Fluoro citrate

Although our results support the / -oxidation theory, one point must not be overlooked, namely, that fluoroacetic acid is not the actual toxic agent and has to be converted into fluoro-citrate before exerting its activity (see p. 142). It should also be noted that American workers1 showed that both methyl y-fluorobutyrate and methyl -fluorocrotonate,... 

The toxicity of the acaricide 2-fluoro-A-methyl-A-(naphth-l-yl)acet-amide (MNFA) (4.152) to mammals is related to its hydrolysis. In this case, however, toxicity was mainly due to the acid formed. Indeed, the 2-fluoro-acetic acid (4.153) liberated by hydrolysis was further metabolized to fluoro-citrate, which inhibits the tricarboxylic acid cycle [101]. 

We may add that, although the enzymically prepared fluoro-citrate is a competitive inhibitor of a very highly purified aconitase, synthetic fluorocitrate (see below) behaves differently for example, it is more toxic to soluble aconitase. There is no very satisfactory explanation of this difference, although stereochemical differences have been suggested. 

Fanshier et al. (1964) have shown that the aconitase-inhibitory effect of synthetic monofluorocitrate is due to one isomer, synthesized enzymatically from fluoroacetyl coenzyme A and oxaloacetate. They separated diastereoisomers of synthetic mono-fluorocitric acid, compared the chemical and enzyme-inhibitory properties of these with enzymatically formed isomers, and found that the DL-erythro form of fluoro-citrate is the diastereoisomer which inhibits aconitase action. Infrared spectroscopy helped to characterize the DL-erythro and DL-threo isomers. 

Chenoweth believes that an explanation of the above results may lie in the reactions occurring before the entrance of fatty acid metabolites into the citric acid cycle. Activated acetate, i.e. acetyl coenzyme A (AcCoA) is the end-product of fatty acid metabolism prior to its condensation with oxalacetate to form citrate. Possibly fluoro-fatty acids behave like non-fluorinated fatty acids. The end-product before the oxalacetate condensation could be the same for all three fluorinated inhibitors, viz. fluoroacetyl coenzyme A (FAcCoA). Fluorocitrate could then be formed by the condensation of oxalacetate with FAcCoA, thereby blocking the citric acid cycle. The specificity of antagonisms must therefore occur before entrance of the metabolites into the citric acid cycle. 

The catalytic efficiency of this enzyme to hydrolyze 5-fluoro-5,6-dihydro-uracil was found to be approximately twice that toward 5,6-dihydrouracil [152], 2-Fluoro-/3-alanine can either be eliminated via the bile after conjugation with bile acids, or be converted to fluoroacetate (4.238) [153], The latter metabolite is transformed to fluorocitrate, a potent inhibitor of the aconi-tase-catalyzed conversion of citrate to isocitrate. This inhibition probably explains the clinical neurotoxicity of 5-fluorouracil [154] [155],... 

Fluoroacetate undergoes a "lethal synthesis"(18) to 2-fluorocitrate which may reversibly inhibit aconitase and which irreversibly binds to a membrane-associated citrate transport protein(19,20). Insecticidal and other biocidal uses of fluoroacetate (or its metabolic precursors) received considerable attention twenty-five years ago( ) but most uses have been abandoned due to high nonspecific vertebrate toxicity of these compounds. Vfe have reported the use of o)-fluoro fatty acids and their derivatives as delayed-action toxicants for targeted... 

The9-amino-8-fluoro-2,4-methano-l,2,3,4-tetrahydro[9-14C]acridine citrate, SM-10888, 283, has been synthesized295 in five steps (equation 155) for cholinergic treatment in Alzheimer disease296-300. 

There are two Krebs cycle inhibitors that are worth mentioning. Malonate inhibits succinate dehydrogenase because of its very similar structure. Fluoro-acetate inhibits cis-aconitase, which is an Fe-S enzyme. The fluoroacetate replaces acetate as a substrate in the citrate synthase reaction when this combines with cis-aconitase, however, no further reaction becomes possible. 

When immobilized in a polymer-plasticizer matrix, (dppe)Pt S2C2(2-py) (CH2CH2OH), can be used for the rapid selective detection of volatile fluoro-, chloro-, and cyanophosphates (Table III, Fig. 10). As with many film immobilized lumiphores, the reactivity is controlled by the immobilizing matrix (39-44, 46, 50-52, 57, 58, 63, 75-77) Such an effect is seen as the sensitivity to phosphate esters increases as plasticizer (triethyl citrate, TEC) concentration increases in the cellulose acetate CA/TEC film (Table IV). 

