Structure-activity relationships among the imidazolinone herbicides

The structure of the imidazolinone herbicides consists of three distinct moieties: the imidazolinone ring, the carboxylic acid and the backbone. The effect of changes in each of these on herbicidal activity, crop selectivity and AHAS enzyme inhibition has been studied. Though both whole-plant and enzyme activity were drastically affected by changes in the carboxylic acid or imidazolinone ring portions of the molecule, a variety of backbones and of substituents on the backbones afforded good activity. Methyl-isopropyl was found to be the best combination of substituents on the imidazolinone ring. While pyridine backbones generally gave the most active herbicides, benzene backbones led to the strongest enzyme inhibition. A QSAR study in the pyridine series generated two equations which proved useful for guiding the analog program toward the synthesis of potent heteropyridyl compounds. Selectivity in wheat is dependent upon differences in the rate of metabolism of key groups. Rapid metabolism of either the imidazolinone ring or backbone alkyl groups occurs rapidly in soybeans compared with susceptible weeds.     

Susceptibility to imazamox in Italian weedy rice populations and Clearfield® rice varieties

The introduction of imidazolinone‐tolerant rice varieties has made selective Oryza sativa (weedy rice) control possible. We hypothesised that Italian weedy rice populations have variable degrees of susceptibility to imazamox prior to imidazolinone‐tolerant variety introduction. To this end, 149 Italian weedy rice populations collected from fields never before cultivated with imidazolinone‐tolerant varieties were tested in a glasshouse‐based, whole‐plant response screening study. Imazamox was applied to all populations post‐emergence at a rate of 70 g a.i. ha^?1, resulting in 70–90% shoot biomass reduction in the majority of cases. The results prompted a second study of the seedling dose response of four weedy rice populations from the initial study group. Three imidazolinone‐tolerant and one conventional rice variety were also included. The seedling roots were cut six days after germination and exposed to different concentrations of imazamox. The root regrowth associated with each concentration‐exposure was then measured. Imazamox concentrations to inhibit weedy rice root growth by 50% varied by about two orders of magnitude, or between 0.0018 and 0.12 mm . Even with this result, imidazolinone‐tolerant varieties were at least 31.8 times less susceptible than weedy rice populations, suggesting that Italian weedy rice populations were not tolerant to imazamox before introduction of these varieties.     

Soil‐less bioassays for early screening for resistance to imazapyr in sunflower (Helianthus annuus L.)

BACKGROUND: Rapid and efficient diagnostic tests for early screening of herbicide resistance are convenient alternatives to field screening methods. There is a need for a quick, reliable and cost‐effective method for rapid diagnosis of imidazolinone resistance in sunflower (Helianthus annuus L.). RESULTS: Two seed germination bioassays were developed. Seeds from three sunflower inbred lines differing in resistance to imidazolinones were germinated either on solid culture medium or placed in plastic pots filled with commercial perlite. After 8 days incubation under controlled conditions, both assays successfully distinguished susceptible genotype from the resistant and intermediate ones. The susceptible genotype showed arrested root growth at all herbicide treatments (root length < 1 cm). The resistant genotype developed a complete root system even when exposed to the highest dose of herbicide. However, no definite differences were observed for the intermediate and resistant genotypes with respect to root growth under the different herbicide treatments. CONCLUSION: The simple and rapid screening assays described in the present study were useful in discriminating imidazolinone resistance at the seedling stage. Therefore, these bioassays could be potential tools for early screening of imidazolinone resistance genes from large sunflower populations. Copyright © 2009 Society of Chemical Industry     

Imidazolinone inhibition of acetohydroxyacid synthase in vitro and in vivo

Imidazolinone herbicides inhibit the first enzyme of branched-chain amino acid biosynthesis, acetohydroxyacid synthase. The inhibition of the enzyme in vitro by these herbicides increases with incubation time, but is not irreversible, as deduced by reaction progress curves. In contrast to this result is the apparent irreversible inhibition of the enzyme by these imidazolinones that occurs when the herbicide is applied to intact corn plants. Plants treated with imidazolinone herbicide and then extracted showed dramatically reduced enzyme activity. This effect on extractable enzyme level occurred with several different imidazolinone herbicides in either foliar or soil application. The decrease in extractable enzyme activity could be observed within four hours after treatment. Herbicides other than imidazolinones did not reduce the extractable enzyme level. These findings suggest that the enzyme- imidazolinone interaction in vivo may be different from the interaction observed in vitro.     

