Chiral Triazole Fungicide Difenoconazole: Absolute Stereochemistry, Stereoselective Bioactivity, Aquatic Toxicity, and Environmental Behavior in Vegetables and Soil

Abstract

In this study, the systemic assessments of the stereoisomers of triazole fungicide difenoconazole are reported for the first time, including absolute stereochemistry, stereoselective bioactivity toward pathogens (Alternaria sonali, Fulvia fulva, Botrytis cinerea, and Rhizoctonia solani), and toxicity toward aquatic organisms (Scenedesmus obliquus, Daphnia magna, and Danio rerio). Moreover, the stereoselective degradation of difenoconazole in vegetables (cucumber, Cucumis sativus and tomato, Lycopersicon esculentum) under field conditions and in soil under laboratory-controlled conditions (aerobic and anaerobic) was investigated. There were 1.33-24.2-fold and 1.04-6.78-fold differences in bioactivity and toxicity, respectively. Investigations on the stereoselective degradation of difenoconazole in vegetables showed that the highest-toxic and lowest-bioactive (2S,4S)-stereoisomer displays a different enrichment behavior in different plant species. Under aerobic or anaerobic conditions, (2R,4R)- and (2R,4S)-difenoconazole were preferentially degraded in the soil. Moreover, difenoconazole was configurationally stable in the test soil matrices. On the basis of biological activity, ecotoxicity, and environmental behavior, it is likely that the use of pure (2R,4S)-difenoconazole instead of the commercial stereoisomer mix may help to increase the bioactivity and reduce environmental pollution.

Chiral profiling of azole antifungals in municipal wastewater and recipient rivers of the Pearl River Delta, China

“…The estimated half-lives of difenoconazole stereoisomers ranged from 169.0 to 238.9 days and from 177.7 to 315.0 days under aerobic and anaerobic conditions, respectively (Dong et al 2013). Many azole antifungals contain one or more chiral centers in their structures and consequently have one or more enantiomer pairs.…”

“…Many azole antifungals contain one or more chiral centers in their structures and consequently have one or more enantiomer pairs. Chiral triazole fungicide difenoconazole was found to be stereoselective in both fungicidal activity and toxicity towards nontarget organisms (Dong et al 2013). Fipronil was enantioselectively transformed by rainbow trout indicated by changes of its enantiomeric fraction over time (Knowick et al 2006).…”

“…Difenoconazole showed moderately and slightly enantioselective degradation in soil under aerobic and anaerobic conditions, with enrichment of (2S,4S)-and (2S,4R)-difenoconazole, respectively (Dong et al 2013). Therefore, it is necessary to reveal the enantiomer-specific fate of the azole antifungals in the environment in order to assess accurately their ecological effects as well as provide guidance for future application of these antifungals (Li et al 2012;Dong et al 2013).…”

Stereoselective metabolism, distribution, and bioaccumulation brof triadimefon and triadimenol in lizards

“…Nevertheless, the bioactivity, toxicity, metabolism, excretion, distribution, and bioaccumulation of these enantiomers may be entirely different (Williams, 1996). The enantiomers of chiral pesticides could be different when binding to structure-sensitive biological receptors and naturally occurring chiral biomolecules because of their different molecular configurations (Dong et al, 2013). Stereoselectivity in the processes of absorption, distribution, metabolism, and bioaccumulation in organisms may result in ecotoxicological effects that are beyond the traditional knowledge that treat them as single compounds in risk assessment (Buser et al, 2002;Dong et al, 2013;Wong, 2006).…”

“…The enantiomers of chiral pesticides could be different when binding to structure-sensitive biological receptors and naturally occurring chiral biomolecules because of their different molecular configurations (Dong et al, 2013). Stereoselectivity in the processes of absorption, distribution, metabolism, and bioaccumulation in organisms may result in ecotoxicological effects that are beyond the traditional knowledge that treat them as single compounds in risk assessment (Buser et al, 2002;Dong et al, 2013;Wong, 2006). TF has one chiral center and consists of an equimolecular mixture of the two enantiomers while TN has two chiral centers and consists of four stereoisomers including two pairs of diastereomers.…”