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To probe the origins of this dependence on terminal chalcogenide identity, we prepared and crystallographically characterized a synthetic model complex of the NDH active site, [(bdt)W(O)2Se]2\u2013, a dioxotungsten(VI) selenide complex supported by benzene-1,2-dithiolate (bdt), for comparison to the previously reported [(bdt)W(O)3]2\u2013 and [(bdt)W(O)2S]2\u2013 analogues. Electronic structure analyses combining experimental UV\u2013vis spectroscopy and DFT calculations indicate that replacement of terminal oxo ligands by heavier chalcogenides introduces accessible low-energy acceptor orbitals associated with more spatially distributed W\u2550E (E = S, Se) interactions. Treatment of the terminal selenido and sulfido complexes with BH4\u2013 led to reduced tungsten products accompanied by liberation of free hydroselenide (HSe\u2013) and hydrosulfide (HS\u2013), respectively, whereas the corresponding trioxo analogue was unreactive under analogous conditions. These findings provide direct experimental support for the proposal that terminal heavy chalcogenide ligands play an active electronic role in enabling biological hydride-transfer reactivity in molybdenum hydroxylase enzymes.<\/jats:p>","DOI":"10.1021\/jacs.6c10969","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:22:14Z","timestamp":1785849734000},"page":"33797-33802","source":"Crossref","is-referenced-by-count":1,"title":["The Role of Terminal\nHeavy Chalcogenide Ligands in\nEnabling Hydride Transfer Reactivity of W\u2550E (E = S, Se) Models\nfor Molybdenum Hydroxylases"],"prefix":"10.1021","volume":"148","author":[{"given":"Ananthu V.","family":"Modappilappally","sequence":"first","affiliation":[{"name":"University of Illinois Chicago , , , ,","place":["Chicago, Illinois, United States, 60607"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6923-5164","authenticated-orcid":true,"given":"Neal P.","family":"Mankad","sequence":"additional","affiliation":[{"name":"University of Illinois Chicago , , , ,","place":["Chicago, Illinois, United States, 60607"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"issue":"7","key":"2026081210070580500_cit1","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.1021\/cr950061t","article-title":"The Mononuclear\nMolybdenum Enzymes","volume":"96","author":"Hille","year":"1996","journal-title":"Chem. 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Chem."},{"issue":"7","key":"2026081210070580500_cit5","doi-asserted-by":"publisher","first-page":"3963","DOI":"10.1021\/cr400443z","article-title":"The Mononuclear Molybdenum Enzymes","volume":"114","author":"Hille","year":"2014","journal-title":"Chem. Rev."},{"issue":"13","key":"2026081210070580500_cit6","doi-asserted-by":"publisher","first-page":"7208","DOI":"10.1073\/pnas.97.13.7208","article-title":"Selenium-Dependent Metabolism of Purines: A Selenium-Dependent\nPurine Hydroxylase and Xanthine Dehydrogenase Were Purified from Clostridium\nPurinolyticum and Characterized","volume":"97","author":"Self","year":"2000","journal-title":"Proc. Natl.\nAcad. Sci. U. S. A."},{"issue":"5","key":"2026081210070580500_cit7","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/S0021-9258(18)91829-6","article-title":"Nicotinic Acid Metabolism: III. Purification and Properties\nof a Nicotinic Acid Hydroxylase","volume":"244","author":"Holcenberg","year":"1969","journal-title":"J. Biol. Chem."},{"issue":"1","key":"2026081210070580500_cit8","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1021\/bi951793i","article-title":"Properties of the Selenium- and Molybdenum-Containing\nNicotinic Acid Hydroxylase from Clostridium Barkeri","volume":"35","author":"Gladyshev","year":"1996","journal-title":"Biochemistry"},{"issue":"1","key":"2026081210070580500_cit9","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1073\/pnas.91.1.232","article-title":"Nicotinic Acid Hydroxylase from Clostridium\nBarkeri: Electron Paramagnetic Resonance Studies Show That Selenium\nIs Coordinated with Molybdenum in the Catalytically Active Selenium-Dependent\nEnzyme","volume":"91","author":"Gladyshev","year":"1994","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026081210070580500_cit10","doi-asserted-by":"crossref","DOI":"10.1002\/9781119951438.eibc0700","article-title":"Mo\u2013Se-Containing\nNicotinate Dehydrogenase","volume-title":"Encyclopedia\nof Inorganic and Bioinorganic Chemistry","author":"Dobbek","year":"2011"},{"issue":"27","key":"2026081210070580500_cit11","doi-asserted-by":"publisher","first-page":"11055","DOI":"10.1073\/pnas.0902210106","article-title":"The Mo-Se\nActive Site of Nicotinate Dehydrogenase","volume":"106","author":"Wagener","year":"2009","journal-title":"Proc.