A series of 1, 3-dithiane derivatives bearing various kinds of substituents at the 2-position or the 5-position was synthesized, and their Insecticidal activity was examined. Unsubstituted and substituted 1, 3-dithianes with a hydroxy group or an acyloxy group at the 5-position were mostly inactive against rice stem borers and two-spotted spider mites. Introduction of dialkylamino, especially dimethylamino, group at the 5-position increased the biological potency. Electron-withdrawing group (s) at the 2-position, especially cyano group, were effective in enhancing the activity against twenty-eight-spotted ladybirds. 2-Cyano-2-(N, N-diethylthiocarbamoyl)thio-5-dimethylamino-1, 3-dithiane (11i) and 2, 2-dicyano-5-dimethylamino-1, 3-dithiane (11m) had the strongest activity against the insects and mites.b

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A series of 2-cyano-5-dimethylamino-1, 3-dithianes was synthesized and their insecticidal and miticidal activities were examined. Most of the compounds prepared in this study exhibited potent activities against rice stem borers, two-spotted spider mites, small brown plant hoppers, common cutworms and twenty-eight-spotted ladybirds. Substitution of electron-withdrawing groups (chloro, bromo, nitro or trifluoromethyl) on the benzene ring in aryl derivatives or alkyl group having a carbon six to ten on the nitrogen atom of carbamoyl in carbamoyl derivatives such as 2-(4-bromophenyl)-2-cyano-5-dimethylamino-1, 3-dithiane (2a-4) and 2-cyano-5-dimethylamino-2-(N-n-nonylcarbamoyl)-1, 3-dithiane (2b-13), respectively, enhanced the activities.

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The storage stability of triflumizole and its metabolite, FM-6-1, in the final solutions of cleaned sweet pepper and lily scale was studied in dark and light conditions. Triflumizole and FM-6-1 rapidly decreased with storage time in the final acetonitrile solution of sweet pepper. After 168hr, triflumizole and FM-6-1 decreased to 3.7% and 33.9%, respectively. The decrease was more remarkable during the storage at 30°C than at 5°C, and in the light than in the dark. In the lily-scale solution, triflumizole and FM-6-1 did not degrade even at 30°C in the laboratory light. The difference of triflumizole and FM-6-1 in stability in the solutions of sweet pepper and lily scale may be attributed to the content of chlorophyll extracted from these crops. Triflumizole and FM-6-1 also decreased with time in an acetonitrile solution containing chlorophyll in the light, and degraded almost 1- to 2-fold faster than in the sweet-pepper solution. In both sweet-pepper solution and chlorophyll solution, new compounds appeared as triflumizole and FM-6-1 decreased and increased with storage time. The results indicated that the stability of triflumizole and FM-6-1 in the final acetonitrile solution of sweet pepper was affected by chlorophyll present in the solution, storage temperature and light.

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Effects of formulation factors such as mass median diameter (D) and wall thickness (T) on the rainfastness, phytotoxicity and acute mammalian toxicity of fenvalerate and fenpropathrin microcapsules were investigated. The rainfastness of fenvalerate microcapsules to cabbage was mainly regulated by T, increasing with a decrease in T. The microcapsules with T of less than ca. 0.05μm was superior to a fenvarelate emulsifiable concentrate in rainfastness. D was not a dominant factor, although the effect was not negligible. The phytotoxicity of fenvalerate microcapsules to cabbage, Chinese cabbage and cucumbers decreased with an increase in T. D was not a dominant factor, although the effect was not clear. The acute oral toxicity of fenpropathrin microcapsules in rats decreased with an increase in D·T. It seemed to be regulated by the release rate of the active ingredient from the microcapsules.

