Research on Controllable Degradation of Novel Sulfonylurea Herbicides in Acidic and Alkaline Soils

Article abstract of DOI:10.1021/acs.jafc.7b03029

The degradation issue of sulfonylurea (SU) has become one of the biggest challenges that hamper the development and application of this class of herbicides, especially in the alkaline soils of northern China. On the basis of the previous discovery that some substituents on the fifth position of the benzene ring in Chlorsulfuron could hasten its degradation rate, apparently in acidic soil, this work on Metsulfuron-methyl showed more convincing results. Two novel compounds (I-1 and I-2) were designed and synthesized, and they still retained potent herbicidal activity in tests against both dicotyledons and monocotyledons. The half-lives of degradation (DT₅₀) assay revealed that I-1 showed an accelerated degradation rate in acidic soil (pH 5.59). Moreover, we delighted to find that the degradation rate of I-1 was 9-10-fold faster than that of Metsulfuron-methyl and Chlorsulfuron when in alkaline soil (pH 8.46), which has more practical value. This research suggests that a modified structure that has potent herbicidal activity as well as accelerated degradation rate could be realized and this approach may provide a way to improve the residue problem of SUs in farmlands with alkaline soil.

Full text of DOI:10.1021/acs.jafc.7b03029

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Article
Research on Controllable Degradation of Novel
Sulfonylurea Herbicides in Acidic and Alkaline Soils
Shaa Zhou, Xue-Wen Hua, Wei Wei, Yu-Cheng Gu, Xiaoqing Liu, Jinghuo Chen, Minggui Chen, Yong-Tao
Xie, Sha Zhou, Xiang-De Meng, Yan Zhang, Yong-Hong Li, Baolei Wang, Haibin Song, and Zheng-Ming Li
J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.7b03029 • Publication Date (Web): 16 Aug 2017
Downloaded from http://pubs.acs.org on August 17, 2017
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Page 1 of 37
Journal of Agricultural and Food Chemistry
Research on Controllable Degradation of Novel
Sulfonylurea Herbicides in Acidic and Alkaline Soils
Shaa Zhou,† XueꢀWen Hua,‡ Wei Wei,† YuꢀCheng Gu,§ XiaoꢀQing Liu,† JingꢀHuo
Chen,† MingꢀGui Chen,† YongꢀTao Xie,† Sha Zhou,† XiangꢀDe Meng,† Yan Zhang,†
YongꢀHong Li,† BaoꢀLei Wang,† HaiꢀBin Song,† ZhengꢀMing Li*,†
†
State Key Laboratory of ElementoꢀOrganic Chemistry, Collaborative Innovation Center of
Chemical Science and Engineering (Tianjin), College of Chemistry, Nankai University,
Tianjin 300071, China
‡ College of Agriculture, Liaocheng University, Liaocheng 252000, China
§ Syngenta Jealott's Hill International Research Centre, Bracknell, Berks, RG42 6EY, UK
* Address correspondence to this author at State Key Laboratory of
ElementoꢀOrganic Chemistry, Nankai University, No. 94, Weijin Road, Nankai
District, Tianjin 300071, China (telephone: +86 022ꢀ23503732; Fax: +86
022ꢀ23503732; eꢀmail: nkzml@vip.163.com)
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Abstract: The degradation issue of sulfonylurea (SU) has become one of the biggest
challenges that hamper the development and application of this class of herbicides,
especially in alkaline soils of Northern China. On the basis of previous discovery that
some substituents on the 5th position of the benzene ring in Chlorsulfuron could
hasten its degradation rate apparently in acidic soil, this work on Metsulfuronꢀmethyl
showed more convincing results. Two novel compounds (I-1 and I-2) were designed
and synthesized, at the same time, they still retained potent herbicidal activity against
both tested dicotyledon and monocotyledon. The halfꢀlives of degradation (DT50)
assay revealed that I-1 showed accelerated degradation rate in acidic soil (pH 5.59).
