We report a new polymorph of (1
E,4
E)-1,5-bis(4-fluorophenyl)penta-1,4-dien-3-one, C
17H
12F
2O. Contrary to the precedent literature polymorph with
Z′ = 3, our polymorph has one half molecule in the asymmetric unit disordered over two 50% occupancy sites. Each site corresponds to one conformation around the single bond vicinal to the carbonyl group (so-called
anti or
syn). The other half of the bischalcone is generated by twofold rotation symmetry, giving rise to two half-occupied and overlapping molecules presenting both
anti and
syn conformations in their open chain. Such a disorder allows for distinct patterns of intermolecular C—H
O contacts involving the carbonyl and
anti-oriented β-C—H groups, which is reflected in three
13C NMR chemical shifts for the carbonyl C atom. Here, we have also assessed the cytotoxicity of three symmetric bischalcones through their
in vitro antitumour potential against three cancer cell lines. Cytotoxicity assays revealed that this biological property increases as halogen electronegativity increases.
Supporting information
CCDC reference: 1913498
Data collection: APEX2 (Bruker, 2003); cell refinement: SAINT (Bruker, 2003); data reduction: SAINT (Bruker, 2003); program(s) used to solve structure: SHELXS2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: WinGX (Farrugia, 1999); software used to prepare material for publication: publCIF (Westrip, 2010) and Mercury (Macrae et al., 2008).
(1
E,4
E)-1,5-Bis(4-fluorophenyl)penta-1,4-dien-3-one
top
Crystal data top
C17H12F2O | F(000) = 560 |
Mr = 270.27 | Dx = 1.322 Mg m−3 |
Monoclinic, C2/c | Cu Kα radiation, λ = 1.54178 Å |
a = 30.184 (3) Å | Cell parameters from 1008 reflections |
b = 5.8907 (5) Å | θ = 8.7–66.1° |
c = 7.7144 (6) Å | µ = 0.84 mm−1 |
β = 98.040 (5)° | T = 296 K |
V = 1358.18 (19) Å3 | Prism, yellow |
Z = 4 | 0.15 × 0.10 × 0.10 mm |
Data collection top
Bruker APEXII CCD diffractometer | 873 reflections with I > 2σ(I) |
CCD scans | Rint = 0.040 |
Absorption correction: multi-scan (SADABS; Blessing, 1995) | θmax = 66.8°, θmin = 8.7° |
Tmin = 0.744, Tmax = 0.920 | h = −34→35 |
4490 measured reflections | k = −7→6 |
1148 independent reflections | l = −8→9 |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.045 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.129 | H-atom parameters constrained |
S = 1.06 | w = 1/[σ2(Fo2) + (0.0631P)2 + 0.1789P] where P = (Fo2 + 2Fc2)/3 |
1148 reflections | (Δ/σ)max < 0.001 |
177 parameters | Δρmax = 0.14 e Å−3 |
0 restraints | Δρmin = −0.13 e Å−3 |
Special details top
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes)
are estimated using the full covariance matrix. The cell esds are taken
