{"doi":"10.1021/jacs.3c03062","title":"Computational Description of Alkylated Iron–Sulfur Organometallic Clusters","abstract":"The radical S -adenosyl methionine (SAM) enzyme superfamily has widespread roles in hydrogen atom abstraction reactions of crucial biological importance. In these enzymes, reductive cleavage of SAM bound to a [4Fe-4S] 1+ cluster generates the 5′-deoxyadenosyl radical (5′-dAdo•) which ultimately abstracts an H atom from the substrate. However, overwhelming experimental evidence has surprisingly revealed an obligatory organometallic intermediate Ω exhibiting an Fe-C5′-adenosyl bond, whose properties are the target of this theoretical investigation. We report a readily applied, two-configuration version of broken symmetry DFT, denoted 2C-DFT, designed to allow the accurate description of the hyperfine coupling constants and g-tensors of an alkyl group bound to a multimetallic iron–sulfur cluster. This approach has been validated by the excellent agreement of its results both with those of multiconfigurational complete active space self-consistent field computations for a series of model complexes and with the results from electron nuclear double-resonance/electron paramagnetic resonance spectroscopic studies for the crystallographically characterized complex, M–CH 3, a [4Fe-4S] cluster with a Fe–CH 3 bond. The likewise excellent agreement between spectroscopic results and 2C-DFT computations for Ω confirm its identity as an organometallic complex with a bond between an Fe of the [4Fe-4S] cluster and C5′ of the deoxyadenosyl moiety, as first proposed.","journal":"Journal of the American Chemical Society","year":2023,"id":352688,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9605,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1098533,"name":"M Wittkop","orcid":"0009-0003-9844-2295","position":1,"is_corresponding":false},{"id":925661,"name":"Madeline B. Ho","orcid":"0000-0001-6351-2132","position":2,"is_corresponding":false},{"id":744434,"name":"William E. Broderick","orcid":"0000-0001-5782-7322","position":3,"is_corresponding":false},{"id":744435,"name":"Joan Broderick","orcid":"0000-0001-7057-9124","position":4,"is_corresponding":false},{"id":382712,"name":"Brian M. Hoffman","orcid":"0000-0002-3100-0746","position":5,"is_corresponding":false},{"id":258617,"name":"Martín A. Mosquera","orcid":"0000-0003-2170-5651","position":6,"is_corresponding":false},{"id":680905,"name":"Richard J. Jodts","orcid":null,"position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T01:12:54.209378Z","pmid":"37307050","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}