Behaviour of N-CH3 Group in Tropane Alkaloids and Correlations in their Properties

ROXANA RUDYK; CHECA MARIA ALEJANDRA; KARINA GUZETTI; MAXIMILIANO ALBERTO IRAMAIN; SILVIA ANTONIA. BRANDÁN

Indian Journal of Research

Paripex

Año: 2018 vol. 10 p. 70 - 97

2250-1991

In this work, the influence of common >N-CH3 group presentin the three free base, cationic and hydrochloride/bromidestructures of scopolamine, heroin, morphine, cocaine andtropane alkaloids in gas and aqueous solution phases has beeninvestigated theoretically by using B3LYP/6-31G*calculations and the Polarized Continuum model (PCM) inorder to find possible correlations in their properties. Hence,the N-C distances, Mulliken and Merz-Kollman (MK)charges, bond orders, stabilization and solvation energies,frontier orbitals, some descriptors and their topologicalproperties were compared and analysed among them. Thepresence of two fused piperidine and pyrrolidine rings in thethree species of scopolamine, cocaine and tropane alkaloidsproduces changes in the charges, stabilization and solvationenergies and densities of their rings linked to that group inthese alkaloids, as compared with heroin and morphine. Here,the higher solvation energies observed for the heroin speciesare supported by the Mulliken and MK charges on C and Natoms of >N-CH3 groups. On the other hand, the higherreactivities of three cocaine species in the two media could beeasily justified by the most negative MK charges observed onthe N atoms. The presence of only one ring of six members inthe heroin and morphine species linked to >N-CH3 groupscould justify the low electronic densities of their ringsdifferent from scopolamine, cocaine and tropane alkaloids. Inaddition, the higher N-C distances observed in the three formsof heroin and morphine in both media suggest low electronicdensities of their rings and higher stabilities, as comparedwith scopolamine, cocaine and tropane. The incorporation ofadditional groups and rings in tropane alkaloid increase theirreactivity, as evidenced in the cocaine species. Finally, theLipinski?s and Veber rules justify broadly the potentialpharmacological properties of these alkaloids.