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There are two competing mechanisms for oxidative N-dealkylation: the single-electron transfer (SET) mechanism, championed by Guengerich and McDonald,53-59 and the hydrogen atom transfer (HAT) mechanism, advocated by Dinnocenzo and Jones,60-64 Both mechanisms postulate the intermediacy of a carbon-based radical, but differ in the mechanistic events leading to its formation (Figure 2). The HAT pathway postulates direct formation of the radical by transfer of a hydrogen atom from the a-carbon atom to heme FeO3 +, to form heme FeOH3 +. In contrast, the SET pathway requires two steps, initiated by single-electron transfer from the nitrogen lone pair to heme FeO3 +, to form heme FeO2 +, followed by transfer of H + from the a-carbon atom to heme FeO2 +, forming heme FeOH3 + and the a-carbon radical. Oxygen rebound by either mechanism then forms the carbinolamine. Carbinolamines are chemically unstable, and dissociate to generate the secondary amine and aldehydes as products, or eliminate water to generate the iminium ion. The iminium ion if formed can reversibly add water to reform the carbinolamine, or add a different nucleophile if present (Figure 2). If the nucleophile is within the same molecule and four or five atoms removed from the iminium carbon atom, cyclization can occur and form a stable five- or six-membered ring system. For

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