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Mechanism of the Hydrolysis of Endosulfan Isomers Swatantra Pratap Singh, Saumyen Guha, Purnendu Bose, and Sooraj Kunnikuruvan J. Phys. Chem. A, Just Accepted Manuscript • DOI: 10.1021/acs.jpca.7b02012 • Publication Date (Web): 19 Jun 2017 Downloaded from http://pubs.acs.org on June 19, 2017

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The Journal of Physical Chemistry

Mechanism of the Hydrolysis of Endosulfan Isomers

1 2 3 4

by

5

Swatantra Pratap Singh†#, Saumyen Guha†*, Purnendu Bose†* and Sooraj Kunnikuruvan‡ †

6 7 8 9

‡

Department of Civil Engineering, Indian Institute of Technology Kanpur

Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur – 208016, INDIA

#Present Address

Department of Desalination and Water Treatment, Zuckerberg Institute of Water

Research, Ben-Gurion University of Negev, Sede-Boqer-89990, Israel

10 11

Revised Manuscript

12

for

13

Possible Publication

14 15

To

16

Journal of Physical Chemistry A

17

May 2017

18 19

*Corresponding Authors: Purnendu Bose Professor & Head Department of Civil Engineering Indian Institute of Technology, Kanpur Kanpur-208016 Email: [email protected]

Saumyen Guha Professor Department of Civil Engineering Indian Institute of Technology, Kanpur Kanpur-208016 Email: [email protected]

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1 ACS Paragon Plus Environment


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ABSTRACT:

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The objective of this study was to elucidate the mechanism of abiotic hydrolysis of ES-

23

isomers, i.e., Endosulfan-1 (ES-1) and Endosulfan-2 (ES-2) using a combination of

24

experiments and Density Functional Theory (DFT) calculations. Hydrolysis of both ES-1

25

and ES-2 resulted in the formation of Endosulfan Alcohol (ES-A). The rate of hydrolysis

26

was first order in all cases and increased with both pH and temperature. Rate expressions

27

describing the hydrolysis rates of ES-1 and ES-2 as a function of pH and temperature were

28

obtained and validated with independent data sets. Density Functional Theory (DFT)

29

calculations were performed using three functionals (M06-2X, B3LYP and MPW1K) and

30

both IEFPCM-UFF and SMD to introduce solvent effects. The geometry optimization of

31

molecules ES-1 and ES-2 showed that the free energy of ES-1 was larger and therefore, ES-2

32

was more thermodynamically stable isomer. DFT calculations also supported a hydrolysis

33

mechanism involving two successive attacks by OH- ions on C-O bonds resulting in the

34

attachment of OH- and the elimination of

35

was rate limiting.

36

supported the experimentally observed result of faster hydrolysis of ES-2 compared to ES-1.

37

The MPW1K functional along with IEFPCM-UFF for solvent effect simulated the free

38

energy of activation the closest for both ES-1 and ES-2 with less than 3% error with respect

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to the values computed from the experimental observations. Kinetic rate expression for ES

40

hydrolysis derived based on the proposed mechanism was identical to the rate expression

41

derived from experiments. It was deduced that the hydrolysis rates of both ES isomers may

42

vary over three orders of magnitude depending on the prevalent pH and temperature.

S O 3−

from the ES molecule but only the first attack

Calculations with all functionals and solvent effect combinations

43


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INTRODUCTION

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The organochlorine pesticide Endosulfan (ES) was introduced in 1950s as a replacement of

46

DDT and has since been widely used all over the world. 1 1 1 1 1 1 1 The largest users of this

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pesticide were India and USA.1

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pollutants (POPs) in the Stockholm convention in 2011,2 all the countries are phasing out ES

49

usage. ES is highly toxic to fishes and other aquatic species.3-5 Toxicity to mammals include

50

reported cases of gonadal toxicity, genotoxicity, and neurotoxicity.6-7 It is an endocrine

51

disrupter in humans with primary effect on the central nervous system. Amongst the reported

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cases of ES toxicity, the Kerala tragedy in India is well-known.8-10 ES was categorized as

53

‘extremely toxic’ by USEPA and EU, and ‘moderately toxic’ by WHO.

