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Herein, we report the first formation of a high-valent Mn(V)\u2013nitrido complex within a de novo designed protein scaffold and demonstrate that a reactive precursor to this species can be catalytically intercepted for enantioselective aziridination. A Mn(V)\u2261N unit derived from an abiological diphenyl porphyrin is confined within a designed helical bundle protein, where the protein environment suppresses bimolecular decay and enables detailed spectroscopic characterization. Electron paramagnetic resonance, resonance Raman, and circular dichroism spectroscopies confirm formation of a low-spin Mn(V)\u2013nitrido species that is stable for weeks at room temperature and exhibits minimal perturbation of the Mn\u2261N unit upon modulation of the axial histidine ligand, while catalytic activity and stereochemical outcome are sensitive to its presence. Mechanistic studies identify monochloramine (NH2Cl) as the operative nitrogen-atom donor and support the involvement of a transient Mn-bound N-transfer intermediate en route to nitrido formation. Under catalytic conditions, this intermediate is intercepted to perform aziridination with TON \u2248 180 and an enantiomeric ratio of 65:35. Together, these results establish de novo protein design as a platform for stabilizing high-valent metal\u2013nitrido species and harnessing their reactivity for nitrogen-atom transfer chemistry beyond the limits of natural metalloenzymes and small-molecule catalysts.<\/jats:p>","DOI":"10.1021\/jacs.6c04004","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:21:21Z","timestamp":1780510881000},"page":"23443-23448","source":"Crossref","is-referenced-by-count":1,"title":["Highly Stable Mn(V)-Nitrido\nand Nitrogen-Atom Transfer\nReactivity within a\n                    <i>de Novo<\/i>\n                    Protein"],"prefix":"10.1021","volume":"148","author":[{"given":"Jithin","family":"Thomas","sequence":"first","affiliation":[{"name":"University of California , \u2500 Riverside , , ,","place":["Riverside, California, United States, 91730"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudha","family":"Yadav","sequence":"additional","affiliation":[{"name":"The Johns Hopkins University , , , ,","place":["Baltimore, Maryland, United States, 21218"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8761-4667","authenticated-orcid":true,"given":"Paul H.","family":"Oyala","sequence":"additional","affiliation":[{"name":"California Institute of Technology , , , ,","place":["Pasadena, California, United States, 91125"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8089-8436","authenticated-orcid":true,"given":"Veronica","family":"Carta","sequence":"additional","affiliation":[{"name":"University of California , \u2500 Riverside , , ,","place":["Riverside, California, United States, 91730"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6244-6804","authenticated-orcid":true,"given":"Alec H.","family":"Follmer","sequence":"additional","affiliation":[{"name":"University of California , \u2500 Davis , , ,","place":["Davis, California, United States, 95616"]},{"name":"SLAC National Accelerator Laboratory , , , ,","place":["Menlo Park, California, United States, 94025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4645-1045","authenticated-orcid":true,"given":"David P.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"The Johns Hopkins University , , , ,","place":["Baltimore, Maryland, United States, 21218"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3392-3170","authenticated-orcid":true,"given":"Samuel I.","family":"Mann","sequence":"additional","affiliation":[{"name":"University of California , \u2500 Riverside , , ,","place":["Riverside, California, United States, 91730"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"2026073023072470700_cit1","doi-asserted-by":"publisher","first-page":"3591","DOI":"10.1002\/1521-3773(20021004)41:19&lt;3591::AID-ANIE3591&gt;3.0.CO;2-Z","article-title":"The elusive terminal imido of manganese(V)","volume":"41","author":"Eikey","year":"2002","journal-title":"Angew. 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Technol."},{"key":"2026073023072470700_cit35","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1021\/es60165a008","article-title":"Kinetics\nof monochloramine decomposition\nin the presence of bromide","volume":"14","author":"Trofe","year":"1980","journal-title":"Environ. Sci. Technol."},{"key":"2026073023072470700_cit36","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1021\/ja01173a033","article-title":"Kinetic Studies\non the Chloramines. I. The Rates of\nFormation of Monochloramine, N-Chlormethylamine and N-Chlordimethylamine","volume":"71","author":"Weil","year":"1949","journal-title":"J. Am. Chem. Soc."},{"key":"2026073023072470700_cit37","doi-asserted-by":"publisher","first-page":"20556","DOI":"10.1021\/jacs.4c05761","article-title":"Reaction\nDiscovery Using Spectroscopic Insights from an Enzymatic C-H Amination\nIntermediate","volume":"146","author":"Das","year":"2024","journal-title":"J. Am. Chem. 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