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Assessing the passage of small pesticides through reverse osmosis membranes

Takahiro Fujioka, Hitoshi Kodamatani, Wang Yujue, Koh Dan Yu, Elvy Riani Wanjaya,
Han Yuan, Mingliang Fang, Shane Allen Snyder

PII: S0376-7388(19)32185-4
DOI: https://doi.org/10.1016/j.memsci.2019.117577
Reference: MEMSCI 117577

To appear in: Journal of Membrane Science

Received Date: 22 July 2019

Revised Date: 9 October 2019
Accepted Date: 16 October 2019

Please cite this article as: T. Fujioka, H. Kodamatani, W. Yujue, K.D. Yu, E.R. Wanjaya, H. Yuan, M.
Fang, S.A. Snyder, Assessing the passage of small pesticides through reverse osmosis membranes,
Journal of Membrane Science (2019), doi: https://doi.org/10.1016/j.memsci.2019.117577.

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 100
80
Rejection [%]

60
40
Diuron
20 (Hydrogen bonding)

0
20 25 30 35
Minimum projection area [Å2]
1 Assessing the passage of small pesticides through reverse osmosis
2 membranes

3 Takahiro Fujioka 1,*, Hitoshi Kodamatani 2, Wang Yujue 3, Koh Dan Yu 3,

4 Elvy Riani Wanjaya 3, Han Yuan 3, Mingliang Fang 3,4, Shane Allen Snyder 3,4

1
5 Graduate School of Engineering, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521,
6 Japan

2
7 Division of Earth and Environmental Science, Graduate School of Science and Engineering,
8 Kagoshima University, 1-21-35 Korimoto, Kagoshima 890-0065, Japan

3
9 Analytics Cluster, Nanyang Environment & Water Research Institute (NEWRI), Nanyang
10 Technological University, 1 Cleantech Loop, CleanTech One, Singapore 637141, Singapore

4
11 School of Civil and Environmental Engineering, Nanyang Technological University, 50
12 Nanyang Avenue, Singapore 639798, Singapore

13 _______________________
14 * Corresponding author: Takahiro Fujioka, Email: tfujioka@nagasaki-u.ac.jp, Ph +81 95 819 2695
15 Abstract

16 Attenuation of trace organic chemicals (TOrCs), including pesticides, by reverse osmosis (RO)

17 membrane treatment is critical for ensuring public health protection in potable water reuse. This

18 study aimed to elucidate the mechanisms underlying the poor rejection of small pesticides by

19 polyamide-based RO membranes. Rejection of the selected TOrCs (four N-nitrosamines and 158

20 pesticides) was primarily governed by size exclusion, charge interactions, and dipolar

21 interactions when evaluated at high water temperatures. Further investigation indicated that small

22 and uncharged secondary amide pesticides showed low and highly variable rejections, compared

23 to similarly sized counterparts with no amide functional groups. Remarkably, three secondary

24 amide pesticides that have no other atoms holding a high partial negative charge showed very

25 low rejections (34–65%), likely due to the cooperativity of hydrogen bonding which occurs

26 between amide functional groups of the pesticides and RO membranes. In contrast, secondary

27 amide pesticides that have an atom holding a high partial negative charge showed higher

28 rejections (72–98%) which is due to the inducted electrostatic repulsion. This study proposed

29 that secondary amide pesticides that have no other atoms holding a high partial negative charge

30 can be poorly rejected. The findings are useful to predict the rejection level of unregulated

31 TOrCs.

32 Keywords: secondary amides; trace organic chemicals; NDMA; hydrogen bonding; potable

33 water reuse.

34

1
35 1 INTRODUCTION

36 Potable water reuse has been increasingly adopted in many regions of the world that have been

37 plagued by droughts [1]. It is typically carried out by converting municipal wastewater to highly

38 pure water through advanced wastewater treatment. The majority of recent advanced wastewater

39 treatment systems for potable water reuse include microfiltration (MF) or ultrafiltration (UF),

40 reverse osmosis (RO), and ultraviolet (UV) or UV-based advanced oxidation processes [2].

41 Advanced wastewater treatment using RO plays a role in attenuating salts, pathogens, and trace

42 organic chemicals (TOrCs), which include pesticides, disinfection by-products (DBPs),

43 endocrine disrupting compounds, and pharmaceuticals and personal care products (PPCPs) [3, 4].