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The cis- and trans-isomers of 1-(4-chlorophenyl)-2-(1H-1, 2, 4-triazol-1-yl)cycloheptanol (1, 2) were compared in antifungal and plant growth-inhibitory activities. The cis-isomer of triazolylcycloheptanol had stronger antifungal activity against most fungi than the trans-isomer in vitro. Against Rosellinia nacatrix, however, the trans-isomer showed much stronger antifungal activity than the cis-isomer. In preventive activity against cucumber gray mold, powdery mildew, sclerotinia rot and rice blast, the cis-isomer was much stronger than the trans-isomer. In disease-controlling activity against wheat powdery mildew and oat crown rust, the cis-isomer was slightly stronger than the trans-isomer, whereas against rice sheath blight both isomers were similarly active. On the other hand, the trans-isomer had much stronger inhibitory activity than the cis-isomer on the growth of rice seedlings. Diastereomers of 1-substituted-2-(1H-1, 2, 4-triazol-1-yl) cyclohexanols (3-8) were also compared in biological activity. In disease-controlling activity the cis-isomers were more effective than the corresponding trans-isomers against cucumber gray mold and powdery mildew. In plant growth inhibitory activity the trans-isomers were more effective than the cis-isomers on rice seedlings. Between the two enantiomers of cis-1-(4-chlorophenyl)-2-(1H-1, 2, 4-triazol-1-yl)cycloheptanol (1), the preventive activity of the (l)-enantiomer was about two times stronger than that of the (d)-enantiomer against cucumber gray mold and powdery mildew. The (l)-enantiomer also had stronger growth inhibitory activity on rice seedlings than the (d)-enantiomer.

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A bacterial strain E-6 was isolated from groundwater in which the microbial community failed to degrade 0.1μg C/ml of 2, 4-dichlorophenol (DCP). Pure culture of E-6 degraded 0.1μg DCP-C/ml in filter-sterilized groundwater, irrespective of inoculum size. However, when inoculated into the groundwater containing a microbial community, E-6 failed to degrade DCP, except when the inoculum size was as large as 10⁶cell/ml. These results suggest that the lack of mineral nutrients, the low concentrations of DCP and the possible presence of toxic substances were not responsible for the failure of DCP degradation by E-6 in the community. The failure may have been attributable both to the cometabolism of DCP by E-6 and to the elimination of uncharacterized dissolved organic carbon (DOC) by the microbial community, i. e. the cometabolism of DCP and the elimination of DOC caused E-6 to fail to increase its cell density high enough to make DCP degradation detectable.

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Binding of auxin-type herbicides to maize membrane-bound auxin binding protein was compared with their physiological activities. There was a good correlation between the binding and the growth promoting activity of the herbicides, but the ethylene production or the inhibition of shoot growth did not completely correlate with the binding. Benazolin [4-chloro-2-oxobenzothiazolin-3-yl-acetic acid] did not bind to maize auxin binding protein, but it stimulated ethylene production. Quinclorac [3, 7-dichloro-8-quinolinecarboxylic acid] did not bind to maize auxin binding protein, but it strongly inhibited maize shoot growth. These results may suggest that the stimulation of ethylene production and the growth inhibition by auxin-type herbicides are not triggered by their binding to the putative maize membrane-bound auxin receptor.

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The activity of a new juvenile hormone analogue, NC-170 [4-chloro-5-(6-chloro-3-pyridylmethoxy)-2-(3, 4-dichlorophenyl)-pyridazin-3(2H)-one], was evaluated on four species of leafhoppers, Nephotettix cincticeps, N. nigropictus, N. virescens and Recilia dorsalis. When NC-170 was topically applied to mid-penultimate larvae, their metamorphosis was strongly inhibited. The compound with the ID₅₀'s of 5.2×10^-11 to 3.7×10^-12g/larva was 10 to 30 times as active as natural JH-1. The critical period of the morphogenetic activity was limited in a 24hr span before and after the 4th larval molt. The affected insects did not develop into normal adults, but into supernumerary larvae (SL1). About 5 days later, the SL1 could not complete the molt into secondary supernumerary larvae (SL2) and subsequently died. Furthermore, NC-170 showed good sterile effects. When newly emerged female N. cincticeps adults were continuously exposed to NC-170, the hatchability of oviposited eggs severely reduced, even at a concentration of 4ppm. In a field trial, NC-170 showed good foliar persistency in paddy fields and single spray treatment with 100ppm NC-170 considerably suppressed the population density of N. cincticeps for more than 6 weeks.