咪唑啉酮类除草剂的应用及降解

咪唑啉酮类除草剂虽具有高效广谱的特点,但有较长的残留活性,长期使用会造成作物药害,并且会制约正常的作物轮作。因此,如何解决其残留问题已成为目前的重要课题。本文介绍了咪唑啉酮类除草剂的种类和特性,阐述了此类除草剂在杂草体内的作用方式、代谢机制、应用情况及其在土壤中的降解途径,并对该类除草剂的应用与降解研究进行了展望。     

典型咪唑啉酮类除草剂的微生物降解研究进展

咪唑啉酮类除草剂是中国广泛应用的除草剂,具有杀草谱广、活性高、选择性强等优点,但其在土壤中残留期长,影响后茬作物。本文综述了典型的咪唑啉酮类除草剂甲氧咪草烟、咪唑乙烟酸和甲咪唑烟酸残留对后茬作物的影响,探究了降解部分咪唑啉酮类除草剂(甲氧咪草烟、咪唑乙烟酸和咪唑烟酸)的微生物所属类群及降解途径,分析了影响微生物降解咪唑啉酮类除草剂的因素,对目前除草剂污染修复存在的问题进行了讨论,并对未来发展进行了展望。该文对研究咪唑啉酮类除草剂的微生物降解有一定的参考作用。     

Root absorption and translocation of 5-substituted analogs of the imidazolinone herbicide,imazapyr

In preparation for assessing quantitative structure-activity relationships (QSAR) for root absorption and translocation of imidazolinones herbicides, 13 radiolabeled analogs of imazapyr (2-(4-isopropyl–4-methy1–5-oxo-2-imidazolin-2-yl) nicotinic acid) substituted in the 5-position of the pyridine ring were evaluated in corn (Zea mays L.) and sunflower (Helianthus annuus L.). The compounds (10 μm) were supplied to the roots through a hydroponic solution for 8 h and, following harvest, plant tissues were either combusted to measure total uptake of radiolabeled material or were extracted for determination of the extent of degradation of the parent compound. Root absorption in both species varied by two orders of magnitude among analogs while translocation, expressed as a percentage of absorption, varied by only three- or four-fold. Few differences were observed for translocation of radioactivity from sunflower stems to leaves. Although six of the analogs were partially metabolized in corn, little metabolism of the imidazolinone analogs occurred in sunflower. These data indicate that meaningful models of root absorption and subsequent translocation to shoots may be developed for 5-substituted analogs of imazapyr, particularly when applied to sunflower.     

除草剂靶酶-AHAS酶及基因突变体与除草剂设计(Ⅱ).AHAS及W464突变酶与除草活性分子的相互作用

乙酰羟基酸合成酶(AHAS)是磺酰脲类、咪唑啉酮类、三唑嘧啶磺酰胺类及水杨酸类除草剂的作用靶标,大田使用中杂草对这几类除草剂产生抗性的主要因素是AHAS酶的突变。利用大肠杆菌AHAS Ⅱ中464位的色氨酸突变体(W464A、W464F、W464L、W464Y),研究了野生型和突变酶对商品化除草剂(氯嘧磺隆、氯磺隆、咪唑乙烟酸、咪唑喹啉酸)以及烷硫基磺酰脲的敏感性。野生型E. coli AHAS Ⅱ对这些化合物的抑制作用较为敏感,而突变酶对其呈现出不同程度的抗性,使商品化除草剂的抑制常数增加了10~1.0×104倍不等,烷硫基磺酰脲的抑制常数增加幅度较小。烷硫基磺酰脲 1a 对W464L突变酶的高抑制活性,暗示着发展针对靶酶抗性的除草剂的可能性。     

