19F NMR chemical shifts are sensitive to remote functional group variations

Abstract

Covalently identical ortho-F nuclei display dual 19F NMR signals in di-ortho-F substituted N-phenyl γ-lactams. We found that the deshielding 19F signal (δdown) was significantly affected by C9-substituent, especially when C9- substituents are steric bulky. Notably, the deshielded 19F chemical shift is sensitive to chirality variations at C9-alkyls, while the shielded 19F NMR signal δup manifests negligible changes among various C9-alkyl derivatives. Calculated molecular electrostatic surface potentials (ESPs) were used to interpret the experimental observations. 19F NMR signal assignments in an exemplary rotameric molecule are presented based on our understanding on structure-19F shielding relationship. Our work described here provides basics to deciphering 19F shielding in biologically important molecules and drugs, and to use of 19F chemical shifts in monitoring molecular dynamics and conformations.