Abstracts
Perfluidone
CAS No. 37924-13-3
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ACTIVITY: Herbicide (anilide)

Note: WHO: believed obsolete or discontinued

CAS Name: 1,1,1-trifluoro-N-[2-methyl-4-(phenylsulfonyl)phenyl]methanesulfonamide

Structure:


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Biochem Pharmacol 1985 Aug 15;34(16):2945-52

Protonophoric properties of fluorinated arylalkylsulfonamides. Observations with perfluidone.

Olorunsogo OO, Malomo SO, Bababunmi EA.

The acidity and lipophilicity of the fluorinated arylalkylsulphonamides are determined by the nature of the substituents on their aromatic rings. Herbicidal and anti-inflammatory effects of these compounds appear to increase with their lipophilicity. According to Mitchell's chemiosmotic theory, lipophilic weak-acid uncoupling agents act by transporting protons across the inner mitochondrial membrane and thus destroying the proton-electrochemical potential gradient required for ATP synthesis and ion transport. 1:1:1-Trifluoro-N-[2-methyl-4-(phenylsulphonyl) phenyl]methanesulphonamide (Perfluidone), a pre- and post-emergence herbicide (at 20 microM concentration), in isolated rat-liver mitochondria caused
(1) a 2-fold stimulation of metabolic state-4 respiration,
(2) a reduction of respiratory control ratio (RCR) by at least 50%,
(3) an enhancement of latent ATPase activity by 40%,
(4) a significant passive swelling of mitochondria in 0.15 N NH4Cl(delta A520 = -0.46 +/- 0.003),
(5) proton intrusion during state-4 respiration (356 ng H+/min/mg protein; ng H+/min/mg protein with 5 microM perfluidone), and (6) at least 100% stimulation of oligomycin-inhibited respiration.
These profiles are qualitatively comparable with those of the classical lipophilic weak-acid uncoupler, carbonylcyanide-trifluoro-methoxyphenylene hydrazone (FCCP), which acts by promoting the electrogenic transport of H+ ions across mitochondrial membrane.

PMID: 2992524 [PubMed - indexed for MEDLINE]



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Toxicology 1985 Jun 14;35(3):231-40

Sensitivity of oligomycin-inhibited respiration of isolated rat liver mitochondria to perfluidone, a fluorinated arylalkylsulfonamide.


Olorunsogo OO, Malomo SO.

Oxygen electrode polarographic measurements of the rate of oxygen consumption by isolated rat liver mitochondria revealed that oligomycin inhibition of respiration was offset to different degrees by varying concentrations of perfluidone (1,1,1-trifluoro-N-(2 methyl-4-(phenylsulfonyl) methanesulfonamide). Using any of pyruvate-malate, succinate or ascorbate-TMPD (N,N,N',N'-tetramethyl-p-phenylenediamine) as substrate, this herbicidal and anti-inflammatory agent at 100 microM concentration caused a 5-fold stimulation of oligomycin-inhibited respiration. Higher concentrations of the herbicide (greater than or equal to 120 microM) gave lower stimulatory effects. Similar stimulatory effects were obtained with 1 microM FCCP (carbonylcyanide p-trifluoromethyoxyphenyl-hydrazone), a classical protonophore. Our results also show an enhanced oligomycin-sensitive ATPase action in intact mitochondria incubated with ATP and varying concentrations of perfluidone. Maximum enhancement effect (111.3%) was obtained at 120 microM perfluidone. FCCP (1 microM) stimulated this ATPase action by 130%. An initial inhibition of respiration by oligomycin is due to an interaction with the proton well of FOF1-ATP synthetase (Lardy, H.A. et al., Arch. Biochem. Biophys., 78 (1953) 587). Perfluidone probably increases the proton conductance of mitochondrial inner membrane in the same manner as FCCP and thus causes an increase in mitochondrial respiratory rate. As protons move into the matrix, delta mu H+, the proton electrochemical potential gradient becomes very small and the F0F1-ATP synthetase functions in the direction of hydrolysis of ATP rather than its shnthesis (Mitchell, P., Eur. J. Biochem., 95 (1979) 1). These findings therefore indicate that perfluidone acts in a way similar to FCCP, a classical uncoupler and protonophore.

PMID: 3160138 [PubMed - indexed for MEDLINE]


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Chem Biol Interact 1984 Nov;52(1):67-78

Mitochondrial bioenergetics during exposure of rats to perfluidone, a fluorinated arylalkylsulphonamide.

