Fluoride reactivation method

Recently, Noort et al developed a procedure that is based on straightforward isolation of adducted BuChE from plasma by means of affinity chromatography with a procainamide column, followed by pepsin digestion and LC/electrospray tandem MS analysis of a specific nonapeptide containing the phosphonylated active site serine-198 residue (5). This method surpasses the limitations of the fluoride-reactivation method, since it can also deal with dealkylated ( aged ) phosphonylated BuChE. The method allowed the positive analysis of several serum samples of Japanese victims of the terrorist attack in the Tokyo subway in 1995. Furthermore, the method could be applied for detection of ChE modifications induced by, e.g., diethyl paraoxon and pyridostigmine bromide, illustrating the broad scope of this approach. This new approach... 

Blood Fluoride reactivation method Phospho-rylated BuChE (+ other proteins) GC-MS GC-HR-MS With large volume injection Phosphonofluo- ridates i.s. deuterated OP or plasma exposed to deuterated OP Easily accessible internal standards and reference compounds LOD 10 pg/ml (0.05-0.1% BuChE inhibition) Not applicable to all OP s... 

Application of the fluoride-reactivation method to serum samples of victims from the Tokyo subway attack, and of the Matsumoto incident, yielded, sarin concentrations in the range of 0.2-4.1ng/ml serum (44). Evidently, these casualties had been exposed to an organophosphate with the formula i-PrO(CH3)P(0)X, presumably with X = F (sarin). 

A major drawback of the fluoride reactivation method is that not all nerve agent adducts are amenable to fluoride reactivation, with the aged adduct of soman the best known example. This problem can be solved by looking at the BuChE enzyme itself Fidder et al (2002) published a method based on the LC-MS analysis of a nerve agent phosphylated nonapeptide derived after pepsin digestion of inhibited butyrylcholinesterase. The authors presented a procedure to extract BuChE from plasma using... 

Barr, J.R. (2004). Improvements of the fluoride reactivation method for the verification of nerve agent exposure. J. Anal. Toxicol. 28(5) 364-71. 

The fluoride reactivation method has been applied to a human case of self-poisoning by chlorpyrifos (van der Schans et al., 2013). Blood drawn from the patient 49 days after she ingested chlorpyrifos yielded two products, both released from albiunin with potas-siiun fluoride. The released products were identified by LC-MS using multiple reaction monitoring (MRM). The products were diethoxyfluorophosphafe (representing an albumin adduct with chlorpyrifos oxon) and... 

Additional acylation studies were also reported (24), (26). In the first case it is claimed that acylation of thiophene is achieved by means of HC104 and acetic anhydride affording a 65 % yield of 2-acetylthiophene. In the second paper Levine and coworkers reported that while 2,5-dimethylthiophene could be readily acetylated, 2,5-dichlorothiophene acetylated sluggishly. This is, however, readily explained, since the presence of chlorine atoms on the thiophene ring decreased its reactivity in electrophilic substitution reactions. In the case of methyl substitution, however, the 3 and 4 positions of the ring are activated toward electrophilic substitution by the inductive and hyperconjugative effects. Thus 2,5-dimethylthiophene was successfully acylated by the boron fluoride etherate method in high yield with three aliphatic anhydrides. 

The new rert-alkylation method was highlighted by the selective functionalization of difluoroalkane with different reactivity profile including tert-alkyl/pnm-alkyl and tert-alkyl/ ec-alkyl fluorides. This method provides a facile route to new types of orga-nofluorine compounds which are increasingly important in biochemical/biological, pharmacological, and material science [98]. For instance, reaction of difluoroalkane 102 with ketene silyl acetal 99 (R = H, = Me) was catalyzed by 10 mol%... 

The order of reactivity of the hydrogen halides parallels their acidity HI > HBr > HCl >> HF Hydrogen iodide is used infrequently however and the reaction of alco hols with hydrogen fluoride is not a useful method for the preparation of alkyl fluorides Among the various classes of alcohols tertiary alcohols are observed to be the most reactive and primary alcohols the least reactive... 

In media such as water and alcohols fluoride ion is strongly solvated by hydro gen bonding and is neither very basic nor very nucleophilic On the other hand the poorly solvated or naked fluoride 10ns that are present when potassium fluoride dis solves m benzene m the presence of a crown ether are better able to express their anionic reactivity Thus alkyl halides react with potassium fluoride m benzene containing 18 crown 6 thereby providing a method for the preparation of otherwise difficultly acces sible alkyl fluorides... 

Niobic Acid. Niobic acid, Nb20 XH2O, includes all hydrated forms of niobium pentoxide, where the degree of hydration depends on the method of preparation, age, etc. It is a white insoluble precipitate formed by acid hydrolysis of niobates that are prepared by alkaH pyrosulfate, carbonate, or hydroxide fusion base hydrolysis of niobium fluoride solutions or aqueous hydrolysis of chlorides or bromides. When it is formed in the presence of tannin, a volurninous red complex forms. Freshly precipitated niobic acid usually is coUoidal and is peptized by water washing, thus it is difficult to free from traces of electrolyte. Its properties vary with age and reactivity is noticeably diminished on standing for even a few days. It is soluble in concentrated hydrochloric and sulfuric acids but is reprecipitated on dilution and boiling and can be complexed when it is freshly made with oxaHc or tartaric acid. It is soluble in hydrofluoric acid of any concentration. 

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