Intramolecular deuterium isotope effect hydroxylation

In a more recent study (105), the intramolecular deuterium isotope effect and the relative rates of benzylic hydroxylation for six para-substituted (OCH3, CH2D, H, Cl, Br,... 

TABLE 4.2 Intramolecular deuterium isotope effects for benzylic hydroxylation of substituted toluenes catalyzed by CYP1A2, CYP1B1, CYP2C9, CYP2E1, and CYP101... 

Fig. 18. The expected percentages of various labelled products of the dioldehydratase reaction using 25 as substrate. The calculation was based on the following facts and assumptions (1) The enzyme does not differentiate between the enantiotopic hydrogen positions (conclusion from experiments with species 17 and 18 shown in Fig. 14) (2) in the competition between vicinal hydrogen atoms there is an intramolecular kinetic deuterium isotope effect of 2.6 (Fig. 15) (3) this effect is 10 for geminal hydrogen atoms (4) the migrating hydroxyl group substitutes one of the hydrogen atoms in the vicinal position stereospecifi-cally (i.e., with inversion).

Differences in the deuterium isotope effects for the oxidation of carbons adjacent to nitrogen vs oxygen suggest that the two reactions are mediated by different mechanisms. The intramolecular isotope effect for O-deethylation of deuterium substituted 7-ethoxycoumarin is 13 and for O-demethylation of 4-nitroanisole with a trideuterio methyl group is lO - In contrast, an isotope effect of 2-3 is obtained for the N-dealkylation of N-methyl-N-trideuteriomethylaniline The intrinsic isotope effects for O-dealkylation thus approach those for normal carbon hydroxylation reactions, but the isotope effects for N-dealkyla-tion are much lower. 

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