A B3LYP study of intramolecular hydrogen bonding and proton transfer in naphthazarin: a model system for daunomycin/adriamycin

The geometries and electronic structures of the different tautomeric forms of naphthazarin, 1,4-dihydroxy-5,8-naphthoquinone (1a) and their rotamers h ave been determined along with the hydrogen-bond interaction energies using the Becke3-Lee-Yang-Parr (B3LYP) nonlocal density functional and the 6-311 G(d,p) basis set. The tautomer with the two hydrogen atoms on the two diffe rent rings is found to be an equilibrium structure and not a saddle point. The intramolecular hydrogen-bond interaction energies ranged from 13 to 19 kcal/mol. The B3LYP/6-311G**-calculated barrier energies for the intramolec ular stepwise proton-transfer process are less than 5 kcal/mol. These barri er energies are in the range predicted for malonaldehyde, and for one of th e steps, the proton transfer is calculated to be barrierless suggesting tha t proton transfer may be feasible even at room temperature in these systems . All hydrogen bonds are asymmetric even in those cases where the contracti on of the R(O...O) distance to less than 2.4-2.5 Angstrom was calculated. I n the transition states, the R(O...O) distance contracts further to 2.311 A ngstrom, but the hydrogen bond is still asymmetric. However, the hydrogen b ond may approach the behavior of a symmetric one with the H atom jumping ba ck and forth. Transition states with the same energy and almost the same ge ometry but with displacements of the H atoms in different dimensions, as re vealed by the animation of the imaginary frequencies, suggested that the tr ansition states might exhibit a multi-dimensional potential barrier. (C) 20 01 Elsevier Science B.V. All fights reserved.