Hill reaction inhibitor

The eleven equations shown in Table VI express the activity of a group of Hill Reaction inhibitors (4-11). A common structural feature, in all the sets except Number 5, seems to be a nitrogen atom having considerable double bond character. Activity is... 

Since the triazin-3-ones appear to be Hill reaction inhibitors and may be considered as a class of cyclic ureas, disubstitution of the aromatic ring would be expected to Increase activity. The 2-(3,4-dichlorophenyl)-1,2,4-triazin-3-one, however, was found to require >4 kg/ha for acceptable weed control, despite a respectable PI50 of 6.9 (Table II). This difference in weed control between the two compounds suggests the aromatic substitution pattern in this class is quite different from that of a "urea" like compound. This, apparently, is the case (Table III). 2,4-Disubstitution as well as the choice of halogen is important for activity. The most effective combination appears to be a fluorine at the 2-position of the aromatic ring with either a chlorine or bromine at the 4-position. However, it is only with the fluorine/bromine combination that some degree of crop tolerance is observed, and then only at the lowest acceptable weed control rate. 

Synergic in vitro effects of some mixtures can be determined by Hill reaction inhibition. This method is useful only when the components have quite different herbicidal activities and one of them is not a Hill reaction inhibitor. With the help of paper chromatography, a 40% synergic effect of an atrazine-defenuron (3 2) mixture was detected (166). 

The use of herbicides that inhibit or interact with the photosynthetic machinery is seen, superficially, to be advantageous because of the likelihood of fewer problems of animal toxicity. However, the identical nature of the process in both crop and weed species, apart from C4 plants, means that herbicide selectivity must be achieved by differential uptake, movement, or metabolism. Following the discovery of the herbicidal action of N (4-chlorophenyl)-N,N-dimethylurea (subsequently known as CMU or monuron) by Bucha and Todd in 1951, Wessels and Van der Veen and Cooke showed that this compound was a potent inhibitor of photosynthetic electron transport. This, the first so-called Hill reaction inhibitor, was followed subsequently by numerous other phenylureas, triazines, uracils,... 

Research had confirmed that no parent simazine residues were found in treated com plants, and additional data on the dissipation pathway of simazine needed to be developed. Research also indicated that triazines interfered with the photosynthetic process on susceptible growing weeds, as evidenced by the appearance of chlorotic leaves. Steps were undertaken to elucidate simazine s dissipation pathway and herbicidal mode of action. In Basel, Dr. Gast (1958) showed that the accumulation of starch by common coleus (Coleus blumei Benth.) plants was inhibited from treatment with 2-chloro-4,6-bis-(alkyl-amino)-triazines due to the inhibition of sugar synthesis. At the same time, Moreland et al. (1958) found weed control activity could be reduced by supplying carbohydrates to the plants through their leaves and that simazine was a strong inhibitor of the Hill reaction in photosynthesis. Exer (1958) found that triazines inhibited the Hill reaction as strongly as urea of the CMU (monuron) type. 

In a study designed to determine the mode of action of atrazine in higher plants, Shimabukuro and Swanson (1969) concluded that atrazine inhibits the Hill reaction and its noncyclic phosphorylation, while being ineffective against cyclic photophosphorylation. Atrazine readily penetrated the chloroplast of resistant as well as susceptible plants. In tolerant plants such as sorghum, the metabolism of atrazine was postulated to occur outside the chloroplasts to form water-soluble and insoluble residues that reduced the concentration of photosynthetic inhibitors in the chloroplasts. 

Good, N.E. (1961). Inhibitors of the Hill reaction. Plant Physiol., 36 788-803. 

Artificial electron acceptors, such as ferricyanide, can be substituted for NADP these give rise to oxygen evolution but involve only a short segment of the oxidation chain. This partial reaction is known as the Hill reaction and compounds that disrupt it are known as Hill inhibitors. Herbicides that inhibit the Hill reaction, by blocking electron transport, prevent the production of ATP and NADPH required for carbon dioxide fixation. 

Herbicides that inhibit the photochemical reactions of isolated chloroplasts have been called routinely inhibitors of the Hill reaction. This has been done primarily for convenience and because, for many years, their action was evaluated under nonphosphorylating conditions, frequently with ferricyanide as the electron acceptor. In the past few years, more sophisticated studies have been conducted with herbicides and more is known about their differential actions. Consequently, Moreland and Hilton (2) separated herbicidal inhibitors of the photochemically induced reactions into the following classes (a) electron transport inhibitors, (b) uncouplers, (c) energy transfer inhibitors,... 