Since it’s induction into the list of persistent organic

54 55

ES is commercially available as a mixture of two diasteromers, α-Endosulfan (ES-1) and β-

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Endosulfan (ES-2), in approximately 7:3 ratio. While ES-2 has a symmetric structure, ES-1

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can have any one of the two possible asymmetrical enantiomers which may readily

58

interchange.11 This difference in molecular structure leads to large differences in physical

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properties such as, melting points, Henry’s constants, partition coefficients and activation

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energies for reaction.12-15 As a result, fate of these isomers differ in different environmental

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compartments.16 Air-water partitioning studies suggested faster volatilization of ES-1.12-13

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Long-range transport studies have also concluded more widespread transport of ES-1 in

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atmosphere.17-18 Irreversible conversion of ES-2 to ES-1 have been reported from symmetric

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ES-2 to asymmetric ES-1.11, 19

65 66

Abiotic hydrolysis of both ES-1 and ES-2 was reported in soil-water matrix in neutral to

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alkaline pH range.15,

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Endosulfan Alcohol (ES-A) was the primary abiotic hydrolysis product in both cases. In

20-24

The half-lives of ES isomers decreased with increasing pH.15



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most environmental systems, ES-2 hydrolysis rate was reported to be faster compared to ES-

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115, 20-21, 23 although, the later has more entropy due to asymmetrical structure.11

71 72

Expectedly, faster abiotic hydrolysis at higher pH was reported20-21, 23 for both ES isomers.

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Suspensions of sea sand, TiO2, R-Fe2O3, R-FeOOH, Laponite, and SiO2 were reported to

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enhance the hydrolysis of both the ES isomers, whereas suspended creek sediment inhibited

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hydrolysis.23 Microbially mediated conversion of ES in soil-water matrix was reported in

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aerobic environment through either hydrolytic or oxidative pathway, resulting in the

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formation of ES-A or Endosulfan Sulphate (ES-S) as the first intermediate.21, 25 In anaerobic

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environment, the oxidative pathway was absent and hydrolysis was the only first step of ES

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biodegradation pathway.26

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metabolites of ES isomers further down the pathway were Endosulfan Lactone (ES-L) and

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Endosulfan Ether (ES-E).

In both the environment, other reported biodegradation

82 83

Therefore, abiotic hydrolysis is an important first step of all natural attenuation processes for

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ES.16, 21 Degree of partitioning of ES to various environmental components and its transport,

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bio-accumulation and bio-magnification, all depend to a large extent on the rate and extent of

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abiotic hydrolysis because the hydrolysis product ES-A is less hydrophobic and relatively

87

non-toxic compared to the parent ES-isomers.

88 89

A quantum-chemical computational approach can be used for the investigation of reaction

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pathways and reaction intermediates in chemical systems.27-28 Density Functional Theory

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(DFT) is one such well-established quantum mechanical modeling approach in computational

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chemistry.29-30 Mechanism and pathway of acidic, neutral and alkaline hydrolysis of many

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organic compounds have been explored in recent years using DFT modeling.31-33


The

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objective of the present study was to elucidate the mechanism of abiotic hydrolysis of ES-

95

isomers using a combination of experimental investigations and DFT modeling, and explain

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faster hydrolysis of ES-2 compared to ES-1.

97 98

MATERIALS & METHODS

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Chemicals. Technical grade mixture of ES-isomers was kindly provided by United

100

Phosphorous Ltd., Ankaleshwar, India and pure isomers of ES were separated from it by thin

101

layer chromatography (TLC) in 7:3 hexane-acetone medium. Purity of ES-1 and ES-2 thus

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obtained was estimated using GC-ECD to be 98% and 97% respectively. Market grade ES

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(Endotaf 35) manufactured by Rallis India was purchased from the local market at Kanpur,

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India.

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standard 2,4,5,6- tetrachloro-m-xylene (>99% purity) were purchased from Sigma-Aldrich,

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India. All solvents used were of HPLC grade (>99% purity) and chemicals were of analytical

107

reagent grade (AR Grade).

