CHEMICAL AND QUANTUM-MECHANICAL STUDIES OF THE FREE-RADICAL C-C BOND FORMATION IN THE LIPOXYGENASE-CATALYZED DIMERIZATION OF OCTADECA-9,12-DIYNOIC ACID

Triple bond analogues of poly-unsaturated fatty acids are well-known i nactivators of lipoxygenases. In an earlier study we proposed that, si nce 11-oxo-octadeca-9,12-diynoic acid (11-oxo-ODYA) is the only oxygen ated product formed during the irreversible inactivation of soybean li poxygenase-1, the inactivation should proceed via a C11 centered octad eca-9,12-diynoic acid radical (ODYA radical).(1) In the present study we investigated the lipoxygenase-catalysed formation of the ODYA radic al. In the reaction of lipoxygenase with ODYA in the absence of dioxyg en and in the presence of 13(S)-hydroperoxy-octadeca-9Z, 11E-dienoic a cid (13-HPOD), free ODYA radicals were formed which resulted in the fo rmation of three dimeric ODYA products in which one ODYA moiety is lin ked via its C9 (12%), C11 (72%) or C13 (16%) to the C11 methylene of t he other ODYA moiety. With the ab initio Hartree-Fock method, using th e 2,5-heptadiynyl radical as a model compound, the electron spin in th e ODYA radical was calculated to be located for 12.0, 75.0 and 12.0% o n carbon atoms C9, C11 and C13 of the ODYA radical, respectively, The ODYA-ODYA dimer formation could thus be explained on the basis of the electron spin distribution in the ODYA radical. The dimer formation, i . e. reaction of an ODYA radical with an ODYA molecule was compared wi th the reaction of the ODYA radical with dioxygen. On the basis of thi s comparison it is concluded that a) the ODYA dimer formation occurs a t the carbon atom with the highest electron spin population; b) ODYA d imer formation is predominantly a kinetically determined process; c) t he electron spin distribution in the ODYA radical can be used to predi ct the composition of the dimer mixture; and d) the regiospecific oxyg en addition in the formation of 11-oxo-ODYA is enzymatically controlle d. Copyright (C) 1997 Elsevier Science Inc.