44 The attenuation of these TOrCs by an RO process can be ensured through periodical water

45 quality testing by approved analytical methods. However, for continuously ensuring regulatory

46 compliance, the infrequent and costly analysis remains a challenge. To date, no monitoring

47 technique has been fully established to continuously and conservatively ensure the attenuation of

48 TOrCs by the RO process or the integrity of RO membranes for TOrC removal [5].

49 As a surrogate indicator for TOrC removal by RO, the authors have recently suggested a low

50 molecular weight (MW) DBP, N-nitrosodimethylamine (NDMA; MW of 74 g/mol), which can

51 be monitored online using high-performance liquid chromatography followed by photochemical

52 reaction and chemiluminescence detection [6, 7]. The NDMA can be considered as a

53 conservative surrogate because it is not well rejected by RO membranes and is typically

54 identified at higher concentrations than the method detection limit (e.g., 1–2 ng/L) in both RO

55 feedwater and permeate [8]. Previous pilot-scale studies conducted by the authors demonstrated

56 that online monitored NDMA rejection was always lower than the rejection of PPCPs [7].

57 Nevertheless, the reliability of NDMA as a conservative surrogate for TOrC removal is still

2
58 questionable, since its conservativeness cannot be guaranteed with the current knowledge about

59 the rejection mechanisms.

60 Despite many studies addressing the rejection mechanisms of TOrCs over the past decade [9-15],

61 the cause of some poorly rejected TOrCs has not been adequately understood. The rejection of

62 TOrCs at high temperatures is of great interest, because wastewater temperature can vary

63 seasonally and TOrC rejection decreases according to an increase in temperature due to the

64 increasing diffusivity of the solutes [16, 17]. According to the previous studies, the transport of

65 TOrCs through nanofiltration (NF) and RO membranes is governed by three major interactions

66 (i.e., size, charge, and hydrophobicity) that occur between compounds and membranes. The

67 rejection of TOrCs by polyamide-based membranes is primarily governed by size interaction and

68 charge interaction, whereas highly hydrophobic TOrCs (e.g., LogD = ≥ 2) can show lower

69 rejection than hydrophilic TOrCs (e.g., LogD = < 2) [18, 19]. As a result, pesticides, most of

70 which are highly hydrophobic, are of great interest [20, 21]. One notable pesticide is diuron,

71 which is an aromatic pesticide with a relatively high molecular weight of 233 g/mol. For

72 example, Chen et al. [22] reported that the rejection of diuron by a polyamide NF membrane

73 element (50%) was the lowest among 11 selected pesticides with molecular weights of 198–286

74 g/mol (60–100%). Similar observations associated with the low rejection of diuron have been

75 reported elsewhere [23-27]. However, to the best of our knowledge, no basic theory for

76 clarifying the mechanisms of the poorly rejected pesticides has been established.

77 This study aimed to elucidate the mechanisms underlying the poor rejection of several pesticides

78 by polyamide-based RO membranes. The rejection mechanisms were comprehensively assessed

79 by analyzing the role of molecular interactions (i.e., size exclusion, and electrostatic,

3
 80 hydrophobic, dipolar, and hydrogen bond interactions) using a diverse range of compounds (four

81 N-nitrosamines and 158 pesticides).

82 2 MATERIALS AND METHODS

83 2.1 Chemicals

84 Analytical grade solutions of four N-nitrosamines – NDMA, N-nitrosomethylethylamine

85 (NMEA), N-nitrosopyrrolidine (NPYR), and N-nitrosomorpholine (NMOR) – were purchased

86 from Ultra Scientific (Kingstown, RI, USA). A stock solution containing the N-nitrosamines was

87 prepared at 10 mg/L in pure methanol. In addition to N-nitrosamines, a total of 158 analytical

88 grade pesticides (Agilent Technologies, Singapore) covering a wide range of molecular weights

89 (MWs) and other molecular properties were used in this study (Table 1 and Table S1).

90 Commercial Marvin (version 18.30, ChemAxon, Budapest, Hungary) was used for drawing and

91 characterizing chemical structures, and calculating molecular properties (minimum projection

92 area, LogD, pKa, dipole moment, and counts of hydrogen bond acceptor or donor). The

93 minimum projection area (MPA) of a compound is a two-dimensional projected area of the

94 chemical calculated based on the van der Waals radius (Figure S1). LogD, which is the octanol-

95 water coefficient of the chemical, was calculated at a test solution pH of 8.0. The selected

96 chemicals were determined to be uncharged (≤50% ionized) or charged (>50% positively or

97 negatively charged, or zwitterion). The total dipole moment of a chemical was calculated as a

98 vector expressed in the principal axis frame. Counts of hydrogen bond acceptor or donor were

99 determined at pH 8. Analytical grade NaCl was purchased from Merck KGaA (Darmstadt,

100 Germany) and analytical grade NaHCO3 was purchased from VWR Singpapore Ltd (Singapore).

4
101 Two stock solutions containing the pesticides were prepared at 5 mg/L in Milli-Q water with 10

102 mM NaCl and 1 mM NaHCO3.

