{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:04:47Z","timestamp":1789567487320,"version":"build-2803163510"},"reference-count":33,"publisher":"American Chemical Society (ACS)","issue":"36","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22301004"],"award-info":[{"award-number":["22301004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFD1702102"],"award-info":[{"award-number":["2023YFD1702102"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The gem-difluoroalkylthio (\u2212SCF2\u2212) moiety has achieved great success in medicinal chemistry, but its application in agrochemicals remains underexplored because of synthetic challenges. Herein, we report a series of 1,2,4-triazole derivatives bearing the gem-difluoromethylthio group and evaluate their antifungal activities against ten phytopathogenic strains. Compound 7n exhibits potent broad-spectrum activity, with EC50 values of 0.007, 0.121, 0.122, and 0.068 \u03bcg\/mL against Botrytis cinerea, Phytophthora capsici, Curvularia lunata, and Alternaria solani, respectively, outperforming tebuconazole. In vivo, 7n shows protective and curative efficacy comparable to tebuconazole on apple fruits, tomato fruits, and Suzhou Qing leaves. Mechanistic studies, including scanning electron microscopy (SEM), transcriptomics, qRT-PCR, and molecular docking, indicate that 7n disrupts mycelial morphology, interferes with membrane-associated processes, and inhibits sterol biosynthesis by targeting CYP51. These findings highlight the \u2212SCF2\u2013 group as a promising scaffold for novel agricultural fungicides.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c06979","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T23:02:01Z","timestamp":1788562921000},"page":"28314-28325","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis, and Fungicidal Activity Evaluation\nof 1,2,4-Triazole Fungicides Featuring\n                    <i>gem<\/i>\n                    -Difluoromethylthio\nMoiety"],"prefix":"10.1021","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1491-7605","authenticated-orcid":true,"given":"Junqing","family":"Liang","sequence":"first","affiliation":[{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]},{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]},{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Miao","sequence":"additional","affiliation":[{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]},{"name":"University of Science and Technology of China , , ,","place":["Hefei, China, 230026"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqian","family":"Xu","sequence":"additional","affiliation":[{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zili","family":"Ren","sequence":"additional","affiliation":[{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]},{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]},{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7139-9501","authenticated-orcid":true,"given":"Yuntian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]},{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]},{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8731-1068","authenticated-orcid":true,"given":"Quan","family":"Gao","sequence":"additional","affiliation":[{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]},{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]},{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7652-5538","authenticated-orcid":true,"given":"Jiawang","family":"Wang","sequence":"additional","affiliation":[{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]},{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]},{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3653-3450","authenticated-orcid":true,"given":"Haiqun","family":"Cao","sequence":"additional","affiliation":[{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]},{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]},{"name":"Anhui Agricultural University , , ,","place":["Hefei, China, 230036"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"2026091609100303500_cit1","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1126\/science.1131943","article-title":"Fluorine in Pharmaceuticals: Looking\nBeyond Intuition","volume":"317","author":"Mu\u0308ller","year":"2007","journal-title":"Science"},{"key":"2026091609100303500_cit2","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1039\/B711844A","article-title":"Understanding\nOrganofluorine Chemistry. An Introduction to the C-F Bond","volume":"37","author":"O\u2019Hagan","year":"2008","journal-title":"Chem. Soc. Rev."},{"key":"2026091609100303500_cit3","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1038\/nature10108","article-title":"Catalysis for Fluorination and Trifluoromethylation","volume":"473","author":"Furuya","year":"2011","journal-title":"Nature"},{"key":"2026091609100303500_cit4","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1039\/B610213C","article-title":"Fluorine in\nMedicinal Chemistry","volume":"37","author":"Purser","year":"2008","journal-title":"Chem. Soc. Rev."