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Take an Advantage of Sustainable Forest Resource in Agriculture: A Value-added Application of Volatile Turpentine Analogues as Botanical Pesticides based on Amphipathic Modification and QSAR Study Jian Li, Jingjing Li, Yanqing Gao, Shibin Shang, Zhanqian Song, and Guomin Xiao ACS Sustainable Chem. Eng., Just Accepted Manuscript • DOI: 10.1021/ acssuschemeng.6b00819 • Publication Date (Web): 14 Aug 2016 Downloaded from http://pubs.acs.org on August 15, 2016

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ACS Sustainable Chemistry & Engineering

Take an Advantage of Sustainable Forest Resource in Agriculture: A Value-added Application of Volatile Turpentine Analogues as Botanical Pesticides based on Amphipathic Modification and QSAR Study Jian Li, &† Jingjing Li, &† Yanqing Gao *‡, Shibin Shang, # Zhanqiang Song, # and Guomin Xiao **§ †

College of Forestry, Northwest A&F University, Number 3, Taicheng Road,

Yangling 712100, Shaanxi, People’s Republic of China. ‡

College of Plant Protection, Northwest A&F University, Number 23, Xinong Road,

Yangling 712100, Shaanxi, People’s Republic of China. #

Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry,

Longpan Road, Nanjing 210042, Jiangsu, People’s Republic of China. §

School of Chemistry and Chemical Engineering, Southeast University, Number 2,

Dongnan daxue Road, Nanjing 211189, Jiangsu, People’s Republic of China. Corresponding author: *

(Y.

G.)

Phone:

+86-029-87091977.

Fax:

+86-029-87082392.

E-mail:

[email protected] . **

(G.

X.)

Phone:

+86-025-52090612,

Fax:

+86-025-52090612.

E-mail:

[email protected] &

The authors contributed equally to this work and should be considered co-first

authors.

A

ACS Paragon Plus Environment


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ABSTRACT: As a continuous study on the integrated application of volatile β-pinene as an abundant bioresource, the further and broader activity assessment of β-pinene analogues was necessary. Based on previous research, the larvicidal activities were carried out against two agricultural insect pests Plutella xylostella and Mythimna separata. In accordance to the overall insecticidal effect, it was remarkable

that compounds 5k and 5l demonstrated extreme activity, with LC50 values 1.846 and 1.621 µg/mL against Plutella xylostella. The preliminary structure-activity relationship (SAR) was analyzed, and compounds with appropriate amphipathic feature displayed more desirable performance. Meantime, the quantitative structure-activity relationship (QSAR) model (R2 = 0.9485, F = 82.94, S2 = 0.0067) was built. The model indicated the most important structural feature was the µc value, which represented the total hybridization components of the molecular dipole. The work provided a potential and alternative approach to take an advantage of forest resource in agriculture. Keywords: Turpentine, β-pinene, Insecticidal activity, QSAR

B


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INTRODUCTION Take into account food production and security, rational prevention of some crop-threatening pest is critical for modern agriculture.1,2 Plutella xylostella, for instance, a serious and popular lepidoptera pest, nibbles leaves of cruciferous vegetation, which results in great deal of damage to many vegetable crops.3 In the process of crop protection against pest, some types of chemical pesticide played a crucial role. However, there are some disadvantages, such as, the side effect to no-target organism such as human, animal, plant and insect resistance, to restrict the integrated pest management.4,

5

Thus, some novel and eco-friendly pesticides are

needed to be explored urgently, and the bio-renewable natural resources provide some clues. 6,7 In secondary metabolites, some single compounds can be obtained, such as terpenoids, alkaloids and flavonoids, which can be used as lead compounds to develop the potential pesticides of high efficient, less resistance and lower pollution.8,9 Pines are widely distributed around the world, and the integrated application of this forest resource deserves the widespread and deep research. Resin, secondary metabolites secreted from canals, includes a diverse array of resin acids and more complex volatile oil. In the periodic process of resin tapping, the resin can outflow repeatedly to resist external insect bites and other damage. As an abundant ingredient of resin, turpentine is monoterpene mixture, including α-pinene, β-pinene, camphene, myrcene and so on. These compounds have excellent performance and potential for use in many fields.10,11 For instance, β-pinene and its analogues have agricultural activities, such as antifeedant,

