Substituent effects on the pre-steady-state kinetics of oxidation of benzyl alcohols by liver alcohol dehydrogenase.

1 The oxidation of benzyl alcohols by liver alcohol dehydrogenase under conditions [S]0≫ [E]0 is a biphasic process with exponential rise to a steady state. The rate constants for the transient phase were determined by a curve-fitting procedure. 2 A large isotope effect was obtained for p-methoxybenzyl alcohol, indicating that hydrogen transfer is rate-determining for the transient phase. Rate constants for the hydrogen transfer step, k3, were obtained for the various alcohols and correlated with the Hammett σ constant by plotting log k3 against σ. The slope of this line (ϱ=–0.76) is consistent with rate-limiting hydride transfer; a mechanism is proposed to account for the low magnitude of ϱ. 3 The pre-steady-state rate constants, kb, for all benzyl alcohols (< 20 s−1) are lower than that for ethanol. 2-Methylpropan-1-ol and cyclohexylmethanol have pre-steady-state rate constants of about 150 s−1, indicating that the lower kb values for benzyl alcohols are due to the electron-withdrawing effect of the benzene ring, rather than to steric effects.

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