Ab Initio and DFT Computational Study …
227
MYRA. It has also to be considered that the possible MYRA-water H-bonds depend
on the characteristics of the conformer.
The calculated adducts with 14, 15 or 16 water molecules are too few to enable
trend identification, above all with regard to conformer-type (given the high number
of possible adducts with several water molecules for each conformer, considering
an adequate number would become a separate study). All the same, the calculated
adducts highlight preferred geometries around specific areas of MYRA (e.g., the area
of the first IHB), as well as the roles of bridging water molecules. They also suggest
that the MYRA-water H-bond lengths decrease as the number of water molecule
attached to the MYRA molecule, and bridged by other water molecules, increases.
It is interesting to note that none of the adducts shows breaking of the first IHB.
This is consistent with the findings for other ACPLs, indicating that the first IHB
is maintained in water solution [14]. The adducts with explicit water molecules are
suitable to signify the outcome of the competition [40] between intramolecular Hbonding and intermolecular H-bonding (formation of solute-solvent H-bonds), and
studies of this type have indicated breaking of weaker IHBs in ACPLs [11].
3.5 Comparison of the Results Obtained for the Considered
Molecular Structures
The role of a model structure is to provide preliminary information on the part of a
molecule (or a set of molecules) to which it corresponds. It is interesting to evaluate
how good the model is, i.e., how the information it provides is close to the results for
the molecules it models. Since high energy conformers do not influence the biological
activity of a molecule, comparisons are carried out for conformers with relative
energy lower than 5.7 kcal/mol (which includes enough high energy conformers
to provide sufficiently comprehensive information, but excludes the highest energy
conformers).
The comparison with MODL has a meaning for the conformers of MYRA, cDBPO and t-DBPO having the same geometry of R and different geometries of
ABDE. The computed properties of MODL are compared with the properties of
the corresponding conformers of the three molecules (Tables S83–S87; Figs. S76–
S80). Comparisons of the properties of the three molecules are also carried out; for
the conformers having different geometries of R and the same geometry of ABDE,
comparisons can only concern corresponding conformers of the three molecules,
because the geometry of ABDE is that of the lowest energy conformer of MODL.
The relative energies of corresponding conformers of MODL and the three
molecules (Table S83; Fig. S76) are very close for conformers with relative energy
lower than 4.86 kcal/mol, and some discrepancies appear only for conformers with
higher energy. Similarly, the values of the H···Obond length (Table S84; Fig. S77)
and of the O···O distance (Table S84) of the first IHB are very close for conformers
with relative energy lower than 4.86 kcal/mol, with differences smaller than 0.002 Å;
227
MYRA. It has also to be considered that the possible MYRA-water H-bonds depend
on the characteristics of the conformer.
The calculated adducts with 14, 15 or 16 water molecules are too few to enable
trend identification, above all with regard to conformer-type (given the high number
of possible adducts with several water molecules for each conformer, considering
an adequate number would become a separate study). All the same, the calculated
adducts highlight preferred geometries around specific areas of MYRA (e.g., the area
of the first IHB), as well as the roles of bridging water molecules. They also suggest
that the MYRA-water H-bond lengths decrease as the number of water molecule
attached to the MYRA molecule, and bridged by other water molecules, increases.
It is interesting to note that none of the adducts shows breaking of the first IHB.
This is consistent with the findings for other ACPLs, indicating that the first IHB
is maintained in water solution [14]. The adducts with explicit water molecules are
suitable to signify the outcome of the competition [40] between intramolecular Hbonding and intermolecular H-bonding (formation of solute-solvent H-bonds), and
studies of this type have indicated breaking of weaker IHBs in ACPLs [11].
3.5 Comparison of the Results Obtained for the Considered
Molecular Structures
The role of a model structure is to provide preliminary information on the part of a
molecule (or a set of molecules) to which it corresponds. It is interesting to evaluate
how good the model is, i.e., how the information it provides is close to the results for
the molecules it models. Since high energy conformers do not influence the biological
activity of a molecule, comparisons are carried out for conformers with relative
energy lower than 5.7 kcal/mol (which includes enough high energy conformers
to provide sufficiently comprehensive information, but excludes the highest energy
conformers).
The comparison with MODL has a meaning for the conformers of MYRA, cDBPO and t-DBPO having the same geometry of R and different geometries of
ABDE. The computed properties of MODL are compared with the properties of
the corresponding conformers of the three molecules (Tables S83–S87; Figs. S76–
S80). Comparisons of the properties of the three molecules are also carried out; for
the conformers having different geometries of R and the same geometry of ABDE,
comparisons can only concern corresponding conformers of the three molecules,
because the geometry of ABDE is that of the lowest energy conformer of MODL.
The relative energies of corresponding conformers of MODL and the three
molecules (Table S83; Fig. S76) are very close for conformers with relative energy
lower than 4.86 kcal/mol, and some discrepancies appear only for conformers with
higher energy. Similarly, the values of the H···Obond length (Table S84; Fig. S77)
and of the O···O distance (Table S84) of the first IHB are very close for conformers
with relative energy lower than 4.86 kcal/mol, with differences smaller than 0.002 Å;