Moreover, we delighted to find that the degradation rate of I-1 was 9~10 folds faster
than that of Metsulfuronꢀmethyl and Chlorsulfuron when in alkaline soil (pH 8.46),
which have more practical value. This research suggests that a modified structure
which has potent herbicidal activity as well as accelerated degradation rate could be
realized and this approach may provide a way to improve the residue problem of SUs
in farmlands with alkaline soil.
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Keywords: Sulfonylurea herbicide, Metsulfuronꢀmethyl, herbicidal activity, soil
degradation, DT50.
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18 Introduction
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Sulfonylurea (SU) herbicides have been widely applied due to their ultraꢀlow
dosage, broad spectra and good selectivity.1ꢀ2 Their sole target is Acetolactate
Synthase (ALS) which exists only in plants and microbes, not in mammals. The
inhibition of ALS results in the disruption of three essential amino acids synthesis in
meristem and eventually death of weeds.3ꢀ6
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Many sulfonylurea herbicides have been introduced into China and are widely
available in Chinese plant protection market.7 The common cultivation practice in
China is to rear 2~3 different crops successively within a year on the same plot of
land. The short crops cycle demands herbicides with high activity, low toxicity and
fast degradation rate. Due to the relatively long persistence of Chlorsulfuron,
Metsulfuronꢀmethyl and Ethametsulfuron that can injure next season crops including
wheat, corn, paddy rice, cotton and bean,8ꢀ10 the Ministry of Agriculture of China
suspended their field application in 2014.11 From an environmental and ecological
standpoint, we took a green approach to study this issue according to the Anastas 10th
Principle of Green Chemistry—Design for Degradation.12
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pH is one of the most important factors that influences the degradation rate of
sulfonylurea herbicides in soil. Walker et al reported that the DT50 of
Metsulfuronꢀmethyl was 23 days in pH 5.8 soil and 73 days in pH 7.3 soil.13 Yadav et
al found that there was 83% dissipation of Metsulfuronꢀmethyl in low pH 5.6 soil and
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53% in high pH 8.1 soil after 120 days.14 After research of the hydrolysis of
sulfonylurea herbicides in water at different pH, we concluded that the 5th position on
the benzene ring in SU structures is the key factor influencing their degradation
behaviors.15ꢀ18 Our previous study reported that the introduction of some substituents
onto the 5th position of the benzene ring in Chlorsulfuron could speed up its
degradation rate in acidic soil relatively.19ꢀ20 Based on these previous findings,
dimethylamino and diethylamino groups were introduced into the Metsulfuronꢀmethyl
structure (Figure 1) to investigate their influence on biological activities as well as
soil degradation behaviors. Considering the difference of soil pH in China and the soil
degradation of sulfonylurea herbicides has strong negative correlation with soil
pH,13ꢀ14, 21 two representative standard soil samples (pH 5.59 Jiangxi Province and pH
8.46 Hebei Province) were selected to carry out our research.
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50 Materials and Methods
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Instruments and Materials. All reaction reagents were analytical grade, all
analytical reagents for high performance liquid chromatograph (HPLC) were HPLC
grade including methanol and acetonitrile. The melting points were determined on an
Xꢀ4 binocular microscope melting point apparatus (Beijing Tech Instrument Co.,
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Beijing, China), and the temperatures were uncorrected. H and C nuclear magnetic
resonance (NMR) spectra were obtained on a Bruker AVꢀ400 spectrometer (Bruker
Co., Switzerland) in Acetoneꢀd6 or DMSOꢀd6 solution with tetramethylsilane (TMS)
as the internal standard, and chemicalꢀshift values (δ) were given in parts per million
(ppm). Highꢀresolution mass spectrometry (HRMS) data were obtained on a Varian
QFTꢀESI instrument. Ultraviolet (UV) spectra were performed on a TUꢀ1810
ultravioletꢀvisible spectrophotometer (Persee general analysis Co., Beijing, China).
HPLC data were obtained on a SHIMADZU LCꢀ20AT (SHIMADZU Co., Japan).
Column chromatography purification was carried out using silica gel (200~300
mesh).
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General Procedure for the Synthesis of Target Compounds I-1.
