Understanding the Topography of the Photosystem II Herbicide Binding Niche: Does QSAR Help?

For thirty years the study o f Quantitative Structure Activity Relationships (QSAR) has been an active area o f research aimed at developing an understanding o f the interactions be­ tween inhibitors o f photosynthetic electron transport and the herbicide binding site in the Pho­ tosystem II (PS II) reaction centre. Many QSAR studies o f PS II inhibitors with diverse chemi­ cal structures have emphasized the hydrophobic nature o f the binding domain, with lipophilicity being the dominant determinant o f Hill inhibition activity. The cyanoacrylate classes o f PS II inhibitors also show a diversity o f active structures and considerable variation in inhibi­ tion potency with minor alterations to structure. QSAR analysis and examination o f chirality in cyanoacrylate inhibitors has also shown the importance o f steric factors in determining ac­ tivity. Different modes o f binding for different classes o f cyanoacrylates have been identified; a classical urea-type relationship between activity and hydrophobicity and another type o f inter­ action in which the lipophilicity or electronic nature o f phenyl substituents plays little part and the size o f the substituents is o f primary importance. Because size and shape are parameters o f great importance in determining the topography o f a binding site, QSAR studies o f flexible PS II inhibitors such as cyanoacrylates will continue to be important in elucidating the intrica­ cies o f inhibitor/PS II interactions.