12

repellent13,14 and antimicrobial. It was promising to

develop some eco-friendly pesticide from β-pinene, which can be applied in the C



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control of crop insect pests. However, during the design and modification of potential pesticides derived from β-pinene, there are many factors that need to be considered.15 Firstly, the primary factors in the activity are smooth contact and permeabilisation between the insecticide and action target .16,17 In order to improve the amphipathic characteristic and better biphasic solubility, the ester and amide groups were introduced into β-pinene. In addition to monoesters, diesters and bisamides were prepared through Diels-Alder (D-A) reaction of β-pinene and maleic anhydride (an agent proved to have antimicrobial activity).18 Secondly, some new technology is needed searching to reduce the time and cost in the activity screening from mickle candidates for the crop diseases control.19 QSAR, an efficient mean for biological activity screening and mechanism of action, was carried out through some quantification software packages. After the essential structural features for the activity were defined, the study on the mechanism of action should be more targeted. The objective of this study was to continue expanding the application of volatile β-pinene in high value-added field, and develop broad-spectrum biological activity in agriculture.

D


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MATERIALS AND METHODS Synthetic procedures and identification β-pinene (1) was obtained from a commercial source (Jiangxi Jishui Hongda natural spices Ltd.). All the other chemicals used in the synthesis were of reagent grade, and the purity was chemically pure (≥ 99.5 %). Nicolet IS10 spectrophotometer was applied for the Fourier transform infrared (FT-IR) spectra. Bruker AV-300 nuclear magnetic resonance spectrometer was used to measure the 1H NMR spectra with CDCl3 or DMSO-d6 as the solvent and TMS as an internal standard. Agilent-5973 spectrophotometer was utilized for the MS spectra. Bruker Q-TOF mass spectrometer equipped with electrospray ionization source was applied for ESI mass spectral data. Thin-layer chromatography (TLC) was employed to monitor progress of reactions and determine the reaction whether to end, which was carried out by Merck silica gel 60 GF254 plates, with eluent of petroleum ether/ethyl acetate (v/v = 8:1) and visualized under 254 nm UV light. Synthesis of 4-isopropylcyclohexa-1, 3-dienecarboxylates (compounds 5a-n). β-pinene was used as raw material, through alkaline oxidation, dehydration, isomerism, and acylation, the nopinic acid (2), dehydrocumic acid (3), chloride (4) were prepared according to the method described previously (Li et al., 2015).20 The 12 resulting compounds 5a-5l were obtained by esterification reaction between dehydrocumic acid chloride and corresponding alcohols (molar ratio=1:1). The alcohols used in the reaction were aliphatic alcohols (such as methanol, ethanol, propanol, butanol, pentanol, glycol, diethylene glycol and so on) and alicyclic alcohol E



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(cyclohexanol). In addition, the above dehydrocumic acid chloride (4) was added drop wise to the two diol (molar ratio=2:1), respectively. Using the same procedure discussed above, the other two ester 5m and 5n were prepared. The preparation and the structures of title compounds were shown in Figure S16 of Supporting Information, where R1 represented the chain hydrocarbon of alcohols, R2 represented the bottom group. Synthesis of dialkyl 1-isopropyl-4-methylbicyclo [2.2.2] oct-5-ene-2, 3-diamides (compounds 7a-d)

The four resulting diamide derivatives 7a-d were prepared through Diels–Alder reaction and amidation.(21) A solution of β-pinene (50 g, 0.37 mol), maleic anhydride (20.0 g, 0.2 mol) and metaphosphate (5.0 g, 0.063 mol) was catalyzed with micro iodine. The reactants were heated to 140 °C for 6 h. The above resulting compounds were dissolved in dichloromethane and added excess amines (methylamine, ethylamine, propylamine, and isopropylamine) at low temperature. The reactant was stirred at ambient temperature overnight. Firstly, the reactants were treated with dilute hydrochloric acid, which removed the base produced in the reaction. Secondly, the reactants were treated with sodium bicarbonate solution, which eliminated excess acid. Finally, the reactants were treated with distilled water. The four resulting diamide derivatives 7a-d from β-pinene were obtained. Synthesis

of

dialkyl

1-isopropyl-4-methylbicyclo

[2.2.2]

oct-5-ene-2,

3-

dicarboxylates (compounds 8a-e) Through the similar process described above, a solution of β-pinene (27.0 g, 0.2 F