5
103 Table 1: Properties of four N-nitrosamines and 158 pesticides.
Compound MW MPA Compound MW MPA Compound MW MPA
2 2 2
[g/mol] [Å ] [g/mol] [Å ] [g/mol] [Å ]
Uncharged Dimethachlor 255.7 50.5 Ipconazole 333.9 60.0
NDMA 74.1 19.4 Propyzamide 256.1 39.7 Zoxamide 336.6 46.3
NMEA 88.1 22.3 Ethidimuron 264.3 33.5 Fenbuconazole 336.8 53.8
NPYR 100.1 25.0 Diethofencarb 267.3 53.4 Bitertanol 337.4 49.5
NMOR 116.1 26.9 Silthiofam 267.5 49.6 Tepraloxydim 341.8 42.3
Propham 179.2 32.4 Methoprotryne 271.4 48.6 Propiconazole 342.2 55.4
Acephate 183.2 32.3 Metazachlor 277.8 52.4 Boscalid 343.2 49.3
Fuberidazole 184.2 24.2 Oxadixyl 278.3 47.7 Azinphos-ethyl 345.4 46.3
Molinate 187.3 37.3 Metalaxyl 279.3 53.2 Triflumizole 345.8 53.2
Tricyclazole 189.2 27.7 Propetamphos 281.3 49.7 Tebufenozide 352.5 67.6
Aldicarb 190.3 35.1 Fosthiazate 283.4 42.5 Beflubutamid 355.3 54.7
Butocarboxim 190.3 38.8 Metolachlor 283.8 56.1 Triflumuron 358.7 54.8
Carbendazim 191.2 25.5 Penconazole 284.2 51.1 Chlorfenvinphos 359.6 53.4
DEET 191.3 41.2 Vamidothion 287.3 42.3 Clethodim 359.9 50.1
Trimethacarb 193.2 35.1 Myclobutanil 288.8 50.9 Flufenacet 363.3 42.2
Cycluron 198.3 34.6 Isoprothiolane 290.4 47.4 Benzoximate 363.8 47.5
Pyrimethanil 199.3 31.3 Thiamethoxam 291.7 38.8 Picoxystrobin 367.3 54.3
Thiabendazol 201.3 25.0 Cyproconazole 291.8 49.2 Methoxyfenozide 368.5 49.1
Metamitron 202.2 28.5 Uniconazole-P 291.8 48.0 Tetraconazole 372.2 54.1
Fenobucarb 207.3 44.2 Triadimefon 293.8 47.7 Spirotetramat 373.4 57.4
Promecarb 207.3 38.8 Paclobutrazol 293.8 49.3 Profenofos 373.6 50.1
Quinoclamine 207.6 25.2 Triadimenol 295.8 47.9 Fluquinconazole 376.2 47.8
Aminocarb 208.3 35.5 Imazalil 297.2 46.0 Prochloraz 376.7 58.3
Propoxur 209.2 40.6 Quinalphos 298.3 45.6 Bromuconazole 377.1 48.7
Ethirimol 209.3 34.8 Phoxim 298.3 52.6 Fluopicolide 383.6 42.4
Chlorotoluron 212.7 29.9 Phosphamidon 299.7 45.3 Sulfentrazone 387.2 45.6
Metribuzin 214.3 34.4 Flutriafol 301.3 49.3 Pyraclostrobin 387.8 52.3
Cymiazole 215.4 29.2 Furalaxyl 301.3 54.6 Dimethomorph 387.9 66.3
Pyracarbolid 217.3 32.9 Methidathion 302.3 34.7 Alanycarb 399.5 73.8
Thiofanox 218.3 39.9 Fenamiphos 303.4 49.6 Azoxystrobin 403.4 63.5
Carbofuran 221.3 40.8 Diazinon 304.4 50.7 Difenoconazole 406.3 60.9
Chloridazon 221.6 29.9 Pirimiphos-methyl 305.3 47.9 Trifloxystrobin 408.4 58.0
Mexacarbate 222.3 41.9 Buprofezin 305.4 56.1 Metrafenone 409.3 60.8
Acetamiprid 222.7 30.8 Tebuconazole 307.8 54.1 Mandipropamide 411.9 58.0
Monocrotophos 223.2 41.2 Diflubenzuron 310.7 27.9 Bispyribac 430.4 54.7
Mepanipyrim 223.3 38.0 Fenamidone 311.4 53.1 Fipronil 437.2 44.1
Mevinphos 224.2 40.2 Triazophos 313.3 46.3 Fluoxastrobin 458.8 63.7
Cyprodinil 225.3 37.7 Kresoxim-methyl 313.4 51.2 Chlorantraniliprole 483.2 68.0
Prometon 225.3 46.3 Hexaconazole 314.2 53.0 Flubendiamide 682.4 84.2
Secbumeton 225.3 42.9 Flusilazole 315.4 54.4 Charged (negative)
Tebuthiuron 228.3 37.7 Bupirimate 316.4 54.6 Thidiazuron 220.3 25.0
Flonicamid 229.2 27.1 Azinphos-methyl 317.3 29.2 Quinmerac 221.6 27.7
Dimethoate 229.3 35.8 Triticonazole 317.8 51.5 Chlorsulfuron 357.8 49.6
Trietazine 229.7 40.5 Metconazole 319.8 54.2 Amidosulfuron 369.4 50.7
Fluometuron 232.2 32.7 Phenthoate 320.4 55.8 Thifensulfuron-methyl 387.4 51.1
Diuron 233.1 28.6 Iprovalicarb 320.4 52.2 Tribenuron-methyl 395.4 48.1
Lenacil 234.3 36.3 Cyazofamid 324.8 49.2 Triasulfuron 401.8 55.3
Carboxine 235.3 34.0 Flumetsulam 325.3 50.7 Oxasulfuron 406.4 63.7
Pirimicarb 238.3 44.0 Benalaxyl 325.4 57.8 Flazasulfuron 407.3 46.8
Clomazone 239.7 40.1 Diniconazole 326.2 52.2 Nicosulfuron 536.8 57.2
Methacrifos 240.2 36.0 Dimoxystrobin 326.4 62.2 Charged (positive)
Ethoprophos 242.3 50.3 Pencycuron 328.8 49.9 Fenpropidin 273.5 46.1
Fludioxonil 248.2 40.3 Epoxiconazole 329.8 48.5 Zwritterion
Linuron 249.1 28.0 Halofenozide 330.8 54.9 Imidacloprid 255.7 36.9
Prosulfocarb 251.4 39.1 Fenarimol 331.2 55.4
Thiacloprid 252.7 36.9 Isoxaben 332.4 51.8
104 * MPA was calculated using Marvin software (ChemAxon, Budapest, Hungary).

