N-Methylanilinocyanoacrylate Photosystem II Inhibitors. Structure-Activity Relationships

Many 3-N-methylanilino cyanoacrylate derivatives are potent inhibitors of photosynthetic electron transport at the PS II level in a thylakoid system isolated from Pisum sativum. These inhibitors are somewhat unusual in that they take more than 15 min to equilibrate with the binding site in contrast to most classical PS II inhibitors which tend to equilibrate rapidly i.e. within the mixing time of seconds. The effects of mono-and disubstituents in the aryl nucleus on inhibitory activity were studied. The nature and position of the substituent had no detectable influence on equilibration rate but a pronounced influence on inhibitory activity as measured by equilibrium pI50 values. Substituent position enhanced inhibitory activity in the order 3′ > 2′ ⋙ 4′ . As regards the nature of the substituent, size appeared to be the most important parameter -the smaller the substituent the greater the activity. Such influences were in contrast to those in analogous 3-anilino-and 3-benzylamino-2-cyano-acrylate series where the comparable order of substituent position effect was 3′ and 4′ ⋙ 2′ and where substituent hydro-phobicity rather than size was the most important factor. Disubstituted fluoro derivatives have given interesting insights into the preferred orientation of these inhibitors at the binding site with the 2′-and 5′-positions interacting positively, the 4′-position, negatively, and the 3′-position neutrally.