The effect of structure on nitroxide EPR spectral linewidth.
Nitroxides with narrow linewidths are essential for low-frequency EPR spectroscopy and in vivo EPR imaging. In developing a framework for designing narrow-line nitroxides, we sought to understand the unexpectedly narrow line width of 4-oxo-2,2,6,6-tetramethyl-1-piperidinyloxyl (5). Computational modeling revealed that the carbonyl double bond in the 4-position allows conformational diversity that results in the observed narrowing of the EPR spectral line. In view of this finding, we synthesized two new nitroxides bearing an exocyclic double bond: 4-methoxycarbonylmethylidene-2,2,6,6-tetramethyl-1-piperidinyloxyl (7) and 4-acetoxymethoxycarbonylmethylidene-2,2,6,6-tetramethyl-1-piperidinyloxyl (9). These nitroxides, like nitroxide 5, exhibited narrow linewidths-consistent with the results of modeling. Nitroxide 8 (4-carboxymethylidene-2,2,6,6-tetramethyl-1-piperidinyloxyl), as a prototype, allows for a variety of structural diversity, such as nitroxide 9,that can, for instance, target tissue compartments for in vivo EPR imaging.
Burks
Scott R
SR
Center for Biomedical Engineering and Technology, and Center for EPR Imaging In Vivo Physiology, University of Maryland, Baltimore, Maryland 21201, USA.
Makowsky
Mallory A
MA
Yaffe
Zachary A
ZA
Hoggle
Chad
C
Tsai
Pei
P
Muralidharan
Sukumaran
S
Bowman
Michael K
MK
Kao
Joseph P Y
JP
Rosen
Gerald M
GM
D018360:Crystallography, X-Ray; D004578:Electron Spin Resonance Spectroscopy; D007477:Ions / Q000737:chemistry*; D015394:Molecular Structure; D009589:Nitrogen Oxides / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry*
C553894:4-oxo-2,2,6,6-tetramethyl-1-piperidinyloxyl; D007477:Ions; D009589:Nitrogen Oxides; D010880:Piperidines