Cyanoacrylate Inhibitors as Probes for the Nature of the Photosystem II Herbicide Binding Site

Abstract

Three series of phenyl-substituted 2-cyanoacrylates were evaluated using simple quantitative structure activity relationships (QSAR) in an attempt to elucidate the nature of the regions of the binding site occupied by different parts of the molecules. Inhibition of the Hill reaction by substituted 3-phenylamino-2-cyanoacrylates correlated well with the lipophilicity of the substituent. The hydrophobic effect was also dominant when the Hill activity of a series of 3-benzylamino-2-cyanoacrylates was analyzed, although potency was considerably higher in the latter series. Lipophilicity and the electronic nature of the substituents were not major determinants in the Hill inhibitory activity of a series of substituted phcnoxycthyl 2-cyanoacrylic esters. In this case, a significant correlation was found with the molar rcfractivity (MR) of meta substituents, a parameter reflecting substituent size. The results indicate that the phenyl moiety of substituted 3-phenylamino- and 3-bcnzyl- amino-2-cyanoacrylates interacts with an essentially lipophilic binding domain, though it is likely that the two series are oriented differently with the 3-bcnzylamino series able to bind with greater affinity. In the phcnoxycthyl ester series, the substituted phenyl group interacts with a different environment, wherein ortho- and we7tf-substitution is tolerated, dependent on the bulk of the substituent, but /wra-substitution is detrimental to affinity for this region of the site.