1ꢀ(2ꢀMethoxycarbonylꢀ5ꢀdimethylaminophenylsulfonyl)ꢀ3ꢀ(4ꢀmethoxyꢀ6ꢀmethylꢀ1,3,
5ꢀtriazinꢀ2ꢀyl)urea I-1 was synthesized by the following method.22 To a toluene
solution of 10a (1.0 mmol), 2ꢀaminoꢀ4ꢀmethoxyꢀ6ꢀmethylꢀ1,3,5ꢀtriazine (1.2 mmol)
was added under stirring. The mixture was heated to reflux with continuous removal
of the azeotrope formed by ethanol and toluene. After completion of the reaction, the
solvent was evaporated in vacuum and the residue was purified on silica gel column
eluting with petroleum/ethyl acetate (v/v, 1:1) to obtain I-1.
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1ꢀ(2ꢀMethoxycarbonylꢀ5ꢀdimethylaminophenylsulfonyl)ꢀ3ꢀ(4ꢀmethoxyꢀ6ꢀmethylꢀ1,
o
1
3,5ꢀtriazinꢀ2ꢀyl)urea (I-1). White solid, yield 87%, m.p. 195ꢀ197 C. H NMR (400
MHz, Acetone) δ 12.60 (s, 1, NH), 9.59 (s, 1, NH), 7.77 (d, 1, J = 8.7 Hz, PhꢀH), 7.60
(d, 1, J = 2.7 Hz, PhꢀH), 6.95 (dd, 1, J = 8.8, 2.8 Hz, PhꢀH), 4.06 (s, 3, CO2CH3), 3.84
13
(s, 3, OCH3), 3.13 (s, 6, N(CH3)2), 2.56 (s, 3, CH3). C NMR (101 MHz, DMSO) δ
178.6, 170.2, 166.0, 163.9, 151.4, 148.5, 138.7, 132.7, 115.1, 114.4, 114.2, 55.3, 52.3,
39.7, 25.1. HRMS (ESI) Calcd for C16H21N6O6S [M+H]+ 425.1243, found 425.1239.
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I-2 was prepared with the same procedure.
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1ꢀ(2ꢀMethoxycarbonylꢀ5ꢀdiethylaminophenylsulfonyl)ꢀ3ꢀ(4ꢀmethoxyꢀ6ꢀmethylꢀ1,3,
o
1
5ꢀtriazinꢀ2ꢀyl)urea (I-2). White solid, yield 85%, m.p. 189ꢀ191 C. H NMR (400
MHz, Acetone) δ 12.58 (s, 1, NH), 9.54 (s, 1, NH), 7.74 (d, 1, J = 8.8 Hz, PhꢀH), 7.61
(d, 1, J = 2.8 Hz, PhꢀH), 6.93 (dd, 1, J = 8.8, 2.8 Hz, PhꢀH), 4.06 (s, 3, CO2CH3), 3.83
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(s, 3, OCH3), 3.54 (q, 4, J = 7.1 Hz, N(CH2CH3)2), 2.56 (s, 3, CH3), 1.23 (t, 6, J = 7.1
Hz, N(CH2CH3)2). 13C NMR (101 MHz, DMSO) δ 178.6, 170.2, 166.0, 164.0, 149.0,
148.6, 138.8, 133.0, 114.3, 113.8, 99.6, 55.3, 52.3, 44.3, 25.1, 12.1. HRMS (ESI)
Calcd for C18H25N6O6S [M+H]+ 453.1556, found: 453.1548.