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mol) and metaphosphate (2.7 g, 0.034 mol) were added to 0.1 mol the above maleates (methyl maleate, ethyl maleate, propyl maleate, isopropyl maleate, N-butyl maleate), and the reaction was catalyzed with micro iodine. After purification by silica gel chromatography with ethyl acetate/petroleum ether (v/v = 1:10) as eluent, the five resulting compounds 8a-8e were obtained. Larvicidal activity The larvicidal activities of β-pinene analogues against P. xylostella and M. separate were evaluated as described in the literature procedures.(22) In the evaluation, the mortality percentage of series concentrations of dimethylsulphoxide solution was mean value obtained through three independent experiments, and the standard deviations (SD) values were limited within ± 5%. Based on the series mortality percentage, the LC50 results were calculated by SPSS statistic program version 17.0.23 Flubendiamde (a commercial pesticide) was used as a positive control, and pure dimethylsulphoxide without the title compounds was tested as the negative control. Larvicidal activity of derivatives of β-pinene analogues against P. xylostella The larvicidal activity of derivatives of β-pinene analogues against P. xylostella was tested by the dipping method in line with the reported methods.24, 25 Fresh and clean cabbage leaves were cut into leaf disks (1 cm in diameters), and were dipped into the sample solution for 10 s. After naturally air drying on filter paper, the treated leaf disks were placed in cylindrical bottles, and ten 2nd-instar larva were placed. The larva were reared and observed continuously for three days after the treatment. Larvicidal activity of derivatives of β-pinene analogues against M. separata G



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The larvicidal activity of derivatives of β-pinene analogues against M. separata was tested by the dipping method, in line with the reported methods26, 27 Fresh and clean corn leaves were cut into leaf squares (1 × 1 cm), and were dipped into the sample solution for 5 s. After naturally air dried on filter paper, the leaf discs were placed into Petri dish. The larva were reared and observed continuously for three days after the treatment. The relative mortality percentage (RMP) of larvae after exposure to test chemicals was calculated by Eq. (1) RMR (%) = (MR – CMR)/CMR × 100

(1)

where MP and CMP were the mortality rate of the test samples and the negative control, which were calculated by the average mortality percentage. The LC50 values were computed by probit analysis with SPSS statistic program version 17.0 (SPSS Inc.), through which the regression equation y=a+bx of insecticidal activity could also be obtained. Building and validation of the QSAR model The building and validation of the QSAR model was in accordance with the common procedure. Briefly, optimization of the most stable configuration were obtained with a Gaussian 03W package of programs (Gaussian Inc.),28 and all the molecular descriptors were calculated by CODESSA 2.7.15 (The copyright of this version is held by the Center of Heterocyclic Chemistry, University of Florida, U.S.A.). For determination of the most significant structural features for larvicidal activity against P. xylostella, the heuristic analysis was to build the QSAR model. H


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During the model development process, the R2 (the squared correction coefficient), S2 (the squared standard error of the estimates), and the F (Fisher significance ratio) were determined to assess the predictability of a given model. In this study, a model displaying good predictability between compound structure and log LC50 values was developed. To ensure high quality of the final QSAR results, two verification methods, internal validation and the “leave-one-out” cross-validation were used for determination.29 RESULTS AND DISCUSSION Synthesis The synthesis process of derivatives from turpentine-maleic anhydride was two-step reaction, which were D-A reaction and esterification/amidation. In order to facilitate the subsequent separation and purification, we have tried both orders of the two reactions. It was shown that the suitable process for ester compounds 8a-e was first esterification and then D-A reaction. However, the appropriate reaction scheme was converse for compounds 7a-d. The result was possibly due to steric hindrance of alcohol groups. There are many acid catalysts that can be used for esterification, such as toluenesulfonyl chloride, sulfuric acid, and p-toluenesulfonic acid. In order to obtain a high yield of title compounds, p-toluenesulfonic acid was used as the acid catalyst for esterification. Larvicidal activity and structure-activity relationships (SAR) of title compounds against P. xylostella. From Table 1, the β-pinene analogues displayed good larvicidal activity against P. I



