Toxicity group 15 compounds

Advantages of the Stille reaction include neutral conditions under which the reaction takes place, often with full retention of stereochemistry, and compatibility with nearly all functional groups thus eliminating additional steps required for protection and deprotection. Conversely, a highly undesirable drawback is the use of toxic tin compounds and the ensuing difficult removal of these from the reaction mixture. 

Line stmctures of four toxic organophosphoms compounds. Each has a modified phosphate group with atoms of other elements replacing one or more O atoms. 

The disposal and destruction of chlorinated compounds is a subject of great importance. In fact, in 1993, some environmental groups had proposed the need for a chlorine-free economy. The cost of complete elimination of chlorinated compounds is quite staggering with the latest estimate as high as 160 billion/year.46 The most common method to destroy chlorocarbons is by high-temperature thermal oxidation (incineration).47 The toxic chlorinated compounds seem to be completely destroyed at high temperatures however, there is concern about the formation of toxic by-products such as dioxins and furans.48... 

In Chapter rv we have described toxic fluorine1 compounds containing the >POF grouping. Such compounds possessed quick knock-out action, and many of them were powerful myotics. Compounds of the fluoroacetate series are characterized by the CH2F- group. Many of them are highly toxic with delayed action, but are completely devoid of myotic activity. The action is, broadly speaking, that of a convulsant poison (but see p. 136). 

From a study of the fluoroacetates so far mentioned, it appears that any compound which can give rise to fluoroacetic acid (or the fluoroacetate ion), either by hydrolysis or by oxidation (or both), is toxic. The toxic grouping is thus F-CH2-CO, and any substitution in this radical destroys the toxicity as far as relatively simple compounds are concerned. We had reached this conclusion by May 1943.1 We subsequently showed that esters of / -fluoropropionic acid were non-toxic, whereas esters of y-fluorobutyric acid were shown by American workers to be toxic. In 19442 we reported the synthesis of ethyl 5-fluoro-pentanecarboxylate, F,[CH2]g C02Et (I). This is a stable, colourless liquid and we showed that it possessed very potent toxic properties of the fluoroacetate type. By subcutaneous injection of the propylene glycol solution into mice the l.d. 50 was 4 mg./kg. Methyl fluoroacetate (II) may be taken as a convenient standard (p. 115) and has a l.d. 50 of about 6 mg./kg. for saline solutions, and 15 mg./kg. for propylene glycol solution.3 Therefore ethyl 5-fluoropentanecarboxylate was about 7 times as toxic as methyl fluoroacetate (molecule for molecule).4... 

A number of 5-nitro-2-furaldehyde derivatives, called nitrofurans, are used in the treatment and/or prophylaxis of microbial infections, primarily in the urinary tract. Recent evidence suggests that the reduction of the 5-nitro group to the nitro anion results in bacterial toxicity. Intermediate metabolites modify various bacterial macromolecules that affect a variety of biochemical processes (e.g., DNA and RNA synthesis, protein synthesis) this observation may explain the lack of resistance development to these drugs. Evidence also indicates that the nitro anion undergoes recycling with the production of superoxide and other toxic oxygen compounds. It is presumed that the nitrofurans are selectively toxic to microbial cells because in humans, the slower reduction by mammalian cells prevents high serum concentrations. 

In addition to physical properties, substructure-based filters can be applied to reduce further the number of molecules, for instance molecules with undesirable functionality for example, reactive or toxic groups can be removed and molecules with particular features (or atoms) can be actively selected. There may be particular functionality that it is desirable to avoid due to assay format, such as fluorophores in fluorescence-based approaches. Structural features for these inclusion and exclusion criteria can be readily formulated using SMILES-based procedures and this type of substructure-based compound selection technique can also be employed in the generation of focused sets of fragment molecules. 

The first two examples in Figure 1.20 illustrate that the structural formulas of alkyl and aromatic phosphine compounds may be derived by substituting organic groups for the H atoms in phosphine (PH3), the hydride of phosphorus, discussed as a toxic inorganic compound in Section 12.10. Methylphosphine is a colorless, reactive gas. Crystalline, solid triphenylphosphine has a low reactivity and moderate toxicity when inhaled or ingested. 

Diallylphosphonate, shown in Figure 18.3, has two alkenyl substituent groups. Information is lacking on its toxicity, although compounds with allyl groups tend to be relatively toxic. Incidents have been reported in which this compound has exploded during distillation. 

In addition to property-related filter functions, structure-based filters play a major role in VS. Reactive or toxic group filters are based on dictionaries of undesired chemical moieties and are used to remove compounds from databases that are not... 

The absence of the furano group (compounds 6 and 7) reduces the activity of the chemicals considerably. Also, oxidation of the heterocyclic ring to y-lactone decreases the toxicity, as is evident from the comparison of compounds 11, 16, 17 and 18 with the analogues 15, 1, 2 and 8. Furthermore, a statistical analysis performed using Student s t test (comparison between averages) shows that the furano compounds are significantly more toxic than lactones (P< 0.01). 

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