The mode of action of isoxaflutole. I. Physiological effects, metabolism, and selectivity

Isoxaflutole (5-cyclopropyl isoxazol-4-yl-2-mesyl-4-trifluoromethylphenyl ketone) is a novel herbicide for preemergence control of a wide range of important broadleaf and grass weeds in corn and sugarcane producing characteristic foliar bleaching activity in susceptible species prior to plant death. Following either foliar or root uptake, isoxaflutole is rapidly converted to a diketonitrile derivative (2-cyclopropyl-3-(2-mesyl-4-trifluoromethylphenyl)-3- oxopropanenitrile) by opening of the isoxazole ring. This diketonitrile undergoes degradation to a benzoic acid derivative (2-mesyl-4-trifluoromethyl benzoic acid) in treated plants and the extent of this degradation is correlated to the degree of susceptibility, being most rapid in tolerant corn and slowest in susceptible Abutilon theophrasti. Following a preemergence application of [phenyl(U)-14C]- isoxaflutole, equivalent to 250 g ai ha(-1) only 10% of the extracted 14C activity was the active diketonitrile in corn, compared to 90% in A. theophrasti. The rate of diketonitrile degradation was intermediate in moderately susceptible Ipomea spp. The foliar symptoms are associated with an accumulation of phytoene in treated leaves of Brassica kaber, typical of herbicidal inhibitors of phytoene desaturase. However, neither the diketonitrile derivative nor isoxaflutole inhibits the desaturation of radiolabeled phytoene by a microsomal extract of carrot cell cultures. However, the diketonitrile does inhibit 4-hydroxyphenylpyruvate dioxygenase, preventing the biosynthesis of homogentisate, the precursor of plastoquinone and alpha-tocopherol. The content of both these prenylquinones in emerging leaves of isoxaflutole-treated plants decreases prior to the accumulation of phytoene and the decrease in carotenoids. The mode of action of isoxaflutole is suggested to be due to an indirect inhibition of phytoene desaturase resulting from the absence of plastoquinone, an essential cofactor for the desaturase.