Spin adducts of several N-2-(2-alkoxycarbonyl-propyl)-α-pyridylnitrone derivatives with superoxide, alkyl and lipid-derived radicals

Abstract

Several derivatives of N- t-butyl-α-phenylnitrone (PBN) such as N-2-(2-ethoxycarbonyl-propyl)-α-phenylnitrone (EPPN) have recently been reported to form superoxide spin adducts ( t 1/2 ca. 2–7 min at pH 7.0), which are considerably more stable than their respective PBN or DMPO adducts ( t 1/2 ca. 10 and 45 s, respectively). In continuation of our studies on structure optimization of EPPN derivatives, a series of 12 novel spin traps with 2-, 3- and 4-pyridinyl substituents was synthesized and fully characterized by 1 H NMR, 13 C NMR and IR spectroscopy. In addition to the replacement of the phenyl ring by a 2-, 3- or 4-pyridinyl substituent, the ethoxy group of the parent compound EPPN was replaced by either a propoxy, iso-propoxy, or cyclopropylmethoxy moiety. Superoxide adducts of all PPyN derivatives were considerably more stable than those of the respective EPPN derivatives with half-lives ranging from about 6 to 11 min. In addition, alkoxyl radical adducts were also considerably more stable than those of the EPPN series. Hydroxyl radical adducts were not detected, on the other hand, very stable spin adducts were formed from a series of carbon centered radicals, e.g. from the methyl or hydroxymethyl radical. The novel spin traps are offering an alternative to PBN or POBN, especially where the higher stability of oxygen-centered radical adducts is of major importance. All of them can easily be synthesized from commercially available compounds in two or three steps.