Elimination, radical substrate reactivity

When a 2 -Cl or -F analog of UDP was used in place of the substrate an irreversible side reaction occurred by which Cl or F, inorganic pyrophosphate, and uracil were released 349 When one of these enzyme-activated inhibitors containing 3H in the 3 position was tested, the tritium was shifted to the 2 position with loss of Cl and formation of a reactive 3 -carbonyl compound (Eq. 16-24) that can undergo P elimination at each end to give an unsaturated ketone which inactivates the enzyme. This suggested that the Fe-tyrosyl radical abstracts an electron (through a... 

The main feature of carbanions derived from nitriles lies in the dependence on the aromatic substrate involved thus, two different outcomes of the substitution reaction are possible formation of the substitution compound by ET to the substrate from the radical anion intermediate 7, formed by coupling of phenyl radicals and acetonitrile anion, or formation of products from elimination of the cyano group as is the case with phenyl halides [31,32] (Sch. 3). The same reactivity pattern is found with halothiophenes [33]. 

The radical cations initially formed during the direct oxidation of hydrocarbons [Eq. (1)] are highly reactive species, and their formation is usually followed by a fast reaction in solution. This involves typically a nucleophile (Nu or NuH) or a base (B), resulting in the formation of either an addition product, I, or an elimination product, II, as illustrated by Eqs. (2) and (3). Reaction (2) may be observed for almost any radical cation when a suitable nucleophile is present, whereas reaction (3) is typically observed for alkyl-substituted aromatic hydrocarbons having at least one hydrogen atom in an a position. Other common follow-up reactions are dimerization [Eq. (4)] and the coupling of a radical cation and a molecule of substrate [Eq. (5)]. The neutral molecule in Eq. (5) may also be a hydrocarbon different from R-H ... 

Fig. 4. Mechanism of lipid peroxidation and its inhibition by vitamin E. Lipid peroxidation is initiated by generating a relatively nnreactive carbon-centered radical upon hydrogen abstraction by a hydroxyl radical (1). The fast formation (2) of the more reactive peroxyl radicals (ROO) ensures rapid attack of any peroxidizable substrate either by abstraction of a hydrogen atom (3a) or addition to a double bond (3b). The propagation is teiminated by mutual elimination of peroxyl radicals (4) or by suppression of free-radical formation in the presence of a-tocopherol (a-TOH) (5a). The tocopheryl radical is believed to be neutralized by ascorbic acid (AscAH) (5b) and radical oxygen, and a-tocopherol then re-enters the inhibition cycle.

The chemical mechanism of flavin reduction in these enzymes has been debated for years. To date, there is no consensus however, most proposed mechanisms envision N5 as the reactive position of the flavin. The mechanisms that have been considered include a direct hydride transfer from the substrate a-carbon to the flavin and a family of mechanisms in which deprotonation of the a-carbon forms a carbanionic intermediate. Three mechanisms of reaction of the hypothetical carbanion have been proposed. It could reduce the flavin by direct single-electron transfers. Alternatively, it may form a covalent adduct, either after a single-electron transfer and radical coupling, or by direct nucleophilic attack. The adduct would then eliminate reduced flavin. 

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