Luis O. Ruzo

Photochemical conversion of a dicofol impurity, α-chloro-DDT, to DDE

Examen des proprietes chromatographiques et spectroscopiques du dicofol et de lα-chloro DDT et de leurs produits de photolyse, apres irradiation de solutions dans lhexane. Mise en evidence dune decomposition du dicofol en dichloro-4,4 benzophenone, dechlorodicofol et biphenyle (dichloro), tandis que lα-chloro-DDT subit une dechloration photochimique et est une source de DDE pour lenvironnement

Metabolism and degradation of the pyrethroids tralomethrin and tralocythrin in insects

Abstract Tralomethrin and tralocythrin undergo debromination, forming deltamethrin and cypermethrin, respectively, following topical administration to house flies, feeding to cabbage looper larvae, or incubation with house fly homogenates and cockroach nerve cords. The debromination is probably not an enzymatic process since it occurs rapidly on incubation with glutathione, cysteine, and albumin. Following debromination, an esterase(s) in house fly homogenate hydrolyzes delta-methrin and cypermethrin. The insecticidal activity of tralomethrin and tralocythrin may be due in part to the liberation of deltamethrin and cypermethrin in the insect or its nervous system.

Superoxide-mediated dehydrohalogenation reactions of the pyrethroid permethrin and other chlorinated pesticides

Abstract Superoxide generated in DMF readily converts the dihalovinyl group of permethrin and related compounds to a haloethynyl moiety and yields major products from elimination reactions of DDT, cis -chlordane, and 1,2-dibromo-3-chloropropane (DBCP).

Comparative Metabolism of Pyrethroids Derived from 3-Phenoxybenzyl and α-Cyano-3-Phenoxybenzyl Alcohols

Abstract Fenothrin, permethrin, Cypermethrin, decamethrin, fenpropanate and fenvalerate are highly insecticidal pyrethroids prepared by esterification of 3-phenoxybenzyl alcohol or α-cyano-3-phenoxybenzyl alcohol with chrysanthemic acid or other acids of similar configuration. These pyrethroids are rapidly metabolized in rats by hydrolysis and by oxidation at the 4′-position of the alcohol moiety and to a lesser extent at the aliphatic substituents. These sites are also involved in metabolism of the permethrin isomers in cows, chickens, insects, plants and soils, of decamethrin in mice and plants, and of fenvalerate in soils. Additional sites of oxidation of the permethrin isomers, decamethrin or fenvalerate in some animals are the 2′-, 5- and 6-positions of the alcohol moiety. Various combinations of oxidation, hydrolysis and conjugation lead to >50 identified metabolites of the permethrin isomers in various insects and mammals. In vitro studies with microsomal oxidase preparations from mammals, insects and fish reveal some or all of these sites of hydroxylation and further oxidation of the hydroxymethyl substituents to the corresponding aldehydes and carboxylic acids. The selective toxicity of pyrethroids between insects and mammals may be further increased by replacing substituents biodegraded rapidly in insects with others more resistant to insect but not mammalian pyrethroid carboxyesterases and microsomal oxidases.

Neurophysiological activity and toxicity of pyrethroids derived by addition of methylene, sulfur or oxygen to the chrysanthemate 2-methyl-1-propenyl substituent☆

Abstract Conversion of chrysanthemates to their cyclopropane, episulfide, and epoxide derivatives by addition of methylene, sulfur, or oxygen, respectively, to the 2-methyl-1-propenyl double bond yields products generally of reduced toxicity but enhanced neurophysiological activity and photostability. The reduced toxicity is established with cis-cyphenothrin derivatives administered intracerebrally to mice and topically to house flies and with cis-phenothrin derivatives applied topically to American cockroaches and house flies, even in the presence of piperonyl butoxide for the house flies. In contrast, cyclopropane, episulfide, and epoxide derivatives of phenothrin are more potent than the parent compound in eliciting repetitive firing following stimulation of a cercal sensory nerve of the American cockroach in vitro. The individual 1′R and 1′S isomers of epoxides derived from (1R,cis,αS)cyphenothrin, (1R,cis)phenothrin, and (1R,trans)tetramethrin differ in potency by up to 20-fold for insecticidal activity, >30-fold for intracerebral toxicity to mice, and ∼100,000-fold in the cercal sensory nerve assay. In each case the epoxide isomer of higher Rf is more potent than that of lower Rf when derived from a trans-chrysanthemate and vice versa from a cis-chrysanthemate.

Phosphinyliminodithiolane insecticides: Oxidative bioactivation of phosfolan and mephosfolan

Abstract 2-(Diethoxyphosphinylimino)-1,3-dithiolane (phosfolan) and its 4-methyl analog (mephosfolan) are proinsecticides as determined by microsomal mixed-function oxidase (MFO) activation to potent acetylcholinesterase (AChE) inhibitors. They are similarly activated by peracid oxidation which yields the sulfoxide and sulfone derivatives. The hydrolytically unstable S -oxides are irreversible AChE inhibitors that are 160- to 47,000-fold more potent than phosfolan and mephosfolan. MFO S -oxidation is indicated for both proinsecticides by (a) NADPH-dependent increases in potency as AChE inhibitors to an extent expected of sulfoxides, and (b) formation of the S -oxide hydrolysis product diethyl phosphoramidate.

Phosphinyliminodithiolane insecticides: Novel addition reactions of phosfolan and mephosfolan sulfoxides and sulfones

Abstract The sulfoxides and sulfones of phosfolan [2-(diethoxyphosphinylimino)-1,3-dithiolane] and mephosfolan (its 4-methyl analog) react by nucleophilic attack of water, methanol, and thiols at the imino carbon rather than at the phosphorus. Some of the addition products are in turn reactive. Thiolcarbamates formed on hydrolysis of the sulfoxides and sulfones further react with water at physiological pH giving diethyl phosphoramidate via a carbamic acid and with methanol yielding a methyl carbamate. Sulfenic acids from sulfoxide addition reactions readily condense with thiols, e.g., phosfolan sulfoxide readily forms a bis conjugate from addition of two molecules of glutathione. These addition reactions may serve as models for inhibition of acetylcholinesterase, detoxification, and tissue binding.

PHOTOOXIDATION REACTIONS OF PYRETHROID INSECTICIDES

The reactions of a variety of pyrethroids with triplet and singlet oxygen and with ozone have been studied. The principal identified oxidation processes of pyrethroids involve allylic oxidation, epoxidation, hydroperoxide formation and cleavage of the alkene substituent on the cyclopropane ring. Secondary reactions are detected during and after ester cleavage. A mutagenic photoproduct of allethronyl esters is described. It is formed by di-π-methane rearrangement of the allyl group, followed by epoxidation of the double bond in the cyclopentenolone ring.

PHOTODEGRADATION OF PESTICIDES IN SOLUTION: ISOMERIZATION, DEHALOGENATION AND ESTER CLEAVAGE REACTIONS OF THE PYRETHROID INSECTICIDES

The photodegradation of pesticides can be conveniently studied in aqueous or organic solutions since photoproducts, reactivity comparisons and the effect of additives, such as sensitizers, oxidizing agents, heavy atoms, etc., can be readily determined.