Computational study of mbandakamine A: a dimeric naphthylisoquinoline alkaloid with antimalarial activity

• Published in: Theoretical chemistry accounts 2018-11, Vol.137 (11), p.1-18, Article 139
• Main Authors: Bilonda, Mireille K., Mammino, Liliana
• Format: Article
• Language: English
• Subjects: Acetonitrile; Alkaloids; Atomic/Molecular Structure and Spectra; Chemistry; Chemistry and Materials Science; CHITEL 2017 - Paris - France; Chloroform; Dimers; Hydrogen bonds; Inorganic Chemistry; Naphthalene; Organic Chemistry; Physical Chemistry; Regular Article; Theoretical and Computational Chemistry
• ISSN: 1432-881X; 1432-2234
• DOI: 10.1007/s00214-018-2323-z

Mbandakamine A is one of the naphthylisoquinoline alkaloids isolated from the leaves of Congolese Ancistrocladus species and shows good antimalarial activity. It is also one of the first discovered dimeric naphthylisoquinolines with an unsymmetrically coupled central biaryl axis. The molecule consists of two units, with each unit containing one naphthalene moiety and one isoquinoline moiety. The substituents on the rings comprise four OH groups and four OCH 3 groups. Each OH group can be H-bond donor, either to the methoxy group in the same moiety or to another OH from another moiety; they can also be H-bond acceptors to another OH. Conformers can have up to three O–H···O intramolecular hydrogen bonds (IHBs) simultaneously, O–H···N or N–H···O and also other H-bond-type interactions (O–H··· π , C–H···O and C–H···N). A detailed conformational study 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). Because IHBs have a relevant role in determining conformational preferences, all combinations of IHBs and IHB-type interactions were considered, for a total of 107 conformers. The results highlight the stabilizing effect of the various types of IHBs and also of the mutual orientation of the four aromatic moieties and of the presence of stacking interactions.