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xylostella, which was more significant compared with compound 3. To be specific, compounds with free hydroxyl (5k and 5l) at 1-carboxylates demonstrated extremely activity, with LC50 values 1.846 and 1.621 µg/mL against P. xylostella, which were similar to flubendiamde, a commercialized agriculture insecticide. The diester compounds 8a-e had an RMR value of 96 % against P. xylostella at 20 µg/mL. In regard to different kinds of β-pinene analogues, the level of larvicidal activity was diesters (8a-e) > bisamides (7a-d) > monoesters (5a-n). Table 1 Larvicidal activity of compounds against P. xylostella Mortality rate (%) at a concentration of (µg/mL) Compound

40

20

10

5

2.5

1

LC50

y=a+bx

R2

log LC50

3

85

49

23

13

10

6

22.079±d

y=-2.416+0.109x

0.981

1.344

5a

100

55

24

14

9

6

17.315±c

y=-2.833+0.164x

0.987

1.238

5b

100

57

29

18

10

6

16.425±c

y=-2.601+0.158x

0.954

1.216

5c

100

90

65

40

29

15

7.574±bc

y=-1.530+0.202x

0.970

0.879

5d

100

70

43

28

17

11

12.679±c

y=-1.945+0.153x

0.959

1.103

5e

100

92

75

53

33

23

5.582±bc

y=-1.147+0.205x

0.962

0.747

5f

100

91

72

47

30

17

6.562±bc

y=-1.385+0.211x

0.955

0.817

5g

100

89

57

34

23

15

8.779±bc

y=-1.748+0.199x

0.994

0.943

5h

100

93

72

46

31

19

6.326±bc

y=-1.386+0.219x

0.979

0.801

5i

100

92

67

43

29

17

7.035±bc

y=-1.485+0.211x

0.982

0.847

5j

100

88

55

34

22

15

9.063±bc

y=-1.759+0.194x

0.994

0.957

5k

100

97

86

67

56

42

1.846±b

y=-0.392+0.212x

0.990

0.266

5l

100

97

87

70

56

43

1.621±b

y=-0.351+0.216x

0.985

0.210

5m

100

67

42

27

16

11

13.224±c

y=-1.976+0.149x

0.955

1.121

5n

45

22

15

8

5

0

41.365±d

y=-3. 060+0.074x

0.989

1.617

7a

100

92

75

53

34

23

5.531±bc

y=-1.128+0.204x

0.963

0.743

7b

100

94

78

54

35

21

5.259±bc

y=-1.210+0.230x

0.962

0.721

7c

100

97

82

60

40

30

3.989±b

y=-0.978+0.245x

0.998

0.601

7d

100

94

80

58

39

26

4.515±b

y=-0.986+0.218x

0.961

0.655

8a

100

97

83

61

42

30

3.808±b

y=-0.940+0.247x

0.988

0.581

8b

100

97

87

67

40

30

3.515±b

y=-0.964+0.274x

0.960

0.546

8c

100

96

84

65

41

31

3.599±b

y=-0.862+0.240x

0.966

0.556

8d

100

97

83

64

46

37

3.039±b

y=-0.681+0.224x

0.994

0.483

8e

100

98

85

69

49

33

2.877±b

y=-0.738+0.257x

0.986

0.459

Flubendiamde

100

100

100

96

81

60

0.442±a

y=-0.314+0.709x

1.000

-0.355

J


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Values in columns followed by similar letters were not signiﬁcantly different according to Fisher’s protected LSD test (P = 0.05)

