Crystal structures, DFT calculations and Hirshfeld surface analysis of two (E)-3-(aryl)-1-(naphthalen-1-yl)prop-2-en-1-one chalcone derivatives, potential Mycobacterium tuberculosis Enoyl ACP reductase (InhA) inhibitors and optical materials: conformational differences within the prop-2-en-1-one unit

Article abstract of DOI:10.1016/j.molstruc.2021.131091

A combined structural and computational study has been conducted on two chalcone compounds, namely (E)-3-(4-bromophenyl)-1-(4,8-dimethoxynaphthalen-1-yl)prop-2-en-1-one (1), and (E)-3-(3,4-dichlorophenyl)-1-(4,8-dimethoxynaphthalen-1-yl)prop-2-en-1-one (2). These compounds are members of a series of compounds identified from a molecular modelling study as potentially active Mycobacterium tuberculosis Enoyl ACP reductase (InhA) inhibitors. In addition, the computational study indicated that the compounds have potential as optical materials. The combined study revealed that both molecules in the solid state displayed similar overall molecular conformations between a ‘‘T’’ and a ‘‘Y’’ shape, but with different arrangements in the bridging prop-2-en-1-one unit: an anti-periplanar in 1 and a syn-periplanar in 2. The experimental and calculated bond lengths and angles for anti-periplanar 1 and syn-periplanar 2 were generally in good agreement.Theoretical calculations at the B3LYP/DGTZVP level in the gas phase, DMSO and water media indicated that for both compounds, the syn-periplanar form was the energy local minimum while the anti-periplanar form was the energy global minimum. However, the energy differences are very small, with slight variations when using the different basis sets (0.80 and 0.84 kcal/mol using the B3LYP/DGTVP theory level in gas phase, 0.28 and 0.32 in DMSO and 0.27 and 0.31 kcal/mol in water). The differences in the solid state arrangements within the bridging prop-2-en-1-one unit in 1 and 2 arise from variations in the intermolecular interactions, with halogen bonds being considered to be an important factor in stabilizing a syn-periplanar arrangement in compound 2. PLATON and Hirshfeld surface analyses confirmed the important intermolecular interactions in 1 and 2. Calculations were also carried out on the electronic and vibrational spectra, dipole moments and charge distributions of 1 and 2. The HOMO was located in the dimethoxynaphthalenyl region of the molecule with mild donor character, while the LUMO was located in the propenyl and phenyl regions of each molecule. The energy gaps between these orbitals are 3.35 eV for 1 3.25 eV for 2. The delocalization present in compounds 1 and 2 facilitates the HOMO-LUMO charge transfer process. The total electronic molecular dipolar moments (μ_Total) were calculated to be 4.1511 and 5.9316 D for 1 and 2, respectively. The values of μ_Total found for 1 and 2 are both larger than reported values for similar compounds, indicating that the compounds studied here should exhibit a good non-linear optical response.

Full text of DOI:10.1016/j.molstruc.2021.131091

Journal of Molecular Structure 1246 (2021) 131091
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstr
Crystal structures, DFT calculations and Hirshfeld surface analysis of
two (E)-3-(aryl)-1-(naphthalen-1-yl)prop-2-en-1-one chalcone
derivatives, potential Mycobacterium tuberculosis Enoyl ACP reductase
(InhA) inhibitors and optical materials: conformational differences
within the prop-2-en-1-one unit
Magaly Girão Albuquerquea, Raoni Schroeder B. Gonçalvesa,∗
,
Camilo Henrique da Silva Limaa, Fernanda Lima de Azevedo Maiaa,
Sérgio de Paula Machadoa, Laudicéa do Nascimento Oliveiraa, Talis Uelisson da Silvaa,
James L. Wardell b,c, Solange M.S.V. Wardell d,∗
a Instituto de Química, Universidade Federal do Rio de Janeiro, Av. Athos da Silveira Ramos, 149 - Cidade Universitária, Rio de Janeiro, RJ 21941-909, Brazil
b Department of Chemistry, University of Aberdeen, Meston Walk, Old Aberdeen AB24 3UE, Scotland
c Instituto de Tecnologia em Fármacos e Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, RJ 21041-250 Brazil
d CHEMSOL, 1 Harcourt Road, Aberdeen AB15 5NY, Scotland
a r t i c l e i n f o
a b s t r a c t
Article history:
A
combined structural and computational study has been conducted on two chalcone compounds,
Received 19 April 2021
Revised 18 June 2021
Accepted 9 July 2021
Available online 20 July 2021
namely (E)-3-(4-bromophenyl)-1-(4,8-dimethoxynaphthalen-1-yl)prop-2-en-1-one (1), and (E)-3-(3,4-
dichlorophenyl)-1-(4,8-dimethoxynaphthalen-1-yl)prop-2-en-1-one (2). These compounds are members
of a series of compounds identified from a molecular modelling study as potentially active Mycobacterium
tuberculosis Enoyl ACP reductase (InhA) inhibitors. In addition, the computational study indicated that the
compounds have potential as optical materials.
Keywords:
Mycobacterium tuberculosis Enoyl ACP
reductase (InhA) inhibitors
X-ray crystallography
The combined study revealed that both molecules in the solid state displayed similar overall molecular
conformations between a ‘‘T’’ and a ‘‘Y’’ shape, but with different arrangements in the bridging prop-2-
en-1-one unit: an anti-periplanar in 1 and a syn-periplanar in 2. The experimental and calculated bond
lengths and angles for anti-periplanar 1 and syn-periplanar 2 were generally in good agreement.Theoretical
calculations at the B3LYP/DGTZVP level in the gas phase, DMSO and water media indicated that for both
compounds, the syn-periplanar form was the energy local minimum while the anti-periplanar form was
the energy global minimum. However, the energy differences are very small, with slight variations when
using the different basis sets (0.80 and 0.84 kcal/mol using the B3LYP/DGTVP theory level in gas phase,
0.28 and 0.32 in DMSO and 0.27 and 0.31 kcal/mol in water). The differences in the solid state arrange-
ments within the bridging prop-2-en-1-one unit in 1 and 2 arise from variations in the intermolecular
interactions, with halogen bonds being considered to be an important factor in stabilizing a syn-periplanar
arrangement in compound 2. PLATON and Hirshfeld surface analyses confirmed the important intermolec-
ular interactions in 1 and 2.
B3LYP/DGTZVP level calculations
chalcones
Hirshfeld surface analysis
Calculations were also carried out on the electronic and vibrational spectra, dipole moments and charge
distributions of 1 and 2. The HOMO was located in the dimethoxynaphthalenyl region of the molecule
with mild donor character, while the LUMO was located in the propenyl and phenyl regions of each
molecule. The energy gaps between these orbitals are 3.35 eV for 1 3.25 eV for 2. The delocalization
present in compounds 1 and 2 facilitates the HOMO-LUMO charge transfer process.
∗
Corresponding authors.
https://doi.org/10.1016/j.molstruc.2021.131091
0022-2860/© 2021 Elsevier B.V. All rights reserved.