6
105 2.2 Membranes and RO treatment

106 This study used a low pressure RO membrane – namely ESPA2, which is widely used in many

107 water recycling projects [8]. The RO membrane was supplied as flat sheet coupons by

108 Hydranautics/Nitto (Osaka, Japan). RO treatment was conducted using a bench-scale system

109 comprised of a stainless steel membrane cell (Iwai Pharma Tech, Tokyo, Japan), high-pressure

110 constant flow pump (KP-12, FLOM, Tokyo, Japan), pressure regulating valve (Swagelok, Solon,

111 OH, USA), and digital flow meter (F7M, Azbil Co., Tokyo, Japan) (Figure S2). The cross-flow

112 membrane cell has an integrated magnetic stirrer for mixing feed solution at the membrane

113 surface to minimize concentration polarization. The membrane cell held a circular flat-sheet

114 membrane coupon with effective surface area of 36.3 cm2. The RO concentrate and permeate

115 were recirculated into the reservoir.

116 Prior to each rejection test, each RO membrane coupon underwent a stabilization phase by

117 treating Milli-Q water at 1000 kPa. Thereafter, the Milli-Q water was replaced with a 200 mL

118 solution containing 10 mM NaCl and 1 mM NaHCO3. RO treatment was conducted at a constant

119 permeate flux of 20 L/m2h, a constant feed flow rate of 30 mL/min, and a constant feed

120 temperature of 35°C. The high temperature was determined to simulate the summer during a

121 long-term operation, which leads to the lowest performance for TOrC removal due to its high

122 temperature. In addition, a stock solution of N-nitrosamines or pesticides was added to the RO

123 feed to achieve 1.0 µg/L or 5.0 µg/L, respectively. It is noted that the rejection tests for four N-

124 nitrosamines and 158 pesticides were separately conducted to avoid interferences with their

125 analysis. The system was then continuously operated for approximately 70 h before collecting

126 samples from the RO feed and permeate. The RO feed and permeate samples were collected in

127 1.5 mL amber vials for the analysis of N-nitrosamines and pesticides. The extended treatment

7
128 period was determined to reach the steady state condition for adsorption, because most pesticides

129 used in this study are hydrophobic (LogD = > 2), and adsorption onto the membrane can cause

130 overestimation of their rejections [28].

131 2.3 Analytical techniques

132 Concentrations of pesticides were analyzed using Agilent 1290 infinity II Binary liquid

133 chromatography (LC) system coupled with Agilent 6460 triple quadrupole (QqQ) mass

134 spectrometer (Agilent Technologies, Santa Clara, CA, USA). The mass spectrometer was fitted

135 with electrospray ionization (ESI) interface in positive and negative mode with Agilent jet

136 stream technology. Identification and quantification of all target compounds were conducted via

137 tandem mass spectrometry. Further information of the pesticide analysis is provided in Text S1

138 and Table S2. Concentrations of four N-nitrosamines were analysed using high-performance

139 liquid chromatography-inline anion exchange reaction-photochemical reaction-

140 chemiluminescence detection (HPLC-AEM-PR-CL) technique [6, 29]. The analysis was

141 performed with an eluent of 1 mM phosphate buffer (pH6.8) and methanol (95:5 v/v) and the

142 sample injection volume of 200 µL.

143 3 RESULTS AND DISCUSSION

144 3.1 Size exclusion and electrostatic interaction

145 The importance of size exclusion on TOrC rejection by polyamide-based RO membranes was

146 evaluated using four N-nitrosamines and 158 pesticides. In general, the rejection of the tested

147 compounds increased with an increase in their molecular weight (Figure 1a). However, many of

148 the uncharged pesticides with molecular weights of 180–300 g/mol showed high variations in

149 rejection. Another two-dimensional parameter, referred to as the minimum projection area

8
150 (MPA), appeared to be more strongly correlated with the rejection of uncharged pesticides

151 (Figure 1b). The role of size exclusion can be explained by the phenomena that TOrCs with low

152 two-dimensional areas have more clearance with the free volume hole of the membrane structure,

153 resulting in lower rejection. In fact, when curve fitting with the monomolecular growth model

154 was used, MPA (R2adj = 0.6) showed a better fit than molecular weight (R2adj = 0.5). The results

155 indicate that MPA is a suitable parameter to describe the rejection level of uncharged compounds

156 such as pesticides and N-nitrosamines, which confirms the importance of size exclusion in the

157 rejection of uncharged TOrCs. However, large variations of rejection for uncharged pesticides at

158 an MPA of approximately 27–30 Å2 (e.g., diflubenzuron, diuron, chlorotoluron) (Figure 1b)

159 indicates that size exclusion is not the only mechanism governing TOrC rejection. Therefore, the

160 influence of other chemical properties on the rejection of uncharged TOrCs was further

161 evaluated in the following sections.

162 Evaluating the impact of electrostatic interactions on their rejection was difficult in this study,

163 because almost all of the charged pesticides were large in size and uncharged pesticides with

164 equivalent MPAs were also highly rejected. However, the rejection of negatively charged

165 pesticides was found to be higher than the fitted line of uncharged pesticides, with the exception

166 of the smallest charged pesticide (thidiazuron, 43%) (Figure 1b). In contrast, the rejections of a

167 positively charged pesticide (fenpropidin) and zwitterion (imidacloprid) were equivalent to those

168 of similarly sized uncharged pesticides. The rejection of negatively charged TOrCs by RO

169 membranes can be enhanced with electrostatic repulsion that occurs against the negatively

170 charged membrane surface. The skin layer of the polyamide RO membrane, which is formed by

171 a cross-linking of meta-phenylenediamine and trimesic acid trichloride monomers, has remaining

172 carboxyl functional groups (-COOH) that are dissociated (-COO-) and negatively charged at pH

9
173 8 [30, 31]. However, the cause of the poor rejection of thidiazuron remains unclear. Thus, other

174 molecular properties have been accounted for to explain thidiazuron rejection in Section 3.5.

100
(a)
y = A×(1-exp(-k×(x-xc)))
80
R2adj = 0.50
Rejection [%]

60

Uncharged
40
( N-nitrosamines)
Charged (-)
20 Charged (+)
Zwitterion
0
100 200 300 400 680
Molecular weight [g/mol]
100
(b)
80 y = A×(1-exp(-k×(x-xc)))
Rejection [%]

R2adj = 0.60
Chlorotoluron
60
Diflubenzuron
Thidiazuron
40
Diuron

20

0
20 30 40 50 60 70 80
Minimum projection area [Å2]
175
176 Figure 1 – Effect of (a) molecular weight and (b) minimum projection area (MPA) of four N-
177 nitrosamines and 158 pesticides on their rejection by the ESPA2 reverse osmosis (RO)
178 membrane (10 mM NaCl and 1 mM NaHCO3; feed temperature of 35 ºC, permeate flux of 20
179 L/m2h, and pH of 8.1; error bars show the range of duplicate RO treatment experiments).
180 Rejection data is provided in Figure S3.

