title: The effect of structure on nitroxide EPR spectral linewidth.
abstract: 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.
authors.affiliation: Center for Biomedical Engineering and Technology, and Center for EPR Imaging In Vivo Physiology, University of Maryland, Baltimore, Maryland 21201, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Burks
authors.forename: Mallory A
authors.initials: MA
authors.lastname: Makowsky
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Yaffe
authors.forename: Chad
authors.initials: C
authors.lastname: Hoggle
authors.forename: Pei
authors.initials: P
authors.lastname: Tsai
authors.forename: Sukumaran
authors.initials: S
authors.lastname: Muralidharan
authors.forename: Michael K
authors.initials: MK
authors.lastname: Bowman
authors.forename: Joseph P Y
authors.initials: JP
authors.lastname: Kao
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Rosen
mesh_terms: 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*
chemical_list: C553894:4-oxo-2,2,6,6-tetramethyl-1-piperidinyloxyl; D007477:Ions; D009589:Nitrogen Oxides; D010880:Piperidines