Cyanide potency

As a class of compounds, the two main toxicity concerns for nitriles are acute lethality and osteolathyrsm. A comprehensive review of the toxicity of nitriles, including detailed discussion of biochemical mechanisms of toxicity and stmcture-activity relationships, is available (12). Nitriles vary broadly in their abiUty to cause acute lethaUty and subde differences in stmcture can greatly affect toxic potency. The biochemical basis of their acute toxicity is related to their metaboHsm in the body. Following exposure and absorption, nitriles are metabolized by cytochrome p450 enzymes in the Hver. The metaboHsm involves initial hydrogen abstraction resulting in the formation of a carbon radical, followed by hydroxylation of the carbon radical. MetaboHsm at the carbon atom adjacent (alpha) to the cyano group would yield a cyanohydrin metaboHte, which decomposes readily in the body to produce cyanide. Hydroxylation at other carbon positions in the nitrile does not result in cyanide release. 

Spectrophotometric deterrnination at 550 nm is relatively insensitive and is useful for the deterrnination of vitamin B 2 in high potency products such as premixes. Thin-layer chromatography and open-column chromatography have been appHed to both the direct assay of cobalamins and to the fractionation and removal of interfering substances from sample extracts prior to microbiological or radioassay. Atomic absorption spectrophotometry of cobalt has been proposed for the deterrnination of vitamin B 2 in dry feeds. Chemical methods based on the estimation of cyanide or the presence of 5,6-dimethylben2irnida2ole in the vitamin B 2 molecule have not been widely used. 

Some other types of treatment processes that can be employed in the hydrogen cyanide industry include ozonation, to oxidize the wastewater chlorine. Potency of sulfur oxide is also high in the oxidation process. 

The presence of a quaternary carbon atom at the 4 position of the piperidine in the form of a spiro substituent seems to enhance potency. The starting piperidin is the product from the formal additon of cyanide and aniline to the 4 position of A-benzyl-4-piperidone (see Chapter 7 [28-3] for preparation). Reaction of that with formamide serves to form the spiro-imidazoline ring (21-4). The benzyl protecting group is then removed by hydrogenolysis over palladium to give the secondary... 

In a human neuroblastoma cell line, Cova et al. (1992) found acrylonitrile to be highly toxic, showing an EC50 of 72.5 nM for cytotoxicity. The cytotoxic potency of potassium cyanide was 2.5 J,M, thus acrylonitrile toxicity in these cells cannot be attributed to its metabolism to cyanide. 

Variants of the ethyl ketone function of methadone, an aspect already broached with mention of dextromoramide, include ester, sulphone, and secondary alcohol functions in addition to (-amides. The ethyl ester analog 14a obtained by treating the acid chloride derived from methadone cyanide with ethanol is markedly inferior in potency to methadone, while the sulfone 14b (obtained by aminoalkylation of benzhydryl ethyl sulfone) is equipotent... 

At a temperature range of 427-548°C and a pressure range of 55-300 torr, MIC has been shown to decompose into HCN (Blake and Ijadi-Maghsoodi, 1982). However, the temperature inside the culprit MIC-containing tank was estimated to be only 250°C (Varadarajan et al, 1985) at which temperature MIC does not degrade into HCN. There is evidence that MIC can combine with HCN even at low temperatures (Slotta and Tschesche, 1927) however, this reaction can only reduce toxicities of both HCN and MIC and not make more lethal cyanogens as speculated by Sriramachari (2004) because the toxic potency of cyanides depends upon the dissociation of the -CN ion (Goldstein e/u/., 1968). 

Studies have concluded that the rate of abstraction of the hydrogen atom next to the cyano group will determine the potency of the nitrile (15). Armed with just this information, students can be asked to identify the structural features that influence the rate of hydrogen abstraction. The factors that influence the rate of cyanide release are the same as those familiar to organic chemistry students, namely electronic and steric effects. A compilation of these structural features can be assembled for other classes of molecules and be apllied by the students to other molecules. 

Hydrazones prepared by the reaction of aryldiazonium salts with malononitrile (trivially named carbonyl cyanide phenylhydrazones, or CCPs) have been known as uncouplers for many years [114]. Studies on the relationship between physicochemical properties and uncoupling potency have been reported [90, 91], and these show that this relationship is very similar to those for other classes of weakly acidic protonophoric uncouplers. Thus, two of the most potent uncouplers of... 

A radioisotope dilution assay and an assay based on animal growth are the most reliable methods for the determination of vitamin B12 activity. The tracer technique is highly specific for cyanocobalamin or analogs which are convertible to cyanocobalamin. The assay is specific for cyanocobalamin if cyanide treatment of the sample is avoided total cobalamins convertible to cyanocobalamin are determined if a given sample is first treated with cyanide. The method consists in the addition of a known amount of pure [ Co]-cyanocobalamin. A series of selective extractions and adsorptions to remove interfering substances is completed and the radioactivity and color of the purified sample are measured. From these data, it is possible to calculate the amount of cobalamin present in the original sample. The isotope dilution method is accurate and precise and can be used for both relatively pure samples and for crude extracts of low potency. 

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