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Prothiophos oxon or its S-alkyl homologs (alkyl: methyl, ethyl and butyl) was incubated with a mixture of rat liver microsome and cytosol at 37°C for 30min in the following conditions: (a) without NADPH and GSH, (b) with NADPH (condition for S-oxide formation) and (c) with both NADPH and GSH. Each reaction mixture was lyophilized after adding sucrose and fed to adult female houseflies (susceptible Takatsuki strain). Their mortality was observed at intervals until 48hr. Dose for each compound was adjusted based on its LD₅₀ value so that the time required for the residual oxon to exert its insecticidal activity was delayed. In the case of S-methyl compound, the mortality in (c) was similar to that in (a), although the remaining oxon in (c) was about half of that in (a). This suggests that the insecticidal effect in (c) may also have been given by something other than the oxon. The mortality in (c) was also higher than that in (b), although the amount of the remaining oxon was the same. Considering the unstability of the S-oxide formed in the reaction mixture in (b), something stabilized in (c) may have contributed to the insecticidal activity. Without cytosol, the mortality in (c) decreased. The similar tendency was observed with other compounds. When bovine erythrocyte AChE was added to the above incubation mixture, the AChE was inhibited by the reaction mixture strongly in (c) and when more GSH was added regardless of the S-alkyl groups used. The reaction mixture was given to susceptible and resistant (higher glutathione S-transferase activity) strains. The death started later in the resistant strain than in the susceptible strain in (a), but was accelerated in (c) and the period of high mortality was longer in (c) than in (a). The mortality was different between (a) and (c) only during the initial period in the susceptible strain. The above result is well explained by postulating that S-alkyl phosphorothiolate compounds produce S-oxides that inhibit ACNE, while the S-oxides give another active intermediates conjugated by the GSH-glutathione S-transferase system that also inhibit AChE. These two actions combined are to give an insecticidal effect.

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Safer emulsifiable concentrates (ECs) of pyrethroids were investigated with polyethylene glycol (PEG) or polypropylene glycol (PPG). When the average molecular weight of PEG and PPG was more than 150 and 134, respectively, fenpropathrin was miscible with them at least to 10wt%, while esfenvalerate was also miscible to 20wt%. When the average molecular weight of PEG and PPG was 150 to 600 and 134 to 300, respectively, fenpropathrin 5 and 10wt% ECs, and esfenvalerate 5, 10 and 20wt% ECs without emulsifiers had good emulsion stability. A fenpropathrin 5wt% EC composed of PEG 300 showed 100% of emulsion dispersibility at 5 to 20°C, and approximately 80% at 25 and 30°C. When a small amount of suitable emulsifiers was added to the EC, the emulsion stability improved at a temperature as high as 30°C. Compared with conventional ECs, the acute oral toxicity of fenpropathrin and esfenvalerate 5wt% ECs composed of PEG or PPG, and fenvalerate, permethrin, d-phenothrin and cypermethrin 10wt% ECs composed of PEG remarkably decreased. The eye irritation of esfenvalerate 5wt% ECs composed of PEG or PPG also decreased. ECs composed of PEG or PPG were superior to conventional ECs in smell and inflammability. They were also better in storage stability, cold test, spontaneous emulsification and insecticidal activity.

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Theoretical studies were conducted by computer simulation on condition that a combination of two compounds might produce a joint action. A simple model was employed with the main components of a single enzyme for degradation and the site of action for inhibition, in addition to cuticular penetration and activation factors. Studies were based on the assumption that two compounds inhibit the degradation enzyme either competitively or non-competitively. The following factors governing the joint action of insecticides were elucidated: 1. Potentiation appears at V_B<<V_AI_B/I_A, K_B<<K_BI_A/I_A, and K_B<<I_B, where A and B denote compounds A and B, and the degradation of each compound is under control of maximum degradation velocity (V_A and V_B) and Michaelis constant (K_A and K_B) of the Michaelis-Menten type rate equations. I_A and I_B denote concentrations of compounds A and B affording 50% inhibition of the target in the presence of degradation process. The situation indicates that compound A should be highly able to inhibit the target and at the same time should be susceptible to degradation. Compound B should be able to inhibit the degradation of compound A at a lower concentration than required to inhibit the target. The more the properties of compounds A and B fulfill the above condition, the greater the potentiation would be. In another word, compound B inhibits the degradation of compound A resulting in an increased accumulation of compound A, which in turn leads to a stronger inhibition of the target. 2. Potentiation is maximum when the ratio of compounds A and B is equal to the ratio of I_A and I_B (this could be substituted for convenience by the ratio of LD₅₀ of the compounds). 3. The slower the cuticular penetration of the two compounds, the smaller the potentiation. 4. The larger the role in degradation of a particular enzyme involved in interaction of the two compounds, the larger the potentiation.

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In vitro studies were carried out to substantiate the result obtained from theoretical analysis that the level of potentiation produced by joint action of insecticides could be predicted by using such parameters as the affinity of each insecticide to the degradation enzyme involved, the rate of degradation, and the I₅₀ for target inhibition in the presence of the degradation enzyme. These parameter values were determined in a simple model system that consists only a single enzyme for degradation, carboxylesterase from the porcine liver, and the target for inhibition AChE from the electric eel. The results showed that a combination of malaoxon and paraoxon as well as malaoxon and dichlorvos among various combinations of insecticides evaluated fulfilled the conditions for potentiation satisfactorily. A comparison of I₅₀ for AChE inhibition actually demonstrated a high level of potentiation with the above two combinations. Furthermore, the mixing ratio of two insecticides which produced the maximum potentiation level was equal to the ratio of I₅₀ of individual insecticides. These results were in agreement with what the theoretical analysis by computer simulation suggested.

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N-(3, 5-dichlorophenyl)-N′-methoxyformamidine (DPMF) with specific fungicidal activity against a benzimidazole-resistant isolate of Botrytis cinerea was synthesized and its fungitoxic properties were studied. DPMF had fungicidal effects similar to those of methyl N-(3, 5-dichlorophenyl)carbamate (MDPC) in terms of negatively correlated cross-resistance to benzimidazole fungicides. In microscopic observation DPMF nearly equaled MDPC in the morphological effect on B. cinerea. Based on the fungicidal properties, structural similarity of DPMF and MDPC was studied by computational techniques in order to rationalize their bioisosterism. The results suggested that their functional groups were similar in terms of molecular shape and electrostatic potential distributions when they are compared in one of the energy-minimum conformations.

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A leaf immersion method to evaluate leaf surface wettability was investigated. Retention figures of immersion solutions containing a dye (Direct Fast Scarlet 4BS) 1.0% and surfactant(s) 0.2% on leaf surfaces were classified into six types (A-E and O) and the specific retentions (Up-2) on leaf surfaces were obtained at immersion lengths of more than 10cm for Gramineae and 5cm for soybean, cowpea and others with a solution making a continuous thin film (A-1 retention). Up-2 and whole-leaf retentions were measured for 23 crops from eight families. The former fell in a narrow range of ca. 0.6-1.1μl/cm² for all the leaves but the latter was divided into two groups; almost the same retention (Cucurbitaceae, Brassicaceae and Malvaceae) and fairly varied retention (Gramineae, Legminosae and Solanaceae). It was possible to evaluate wettability on specific retention figures with the leaf immersion method we have developed.

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4-Isobutyl-2-methoxy-1, 3, 2-thiazaphospholidine 2-sulfide (iBMTS) and the related thiazaphospholidines were prepared by reacting phosphorodichloridothionate and β-aminothiols, which were obtained from the corresponding β-aminoalcohols via β-aminoalkyl hydrogen sulfate and 2-mercaptothiazoline followed by hydrochloric acid-catalyzed hydrolysis. Thiazaphospholidines had a higher insecticidal activity than the corresponding oxazaphospholidines against female Musca domestica houseflies by topical application. Methoxy derivatives were more potent insecticides than ethoxy derivatives. Oxazaphospholidines with a more bulky hydrophobic branched-alkyl substituent at C₄ or phenyl at C₅ were more potent than those with a less bulky hydrophobic substituent. In thiazaphospholidines, however, the effect of introduction of a bulky hydrophobic substituent at C₄ was not as significant as in oxazaphospholidines in increasing the insecticidal activity. Neither oxazaphospholidines nor thiazaphospholidines activated adenylate cyclase of Periplaneta americana ventral-nervecord homogenates, but both reduced octopamine-stimulated adenylate-cyclase activity.

