Computational Study of Jozimine A2, a Naphthylisoquinoline Alkaloid with Antimalarial Activity

Progress in Theoretical Chemistry and Physics
2018.0

Abstract

Jozimine A2 is a dioncophyllaceae-type naphthylisoquinoline alkaloid isolated from the root bark of an Ancistrocladus species from the Democratic Republic of Congo and exhibiting high antimalarial activity. It is the first naturally occurring dimeric naphthylisoquinoline of this type to be discovered. Its molecule consists of two identical 4′-O-demethyldioncophylline A units, with each unit containing an isoquinoline moiety and a naphthalene moiety. A thorough conformational study of this molecule was performed in vacuo and in three solvents with different polarities and different H-bonding abilities (chloroform, acetonitrile and water), using two levels of theory, HF/6-31G(d,p) and DFT/B3LYP/6-31+G(d,p). Intramolecular hydrogen bond (IHB) patterns were investigated considering all the possible options. Preferences for the mutual orientations of the moieties were identified through the potential energy profiles for the rotation of the single bonds between moieties. Harmonic vibrational frequencies were calculated to confirm the true-minima nature of stationary points, to obtain the zero point energies and to get indications about IHB strengths from red shifts. Intramolecular hydrogen bonds (O−H⋯O IHBs and O−H⋯π interaction) are the most stabilizing factors. The mutual orientations of the four moieties also have considerable influence and they prefer to be perpendicular to each other. © 2018, Springer International Publishing AG, part of Springer Nature.

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