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X-ray Diffraction Analysis. A colorless crystal of I-1 was obtained by
selfꢀevaporation in the mixture solvent of dichloromethane and nꢀhexane. The crystal
with dimensions of 0.20 ×0.20 ×0.20 mm was mounted on a glass fiber for Xꢀray
diffraction analysis. The data was collected at 113 K on a Rigaku Saturn 724 CCD
diffractometer (Rigaku Co. Japan) with graphite monochromated Mo Kα radiation (λ
= 0.71075 Å), θmax = 25.01o. The molecular formula is C16H20N6O6S, and the formula
weight is 424.44 g·molꢀ1. The crystal was a monoclinic system, space group P 21/c,
with cell parameters existed as ɑ = 13.5479(19) Å, b = 9.9822(12) Å, c = 15.552(2) Å;
cell ratio as ɑ/b = 1.3572, b/c = 0.6419, c/ɑ = 1.1479; calculated density was 1.46883
g/cm3; V = 1919.22(43) Å3; Z = 4, ꢀ (Mo Kα) = 0.217 mmꢀ1. In total, 14901 integrated
reflections were collected, reducing to a data set of 3263 unique with Rint = 0.0405
and the completeness of data was 96.8%. Data were collected and processed using
CrystalClear (Rigaku). An empirical absorption correction was applied using
CrystalClear (Rigaku). The structure was solved by direct methods with the
SHELXSꢀ97 program.23 Fullꢀmatrix leastꢀsquares refinement based on F2 gave final
values of R = 0.1195, wR = 0.3482. Hydrogen atoms were observed and refined with
a fixed value of their isotropic displacement parameter.
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Biological Assay. The root growth inhibition of oil seed rape (Brassica campestris)
was tested using the reported method.24 Pot trials for herbicidal activities against oil
seed rape (Brassica campestris), amaranth (Amaranthus retroflexus), barnyard grass
(Echinochloa crusgalli) and crab grass (Digitaria sanguinalis) were tested in
greenhouse (25 ± 2 oC) according to the procedures in the literature.24, 25
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Molecular Docking. The surflexꢀdock method26 was applied to study the binding
mode of SU structures with the AHAS using the SYBYL 6.9 software package. I-1
was manually docked into the active site of yeast AHAS on the basis of the crystal
complex of Chlorimuronꢀethyl and yeast AHAS27 which was retrieved from the
RCSB Protein Data Bank (PDB code: 1N0H). The receptor and the ligand molecule
were prepared by standard procedures.
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Soil Degradation Experimental Strategies. Soil Selection. To investigate the
degradation behaviors of Metsulfuronꢀmethyl and its derivatives, a red acidic soil (pH
5.59) from Ji’an, Jiangxi Province and an alkaline soil (pH 8.46) from Cangzhou,
Hebei Province in China were selected. The soil from the fresh farmland was sampled
from the upper layer (0ꢀ25 cm), airꢀdried in the shade and passed through a 2 mm
sieve according to the Chinese National Standard GB/T 31270.1ꢀ2014.28 The soil
texture, pH value, organic matter, cation exchange capacity (CEC) and mechanical
composition of the test soils were listed in Table 1, which were determined by Tianjin
Institute of Agriculture Resource and Environment.
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HPLC Processing and Establishment of Standard Curves. The samples were
analyzed by HPLC following the Chinese National Standard GB/T 16631ꢀ2008.29 The
method employed a Shimadzu HPLC (series LCꢀ20AT), equipped with a binary pump
(Shimadzu, LCꢀ20AT), an UV/VIS detector (Shimadzu, SPDꢀ20A), an auto sampler
(Shimadzu, SILꢀ20A), a column oven (Shimadzu, CTOꢀ20AC) and a Shimadzu
shimꢀpack VPꢀODS column (5 mm, 250 mm × 4.6 mm) connected to a Shimadzu
shimꢀpack GVPꢀODS (10 mm × 4.6 mm) preꢀcolumn, and a computer (model Dell)
for carrying out the data analysis. Chromatographic pure methanol, acetonitrile and
ultraꢀpure water (pH 3.0) were used as mobile phase. After that, standard curves used
for quantitative conversion were established with the injection volume of 10 µL and
the temperature was set at 20 oC.
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Measurement of the Recovery Rate. Appropriate extraction solvents were adopted
and mixed to guarantee the eligible average recovery rate, standard deviation and
coefficients of variation (Table 2) according to the Chinese Agricultural Industry
Standard NY/T 788ꢀ2004.30 The concentrations of target compound in soil were 5, 2,
0.5 mg·kgꢀ1, and the soil humidity was kept at 60% of the water holding capacity.
