Principles and Applications of CF₂X Moieties as Unconventional Halogen Bond Donors in Medicinal Chemistry, Chemical Biology, and Drug Discovery.

ABSTRACT: As an orthogonal principle to the established (hetero)aryl halides, we herein highlight the usefulness of CF₂X (X = Cl, Br, or I) moieties. Using tool compounds bearing CF₂X moieties, we study their chemical/metabolic stability and their logP/solubility, as well as the role of XB in their small molecular crystal structures. Employing QM techniques, we analyze the observed interactions, provide insights into the conformational flexibilities and preferences in the potential interaction space. For their application in molecular design, we characterize their XB donor capacities and its interaction strength dependent on geometric parameters. Implementation of CF₂X acetamides into our HEFLibs and biophysical evaluation (STD-NMR/ITC), followed by X-ray analysis, r

SUBMITTER: Vaas S 

PROVIDER: S-EPMC10424184 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature