GENERAL ACID CATALYSIS OF THE REDUCTION OF P-BENZOQUINONE BY AN NADH ANALOG - EVIDENCE FOR CONCERTED HYDRIDE AND HYDRON TRANSFER

Rate constants for general acid catalysis of the reduction of p-benzoquinone by an NADH analog, [9-H-1(2)]- and [9-H-2(2)]-10-methylacridan, were determined in water and deuterium oxide at 25-degrees-C. Catalysis by substituted acetic acids follows a Bronsted correlation with slope alpha = 0.85. There is a 60-fold negative deviation for hydronium ion catalysis and a 6-fold positive deviation for catalysis by cacodylic acid. For RCOOH catalysts, solvent isotope effects k(AH)L/k(AD)L range from 1.2 to 3.0 for [9-L2]-10-methylacridans (L = H-1, H-2). Substrate deuterium isotope effects k(AL)H/K(AL)D = 1.5 +/- 0.1 in water or deuterium oxide are small and essentially independent of the catalyst pK(a). Several reaction mechanisms are discussed, including reactions involving the semiquinone radical and radical anion generated by one-electron transfers. It is concluded that these results are most consistent with a concerted one-step hydride transfer assisted by proton transfer from the catalyst to form 4-hydroxycyclohexa-2,5-dienone that enolizes rapidly to hydroquinone.