Before the insecticides exert larvicidal activity, the first step is the penetration of the cell wall and then contact the target.30, 31 There are some structural characteristics influencing insect wall permeabilization, such as the amphipathic feature and steric hindrance of insecticides. Based on the permeabilization mechanism, the analogues with appropriate hydrophobic chain length would penetrate insect body wall and possess better larvicidal activity. In order to increase the permeabilization property of the lead compound (3, dehydrocumic acid), the ester and amide groups can be introduced for structure modification, which strengthened the contact and interaction between chemicals and insect body wall, and leaded to a better insecticidal activity. As showed in Table 1, the level of larvicidal activity was diesters (8a-e) > bisamides (7a-d) > monoesters (5a-n), which was in compliance with the mechanism described above. For diesters (8a-e) and bisamides (7a-d), with the increase in the carbon chain length of the R substituent, the activity of compounds was higher, that was, 8e > 8d > 8c > 8b > 8a, 7d > 7c > 7b > 7a. For monoester compounds 5a-n, from compounds 5a to 5e, the activity of compounds was gradually increasing, but from compound 5f to 5n, the activity of compounds gradually decreasing in general. It was noteworthy that the butyl ester 5e possessed the most appropriate hydrophobic chain length (R1=C4). The butyl ester (5e-h) exhibited an apparent steric hindrance affected rule, and the larvicidal activity was N-butyl (5e) > isobutyl (5f) ≈ sec-butyl (5h) > tert-butyl (5g). Based on the above discussion, it was the amphipathic nature of compounds that was the most important factor in determining activity when carbon atoms for the K



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substituent were less than four; otherwise, the steric effect played an essential role. It was needed to be explained that compounds 5k and 5l displayed outstanding larvicidal activity, which could due to electrostatic interaction caused by appropriate lipid chain length and free hydroxyl.32 In this study, the most appropriate lipid chain length of the substitute was C4, and the compounds with log P value range 3.5-5.0 obtained the most appropriate hydrophilic and lipophilic property. QSAR study on larvicidal activity against P. xylostella The calculation and selection of several significant molecular descriptors from six groups of descriptors was a part of the model development process. The most important descriptors in this work were electrostatic and quantum-chemical descriptors. Several regression approaches available have been attempted to establish relationship between activity and molecular descriptors, the heuristic regression was chosen to obtain a QSAR model with satisfactory values of R2, F and S2. The “breaking point” rule was applied to determine the number of the descriptors. In the linear fit of R2 value and descriptors number, the R2 value trend was significantly different before the four and after. Additionally, the number of the molecular descriptors met the rule given by Eq. (2) k ≤ (n/3) - 1

(2)

which means that the number of molecular descriptors k is no more than one third of the sample number plus one [(n/3)-1]. Finally, the 4-descriptors QSAR model was determined as the best model. In supplementary material, the four significant descriptors and their values were listed.

L


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The final quantitative model had the following statistical characteristic: R2 = 0.9485, F = 82.94, S2 = 0.0067. The four descriptors were shown in Table 2. The experimental and predicted log LC50 values were listed in Supporting Information, and the experimental and predicted log LC50 values were compared in Fig. 1. The equation of 4-descriptors QSAR model was described in the following Eq. (3). The QSAR model contained the sample number N = 23, and satisfactory values were R2 = 0.9485, F = 82.94, S2 = 0.0067. In Eq. (3), a positive sign (+) appeared in the model indicated that descriptor value had a positive correlation with log LC50, meant that the log LC50 value was higher as the descriptor value was larger. In contrary, a negative sign (-) indicated a negative correlation. log LC50 = -3.7956 - 0.5362 × µc

+ 5.7937 ×nf - 6.5242 ×

+1.798 × ∆ Hf

(3) Table 2 The best four-descriptor model. Descriptor No.

X

±△X

t-Test

Descriptor

0

-3.7956e+00

6.3548e-01

-5.9729

Intercept

1

-3.9610e-02

2.1725e-02

-1.8233

µh a

2

5.7937e+00

5.7262e-01

10.1179

nf b

3

-6.5242e+00

8.1608e-01

-7.9946

c

4

4.8790e-01

3.4843e-02

14.0025

∆Hf d

a

Tot point-charge comp. of the molecular dipole b No. of occupied electronic levels of atoms c Max net atomic charge for a H atom

