Noncovalent Interactions Of Fluorine With Amide And CH₂ Groups

This thesis is divided into four chapters.The first chapter is the introduction,which summarizes the progress of fluorine-containing drugs and the research progress of non-covalent interactions between fluorinated ligand–protein.In chapter2,¹⁹F NMR was developed as a tool to detect rotations in fluorine substituted phenyl compounds.The third chapter discusses the influence of electron effect on the non-covalent interaction between fluorine with amide and CH₂ groups.In chapter 4,the non-covalent interaction between fluorine with amide and CH₂ groups is summarized,and the prospect of this application is prospected.Fluorine noncovalent interactions with amide and CH₂ groups play important roles in the paradigm of fluorinated ligand–protein recognition.¹⁹F NMR spectroscopy is a sensitive method in monitoring changes of F local environments and has been used to probe protein conformational changes.In this report,studies of electronic effects on C–F···amide and C–F···CH₂ interactions are described.Using an amidine as a surrogate for the amide group in the N–phenylγ–lactam scaffold,we prove that the F nucleus associated with the deshielded ¹⁹F NMR signal(F_down)engages in close contacts with the amide,and decreasing electron density on the amide/amidine enhances F multipolar interactions.Systematic studies on different substituted N–phenylγ–lactams reveal that electron–poor Fdown nuclei afford strong C–F···amide interactions,while electron–rich F_up nuclei make better C–F···CH₂ contacts.These findings are in agreement with experimental data from both structural database mining and spectroscopic studies in relevant systems.