10
181 3.2 Hydrophobic interaction

182 Hydrophobicity of TOrCs can also be an important additional factor to vary rejection [20, 32, 33].

183 Rejection of TOrCs with strong hydrophobicity can be lower than that of hydrophilic TOrCs,

184 because the former can be concentrated at the RO membrane surface, leading to an increase in

185 their concentrations in the RO permeate. However, in this study, hydrophobicity alone did not

186 show any correlation with compound rejection (Figure S4), indicating that hydrophobicity

187 interactions are less preferential than size exclusion. Therefore, the impact of hydrophobic

188 interactions on pesticide rejection was evaluated by applying six classifications of

189 hydrophobicity and comparing their rejections at a given MPA (Figure 2). As a result, the

190 impact of hydrophobic interactions on pesticide rejection was not apparent for small and

191 uncharged pesticides (e.g., MPA = < 35 Å2). For example, several hydrophobic compounds

192 (LogD = ≥ 2.0) showed higher rejection than hydrophilic compounds (LogD = < 1.9) when

193 evaluated at equivalent MPAs. This indicates that the rejection of low MPA pesticides is also

194 influenced by factors other than size exclusion and hydrophobic interactions. Therefore, the roles

195 of other molecular interactions for the rejection of uncharged and low MPA compounds (MPA of

196 <35 Å2) were further evaluated in the following sections.

11
 100

80
Rejection [%]

LogD
60 5.0–5.9
4.0–4.9
40 3.0–3.9
2.0–2.9
1.0–1.9
20 ≤0.9

0
20 30 40 50 60 70 80
2
Minimum projection area [Å ]
197
198 Figure 2 – Effect of hydrophobicity on the rejection of uncharged compounds by the ESPA2
199 reverse osmosis (RO) membrane. The results were obtained from Figure 1. Error bars show the
200 range of duplicate RO treatment experiments.

201 3.3 Dipolar interaction

202 Dipole moment (DM), which is the level of charge separation in a compound, can also influence

203 the rejection of TOrCs [34-36]. Regarding the molecular interaction between dipole TOrCs and

204 the RO membrane surface, the positive end of the dipole TOrCs can be favorably attracted to the

205 negatively charged functional group of an RO membrane (i.e., COO–) (dipole-charge interaction),

206 which can cause an increase in the TOrC concentration at the RO membrane surface and

207 consequently lead to low rejection. The compounds tested in this study hold a diverse range of

208 DM; thus, its impact was comprehensively assessed. The results indicated that highly polar (DM

209 = ≥ 6) compounds, with the exception of diuron, showed a proportional increase in rejection as a

210 function of MPA (Figure 3). Compounds with lower polarity (DM = < 6) showed higher

211 rejections than their similarly sized counterparts, which is in line with the theory (i.e., dipole-

212 charge interaction). It is noted that DM was not the only parameter that determines rejection,

213 because the compounds with DM of 6–7 debye showed a considerable variation in rejection (14–

12
214 88%) (Figure S5). The results indicate that the rejection of uncharged TOrCs varies according to

215 their molecular size and DM. However, seven pesticides (chemicals circled with a dotted line in

216 Figure 3) showed substantially lower rejection than their similarly sized counterparts, indicating

217 that other parameters are involved in governing their rejection. Therefore, further evaluation was

218 conducted with a particular focus on these poorly rejected pesticides.

100
DM
Propham
≥ 6.0
80 3.5–5.9 Carboxine
Rejection [%]

1.0–3.4 Methi
-dathion
60 NPYR Chlorotoluron
Pyra
Diflubenzuron -carbolid

40 NMEA
Diuron

20
NDMA

0
15 20 25 30 35
Minimum projection area [Å2]
219
220 Figure 3 – Effect of dipole moment (DM) on the rejection of small (MPA = < 35 Å2) and
221 uncharged compounds by the ESPA2 reverse osmosis (RO) membrane. The results were
222 obtained from Figure 1. Error bars show the range of duplicate RO treatment experiments.

