research papers
Table 3
In comparison to the previously reported structure of 1
(Butcher et al., 2007), the aforementioned C(5) and C(4)
motifs are conserved. Nevertheless, there are other subtle
differences in the packing of both structures, as will be
discussed in sequence.
Determination of the IC50 (mmol lꢃ1) of synthetic bischalcones against
tumour cell lines.
The trust range was 95% and NT denotes not tested.
Compound
PC3
HCT-116
SnB19
As can be seen in Fig. 7, in the packing of both polymorphs
of 1, chains running along the [100] and [010] directions
formed through C—Hꢀ ꢀ ꢀF contacts are present. Fig. 7(a) was
built-up only with C3A—H3Aꢀ ꢀ ꢀF1A and C3B—H3Bꢀ ꢀ ꢀF1B
contacts. The geometries of the C—Hꢀ ꢀ ꢀF contacts are
summarized in Table 2 (our polymorph) and in Table S1 of the
supporting information (literature polymorph). All the
metrics for these nonclassical hydrogen bonds reveal a better
directionality of the contacts in our polymorph than in that of
Butcher’s polymorph (e.g. the C—Hꢀ ꢀ ꢀF angles are closer to
180ꢁ herein; Fig. 7 and Table 2, and Table S1 of the supporting
information). The metrics for these intermolecular inter-
actions are within the expected range (Shukla & Chopra,
2015). This improvement in the angles of the C—Hꢀ ꢀ ꢀF
contacts may indicate more stability of our polymorph
compared with the literature form, which agrees well with the
lower Z0 value in the crystal form reported here due to opti-
mization of the geometry of the intermolecular contacts for all
molecules (Desiraju, 2007). The polymorphism phenomenon
is also seen in an intermolecular fashion when comparing the
structures on the (010) plane. The arrangement of the C—
Hꢀ ꢀ ꢀF hydrogen-bonded chains can be described as ladder-
like in our polymorph, wherein the molecules are disposed
1
18.74
(17.11–20.59)
32.55
(28.28–37.48)
>60
5.15
(4.48–5.89)
8.01
(7.19–8.97)
12.98
(11.48–14.71)
0.22
(0.17–0.31)
27.00
(24.44–29.85)
43.18
(38.08–49.01)
>60
2
3
Doxorubicin
0.81
(0.63–0.99)
NT
chemical environments), we have performed a powder X-ray
diffraction analysis on the same sample from which our
analyzed single crystal was isolated and on which the ss-NMR
spectrum was acquired. The experimental powder X-ray
diffractogram was performed for the new polymorph and then
compared with the theoretical diffractograms simulated with
Mercury (Macrae et al., 2008) for both polymorphs. As can be
seen in the low 2ꢄ region of the diffractogram (Fig. 6a), there
are peaks only for the literature polymorph (Butcher et al.,
2007). This is caused due to the presence of a large interplanar
spacing, evidenced by the long unit-cell length a of
90.019 (14) A. Those initial peaks (ca 2 and 4 in 2ꢄ) corre-
spond to the (200) and (400) planes. This difference is still
observed in the range of 2ꢄ from 5 to 10ꢁ (Fig. 6b). Meanwhile,
with an increase of the 2ꢄ value, the diffraction patterns of the
two polymorphs become similar. Even so, some peaks are still
present only in the polymorph reported by Butcher et al.
(2007), such as those around 20 and 28ꢁ in 2ꢄ. Therefore, the
experimental diffractogram was overlaid with the simulated
profile from our crystal structure and that simulated from the
literature structure (Fig. 6), allowing one to conclude that
these two structures are doubtless distinct polymorphs and
that the literature polymorph is not present concomitantly
with the polymorph we report here.
The explanation of the three NMR signals based on the C—
Hꢀ ꢀ ꢀO interactions is further justified taking into account the
energetic relevance of such contacts for this compound.
Preferably, in the gas phase, the molecules mostly have an anti
conformation in both molecular sides (AA conformer)
because of its lower energy. The fully optimized AS and SS
(the last with a syn conformation in both molecular sides)
conformers of 1 at the B3LYP/6-31++G(d,p) level of theory
present an energy higher than that of the lowest energy AA
conformer by 2.0 and 4.6 kcal molꢃ1, respectively. Therefore,
the presence of the C—Hꢀ ꢀ ꢀO hydrogen bonding justifies the
presence of the higher energy AS conformer in the solid state
and changes in the geometry of these contacts can change the
shielding of the C9 nucleus, since these are responsible for
stablizing a higher energy conformer in the solid state.
Besides the C—Hꢀ ꢀ ꢀO interaction, another nonclassical
hydrogen bond is found between bischalcone molecules. This
contact is of the type C—Hꢀ ꢀ ꢀF and is responsible for the
formation of C(4) motifs on both sides of all molecules (Fig. 7).
ꢁ
˚
˚
side-by-side, with a regular displacement of 3.16 A (Fig. 7a).
This displacement was calculated as being the distance
between the l.s. plane fitted through all non-H bischalcone
atoms and the O atom of a neighbouring molecule (because
molecular planes are not perfectly planar in the previous
polymorph). In the structure described here, this displacement
is the same along the c axis. Meanwhile, in the previously
reported structure (Butcher et al., 2007), there are different
values for such this displacement (i.e. the distance between the
mentioned l.s. planes), even being negligible for the corre-
sponding distance between molecules I and II. These distances
were calculated for the previously reported structure (Butcher
et al., 2007), resulting in values of 2.54 (between the l.s. plane
of I and the major-occupancy O atom of III), 3.53 (between
the l.s. plane of II and the major-occupancy O atom of III) and
˚
0.41 A (between the l.s. plane of I and the O atom of II), as
illustrated in Fig. 7(b).
3.2. Cytotoxicity assay
All three compounds were tested for cytotoxic potential
against three tumour cell lines. Initially, the compounds were
tested at a single concentration of 25 mg mlꢃ1 against the
tumour cell lines.
All compounds had a percentage of tumour growth inhi-
bition greater than 75% against all tumour cell lines tested,
except for compound 3 which had an inhibition less than 75%
against PC-3 and SNB-19 cells. The compounds were then
diluted for the IC50 determination. To evaluate the cytotoxic
ꢂ
Acta Cryst. (2019). C75
Ferreira et al.
A new polymorph of a bischalcone 7 of 8