Chloroplast pyridazinones

The close agreement between the experimental and calculated (Equation 9) ratios of 18 2/18 3 support exclusion of the 4-hydroxylphenyl analogue from the calculations. Examination of Equation 9 shows an interdependence between the biological activity and the hydrophobic properties of the chemical used, commonly found with many QSAR equations. This interdependent relationship is determined by the and terms, respectively. These terms control phenomena of hydrophobic interactions with receptors and phenomena of transport and distribution within the total biological systems. The occurrence of squared terms of the hydrophobic parameter in structure-activity correlations has been explained on the assumption that the compound has to penetrate several lipophilic-hydrophilic barriers or compartments on its way to the site of action (16, 17). This is consistent with the uptake of pyridazinones by roots and sbsequent translocation to the shoots (chloroplast) as the site of action (13). 

Metflurazon inhibits photosynthesis and prevents the development of chloro-plastids in sensitive plants (Hilton et al., 1969). The authors also report on their investigation of the mode of action of 4 pyridazinone herbicides on barley. Metflurazon and its phenyl- and unsubstituted amino analogues, structurally similar to pyrazon, also inhibited the Hill reaction and photosynthesis, but showed two further biological features they resisted metabolic oxidation and inhibited chloroplast formation. The latter effect is similar to that of amitrol and dichlormate, but 100-1000 times stronger. 

Mild-Trypsin Digestion. When a preparation of stripped chloroplasts (thylakoids) is incubated with trypsin, the electron transport block imposed by photosynthetic inhibitors is almost completely overcome. Based on responses obtained, inhibitors can be divided into 3 groups (Table IV). Chemicals in Group 1 behave like DCMU, i.e., most of the reducing activity is restored in trypsin-treated chloroplasts relative to untreated controls (i7-phenylureas, s-triazines, i7-acylanilides, i 7-phenylcarbamates, uracils, pyridazinones, and triazinones). loxynil and i-dinoseb... 

A large number of commercial herbicides interfere with electron transport and ATP production in isolated chloroplasts and mitochondria (1.). These herbicides can be divided into two groups electron transport inhibitors and inhibitory uncouplers ( 1, 2, The dimethylphenylureas, substituted uracils, s-triazines, and pyridazinones have been classified as electron... 

Substituted pyridazinone herbicides directly inhibit photosystem II, chloroplast pigment biosynthesis, and membrane lipid biosynthesis. Depending on the substitution, pyridazinones can specifically inhibit the synthesis of linolenic acid in galacto-lipids and phospholipids preferentially alter the fatty acid composition of monogalactosyl diglycerides compared with digalactosyl diglycerides and cause a build-up of saturated fatty acids in the chloroplast membranes. 

The differential responses of plant species and tissues to substituted pyridazinones suggest that control of linolenic acid biosynthesis may vary depending on plant species and even tissue. An interaction between triazine herbicides and the lipid composition of chloroplast membranes may influence sensitivity of weed biotypes to the triazine herbicides. 

Numerous herbicides are known to inhibit photosystem II (PS II) - dependent electron transport. The values for inhibition by selected pyridazinones of electron transport in isolated barley chloroplasts are shown in Table I. The value for diuron [3-(3,4-dichlorophenyl)-1,1-dimethyl urea] may be used to relate these results to those in other literature. 

The competitive binding experiments of Tischer and Strotmann (4) suggest that the phenylureas, biscarbamates, triazines, tria-zinones, and pyridazinones inhibit electron transport by interaction with the same component of PS II. Action at this site seemed to account for the phytotoxicity of pyrazon [5-amino-4-chloro-2-phenyl-3(2H)-pyridazinone]. In addition to action at this site, compounds with molecular substitutions onto the structure of pyrazon (Figure 1) also interfere with the formation of chloroplast membrane lipids, namely the chlorophylls, carotenoids, and glycerolipids. 

The chlorophylls and carotenoids are the pigmented lipids associated with chloroplast membranes. Substituted pyridazinones reduce the accumulation of these pigments (Table II). 

Effect of substituted pyridazinones on chloroplast pigment accumulation in 4-day-old wheat shoots (2). 

Chloroplast membranes differ from most other membranes in that the major portion of the non-pigmented lipids of the chloroplast are the linolenic acid-rich galactolipids, with sulfo-lipids and phospholipids present as the minor lipid constituents. The third site of action affected by pyridazinones in wheat shoots is the formation of galactolipids (, 3 ). The data in Table III summarize the effects of substituted pyridazinones on the relative fatty acid composition of wheat shoots. 

Pyrazon inhibited PS II (Table I) but did not interfere with the accumulation of chloroplast pigments (Table II) or influence the composition of glycerolipids (Table III). Therefore, even though the other substituted pyridazinones also inhibit PS II, their actions on chloroplast pigments and/or glycerolipids are not likely to result from PS II inhibitions. Further evidence that inhibition of PS II does not result in membrane lipid changes is presented in Table IV. 

Primary herbicidal effects are followed by secondary ones that show up before death of the plant cell. The 70-S ribosomes of wheat chloroplasts are decreased by bleaching pyridazinones in the light, but not in the dark ( 9) A prominent mode of action is observed upon the composition of fatty acids by, e.g., BAS 13338 (SAN 9785) (24, 5), which does not substcuatially interfere with carotenoid biosynthesis. Good direct inhibition of photosynthetic electron transport (I50 3 x 10 7m) is observed with the phenylpyridazinone BAS 100822 electron transport inhibition of other phenyl-pyridazinones is less than with BAS 100822 (28). 

Camp P.J. and Randall D.D., 1985. Purification and charaterization of the pea chloroplast pyruvate dehydrogenase complex. Plant Physiol. 77, 571-577. Fedtke C., 1982. Pyridazinones In Biochemistry and Physiology o7 Herbicide Action, Fedtke C. ed., Springer-Verlag, Heidelberg, pp. 108-HO. 

Other laboratories have also carried out simultaneous measurements of the lipid or lipid metabolism changes associated with pyridazinone-induced in plastid morphology. Davies and Harwood examined the effects of Sandoz 6706 and Sandoz 9785 on lipid metabolism and membrane structure in greening barley. Changes seen in chloroplast structures included a slowing of normal differentiation on greening and the appearance of large... 

In conclusion, one of the possible sites of action of the substituted pyridazinones occurs at the level of fatty acid desaturation. In particular, desaturations involving linoleate or hexadecadienoate substrates are inhibited when MGDG is the substrate. Some pyridazinones also inhibited the formation of trans-A3-hexadecenoate, the unusual acyl group of chloro-plast PG. There is evidence that pyridazinone treatment of sensitive plants gives rise to structural changes in chloroplast membranes, but the link of these alterations to inhibition of fatty acyl desaturation is unproven. 

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