into account individually in the estimation of esds in distances, angles
and torsion angles; correlations between esds in cell parameters are only
used when they are defined by crystal symmetry. An approximate (isotropic)
treatment of cell esds is used for estimating esds involving l.s. planes. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | Occ. (<1) |
C4A | 0.6814 (8) | 0.099 (4) | 0.085 (2) | 0.080 (4) | 0.5 |
C5A | 0.6399 (8) | 0.014 (3) | 0.044 (2) | 0.078 (4) | 0.5 |
H5A | 0.635009 | −0.130419 | −0.004262 | 0.094* | 0.5 |
C2A | 0.6525 (8) | 0.444 (3) | 0.191 (3) | 0.082 (3) | 0.5 |
H2A | 0.657795 | 0.590749 | 0.232641 | 0.098* | 0.5 |
C6A | 0.6024 (5) | 0.1616 (17) | 0.0799 (17) | 0.067 (2) | 0.5 |
H6A | 0.572993 | 0.113930 | 0.049982 | 0.080* | 0.5 |
C8B | 0.5441 (2) | 0.5655 (9) | 0.2198 (5) | 0.0741 (11) | 0.5 |
H8B | 0.566127 | 0.676994 | 0.225990 | 0.089* | 0.5 |
C9 | 0.500000 | 0.6399 (4) | 0.250000 | 0.0739 (6) | |
C1A | 0.6118 (4) | 0.3755 (14) | 0.1597 (11) | 0.068 (2) | 0.5 |
C3A | 0.6907 (6) | 0.304 (3) | 0.165 (2) | 0.078 (3) | 0.5 |
H3A | 0.719934 | 0.351665 | 0.201368 | 0.094* | 0.5 |
C7A | 0.57605 (12) | 0.5132 (6) | 0.1977 (3) | 0.0606 (7) | 0.5 |
H7A | 0.583197 | 0.665009 | 0.219610 | 0.073* | 0.5 |
C7B | 0.55635 (17) | 0.3624 (6) | 0.1855 (4) | 0.0718 (8) | 0.5 |
H7B | 0.535252 | 0.247067 | 0.184062 | 0.086* | 0.5 |
C8A | 0.53286 (18) | 0.4571 (11) | 0.2071 (5) | 0.0719 (10) | 0.5 |
H8A | 0.523243 | 0.308082 | 0.187627 | 0.086* | 0.5 |
F1B | 0.7249 (2) | 0.0741 (8) | 0.0571 (10) | 0.1296 (17) | 0.5 |
C2B | 0.6426 (8) | 0.427 (3) | 0.207 (3) | 0.101 (7) | 0.5 |
H2B | 0.640642 | 0.557907 | 0.272500 | 0.121* | 0.5 |
F1A | 0.7162 (2) | −0.0331 (7) | 0.0539 (9) | 0.1216 (16) | 0.5 |
C3B | 0.6810 (6) | 0.362 (3) | 0.170 (3) | 0.091 (4) | 0.5 |
H3B | 0.706072 | 0.453802 | 0.196703 | 0.109* | 0.5 |
C5B | 0.6471 (8) | 0.031 (3) | 0.034 (2) | 0.088 (6) | 0.5 |
H5B | 0.649620 | −0.101089 | −0.029744 | 0.105* | 0.5 |
C1B | 0.6027 (3) | 0.2985 (14) | 0.1472 (11) | 0.0596 (16) | 0.5 |
C6B | 0.6088 (5) | 0.093 (2) | 0.0673 (17) | 0.066 (2) | 0.5 |
H6B | 0.584355 | −0.001676 | 0.037142 | 0.079* | 0.5 |
C4B | 0.6846 (7) | 0.157 (4) | 0.090 (2) | 0.084 (5) | 0.5 |
O1 | 0.5095 (2) | 0.8393 (4) | 0.2453 (17) | 0.1042 (17) | 0.5 |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C4A | 0.099 (8) | 0.072 (7) | 0.067 (4) | 0.021 (5) | 0.004 (4) | −0.009 (4) |
C5A | 0.096 (8) | 0.054 (4) | 0.081 (7) | 0.001 (5) | −0.001 (5) | 0.005 (4) |
C2A | 0.116 (8) | 0.054 (4) | 0.075 (7) | 0.001 (5) | 0.007 (5) | 0.002 (4) |
C6A | 0.070 (4) | 0.055 (7) | 0.074 (4) | 0.010 (4) | 0.008 (3) | 0.005 (4) |
C8B | 0.085 (4) | 0.065 (3) | 0.072 (2) | −0.010 (2) | 0.0129 (18) | 0.0033 (19) |