223 3.4 Hydrogen bonding

224 The cause of the variation in rejection among the small and uncharged pesticides was evaluated

225 by focusing on their molecular structure and functional groups. Overall, the presence of a

226 secondary amide functional group, −C(O)NH−, in pesticides was found to play a key role in

227 determining their removal. For example, the secondary amide pesticides that have atoms holding

228 a high partial negative charge showed the lowest rejection (34–65%) with the exception of

229 cyluron (Figure 4, Table 2). In contrast, the pesticides holding no amide functional groups were

230 highly rejected (83–96%) with the exception of methidathion (72%). The rejection of secondary

13
231 amide pesticides can be higher when they have an atom holding a high partial negative charge:

232 an ether functional group (−O−) (72–80%) or other strong electronegative (EN) atoms holding a

233 high partial negative charge (93–98%) (Table S3). The impact of a secondary amide group on

234 the rejection of pesticides can be explained by the role of hydrogen bonding. Hydrogen bonding

235 occurs between the hydrogen bond acceptor (HB-A), which has a basic electron lone pair, and

236 the hydrogen bond donor (HB-D), which is a partially stripped proton [37]. The secondary amide

237 of the pesticides contains a HB-A (oxygen atom) and HB-D (hydrogen atom); thus, hydrogen

238 bonding can commonly occur with a HB-D (hydrogen atom) and HB-A (oxygen atom) of the

239 membrane’s polyamide, respectively. Secondary amide pesticides that are attracted to polyamide

240 RO membranes through hydrogen bonding increase in concentration at the RO membrane

241 surface, which ultimately leads to low rejection.

(d) No amide
(c) 2° amide & an atom holding high PNC
(b) 2° amide & an ether functional group
(a) 2° amide & no other atoms holding high PNC

100 Fuberidazole
Acephate
Ethidimuron

Cycluron
Fluometuron
Rejection [%]

80 Carboxine
Linuron Propham
Pyracarbolid Methidathion

60 Chlorotoluron

Diflubenzuron

40
Diuron

28 30 32 34
242 Minimum projection area [Å2]
243 Figure 4 – Rejection of small (MPA = 27–35 Å2) and uncharged pesticides by the ESPA2
244 reverse osmosis (RO) membrane. The pesticides were classified into four categories: secondary
245 (2°) amide pesticides that have (a) no atoms holding a high partial negative charge (PNC), (b) an
246 ether group (high PNC), and (c) atoms holding a high PNC, and (d) pesticides that have no
247 amides. Error bars show the range of duplicate RO treatment experiments.

14
248 Table 2 – Molecular properties of low minimum projection area (MPA) (27–35 Å2) and
249 uncharged secondary amide pesticides that have (a) no atoms holding a high partial negative
250 charge, (b) an ether group. The parameters were calculated using Marvin software (ChemAxon,
251 Budapest, Hungary).
Name Diflubenz Diuron Chlorotol Cycluron Linuron Propham Pyracarb Carboxin
uron uron olid e
a
Structure

Classification ├──────────(a)──────────┤ ├──────────(b)──────────┤

2
MPA [Å ] 27.9 28.6 29.9 34.6 28.0 32.4 32.9 34.0
DM [Debye] 1.0 6.2 4.3 4.8 6.4 2.3 4.5 4.8
HB donor 2 1 1 1 1 1 1 1
HB acceptor 2 1 1 1 2 2 2 2
Rejection [%] 53 34 65 95 77 79 72 80
a –
252 Hydrogen bond (HB) acceptors and donors with a partial charge of below -0.15 and above 0.15 e at pH
253 8 are presented with their partial charge in red and blue, respectively. Other atoms with a partial charge of
–
254 below -0.15 or above 0.15 e are presented in green.

255 The strength of hydrogen bonds in amide compounds can be reinforced by cooperativity via

256 resonance of the hydrogen bonds (Figure 5a) in a similar way to amides in proteins [38, 39],

257 which may have made the major difference in rejection between secondary amide and no amide-

258 containing pesticides. The cooperativity of hydrogen bonding is likely to be the main cause of

259 the very low rejections of three secondary amide pesticides that have no atoms holding a high

260 partial negative charge (i.e., diflubenzuron, diuron, and chlorotoluron) (34–65%). The only

261 exception was cycluron (rejection = 95%), which holds a cyclooctane in its structure in contrast

262 to the other chemicals with a benzene (Table 2). Unlike benzene that has a planar structure,

263 cyclooctane is conformationally complex and can have because many of its conformers have

264 comparable energy [40]. The chair conformer is the most stable structure of cyclooctane, and the

265 MPA of cycluron (34.6 Å2 in Table 2) was determined based on its stable structure with a chair-

266 like confirmation of cyclooctane (Figure S6). In other words, the MPA of cycluron with other

15
267 conformations can be higher, which can result in a higher rejection of cycluron. However, these

268 speculated mechanisms cannot be further evaluated in this study, because cycluron was the only

269 small chemical that have a cyclooctane in its structure and an MPA of below 35 Å2. There could

270 be some other mechanisms underlying the high rejection of cycluron, thus, further investigation

271 is needed to decode its rejection mechanism.