M.G. Albuquerque, R.S.B. Gonçalves, C.H.d.S. Lima et al.
Journal of Molecular Structure 1246 (2021) 131091
The total electronic molecular dipolar moments (μTotal ) were calculated to be 4.1511 and 5.9316 D for
1 and 2, respectively. The values of μTotal found for 1 and 2 are both larger than reported values for
similar compounds, indicating that the compounds studied here should exhibit a good non-linear optical
response.
© 2021 Elsevier B.V. All rights reserved.
the residue and the aqueous phase was extracted with chloroform
(3×50 mL). The combined organic phases were dried over sodium
sulfate and concentrated under vacuum. The product was obtained
1. Introduction
Chalcones form a well-studied chemical group having a 1,3-
diaryl-2-propen-1-one framework. Much of the study of chalcones,
both man-made and natural compounds, has centred on their
wide-ranging uses as biological agents [1–4]. Moreover, their po-
tential utility extends beyond biological uses and includes such ar-
eas as optical materials [5–9] and sensors [10,11].
in 86% yield and used in the following step without further purifi-
cation.
2.2. Synthesis of 1-(1,5-dimethoxynaphthalen-8-yl)ethenone, 3
To a solution of 1,5-dimethoxynaphthalene (2.5g, 13.3 mmol) in
freshly distilled acetic anhydride (20 mL) at 0° C under argon, was
added dropwise with stirring, boron trifluoride etherate (5.2 mL,
42.2 mmol). The reaction mixture was stirred at 0°C for 40 min,
10% NaOH aqueous solution (100 mL) was added and the mix-
ture was extracted with ethyl acetate (3×20 mL). The collected
organic phases were washed with brine, dried over Na2SO4 and
concentrated under vacuum. The crude product was purified by
flash chromatography (using 20% ethyl acetate/hexane as eluent):
the purified product, 3, was obtained in a 55% yield.
We wish to report a detailed structural and computational
study of two chalconederivatives, namely (E)-3-(4-bromophenyl)-
1-(4,8-dimethoxynaphthalen-1-yl)prop-2-en-1-one, 1, and (E)-3-
(3,4-dichlorophenyl)-1-(4,8-dimethoxynaphthalen-1-yl)prop-2-en-
1-one, 2, see Scheme 1. These compounds are part of a series
of compounds, found to have great potential as anti-tuberculosis
(TB) agents and properties indicating potential as non-linear
optical materials. Iinvestigations of the potential of chalcones as
anti-tuberculosis (TB) agents have attracted our intention [12–18].
TB is one of the major causes of deaths worldwide and it was the
leading cause among infectious diseases until the COVID-19 emer-
gence. The discovery of new drugs against TB using a target-based
approach is a promising strategy, such as in the development
of new Mycobacterium tuberculosis Enoyl ACP reductase (InhA)
inhibitors [19–24]. Our group has worked on the development
of such inhibitors employing molecular modelling tools and a
virtual screening protocol. In the approach to the identification of
suitable candidates, a number of diaryl ether derivatives [20,21]
underwent tri-dimensional pharmacophore model construction
using the PharmaGist server [25]. The candidates selected in
the ZincPharmer server, using the pharmacophore model [26],
were submitted to a molecular docking and molecular dynamics
2.2.1. General synthesis of chalcones 1 and 2
Chalcones 1 and 2 were prepared by the reaction between
compound 3 and the appropriate substituted benzaldehyde, see
Scheme 1.
A mixture of 1-(4,8-dimethoxynaphthalen-1-yl) methyl ketone,
3 (0.24 g, 1.06 mmol), KOH (0.17, 4.24 mmol), the benzaldehyde
(1.2 mmol) and aqueous methanol (40 mL, v:v MeOH: H2O = 4:1)
was heated at 90°C, with magnetic stirring overnight. The reac-
tion mixture was rotary evaporated and to the residue was added
aqueous H2SO4 (15 mL, 6M) and the resulting solution was ex-
tracted with chloroform (3×10 mL). The combined organic phases
were washed with brine, dried over Na2SO4 and concentrated un-
der vacuum. The crude product was purified by flash chromatogra-
phy (using 20% ethyl acetate/hexane as eluent).
simulation study, using
which resulted in the identification of ZINC4026219 as a potential
candidate. Biological assays have been performed on series
of (E)-3-(4-phenyl)-1-(4,8-dimethoxynaphthalen-1-yl)prop-2-en-
a previously published protocol [27],
a
2.2.2. (E)-3-(4-Bromophenyl)-1-(4,8-dimethoxynaphthalen-1-yl)prop-
1-one compounds, and will be published as a separate article,
which will also include the results of the docking experiments.
The X-ray structural study indicated that 1 and 2 exhibited an
interesting molecular conformational differences, which war-
2-en-1-one,
1
ranted
a comprehensive computational study to cover factors
relevant to other properties of compounds 1 and 2, e.g., as optical
materials [5–9], especially as there are reports indicating that
naphthalenyl-chalcones, in particular, exhibit particularly useful
optical properties [28–30]. Compounds 1 and 2, with methoxy
substituents in the naphthalenyl moiety and halogen substituents
in the phenyl group, fit into the category of push-pull chalcones
[28], and references therein] known to have significant non-linear
optical properties.
2. EXPERIMENTAL SECTION
2.1. Experimental procedure
Synthesis of 1,5-dimethoxynaphthalene: A reaction mixture
of 1,5-dihydroxynaphthalene, 2, (5.05 g, 31.5 mmol), iodomethane
(8.94 g, 63.0 mmol), K2CO3 (4.76g, 34.4 mmol) and acetonitrile
(120 mL) was heated at 80°C with stirring for 24h, cooled to room
temperature, and rotary evaporated. Water (200 mL) was added to
Yield: 52%, yellow solid, m.p. 162 – 164°C. 1H NMR (CDCl3, 500
MHz) δ: 7.93 (1H, d, H-4, J = 8.5 Hz), 7.47-7.43 (3H, m, H-3, H-
3’’ e H-5’’), 7.31-7.25 (3H, m, H-7, H-2’’ e H-6’’), 7.05 (1H, d, H-3’,
J = 16.1 Hz), 7.00 (1H, d, H-2’, J=16.1 Hz), 6.90 (1H, d, H-2, J=7.6
Hz), 6.86 (1H, d, H-6, J=7.9 Hz), 4.04 (3H, s, -OCH3), 3.80 (3H,
2