Different extraction solvents were decanted into the homogeneous soils, followed by
shaking for 3 h at 200 rpm·minꢀ1 with a SHZꢀ88 thermostatic oscillator (Jintan
Medical Instrument Factory, Jiangsu, China). The samples were then centrifuged for 2
min at 6500 rpm·minꢀ1 with a Thermo Scientific Legend Mach 1.6 R centrifuge to
obtain supernatant which was then concentrated in vacuum at room temperature. After
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the residue was extracted by dichloromethane (30 mL × 2) and distilled water (30
mL), the combined organic solution was dried by anhydrous sodium sulfate, filtered
and concentrated. The product was dissolved in acetonitrile (10 mL), and filtered
through a millipore filter (organic, nylon 66, 0.22 µm) for HPLC analysis. The
addition recovery rate were measured and calculated according to the corresponding
average values of 5 replicates.
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Cultivation of Samples and Management. Testing soil (20.00 g) was weighed
into 6 groups in 100 mL conical flasks, triplications in each group, and the standard
sample solutions were added to a concentration of 5 a.i. mg·kgꢀ1. Then an appropriate
volume of distilled water was added to adjust the soil moisture content to
approximately 60% of water holding capacity and thoroughly mixed. The bottles were
then sealed with Para film and put into a SPXꢀ150BꢀZ biochemical incubator (Boxun
o
Industrial Co., Shanghai, China) at 25 ± 1 C and 80% humidity in the dark. In the
process of cultivation, the moisture content in conical flasks was adjusted regularly to
maintain the original waterꢀholding state. The samples were taken periodically for
HPLC analysis at 6 different intervals and each sample was repeated 3 times.
According to previous studies, the initial degradation of sulfonylurea herbicides
follows the firstꢀorder kinetic equation.19,31ꢀ34 The degradation curves of firstꢀorder
kinetic equation of tested compounds were established according to the data from six
samplings. After that, halfꢀlives of degradation (DT50) were calculated using the
formula: DT50 = LN(2)/K.
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168 Results and Discussion
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Chemistry. The synthetic procedures of all compounds were showed in Figure 2.
The reactions of diazotization of 1, ammoniation of 2 and successive reduction of 5
were prepared according to reported methods,19 and 10 was synthesized through the
reaction of 9 and ethyl chlorocarbonate using the procedure in literature.24 Compound
4 was obtained in the aqueous solution of chromium trioxide by adding concentrated
sulfuric acid and 2ꢀmethylꢀ5ꢀnitrobenzenesulfonamide successively, for 24h at room
temperature.35 The ringꢀopening reaction of 4 was prepared by leading in hydrogen
chloride gas continuously in methanol.17 The protection and deprotection of
sulphonamide were carried out for the alkylation of aniline, and DMFꢀDMA was
taken as the protective agent.36ꢀ38 The intermediate 8a was obtained as previous
reported.19 Compound 8b can be prepared as 8a, and can also be synthesized by the
following procedure that 7 was dissolved in glacial acetic acid, and then NaBH4 was
added in batches, the mixture was stirred overnight to adjust pH until there was no
longer white solid produced,39 this method was more effective and with more higher
yield than 8a.
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In assay of alkaline soil degradation, the soil extraction of I-2 failed due to an
unexpected peak overlapped with the sample which resulted in a ＞130 % recovery.
By numerous replacement of the mobile phases and change of their ratios, we
successfully separated the mixed peaks by HPLC condition as CH3OH/CH3CN/H2O
(pH 3.0) = 35/35/30. As a result, the alkaline soil degradation of I-2 was determined
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in another batch, taking Chlorsulfuron as a control.