Identification of resistance to either paraquat or ALS-inhibiting herbicides in two Western Australian Hordeum leporinum biotypes

BACKGROUND: Hordeum populations are becoming increasingly difficult to control in cropping fields. Two herbicide‐resistant H. leporinum populations were identified during a random crop survey after herbicides were applied. The study aimed to determine the herbicide resistance profile of these H. leporinum biotypes to a range of herbicides used for their control. RESULTS: Based on dose–response studies, one H. leporinum population was very highly resistant to sulfosulfuron and sulfometuron (both sulfonylurea herbicides) and also displayed low‐level resistance to imazamox (an imidazolinone herbicide). Reduced sensitivity of the ALS enzyme was identified with in vitro activity assays. Gene sequence analysis revealed a proline‐to‐threonine substitution at amino acid position 197 of ALS, which is likely to be the molecular basis for resistance in this population. Herbicide screening also revealed a different H. leporinum population with resistance to the bipyridyl herbicide paraquat. CONCLUSION: This study established the first cases of (1) sulfonylurea‐to‐imidazolinone cross‐resistance and (2) field‐evolved paraquat resistance in a Hordeum species in Western Australia. Copyright © 2012 Society of Chemical Industry     

Complex formation of picloram and related chemicals with metal lons

The complex formation of metal ions with pyridine carboxylic acids was estimated with polarography and spectrophotometry. Picloram (4-amino-3,5,6-trichloropicolinic acid), α-picolinic acid, fusaric acid, dipicolinic acid, and quinolinic acid formed complexes with Fe(III) or Cu(II) whose coordination involves, most probably, a lone pair of electrons of pyridine nitrogen and a carboxylic group. Picloram-metal complexes were, however, estimated to be relatively unstable compared to other pyridine-α-carboxylic acids tested. Effects of pyridine carboxylic acids on oxidation of indole-3-acetic acid (IAA) were tested in vitro in a horseradish protoheme peroxidase system. No significant effect of the pyridine carboxylic acids was observed at 2 × 10^?4M. Also, no concentration effect of picloram (10^?5 to 3 × 10^?3M) was obtained. These results suggest that the phytotoxic action of picloram may not result from the depletion of free metal ions in plants nor inhibition of activity of metal-containing enzymes through strong chelation as hypothesized. Thus, auxin activity of picloram should be explained in other wasy.     

The structural rearrangement of iprodione in ethanolic solution

Iprodione, in ethanolic solution, was found to undergo structural rearrangement over a period of days to give a solid product which was shown by mass spectrometry to be an isomer. Mechanistic considerations led to a proposed structure, which was verified by synthesis of an authentic specimen by an unambiguous route. The biological implications of these findings are discussed.     

Recent advances in the stereoselective synthesis of L-phosphinothricin

L -Phosphinothricin, the parent α-amino acid of the herbicide glufosinate-ammonium, has been obtained in high enantiomeric purity by three different methods. The stereoselective alkylation of a D -valine-derived bis-lactim ether, followed by the hydrolysis of the heterocyclic intermediate, represents an attractive approach for gram-scale quantities in the laboratory. Another very efficient access to L -phosphinothricin consists of the asymmetric hydrogenation of a prochiral α-acylamido acrylate with a chiral bis-phosphine-rhodium catalyst, while the reaction of chiral pre-built C-4-fragments, like L -vinylglycine or L -2-amino-4-halobutyric acid, which can be obtained from the inexpensive starting materials L -aspartic acid and L -glutamic acid, with (methyl)phosphinic acid derivatives represents a third route which allows the production of nearly enantiomerically pure L -phosphinothricin.     

