Gerrit J. deBoer

Discovery and Characterization of Sulfoxaflor, a Novel Insecticide Targeting Sap-Feeding Pests

The discovery of sulfoxaflor [N-[methyloxido[1-[6-(trifluoromethyl)-3-pyridinyl]ethyl]-λ(4)-sulfanylidene] cyanamide] resulted from an investigation of the sulfoximine functional group as a novel bioactive scaffold for insecticidal activity and a subsequent extensive structure-activity relationship study. Sulfoxaflor, the first product from this new class (the sulfoximines) of insect control agents, exhibits broad-spectrum efficacy against many sap-feeding insect pests, including aphids, whiteflies, hoppers, and Lygus, with levels of activity that are comparable to those of other classes of insecticides targeting sap-feeding insects, including the neonicotinoids. However, no cross-resistance has been observed between sulfoxaflor and neonicotinoids such as imidacloprid, apparently the result of differences in susceptibility to oxidative metabolism. Available data are consistent with sulfoxaflor acting via the insect nicotinic receptor in a complex manner. These observations reflect the unique structure of the sulfoximines compared with neonicotinoids.

The impact of uptake, translocation and metabolism on the differential selectivity between blackgrass and wheat for the herbicide pyroxsulam

BACKGROUND Wheat shows selectivity to pyroxsulam, a new broad-spectrum herbicide with high activity on blackgrass. Studies were performed to establish whether uptake, translocation or metabolism were responsible for the differential activity in wheat compared with blackgrass. In addition, the effect of the safener cloquintocet-mexyl on metabolism was evaluated in wheat and blackgrass shoots. RESULTS Root uptake of pyroxsulam in blackgrass was significantly higher than in wheat, suggesting a possible activity enhancement in blackgrass owing to root uptake. Translocation to foliage from root uptake as well as translocation out of treated foliage following foliar applications was low in wheat compared with blackgrass, likely owing to the rapid metabolism of pyroxsulam in wheat. Wheat metabolized pyroxsulam significantly faster than blackgrass to the less active O-dealkylation product. Wheat shoots metabolized pyroxsulam faster when the safener cloquintocet-mexyl was present, but cloquintocet-mexyl did not increase the rate of metabolism in blackgrass. CONCLUSIONS The selectivity of pyroxsulam to wheat relative to blackgrass was connected primarily with differences in the rate of metabolism and generation of an inactive metabolite. Metabolism in wheat restricted subsequent movement of radioactivity out of the treated leaf. The rapid metabolism in wheat was increased by the addition of cloquintocet-mexyl.

Systemic properties of myclobutanil in soybean plants, affecting control of Asian soybean rust (Phakopsora pachyrhizi)

BACKGROUND The demethylation inhibitor (DMI) fungicide myclobutanil can be an effective component of spray programmes designed to control the highly destructive plant pathogen Phakopsora pachyrhizi Syd. & P. Syd., causal agent of Asian soybean rust. Myclobutanil is known from previous studies in grapevines to be xylem mobile. This study investigates the mobility profile of myclobutanil in soybean as an important component of its effective field performance. RESULTS Over a 12 day period under greenhouse conditions, a constant uptake of myclobutanil from leaflet surfaces into the leaflet tissue was observed. Once in the leaflet, myclobutanil was seen to redistribute throughout the tissue, although no movement out of leaflets occurred owing to a lack of phloem mobility. The ability of myclobutanil to redistribute over distance within the soybean plant was revealed when visualizing movement of the compound to foliage above the point of application on the plant stem. An efficacy bioassay demonstrated that the systemic properties of myclobutanil allow control of disease at a point remote from the initial site of compound application. CONCLUSION It is suggested that the high degree of xylem systemicity displayed by myclobutanil in soybean foliage is a contributory factor towards its commercial effectiveness for control of Asian soybean rust.

Pro-insecticidal approach towards increasing in planta activity.

