Molinate sulfoxide

Molinate has a low toxicity to rats, oral LDso=720 mg/kg, and is rapidly metabolized by plants to CO2 (1) (5) and naturally occurring plant constituents (1). Molinate is also readily metabolized by soil microorganisms (6). After incubation of molinate with Bacillus sp. 24, Nocardia sp. 119, and Micrococcus sp. 22r which were isolated from Russian garden soils and rice field drains (7,8), it was found that molinate was completely degraded into various hydroxy and oxidized products in the medium. Molinate can be metabolized to its corresponding sulfoxide in the mouse in vivo and by the microsome-NADPH system of mouse liver (9, 10). Hubbell et al. (11) and DeBaun et al. (12) also found molinate sulfoxide along with other polar and nonpolar metabolites in rat urine. 

Baker Chemical Co. Molinate sulfoxide was prepared by reacting [ring- Cjmolinate with equimolar m-chloroperbenzoic acid in chloroform (10). The product was puriTied by preparative thin-layer chromatography (TLC) using acetone hexane (1 1) as the developing solvent. The final radiopurity was 98%,... 

The five major organosoluble metabolites in the water were molinate sulfoxide, 3- and 4-hydroxy molinate, 4-keto molinate, and keto hexamethyleneimine (keto HMI). The amount of each metabolite in tap water remained fairly constant (below 2%) throughout the 14 days. In water previously containing fish, molinate sulfoxide was 2.1% 4 days after treatment, while other metabolites remained below 2% for the first 7 days. By the 14th day, however, molinate sulfoxide totaled 12.8% and 4-hydroxy and 3-hydroxy molinate were 2.2 and 3.7%, respectively. 

In the presence of carp, molinate was rapidly transformed into more polar metabolites. Twenty-four hours after treatment, conversion of molinate to organosoluble metabolites was extensive (Table II). The proportion of molinate sulfoxide increased from 1.2% on day 1 to 10.2% by the 14th day. Molinate, hydroxylated at the 4 position, decreased from 10.8% to 4.6% in 14 days. However, 4-keto and 3-hydroxy molinate together gradually increased over the 14 days from 6.9% to 77.7%. Another metabolite, a keto HMI,... 

Molinate Metabolism in Carp Hepatic Mixed-function Oxidase System. Incubation of molinate with carp liver microsomes produced four major organosoluble metabolites (molinate sulfoxide, 3- and 4-hydroxy molinate, and keto HMI). Parameters affecting... 

Methyl vinyl ketone, see 2-Methyl-l, 3-butadiene Molinate sulfoxide, see Molinate Monobutyl phosphate, see Tributyl phosphate Monobutyl phthalate, see Benzyl butyl phthalate Mono-n-butyl phthalate, see Di-n-butyl phthalate Monobutyl phthalate, see Di-n-butyl phthalate Monochlorobenzidine, see 3,3 -Dichlorobenzidine Monochlorobiphenyl, see Chlorobenzene, PCB-1221, PCB-1254... 

Soil. Hydrolyzes in soil forming ethyl mercaptan, carbon dioxide, and dialkylamine (half-life approximately 2-5 wk) (Hartley and Kidd, 1987). At recommended rates of application, the half-life of molinate in moist loam soils at 21-27 °C was approximately 3 wk (Humburg et al., 1989). Rajagopal et al. (1984) reported that under flooded conditions, molinate was hydroxylated at the 3- and 4-position with subsequent oxidation forming many compounds including molinate sulfoxide, carboxymethyl molinate, hexahydroazepine-l-carbothioate, 4-hydroxymolinate, 4-hy-droxymolinate sulfoxide, hexahydroazepine, 5-methyl hexahydroazepine-l-carbothioate, 4-keto-molinate, 4-hydroxyhexahydroazepine, 4-hydroxy-Wacetyl-hexahydroazepine, carbon dioxide, and bound residues. 

ChemicaPPhysical. Metabolites identified in tap water were molinate sulfoxide, 3- and 4-hydroxymolinate, ketohexamethyleneimine, and 4-ketomolinate (Verschueren, 1983). In water, molinate reacted with OH radicals at a rate of 7.7 x lO /M-h at 25 °C (Armbrust, 2000). 

Products of Semiconductor-catalyzed Molinate emd Thiobencarb Oxidation. Examination of the photooxid tion products of molinate by GC-MS provided evidence of seven substemces sufficiently stable 2uid concentrated to be chromatographed and detected by mass spectrometry (molinate sulfoxide und sulfone decomposed). 

Comparison of spectra and retention times with those of euialytical standards and literature reports (15, 16) confirmed the presence of molinate (I), the oxidation products 4-hydroxymolinate (II) and 4-Retomolinatee (III) (the most stable Intermediate product), an additional Reto isomer, and a ring unsaturated isomer (IV) (Figure 1). Molinate sulfoxide (V) and sulfone (VI) were detected by HPLC. Ibe presence of hexamethyleneimine (VII) was verified by its a,a,a-trifluoro-3,5-dinitrotoluene derivative (17). 

Chemical/Physical. Metabolites identified in tap water were molinate sulfoxide, 3- and 4-hydroxymolinate, ketohexamethyleneimine and 4-ketomolinate (Verschueren, 1983). 

Figure 3. Effect of temperature on conversion of molinate to its sulfoxide by carp liver microsomal mfo (liver microsomal protein 6 mg/mL, pH 7.4, NADPH 3 mg incubated for 15 min)...

Molinate is well absorbed by the oral route. It is widely distributed with highest concentrations remaining in the circulation. There is no evidence for accumulation of molinate. It is nearly completely excreted within 48 h, primarily via the urine. The primary biotransformation pathway for molinate in rats is S-oxidation to sulfoxide, followed by hydrolysis (hexamethyleneimine) or conjugation (mercaptu-rate). In humans, ring hydroxylation is the primary route followed by glucuronidation. 

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