in O−H⋯π interaction have greater values of ΔG solv than the conformers in which
O41−H50 and O46−H60 are simultaneously engaged in O−H⋯π interaction.
In acetonitrile, the conformers with all the OHs engaged in IHBs have the
greatest values of ΔG solv . The conformers in which neither O41−H50 nor O46
−H60 are engaged in O−H⋯π IHBs have the smallest absolute values of ΔG solv
and conformers in which only either O41−H50 or O46−H60 is engaged in the O
−H⋯π IHB have values of ΔG solv greater than the conformers in which they are not
engaged in them. The behaviour in acetonitrile is different with respect to the
behaviour in water. The importance of solute-solvent H-bonds for acetonitrile may
not be as relevant as in water, both because acetonitrile can only be H-bond
acceptor and because N is a weaker acceptor than O. The trend in chloroform is
almost similar to the trend in acetonitrile, but the conformers having all the possible
O−H⋯π interactions have slightly greater ΔG solv than the other conformers.
Conformers of S/S′ symmetric pairs may have slightly different ΔG solv value s.
The dipole moments (Table 6) increases in chloroform with respect to in vacuo
and in acetonitrile with respect to chloroform, but decreases slightly in water with
respect to acetonitrile. This might be related to the fact that acetonitrile has greater
dipole moment than water (although several of its effects on solute molecules
appear to be intermediate between those of chloroform and those of water). Conformers of S/S′ symmetric pairs have the same value of dipole moment in the
solvents considered.
The HOMO-LUMO energy gap increases with the solvent polarity. Conformers
with all the O−H⋯π and C−H⋯O interactions (c-d-e-f-g-h) have the highest values
of the HOMO-LUMO energy gap in all the media, and conformers with only one O
−H⋯O IHB (O43−H52⋯O42 or O44−H54⋯O45) have the lowest energy
gap. The range of the HOMO-LUMO energy gap in vacuo is mostly 221.17
−236.56/HF and 85.43−100.79/DFT. The gap mostly increases in solution, but it
decreases in some cases; the change with respect to in vacuo is −0.41−4.34/HF and
−0.25−4.15/DFT in chloroform; −0.43−6.04/HF and −3.39−1.84/DFT in acetonitrile and −0.15−8.56/HF and −0.13−8.34/DFT in water. Conformers of S/S′
symmetric pairs may have slightly different HOMO-LUMO gaps.
4 Discussion and Conclusions
A computational study of jozimine A 2 —a naphthylisoquinoline alkaloid with antimalarial activity—has been carried out at the HF/6-31G(d,p) and the DFT/B3LP/
6-31+G(d,p) levels in vacuo and in chloroform, acetonitrile and water. The results
highlight the main properties of this molecule. Conformational preferences and
other properties are influenced by the presence of O−H⋯O IHBs (in the naphthalene moieties) and other IHB-type interactions, such as O−H⋯π (between some
OH and a π ring in the same or in another moiety) and C−H⋯O (between a CH and
an OH of the same isoquinoline moiety), and by the mutual orientation of the
Computational Study of Jozimine A 2 , a Naphthylisoquinoline …
325
O41−H50 and O46−H60 are simultaneously engaged in O−H⋯π interaction.
In acetonitrile, the conformers with all the OHs engaged in IHBs have the
greatest values of ΔG solv . The conformers in which neither O41−H50 nor O46
−H60 are engaged in O−H⋯π IHBs have the smallest absolute values of ΔG solv
and conformers in which only either O41−H50 or O46−H60 is engaged in the O
−H⋯π IHB have values of ΔG solv greater than the conformers in which they are not
engaged in them. The behaviour in acetonitrile is different with respect to the
behaviour in water. The importance of solute-solvent H-bonds for acetonitrile may
not be as relevant as in water, both because acetonitrile can only be H-bond
acceptor and because N is a weaker acceptor than O. The trend in chloroform is
almost similar to the trend in acetonitrile, but the conformers having all the possible
O−H⋯π interactions have slightly greater ΔG solv than the other conformers.
Conformers of S/S′ symmetric pairs may have slightly different ΔG solv value s.
The dipole moments (Table 6) increases in chloroform with respect to in vacuo
and in acetonitrile with respect to chloroform, but decreases slightly in water with
respect to acetonitrile. This might be related to the fact that acetonitrile has greater
dipole moment than water (although several of its effects on solute molecules
appear to be intermediate between those of chloroform and those of water). Conformers of S/S′ symmetric pairs have the same value of dipole moment in the
solvents considered.
The HOMO-LUMO energy gap increases with the solvent polarity. Conformers
with all the O−H⋯π and C−H⋯O interactions (c-d-e-f-g-h) have the highest values
of the HOMO-LUMO energy gap in all the media, and conformers with only one O
−H⋯O IHB (O43−H52⋯O42 or O44−H54⋯O45) have the lowest energy
gap. The range of the HOMO-LUMO energy gap in vacuo is mostly 221.17
−236.56/HF and 85.43−100.79/DFT. The gap mostly increases in solution, but it
decreases in some cases; the change with respect to in vacuo is −0.41−4.34/HF and
−0.25−4.15/DFT in chloroform; −0.43−6.04/HF and −3.39−1.84/DFT in acetonitrile and −0.15−8.56/HF and −0.13−8.34/DFT in water. Conformers of S/S′
symmetric pairs may have slightly different HOMO-LUMO gaps.
4 Discussion and Conclusions
A computational study of jozimine A 2 —a naphthylisoquinoline alkaloid with antimalarial activity—has been carried out at the HF/6-31G(d,p) and the DFT/B3LP/
6-31+G(d,p) levels in vacuo and in chloroform, acetonitrile and water. The results
highlight the main properties of this molecule. Conformational preferences and
other properties are influenced by the presence of O−H⋯O IHBs (in the naphthalene moieties) and other IHB-type interactions, such as O−H⋯π (between some
OH and a π ring in the same or in another moiety) and C−H⋯O (between a CH and
an OH of the same isoquinoline moiety), and by the mutual orientation of the
Computational Study of Jozimine A 2 , a Naphthylisoquinoline …
325