M.G. Albuquerque, R.S.B. Gonçalves, C.H.d.S. Lima et al.
Journal of Molecular Structure 1246 (2021) 131091
Scheme 1. Preparation of compounds 1 and 2.
s, -OCH3). 13C NMR (CDCl3, 100 MHz) δ: 197.88, 156.42, 154.79,
140.66, 134.04, 132.05, 129.72, 129.42, 126.91, 126.14, 125.68,
124.08, 123.72, 114.96, 107.04, 103.60, 55.76, 55.54.IR ν, cm−1
:
3440, 3058, 3009, 2964, 2937, 2853, 2834, 1920, 1891, 1834, 1744,
1667, 1606, 1585, 1562, 1508, 1483, 1460, 1444, 1410, 1398, 1376,
1334, 1318, 1288, 1261, 1224, 1190, 1162, 1109, 1092, 1075, 1067,
1051, 1005, 979, 939, 918, 879, 866, 805, 785, 770, 760, 728, 692,
639, 623, 606, 584, 524, 506, 485, 465.
2.2.3. 5 (E)-3-(3,4-dichlorophenyl)-1-(4,8-dimethoxynaphthalen-1-
yl)prop-2-en-1-one,
Fig. 1. Chemical structure of ZINC40264219.
2
using spherical harmonics, implemented in SCALE3 ABSPACK scal-
ing algorithm. The programs ORTEP-3 for Windows [32] and MER-
CURY [33] were used in the preparation of the Figures. SHELXL97
[34] and PLATON [35] were used in the calculation of molecu-
lar geometry. The structures were solved by direct methods us-
ing SHELXS-97 [36] and fully refined by means of the program
SHELXS-97 [34]. All hydrogen atoms were placed in calculated po-
sitions .Crystal data and structure refinement details are listed in
Table 1.
Fig. 1.
2.4. DFT calculations
The optimized geometries were obtained with the functional
B3LYP Exchange-correlation hybrid [37,38]. The DGTZVP basis set
[39,40] was used. Solvent effects were considered using the Polar-
ized Continuum Method (PCM) [41-43]. The theoretical IR spectra
for each compound was obtained. Absence of imaginary frequen-
cies indicated the structures corresponding to minimum energy. All
calculations were performed with the Gaussian 09 package [44].
Yield: 15%, yellow solid, m. p. 109-113°C. 1H NMR 1H (CDCl3,
500 MHz) δ: 7.92 (1H, d, H-4, J = 8.5 Hz), 7.48 (1H, s, H-2’’), 7.43
(1H, t, H-3, J = 8.5 Hz), 7.38 (1H, d, H-5’’, J = 8.4 Hz), 7.29 (1H, d,
H-7, J = 7.9 Hz), 7.25 (1H, d, H-6’’, J = 8.4 Hz), 7.00 (1H, d, H-3’,
J = 16.1 Hz), 6.96 (1H, d, H-2’, J = 16.1 Hz), 6.89 (1H, d, H-2, J = 7.7
Hz), 6.84 (1H, d, H-6, J = 7.9 Hz), 4.02 (3H, s, -OCH3), 3.79 (3H, s,
-OCH3).
2.5. Hirshfeld surface analysis
13C NMR (CDCl3, 100 MHz) δ: 197.39, 156.55, 154.70, 138.90,
135.24, 133.68, 133.14, 130.79, 130.65, 129.59, 129.18, 126.91,
126.19, 125.77, 123.67, 115.06, 107.13, 103.62, 55.77, 55.55. IR ν,
cm−1: 3448, 3108, 3005, 2932, 2853, 1874, 1647, 1630, 1589, 1553,
1512, 1464, 1410, 1383, 1325, 1289, 1257, 1241, 1198, 1192, 1175,
1150, 1126, 1084, 1058, 1027, 1009, 978, 955, 916, 889, 870, 823,
812, 779, 757, 678, 657, 608, 567, 555, 528, 475 461, 438, 409.
The Hitshfeld surfaces (HS) were obtained using the Crystal Ex-
plorer 17.5 package [45]. All conformers were determined within a
˚
radius of 6 A from the HS. Hydrogen bonds for each compound
were determined and only arrangements having hydrogen bond
connections to the surface were analysed.
3. Results and Discussion
2.3. Experimental X-ray crystallography
3.1. Molecular structures
˚
Data for compound 1, using Mo-Kα radiation (λ = 0.71075 A)
˚
and compound 2, using CuKα radiation (λ= 1.54184 A), were ob-
3.1.1. X-Ray determination
tained at 100 K by means of a XtaLAB AFC11 (RCD3): quarter-chi
single diffractometer of the National Crystallography Service, based
at the University of Southampton, UK. Data collection, data re-
duction and unit cell refinement were achieved with CrysAlisPro
1.171.40.39a [31]. Correction for absorption was achieved using
CrysAlisPro 1.171.40.39a [31] via an empirical absorption correction
The samples used in the crystal structure determination were
grown by slow evaporation of methanol solutions at room tem-
perature. Compound 1 crystallizes in the monoclinic space group,
P21/c, with z = 4, and compound 2 crystallizes in the monoclinic
space group, P21/n, with z = 4. Each asymmetric unit contains one
chalcone molecule.
3