Some good inhibitors of the Hill reaction, however, do not contain the carbonyl oxygen-nitrogen moiety. Examples are the dinitroanilines, diphenylethers, 2,4-dinitrophenols, halogenated benzonitriles, and pyridinols. Hence, the postulates proposed are not all inclusive. Three of these herbicides are phenols. Under physiological pH s, the molecules can be expected to be ionized, and it may be the ionized form of the molecule that binds to the receptor. 

Soskic, M. and Sabljic, A. (1995). QSAR Study of 4-Hydroxypyridine Derivatives as Inhibitors of the Hill Reaction. Pestic.ScL, 45,133-141. 

Soskic, M., Plavsic, D. and Trinajstic, N. (1996a). 2-Difluoromethylthio-4,6-bis-(monoalkyl-amino)-l,3,5-triazines a Inhibitor of Hill Reaction A QSAR Study with Orthogonalized Descriptors. J.Chem.Inf.Comput.Sci., 36,146-150. 

The triazine herbicides are selective inhibitors of the Hill reaction in plant photosynthesis. In mammals, atrazine disrupts luteinizing hormone and prolactin secretion through direct action on the hypothalamus-pituitary axis. 

Diuron is a selective inhibitor of the Hill reaction in plant photosynthesis. 

Diuron [3-(3,4-dichlorophenyl)-l,l-dimethylurea] is a potent PS II inhibitor causing necrosis, whereas the related urea Fluometuron (Chart I) induces albinism in growing plants. Pyrazon [5-amino-4-chloro-2-phenyl-3(2H)-pyridazinone] inhibits the Hill reaction and photosynthetic CO fixation. meta-Trifluoromethyl substitution on... 

Since the ureas, carbamates and vinylogous carbamates are all PS II inhibitors (Figure 1), it is not surprising that these compounds are also powerful PS II inhibitors. The more active compounds (Table I) were considerably more active than atrazine (Table II) in the Hill reaction assay. The Hill reaction assay frequently does not correlate with whole plant (greenhouse) activity ( 1 and 2 and references cited therein). However, vinylogous ureas do correlate fairly well (Table III). Other assays including the carotinoid biosynthesis and acetolactate synthesis (ALS) assays showed little or no activity for these compounds. 

In addition to many early examples, biological response has been found to be quantitatively linearly dependent on log P or it in the inhibition of the Hill reaction >activity of penicillins, toxicity of benzoic acids to mosquito larvae , phenol coefficients , cholinesterase inhibitors , and catechol-amine activity . 

Although p (J) values are slightly smaller than pI q s obtained for the Hill reaction, they remain very similar except for ioxynil. Generally speaking, quantitative measurements of the fluorescence parameters described herein showed that DCMU-type inhibitors disconnect the two photosystems progressively as concentrations of the inhibitors are increased. Ioxynil does not behave in this manner. Ioxynil may not interfere at exactly the same site as the DCMU-type inhibitors, or it may have a secondary point of interference with the photosynthetic electron transport chain. 

Diuron is a particularly potent inhibitor of the Hill reaction (Table I), but it does not significantly alter membrane lipid composition. The possibility that the effects of the pyridazinones on membrane lipids result from pbotooxidation as a secondary consequence of the carotenoid inhibition is not likely. Wheat shoots treated with BASF 13 338 have normal levels of carotenoids and chlorophylls (Table II), but linolenic acid levels are severely depressed (Table III). Thus, inhibition at the lipid site can occur without inhibition at the pigment site. Also, BASF 13 338 preferentially reduces linolenic acid, whereas the double bonds of all the unsaturated fatty acids would be susceptible to photooxidation. San 9774 preferentially alters the fatty acid composition of MGDG compared to DGDG (Table III). The preferential alteration of a single class of membrane lipids is inconsistent with the photooxidation hypothesis. 

Furthermore/ addition of H003 to formate-treated Chlainydomonas cells produced 4 fold stimulation of the Hill reaction (Table 1) in the presence of the inhibitor DBMIB that inhibits electron flow between the two photosystems and, thus, OO2 fixation. 

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