Oxidative phosphorylation herbicides

Dinitrophenols had been used as insecticides since 1892 but it was not until the 1930s that their value as herbicides was discovered and 4,6-dinitro-o-cresol (DNOC) was introduced. The trouble with dinitrophenols was their toxicity to all living organisms that respire. Their mode of action is through the uncoupling of oxidative phosphorylation, an effect that leads to a rapid death of any organism that comes into contact with the chemical, including the operator. 

Partial reactions not dependent on photosystem II, such as cyclic phosphorylation or the photoreduction of NADP with an electron donor that circumvents photosystem II (ascorbate + DPIP), are either not inhibited or inhibited only weakly. These herbicides also do not inhibit mitochondrial oxidative phosphorylation. 

Uncouplers. Uncouplers dissociate electron transport from photophosphorylation. Both noncyclic and cyclic phosphorylation are inhibited, but electron transport reactions are either unaffected or stimulated. Because uncouplers relieve the inhibition of electron transport imposed by energy transfer inhibitors, they are considered to act at a site closer to the electron transport chain than the site of phosphate uptake. In Figure 2, they are shown (site 2) as dissipating some form of conserved energy represented as on the noncyclic and cyclic ATP-gener-ating pathways. Perfluidone is the only herbicide identified to date that functions as a pure uncoupler at pH 8.0 (2). Compounds that uncouple photophosphorylation also uncouple mitochondrial oxidative phosphorylation. 

These are contact herbicides which, in high concentrations, causes foliar desiccation and collapse. Their mode of action appears to be their ability to nnconple oxidative phosphorylation and hence inhibit ATP synthesis. Since this process is common in plants and mammals, it is not surprising that dini-trophenols have high mammalian toxicides. 

Phenoxy herbicides (2,4-D, mecoprop, dichlorprop) are used to control broad-leaved weeds. Ingestion causes nausea, vomiting, p5rrexia (due to uncoupling of oxidative phosphorylation), hyperventilation, hypoxia and coma. Their elimination is enhanced by urine alkalinisation. Organochlorine pesticides, e.g. dicophane (DDT), may cause convulsions in acute overdose. Treat as for status epilepticus. 

Ioxynil and bromoxynil are photosynthesis inhibiting herbicides. They inhibit the electron flow near the quinone component of electron transport (Wain, 1964 Smith et al., 1966 Paton and Smith, 1965,1967). In addition to the strong inhibition of oxidative phosphorylation, both herbicides prevent COj fixation (Friend and Olson, 1967). 

The herbicidal action of trifluralin is evidently the result of the inhibition of several biochemical processes of the plant. Treatment with trifluralin changes the sugar content and the composition of oils and fats in plants, and the activity of several enzymes is considerably reduced (Dukes and Biswas, 1967 Schweizer, 1970 Ashton et al., 1968 Fenner and Meggitt, 1970 Fenner, 1970). Treatment with trifluralin also inhibits cell formation and oxidative phosphorylation (Negi et al.,... 

The general and primary action of carbamate herbicides is their inhibiting effect on mitosis, as has been shown by several workers in hundreds of experiments. Of the biochemical reactions of plant cells, carbamate herbicides inhibit oxidative phosphorylation and the synthesis of ATP, RNA and protein. As a result of these processes abnormal cells with anomalous nucleotides are formed in sensitive plants, which finally leads to the destruction of the plant. 

The biochemical action of arsenic herbicides is primarily interference in phosphorus metabolism. They probably kill plants be the uncoupling of oxidative phosphorylation and by the blocking of the enzymes containing suifhydryl groups. 

Mitochondrial Responses. The herbicides referred to as inhibitory uncouplers were so named because at low molar concentrations they satisfy most, if not all, of the criteria established for uncouplers of oxidative phosphorylation. However, at higher molar concentrations, they also inhibit mitochondrial electron transport ( 1). ... 

The cyanophenol herbicides arrived as an intelligent replacement for Truffaut s dinitro-o-cresol. A typical example is ioxynil (6.71) 2,6-di-iodo-4-cyanophenol (Wain, 1963). It is a contact herbicide which powerfully uncouples oxidative phosphorylation (Section 4.5), in fact much more strongly than 2,4-dinitrophenol does (Kerr and Wain, 1964). It and the less expensive, if slightly slower acting, 2,6-dibromo-4-cyanophenol (bromoxynil), are used against young dicotyledonous weeds in cereal crops. They are also available as the octoate esters, for better penetration. 

Transformation of pyruvate to acetyl-CoA is linked to glycolysis and to the Krebs cycle and oxidative phosphorylation. The pyruvate dehydrogenase complex (PDHc) catalyzes the oxidative decarboxylation of pyruvate and acetylation of coenzyme A (CoA) to acetyl-CoA. This enzyme has been viewed as a potential herbicide target [238], In the perspective of structural optimization of a potent new herbicide, He et al. synthesized a series of structures 307 [239-241], which were a priori designed to inhibit the PDHc. 

Several polyfluoroalkyl amine and aniline derivatives have been recently reported with either herbicidal (1-3) or insecticidal (4-8) utility. As lipophilic weak acids, their modes of action have been linked to uncoupling of mitochondrial oxidative phosphorylation which produces ATP in cells throughout the plant and animal kingdoms. Early in 1988, we reported that the perfluorinated carboxanilide EL-499 (1 2, Figure 1.) represents a novel class of soil insecticide derived from electrofluorination technology and is under investigation for the control of corn root worm larvae in corn. (8) In contrast with EL-499, normal chain perfluorinated carboxanilides were described as labile to mild hydrolytic conditions at room temperature and thus exhibited little acute larvicidal... 

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