M.G. Albuquerque, R.S.B. Gonçalves, C.H.d.S. Lima et al.
Journal of Molecular Structure 1246 (2021) 131091
Table 1
Experimental details.
1
2
Empirical formula
Formula weight
Temperature, K
C21H17BrO3
397.26
C21H16Cl2O3
387.24
100(2)
100(2)
˚
Wavelength, A
0.71073
1.54184
Crystal system Space group
Unit cell dimensions
Monoclinic, P21/c
Monoclinic, P21/n
˚
a, A
14.5736(20
7.31180(12)
15.9357 (3)
92.5250(14)
1696.45(5)
7.10330(8)
9.39400(11)
26.6746(3))
94.5130(10)
1774.43(4)
4
˚
b, A
˚
c, A
β,o
˚
Volume, A3
Z
4
Density (calc.) Mg/m3
Absorption coefft mm-1
F(000)
1.555
1.450
2.440
3.447
808
800
Crystal size mm
Theta range for data collection
Index
0.386 x 0.184 x 0.060
2.559 to 27.484°.
-18<=h<=18,
-9<=k<=9,
-19<=l<=20
20173
0.360 x 0.160 x 0.10060
3.324 to 67.078°.
-8<=h<=8,
ranges
-11<=k<=11,
-3119<=l<=31
30798
Reflections collected
Independent reflections
Completeness to theta
Absorption correction
Max. and min. transmission
Refinement method
3894[R(int) = 0.0400]
99.9 %
3148 [R(int) = 0.0516]
99.4 %
Gaussian
Semi-empirical from equivalents
1.000 and 0.424
Full-matrix least-squares on F2
3148/0/237
1.000 and 0.487
Full-matrix least-squares on F2
3894/0/228
0.83
Data / restraints/parameters
Goodness-of-fit on F2
Final R indices [I>2sigma(I)]
All data
1.062
0.029, 0.095
0.035, wR2 = 0.105
0.38 and -0.59
1917405
0.040, 0.119
0.041 wR2 = 0.120
0.76 and -0.42
2076631
˚
Largest diff. peak and hole e.A-3
CCDC no
Table 2
Intramolecular parameters (A, o).
˚
(a) Intramolecular hydrogen bonds
•••
•••
•••
•••
A
Compound
D—H
A
D—H
0.95
H
A
D
A
D—H
100
•••
1
C13—13
O11
2.54
2.856(2)
(b) Selected bond lengths in the linker unit: C1-C11(O11)-C12-C13-C14,
Bond
1
2
Average values in unhindered methoxy chalcones, 4 [46]
C1-C11
1.502(2)
1.226(2)
1.486(3)
1.334(2)
1.463(3)
1.517(3)
1.221(2)
1.472(3)
1.333(3)
1.462(3)
1.465
1.252
1.472
1.336
1.459
C11-O11
C11-C12
C12-C13
C13-C14
(c) Interplanar angles
Angles between planes
Compound Naphthenyl ring and C1-C11(O11)-C12-C13-C14 C1-C11(O11)-C12-C13-C14 and phenyl ring Phenyl ring and naphthenyl ring
1
2
53.83(7)
73.12(8)
5.83(8)
3.12(9)
50.20(7)
70.01(8)
The atom arrangements and crystallographic numbering
schemes for 1 and 2 are shown in Fig. 2. As is apparent from
Fig. 2 and from the torsional angles listed in Table 2, the molecu-
lar conformations of the two molecules in the solid state exhibit
differences within the prop-2-en-1-one unit: the carbonyl oxygen,
O11, and its vicinal hydrogen (H12) are anti-periplanar in 1 and
syn-periplanar in 2. One consequence of this is that O11 is involved
in different intramolecular hydrogen bonds in the two molecules:
in compound 1 C13—H13•••O11 hydrogen bond is present and in
compound 2, C12—H12•••O11 hydrogen bond is present.
Each molecule has a conformation between a ‘’T’’ and a ‘’Y’’
shape: the angles between the best planes through the naph-
thalenyl and phenyl rings in 1 and 2 are 50.20(7) and 70.01(8)o,
respectively, see Fig. 2 and Table 2. The linker groups, -C11(O11)-
C12=C13-, and the phenyl rings in each compound are near co-
planar with small interplanar angles of 5.83(8) and 3.12(9)° for
1 and 2, respectively. The interplanar angles in Table 2 indicate
that the rotations from planarity occur in opposite senses in pass-
ing from the naphthalenyl ring to the linker unit and then to
the phenyl ring. For each compound, the large angle between the
planes of the naphthalenyl ring and the rest of the molecule is due
to the steric hindrance generated by the methoxy substituent on
C8 of the napththalenyl ring. It is noticeable too that the smaller
O)n examination of the molecular conformations, there appears
to be no steric reason by which the two molecules do not both
have syn-periplanar or anti-periplanar conformations.
4

M.G. Albuquerque, R.S.B. Gonçalves, C.H.d.S. Lima et al.
Journal of Molecular Structure 1246 (2021) 131091
Fig. 2. Atom arrangements, crystallographic numbering schemes and views of the conformations of 1 and 2. Probability ellipsoids are drawn at the 50% level.
interplanar angle between the naphthalenyl ring and the prop-
2-en-1-one linker unit occurs in compound 1. The antiperipla-
nar arrangement of the carbonyl oxygen and its vicinal hydrogen
atom in compound 1 results in the carbonyl group being situated
away from the C8 methoxy group. As highlighted in a recent re-
port [43], the vast majority of simple methoxy substituted (E)-1-
(2-hydroxyphenyl)-3-phenylprop-2-en-1-one derivatives have near
planar cores with interplanar angles between the terminal aryl
groups generally less than 15o.
3.1.2. Theoretical study of the molecular structure
The crystallographic structures of and
1
2 were used as
the inputs in the calculations. The theoretical calculations at
B3LYP/DGTZVP level indicate that, for both compounds, the syn-
periplanar form was found as an energy local minimum while the
anti-periplanar form was found to be a global energy minimum,
with the anti-periplanar form being the more stable for both com-
pounds. Thus, the crystallographic structure of 1 matched a global
minimum while the crystallographic structure of 2 matched a lo-
cal minimum. However, the energy differences are found to be
very small with slight variations when using different basis sets,
e.g., the relative energy for compounds 1 and 2, is 0.80 and 0.84
kcal/mol using the B3LYP/DGTVP theory level in gas phase, respec-
tively. These values became 0.28 and 0.32 in DMSO and 0.27 and
0.31 kcal/mol in water, respectively, see Table 4.
A comparison of the bond lengths in the linker unit, -C11(O11)-
C12=C13-, in 1 and 2, with standard single and double bond
lengths indicates a degree of delocalization in the linker, see
Table 2: also listed in Table 2 are the average values for sim-
ple methoxy substituted (E)-1-(2-hydroxyphenyl)-3-phenylprop-2-
en-1-one derivatives, 4, [46]. The C1-C11 benzylic bonds adjacent
to the naphthalenyl groups are noticeably longer and, the car-
bonyl bonds, C11=O1, slightly shorter in 1 and 2, derivatives i.e.,
are closer to single C-C and double C=O bond lengths than those
in in the methoxy methoxy substituted (E)-1-(2-hydroxyphenyl)-
3-phenylprop-2-en-1-one, 4. However, the formal C=C bonds in
all the linkers have a consistent length as do the other ben-
zylic bonds, C13-C14, adjoining the phenyl groups. This suggests
the delocalization does not extend so strongly from the phenyl
to the naphthalenyl groups in 1 and 2, as in the less hindered
molecules. A complete list of the experimental bond angles and
lengths and a comparison with computed parameters, are shown
in Table 3.
Table 3 lists a comparison of the bond lengths and angles ob-
tained in the X-ray determination and by the theoretical calcula-
tions for 1 in the anti-periplanar and for 2 in the syn-periplanar
forms. As shown in Table 3, there is generally good agreement
between the experimental and theoretical bond lengths and an-
gles. The calculated bond distances and angles are mainly within
a maximum error of 4% of the experimental X-ray values. As listed
in Table 3, the vicinal O11-C11-C12-H12 dihedral angle calculated
for 1 of 179.07o is particularly close to the experimental values of
178.65o. The comparison for compound 2 shows a slightly greater
discrepancy with values 8.34 (calculated) and 2.89o (experimental).
The data indicate that the syn-periplanar conformation is indeed
a local minimum energy structure and not solely a consequence
of solid-state packing. In general, of all the geometric parameters,
dihedral angles, particular for compound 2, exhibit slightly larger
calculated/experimental differences due to the influences of the
The different orientations involving the carbonyl oxygen have
significant effects on the packing and intermolecular interac-
tions displayed by the two compounds, as discussed later, see
Section 3.2.
5

