Conformational and electrostatic properties of naphthazarin, juglone, and naphthoquinone: An ab initio theoretical study

Conformational features of naphthazarin, juglone, and naphthoquinone have been examined via ab initio (Hartree-Fock) SCF calculations at 3-21G level. The results suggest a planar structure for all the three molecules and internally hydrogen-bonded structure for naphthazarin and juglone to be their preferred conformation. The optimized structural features are essentially the same as their crystal geometries. Molecular electrostatic potential (MEP) calculations using ab initio SCF methods ranging from 3-21G to 6-31G levels have been performed to visualize their three-dimensional pharmacophoric patterns and topography. The results indicate that two factors-(i) the depth, extent, and relative location of negative potential around hydroxyl and quinonoid oxygens, and (ii) a gradual loss of negative potential over the molecular plane due to the presence and orientation of the hydroxyl groups in the phenolic part of the molecules-are crucial for recognition interaction of the compounds with their receptors. Aqueous solvation seems to have significant influence on the MEP profiles of the molecules. Although intrinsic nucleophilicity increases for all the compounds, including the different conformers, due to aqueous solvation, the intrinsic electrophilicity shows remarkable decrease for all. It appears that the acidic nature of the hydrogens in these compounds and conformers decreases sharply along with shifts of positions while going from the gas phase to the aqueous phase. These observations may help to explain the mechanism of action(s) of the anthracyclin family of cytotoxic antibiotics.