Pesticide standards (ES-1, ES-2, ES-S, ES-A, ES-L and ES-E) and the internal

108 109

Hydrolysis Experiments. Experiments were conducted in borosilicate glass vials of 40 mL

110

volume with screw caps and Teflon-faced septa. Each vial contained de-ionized water and

111

measured amount of 0.02M phosphate buffer required to set the initial pH to the desired level.

112

Total volume of water and buffer was 40 mL, such that no headspace existed in the vials.

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Experiments were conducted at the following pH values: 6.0, 7.0, 7.5, 8.0, 8.5 and 9.0. Stock

114

solutions (50.0 mg/L) of ES-1 and ES-2 in acetone were used and desired volume was

115

introduced to each vial using a micro syringe. The vials were sealed and kept in a temperature

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controlled (within ±2ºC) water-bath equipped with a shaker table for mixing.

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predetermined time intervals, vials were removed in duplicate and processed immediately for

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extraction and analysis. 5 ACS Paragon Plus Environment

At


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Endosulfan Extraction. ES extraction procedure was adopted from Tiwari and Guha,34. A

120

measured volume of the sample was transferred to a vial containing ethyl acetate and 250 mg

121

NaCl. The ratio of sample to ethyl acetate volume was 1:4. The vial was tightly capped and

122

put on a vortex mixer (Vertex Genie-2, Scientific Industries, USA) for 10 minutes. The

123

contents were centrifuged (BiofugeStratos, Heraeus, Germany) at 3000×g for phase

124

separation. The ethyl acetate fraction was collected and passed through anhydrous sodium

125

sulfate to remove moisture. The percent recoveries of ES-1, ES-2 and ES-A were 98.6 ± 11.3,

126

97.4 ± 6.6 and 92.01 ± 7.3 respectively.

127 128

Analytical Methods. ES-1, ES-2 and ES-A concentrations were measured using a gas

129

chromatograph (Model Clarus 500, Perkin-Elmer, USA) equipped with an electron capture

130

detector and a capillary column (MXT-5) of size 30 m × 0.28 mm × 0.25 µm. Nitrogen was

131

used as the carrier gas at 68.95 kPa (10 psi) and as the makeup gas at 30 mL/min. Injector and

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detector temperatures were 250 and 375°C, respectively. The oven temperature program was

133

as follows; start at 120ºC hold for 1 minute, increase to 170ºC @ 10ºC/min hold for 8

134

minutes, increases to 220ºC @ 18ºC/min hold for 8 minutes, increase to 240ºC @ 12ºC/min

135

hold for 5 minutes.

136 137

Computational Methods. Density Functional Theory (DFT) computations were carried out

138

using Gaussian 09 program package.35 Calculations were done using M06-2X, B3LYP and

139

MPW1K functionals36-40 with 6-311++G (d, p) basis set. Geometry optimization of all the

140

chemical species involved in the hydrolysis reaction mechanism were performed in the

141

presence of water as solvent. In order to introduce solvent effects the integral equation

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formalism of polarizable continuum model with UFF radii (IEFPCM-UFF) and SMD solvent

143

models were used.41-44 All free energy computations were carried out at 298.15 K and 1 atm.


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More details of the computations of free energies, free energy barrier and rate constants

145

(using Eyring equation) are given in the supporting information (Section S2).

146

RESULTS & DISCUSSION

147

Experiments carried out at pH 7 and 32 ± 3ºC

148

ES-isomers Hydrolysis Kinetics.

149

demonstrated that abiotic hydrolysis of both ES-1 (Figure 1a) and ES-2 (Figure 1b) produced

150

stoichiometric, i.e., equi-molar quantities of ES-A. For experiments with ES-1, no ES-2 was

151

detected at any time during the experiment and vice versa. This showed that in the water

152

phase, there was neither spontaneous conversion of ES-2 to ES-1, nor ES-2 first converted to

153

ES-1 prior to hydrolysis as postulated by some.11 Rice et al. (1997) showed that temperature

154

dependent conversion of ES-2 to ES-1 was possible in the air phase. Since, there was no air

155

phase in these experiments, the results show, such spontaneous abiotic conversion is not

156

possible in water phase alone.12-13 (a) ES-1

(b) ES-2

0.8

Concentratiom, µmol L-1

Concentration, µmol L-1

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0.6 0.4 0.2 0.0

0.6 0.4 0.2 0.0

0

40 80 Time, Hours

0

120

40 80 Time, Hours

120

ES-A

ES-1 or ES-2

Total (Sum of ES-1, ES-2, and ES-A)

157 158

0.8

Figure 1.

