Oxidative Activation and Degradation of Organophosphorus Pesticides Mediated by Iron Porphyrins

Abstract

Oxidative metabolism catalyzed by cytochrome P450 enzymes (P450) is one of the most important degradative pathways for xenobiotics including pesticides. Many types of reactions such as hydroxylation of alkyl and aromatic carbons, dealkylation via stepwise oxidation, epoxidation of alkene and oxidation at nitrogen and sulfur atoms are known to be catalyzed. [1][2][3] The atomic oxygen originating from molecular oxygen is bound to iron of the protoporphyrin IX moiety in P450 and its transfer to a substrate proceeds in the presence of NADPH.The Fe (valence, IV; spin state, Sϭ1) porphyrin-oxygen cation radical has been strongly suggested as the prosthetic moiety in an active state by extensive theoretical studies and the triplet oxene is considered to be the most appropriate model. 4) In order to examine the mode of action of P450-catalyzed oxidation at a molecular level, Keserü et al. have applied computational methods including molecular orbital (MO) calculations and molecular dynamic simulations to the carbofuran-P450cam complex utilizing the three-dimensional structure of the enzyme. 5) Either hydrogen bonding or steric constraint imposed by the polypeptide backbone was found to highly control the oxidation of carbofuran near the active site and the major metabolic hydroxylation at the 3-position was correctly elucidated. Another approach has been to use synthetic metalloporphyrins as a model of P450 especially in the field of drug metabolism. 3,6,7) The various types of electrondeficient iron porphyrins have been recently synthesized to increase oxidative reactivity and moreover, the introduction of bulky phenyl groups at meso-positions of the porphyrin ring has successfully hindered the unfavorable formation of the moxo dimer in the catalytic oxidation. 8) The co-existence of an oxidant such as hydrogen peroxide in organic solvent was found to well simulate the P450-catalyzed reactions of many chemicals including several carbamate insecticides. 3,9) The oxidative desulfuration of phosphorothioate pesticides to form the corresponding oxon or S-oxidation of the alkylthio group to sulfoxide and sulfone is a well-known metabolic reaction catalyzed by P450. 10) These reactions have been extensively examined for the various radiolabels of parathion, and phosphoxathiirane is proposed to be a key intermediate which is activated to the oxon with a release of an elemental sulfur or reacts with water to form the corresponding phenol. 11) Oxidative desulfuration through this intermediate was found to be feasible in a theoretical analysis using a reaction coordinate method in MO calculations of model compounds. 12) In order to examine the applicability of synthetic iron porphyrins as a biomimetic model of P450, we carried out the oxidation of several organophosphorus pesticides using three types of iron porphyrins. The reactivity and product distribution were also examined with the aid of MNDO-J. Pestic. Sci., 30(2), 103-110 (2005) * To whom correspondence should be addressed. E-mail: fujisawat1@sc.sumitomo-chem.co.jp ©...

Evaluation of the Strain Bacillus amyloliquefaciens YP6 in Phoxim Degradation via Transcriptomic Data and Product Analysis

“…Various oxidative activities (aldehyde dehydrogenase, a number of monooxygenases, and NADPH-cytochrome P450 reductase) were also found to be significantly upregulated. They were reported to act on the desulfurization of the P=S group [36,37,38]. Notably, NADPH-cytochrome P450 reductase is a subunit of cytochrome P450 monooxygenase [39], an enzyme which is considered as one of most versatile biocatalysts [40], with confirmed O-dealkylation catalytic activity [41,42], indicating that it is an important gene in the degradation of phoxim by participating in the process of desulfurization and/or O-dealkylation.…”

Theoretical and organic chemical approaches to environmental behavior and metabolism of pesticides

“…Since the oxidative desulfuration of the thiophosphoryl OP pesticide to form oxon is known to be catalyzed by P450, we conducted our model reactions using three iron porphyrins and H 2 O 2 to measure the oxidative dissipation rates (k) of four OPs, as listed in Table 3. 56) By assuming the same electrostatic interaction of the tested OPs with each OPCR from their structural similarities, the MO interaction between them was conveniently utilized to evaluate the oxidation. We estimated the E dπ-pπ values of OPCRs via regression analysis of the k values using the equation described in footnote e) of Table 3.…”

Iron-Porphyrin catalyzed oxidation of permethrin and fenvalerate

“…3) Among these methods, chemical oxidation by peroxide in the presence of a synthetic iron-porphyrin as a catalyst has been demonstrated to be an effective tool to obtain oxidative degradates for carbamate insecticide, 4) organophosphorus pesticides, 5) insect growth regulator 6) and triazine herbicide. 7) This reaction corresponds to the shunt pathway in CYP450 catalysis to produce the reactive intermediate, oxoiron (IV) porphyrin cation radical, (d) in Fig.…”