CONFORMATIONAL AND ELECTROSTATIC PROPERTIES OF NAPHTHAZARIN, JUGLONE,AND NAPHTHOQUINONE - AN AB-INITIO THEORETICAL-STUDY

Conformational features of naphthazarin, juglone, and naphthoquinone h ave been examined via ab initio (Hartree-Fock) SCF calculations at 3-2 1G level. The results suggest a planar structure for all the three mol ecules and internally hydrogen-bonded structure for naphthazarin and j uglone to be their preferred conformation. The optimized structural fe atures are essentially the same as their crystal geometries. Molecular electrostatic potential (MEP) calculations using ab initio SCF method s ranging from 3-21G to 6-31G levels have been performed to visualize their three-dimensional pharmacophoric patterns and topography. The re sults indicate that two factors-(i) the depth, extent, and relative lo cation of negative potential around hydroxyl and quinonoid oxygens, an d (ii) a gradual loss of negative potential over the molecular plane d ue to the presence and orientation of the hydroxyl groups in the pheno lic part of the molecules-are crucial for recognition interaction of t he compounds with their receptors. Aqueous solvation seems to have sig nificant influence on the MEP profiles of the molecules. Although intr insic nucleophilicity increases for all the compounds, including the d ifferent conformers, due to aqueous solvation, the intrinsic electroph ilicity shows remarkable decrease for all. It appears that the acidic nature of the hydrogens in these compounds and conformers decreases sh arply along with shifts of positions while going from the gas phase to the aqueous phase. These observations may help to explain the mechani sm of action(s) of the anthracyclin family of cytotoxic antibiotics.