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

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/1h)J(FH) coupling.