R

Figure 3 Mechanism for the O-dealkylation of ethers.

susceptible to oxidation than is the adjacent a-C-H bond. Nevertheless, S-dealkylation does occur, but whether it is driven by cytochrome P450 or some other enzyme system is not clear.

Halogen dealkylation mirrors O-dealkylation both in terms of mechanism and the commonality of the process, that is, while an aliphatic halogen substituent is not a common structural component, virtually any drug that contains a C-H bond adjacent to a halogen atom will be subject to cytochrome P450-catalyzed oxidative dehalogenation. Halogen atoms can also be removed either reductively, as will be discussed later, or by glutathione displacement, and as such represent a chemical group that is fairly labile in a biological environment.

Aliphatic halogen atoms are present in a number of common solvents and industrial chemicals to which people are exposed. For example, the fuel additive and suspected human carcinogen 1,2-dibromoethane (56) is oxidatively transformed to bromoacetaldehyde (57) by CYP2E (eqn [19]).84 Aliphatic halogen atoms are also a major structural component of most inhalation anesthetics.

BrCH2CH2Br

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