DFT computational studies of intramolecular hydrogen-bonding interactions in a model system for 5-iminodaunomycin

Intramolecular hydrogen-bonding interactions in 1,4-dihydroxy-5,8-naphthoquinone imine (1a: an oversimplified model system for 5-iminodaunomycin (5IDN)), its tautomers (2a-4a), and the rotamers of 1a-4a have been studied by the Becke-Lee-Yang-Parr (BL,YP) and Becke3-Lee-Yang-Parr (B3LYP) nonlocal density functionals. The relative decreasing order of strength of the hydrogen bonds was found to be N ... H-O (strong) greater than or equal to O ... H-O (strong) > O ... H-N (weak/normal?), in contrast to the experimentally observed one: O ... H-O (strong) > N ... H-O (normal) > O ... H-N (weak), which was based on experimental NMR data on 5IDN (G.L. Tong, D.W. Henry, E.M. Acton, J. Med. Chem. 22 (1979) 36; J.W. Lown, H.H. Chen, J.A. Plambeck, Biochem. Pharmacol. 28 (1979) 2563). The imidine, or the enaminone, form (4a) is predicted to be the most stable tautomer with the relative decreasing order in stability of the tautomers being: 4a > 2a > 1a > 3a. The BLYP/6-31G* calculated barrier energies which are less than 5 kcal/mol are in the range predicted for malonaldehyde and at least in One case the proton transfer is almost barrierless suggesting that proton transfer may be feasible even at room temperature in these systems. The B3LYP/6-311G** calculated geometries and O ... H and O ... O hydrogen-bond distances in the enolone fragment of the tautomers are in good agreement with those determined experimentally for malonaldehyde and naphthazarin, while the BLYP/6-31G** and BLYP/6-31G* geometries and hydrogen-bond distances are not as good. (C) 2000 Elsevier Science B.V. All rights reserved.