Hydrolysis of ES-isomers at pH 7; (a) ES-1, and (b) ES-2.

159



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Formation of ES-A by abiotic hydrolysis of ES isomers was consistent with the earlier

161

studies.20, 23 In order to determine the rates of hydrolysis at various pH (6.0, 7.0, 7.5, 8.0, 8.5,

162

and 9.0), additional hydrolysis experiments were carried out at a constant temperature of 35ºC

163

for both the isomers, ES-1 (Figure S.1a and Figure S.1b) and ES-2 (Figure S.1c and Figure

164

S.1d). In all cases, the hydrolysis rate was first order and increased with pH. Hydrolysis rate

165

of ES-2 was faster than ES-1 at all pH. This is also reported in earlier studies,15, 23 although

166

the exact relation between OH- ion concentration and hydrolysis rate constant was not

167

explored earlier. The hydrolysis rate was expressed using the first-order expression,

168

dC = −k H [OH − ]a .C = −k .C dt

(Eq. 1)

169

Where C is the concentration of ES at time t, k (h-1) is the first order hydrolysis rate constant,

170

kH (h-1 mol-1 L) is the intrinsic ES hydrolysis rate constant, [OH-] is the k concentration (in

171

M) and ‘a’ is the empirical order of [OH-] interaction. The value of ‘a’ would show moles of

172

hydroxide required for the hydrolysis of one mole of ES. It was expected that the value of ‘a’

173

would be either one or two. The ‘k’ values for ES-1 and ES-2 are summarized in Table S1.

174 175

Effect of pH. Effect of pH on the hydrolysis rate was described by the Eq. 3. The values of

176

kH were computed using following logarithmic transformation,

177

Log (k) = Log (kH) + a.Log [OH-]

(Eq. 2)

178

Plots of Log [k] vs.Log [OH-] for ES-1 and ES-2 are shown in Figure 2a and Figure 2b,

179

respectively. These plots show that one mole of hydroxide is required for hydrolysis of one

180

mole of ES (i.e., a = 1). The coefficients of regression were high in both cases and the kH

181

values for ES-1 and ES-2 were 7.211×103 and 9.958×103 h-1mol-1 L, respectively.


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(a) ES-1 0

0

-1

-1 Log (k)

Log (k)

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-2

(b) ES-2

-2

-3

-3

R2=0.964 -4 -8.0 -7.5 -7.0 -6.5 -6.0 -5.5 -5.0

R2=0.962 -4 -8.0 -7.5 -7.0 -6.5 -6.0 -5.5 -5.0

Log [OH-]

Log [OH-]

182 183 184

Figure 2.

Relation Between ES Hydrolysis Rate Constant (kH) and [OH-] Concentration; (a) ES-1, and (b) ES-2

185 186

Effect of Temperature. In order to determine the effect of temperature on kinetics of

187

hydrolysis, experiments were conducted at temperatures of 10, 20, 30 and 40ºC at a constant

188

pH of 9.0. The data is summarized in Figure S2a (for ES-1) and Figure S2b (for ES-2). The

189

hydrolysis rates fitted well with the first order model in all cases, with the intrinsic rate of

190

hydrolysis increasing with temperature. Modified Arrhenius equation45 was used to simulate

191

the effect of temperature on the intrinsic rate of hydrolysis as follows,

192

k H = k H 2 0 .θ

(Eq. 3)

(T − 20 )

193

Where, kH20 (h-1 mol-1 L) is the intrinsic ES hydrolysis rate constant at 20ºC, θ is the

194

temperature coefficient and T is the temperature in ºC. The Eq. 1 becomes,

195

dC = −k H 20 .θ (T −20) .[OH − ].C dt

(Eq. 4)

196

The rate parameter kH20 can be computed using the values of kH computed at different

