A Herbicidal Inhibitor of Isopropylmalate Isomerase

N itronate com pounds resembling the aa-carboxylate reaction interm ediate in the reaction catalyzed by isopropylm alate isomerase were investigated as enzyme inhibitors and potential herbicides. The nitronic acids o f l-hydroxy-2-nitrocyclopentane-l-carboxylic acid, nitroisop ropylm alate and o f l-hydroxy-2-nitrocyclohexane-l-carboxylic acid were all po ten t inhibi­ tors o f isopropylm alate isomerase. The n itroalkane/n itronate pK a values o f these were 7.3, 9.5 and 11.1, respectively. The perturbed pK a values o f the first and last com pound were under­ standable on the basis o f the opposing effects o f 5and 6-m em bered ring strain on the ioniza­ tion o f the n itro group. As the only com pound significantly in the n itronate form a t physiolog­ ical pH , it was not surprising tha t l-hydroxy-2-nitrocyclopentane-l-carboxylic acid was the best herbicide. Its specific m ode o f action was confirm ed by the fact tha t l-hydroxy-2-nitrocyclopentane-l-carboxylic acid inhibited the growth o f carro t cells in liquid culture and was specifically reversed by leucine.