Biomimetic Chemistry as a Useful Tool for Studying Reactive Metabolites of Pesticides

Abstract

Most organophosphate (OP) pesticides require metabolic activation before attacking the target site, as opposed to chemical nerve agents, such as VX and sarin, which inhibit the enzyme directly. The majority of OP pesticides exhibit weak anticholinesterase activity in vitro compared to their In Vivo activity. Biooxidation is probably the principal route by which these pesticides are activated or detoxified. The oxidized product, usually a short-lived intermediate, may either hit the target directly or hydrolyze rapidly or, following a rearrangement reaction, convert to another species with enhanced reactivity (metaphosphate) or lose its phosphorylation or carbamoylation properties. Biomimetic studies of these processes, using various model systems, have important advantages: in some cases they allow for identifying short-lived intermediates, formed metabolically, and direct monitoring of the systems' properties by NMR. Once identified, they may be synthesized in large amount to investigate their adverse effects, if any. Biomimetic studies allow for monitoring reactions at low temperature seeking transient intermediates and evaluation of activation and detoxification mechanisms as well as mode of action based on chiral isomers. This, in turn, allows for determination of whether certain compounds act directly, on preactivation, or both, and the possible design of safer pesticides. This paper covers over three decades of extensive fundamental and applied research that has been carried out at the Environmental Chemistry and Toxicology Laboratory (ECTL) at the University of California at Berkeley under the supervision of Prof. John E. Casida.

Hydrolysis Studies of Phosphodichloridate and Thiophosphodichloridate Ions

“…Subsequent decarboxylation of the carbonate adducts led to the dichloridic acid species that become deprotonated by additional bicarbonate ions to afford dichloridate salts 1 and 2. 7 We chose to use acetonitrile in place of acetone in our procedures owing to its higher boiling point facilitating more accurate handling of volumetric solutions. We adopted the same reaction times as used by Segall et al, and we were able to prepare both dichloridate salts 1 and 2 in homogeneous forms without needing to perform further optimizations.…”

“…The syntheses of dichloridates 1 and 2 have been reported by Segall et al where bicarbonate ion was used as the oxygen nucleophile to displace chloride, and acetone was employed as the solvent. Subsequent decarboxylation of the carbonate adducts led to the dichloridic acid species that become deprotonated by additional bicarbonate ions to afford dichloridate salts 1 and 2 . We chose to use acetonitrile in place of acetone in our procedures owing to its higher boiling point facilitating more accurate handling of volumetric solutions.…”

The aqueous N-phosphorylation and N-thiophosphorylation of aminonucleosides

“…The preparation of potassium phosphodichloridate and potassium thiophosphodichloridate has been reported previously. 20,34 Phosphorylation procedure…”

Degradation dynamics, residues, processing factors, and dietary risk assessment of bisultap in citrus by LC‐MS/MS

“…Biomimetic pesticides are novel pesticides synthesized by altering the chemical structures of natural products used as lead compounds. 1 The primary sources of biomimetic pesticides are animals, plants and microorganisms. 2 The nereistoxin group of insecticides is the most prevalent type of animal-derived bionic pesticide.…”