Molecular dynamics and NMR reveal the coexistence of H-bond-assisted and through-space JFH coupling in fluorinated amino alcohols

Abstract

The J_FH coupling constants in fluorinated amino alcohols were investigated through experimental and theoretical approaches. The experimental J_FH couplings were only reproduced theoretically when explicit solvation through molecular dynamics (MD) simulations was conducted in DMSO as the solvent. The combination of MD conformation sampling and DFT NMR spin–spin coupling calculations for these compounds reveals the simultaneous presence of through-space (TS) and hydrogen bond (H-bond) assisted J_FH coupling between fluorine and hydrogen of the NH group. Furthermore, MD simulations indicate that the hydrogen in the amino group participates in both an intermolecular bifurcated H-bond with DMSO and in transmitting the observed J_FH coupling. The contribution of TS to the J_FH coupling is due to the spatial proximity of the fluorine and the NH group, aided by a combination of the non-bonding transmission pathway and the hydrogen bonding pathway. The experimental J_FH coupling observed for the molecules studied should be represented as ^4TS/1hJ_FH coupling.