M.G. Albuquerque, R.S.B. Gonçalves, C.H.d.S. Lima et al.
Journal of Molecular Structure 1246 (2021) 131091
Table 3
Comparison of geometric parameters obtained from the X-ray determination from data at 100K and the theoretical calculations using
B3LYP/ DGTZVP/PCM/(H2O).
(a) Bond lengths
Parameter
Compound 1
Compound 2
X-ray
B3LYP/DGTZVP/PCM (H2O)
X-ray
B3LYP/DGTZVP/PCM (H2O)
C11-O11
C4-O4
1.226(2)
1.363(2)
1.367(2)
1.439(3)
1.430(3)
1.334(2)
1.502(2)
1.9030(16)
-
1.24
1.36
1.37
1.43
1.43
1.35
1.51
1.92
1.221(2)
1.363(2)
1.371(2)
1.434(2)
1.432(3)
1.333(3)
1.517(3)
1.24
1.36
1.36
1.43
1.43
1.35
1.51
C9-O9
O4-C21
O9-C20
C12-C13
C11-C1
C17-Br
C17-Cl2
C16-Cl1
O11—-H12
O11—-H13
1.734(2)
1.7352(19)
2.58
1.75
1.75
2.54
3.91
-
3.20
3.32
2.49
2.54
3.77
(b) Bond angle
Compound 1
Compound 2
Parameter
X-ray
B3LYP/DGTZVP/PCM (H2O)
X-ray
B3LYP/DGTZVP/PCM (H2O)
C4-O4-C21
C9-O9-C20
O11-C11-C1
O11-C11-C12
C11-C1-C2
C11-C12-C13
O4-C4-C3
116.33(14)
117.49(14)
120.92(19)
122.37(16)
116.05(17)
122.26(16)
124.51(16)
123.87(16)
119.67(13)
118.45
119.03
120.31
122.10
114.89
121.24
124.438
123.67
119.48
116.77(15)
117.27(15)
119.35(17)
121.40(17)
115.96(17)
122.27(17)
124.12(18)
123.78(19)
118.33
119.02
120.15
119.74
115.88
123.97
124.36
123.75
O9-C9-C8
C18-C17-Br
C18-C17-Cl2
C15-C16-Cl1
Cl2-C17-C16
118.54(14)
118.60(14)
121.53(15)
118.97
118.57
121.60
(c) Dihedral angle
Compound 1
Compound 2
Parameter
X-ray
B3LYP/DGTZVP/PCM (H2O)
X-ray
B3LYP/DGTZVP/PCM (H2O)
O11-C11-C12-C13
O11-C11-C1-C2
O11-C11-C12-H12)
C12-C13-C14-C19
C11-C12-C13-C14
C21-O4-C4-C3
2.2(3)
3.92
177.1(2)
-98.9(2)
2.89
169.06
-75.98
-8.34
-47.4(2)
-177.84
-53.60
-178.65
-178.92
177.86
0.13
-175.79(18)
-178.1917)
-5.5(3)
172.3(2)
-176.2(2)
-3.9(3)
179.30
-177.77
-0.12
C20-O9-C9-C8
-10.3(3)
179.73(14)
-3.68
-3.1 (3)
-1.69
C19-C18-C17-Br
C19-C18-C17-Cl2
C14-C15-C16-Cl1
Cl2-C16-C17-Cl1
C18-C17-C16-Cl1
C15-C16-C17-Cl2
179.93
-175.85(17)
-179.19(16)
-4.1(3)
179.94
-180.00
0.071
176.53(17)
176.42(17)
-179.94
-179.94
crystal environment. As is generally accepted, the effect of the con-
densed phase on the crystalline state is not taken into account in
calculations, e.g., see [47].
anti-forms. These results indicate that the presence of a halogen
in the meta position has no specific nor significant influence on
the energy difference between the gaseous structures. The results
in Table 4 further reinforce the conclusions that the differences in
energies of the syn and anti-forms are generally very small.
It is important to remember that these calculations only con-
sider isolated molecules and do not take into account intermolec-
ular interactions and packing effects, and that the solvent only ef-
fects the dielectric around the molecule [41]. Similar results were
obtained using D95V [48] and 6-311G(d,p) [49,50] base sets.
The energies of the structures generated on rotation in steps
of 30° around the O11-C11-C12-H(vicinal) dihedral angle with sol-
vent effect (water), are listed in Table 5. A greater energy barrier is
observed in the syn-periplanar to anti-periplanar conversion for 2,
than required for the reverse conversion in 1. The transition states
observed for 1 have lower energies than the ones observed for 2,
which thus indicates that the conformational change round O11-
C11-C12-H(vicinal) is more spontaneous in 1. In 1, a maximum rel-
ative energy of 7.52 kcal/mol for 90 and 120 rotations is calcu-
º
3.2. Crystal structures of compounds 1 and 2
lated, whereas in 2, structures with relative energies greater than
9.00 kcal/mol and with, at least one or more imaginary frequency
are determined.
3.2.1. Compound 1
The intermolecular interactions in 1 are C—H•••O and C—
Calculations were also carried out on other halo substituents,
namely the m-chloro-, p-chloro-, m-bromo- and 3,4-dibromo-
analogues, see Table 4. For these 3-chloro and 3-bromo derivatives,
no significant energy differences were calculated between syn- and
H
•••Br hydrogen bonds, C—Br•••π and π•••π stacking interac-
tions obtained using PLATON [35], see Table 6 for details. Of the
oxygen atoms, only the carbonyl oxygen is involved in the in-
termolecular interactions: the C21—H21A•••O11 hydrogen bonds
6

