Paramagnetic perturbation of the 19F NMR chemical shift in fluorinated cysteine by O2: a theoretical study

We present a combined molecular dynamics and density functional theory study of dioxygen-induced perturbation of the (19)F NMR chemical shifts in an aqueous solution of fluorinated cysteine under 100 atm of O(2) partial pressure. Molecular dynamics simulations are carried out to determine the dominant structures of O(2) and the fluorinated cysteine complexes in water, and the collected structural information is exploited in computation of (19)F chemical shifts using density functional theory. The obtained results indicate that the density redistribution of the O(2) unpaired electrons between the dioxygen and fluorinated cysteine is responsible for the experimentally observed perturbation of the (19)F NMR chemical shifts, where the Fermi contact interaction plays the key role. The O(2)-induced paramagnetic (19)F chemical shift, averaged over the simulation trajectory, is comparable with the reported experimental values, proving the availability of the developed strategy for modeling (19)F NMR chemical shifts in the presence of paramagnetic agents in an aqueous solution. The applicability of the combined molecular dynamics/density functional theory approach for dioxygen NMR perturbation to all resonating nuclei including (1)H, (13)C, (15)N, and (19)F is emphasized, and the ramification of this for investigations of membrane protein structures is discussed.