},{"issue":"21","key":"2026091609100303500_cit5","doi-asserted-by":"publisher","first-page":"10710","DOI":"10.1021\/acs.chemrev.8b00037","article-title":"In Vivo Photopharmacology","volume":"118","author":"Hu\u0308ll","year":"2018","journal-title":"Chem. Rev."},{"key":"2026091609100303500_cit6","doi-asserted-by":"publisher","first-page":"4359","DOI":"10.1021\/jm800219f","article-title":"The Many\nRoles for Fluorine in Medicinal Chemistry","volume":"51","author":"Hagmann","year":"2008","journal-title":"J.\nMed. Chem."},{"key":"2026091609100303500_cit7","doi-asserted-by":"publisher","first-page":"21344","DOI":"10.1021\/acs.jafc.4c04239","article-title":"Application of Difluoromethyl\nIsosteres in the Design of Pesticide\nActive Molecules","volume":"72","author":"Zhang","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"2026091609100303500_cit8","doi-asserted-by":"publisher","first-page":"11019","DOI":"10.1021\/acs.jafc.1c08383","article-title":"Trifluoromethylpyridine:\nAn Important Active Fragment for the Discovery of New Pesticides","volume":"70","author":"Zheng","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"2026091609100303500_cit9","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1248\/cpb.49.173","article-title":"New Antifungal 1,2,4-Triazoles\nwith Difluoro(substituted sulfonyl)methyl Moiety","volume":"49","author":"Eto","year":"2001","journal-title":"Chem. Pharm. Bull."},{"key":"2026091609100303500_cit10","unstructured":"Denis, D.; Daniel, D.; Laurence, D.; Michel, G.; Yves, G.; Patrick, L.; Dwight, M.\n          8-(Biaryl) Quinoline PDE4 Inhibitors. WO2004\/0008141A, 2004."},{"key":"2026091609100303500_cit11","unstructured":"Kaneko, S.; Tsuruoka, H.; Honzumi, M.; Abe, M.; Yoshida, T.\n          Dipyridylamine Derivative. WO2012\/121314A1, 2012."},{"key":"2026091609100303500_cit12","doi-asserted-by":"publisher","first-page":"9691","DOI":"10.1021\/acs.jmedchem.8b01196","article-title":"Design\nand Activity\nof Specific Hypoxia-Inducible Factor-2\u03b1 (HIF-2\u03b1) Inhibitors\nfor the Treatment of Clear Cell Renal Cell Carcinoma: Discovery of\nClinical Candidate (S)-3-((2,2-Difluoro-1-hydroxy-7 (methylsulfonyl)-2,3-dihydro-1H-inden-4-yl)oxy)-5-fluorobenzoni\ntrile (PT2385)","volume":"61","author":"Wehn","year":"2018","journal-title":"J. Med. Chem."},{"key":"2026091609100303500_cit13","doi-asserted-by":"publisher","first-page":"3065","DOI":"10.1002\/ps.7921","article-title":"Recent Developments\nin Fluorine-Containing Pesticides","volume":"80","author":"Jeschke","year":"2024","journal-title":"Pest Manage.\nSci."},{"key":"2026091609100303500_cit14","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1039\/D1OB02268G","article-title":"Access\nto \u03b1,\u03b1-Difluoro(arylthio)methyl Oxetanes from \u03b1,\u03b1-Difluoro(arylthio)methyl\nKetones and Trimethylsulfoxonium Halides: Scope, Mechanism and Applications","volume":"20","author":"Cai","year":"2022","journal-title":"Org. Biomol. Chem."},{"key":"2026091609100303500_cit15","doi-asserted-by":"publisher","first-page":"12038","DOI":"10.1002\/anie.202017271","article-title":"Solvent-Switched\nOxidation Selectivities with O2: Controlled Synthesis of\n\u03b1-Difluoro(thio)methylated Alcohols and Ketones","volume":"60","author":"Liu","year":"2021","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026091609100303500_cit16","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1002\/jhet.4767","article-title":"Research Progress\nof Triazole Derivatives in the Discovery of Agricultural Chemicals","volume":"61","author":"Song","year":"2024","journal-title":"J. Heterocyclic Chem."},{"key":"2026091609100303500_cit17","doi-asserted-by":"publisher","first-page":"617","DOI":"10.16801\/j.issn.1008-7303.2021.0065","article-title":"Research Progress\nin Chromatographic Separation of Triazole Fungicides Containing Two\nChiral Centers","volume":"23","author":"Tang","year":"2021","journal-title":"Chin. J. Pestic. Sci."},{"key":"2026091609100303500_cit18","doi-asserted-by":"publisher","first-page":"462","DOI":"10.2174\/1568026621999201214232018","article-title":"Recent Advances\nin the Development of 1,2,3-Triazole-Containing Derivatives as Potential\nAntifungal Agents and Inhibitors of Lanoster ol 14\u03b1- demethylase","volume":"21","author":"Haroun","year":"2021","journal-title":"Curr. Top Med. Chem."},{"key":"2026091609100303500_cit19","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s12154-014-0121-1","article-title":"Resistance to Antifungals\nthat Target CYP51","volume":"7","author":"Parker","year":"2014","journal-title":"J. Chem. Biol."},{"key":"2026091609100303500_cit20","doi-asserted-by":"publisher","first-page":"3830","DOI":"10.1128\/AEM.00027-11","article-title":"Impact\nof Recently Emerged Sterol\n14\u03b1-Demethylase (CYP51) Variants of Mycosphaerella graminicola on Azole Fungicide Sensitivity","volume":"77","author":"Cools","year":"2011","journal-title":"Appl. Environ.\nMicrobiol."