M.G. Albuquerque, R.S.B. Gonçalves, C.H.d.S. Lima et al.
Journal of Molecular Structure 1246 (2021) 131091
Table 4
Relative energies of the anti- and syn conformers of 1, 2 and related halo substituted compounds.
I: anti
I: syn
(a) Relative energies, kcal/mol, calculated with B3LYP
Compound
E(kcal/mol)
Compound
E(kcal/mol)
Compound 2
I (R,R1= 3,4-Br2)
syn
0.31
0.00
syn
0.44
0.00
anti
anti
I (R=H,R1= 4-Cl)
Compound 1
syn
0.26
0.00
syn
0.27
0.00
anti
anti
I (R= H,R1=3-Cl)
I (R= H,R1=3-Br)
syn
0.00
0.00
syn
0.00
0.00
anti
anti
(b) Effect of the dielectric media on the relative energy values, kcal/mol, calculated with B3LYP/DGTZVP
Gas phase
DMSO mediuma
Water mediumb
1( syn-periplanar)
1( anti-periplanar)
2( syn-periplanar)
2( anti-periplanar)
0.80
0.00
0.84
0.00
0.28
0.00
0.32
0.00
0.27
0.00
0.31
0.00
a
= dielectric constant 46.7 volts per meter (V/m).
Dielectric constant = 80.1 volts per meter (V/m).
b
Table 5
Rotations about the dihedral angle, O11-C11-C12-H12 calculated using B3LYP/DGTZVP/PCM (H2O).
Compound 1
Compound 2
Rotation about the dihedral angle, O11-C11-C12-H12
Relative energy (kcal/mol)
State
Relative energy (kcal/mol)
State
0
0.00
2.04
6.15
7.59
4.48
2.17
7.52
mínimum
0.00
2.45
8.87
14.84
9.02
3.81
1.52
mínimum
30
mínimum
mínimum
60
transition state
transition state
transition state
minimum
transition state
transition state
-
90
120
150
180
transition state
transition state
transition state
Table 6
Geometric parameters (A, o) for intermolecular interactions in compounds 1 and 2.
˚
(a) Intermolecular hydrogen and halogen bonds
Symmetry
•••
•••
•••
•••
Compound
D—H
C3—
A
D—H
0.95
H
A
D
A
D—H
134
A
code
1
2.83
2.51
2.52
2.53
3.564(2)
3.366(3)
3.445(2)
3.152(2)
-x,3/2+y,
½-z
•••
H3
Br1
1
2
2
C21—
H21A
C18—
0.98
0.95
0.95
145
163
123
x,5/2-y,
½+z
•••
O11
x,-1+y,z
•••
H18
O9
C18—
x,-1+y,z
•••
H18
O11
(b) Y-X—πinteractions
a
•••
•••
•••
•••
Y Cg
Compound
Y—X
Cg
X
Cg
Xperp
γ
Y—X
Cg
Symmetry code
•••
1
2
C17—Br1
Cg4
3.9330(7)
3.878
3.549
9.60
84.08(5)
64.83(7)
4.1887(18)
3.507(2)
-x,-1/2+y,1/2-z
•••
C16—Cl1
Cg4
3.8736(10)
23.62
1-x,2-y,-z
(c) Off-set, face-to-face π••π interactions
•••
Cg(J)
•••
Cg
Cg(I)
Cg
α
β
γ
CgIperp
CgJperp
Symmetry code
•••
•••
•••
1
2
2
Cg(3)
Cg(3)
Cg(3)
Cg(3)
Cg(3)
Cg(3)
3.7444(10)
3.7085(12)
3.8300(12)
0.00(9)
21.8
21.8
23.4
24.2
3.4761(7)
3.4046(9)
3.4924(9)
3.4761(7)
3.4046(9)
3.4924(9)
-x,1-y,-z
-x,2-y,-z
1-x,2-y,-z
0.00(10)
0.00(10)
23.4
24.2
Cg(3) and Cg(4) = centres of gravities of phenyl and naphthalenyl rings, respectively; α = dihedral Angle between Planes I and J (Deg);
˚
β
=
angle Cg(I)–>Cg(J); γ
=
angle Cg(I)–>Cg(J) vector and normal to plane
J
(Deg); Cg-Cg
=
distance between ring Centroids (A);
˚
˚
CgI_Perp = perpendicular distance of Cg(I) on ring J (A); CgJ_Perp = perpendicular distance of Cg(J) on ring I (A).
7

M.G. Albuquerque, R.S.B. Gonçalves, C.H.d.S. Lima et al.
Journal of Molecular Structure 1246 (2021) 131091
•••
O11 hydrogen bonds, (b) off-set, face-to-face π(phenyl)
Br1 hydrogen bonds, (d) a view looking down the spiral chain formed from a combination of C3—H3—Br1 hydrogen bonds
•••
Fig. 3. Compound 1. (a) A part of a C(9) chain generated by C21—H21A
π
paired molecules, (c) a part of a
(phenyl)
•••
C(12) chain of molecules formed from C3—H3
•••
and C7—Br1
π
interactions.
(naph)
generate C(9) chains of molecules [51] propagated in the direc-
while the C16—Cl1•••O4 halogen bonds form C(11) chains in the
direction of the c axis. As drawn in Fig. 5, the rows of the sheet
are formed from the of C18—H18•••O9 and C18—H18•••O11 hy-
drogen bonds and the rows are linked by the C16—Cl1•••O4 halo-
gen bond. Also, it can be seen that the molecules are orientated
in the opposite sense in alternate rows. The non-planarity of this
sheet is illustrated in Fig. 5b. Both methoxy groups are active in the
supramolecular arrangement of 2. The combination of the C16—
tion of the c axis, see Fig 3a. Another structural subset is an off-
•••
set, face-to-face π(phenyl)
π
linked dimer, see Fig. 3b. C—
(phenyl)
H
•••Br hydrogen bonds, C—Br•••π halogen bonds and C—Br•••π
interactions have been variously shown to be important in crys-
tal packing [52-59], and both types are found in 1: bromine atoms
are involved in forming C3—H3•••Br1 hydrogen bonds, see Fig. 3c,
•••
and C7—Br1
π
interactions. Together the C3—H3•••Br1 hy-
(naph)
•••
•••
•••
π
drogen bonds and C7—Br1
π
interactions generate spiral
Cl1
π
and π(phenyl)
interactions produces the
(phenyl)
(naph)
(phenyl)
•••
chains of molecules, propagated in the direction of the b axis, see
Fig. 3d. Involvement of all the intermolecular interactions gener-
ates a 3-D structure. A view of the packing of compound 1 is
shown in Fig. 4.
column shown in Fig. 5c, while the C7—H7
π
and C21—
(naph)
•••
H21
π
interactions generate the arrangement illustrated in
(naph)
Fig. 5d. Overall, a three-dimension structure is obtained. A packing
figure is shown in Fig. 4b.
3.2.2. Compound 2
3.2.3. Comparisons of structures of 1 and 2
The intermolecular interactions in 2 are C—H•••O hydrogen
bonds and C—Cl•••O halogen bonds [57-60] C—H•••π, and off-
set, face-to-face π•••π stacking interactions, obtained using PLA-
TON [35], see Table 6 for details. Unlike the situation in 1, in 2
the C8 methoxy oxygen, O9, as well as the carbonyl oxygen O1,
are involved in C—H•••O hydrogen bonding. Indeed, the proxim-
As indicated above, calculations indicated that there are only
small energy differences between the local energy minimum syn-
form and the global energy anti-forms for compounds 1 and 2.
Thus, for compound 1, the most stable gas-phase form was main-
tained in the crystalline state, but not for compound 2. The inter-
molecular interactions, C—H•••O and C—H•••Br hydrogen bonds,
C—Br•••π and π•••π stacking interactions in 1 thus, collectively
maintain, or at least do not reduce, the relative stability of the anti-
˚
ity of the two oxygens, O9•••O11 = 2.9642(19)A, due to the syn-
periplanar arrangement, allows both to be involved in a bifurcated
interaction with H18 and formation of a R2 (5) ring [51], see
1
form. On the other hand, the collective effect in 2 of the C—H•••O
Fig. 5a. The geometric parameters of the C16—Cl1•••O4(methoxy)
hydrogen bonds and C—Cl•••O halogen bonds C—H•••π, and off-
set face-to-face π•••π stacking interactions do enhance the stabil-
ity of the syn-form relative to the ant- form in the crystalline state.
One significant difference in the types of intermolecular interac-
i
˚
halogen bond a Cl1•••O4 distance of 3.0535(14) A and a C16—
Cl1•••O4 angle of 154.06o are in the ranges of values found in
related compounds [59]. Fig. 5a also illustrates a sheet formed
from a combination of C18—H18•••O9 and C18—H18•••O11 hydro-
gen bonds with the C16—Cl1•••O4(methoxy) halogen bond. Within
this sheet, the two C18—H18•••O9 and C18—H18•••O11 hydrogen
bonds generate C(8),C(11) chains in the direction of the b axis,
tion involved in compounds 1 and 2 is the presence of a C—X•••
O
halogen bond in 2, and the lack of one in 1.
The strength of halogen bonds, [XB], C—X•••O, is in the order
X = I > Br > Cl > F [56]. However, steric effects can change mat-
8