The main oxidation state is V, but there is no Pa5+ aquo ion because of hydrolysis to species such as PaO(OH)2+ and PaO(OH)2+ or the formation of complexes with virtually all anions. The fluoro complexes, PaF6, PaF,-, and PaFjj are of greatest importance and many sohds containing them have been isolated. Other stable complexes are formed with QOj , SO2-, citrate, tartrate, /3-diketones, and so on. 

Schwartz B, Drueckhammer DG, Usher KC, Remington SJ. Alpha-fluoro acid and alpha-fluoro amide analogs of acetyl-CoA as inhibitors of citrate synthase-effect of pK(a) matching on binding-affinity and hydrogen-bond length. Biochemistry 1995 34 15459-15466. 

A novel study on the speciation of aluminum in solution has been reported by Bertsch et al. [35], Fluoro, oxalato, and citrate aluminum complexes were identified as distinct peaks together with free AI(IIl). Post-column reaction/UV detection was used. These studies were used in kinetic, ion-exchange, and toxicological investigations. 

Tetravalent vanadium forms a large number of complexes, all of which involve the vanadyl group, VO, and most of which are ato- complexes. The most common oxalato complex is H2(V0)2(C204)3, which can give a positive test for the presence of the oxalate ion in aqueous solutions. Aqueous solutions of the pure monovanadyl complex do not test for the presence of the oxalate ion. Complexes of sulfate and sulfite analogous to the oxalate complexes have been observed [4]. Ducret [5] suggested the existence of weak fluoro complexes at a pH of approximately 3. A tartrate and two citrate complexes can also be formed with the vanadyl ion. 

Fig. 319. Smooth endoplasmic reticulum induced by daily oral application of 60 mg 2-(5-cyano-N,3,4,-trimethyl-3-aza-pentane-amido)-5-chloro-2 -fluoro-benzophenone HCl per kg body weight in the liver (block 23362) of a male aog (No. 119). Fixed by immersion with 2.5% glutaraldehyde in 0.1 M sodium cacodylate buffer (pH 7.4). Postfixation with 1 % osmium tetroxide in sodium cacodylate buffer. Embedded in Epon 812 and sectioned at 50 nm. Lead citrate and uranyl acetate. Film 635-31...

According to the present concepts of j3-oxidation and the formation of acetyl CoA, fluoroacetyl CoA should be formed from w-fluoroacetates of an even number of carbons. It has been suggested that fluoro-acetate condenses with another compound, the condensation product being toxic. Since fluorocitrate accumulates in systems poisoned with fluoroacetate, it may be concluded that fluoroacetyl CoA is formed and that it then condenses with oxalacetate. The fact that citrate also accumulates " indicates that either fluoroacetate or fluorocitrate is inhibitory for some step subsequent to the formation of citrate. Cfs-aconitate oxidation is not inhibited therefore, the inhibition appears to be exerted upon the conversion of citrate to cis-aconitate by aconitase. Experimental evidence, as well as theoretical considerations, indicates that fluoroacetate also inhibits fatty acid oxidation by forming complexes with magnesium ions. The apparent association constants of Mg(FAc)+(C i) and Mg(FAc)2(C s) were determined by Gillette and Kalnitsky ... 

Biosil Basics Fluoro Guerbet 3.5% Butyl octyl benzoate DImethIcone copolyol beeswax DIoctyIdodecyl fluoroheptyl citrate Glyceryl triacetyl ricinoleate HallStar BST Hexyldecyl benzoate Jeeool CA-2 Jeecol CA-5 Jeecol CA-10 Jeeool CA-20 Jeecol CS-3 Jeecol CS-5 Jeeool CS-10 Jeecol CS-20 Jeecol CS-20-D Jeeool ICA Jeecol ISA Jeecol LA-3 Jeeool LA-4 Jeecol LA-7 Jeecol LA-10 Jeeool LA-12 Jeecol LA-23 Jeecol LA-30 Jeeool NIN Jeecol OA-2 Jeecol OA-4 ... 

Schercomid ODA dispersant, pigments gels Biosil Bask Fluoro Guerbet 3.5% Dio-ctyldodecyl fluoroheptyl citrate dispersant, pigments germicides PPG-40 diethylmonium chloiide Vari-quat CC-42... 

Biosil Basics Fluoro Guerbet 3.5% Dii-sostearyl adipate DIoctyIdodecyl fluo-roheptyl citrate Liquiwax DISA Liquiwax IPL... 

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