Influence of metal salts on the photodegradation of imazapyr, an imidazolinone pesticide

The behaviour of imazapyr (2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)nicotinic acid), a broad spectrum herbicide of the imidazolinone family, has been studied under UV radiation in the presence of metal salts. Complexation interactions between imazapyr and metal ions decreased imazapyr photolysis. A chemometric study compared the photodegradation of imazapyr in aqueous solutions in the presence of Na+, Ca2+ or Cu2+ and their concomitant anionic species (Cl-, NO3-) at various pesticide/metal ion molar ratios. The study showed the major role of metal ions in the degradation of imazapyr and its main photoproducts. The molecules were strongly stabilised on complexation with metal ions, leading to an increase in persistence of the pesticide.     

Sulfonylurea resistance in Stellaria media [L.] Vill.

A sulfonylurea resistant biotype of common chickweed (Stellaria media L. Vill.) was found in a field treated with chlorsulfuron or metsulfuron for eight consecutive years. In pot experiments the biotype was resistant to postemergence treatments with the following acetolactate synthase (ALS) inhibitors: chlorsulfuron, metsulfuron, tribenuron, triasulfuron, rimsulfuron, sulfometuron, flumetsulam and imazapyr. The level of resistance to chlorsulfuron and sulfometuron was higher than to the other sulfonylurea herbicides. Whereas the level of cross resistance to the triazolopyrimidine herbicide, flumetsulam was comparable to that of metsulfuron, that of imazapyr was significantly lower. In contrast to imazapyr the biotype was not resistant to imazethapyr, an other imidazolinone herbicide. ALS in vitro assays revealed that resistance was due to an ALS enzyme that was less sensitive to ALS inhibiting herbicides. Herbicides with different modes of action were equally effective on the susceptible and resistant biotypes.     

Imidazolinone-tolerant crops: history, current status and future

Imidazolinone herbicides, which include imazapyr, imazapic, imazethapyr, imazamox, imazamethabenz and imazaquin, control weeds by inhibiting the enzyme acetohydroxyacid synthase (AHAS), also called acetolactate synthase (ALS). AHAS is a critical enzyme for the biosynthesis of branched-chain amino acids in plants. Several variant AHAS genes conferring imidazolinone tolerance were discovered in plants through mutagenesis and selection, and were used to create imidazolinone-tolerant maize (Zea mays L), wheat (Triticum aestivum L), rice (Oryza sativa L), oilseed rape (Brassica napus L) and sunflower (Helianthus annuus L). These crops were developed using conventional breeding methods and commercialized as Clearfield* crops from 1992 to the present. Imidazolinone herbicides control a broad spectrum of grass and broadleaf weeds in imidazolinone-tolerant crops, including weeds that are closely related to the crop itself and some key parasitic weeds. Imidazolinone-tolerant crops may also prevent rotational crop injury and injury caused by interaction between AHAS-inhibiting herbicides and insecticides. A single target-site mutation in the AHAS gene may confer tolerance to AHAS-inhibiting herbicides, so that it is technically possible to develop the imidazolinone-tolerance trait in many crops. Activities are currently directed toward the continued improvement of imidazolinone tolerance and development of new Clearfield* crops. Management of herbicide-resistant weeds and gene flow from crops to weeds are issues that must be considered with the development of any herbicide-resistant crop. Thus extensive stewardship programs have been developed to address these issues for Clearfield* crops.     

安全剂减轻磺酰脲类和咪唑啉酮类除草剂药害的作用机制

本文综述了安全剂减轻磺酰脲类和咪唑啉酮类除草剂药害的作用及安全剂的作用机制。     

Point mutations including a novel Pro-197-Phe mutation confer cross-resistance to acetolactate synthase (ALS) inhibiting herbicides in Lactuca serriola in Australia

BACKGROUND

Control of prickly lettuce has become increasingly difficult for lentil growers in southern Australia because of widespread resistance to common herbicides, a lack of alternative herbicide options and the prolific production of highly mobile seed. This study aimed to quantify acetolactate synthase (ALS)-inhibiting herbicide resistance in the Mid North (MN) and Yorke Peninsula (YP) of South Australia, characterize the resistance mutations present and investigate population structure and gene flow in this species.