Olorunsogo OO, Malomo SO.

Apart from the symptoms of poisoning which the fluorinated arylalkylsulphonamides share with the classical protonphore and uncoupler of oxidative phosphorylation, carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP), the direct correlation between the lipophilic weak acid properties of these chemicals and their biological activity suggests that permeation of the inner mitochondrial membrane could be the initial step in the molecular mechanism of their biological activity. Mitochondria isolated from the livers of rats intraperitoneally exposed to varying doses (0-80 mg/kg body wt.) of perfluidone (1,1,1-trifluoro-N-(2 methyl-4-(phenylsulphonyl)phenyl methanesulphonamide), a fluorinated arylalkylsulphonamide pesticide, exhibit the following dose-dependent features:
(i) increased state-4 respiration: stimulation being maximal (greater than or equal to 400%) at 80 mg perfluidone per kg body wt.),
(ii) release of respiratory control by ADP: least respiratory control ratios (RCRs) (less than or equal to 1.2) were obtained at 80 mg perfluidone per kg body wt.,
(iii) reduced ADP/O ratios,
(iv) increased mitochondrial passive swelling,
(vi) reduced rates of mitochondrial proton ejection during succinate oxidation,
(vi) reduced rates of respiration-dependent Ca2+ accumulation and
(vii) an enhanced oligomycin-sensitive ATPase action.
These features which are qualitatively identical to those of the classical protonophore FCCP, suggest that permeation of the inner mitochondrial membrane by perfluidone is accompanied by a movement of protons into the matrix such that the proton motive force required for ATP synthesis and ion transport becomes small or not formed at all.

PMID: 6238687 [PubMed - indexed for MEDLINE]


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Eur J Drug Metab Pharmacokinet 1983 Oct-Dec;8(4):321-7

Effect of 1.1.1 trifluoro-N-(2-methyl-4-phenyl sulfonyl) methane sulfonamide (Destun 50WP) on rat hepatic microsomal enzymes, aniline hydroxylase and amino-pyrine N-demethylase.

Thabrew MI, Emerole GO.

Investigations have been carried out to determine the effects of the herbicide 1.1.1 trifluoro-N-(2-methyl-4-phenyl sulfonyl) methane sulfonamide (Destun) on some hepatic microsomal drug metabolizing enzymes in rat. Administration of 100 mg herbicide/kg rat (i.p. or oral) resulted in a stimulation of aniline hydroxylase and p-aminopyrene N-demethylase activities by 1.3 fold and 1.6 fold respectively. A dose-related increase in enzyme activities was observed with a maximum effect at about 100 mg Destun/kg rat. The increased microsomal protein content, liver weight: body weight ratio and decreased sleeping time in the herbicide-treated animals indicated the possibility of Destun being an "inducer". Results of investigations on the kinetic properties of aniline hydroxylase and p-aminopyrene-N-demethylase on administration of Destun suggests that in addition to its inducer effect, the herbicide could stimulate the enzyme activities by decreasing the affinity of these enzymes for their respective substrates.

PMID: 6673969 [PubMed - indexed for MEDLINE]


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Dev Toxicol Environ Sci 1983;11:345-8
 
Perfluidone, a fluorinated arylalkylsulphonamide carries protons across mitochondrial coupling membrane.

Olorunsogo OO, Malomo SO, Bababunmi EA.

PMID: 6677469 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6133695&dopt=Abstract
 
Comp Biochem Physiol C 1983;74(2):473-6
 
Species variations in the sensitivity of the endoplasmic reticulum to the herbicide 1.1.1. trifluoro-N-(2-methyl-4-phenyl sulfonyl phenyl) methane sulfonamide.

Thabrew MI, Emerole GO.

1. The effects of the herbicide 1.1.1. trifluoro-N-(2-methyl-4-phenyl sulfonyl phenyl) methane sulfonamide on the drug metabolising enzyme activities in livers of rat, mouse and guinea pig have been compared.
2. In all three animal models, the herbicide increased the activities of both aniline hydroxylase and p-aminopyrine demethylase. The greatest inductive effect was seen in the rat, while the least effect was evident in the guinea pig.
3. In mouse and guinea pig, 1.1.1. trifluoro-N-(2-methyl-4-phenyl sulfonyl phenyl) methane sulfonamide had no effect on the soluble or microsomal epoxide hydratases or the glutathione S-transferases. In the rat, however, the herbicide significantly decreased the microsomal epoxide hydratase activity, as well as the soluble and microsomal glutathione S-transferase activities.
4. These results are discussed in relation to factors responsible for species differences in the response to foreign compounds.

