Computational Study of Jozimine A 2 ,
a Naphthylisoquinoline Alkaloid
with Antimalarial Activity
Mireille K. Bilonda and Liliana Mammino
Abstract Jozimine A 2 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.
Keywords Alkaloids ⋅ Antimalarials ⋅ Intramolecular hydrogen bond
Jozimine A 2 ⋅ Naphthyl-isoquinoline alkaloids ⋅ Mutual orientation
Solute-solvent interactions
Electronic supplementary material The online version of this chapter (https://doi.org/10.1007/
978-3-319-74582-4_17) contains supplementary material, which is available to authorized users.
M. K. Bilonda ⋅ L. Mammino ( ✉ )
Department of Chemistry, University of Venda, P/bag X5050, Thohoyandou, South Africa
e-mail: sasdestria@yahoo.com
M. K. Bilonda
e-mail: mireillebilonda@yahoo.fr
© Springer International Publishing AG, part of Springer Nature 2018
Y. A. Wang et al. (eds.), Concepts, Methods and Applications of Quantum Systems
in Chemistry and Physics, Progress in Theoretical Chemistry and Physics 31,
https://doi.org/10.1007/978-3-319-74582-4_17
305
a Naphthylisoquinoline Alkaloid
with Antimalarial Activity
Mireille K. Bilonda and Liliana Mammino
Abstract Jozimine A 2 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.
Keywords Alkaloids ⋅ Antimalarials ⋅ Intramolecular hydrogen bond
Jozimine A 2 ⋅ Naphthyl-isoquinoline alkaloids ⋅ Mutual orientation
Solute-solvent interactions
Electronic supplementary material The online version of this chapter (https://doi.org/10.1007/
978-3-319-74582-4_17) contains supplementary material, which is available to authorized users.
M. K. Bilonda ⋅ L. Mammino ( ✉ )
Department of Chemistry, University of Venda, P/bag X5050, Thohoyandou, South Africa
e-mail: sasdestria@yahoo.com
M. K. Bilonda
e-mail: mireillebilonda@yahoo.fr
© Springer International Publishing AG, part of Springer Nature 2018
Y. A. Wang et al. (eds.), Concepts, Methods and Applications of Quantum Systems
in Chemistry and Physics, Progress in Theoretical Chemistry and Physics 31,
https://doi.org/10.1007/978-3-319-74582-4_17
305