TY - JOUR

T1 - Origin of Long-Range Hyperfine Couplings in the EPR Spectra of 2,2,5,5-Tetraethylpyrrolidine-1-oxyls

AU - Polienko, Yuliya F

AU - Dobrynin, Sergey A

AU - Lomanovich, Konstantin A

AU - Brovko, Anastasiya O

AU - Bagryanskaya, Elena G

AU - Kirilyuk, Igor A

N1 - This work was supported by the Russian Science Foundation (grant number 22-73-00098). We thank the Multi-Access Chemical Research Center SB RAS for spectral and analytical measurements. © 2023 The Authors. Published by American Chemical Society.

PY - 2023/10/17

Y1 - 2023/10/17

N2 - 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 βπ*(N-O) to the natural localized molecular orbital βσ(C-H) playing the major role. This interaction is efficient if the ethyl substituent is in the pseudoaxial position of the ring and the CH2-CH3 bond is codirected with (parallel to) N-O. The apparent constant aH increases with the Boltzmann population of this conformation.

AB - 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 βπ*(N-O) to the natural localized molecular orbital βσ(C-H) playing the major role. This interaction is efficient if the ethyl substituent is in the pseudoaxial position of the ring and the CH2-CH3 bond is codirected with (parallel to) N-O. The apparent constant aH increases with the Boltzmann population of this conformation.

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85176150487&origin=inward&txGid=1036fe146f9b9f6d712fc0e59515bec4

U2 - 10.1021/acsomega.3c06090

DO - 10.1021/acsomega.3c06090

M3 - Article

C2 - 37867656

VL - 8

SP - 38723

EP - 38732

JO - ACS Omega

JF - ACS Omega

SN - 2470-1343

IS - 41

ER -