197

temperature using the logarithmic transformation of Eq. 3 as follows,

198

Log ( k H ) = Log ( k H 20 ) + Log (θ ).[T − 20]


(Eq. 5)


199

Plots of Log [kH] vs [T – 20]ºC for ES-1 and ES-2 are shown in Figure 3a and Figure 3b,

200

respectively. The coefficient of regression was very high in both the cases. The values of kH20

201

and θ for ES-1 were 7.35 × 103 h-1mol-1 L and 1.099, respectively. The same values for ES-2

202

were 1.48 × 104 h-1mol-1 L and 1.107, respectively. The difference in the values of the

203

temperature constant ( θ ) for ES-1 and ES-2 were not statistically significant at 95%

204

confidence level. Therefore, an average value of the constant θ = 1.103 can be used in Eq. 4

205

for both the isomers of ES.

206 207

The value of kH20 for ES-2 was nearly double compared to that of ES-1. The values of kH20

208

and θ were used to compute the k values for ES-1 and ES-2 at 298.15 K and the free energy

209

barriers were computed using Eyring equation (Table 1).

(a) ES-1

5.0

5.5

Log (kH)

4.0 3.5 R2=0.987

4.0

3.0

-15 -10 -5 0

R2=0.979 -15 -10 -5 0

5 10 15 20 25

Figure 3.

5 10 15 20 25

(T - 20)ºC

(T - 20)ºC

210

212

4.5

3.5

3.0

211

(b) ES-2

5.0

4.5 Log (kH)

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Relation Between ES Intrinsic Hydrolysis Rate Constant (kH) and Temperature; (a) ES-1, and (b) ES-2.

213 214

Thermodynamic Stability of ES-isomers. Geometry optimization of both ES-1 and ES-2

215

molecules were carried out using DFT calculations. These calculations indicate that the


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216

free energy of the ES-1 molecule is about 3.26 kcal mol-1 larger as compared to the ES-2

217

molecule. DFT calculations indicates that the enthalpy of ES-2 is ~3.69 kcal mol-1 smaller as

218

compared to ES-1. Whereas the entropy of asymmetrical ES-1 (0.135 kcal mol-1 K-1) is

219

larger than symmetrical ES-2 (0.133 kcal mol-1 K-1), which is consistent with earlier studies11.

220

This indicates that the enthalpy is the major factor for the thermodynamic stability of ES2.

221

The higher thermodynamic stability of ES-2 molecule could be attributed to the interaction

222

between the orbitals of two oxygen atoms (O1 and O2 in Figure S4b and S4d) with the

223

double bonded carbon atoms (Cx and Cy in Figure S4b) which lie in the same plane. In case

224

of ES-1 molecule the orbital of one oxygen atom is away from the double bonded carbon

225

(Figure S4a and S4c). The higher melting and lower Henry’s law constant of the ES-2

226

molecule is attributable to the higher thermodynamic stability of ES-2 compared to ES-1.

227 228

Table 1. Comparison of free energy barriers (kcal mol-1) for the first step of hydrolysis of ES

229

isomers (formation of Intermediate-1) using various functionals with 6-311++G(d,p) basis set

230

and IEFPCM-UFF or SMD solvent model (298.15 K and 1 M) with the experimental free

231

energy of activation at 298.15 K. The relative error for the computed barriers with the

232

experimental valve is shown in parenthesis.

233

Elucidation of Reaction Mechanism. Based on experimentally obtained rate expression for

234

ES hydrolysis (Eq. 4), it was presumed that the rate-limiting step in ES hydrolysis involves a Experimental Free Energy of Activation

B3LYP IEFPCMUFF

SMD

MPW1K IEFPCMUFF

SMD

M06-2X IEFPCMUFF

SMD

ES-1→I-1

26.29

23.83 (-9.5%)

29.34 (11.6%)

27.03 (2.8%)

34.01 (29.4%)

23.97 (-8.8%)

31.25 (18.9%)

ES-2→I-1

25.87

21.3 (-17.7%)

27.99 (8.2%)

25.29 (-2.2%)

33.02 (27.6%)

22.42 (-13.3%)

29.73 (14.9%)



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

235

single hydroxide attack on the ES molecule. First, the possibility of nucleophilic attack by

236

hydroxide on the sulphur atom of ES molecule was investigated through DFT calculations.