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Crystal Structure Analysis. The crystal structure of I-1 was showed in Figure 3
(CCDC number. 1540975). The sum angles of O(5)ꢀC(11)ꢀN(2) 123.878(535)o,
O(5)ꢀC(11)ꢀN(3) 120.792(502)o and N(2)ꢀC(11)ꢀN(3) 115.314(471)o was 359.984o,
indicating the plane sp2 hybridization state of C(11) atom. The bonds angles of
O(3)ꢀS(1)ꢀC(1), O(4)ꢀS(1)ꢀC(1), N(2)ꢀS(1)ꢀC(1) were 109.858(271)o, 108.886(256)o
and 105.792(250)o respectively which indicated the sp3 hybridization state of the S(1)
atom. The torsion angle of O(5)ꢀC(11)ꢀN(2)ꢀH(2) was ꢀ175.66(53)o while the
O(5)ꢀC(11)ꢀN(3)ꢀH(3) showed as 8.376(799)o. The benzene ring and the triazine ring
were nonꢀplane for their dihedral angle was 74.041(146)o. From Figure 3, one kind of
Hꢀbond could be found: N(2)ꢀH(2)···N(5), it could be explained as the reason of the
torsion angles of O(5)ꢀC(11)ꢀN(2)ꢀH(2) and O(5)ꢀC(11)ꢀN(3)ꢀH(3).
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Biological Assay. The inhibition rate of the root growth oil seed rape (Brassica
campestris) was measured to evaluate the herbicidal activities of the target
compounds and the corresponding results were listed in Table 3. From the results, it
was observed that the new compound I-1 matched commercial Metsulfuronꢀmethyl in
herbicidal potency at the rate of 0.1 ug·mLꢀ1, whereas I-2 was slightly weaker.
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On this basis, the herbicidal activities of target compounds against dicotyledon
Brassica campestris, Amaranthus retroflexus and monocotyledon Echinochloa
crusgalli, Digitaria sanguinalis were further screened through pot experiments at 15
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and 150 a.i. g·haꢀ1 with Metsulfuronꢀmethyl as a positive control. The results were
showed in Table 4. From the data, it was found that the target compounds retained
their efficient herbicidal activities, where I-1 exhibited excellent inhibition effect
against Digitaria sanguinalis at 150 a.i. g·haꢀ1. The 100% inhibition rate against
Brassica campestris was showed at 15 a.i. g·haꢀ1 by soil treatment as well as foliage
spray. The effect on Echinochloa crusgalli of I-1 was also 100% at 15 a.i. g·haꢀ1 in
postꢀemergence treatment. Overall the introduction of dimethylamino and
diethylamino groups onto the 5th position of the benzene ring in Metsulfuronꢀmethyl
retained or improved their herbicidal activities.
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Molecular Docking Results. I-1 was taken in the molecular docking study for its
hyper herbicidal activity, and the result was illustrated in Figure 4. As it showed the
conformations of the aromatic ring and triazine ring connected to the sulfonyl urea
bridge were situated in approximately mutual vertical position which was similar to
the binding structure of Chlorimuronꢀethyl and AHAS that the heterocyclic part
blocks the substrate access channel. The section of methoxy carbonyl was also located
in the channel to block the substrate. There was a π–π stacking interaction between
the indole side chain of B/Trp 586 and the triazine moiety of I-1. There was also
several Hꢀbonds interaction between the ureaꢀtriazine moiety of I-1 and the guanidine
group of B/Arg 380. The docking results ascertained that I-1 is also a typical AHAS
interaction.5 From the conformation of the docking results, the dimethylamino group
was located along the extended plane of the benzene ring outside the channel, it could
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explain its high biological activity. The conformation of sulfonylurea bridge was
rotated for the better docking with AHAS through the torsion of C(11)ꢀN(3) bond, and
it was consistent with the active conformation of Chlorimuronꢀethyl and
Monosulfuron.40ꢀ41
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Soil Degradation. The degradation curves of firstꢀorder kinetic equation of tested
compounds were established according to the data from six samplings (Figure 5 and
Figure 6). After that, halfꢀlives of degradation (DT50) were calculated (Table 5).
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The soil degradation behaviors of target compounds in acidic soil (pH 5.59) with
Metsulfuronꢀmethyl as a positive control were investigated preliminarily to explore
the corresponding relationship between structural modification and soil degradation.
From the halfꢀlives of degradation, the degradation rate of dimethylamino substituted
compounds I-1 was increased significantly that its DT50 was 2.85 days, 2 folds faster
than Metsulfuronꢀmethyl. Furthermore, the degradation rate of I-2 with its DT50 as
5.11 days, which had approximately the same degradation rate as metsulfuronꢀmethyl
(5.50 days).
