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

Abstract

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.

Electrophilic Substituent Constant σ+ of Electron Donor Substituents in Nonpolar Media

“…Furthermore, the evaluation of the substituent effects of charged groups is difficult in many cases . In particular, the determination of the combined substituent effects, as in the biologically important catechol and catecholate groups, is difficult to carry out using the established methods.…”

Structural and molecular orbital study of ergoline derivatives. Ethyl 2(S)- and 2(R)-cyano-2-(6-methylergolin-8β-yl)methylbutyrate

“…Its most important feature is two 'critical' heteroatoms which interact with the receptors: one of these is an N atom while the other can be an O atom (in compounds like dopamine, aminoindanes, 2-aminotetralins, apomorphines) or an N atom (in the natural and synthetic ergolines). In addition to these investigations, the MEP of the catechol moiety of DA was studied, and some pharmacophoric features of DA agonists were proposed (van de Waterbeemd, Carrupt & Testa, 1985).…”

The Harmony of Molecules

“…Following this work, the use of MEP became very popular in interpreting any similarity of drug molecules with respect to their action [34][35][36][37][38][39][40][41]. Following this work, the use of MEP became very popular in interpreting any similarity of drug molecules with respect to their action [34][35][36][37][38][39][40][41].…”