\nNatl. Acad. Sci. U. S. A."},{"issue":"39","key":"2026081210070580500_cit12","doi-asserted-by":"publisher","first-page":"4358","DOI":"10.1039\/C2CC35345H","article-title":"Oxo-Sulfido- and Oxo-Selenido-Molybdenum(VI)\nComplexes Possessing a Dithiolene Ligand Related to the Active Sites\nof Hydroxylases of Molybdoenzymes: Low Temperature Preparation and\nCharacterisation","volume":"49","author":"Sugimoto","year":"2013","journal-title":"Chem. 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Soc."},{"key":"2026081210070580500_cit29","volume-title":"Atoms in Molecules:\nA Quantum Theory; the International Series of Monographs on Chemistry","author":"Bader","year":"1994"},{"issue":"18","key":"2026081210070580500_cit30","doi-asserted-by":"publisher","first-page":"13854","DOI":"10.1021\/acs.inorgchem.1c01022","article-title":"Two, Three, or Not to Be? Elucidating\nMultiple Bonding in D6 Pseudotetrahedral Oxo and Imide Complexes","volume":"60","author":"Gardner","year":"2021","journal-title":"Inorg. Chem."},{"issue":"26","key":"2026081210070580500_cit31","doi-asserted-by":"publisher","first-page":"6696","DOI":"10.1002\/anie.201403892","article-title":"Synthesis, Characterization,\nand Reactivity of a Uranium(VI) Carbene Imido Oxo Complex","volume":"53","author":"Lu","year":"2014","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026081210070580500_cit32","doi-asserted-by":"publisher","first-page":"22008","DOI":"10.1021\/jacs.6c03753","article-title":"A Synthetic Molybdenum Hydroxylase Compound That Cleaves\nC\u2013H Bonds by Hydride Abstraction","volume":"148","author":"Modappilappally","year":"2026","journal-title":"J.\nAm. Chem. Soc."},{"issue":"32","key":"2026081210070580500_cit33","doi-asserted-by":"publisher","first-page":"8102","DOI":"10.1021\/ja981015o","article-title":"Synthesis, Structures, and Oxo Transfer\nReactivity\nof Bis(Dithiolene)Tungsten(IV,VI) Complexes Related to the Active\nSites of Tungstoenzymes","volume":"120","author":"Lorber","year":"1998","journal-title":"J. Am. Chem. Soc."},{"issue":"1","key":"2026081210070580500_cit34","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1039\/C8SC03968B","article-title":"Expanding\nReversible Chalcogenide Binding: Supramolecular Receptors for the\nHydroselenide (HSe\u2212) Anion","volume":"10","author":"Fargher","year":"2019","journal-title":"Chem. Sci."},{"issue":"3","key":"2026081210070580500_cit35","doi-asserted-by":"publisher","DOI":"10.1002\/asia.202101199","article-title":"Bulky Selenium\nLigand Stabilized\nTrans-Palladium Dichloride Complexes as Catalyst for Silver-Free Decarboxylative\nCoupling of Coumarin-3-Carboxylic Acids","volume":"17","author":"Meena","year":"2022","journal-title":"Chemistry\u2500An\nAsian Journal"},{"issue":"24","key":"2026081210070580500_cit36","doi-asserted-by":"publisher","first-page":"13435","DOI":"10.1021\/jacs.3c03766","article-title":"Taming the Dichalcogenides: Isolation,\nCharacterization, and Reactivity of Elusive Perselenide, Persulfide,\nThioselenide, and Selenosulfide Anions","volume":"145","author":"Li","year":"2023","journal-title":"J. Am.\nChem. Soc."},{"issue":"18","key":"2026081210070580500_cit37","doi-asserted-by":"publisher","first-page":"4518","DOI":"10.1021\/ic010421x","article-title":"Substitution and Oxidation Reactions of Bis(Dithiolene)Tungsten\nComplexes of Potential Relevance to Enzyme Sites","volume":"40","author":"Sung","year":"2001","journal-title":"Inorg. Chem."},{"issue":"4","key":"2026081210070580500_cit38","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1021\/ic030301k","article-title":"An Expanded Set\nof Functional Groups in Bis(Dithiolene)Tungsten(IV,VI)\nComplexes Related to the Active Sites of Tungstoenzymes, Including\nWIV\u2013SR and WVI\u2013O(SR)","volume":"43","author":"Jiang","year":"2004","journal-title":"Inorg. 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