},{"key":"2026091609100303500_cit21","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1094\/PHYTO-10-22-0370-KD","article-title":"Fungicide\nResistance: Progress in Understanding Mechanism, Monitoring,\nand Management","volume":"113","author":"Yin","year":"2023","journal-title":"Phytopathology"},{"key":"2026091609100303500_cit22","doi-asserted-by":"publisher","first-page":"4303","DOI":"10.1021\/acs.jafc.2c00541","article-title":"Novel Dioxolane\nRing Compounds for\nthe Management of Phytopathogen Diseases as Ergosterol Biosynthesis\nInhibitors: Synthesis, Biological Activities, and Molecular Docking","volume":"70","author":"Min","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"2026091609100303500_cit23","doi-asserted-by":"publisher","first-page":"27075","DOI":"10.1021\/acs.jafc.4c07227","article-title":"Design,\nSynthesis, and Assessment of Fungicidal Activity of Active Substructure\n1,2,4-Triazole Containing Coumarin","volume":"72","author":"Lv","year":"2024","journal-title":"J. Agric.\nFood Chem."},{"key":"2026091609100303500_cit24","doi-asserted-by":"publisher","first-page":"4630","DOI":"10.1021\/acs.jafc.3c07628","article-title":"Discovery of Potential Rosin-Based Triazole Antifungal Candidates\nto Control Valsamali for Sustainable Crop Protection","volume":"72","author":"Xu","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"2026091609100303500_cit25","doi-asserted-by":"publisher","first-page":"24549","DOI":"10.1021\/acs.jafc.5c02767","article-title":"Novel 1,2,4-Triazole\nDerivatives\nContaining a Benzenesulfonamide Moiety as Potential Antifungal Agents\nfor Controlling Postharvest Soft Rot in Kiwifruit","volume":"73","author":"Wu","year":"2025","journal-title":"J. Agric. Food Chem."},{"key":"2026091609100303500_cit26","doi-asserted-by":"publisher","first-page":"4797","DOI":"10.1021\/acs.orglett.3c01468","article-title":"N-Difluoromethylthiophthalimide\nReagents for Modular Synthesis of\nDiversified \u03b1-Difluoromethylthiolated Ketones","volume":"25","author":"Liang","year":"2023","journal-title":"Org. Lett."},{"key":"2026091609100303500_cit27","doi-asserted-by":"publisher","first-page":"5747","DOI":"10.1039\/D5OB00520E","article-title":"Organocatalytic Enantioselective\n\u03b1-Difluoromethylketone Thiolation of \u03b2-Keto Esters Using\nPhthalimide-SCF2COAr","volume":"23","author":"Chang","year":"2025","journal-title":"Org. Biomol.\nChem."},{"key":"2026091609100303500_cit28","doi-asserted-by":"publisher","first-page":"6844","DOI":"10.1021\/acs.orglett.9b02474","article-title":"Nickel-Catalyzed\nCoupling Reaction of \u03b1-Bromo-\u03b1-fluoroketones\nwith Arylboronic Acids toward the Synthesis of \u03b1-Fluoroketones","volume":"21","author":"Liang","year":"2019","journal-title":"Org. Lett."},{"key":"2026091609100303500_cit29","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1002\/adsc.201701569","article-title":"Palladium-Catalyzed Benzodifluoroalkylation\nof Alkynes: A Route to\nFluorine-Containing 1,1-Diarylethylenes","volume":"360","author":"Liang","year":"2018","journal-title":"Adv.\nSynth. Catal."},{"key":"2026091609100303500_cit30","doi-asserted-by":"publisher","DOI":"10.1016\/j.agrcom.2024.100030","article-title":"Unlocking Nature\u2019s Potential: Novel Isomagnolone Analogues\nas Broad-spectrum Antimicrobial Agents for Plant Disease Control","volume":"2","author":"Yan","year":"2024","journal-title":"Agric. Commun."},{"key":"2026091609100303500_cit31","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.3390\/microorganisms11051225","article-title":"Membrane Protein Bcest Is Involved\nin Hyphal Growth,\nVirulence and Stress Tolerance of Botrytis cinerea","volume":"11","author":"Zhang","year":"2023","journal-title":"Microorganisms"},{"key":"2026091609100303500_cit32","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.951751","article-title":"Antifungal\nMechanism of (E)-2-Hexenal Against Botrytis cinerea Growth\nRevealed by Transcriptome Analysis","volume":"13","author":"Song","year":"2022","journal-title":"Front. Microbiol."},{"key":"2026091609100303500_cit33","doi-asserted-by":"publisher","DOI":"10.1038\/srep31045","article-title":"Synthesis, Biological\nEvaluation,\nand Molecular Modeling Studies of New Oxadiazole-Stilbene Hybrids\nagainst Phytopathogenic Fungi","volume":"6","author":"Jian","year":"2016","journal-title":"Sci. Rep."}],"container-title":["Journal of Agricultural and Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c06979","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/36\/28314\/68394347\/acs.jafc.6c06979.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/36\/28314\/68394347\/acs.jafc.6c06979.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:14:44Z","timestamp":1789564484000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/36\/28314\/5421799\/Design-Synthesis-and-Fungicidal-Activity"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,4]]},"references-count":33,"journal-issue":{"issue":"36","published-online":{"date-parts":[[2026,9,4]]},"published-print":{"date-parts":[[2026,9,16]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c06979","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,4]]}}}