The Role of Chirality in the Activity of Photosystem II Herbicides

Although significant differences in activity between optical isomers have been recognized in many types of pesticides, the role of stereoselectivity has not been fully characterized for one of the most important classes of commercial herbicides, those that inhibit photosynthetic electron transport. This report describes experiments in which optically active α-methylbenzylamine or sec-butylamine was used as starting material for the synthesis of optically active triazine and urea herbicides. The biological activities of the compounds were determined in two in vitro chloroplast assays - competition for specifically bound [¹⁴C]atrazine and inhibition of photosystem II-medi- ated dye reduction - as well as in whole plant phytotoxicity. In both in vitro assays the (-)-isomer of the N-a-methylbenzyl triazine was about 15-fold more active than the (+)-isomer, and the racemate fell in between and was of about the same potency as atrazine. The same relative activities were also seen for in vivo phytotoxicity. The a-methylbenzyl urea derivatives were much less herbicidally active, but the in vitro assays were able to discriminate between the optical isomers. In both assays, the (-)-isomer of the urea was much more active than the (+)-isomer, with the racemate intermediate. Steric factors play a critical role in the degree of this chiral discrimination, since in both the corresponding triazines and ureas, the optically active molecules synthesized from the enantiomers of 2-butylamine showed only slight differences in activity. Saturation of the phenyl ring of the a-methylbenzyl triazines resulted in molecules which still showed substantial differences in activity related to chirality, further supporting the importance of steric factors, rather than electronic, in this chiral discrimination.