M.G. Albuquerque, R.S.B. Gonçalves, C.H.d.S. Lima et al.
Journal of Molecular Structure 1246 (2021) 131091
Fig. 4. Packing of molecules of (a) compound 1, looking down the c axis, and (b) 2, looking down the b axis.
•••
O9 and C18—H18
••• •••
O11 hydrogen bonds and C16—Cl1 O4 halogen bonds,
Fig. 5. Compound 2. (a) A sheet of molecules obtained from the combination of C18—H18
•••
(b) a view of the sheet shown in Fig 5a indicating its non-planarity, (c) the chain sub-substure obtained from the combination of π(phenyl)—π(phenyl) and C16—HCl1
π
(phenyl)
•••
•••
π
interactions, (d) part of the assembly of molecules obtained rom the combination of C7—H7
π
and C21—H21A
interactions.
(naph)
(naph)
9

M.G. Albuquerque, R.S.B. Gonçalves, C.H.d.S. Lima et al.
Journal of Molecular Structure 1246 (2021) 131091
Fig. 6. Views of the Hirshfeld surfaces of (a) compound 1 and (b) compound 2, with red areas indicating close contacts between molecules.
Fig. 7. Graphical representation of the frontier orbitals: calculated optimized HOMO (A) and LUMO (B) for 1, calculated optimized HOMO (C) and LUMO (D) for 2. Calculations
were carried out with solvent effect (H2O).
10

M.G. Albuquerque, R.S.B. Gonçalves, C.H.d.S. Lima et al.
Journal of Molecular Structure 1246 (2021) 131091
Fig. 8. Representation of the relative orientations of the μTotal vector (blue lines), based on a Mulliken population analysis with colour scheme indicating partial charges of
all atoms in compound 1 (A and C) and in compound 2 (B and D).
˚
ters, e.g in the formation of DNA base pairs wherein XB substi-
tutes for hydrogen bonds, HB, the most stable pairing was given by
bromine as the advantage offered by the greater polarizability of
iodine was overcome by the disadvantage resulting from its greater
size [see 59]. The greater size of bromine in 1, compared to that of
Cl in 2 could thus, account for the lack of a halogen bond in 1.
However, it needs to be pointed out that, the chlorine atom partic-
ipating in the halogen bond in 2 is on the meta site of the attached
phenyl ring and not at the para position, as is the bromine atom in
1 and thus, the positioning of the interacting halogen could be sig-
nificant. However, as pointed out in Section 3.1.2, theoretical calcu-
lations indicate no significant influence on the stability of the po-
sitioning of halogen substituents in the phenyl rings of compounds
related to 1 and 2. Another factor which could lead to an enhance-
ment of the formation of a halogen bond in 2 is the presence of
two halogen substituents in an ortho relationship: as reported [58],
the presence of additional strong electron-withdrawing moieties
strengthens the σ-hole on the halogen bond donor atom, leading
to strong halogen bonds, and the closer the electron-withdrawing
moiety is to the halogen atom, the greater is the effect. Illustrat-
ing this, an increase in the number of fluorine substituents in a
iodobenzene ring has been reported to lead to a decrease in the
N•••I distance in the C—I•••O halogen bond in co-crystals with 4-
(N,N-dimethylamino)pyridine [60].
For both molecules, a 6A cut-off is applied. In all, compound 2 ex-
hibits the larger number of interacting molecules and the greater
number of intermolecular interactions. A more complete list of in-
termolecular interactions, as found by PLATON analyses [35], is
given in Table 6.
3.3. Theoretical study of properties
3.3.1. Electronic structure of 1 and 2
Graphical representations of the HOMO and LUMO frontier or-
bitals were calculated for 1 and 2, see Fig. 7. For each molecule,
the HOMO is located in the dimethoxy-naphthalenyl region of the
molecule and has mild donor character and the LUMO is located
specifically in the propenyl and phenyl regions of each molecule.
The energy gaps between these orbitals for 1 (3.35 eV) and 2
(3.25 eV) suggest greater chemical reactivity for 2 [47]. The delo-
calization present in 1 and 2 must facilitate a HOMO-LUMO charge
transfer process, as observed in related compounds [61].
The percentage involvements of O11, O9 and, O4 in the HOMO
in 1 are calculated to be 4.23, 7.36 and 6.59 %, respectively, and
are similar to those in 2 of 3.94, 7.54 and 7.11 %, respectively. The
similar HOMO contributions indicate that these atoms exhibit simi-
lar capabilities to interact with regions of electronic acceptors. Due
to the similarity of the HOMOs, any differences in the interactions
must be significantly influenced by the syn- / anti arrangement.
3.2.4. Hirshfeld surface analysis
The red areas on the Hirshfeld surfaces for compounds 1 and 2
in Fig. 6 indicate the sites of the major intermolecular close con-
tacts [45]. The red areas shown for compound 1 in Fig. 6a cor-
respond to O11(carbonyl)•••H, C•••H, Br•••H and H•••H contacts:
from the intensities of the red areas, strongest contacts are the
Br•••H contacts. For 2, interactions of the type O11(carbonyl)•••H,
C•••H, H•••H, O9(methoxy)•••H and O4(methoxy)•••H are detected,
with the strongest contacts involving O9•••H and O4•••H, Fig. 6b.
3.3.2. Dipole moments and charge distribution
A larger total electronic molecular dipolar moment (μTotal) was
calculated for 2 (5.9316 D) than for 1 (4.1511 D), as indicated by
the larger dipolar moment vector for 2, Fig. 8. The two compounds
have similar charge distributions, with the most significant differ-
ence occurring at C16, due to the bonds to different halogens, as
shown in Fig. 9 by the darker coloration. The values of μTotal found
for 1 and 2 are both larger than reported for similar compounds
11