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Salithion, one of saligenin cyclic phosphates (SCPs) was effective against organophosphorus (OP)-resistant houseflies. The synergism of some non-insecticidal SCPs, K-1 and K-2, with fenitrothion was found in the resistant strains. One of the OP-selection was the alteration of acetylcholinesterase (AChE) to be insensitive against the oxon-type of OPs, and the insensitive AChE had low affinity with OP-oxons, whereas salioxon had a high inhibitory activity for the enzyme of the resistant insects. On the other hand, the OP-selection also increases high activities of detoxifying enzymes, including glutathione transferase (GSH-t), which also catalyzed the demethylation of fenitrothion. Salithion was stable against the biodegradation. Moreover, SCPs inhibited the degradation of fenitrothion. Both the demethylation of fenitrothion and the glutathione (GSH) conjugation of l-chloro-2, 4-dinitrobenzene were inhibited by the GSH conjugate of SCPs, i. e., S-(2-hydroxybenzyl)glutathione, in a manner of competition with GSH. SCPs inhibited the GSH-t directly and irreversibly in the absence of GSH. In conclusion, SCPs play significant role as effective inhibitors on the important points of OP-resistant mechanisms, AChE and GSH-t, in different mode, that is, a phosphorylation and an alkylation. These actions are considered to contribute to the biological activities of SCPs, i. e., the high insecticidal potency of salithion against OP-resistant insects and the synergistic effect of K-1 and K-2 with some OPs.

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A pesticide formulation should be designed rationally to maximize its pesticidal efficacy by thoroughly investigating the relationship among the formulation factors, the physical properties of the formulation and its pesticidal efficacy. By the rational design of the formulation, pesticides can be used efficiently to the purpose, and maximum efficacy can be obtained by using the smallest amount of pesticide. Standing on this concept, authors studied the influence of the physical properties of aerosol formulations on their insecticidal efficacy. The insecticidal efficacy of an aerosol formulation is thought to be influenced by the behavior of the spray-droplets in the air and by the permeability of the insecticide through the cuticle of the insect to reach the nervous system. Then, the spray-droplet size and the solvent used for the aerosol formulation are thought to be the two most important factors. The spray-droplet size was decisive to maintain the concentration of airborne spray-droplets; the smaller the spray-droplets, the longer the concentration maintained. However, there existed an optimum spray-droplet size to maximize the insecticidal efficacy, which was around 30μm. This result was explained by the effect of the balance of the catch efficiency of airborne spray-droplets by flying insects which was affected by the inertia of spray-droplets, and the maintenance of the concentration of airborne spray-droplets which was affected by their settling speed. Among the solvents used for the aerosol formulation, the most effective one for knockdown efficacy was tetradecane. This solvent was thought to facilitate the insecticide to penetrate into insect through the cuticle.

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¹³C and ¹H NMR spectroscopy were applied on fungicide pharmacology in cellular level, and two-dimensional ¹H NMR spectroscopy in molecular level. Mycelia of Pyricularia oryzae were incubated with [methyl-¹³C]methionine, and ¹³C NMR spectrum of the intact mycelia was measured. After 3hr incubation, N-methyl signal of choline appeared at 54.9ppm showing that methyltransfer from methionine into choline can be observed by the ¹³C NMR. Treatment with 350μM iprobenfos inhibited the choline biosynthesis. Isoprothiolane also inhibited the methyltransfer at the concentration of 140μM. The observed spin-spin relaxation time (T₂) of intracellular water protons reflects the membrane water permeability. Effects of various types of fungicides on the membrane were, then, investigated by using the T₂ of the water protons in the mycelial cells of Botrytis cinerea. Treatment of the cells with ionophores remarkably increased the membrane water permeability, which suggests that the water molecules exchange through the ion channels of the ionophores. Phosphatidylcholine biosynthesis inhibitors, as well as ergosterol biosynthesis inhibitors, slightly increased the membrane water permeability. This result indicates that phosphatidylcholine and ergosterol have no direct relation to the membrane water permeability though some secondary effects were observed through the change in the membrane structure. Some SH inhibitors increased the membrane water permeability probably by binding to the proteins at ion channels. The structure of the complex of a deoxyoctanucleotide, d(GCAATTGC)₂, and berenil, a trypanosidal drug, was analyzed by two-dimensional ¹H NMR spectroscopy. The nuclear Overhauser effects (NOE) between the two molecules and the ring current shifts revealed that berenil binds in the minor groove of d(GCAATTGC)₂ retaining the overall B conformation of the octanucleotide duplex. It is likely that the complex has hydrogen bonds between the berenil amidine protons and the carbonyl oxygen of the external thymine or the purine nitrogen of the internal adenine.

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[in Japanese]

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