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Computational study of naphthylisoquinoline alkaloids with antimalarial activity from Dioncophyllaceae and Ancistrodaceae in vacuo

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Abstract

This study investigates 33 naphthylisoquinoline alkaloids with antimalarial activity isolated from different tropical plants belonging to the Dioncophyllaceae and Ancistrodaceae families. All these molecules have two moieties, a naphthalene moiety and an isoquinoline moiety. A thorough conformational study was carried in vacuo at two levels of theory, HF/6-31G(d,p) and DFT/B3LYP/6-31+G(d,p). Frequency calculations were also performed in vacuo for all the calculated conformers, at both levels of theory. The major stabilizing factors are the intramolecular hydrogen bonds. The mutual orientation of the two moieties also has considerable influence, with marked preference for the naphthalene moiety to be perpendicular to the isoquinoline moiety.

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Authors and Affiliations

  1. Department of Chemistry, University of Venda, Thohoyandou, South Africa

    Liliana Mammino & Mireille K. Bilonda

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  1. Liliana Mammino
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  2. Mireille K. Bilonda
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Correspondence to Liliana Mammino.

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Published as part of the special collection of articles “CHITEL 2015 - Torino - Italy”.

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S-Fig. 1

Atom numbering utilized in this work. The C atoms in the rings are represented only by the numbers denoting their positions. In order to facilitate comparisons, the same atom numbering is utilized for atoms in corresponding positions in all the compounds studied; when needed, some numbers may be skipped for molecules in which some atoms are not present. The figures show the atom numbering of all the molecules considered in this study, to facilitate relating it to the criteria outlined in Fig. 2. Only the H atoms attached to O or N are numbered separately, while the H atoms attached to a C atom are given the same number as the C atom. (DOC 1770 kb)

S-Fig. 2

Optimized geometries of the conformers of the naphthylisoquinoline alkaloids considered in this work and acronyms used to denote them. (DOC 2059 kb)

S-Table 1

List of the naphthylisoquinoline alkaloids studied in this work: their names, their types, the type of coupling between moieties (atoms bonded by the single bond between the two moieties), their sources (plants from which they were derived), and the acronyms used to denote them in this work. (DOC 72 kb)

S-Table 2

Parameters of the intramolecular hydrogen bonds (IHB) of the conformers of the calculated naphthylisoquinoline alkaloids. The table considers all the IHB-type interactions. For the O−H···O IHBs, the length reported is the H···O distance. For the O−H··· π interaction, the length reported is the distance between the H of O−H group and the closest C atom in the aromatic ring. For C−H···O interactions, the length reported is the distance between the H of the CH group and the O atom (the H is given the same number as the C atom to which it is attached. The results are from HF/6-31G(d,p) and DFT/B3LYP/6-31+G(d,p) calculations in vacuo. Conformers with no IHBs (denoted with the letter z) are included in the list for completeness sake (so that the table lists all the calculated conformers) and to highlight the absence of IHBs. (DOC 217 kb)

S-Table 3

Vibrational frequencies (harmonic approximation) of the O−H bonds in the naphthylisoquinoline alkaloids. The frequency values have been scaled by 0.9024 and 0.9857, respectively, for HF/6-31G(d,p) [62] and DFT/B3LYP/6-31+G(d,p) [63] results in vacuo. (DOC 143 kb)

S-Table 4

Relative energy (ΔEcorrect, kcal/mol) corrected for ZPE and ZPE corrections (kcal/mol) of the calculated conformers of naphthylisoquinoline alkaloids. Results from HF/6-31G(d,p) and DFT/B3LYP/6-31+G(d,p) frequency calculations.(DOC 143 kb)

S-Table 5

Relative Gibbs free energies (ΔG, sum of electronic and thermal free energies) and thermal corrections to Gibbs free energy of the calculated conformers of naphthylisoquinoline alkaloids. Results from HF/6-31G(d,p) and DFT/6-31+G(d,p) frequency calculations. (DOC 139 kb)

S-Table 6

Dipole moments of the conformers of the calculated naphthylisoquinoline alkaloids in vacuo. HF/6-31G(d,p) and (DFT/B3LYP/6-31+G(d,p) results, respectively, denoted as HF and DFT in the column headings. (DOC 95 kb)

S-Table 7

HOMO–LUMO energy gaps of the conformers of the calculated naphthylisoquinoline alkaloids in vacuo. HF/6-31G(d,p) and (DFT/B3LYP/6-31+G(d,p) results, respectively, denoted as HF and DFT in the column headings.(DOC 89 kb)

S-Table 8

Absolute energies of the lowest energy conformers of naphthylisoquinoline alkaloids with the same molecular formula. Results from HF/6-31G(d,p) and DFT//6-31G+(d,p) calculations in vacuo (DOC 84 kb)

S-Table 9

Absolute energy of the lowest energy conformers of pairs of NPQ5- and NPQ7-type naphthylisoquinoline alkaloids with the same molecular formula. Results from HF/6-31G(d,p) and DFT/6-31G+(d,p) calculations in vacuo. (DOC 38 kb)

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Mammino, L., Bilonda, M.K. Computational study of naphthylisoquinoline alkaloids with antimalarial activity from Dioncophyllaceae and Ancistrodaceae in vacuo . Theor Chem Acc 135, 101 (2016). https://doi.org/10.1007/s00214-016-1843-7

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