237

The nucleophile was repelled away from the sulphur centre due to the high steric interactions,

238

probably due to the lone electron pair of sulphur atom (Figure S3 and S6).46 The other

239

reasons, why nucleophilic attack at sulphur was ruled out are discussed in detail in supporting

240

information (Section S3). Finally, an SN2-type attack by hydroxide is proposed on either C1 or

241

C2 atom (Figure 4) for the ES-2 molecule and formation of intermediate-1 or 2, where both

242

nucleophile and the leaving-group are present. In case of the ES-1 molecule, an initial step

243

involving a SN2-type attack on the C1 atom resulted in the cleavage of C1-O bond and

244

formation of the intermediate-1 and similarly, an attack on the C2 atom resulted in the

245

formation of the intermediate-2 (Figure 4). Then the intermediate-1 or 2 undergo further

246

reaction with another hydroxide to form ES-A. The possibility of H2O (instead of OH-)

247

acting as a nucleophile was investigated by specifying an attack by H2O molecule on the C1

248

atom of ES-2 (Figure 4). The free energy barrier for such an attack is very high at 55.72 kcal

249

mol-1. This is also consistent with experimental results15 that show little or no hydrolysis of

250

ES below pH 5.

251 252

The optimized structures of ES-1, ES-2, ES-A, and possible intermediates were obtained

253

through DFT calculations. These structures and the corresponding free energy profile are

254

presented in Figure 5. Free energy barrier for the rate determining step (OH- attack on ES-1

255

and ES-2) was computed by employing M06-2X, B3LYP and MPW1K functionals with two

256

solvent models, IEFPCM-UFF and SMD 36, 38, 44 and results are shown in Table 1 along with

257

the same computed from the experimental observations. The table also shows the relative

258

error (in %) of the computed values with respect to the experimental values. Free energy

259

barrier obtained by using B3LYP functional was comparable with that obtained using M06-


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260

2X functional but MPW1K functional with IEFPCM-UFF solvent model produced the most

261

accurate simulation of the experimental activation energy for both ES-1 and ES-2 with

262

relative error of less than 3%. Free energies of activation obtained with SMD solvent model

263

was much larger for all three functionals in comparison to that of IEFPCM-UFF solvent

264

model. Therefore, the free energy of activation reported here are obtained using MPW1K

265

functional and IEFPCM-UFF solvent model unless otherwise specified. One may note, in all

266

models, irrespective of the absolute values, the free energy barrier for ES-1 was always larger

267

than ES-2. This is consistent with widespread reports15, 20-21, 23 and our experimental results

268

of faster hydrolysis rate of ES-2 compared to ES-1.

269

Cl Cl

OH

Cl

C1 C O S Cl Cl 2O O Cl

Cl Cl

OH

Cl

Cl Cl Cl

C C2 1 Cl Cl O O O S Cl

ES-1 (C-1)

ES-2 (C-1)

k1a3b

k1a3f

Cl Cl Cl Cl Cl Cl

k2a3b

OH C1 C2 O S Cl Cl O O Cl ES-1 (C-2)

k2a3f

k1b3b

k1b3f

Cl Cl Cl Cl

O

Cl

Cl Cl Cl Cl

OH C1 C2 O O O S

ES-2 (C-2)

ClCl

OH C1 OH C2 OO S

Cl

k2b3b

k2b3f

OH C1 O S O C2 OH O

Intermediate-2 (I-2)

Intermediate-1(I-1) k3a4b k3a4f

k3b4b

k3b4f

ClCl Cl

C1 OH C2 OH

+

SO32-

270

Cl Cl Cl ES-A

271

Figure 4. Proposed Mechanisms for Hydrolysis of ES-1 and ES-2 (C1 (CH2) and C2 (CH2)

272

are the possible attack sites). 13 ACS Paragon Plus Environment


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273 274

In case of ES-1, an initial attack on the C1 atom was found to have a free energy barrier of

275

27.03 kcal mol-1. In contrast, an initial attack on the C2 atom of ES-1 (Figure 5) was found to