M.G. Albuquerque, R.S.B. Gonçalves, C.H.d.S. Lima et al.
Journal of Molecular Structure 1246 (2021) 131091
Fig. 9. Calculated IR spectra (a) compound 1, (b) compound 2.
Table 7
[8,61], indicating that the compounds studied here should exhibit
good non-linear optical responses.
Principal vibrational modes calculated with B3LYP/DGTZVP/PCM (H2O) level the-
ory.
Vibration (cm-1
)
1
2
3.3.3. Infrared spectra
Exp.
Calc.
Exp.
Calc.
Calculated infrared spectra of compounds 1 and 2, see Fig. 9,
exhibit good agreement with the experimental spectra, as shown
by the comparison of the values of major vibrational modes in
Table 5. The calculated values for the C12-H12 stretching frequen-
cies for 1 and 2 are somewhat different at 3208-3214 and 3193-
3184 cm−1, respectively. The lower frequency found in compound
2 is highly suggestive of an interaction between H12 and its vicinal
carbonyl oxygen atom O11 and thus, supports the syn-periplanar
conformation indicated by the O11-C11-C12-H12 dihedral angle
ν C12-H
ν C13-H
ν C=C
3056-3009
3056-3009
1667
3208-3214
3176
3273-3005
3273-3005
1647
3193-3184
3193-3184
1680-1673
1680-1673
1323
1640-1707
1585
ν C=O
1585
1630-1589
1325
def C=C
1376
1376
outplane
def C-H
1051
1051
1059
1013-973
outplane
stretching frequencies are very similar at 3176 and 3181 cm−1 for
1 and 2 respectively, thereby indicating similar environments and
the absence of any unique interaction. Furthermore, the calculated
˚
and the O11—H12(vicinal) distance of 2.54 A (Table 2). In contrast
to the situation for the C12-H12 stretches, the calculated C13-H13
12

M.G. Albuquerque, R.S.B. Gonçalves, C.H.d.S. Lima et al.
Journal of Molecular Structure 1246 (2021) 131091
˚
[3] S.L. Gaonkar, U.N. Vignesh, Synthesis and pharmacological properties of chal-
cones: a review, Res. Chem. Intermed. 43 (2017) 6043–6077.
distance between O11 and H13 of 3.768 A in 2, clearly rules out
any O11-H13 interaction. The calculated C=C stretching frequen-
cies, 1640-1707 cm−1 for 1 and 1680-1673 cm−1 for 2, are similar.
Table 7.
[4] P. Singh, A. Anand, V Kumar, Recent developments in biological activities of
chalcones: A mini review, Eur. J. Med. Chem. 85 (2014) 758–777.
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minimum while the anti-periplanar form is a global energy mini-
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compounds. The energy differences are found to be very small,
with slight variations obtained when using the different basis
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indicating that the conformational change around O11-C11-C12-
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ꢀ
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derivative: quantum computational approach, Opt. Quant. Electron. 50
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The small differences in energies of the syn-periplanar and anti-
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tance of packing effects in the solid state, in which compounds 1
and 2 have the anti- and syn-periplanar arrangements, respectively.
Halogen bonds are considered a major influence in stabilising the
syn-periplanar arrangement in crystalline 2.
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The theoretical calculations provide information that com-
pounds 1, 2 and related analogues have potential as optical ma-
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Credit author Statement
[15] V. S.Rodrigues-Junior, A. D.Villela, R. S.B.Gonçalves, B.L. Abbadi, R.V. Trindade,
A. López-Gavín, G. Tudó, J. González-Martín, L. AugustoBasso, M. V.N.de Souza,
M.M. Campos, D.S. Santos, Int. J. Antimicrob. Agents 48 (2016) 203–207.
[16] M.D.F. Bispo, R.S.B. Goncalves, C.H. de S.Lima, L.N. de F. Cardoso,
M.C.S. Lourenco, M.V.N. de Souza, Synthesis and Antitubercular Evalua-
Name
Roles
Talis Uelisson da Silva
Data curation [calculations]
Sérgio de Paula Machado
Camilo Henrique da Silva Lima
Magaly Girão Albuquerque
Fernanda Lima de Azevedo Maia
Laudicéa do Nascimento Oliveira
Raoni Schroeder B. Gonçalves
James L Wardell
Co-Supervision [calculations];
Co-Supervision [calculations]
ꢀ
tion of N-Arylpyrazine and N,N -Alkyl-diylpyrazine-2-carboxamide Derivatives,
Data curation [calculations]
J. Heterocylic. Chem. 49 (2012) 1317–1322.
Data curation [synthesis: analysis]
Data curation [synthesis: analysis]
Supervision [synthesis]: writing; Conceptualization
Writing/original draft; revisions
Data curation [Crystallography]
[17] M.C. Dos Santos, J.L.R. Scaini, M.V.C. Lopes, B.G. Rodrigues, N.O. Silva,
C.R.L. Borges, S.C. dos Santos, K.S. Machado, A.V. Werhli, P.E.A. Silva,
M.C.S. Lourenco. E. T.da Silva, M. V.N.de Souza, V.R. de Lima, R.S. B.Gonçalves,
Mefloquine synergism with anti-tuberculosis drugs and correlation to mem-
brane effects: Biologic, spectroscopic and molecular dynamics simulations
studies, Bioorg. Chem. 110 (2021) 104786.
Solange M.S. V. Wardell
Declaration of Competing Interest
There are no conflicts to declare.
Acknowledgments
[18] M.L.F. Bispo, C.H.S. Lima, L.N.F. Cardoso, A.L.P. Candea, F.A.F.M. Bez-
erra, M.C.S. Lourenco, M.G.M.O. Henriques, R.B. Alencastro, C.R. Kaiser,
M.V.N. de Souza, A.G. Albuquerque, Anti-Mycobacterial Evaluation of
7-Chloro-4-Aminoquinolines and Hologram Quantitative Structure-Activity
Relationship (HQSAR) Modeling of Amino-Imino Tautomers, Pharmaceuticals
10 (2017) article no. 52.
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The use of the NCS crystallographic service at the University of
Southampton, UK, and the valuable assistance of the staff there are
gratefully acknowledged. The authors also thank the Fundação de
Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) for the
scholarship: E-26/010.210.513/2019.
Supplementary materials
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found, in the online version, at doi:10.1016/j.molstruc.2021.131091.
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