ammonium Salts on Bacteria and Phytopathogenic Fungi. React. Funct. Polym. 2014, 85, 36–44. (25) Zhong, W.; Dong, C.; Liuyang, R.; Guo, Q.; Zeng, H.; Lin, Y.; Zhang, A. Controllable Synthesis and Antimicrobial Activities of Acrylate Polymers Containing Quaternary Ammonium Salts. React. Funct. Polym. 2017, 121,

33


Page 35 of 38 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


110–118. (26) Huang, Z.; Liuyang, R.; Dong C.; Lei, Y.; Zhang, A.; Lin, Y. Polymeric Quaternary Ammonium Salt Activity Against Fusarium oxysporum f. sp.

cubense race 4: Synthesis, Structure-activity Relationship and Mode of Action. React. Funct. Polym. 2017, 114, 13–22. (27) Dong C.; You, W.; Liuyang, R.; Lei, Y.; Zhang, A.; Lin, Y. Anti-Rhizoctonia

solani Activity by Polymeric Quaternary Ammonium Salt and Its Mechanism of Action. React. Funct. Polym. 2018, 125, 1–10. (28) Wan, X. ; Zhang, Y.; Deng, Y.; Zhang, Q.; Li, J.; Wang, K.; Li, J.; Tan, H.; Fu, Q. Effects of Interaction Between a Polycation and a Nonionic Polymer on Their Cross-assembly into Mixed Micelles. Soft Matter 2015, 11, 4197–4207. (29) Kuroki, A.; Sangwan, P.; Qu, Y.; Peltier, R.; Sanchez-Cano, C.; Moat, J.; Dowson, C. G.; Williams, E. G. L.; Locock, K. E. S.; Hartlieb, M.; Perrier, S. Sequence Control as a Powerful Tool for Improving the Selectivity of Antimicrobial Polymers. ACS Appl. Mater. Interfaces 2017, 9, 40117–40126. (30) Kuroda, K.; Caputo, G. A.; DeGrado, W. F. The Role of Hydrophobicity in the Antimicrobial and Hemolytic Activities of Polymethacrylate Derivatives. Chem.

Eur. J. 2009, 15, 1123–1133. (31) Locock, K. E. S.; Michl, T. D.; Valentin, J. D. P.; Vasilev, K.; Hayball, J. D.; Qu, Y.; Traven, A.; Griesser, H. J.; Meagher, L.; Haeussler, M. Guanylated Polymethacrylates: a Class of Potent Antimicrobial Polymers with Low Hemolytic Activity. Biomacromolecules, 2013, 14, 4021–4031.

34



Page 36 of 38

(32) Gabriel, G. J.; Madkour, A. E.; Dabkowski, J. M.; Nelson, C. F.; Nusslein, K.; Tew,

G.

N.

Synthetic

Mimic

of

Antimicrobial

Peptide

with

Nonmembrane-disrupting Antibacterial Properties. Biomacromolecules, 2008, 9, 2980–2983. (33) Ilker, M. F.; Nusslein, K.; Tew, G. N.; Coughlin, E. B. Tuning the Hemolytic and Antibacterial Activities of Amphiphilic Polynorbornene Derivatives. J. Am. Chem.

Soc. 2004, 126, 15870–15875. (34) Majumdar, P.; Lee, E.; Gubbins, N.; Stafslien, S. J.; Daniels, J.; Thorson, C. J.; Chisholm,

B.

J.

Synthesis

and

Antimicrobial

Activity

of

Quaternary

Ammonium-functionalized POSS (Q-POSS) and Polysiloxane Films Containing Q-POSS. Polymer 2009, 50, 1124–1133. (35) Palermo, E. F.; Sovadinova, I.; Kuroda, K. Structural Determinants of Antimicrobial

Activity

Methacrylamide

and

Random

Biocompatibility

Copolymers.

in

Membrane-disrupting

Biomacromolecules

2009,

10,

3098–3107. (36) Cheng, C. Y.; Wang, J. Y.; Kausik, R.; Lee, K. Y. C.; Han, S. Nature of Interactions

between

PEO-PPO-PEO

Triblock

Copolymers

and

Lipid

Membranes: (II) Role of Hydration Dynamics Revealed by Dynamic Nuclear Polarization. Biomacromolecules 2012, 13, 2624–2633. (37) Kanazawa, A.; Ikeda, T.; Endo, T. Novel Polycationic Biocides: Synthesis and Antibacterial Activity of Polymeric Phosphonium Salts. J. Polym. Sci., Part A:

Polym. Chem. 1993, 31, 335–343. 35


Page 37 of 38 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(38) Ikeda, T.; Hirayama, H.; Yamaguchi, H.; Tazuke, S.; Watanabe, M. Polycationic Biocides with Pendant Active Groups: Molecular Weight Dependence of Antibacterial Activity. Antimicrob. Agents Chemother. 1986, 30, 132–136. (39) Lu, G.; Wu, D.; Fu, R. Studies on the Synthesis and Antibacterial Activities of Polymeric Quaternary Ammonium Salts from Dimethylaminoethyl Methacrylate.

React. Funct. Polym. 2007, 67, 355–366. (40) Álvarez-Paino, M.; Muñoz-Bonilla, A.; López-Fabal, F.; Gómez-Garcés, J. L.; Heuts, J. P.A.; Fernández-García, M. Effect of Glycounits on the Antimicrobial Properties and Toxicity Behavior of Polymers Based on Quaternized DMAEMA. Biomacromolecules 2015, 16, 295–303.

36



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