Enantioselectivity of protoporphyrinogen oxidase‐inhibiting herbicides

Abstract

Protoporphyrinogen oxidase (Protox) was inhibited stereoselectively by three pairs of enantiomers belonging to diphenyl ether (DPE) and pyrazole phenyl ether (PPE) herbicide classes. The ( R ) enantiomers were 10to 44-fold more active than the ( S ) enantiomers as inhibitors of Protox from barley etioplasts. Similarly, the ( R ) enantiomers caused green barley tissue to accumulate greater amounts of porphyrins and caused greater tissue damage than the ( S ) enantiomers. The ( R ) enantiomers competed more successfully with [14C] acifluorfen than the ( S ) enantiomers for the binding sites on Protox. In the PPE class, the in-vitro and in-vivo activity differences were wider in the isopropyl pairs than in the n-propyl pairs. The DPE enantiomers were tested on ten dicotyledonous and six monocotyledonous weed species and ten crops for weed control and crop safety. In general, neither enantiomer had pre-emergence activity on monocotyledons , but the ( R ) enantiomer provided some monocotyledonous weed control when applied post-emergence. On dicotyledons, the ( R ) enantiomer provided excellent preemergence control, whereas the ( S ) enantiomer was inactive. The ( R ) enantiomer caused no injury to corn, cotton, peanuts, rice, sorghum, or soybeans applied pre-emergence, but it severely injured crops when applied post-emergence. There was a positive correlation between the activities of the compounds at the molecular, cellular and whole plant levels. The only molecular property differences found to account for differences in activity between members of chiral pairs were steric parameters.

The Porphyrin Pathway as a Herbicide Target Site

“…It was found that the three dimensional (lengths of x, y, and z coordinates) geometry and van der Waals volume (bulk parameter) of the most active compounds from both herbicide groups matched more closely with the one half structure of the Protogen molecule than the least active analogues. Detailed structural comparisons between Protogen and AF revealed that both the bond and torsion angles of AF at the ether oxygen matched closely with the angles at the methylene bridge between rings B and C of Protogen structure (Figure 4) (20). The nucleophilic superdelocalisabilty of AF and Protogen were the same, while the molecular electronic and nuclear energies of AF were one half the levels of Protogen.…”

“…We found very good correlations between Protox-inhibitory (I 50 ), Proto IX induction, and herbicidal activities of 14 phenopylate analogues in barley (39). On the contrary, very poor correlations were found between the same biological parameters in a DPE series of compounds, suggesting differential movement of herbicides and/or the alteration of chemistry during the course of uptake and movement of molecules to the active sites in plant tissues (20).…”

“…Based on the screening and biochemical research on porphyrin biosynthesis modulators, it has been suggested that the modulators may interact directly with the enzymes of the porphyrin pathway (7,8,(19)(20)(21) by binding to or close to the receptor site. The compounds that interfered with the porphyrin pathway invariably fell into two separate categories: (a) those that were structurally related to one half fraction of a tetrapyrrole molecule such as diphenyl ethers, phenopylates, dipyridyls, and phenanthrolines, and (b) those that were structurally related to one quadrant of a tetrapyrrole molecule such as picolinic acid, nicotinic acid, and substituted pyridyls.…”

“…Figure 4. Three dimensional structures of Protogen and acifluorfen optimized by a quantum mechanics method (20).…”

Isomerization and Peroxidizing Phytotoxicity of Thiadiazolidine Herbicides

“…Little is know n ab out structure-activity rela tionships. E vidence was presented, th a t an active peroxidizer m ust be a com petitive inhibitor of protoporphyrinogen (the substrate for protox), representing ab o u t half the fraction of the n atural substrate, and m ust be bicyclic [8]. T he length of the inhibitor m olecule should be in the 12 Arange.…”