C9 | 0.0732 (15) | 0.0795 (14) | 0.0696 (12) | 0.000 | 0.0120 (9) | 0.000 |
C1A | 0.104 (6) | 0.044 (4) | 0.050 (2) | −0.008 (3) | −0.005 (2) | −0.004 (3) |
C3A | 0.072 (4) | 0.080 (10) | 0.080 (3) | −0.006 (5) | 0.006 (3) | −0.002 (5) |
C7A | 0.070 (2) | 0.0509 (17) | 0.0624 (14) | −0.0034 (18) | 0.0138 (13) | −0.0015 (11) |
C7B | 0.085 (3) | 0.064 (2) | 0.0647 (17) | −0.006 (2) | 0.0035 (16) | 0.0017 (14) |
C8A | 0.079 (3) | 0.063 (3) | 0.073 (2) | −0.011 (3) | 0.0124 (17) | −0.0020 (19) |
F1B | 0.094 (3) | 0.149 (4) | 0.154 (3) | 0.036 (3) | 0.046 (2) | 0.017 (4) |
C2B | 0.165 (17) | 0.079 (8) | 0.059 (4) | 0.001 (8) | 0.015 (7) | −0.008 (5) |
F1A | 0.114 (3) | 0.122 (3) | 0.127 (2) | 0.038 (3) | 0.0131 (19) | −0.015 (3) |
C3B | 0.105 (12) | 0.064 (8) | 0.099 (5) | −0.006 (6) | 0.001 (6) | 0.006 (5) |
C5B | 0.126 (13) | 0.078 (9) | 0.060 (4) | 0.000 (6) | 0.019 (5) | −0.006 (4) |
C1B | 0.077 (4) | 0.046 (5) | 0.056 (2) | 0.007 (3) | 0.010 (3) | −0.004 (3) |
C6B | 0.078 (6) | 0.056 (6) | 0.065 (2) | 0.013 (4) | 0.008 (2) | 0.001 (4) |
C4B | 0.066 (4) | 0.098 (14) | 0.092 (7) | 0.010 (6) | 0.023 (5) | 0.019 (7) |
O1 | 0.105 (6) | 0.0680 (12) | 0.142 (2) | 0.0007 (13) | 0.026 (5) | −0.0001 (18) |
Geometric parameters (Å, º) top
C4A—C5A | 1.35 (4) | C3A—H3A | 0.9300 |
C4A—F1A | 1.36 (2) | C7A—C8A | 1.357 (7) |
C4A—C3A | 1.37 (3) | C7A—H7A | 0.9300 |
C5A—C6A | 1.48 (2) | C7B—C1B | 1.518 (10) |
C5A—H5A | 0.9300 | C7B—H7B | 0.9300 |
C2A—C1A | 1.28 (3) | C8A—H8A | 0.9300 |
C2A—C3A | 1.45 (2) | F1B—C4B | 1.37 (2) |
C2A—H2A | 0.9300 | C2B—C3B | 1.29 (2) |
C6A—C1A | 1.414 (11) | C2B—C1B | 1.44 (2) |
C6A—H6A | 0.9300 | C2B—H2B | 0.9300 |
C8B—C7B | 1.291 (6) | C3B—C4B | 1.36 (3) |
C8B—C9 | 1.452 (5) | C3B—H3B | 0.9300 |
C8B—H8B | 0.9300 | C5B—C6B | 1.27 (3) |
C9—O1 | 1.211 (3) | C5B—C4B | 1.37 (3) |
C9—O1i | 1.211 (3) | C5B—H5B | 0.9300 |
C9—C8A | 1.531 (6) | C1B—C6B | 1.380 (9) |
C9—C8Ai | 1.531 (6) | C6B—H6B | 0.9300 |
C1A—C7A | 1.413 (11) | O1—O1i | 0.588 (10) |
| | | |
C5A—C4A—F1A | 117.5 (19) | C2A—C3A—H3A | 121.8 |
C5A—C4A—C3A | 124 (2) | C8A—C7A—C1A | 129.7 (6) |
F1A—C4A—C3A | 118 (2) | C8A—C7A—H7A | 115.1 |
C4A—C5A—C6A | 116.4 (18) | C1A—C7A—H7A | 115.1 |
C4A—C5A—H5A | 121.8 | C8B—C7B—C1B | 124.6 (6) |
C6A—C5A—H5A | 121.8 | C8B—C7B—H7B | 117.7 |
C1A—C2A—C3A | 123.7 (17) | C1B—C7B—H7B | 117.7 |
C1A—C2A—H2A | 118.1 | C7A—C8A—C9 | 119.8 (5) |
C3A—C2A—H2A | 118.1 | C7A—C8A—H8A | 120.1 |
C1A—C6A—C5A | 119.6 (15) | C9—C8A—H8A | 120.1 |
C1A—C6A—H6A | 120.2 | C3B—C2B—C1B | 120.6 (18) |
C5A—C6A—H6A | 120.2 | C3B—C2B—H2B | 119.7 |
C7B—C8B—C9 | 127.4 (6) | C1B—C2B—H2B | 119.7 |
C7B—C8B—H8B | 116.3 | C2B—C3B—C4B | 119 (2) |
C9—C8B—H8B | 116.3 | C2B—C3B—H3B | 120.3 |
