Direct-dynamics approach to catalytic effects: The tautomerization of 3-hydroxyisoquinoline as a test case

The mechanism of tautomerization of 3-hydroxyisoquinoline (3HIQ) in its fir st excited singlet state is studied theoretically for the isolated molecule and the 1:1 complexes with water (3HIQ/H2O) and acetic acid (3HIQ/AA). It is found that the proton transfer is a tunneling process which is strongly mediated by the motion of the heavier atoms involved in the hydrogen bond b ridges. Therefore it is argued that quantitative assessment of the tremendo us catalytic effect of complexation observed experimentally is possible onl y through the evaluation of multidimensional tunneling rate constants. Thes e are addressed using a direct dynamics approach based on the multidimensio nal instanton model. The potential energy surface, which governs the tautom erization dynamics, is generated from ab initio calculations at CIS/6-31G* and CASSCF(8,8)/6-31G* levels of theory. It is formulated in terms of the n ormal modes of the transition state and consists of 33, 57, and 72 degrees of freedom for 3HIQ, 3HIQ/H2O, and 3HIQ/AA, respectively. The catalytic eff ect of complexation is discussed as an interplay between the static compone nt, reflected in the change of geometries and relative stabilities of the t hree stationary points, and the dynamic one, resulting from the effects of coupling of the tunneling motion to the skeletal modes. Since the coupling parameters reported in the present study are typical for proton transfer al ong hydrogen bridges, the relative weight of these effects in the overall a cceleration of the reaction will be larger in complexes with smaller reduct ion of the barrier height upon complexation. (C) 2000 American Institute of Physics. [S0021-9606(00)00231-2].