272 It was also found that secondary amide pesticides can be highly rejected when another atom

273 holding a high partial negative charge is present in the secondary amide structure. The atoms

274 holding a high partial negative charge include an ether functional group (−O−) (e.g. propham)

275 (Table 2), a nitrile functional group (−C≡N) (e.g., flonicamid), trifluoromethyl functional group

276 (R−CF3) (e.g., flonicamid and fluometuron), and a sulfonyl functional group (R−S(=O)2−R’)

277 (e.g., ethidimuron) (Table S3). For example, linuron (C9H10Cl2N2O2, MPA = 28.6 Å2), which

278 has an ether functional group, is very similar to diuron (C9H10Cl2N2O, MPA = 28.0 Å2) in

279 structure and MPA (Table 2), whereas their rejection varied considerably (77% and 34% for

280 linuron and diuron, respectively). Although these functional groups are not dissociated, it can be

281 speculated that their high partial negative charge can cause electrostatic repulsion with HB-A

282 (oxygen atom) of the membrane’s amide that has a high partial negative charge (Figures 5b and

283 5c). The repulsion force may be greater than the attraction force induced by hydrogen bonding,

284 leading to high rejection.

16
285
286 Figure 5 – Cooperativity of hydrogen bonding and electrostatic repulsion between an amide
287 functional group of an RO membrane and (a) diuron, (b) propham, or (c) flonicamid.

288 Similar to the uncharged secondary amide pesticides, cooperative hydrogen bonding may be

289 sufficiently strong to impact the rejection of charged secondary amide pesticides. Thidiazuron is

290 a secondary amide pesticide with a negatively charged nitrogen atom at pH 8.0 (Table S3);

291 however, its rejection (43%) was considerably lower than similarly sized counterparts as

292 reported in Figure 1. In contrast, another similarly sized pesticide with a negative charge

293 (quinmerac) holds no amide functional group and showed considerably high rejection (98%).

294 Despite the limited number of samples for small and negatively charged pesticides (i.e., two), the

295 results suggest that hydrogen bond interactions may play a role in the rejection of charged

296 pesticides. Overall, the results obtained in this study suggest that secondary amide pesticides can

297 be poorly rejected by RO membranes due to the electrostatic attraction through hydrogen

298 bonding, whereas their rejection can be sufficiently high depending on the presence of other

299 atoms holding a high partial negative charge.

17
300 4 Conclusions

301 The results of this study indicated that the rejection of small and uncharged pesticides is mainly

302 governed by size exclusion, dipolar interaction, and hydrogen bonding. The amide group of

303 secondary amide pesticides can have the cooperativity of hydrogen bonding with amide

304 functional groups of an RO membrane, which can considerably render their rejection. The

305 presence of an atom holding a high partial negative charge in the secondary amide pesticides

306 leads to higher rejection than pesticides that have no atoms holding a high partial negative charge.

307 This suggests that secondary amide pesticides may be poorly rejected depending on the

308 possession of atoms holding a high partial negative charge. The findings are useful to predict the

309 rejection of unregulated TOrCs, including pesticides, in potable water reuse. In addition, this

310 study confirmed that all 158 pesticides consistently showed higher rejection than NDMA due to

311 the size exclusion and hydrogen bonding, which suggests that NDMA can be a conservative

312 performance indicator for removal of pesticides by RO processes.

313 5 ACKNOWLEDGEMENTS

314 This work was supported by JSPS KAKENHI Grant Number JP16KK0132 and JP18H01572.

315 We thank Hydranautics/Nitto for providing RO membrane samples for this investigation. This

316 work is also funded by Singapore Ministry of Education Academic Research Fund Tier 1

317 (M4011732.030), Start Up Grant of Nanyang Technological University (M4081915), Singapore

318 National Environment Agency (M4061617) and Singapore Ministry of Health’s National

319 Medical Research Council under its Clinician-Scientist Individual Research Grant (CS-IRG)

320 (MOH-000141) and Open Fund - Individual Research Grant (OFIRG/0076/2018).

18
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22
RESEARCH HIGHLIGHTS:

• Mechanisms underlying the poor rejection of small pesticides by RO were examined

• Size exclusion, and charge & dipolar interactions play a role in pesticide rejection

• 2° amides holding no high partial negative charge atoms were poorly rejected

• The low rejections were attributed to the cooperativity of hydrogen bonding

Declaration of interests

☒ The authors declare that they have no known competing financial interests or personal relationships
that could have appeared to influence the work reported in this paper.

☐The authors declare the following financial interests/personal relationships which may be considered
as potential competing interests: