Origin of Long-Range Hyperfine Couplings in the EPR Spectra of 2,2,5,5-Tetraethylpyrrolidine-1-oxyls

[Image: see text] Cyclic nitroxides with several bulky alkyl substituents adjacent to the nitroxide group are known to demonstrate a much higher stability to bioreduction than their tetramethyl analogues. Among these so-called “sterically shielded” nitroxides, the pyrrolidine derivatives are the most stable. The EPR spectra of some sterically shielded pyrrolidine-1-oxyls were reported to show one or two large additional doublet splittings with a hyperfine coupling (hfc) constant (ca. 0.2–0.4 mT). To determine the origin of these hfc, a series of 2-R-2,5,5-triethyl-3,4-bis(hydroxymethyl)-pyrrolidine-1-oxyls with methylene groups stereospecifically enriched with deuterium were prepared, and their CW EPR spectra were studied. In addition, these nitroxides were investigated using quantum chemical calculations on the UB3LYP/def2-TZVP level and NBO analysis. The apparent constants were assigned to hfc with γ-hydrogen in the side chain, with the contribution of the NBO orbital (β)π*(N–O) to the natural localized molecular orbital (β)σ(C–H) playing the major role. This interaction is efficient if the ethyl substituent is in the pseudoaxial position of the ring and the CH(2)–CH(3) bond is codirected with (parallel to) N–O. The apparent constant a(H) increases with the Boltzmann population of this conformation.