The Electronic Structure of Dopamine. An ab initio Electrostatic Potential Study of the Catechol Moiety

Electronic properties of dopamine were studied by the ab initio STO-3G MO method. The molecular electrostatic potential (MEP) around the aromatic ring and the catechol group remains practically the same in 3,4-dihydroxytoluene (a model compound) and in neutral dopamine examined in its two extended conformations, namely that found in the crystal (side-chain and aromatic ring almost perpendicular) and the one corresponding to 2-amino-6,7-dihydroxytetralin (6,7-ADTN) (side-chain and aromatic ring almost coplanar). In protonated dopamine and in dopamine hydrochloride, the electrostatic potential of the catechol moiety is overshadowed by the positive charge, but the main features remain discernible. The catechol moiety was examined in its two coplanar conformations containing a ‘flip-flop H-bond’. The electrostatic potential around the catechol moiety is quite complex, with alternating positive and negative maxima. At increasing distances above and away from the catechol moiety, only two peripheral maxima, one negative and one positive, remain perceptible. The ‘flip-flop’ mechanism results in an approximate interchange of these two potential maxima, a fact which tends to level out the structural differences between the α- and β-rotamer of dopamine. Based on these results and on the structure of rigid agonists, some pharmacophoric features of dopamine agonists are proposed.