3.4. Stability studies by using NBO and AIM analyses
The presence of donors (N-H) and acceptors (N atoms) H bonds groups in
both structures of S(-) and R(+) forms of CQ have revealed different
behaviours of MK charges and different mapped MEP 3D surfaces for which,
the predictions of their stabilities in the different media are
important to explain those differences observed. Besides, different
studies have evidenced that acceptors and donors’ groups H bonds have a
fundamental role in their behaviour as pharmacological drugs
[78,79]. For these reasons, in order to investigate intra-molecular
or H bonds interactions in both S(-) and R(+) forms of CQ the second
order perturbation theory analyses of Fock matrix in NBO Basis were
calculated in the two media by using the NBO program [61]. On the
other hand, the AIM 2000 program was also employed to compute the
topological properties of those two forms of CQ [62,63]. Thus,
calculated donor-acceptor interactions of both S(-) and R(+) forms of CQ
in the two media by using the B3LYP/6-311++G** method are presented inTables S3 and S4 . Six different σ→σ* ,π→π* , n→σ* , n→π* π→σ* and π*→π* interactions
predicted for both forms in gas phase are shown in Table S3·and they
clearly favor the R(+) form with a total energy value in gas phase of
9828.18 kJ/mol. However, from Table S4 eight interactions predicted in
solution are observed for the two forms which are, σ→σ* ,σ→π* , π→σ* , π→π* , n→σ* , n→π*, π*→σ*and π*→π* interactions where only the σ→σ* , π→π* ,n→σ* , n→π*, π*→σ* and π*→π* interactions are
observed in both forms while the other two σ→π* and π→σ*interactions are observed only for the S(-) form in solution. Hence, the
total energy value significantly favors the S(-) form of CQ. These
results in both media are not in accordance with those calculated from
the optimization process because according to Table 1, R(+) is the most
stable enantiomer of CQ in solution while S(-) is the most stable form
in gas phase. On the contrary, NBO calculations show that R(+) is the
most stable enantiomer of CQ in gas phase while S(-) is the most stable
form in solution.
With these results different obtained by NBO calculations, it is
necessary to investigate intra-molecular or H bonds interactions in both
S(-) and R(+) forms of CQ by using the Bader’s theory through
topological properties. Hence, the electron density, ρ(r) , the
Laplacian values, ∇2ρ(r), the eigenvalues(λ1, λ2, λ3) of the Hessian matrix and, the|λ1|/λ3 ratio were calculated for both S(-) and
R(+) forms in both media by using the B3LYP/6-311++G** method. The
topological properties predicted for the S(-) form of CQ in the two
media are observed in Table S5 while those obtained for the
R(+) form in both media are presented in Table S6 . Table S5
shows three new H bonds interactions for the S(-) form of CQ in gas
phase which quickly increase to six in solution. In the molecular
graphic presented in Figure 4 for this form in solution these
new C8-H28···H42, N3-H30···H45, C14-H38···C13, C6-H25···H35,
C14-H39···H37 and C16-H44···H27 interactions that generate six new RCPs
can be seen and which are named from RCPN1 to RCPN6 while RCP1 and RCP2
are the rings of quinolin double-ring structure composed of a
chlorobenzene and a pyridine ring. On the contrary, Table S6 shows only
two new H bonds interactions for the R(+) form in gas phase while in
solution the number increases to three in solution, as it can be
observed in the molecular graphic of Figure 5 .