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

Abstract

The geometries and electronic structures of the different tautomeric forms of naphthazarin, 1,4-dihydroxy-5,8-naphthoquinone ( 1a) and their rotamers have been determined along with the hydrogen-bond interaction energies using the Becke3–Lee–Yang–Parr (B3LYP) nonlocal density functional and the 6-311G(d,p) basis set. The tautomer with the two hydrogen atoms on the two different 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 intramolecular stepwise proton-transfer process are less than 5 kcal/mol. These barrier energies are in the range predicted for malonaldehyde, and for one of the steps, the proton transfer is calculated to be barrierless suggesting that proton transfer may be feasible even at room temperature in these systems. All hydrogen bonds are asymmetric even in those cases where the contraction of the R(O⋯O) distance to less than 2.4–2.5 Å was calculated. In the transition states, the R(O⋯O) distance contracts further to 2.311 Å, but the hydrogen bond is still asymmetric. However, the hydrogen bond may approach the behavior of a symmetric one with the H atom jumping back and forth. Transition states with the same energy and almost the same geometry but with displacements of the H atoms in different dimensions, as revealed by the animation of the imaginary frequencies, suggested that the transition states might exhibit a multi-dimensional potential barrier.