PMID: 6133695 [PubMed - indexed for MEDLINE]

From Toxline at Toxnet
Pestic. Biochem. Physiol. 7(1): 62-72; 1977.(7 references)
 
Herbicide perfluidone (1,1,1-trifluoro-N- (2-methyl-4- (phenylsulfonyl)phenyl) methanesulfonamide): its metabolism in rats and chickens.

Paulson GD, Jacobsen AM, Zaylskie RG

PESTAB. Rats and chickens were each given a single oral dose (10 or 100 mg/kg body wt) of 1,1,1-trifluoro-N- (2-methyl-4- (phenylsulfonyl)phenyl- 14C(UO)methanesulfonamide ((14C)perfluidone). Depending on the size of the dose, from 8.4 to 36.2% of the [14C) was eliminated in the urine and from 36.4 to 85.4% was eliminated in the feces within 48 hr after dosing. Less than 1% of the (14C) given to laying hens at (14C)perfluidone was present in the eggs produced during the first 96 hr after dosing. The percentage of the administered (14C) that remained in these animals (body with G.I. tract and contents removed) varied from 0.34 (96 hr after dosing) to 1.68% (48 hr after dosing). 14C-labeled compounds in the urine and feces from the rats and chickens were purified by solvent extraction, column chromatography, and gas-liquid chromatography, and then identified by infrared and mass spectrometry. The parent compound was the major 14C-labeled component in the urine and feces of both animals. 1,1,1-Trifluoro-N- (2-methyl-4- (3-hydroxyphenylsulfonyl) phenyl) methanesulfonamide was present in the feces of both animals. The proposed structures of other metabolites were 1,1,1-trifluoro-N- hydroxy-N- (2-methyl-4- (phenylsulfonyl) phenyl) methanesulfonamide (rat urine) and 1,1,1-trifluoro-N- (2methyl-4- ((methylsulfonyl)-phenylsulfonyl) phenyl methanesulfonamide (chicken urine).

 

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=853723&dopt=Abstract
 
J Sci Food Agric 1977 Feb;28(2):180-4
 
Stimulation of the activity of the IAA-oxidising enzyme system in Lens culinaris roots by dalapon and perfluidone.

Tafuri F, Businelli M, Scarponi L, Marucchini C.

PMID: 853723 [PubMed - indexed for MEDLINE]

From Toxline at Toxnet

J Agric Food Chem 1975 Sep-Oct;23(5):869-72

Metabolic fate of perfluidone herbicide in a lactating cow.

Ivie GW.

PESTAB. Perfluidone (1,1,1-trifluoro-N- (2-methyl-4- (phenylsulfonyl) phenyl-14C) methanesulfonamide) was administered at 5 mg/kg as a single oral dose to a lactating cow. Radiocarbon was rapidly and essentially quantitatively excreted during a 7-day post-treatment period. About 80% of the administered dose appeared in urine, about 20% was recovered in feces, and only 0.1% of the dose was secreted into the milk. Unmetabolized perfluidone accounted for 90-95% of the total radiocarbon present in the urine and milk, and the remaining radioactivity was mainly in the form of two metabolites hydroxylated at the 3 or 4 positions of the phenylsulfonyl ring. These products were excreted almost totally in nonconjugated form. The major urinary metabolite and the only milk metabolite was 4-hydroxyperfluidone, whereas perfluidone and its 3-OH and 4-OH derivatives occurred in approximately equal amounts in feces. (Author abstract reprinted by permission of the American Chemical Society)
From Toxline at Toxnet
 
Weed Sci. 23(5): 344-348; 1975.(16 references)
 
Persistence and movement of perfluidone in soil.

Ketchersid ML, Merkle MG

PESTAB. Perfluidone (1,1,1-trifluoro- N-)2-methyl-4- (phenylsulfonyl) phenyl(-methanesulfonamide) was chemically stable for 2 to 3 weeks on the surface of three Texas soils either air dry or at field capacity and at temperatures of 22 and 46DEG C. Perfluidone was susceptible to photodecomposition when applied to
glass petri dishes and exposed to ultraviolet irradiation. Perfluidone was readily leached through neutral or slightly alkaline soils, with a tendency toward greater downward movement in soils having low clay and organic matter content. However, leaching was less in an acid loamy sand than in either neutral loamy sand or clay soils. (Author abstract by permission)

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