230
N. Tshilande and L. Mammino
the values of MYRA remain slightly higher than those of c-DBPO and t-DBPO; the
values for c-DBPO and t-DBPO are closer to each other.
Tables S122–S140 and Figs. S114–S131 consider the properties of conformers
of the three molecules having different geometries of R and the same geometry of
ABDE. The relative energies (Tables S122–S124; Fig. S114–S116) have close values
in each solvent, with only few discrepancies. The length of the first IHB (Tables S125–
S127; Fig. S117–S119) shows similar trends in the three solvents, with up to 0.052
Å differences between MYRA and the other two molecules, whose values are closer.
The values of the distance between the donor H atom and the closest C atom in
the acceptor aromatic B ring for the O–H···π IHBs (Tables S128–S130; Figs. S120–
S122) are close for all corresponding conformers of the three molecules. The values of
the dipole moment (Tables S131–S133; Figs. S123–S125) are close for corresponding conformers of MYRA and t-DBPO, while those of c-DBPO differ more significantly. The HOMO-LUMO energy gaps (Tables S134–S136; Figs. S126–S128) are
very close in acetonitrile and water, while c-DBPO-d-r-η-p-a-e-j-6y has ≈1 kcal/mol
greater value that the other two molecules in chloroform. The free energy of solvation
(Tables S137–S139, with synopsis in Table 140; Figs. S129–S131) shows rather similar trends within the same solvent. In chloroform, the values for t-DBPO are smaller
than for corresponding conformers of the other two molecules; in acetonitrile, the
values of MYRA are the lowest and the values for c-DBPO are slightly higher than
for corresponding conformers of the other two molecules; in water, MYRA has the
highest values and t-DBPO the lowest.
Since G solv has considerably different ranges of values in the three solvents, it
is suitable for synopsis diagrams showing the trends of the three molecules in the
three solvents in the same synopsis diagrams. Figure S132 shows such diagrams for
the two series of conformers.
4 Discussion and Conclusions
The computational study of biologically active molecules is particularly important
for drug development because it provides crucial information about the properties of
a molecule, which determine its biological activities. The information needs to be as
exhaustive as possible, because the activity may be influenced by the “finest details”
of the molecular structure and properties [41].
The current work has provided detailed information about the conformational
preferences and computable molecular properties of the molecules considered. The
use of three computational methods for most of the lowest energy conformers offers
validation of trends-identification. The use of a model structure provides information
that can be useful for the study of modified molecules in the search for compounds
with enhanced activity. The study in three solvents with different polarities and
characteristics provides information useful for the consideration of the biological
activities of these molecules, because the activity is exerted in a medium within
living organisms. The thorough attention to intramolecular hydrogen bonding is
N. Tshilande and L. Mammino
the values of MYRA remain slightly higher than those of c-DBPO and t-DBPO; the
values for c-DBPO and t-DBPO are closer to each other.
Tables S122–S140 and Figs. S114–S131 consider the properties of conformers
of the three molecules having different geometries of R and the same geometry of
ABDE. The relative energies (Tables S122–S124; Fig. S114–S116) have close values
in each solvent, with only few discrepancies. The length of the first IHB (Tables S125–
S127; Fig. S117–S119) shows similar trends in the three solvents, with up to 0.052
Å differences between MYRA and the other two molecules, whose values are closer.
The values of the distance between the donor H atom and the closest C atom in
the acceptor aromatic B ring for the O–H···π IHBs (Tables S128–S130; Figs. S120–
S122) are close for all corresponding conformers of the three molecules. The values of
the dipole moment (Tables S131–S133; Figs. S123–S125) are close for corresponding conformers of MYRA and t-DBPO, while those of c-DBPO differ more significantly. The HOMO-LUMO energy gaps (Tables S134–S136; Figs. S126–S128) are
very close in acetonitrile and water, while c-DBPO-d-r-η-p-a-e-j-6y has ≈1 kcal/mol
greater value that the other two molecules in chloroform. The free energy of solvation
(Tables S137–S139, with synopsis in Table 140; Figs. S129–S131) shows rather similar trends within the same solvent. In chloroform, the values for t-DBPO are smaller
than for corresponding conformers of the other two molecules; in acetonitrile, the
values of MYRA are the lowest and the values for c-DBPO are slightly higher than
for corresponding conformers of the other two molecules; in water, MYRA has the
highest values and t-DBPO the lowest.
Since G solv has considerably different ranges of values in the three solvents, it
is suitable for synopsis diagrams showing the trends of the three molecules in the
three solvents in the same synopsis diagrams. Figure S132 shows such diagrams for
the two series of conformers.
4 Discussion and Conclusions
The computational study of biologically active molecules is particularly important
for drug development because it provides crucial information about the properties of
a molecule, which determine its biological activities. The information needs to be as
exhaustive as possible, because the activity may be influenced by the “finest details”
of the molecular structure and properties [41].
The current work has provided detailed information about the conformational
preferences and computable molecular properties of the molecules considered. The
use of three computational methods for most of the lowest energy conformers offers
validation of trends-identification. The use of a model structure provides information
that can be useful for the study of modified molecules in the search for compounds
with enhanced activity. The study in three solvents with different polarities and
characteristics provides information useful for the consideration of the biological
activities of these molecules, because the activity is exerted in a medium within
living organisms. The thorough attention to intramolecular hydrogen bonding is