title: Structure-reactivity relationship of piperidine nitroxide: electrochemical, ESR and computational studies.
abstract: We have synthesized several nitroxides with different substituents which vary the steric and electronic environment around the N-O moiety and have systematically investigated the role of substituents on the stability of the radicals. Our results demonstrated the reactivity toward ascorbate correlates with the redox potential of the derivatives. Furthermore, ab initio calculations also indicated a correlation between the reduction rate and the computed singly occupied molecular orbital-lowest unoccupied molecular orbital energy gap, but not with solvent accessible surface area of the N-O moiety, supporting the experimental results and suggesting that the electronic factors largely determine the radicals' stability. Hence, it is possible to perform virtual screening of nitroxides to optimize their stability, which can help to rationally design novel nitroxides for their potential use in vivo.
authors.affiliation: Department of Bio-functional Science, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Higashi-ku, Maidashi, Fukuoka 812-8582, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Fumiya
authors.initials: F
authors.lastname: Mito
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ito
authors.forename: Sokkar
authors.initials: S
authors.lastname: Pandian
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Koji
authors.initials: K
authors.lastname: Nakano
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Murugesan
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sakai
authors.forename: Hideo
authors.initials: H
authors.lastname: Utsumi
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yamada
mesh_terms: D001205:Ascorbic Acid / Q000737:chemistry; D003497:Cyclic N-Oxides / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D009682:Magnetic Resonance Spectroscopy; D010880:Piperidines / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D003497:Cyclic N-Oxides; D010880:Piperidines; C032727:piperidine; D001205:Ascorbic Acid