{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:52:48Z","timestamp":1791183168662,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Sulfonyl exchange electrophiles are increasingly used in covalent probe and drug discovery, yet their intrinsic reactivity and plasma stability remain poorly defined, limiting rational warhead selection. Here we establish a systematic LC\u2010MS framework to quantify the reactivity of sulfonyl imidazole and triazole electrophiles across key biological nucleophiles together with matched plasma stability. Sulfonyl imidazoles display attenuated cysteine reactivity and markedly improved stability while retaining intrinsic tyrosine reactivity, whereas sulfonyl triazoles exhibit high electrophilicity and rapid degradation. These data reveal clear relationships between aryl electronics, leaving group ability, nucleophile selectivity, and\n                    <jats:italic>in vivo<\/jats:italic>\n                    \u2010relevant stability. To demonstrate practical utility, we applied a SuFEx\u2010click transformation to convert the kinase\u2010directed probe XO44 into a sulfonyl imidazole analogue, yielding a stable SuDEx probe (JL\u201051) that maintains the proteome\u2010labeling profile of the parent reagent. The corresponding sulfonyl triazole congener was rapidly hydrolyzed. This work provides a mechanistic foundation and practical strategy for designing next\u2010generation sulfonyl exchange covalent probes.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70353","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:35:06Z","timestamp":1791182106000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intrinsic Reactivity of Sulfonyl Imidazole and Triazole Electrophiles for Covalent Probe Design"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3681-0473","authenticated-orcid":false,"given":"Paramita","family":"Pal","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology Dana\u2010Farber Cancer Institute Boston Massachusetts USA"},{"name":"Department of Pediatrics Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7100-2250","authenticated-orcid":false,"given":"Hannah","family":"Unsworth","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology Dana\u2010Farber Cancer Institute Boston Massachusetts USA"},{"name":"Department of Pediatrics Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8388-5865","authenticated-orcid":false,"given":"Lyn H.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology Dana\u2010Farber Cancer Institute Boston Massachusetts USA"},{"name":"Department of Pediatrics Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/bs.armc.2020.10.001","article-title":"Design of Next\u2010Generation Covalent Inhibitors: Targeting Residues Beyond Cysteine","volume":"56","author":"Jones L. H.","year":"2021","journal-title":"Annual Reports in Medicinal Chemistry"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00542-z"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2024.08.006"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01153"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c01825"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/c5sc00408j"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/d5sc02647d"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201309399"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.5c00001"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.8b00276"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/d0cb00180e"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.3c00371"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/d2cb00078d"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/d2md00258b"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b08536"},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1021\/cr00002a004","article-title":"A Survey of Hammett Substituent Constants and Resonance and Field Parameters","volume":"91","author":"Hansch C.","year":"1991","journal-title":"Chemical Reviews"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-019-0404-5"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2025.100963"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2025.100961"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2025.100906"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42360-w"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.1c00199"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c18691"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.08.009"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl5829"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.2c00633"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.1c01591"}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.70353","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ardp.70353","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.70353","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:35:07Z","timestamp":1791182107000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.70353"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":27,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/ardp.70353"],"URL":"https:\/\/doi.org\/10.1002\/ardp.70353","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-08-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70353"}}