O1—C9—O1i | 28.1 (5) | C4B—C3B—H3B | 120.3 |
O1—C9—C8B | 93.5 (3) | C6B—C5B—C4B | 120.9 (17) |
O1i—C9—C8B | 121.6 (3) | C6B—C5B—H5B | 119.6 |
O1—C9—C8Bi | 121.6 (3) | C4B—C5B—H5B | 119.6 |
O1i—C9—C8Bi | 93.5 (3) | C6B—C1B—C2B | 116.4 (12) |
O1—C9—C8A | 120.8 (3) | C6B—C1B—C7B | 119.2 (8) |
O1i—C9—C8A | 148.4 (3) | C2B—C1B—C7B | 124.0 (11) |
O1—C9—C8Ai | 148.4 (3) | C5B—C6B—C1B | 121.6 (17) |
O1i—C9—C8Ai | 120.8 (3) | C5B—C6B—H6B | 119.2 |
C8A—C9—C8Ai | 90.6 (4) | C1B—C6B—H6B | 119.2 |
C2A—C1A—C7A | 121.3 (12) | C3B—C4B—F1B | 121.9 (18) |
C2A—C1A—C6A | 119.3 (13) | C3B—C4B—C5B | 120.4 (18) |
C7A—C1A—C6A | 119.3 (10) | F1B—C4B—C5B | 117.6 (19) |
C4A—C3A—C2A | 116.3 (19) | O1i—O1—C9 | 76.0 (2) |
C4A—C3A—H3A | 121.8 | | |
| | | |
F1A—C4A—C5A—C6A | 180.0 (12) | O1i—C9—C8A—C7A | 20.9 (13) |
C3A—C4A—C5A—C6A | 4 (3) | C8Ai—C9—C8A—C7A | −163.9 (4) |
C4A—C5A—C6A—C1A | −2 (2) | C1B—C2B—C3B—C4B | −7 (3) |
C7B—C8B—C9—O1 | −169.9 (7) | C3B—C2B—C1B—C6B | 7 (2) |
C7B—C8B—C9—O1i | −168.5 (8) | C3B—C2B—C1B—C7B | 179.7 (13) |
C7B—C8B—C9—C8Bi | 10.8 (3) | C8B—C7B—C1B—C6B | −162.7 (7) |
C3A—C2A—C1A—C7A | 175.8 (13) | C8B—C7B—C1B—C2B | 24.7 (13) |
C3A—C2A—C1A—C6A | −6 (2) | C4B—C5B—C6B—C1B | 6 (2) |
C5A—C6A—C1A—C2A | 3.8 (18) | C2B—C1B—C6B—C5B | −6.2 (18) |
C5A—C6A—C1A—C7A | −178.3 (10) | C7B—C1B—C6B—C5B | −179.4 (11) |
C5A—C4A—C3A—C2A | −6 (3) | C2B—C3B—C4B—F1B | −176.3 (16) |
F1A—C4A—C3A—C2A | 177.9 (13) | C2B—C3B—C4B—C5B | 7 (3) |
C1A—C2A—C3A—C4A | 7 (3) | C6B—C5B—C4B—C3B | −6 (3) |
C2A—C1A—C7A—C8A | −165.4 (11) | C6B—C5B—C4B—F1B | 176.9 (14) |
C6A—C1A—C7A—C8A | 16.8 (10) | C8B—C9—O1—O1i | 178 (3) |
C9—C8B—C7B—C1B | 177.1 (4) | C8Bi—C9—O1—O1i | −3 (3) |
C1A—C7A—C8A—C9 | −179.6 (5) | C8A—C9—O1—O1i | 171 (2) |
O1—C9—C8A—C7A | 13.2 (8) | C8Ai—C9—O1—O1i | −14 (4) |
Symmetry code: (i) −x+1, y, −z+1/2. |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
C3A—H3A···F1Aii | 0.93 | 2.59 | 3.437 (17) | 151 |
C3A—H3A···F1Bii | 0.93 | 2.66 | 3.477 (17) | 146 |
C3B—H3B···F1Aii | 0.93 | 2.82 | 3.563 (19) | 138 |
C3B—H3B···F1Bii | 0.93 | 2.71 | 3.519 (19) | 146 |
C7B—H7B···O1iii | 0.93 | 2.84 | 3.745 (6) | 163 |
C7B—H7B···O1iv | 0.93 | 2.59 | 3.448 (4) | 154 |
Symmetry codes: (ii) −x+3/2, y+1/2, −z+1/2; (iii) −x+1, y−1, −z+1/2; (iv) x, y−1, z. |
Determination of the IC50 (µmol l-1) of synthetic bischalcones against
tumour cell lines (trust range of 95%; NT means not tested) topCompound | PC3 | HCT-116 | SNB-19 |
1 | 18.74 | 5.15 | 27.00 |
| (17.11–20.59) | (4.48–5.89) | (24.44–29.85) |
2 | 32.55 | 8.01 | 43.18 |
| (28.28–37.48) | (7.19–8.97) | (38.08–49.01) |
3 | >60 | 12.98 | >60 |
| | (11.48–14.71) | |
Doxorubicin | 0.81 | 0.22 | NT |
| (0.63–0.99) | (0.17–0.31) | |