Catalysis of an S_N2 pathway by geometric preorganization.

ABSTRACT: Bimolecular nucleophilic substitution (S_N2) mechanisms occupy a central place in the historical development and teaching of the field of organic chemistry¹. Despite the importance of S_N2 pathways in synthesis, catalytic control of ionic S_N2 pathways is rare and notably uncommon even in biocatalysis^2,3, 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_N2 trajectory, using geometric preorganization to compensate for the attenuation of nucleophilicity⁴. Here we sho

SUBMITTER: Lovinger GJ 

PROVIDER: S-EPMC11834864 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature