{"doi":"10.1021/jacs.0c06725","title":"Triple, Mutually Orthogonal Bioorthogonal Pairs through the Design of Electronically Activated Sulfamate-Containing Cycloalkynes","abstract":"Interest in mutually exclusive pairs of bioorthogonal labeling reagents continues to drive the design of new compounds that are capable of fast and predictable reactions. The ability to easily modify S-, N-, and O-containing cyclooctynes (SNO-OCTs) enables electronic tuning of various SNO-OCTs to influence their cycloaddition rates with Type I–III dipoles. As opposed to optimizations based on just one specific dipole class, the electrophilicity of the alkynes in SNO-OCTs can be manipulated to achieve divergent reactivities and furnish mutually orthogonal dual ligation systems. Significant reaction rate enhancements of a difluorinated SNO-OCT derivative, as compared to the parent scaffold, were noted, with the second-order rate constant in cycloadditions with diazoacetamides exceeding 5.13 M –1 s –1 . Computational and experimental studies were employed to inform the design of triple ligation systems that encompass three orthogonal reactivities. Finally, polar SNO-OCTs are rapidly internalized by mammalian cells and remain functional in the cytosol for live-cell labeling, highlighting their potential for diverse in vitro and in vivo applications.","journal":"Journal of the American Chemical Society","year":2020,"id":91899,"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":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":296979,"name":"Jessica M. Roberts","orcid":null,"position":1,"is_corresponding":false},{"id":423697,"name":"Henry R. Kilgore","orcid":"0000-0003-4851-9656","position":2,"is_corresponding":false},{"id":459834,"name":"Amirah S. Mat Lani","orcid":"0009-0001-1015-7963","position":3,"is_corresponding":false},{"id":344174,"name":"Ronald T. Raines","orcid":"0000-0001-7164-1719","position":4,"is_corresponding":false},{"id":295844,"name":"Jennifer M. Schomaker","orcid":"0000-0003-1329-950X","position":5,"is_corresponding":false},{"id":459833,"name":"Yun Hu","orcid":"0000-0002-0385-3362","position":0,"is_corresponding":true}],"reference_count":96,"raw_metadata":null,"created_at":"2026-07-18T22:29:21.932251Z","pmid":"33085477","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":[]}