A Herbicidal Inhibitor of Isopropylmalate Isomerase

Abstract

Nitronate compounds resembling the aci-carboxylate reaction intermediate in the reaction catalyzed by isopropylmalate isomerase were investigated as enzyme inhibitors and potential herbicides. The nitronic acids of 1-hydroxy-2-nitrocyclopentane-1-carboxylic acid, nitroisopropylmalate and of 1-hydroxy -2-nitrocyclohexane-1-carboxylic acid were all potent inhibitors of isopropylmalate isomerase. The nitroalkane/nitronate pK a values of these were 7.3, 9.5 and 11.1, respectively. The perturbed pK a values of the first and last compound were und erstandable on the basis of the opposing effects of 5- and 6-membered ring strain on the ionization of the nitro group. As the only compound significantly in the nitronate form at physiological pH , it was not surprising that 1-hydroxy-2-nitrocyclopentane-1-carboxylic acid was the best herbicide. Its specific mode of action was confirmed by the fact that 1-hydroxy-2-nitrocyclopentane- 1-carboxylic acid inhibited the growth of carrot cells in liquid culture and was specifically reversed by leucine.