Computational Study of Shuangancistrotectorine A: A Naphthylisoquinoline Alkaloid with Antimalarial Activity

Abstract

Shuangancistrotectorines A, B, C, D and E are naphthylisoquinoline alkaloids isolated from the twigs of Ancistrocladus tectorius, an indigenous plant in China and South East Asia. Their molecules are all C2-symmetric, i.e., they consist of two identical units. Each unit contains a naphthalene moiety and an isoquinoline moiety. Shuangancistrotectorine B and E are atropo-diastereomers of shuangancistrotectorine A and D respectively. Shuangancistrotectorine A, B and D exhibit very good and specific antimalarial activity, with shuangancistrotectorine A being the most active. The current work presents the results of a detailed conformational study of shuangancistrotectorine A, 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). Particular attention is given to intramolecular hydrogen bonds’ patterns. The results show that intramolecular hydrogen bonds are the dominant factor influencing conformational preferences and energies, and also the other computable molecular properties. The mutual orientation of the moieties is also an energy-influencing factor, and the results show that all the moieties prefer to be perpendicular to each other. Comparisons with the results of other previously-investigated dimeric naphthylisoquinoline alkaloids are also included.