Final heat of formation of atoms

M


d


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Fig. 1 Experimental log IC50 versus predicted log IC50 The validation of the established QSAR model was carried out by two validation methods. The internal validation method was described as: the compounds 1, 4, 7, etc. was assigned to group A; compounds 2, 5, 8, etc. was to group B; and other compounds belonged to subset C. Two of these three groups were selected randomly as the training set, and the other group was the test set. The values of the corresponding test sets were predicted by the obtained correlation equation from the training set using the identical descriptors. The results of internal validation were listed in Supporting Information. The difference between RTraining2 and RTest2 for the three sets was tiny enough to be ignored, and the average values of RTraining2 and RTest2 were essentially identical to the overall R2 value, which meant the approving predictive power of the obtained model. In the “leave-one-out” method, every fourth compounds 1, 5, 9, etc were an external test set, and the others were the training set. The R2 value of training set and test set were close, and the QSAR developed in this study had good predictability. In regard to the molecular descriptors, the 1st important descriptor was the total N


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point-charge components of the molecular dipole (µc), which measured the hydrophilic/lipophilic property of the compounds.33,34 An appropriate µc value illustrated that the molecules can penetrate fungi cell membrane or wall more smoothly as well as interact with action target.35 For β-pinene analogues in this study, the suitable value range was from 2 to 3. The structural modification of dehydrocumic acid through esterification and amidation can regulate the hydrophilic and lipophilic property of the compounds. Among the β-pinene analogues, diester demonstrated

better

fungicidal

activity.

The

µc

value

measured

the

hydrophilic/lipophilic property of the compounds, which can affect the penetration ability of molecules to fungi cell membrane or wall as well as interact with action target to a large extent. The structural modification of dehydrocumic acid through esterification and amidation can regulate the hydrophilic and lipophilic property of the compounds. Among the β-pinene analogues, diester demonstrated better fungicidal activity. It was illustrated that after disubstituted modification with ester, the hydrophilic and lipophilic property of the compounds was regulated, so the µc value was an essential factor in regulating the activity. For instance, from Fig. 2, the optimized geometries and charge distribution on atoms of compounds 5e, 5f, 5g and 5h were demonstrated simultaneously.

O



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Fig. 2 The optimized geometries and charge distribution of compounds 5e, 5f, 5g and 5h The 2nd most important descriptor obtained in the model was the number of occupied electronic levels nf. The descriptor belonged to quantum-chemical descriptor, and represented or depended directly on the quantum-chemically calculated charge distribution in the molecules, and therefore described the polar interactions between molecules or their chemical reactivity.36 In Fig. 3, the optimized geometries and charge distribution on atoms of compounds 5k and 5l was demonstrated simultaneously. In addition, Fig. 3 showed the molecular electrostatic potential and contour maps indicated the occupied electronic levels of compounds 5k and 5l.37

P


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Fig. 3 The molecular electrostatic potential and contour maps of compounds 5k and 5l. The green parts represent positive molecular orbitals, and the red parts represent negative molecular orbitals The 3rd most important descriptor in the model was the maximum net atomic charge for a H atom . The descriptor belongs to electrostatic descriptor, and reflects characteristics of the charge distribution of the molecule, which represents the geometric mean of atomic electro negativities. The Fig. 4 showed the frontier molecular orbitals (FMOs) of compounds 5k and 5l, which indicated the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). These popular quantum chemical parameters could determine the molecular reactivity and predict the excitation properties and the ability of electron transport.38,39

Fig. 4 Ground state isodensity surface plots for molecular orbitals compounds 5k and 5l The 4th most important descriptor was the final heat of formation of atoms ∆Hf, and reflects the energy of the molecule in its thermodynamic standard state (298.15 K and 101.325 Pa).40, 41 From Eq. (3), the ∆Hf value had a positive effect on log LC50 Q