276

have a free energy barrier of 34.01 kcal mol-1, which is attributed to steric hindrance

277

associated with such an attack. In case of ES-2 molecule, the initial attack by hydroxide can

278

occur either at C1 or C2 atoms with identical free energy barrier of 25.29 kcal mol-1. The

279

presence of two identical reaction centers C1 and C2 increases the probability of nucleophilic

280

attack on ES-2. Whereas for ES-1 nucleophilic attack at C2 was not favored as indicated by

281

the free energy barrier (34.01 kcal mol-1), this increased probability of

282

on ES-2 is also contributes to the faster hydrolysis of ES-2 compared to ES-1. The

283

enhancement in rate here is equivalent to lowering the free energy barrier for the reaction by

284

about RT ln2 (0.4 kcal mol-1 at 298.15 K). It is to be mentioned here that while studying the

285

kinetics this has been taken care.

nucleophilic attack

286 287

The free energy barriers for ES-1 and ES-2 hydrolysis computed from the experimental

288

observations were 26.29 kcal mol-1 and 25.87 kcal mol-1, respectively. The apparent free

289

energy barriers for the rate-limiting step determined from DFT calculations described above

290

were 27.03 kcal mol-1and 25.29 kcal mol-1for ES-1 and ES-2, respectively. The agreement

291

between experimental and DFT-calculated values were within 3% leading to the conclusion

292

that the rate-limiting step during hydrolysis involves a hydroxide attack on the C1 carbon of

293

ES-1 and on either C1 or C2 carbon of ES-2. The initial attack is followed by a second

294

hydroxide attack at the other carbon atom, leading to the formation of the hydrolyzed product

295

ES-A by elimination of

296

hydroxide, this also explains the linear dependence (a=1 in Eq. 1) of first order rate

297

expressing on [OH-] although two hydroxides are required to form the product ES-A.

SO

2− 3

(Figure 4). Since, the rate limiting step is the attack of the first


Page 15 of 25

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298 299

The hydrolysis mechanism proposed above has some literature support; cyclic sulphites are

300

considered to be similar to epoxides,47 which undergo ring-opening reaction with

301

nucleophilic attack on the β-carbon.46-48 Further, the nucleophilic attack in cyclic sulphites is

302

known to occur at C-centre due to the good leaving group character of the sulphur moiety.47

303 304

Theoretical Kinetics. Kinetic rate expression (full derivation given in SI) for the hydrolysis

305

of ES-1 and ES-2 can be derived based on the mechanism identified from the DFT studies,

306

For C1 attack ES − 1 + OH −

307

k

1a 3 f  → ←  k 1a 3 b

For C2 attack ES − 1 + OH −

308

k

1b 3 f  → ← k 1b 3 b

I1 + OH − I 2 + OH −

k

3a 4 f  → ←  k 3a 4b

k

3b 4 f  → ←  k 3b 4 b

ES − A + SO32− ES − A + SO32−

(Eq. 6) (Eq. 7)

309 310

Where, k1a3f, k1b3f are the forward rate constants and k1a3b, k1b3b are the backward rate constants

311

for the conversion of ES-1 to I1 and I2 through OH- attack at C1 and C2 carbons respectively

312

(Figure 4). Thus,

313

d [ ES -1]

314

dt

= {k1a3b [ I1 ] + k1b3b .[ I 2 ] − k1a3f .[ ES − 1] − k1b3f .[ ES − 1]}.[OH −]

(Eq. 8)

315

Applying steady state for concentration of I1 and I2 and substituting value their values in Eq. 8 (Rate

316

constants defined in Figure 4),

317 318

d [ ES-1] dt

 ( k + k1b3f )( k1a3b + k1b3b )  k1b3b ( k 3a4b + k 3b4b ) =  1a3f − ( k1a3f + k1b3f )  [ ES-1]  OH −  + [ ES-A ] SO 32−  ( k1a3b + k1b3b + k 3a4f + k3b4f )  ( k1a3b + k1b3b + k 3a4f + k3b4f ) 

(Eq. 9)

319



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320

Since k1a3b

Mechanism of the Hydrolysis of Endosulfan Isomers - ACS Publications

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