{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lovinger GJ"],"funding":["NIGMS NIH HHS"],"pagination":["1052-1059"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11834864"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["632(8027)"],"pubmed_abstract":["Bimolecular nucleophilic substitution (S<sub>N</sub>2) mechanisms occupy a central place in the historical development and teaching of the field of organic chemistry<sup>1</sup>. Despite the importance of S<sub>N</sub>2 pathways in synthesis, catalytic control of ionic S<sub>N</sub>2 pathways is rare and notably uncommon even in biocatalysis<sup>2,3</sup>, reflecting the fact that any electrostatic interaction between a catalyst and the reacting ion pair necessarily stabilizes its charge and, by extension, reduces polar reactivity. Nucleophilic halogenase enzymes navigate this tradeoff by desolvating and positioning the halide nucleophile precisely on the S<sub>N</sub>2 trajectory, using geometric preorganization to compensate for the attenuation of nucleophilicity<sup>4</sup>. Here we sho"],"journal":["Nature"],"pubmed_title":["Catalysis of an S<sub>N</sub>2 pathway by geometric preorganization."],"pmcid":["PMC11834864"],"funding_grant_id":["F32 GM136042","R37 GM043214","R01 GM043214","R35 GM149244"],"pubmed_authors":["Lovinger GJ","Sak MH","Jacobsen EN"],"additional_accession":[]},"is_claimable":false,"name":"Catalysis of an S<sub>N</sub>2 pathway by geometric preorganization.","description":"Bimolecular nucleophilic substitution (S<sub>N</sub>2) mechanisms occupy a central place in the historical development and teaching of the field of organic chemistry<sup>1</sup>. Despite the importance of S<sub>N</sub>2 pathways in synthesis, catalytic control of ionic S<sub>N</sub>2 pathways is rare and notably uncommon even in biocatalysis<sup>2,3</sup>, reflecting the fact that any electrostatic interaction between a catalyst and the reacting ion pair necessarily stabilizes its charge and, by extension, reduces polar reactivity. Nucleophilic halogenase enzymes navigate this tradeoff by desolvating and positioning the halide nucleophile precisely on the S<sub>N</sub>2 trajectory, using geometric preorganization to compensate for the attenuation of nucleophilicity<sup>4</sup>. Here we sho","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Aug","modification":"2026-03-18T13:35:48.949Z","creation":"2025-08-18T09:54:21.345Z"},"accession":"S-EPMC11834864","cross_references":{"pubmed":["39025123"],"doi":["10.1038/s41586-024-07811-4"]}}