1. N-Methyl-N-alkyl-p-chlorobenzamides (alkyl = Me, Et, nPr, nBu, PhCH2, isoPr and cylcoPr) underwent mono-N-dealkylation exclusively with phenobarbital-induced rat liver microsomes; with each compound both demethylation and dealkylation occurred. 2. The time-courses showed bilinear kinetics, but there was no evidence for general suicide-substrate activity with the cyclopropyl amide, and product ratios did not vary with time. 3. The demethylation/dealkylation ratio varied from 0.3 to 2.0 among the primary alkyl groups but was ca. 40 when the alkyl group was isoPr or cylcoPr. Dealkylation of the benzyl substituent was 2-3 times more favourable than for any other primary alkyl group. Despite wide variations in the demethylation/dealkylation ratios, at near-saturating concentrations of substrates the rates of total oxidation (demethylation plus dealkylation) varied little across the entire series. 4. The results of this study are consistent with a kinetic mechanism involving significant commitment to catalysis, substituent-induced metabolic switching at the product-determining step, a non-catalytic step which is partly rate-limiting in turnover, and a chemical mechanism involving H-atom abstraction as opposed to electron abstraction.
Degradation of pyrithiobac sodium (PE350) was examined in a number of soils and sediments using (14)C-PE350. It degrades primarily via microbial degradation which leads to the separation of the two rings of the molecule. Identification of several metabolites, many of which were minor products, helped to understand the formation of nonextractable residues (NER) and (14)CO2. In all studies, unextractable residues accounted for a large portion (20-60%) of the residues. Traditional kinetics modeling treats NER and CO2 as a single compartment, stated as sink, and formation mechanism of such components individually is ignored. Since studies conducted with radiolabeled test substance provides an accurate measurement of NER and CO2, we have demonstrated that kinetics modeling with these compartments separately can be used to clarify degradation pathways, including the origin of NER and CO2. This work demonstrated that overall metabolism in soils and sediments proceeded via similar pathways, and kinetics modeling was useful in clarifying the degradation route and formation of NER in all studies.
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