A theoretical study of solvent effects on the characteristics of the intramolecular hydrogen bond in Droxidopa

The molecular structures and intramolecular hydrogen bond of Droxidopa have been investigated with density functional theory. It is found that strong hydrogen bonds (O–H...N and O...H–O) exist in the title compound. These hydrogen bonds play essential roles in determining conformational preferences and energy, which would have important effects in biological activity mechanisms that will strongly influence its characteristics in solution. A computational study of a representative number of actual and model structures was carried out in five solvents with different polarities and different types of interactions with solute molecules: water, ethanol, carbon tetrachloride, dimethyl sulfoxide, and tetrahydrofuran, utilizing the polarizable continuum model (PCM) model. The calculations were performed at the B3LYP/6-311 ++G(d,p) level of theory. In addition, the topological properties of the electron density distributions for O–H...N(O) intramolecular hydrogen bond were analyzed in terms of the Bader’s theory of atoms in molecules. Furthermore, the analyses of different hydrogen bonds in this molecule by quantum theory of natural bond orbital (NBO) methods support the density functional theory (DFT) results.