BACKGROUND The adrenergic mode of action was investigated for the development of potential new insecticides. Clonidine-related analogs were tested against Myzus persicae (Sulzer) and Bemisia tabaci (Gennadius). Clonidine analogs lack translation owing to a possible vacuole-trapping mechanism. Physical property modulation via a prodrug approach was attempted to overcome this mechanism. RESULTS Clonidine showed insecticidal activity against M. persicae and B. tabaci. A prodrug of a known open-chain analog of clonidine was developed. While the prodrug had decreased pKa and increased lipophilicity and displayed good activity against M. persicae B. tabaci, the activity did not translate to cotton. Metabolic studies showed that the prodrug was quickly metabolized to the parent compound, and was further metabolized to a known vacuole-trapped oxazoline analog. CONCLUSIONS Adrenergic active compounds, such as clonidine analogs, show potential as insecticides; however, a designed prodrug approach did not overcome the lack of translation in this case. Studies confirmed that the synthesized prodrug analog metabolized in planta to the proposed vacuole-trapped compound. One possible explanation for the failure of this approach is that the rate of metabolism and vacuole trapping is faster than translaminar flow, and therefore the released pesticide is not biologically available to the target organism.

Understanding the Differential Response of Setaria viridis L. (green foxtail) and Setaria pumila Poir. (yellow foxtail) to Pyroxsulam

Green foxtail [Setaria viridis (L) Beauv.] and yellow foxtail [Setaria pumila (Poir.) Roem. & Schult.] are among the most abundant and troublesome annual grass weeds in cereal crops in the Northern Plains of the United States and the Prairie Provinces of Canada. Greenhouse and laboratory experiments were conducted to examine the differential responses of both weed species to foliar applications of the new triazolopyrimidine sulfonamide acetolactate synthase-inhibiting herbicide, pyroxsulam, and to determine the mechanism(s) of differential weed control. Foliar applications of pyroxsulam resulted in >90% control of yellow foxtail at rates between 7.5 and 15 g ai ha-1, whereas the same rates resulted in a reduced efficacy on green foxtail (≤81%). The absorption and translocation of [14C]pyroxsulam in green and yellow foxtail were similar and could not explain the differential whole-plant efficacy. Studies with [14C]pyroxsulam revealed a higher percentage of absorbed pyroxsulam was metabolized into an inactive metabolite in the treated leaf of green foxtail than in the treated leaf of yellow foxtail. Metabolism studies demonstrated that, 48 h after application, 50 and 35% of pyroxsulam in the treated leaf was converted to 5-hydroxy-pyroxsulam in green and yellow foxtail, respectively. The acetolactate synthase (ALS) inhibition assay showed that ALS extracted from green foxtail was more tolerant to pyroxsulam than the enzyme extracted from yellow foxtail was. The in vitro ALS assay showed IC50 values of 8.39 and 0.26 μM pyroxsulam for green and yellow foxtail, respectively. The ALS genes from both green and yellow foxtail were sequenced and revealed amino acid differences; however, the changes are not associated with known resistance-inducing mutations. The differential control of green and yellow foxtail following foliar applications of pyroxsulam was attributed to differences in both metabolism and ALS sensitivity.

Assessment of phloem mobility of xenobiotics in Triticum aestivum and Brachypodium distachyon

Due to evolved resistance and environmental regulations, there is a particular need in the agricultural market for a new graminicide. An essential requirement of a novel, foliar applied graminicide is sufficient phloem mobility in the plant to reach meristematic tissues for the expression of activity leading to the desired control of unwanted vegetative growth. A robust and reliable phloem bioassay utilising a monocot species is highly desirable for early stage experimental compounds. Vascular tissues and translocation patterns of organic compounds in purple false brome (Brachypodium distachyon L. P. Beauv.), a model organism for temperate grasses, were studied and compared with those of wheat (Triticum aestivum L.). Microscopic studies with tracer dyes were used to determine if B. distachyon has a xylem discontinuity between the developing seed and the rachilla xylem, the same as found in T. aestivum. Based on 14C-radiolabelled and non-radiolabelled studies using known xylem and phloem mobile pesticidal compounds, there was a significant difference in the amount of the xylem mobile compounds in the chaff and stem as compared with the phloem mobile compounds found in the grain. The findings described in this report show a clear evidence of xylem discontinuity in B. distachyon, and provide a novel system for a rapid screening of phloem mobility of herbicides in monocot species.