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values. CONCLUSION In order to expand efficient application of forest resources β-pinene to agriculture, series of β-pinene analogues, monoesters, diesters and bisamides were prepared for suitable amphipathic property through structural modification. The larvicidal activity against P. xylostella and M. separata was evaluated. The preliminary structure-activity relationship (SAR) indicated that compounds with appropriate amphipathic feature displayed more desirable performance. The most appropriate chain length of R1 substitute was C4, and the most suitable hydrophilic and lipophilic property was log P value range 3.5-5.0. Meantime, the quantitative structure-activity relationship (QSAR) model (R2 = 0.9485, F = 82.94, S2 = 0.0067) indicated the most important structural feature was the µc value, and the suitable µc value was 2-3. In view of these results, the broad application of volatile β-pinene in exploitation of eco-friendly larvicides can be achieved. SUPPORTING INFORMATION IR, 1H NMR, MS, and elemental analysis data for the target compounds. The preparation of title compounds. The asymmetric unit and crystal packing of compound 2. The “breaking point” rule results. The substituted groups of β-pinene derivatives. Larvicidal activity of compounds against M. separat. Larvicidal activity and structure descriptors of the title compounds. The difference between the experimental log LC50 and predicted log LC50. Internal validation of the QSAR model. R


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ACKNOWLEGEMENTS The National Nature Science Foundation of China (Project No. 31401783 and Project No. 31400509) and Chinese Universities Scientific Fund (Project No. Z109021513) and Open foundation of Key Laboratory of biomass energy and materials of Jiangsu Province (Project No. JSBEM201608) provided financial support for this research. REFERENCES (1) Rios-Diez, J. D.; Saldamando-Benjumea, C. I. Susceptibility of Spodoptera frugiperda (Lepidoptera: Noctuidae) strains from central Colombia to two insecticides, methomyl and λ-cyhalothrin: A study of the genetic basis of resistance. J. Econ. Entomol. 2011, 104, 1698– 1705. (2) Dively, G. P.; Kamel, A. Insecticide residues in pollen and nectar of a cucurbit crop and their potential exposure to pollinators J. Agric. Food Chem. 2012, 60, 4449– 4456. (3) Wang, Y.; Shao, Y. H.; Wang, Y. Y.; Fan, L. L.; Yu, X.; Zhi, X. Y.; Yang, C.; Qu, H.; Yao, X. J.; Xu, H. Synthesis and Quantitative Structure–Activity Relationship (QSAR) Study of Novel Isoxazoline and Oxime Derivatives of Podophyllotoxin as Insecticidal Agents. J. Agric. Food Chem. 2012, 60 (34), 8435–8443. (4) Ishtiaq, M.; Saleem, M. A.; Razaq, M. Monitoring of resistance in Spodoptera exigua (Lepidoptera: Noctuidae) from four districts of the southern Punjab, Pakistan to four conventional and six new chemistry insecticides. Crop Prot. 2012, 33, 13–20. (5) Zhang, D. X.; Li, B. X.; Zhang, X. P.; Zhang, Z. Q.; Wang, W. C.; Liu, F. Phoxim Microcapsules Prepared with Polyurea and Urea−Formaldehyde Resins S



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39-45 (41) Grotti M.; Frache R. Investigation of the formation of solid phase compounds between tellurium and interfering elements in graphite furnace atomic absorption spectrometry Spectrochimica Acta Part B: Atomic Spectroscopy. 1997, 52(9), 1247-1258.

Y



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For Table of Contents Use Only

Take an Advantage of Sustainable Forest Resource in Agriculture: A Value-added Application of Volatile Turpentine Analogues as Botanical Pesticides based on Amphipathic Modification and QSAR Study Jian Li,

†

Jingjing Li,

&†

Yanqing Gao

*‡

, Xing Zhang ‡, Shibin Shang,

#

Zhanqiang Song, # and Guomin Xiao **§ ABSTRACT GRAPHIC

SYNOPSIS: Forest resource volatile β-pinene was exploded as botanical insecticides

Z


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47x26mm (300 x 300 DPI)



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Experimental log IC50 versus predicted log IC50 67x53mm (300 x 300 DPI)


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The optimized geometries and charge distribution of compounds 5e, 5f, 5g and 5h 63x47mm (300 x 300 DPI)



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The molecular electrostatic potential and contour maps of compounds 5k and 5l. The green parts represent positive molecular orbitals, and the red parts represent negative molecular orbitals 63x47mm (300 x 300 DPI)


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Ground state isodensity surface plots for molecular orbitals compounds 5k and 5l 63x47mm (300 x 300 DPI)


A Value-Added Application of Volatile Turpentine ... - ACS Publications

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