RESULTS

Resistance was identified in all populations tested, with average survival of 92% to chlorsulfuron and 95% to imazamox + imazapyr. Five different amino acid substitutions were identified at proline 197 of the ALS gene. There was no significant difference in the median lethal dose (LD₅₀) between plants with these five different substitutions when treated with metsulfuron-methyl; however, the imidazolinone resistance level was higher in plants with a phenylalanine substitution and lower in plants with a serine. Population structure based on 701 single nucleotide polymorphisms and 271 individuals provided evidence for both independent evolution of the same mutation in different populations, as well as frequent short- to medium-distance dispersal accompanied by occasional long-distance dispersal events. The overall inbreeding coefficient (F_IS) was calculated at 0.5174, indicating an intermediate level of outcrossing despite the cross-pollination experiment showing only low outcrossing. In the structure analyses, most individuals from YP were assigned to a single cluster, whereas most individuals from MN were assigned 50% to each of two clusters, indicating some genetic differences between these two regions, but also evidence for dispersal between them.

CONCLUSIONS

Use of imidazolinone herbicides has selected for mutations conferring higher levels of resistance, such as the Pro-197-Phe mutation, and resulted in further spread of resistance in this species. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.     

The importance of trifluoromethyl pyridines in crop protection

The pyridine ring, substituted by a trifluoromethyl substituent has been successfully incorporated into molecules with useful biological properties. During the period 1990 to September 2017, 14 crop protection products bearing a trifluoromethyl pyridine have been commercialized or proposed for an ISO common name, covering fungicides, herbicides, insecticides and nematicides. Chemical processes have been developed to provide trifluoromethyl pyridine intermediates, from non‐fluorinated pyridine starting materials, at scale and with affordable costs of goods. These attractive starting materials were readily adopted by research chemists, and elaborated through simple chemical modifications into new active ingredients. In a second approach, substituted trifluoromethyl pyridine rings have been constructed from acyclic, trifluoromethyl starting materials, which again has served to identify new active ingredients. Molecular matched pair analysis reveals subtle, yet important differences in physicochemical and agronomic properties of trifluoromethyl pyridines compared with the phenyl analogues. This review focuses on the past 27 years, seeking to identify reasons behind the success of such research programmes, and inspire the search for new crop protection chemicals containing the trifluoromethyl pyridine ring. © 2017 Society of Chemical Industry     

除草剂与乙酰乳酸合成酶相互作用的分子机理研究进展

综述了酵母乙酰乳酸合成酶(ScALS)与磺酰脲类除草剂氯嘧磺隆(chlorimuron-ethyl,CE)形成的复合物在0.28 nm分辨率下的晶体结构及拟南芥乙酰乳酸合成酶(AtALS)与磺酰脲类和咪唑啉酮类除草剂复合物的三维结构。除草剂的分子结构与酶、底物并不相似,但它们与酶形成的复合物可阻断底物进入酶活性位点通路而起抑制作用。连接磺酰脲的10个氨基酸残基同样连接咪唑喹啉酸,另有6个残基只与磺酰脲而不与咪唑喹啉酸相连,有2个残基只与咪唑喹啉酸而不与磺酰脲相连,即两种抑制剂占据了特别的重叠位点,但以不同方式连接。抗性杂草的产生是因为突变株ALS的残基位点变异,从而引起除草剂与ALS结合方式的变化。这些研究对进一步理解除草剂与靶分子的作用方式及除草剂的分子药物设计具有重要的指导作用。     

Key chemical inputs to new herbicides: Intermediates,processes and mechanistic investigations

The key chemical inputs that led to the discovery of the three herbicides CGA 215684 (a cyclohexanedione), CGA 244126 (a substituted pyridine) and CGA 152005 (sulfonylurea) and the plant-growth regulant CGA 163935 (a cyclohexanedione) are described.