245
246
247
Then, the alkaline soil (pH 8.46) degradation behaviors of target compounds were
examined to survey their difference in degradation rate in two types of soils, taking
Metsulfuronꢀmethyl and Chlorsulfuron as positive controls.
248
249
From Table 5, the DT50 of compound I-1 was 8.40 days which showed a significant
10 folds faster degradation rate than Chlorsulfuron (84.53 days) and 9 folds faster
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250
251
252
253
254
255
than Metsulfuronꢀmethyl (75.34 days). The DT50 of compound I-2 was 26.56 days
while the DT50 of Chlorsulfuron was longer than 100 days. The experimental data
demonstrated that the introduction of dimethylamino and diethylamino groups onto
the 5th position of the benzene ring in Metsulfuronꢀmethyl could efficiently accelerate
its soil degradation rate. The research provide critical information for the solution to
soil degradation problems in our green chemistry approach especially in alkaline soil.
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
After structural modification, the optimized new structure I-1 upgraded its
degradation rate not only in standardized acidic soil, but also in standardized alkaline
soil. From the degradation results in acidic soil (pH 5.59), DT50 of I-1 accelerated to
2.85 days while I-2 was 5.11 days comparing with the 5.50 days of
Metsulfuronꢀmethyl. Particularly in alkaline soil (pH 8.46), the DT50 of I-1 hastened
nearly 9 folds from 75.34 to 8.40 days in comparison with Metsulfuronꢀmethyl that
there was considerable faster degradation in alkaline soil than acidic soil, the same as
compound I-2. Interestingly I-1 and I-2 also retained their active herbicidal activity in
comparison with the parent structure. The perfect surflexꢀdocking results also
confirmed that I-1 was a typical AHAS interaction. Our study further ascertained that
in Metsulfuronꢀmethyl, the 5th position substituted approach also has apparent
influence on its degradation rate, though the influence mensuration is somewhat
different. This might be due to the difference in their molecular structures.
Considering the particular planting practice in China which requires individual
cultivation cycle for each crop, it convinces us that by modifying SU structures
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271
272
273
274
delicately, a control of their degradation rate which is in accordance with our
cultivation pattern is possible.42 After further understanding of their
structure/activity/degradation relationship, it will be possible to optimize the novel
herbicidal application in the particular planting system.
275
276
ABBREVIATIONS USED
277
278
AHAS: acetohydroxy acid synthase; DMFꢀDMA: N,NꢀDimethylformamide dimethyl
acetal; THF: tetrahydrofuran; RT: room temperature; Trp: tryptophan; Arg: aginine.
279
280
ACKNOWLEDGMENT
281
282
283
284
285
This work was supported by the National Natural Science Foundation of China (No.
21272129), State Key Laboratory of ElementoꢀOrganic Chemistry (Nankai
University), Collaborative Innovation Center of Chemical Science and Engineering
(Tianjin), and Syngenta PhD Scholarship. Thank Whittingham William for polishing
this article.
286
Supporting Information Description
13
287
288
289
1H NMR, C NMR spectra for the target compounds; Crystal data of the compound
I-1; Determination results of tested soils. This material is available free of charge via
the Internet at http: //pubs.acs.org.
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290
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FIGURE CAPTIONS
Figure 1 Design Strategy of Target Compounds.
Figure 2 Synthesis Strategy for Target Compounds.
Figure 3 The Crystal Structure of I-1.
Figure 4 Binding Mode of I-1 to Yeast AHAS.
Figure 5 Degradation Curves in Acidic Soil (pH 5.59).
Figure 6 Degradation Curves in Alkaline Soil (pH 8.46).
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Tables
Table 1 Analysis data of Soils
Mechanical composition
Cation
exchange
capacity
(cmol·kgꢀ1
)
Silt
Clay
Sand
Organic
matter
(%)
Soil
Fine
Coarse
Soils
pH
(1ꢀ0.
05
Coarse
(0.05ꢀ0.
