Submitted to: Springer Verlag
Publication Type: Book / Chapter
Publication Acceptance Date: January 1, 1999
Publication Date: N/A
Interpretive Summary: This book chapter consists of a quantitative structure-activity relationship (QSAR) of a series of 24 diphenyl analogues studied using recent 3-dimensional computer modeling methods. The prediction models derived were an improvement over previously published models obtained with 2-dimensional methods. Determination of activity of enantiomers was made possible using our model. As well, activity of related structures could also be approximated. The remaining of the book chapter consists of an overview of published QSAR studies on other oxygen-bridged compounds known to inhibit the enzyme protoporphyrinogen oxidase.
Technical Abstract: The first commercial inhibitors of protoporphyrinogen oxidase (Protox) were the diphenyl ether (DPE). Nitrofen was introduced in the early 1960's and was followed by several other, more potent Protox inhibitors. The molecular site of action of this class of herbicides was unknown until 1989. Thus, all quantitative structure--activity relationship (QSAR) studies before this time were done solely on the correlation of structure with biological activity. In some of these studies, the 'activity' portion of the QSAR study may not have been completely or even at all associated with Protox inhibition, in that diphenyl ether compounds have several other potential secondary sites of action. In 1992, we published the first QSAR study of DPE herbicides in which inhibition of Protox was correlated with molecular parameters. This earlier work and subsequent published work on the QSAR of Protox inhibitors has largely been performed at a two dimensional level. This chapter reviews this previous work and extends QSAR studies with DPEs to three dimensional descriptors that more precisely describe the requisites for activity of Protox inhibitors at the molecular level. The scope of this chapter will be limited to the Protox-inhibiting herbicides that are bicyclic molecules connected by an oxygen bridge.