01 mm)
(%)
Fine
(<0.00
1 mm)
(%)
texture
(0.01ꢀ0. (0.005ꢀ0
005
mm)
(%)
.001
mm)
(%)
mm)
(%)
Acidic
soil
loam
clay
5.59
8.46
0.763
0.757
13.55
10.39
36
30
10
26
10
8
12
8
32
28
Alkali
ne soil
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Journal of Agricultural and Food Chemistry
Table 2 Analytical Conditions for Soil Degradation.
HPLC analysis
conditions
Adding
Average
recovery
Coefficient
of
Compou
nds
Extraction solvents
(v/v)
concentration
(wavelength, flow rate,
235 nm, 0.8 mL·minꢀ1,
CH3OH/H2O (pH 3.0) =
65/35
(mg·kgꢀ1)
variation/%
1.23
CH3COCH3:CH2Cl2
:CH3OH:H3PO4
5
84.82
78.78
74.06
80.53
76.74
77.58
88.60
85.12
76.90
84.74
77.29
83.73
77.16
74.05
74.13
70.80
73.19
90.65
85.83
72.75
I-1
I-2
2
0.5
5
2.12
3.49
1.27
1.42
2.50
1.61
3.14
3.33
1.76
3.82
1.19
2.87
1.23
0.62
1.04
3.27
1.98
1.51
2.90
aqueous solution
(pH 2.0) = 40:5:5:5
CH3COCH3:CH2Cl2
230 nm, 0.8 mL·minꢀ1,
CH3OH/H2O (pH 3.0) =
70/30
Acidic
soil
: CH3OH: H3PO4
aqueous solution
(pH 2.0) = 40:5:5:5
2
0.5
5
(pH
5.59)
CH3COCH3:CH2Cl2
: H3PO4 aqueous
solution (pH 2.0) =
40:5:5
2
Metsulf
230 nm, 1.0 mL·minꢀ1,
uronꢀme CH3OH/H2O (pH 3.0) =
0.5
2
thyl
55/45
0.5
5
235 nm, 0.8 mL·minꢀ1,
CH3OH/H2O (pH 3.0) =
65/35
CH3COCH3:CH2Cl2
: H3PO4 aqueous
I-1
2
solution (pH 2.0) =
0.5
5
40:5:10
Alkali
ne soil
230 nm, 0.8 mL·minꢀ1,
CH3OH/CH3CN/H2O
(pH 3.0) = 35/35/30
CH3COCH3:CH2Cl2
: H3PO4 aqueous
I-2
2
(pH
solution (pH 2.0) =
0.5
5
8.46)
40:5:5
CH3COCH3:CH2Cl2
Metsulf
230 nm, 1.0 mL·minꢀ1,
: H3PO4 aqueous
solution (pH 2.0) =
40:5:10
uronꢀme CH3OH/H2O (pH 3.0) =
thyl 55/45
2
0.5
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Table 3 Inhibition of the Root Growth of Rape (Brassica campestris).
Inhibition rate (%)
compounds
0.1 µg·mLꢀ1
61.8
1 µg·mLꢀ1
67.9
10 µg·mLꢀ1
68.4
I-1
I-2
45.8
61.4
67.5
Metsulfuronꢀmethyl
61.2
66.6
67.3
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Table 4 Herbicidal Activity of Target Compounds by Soil Treatment and Foliage
Spray.
Inhibition rate (%)
Concentration
Brassica
Amaranthus
retroflexus
Echinochloa
crusgalli
Digitaria
compounds
campestris
sanguinalis
(a.i g·haꢀ1)
Pre
Post
100
100
100
100
100
100
Pre
91.4
100
91.8
100
100
100
Post
92.5
100
97.8
100
100
100
Pre
77.4
100
53.4
100
64.7
96.7
Post
100
100
85.2
100
84.1
98.9
Pre
27.7
98.1
49.9
90
Post
15
150
15
100
100
100
100
100
100
12.2
65.6
0
I-1
I-2
150
15
0
61.5
100
31.7
45.4
Metsulfuronꢀme
thyl
150
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