Molecular docking, Hirshfeld surface analysis and spectroscopic investigations of 1-(adamantan-1-yl)-3-(4-fluorophenyl)thiourea: A potential bioactive agent

Article abstract of DOI:10.1016/j.cplett.2019.136762

In this study, the optimized molecular structure, Hirshfeld surface analysis, vibrational frequencies and corresponding vibrational modes of a potential bioactive agent namely; 1-(adamantan-1-yl)-3-(4-fluorophenyl)thiourea were studied experimentally and theoretically. The theoretical calculations of the title compound were carried out using the density functional theory (DFT/B3LYP and DFT/M06-2X) quantum mechanical method with 6-311++G(d,p) basis set and Gaussian 09W program. The vibrational assignments of the title compound were obtained using VEDA 4 program by %10 precision with the help of potential energy distributions (PED). The experimental (FT-IR and Laser-Raman) spectra were recorded in solid phase at 4000–400 cm^?1 (FT-IR) and 4000–100 cm^?1 (Laser-Raman). Additionally, the experimental and theoretical ¹H and ¹³C NMR chemical shifts in DMSO?d₆ and UV–Vis. Spectral analysis in DMF were studied theoretically and experimentally. The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) analyses were performed. The molecular docking studies of the title compound revealed that it may exhibit antibacterial activity via inhibition of bacterial DNA gyrase PDB: 3U2D enzyme.

Full text of DOI:10.1016/j.cplett.2019.136762

ChemicalPhysicsLetters735(2019)136762
Contents lists available at ScienceDirect
Chemical Physics Letters
journal homepage: www.elsevier.com/locate/cplett
Research paper
Molecular docking, Hirshfeld surface analysis and spectroscopic
investigations of 1-(adamantan-1-yl)-3-(4-fluorophenyl)thiourea:
A potential bioactive agent
⁎
Yusuf Serta, , Lamya H. Al-Wahaibib, Halil Gökcec, Hanan M. Hassand, Aisha Alsfouke,
Ali A. El-Emamf
a Sorgun Vocational School, Bozok University, Yozgat 66100, Turkey
b Department of Chemistry, College of Sciences, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia
c Vocational School of Health Services, Giresun University, 28200 Giresun, Turkey
d Department of Pharmacology and Biochemistry, College of Pharmacy, Delta University for Science and Technology, International Costal Road, Gamasa City 11152,
Mansoura, Dakhliya, Egypt
e Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia
f Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt
H I G H L I G H T S
The vibrational assignments of the title compound were obtained using VEDA 4.
•
•
3D structure is elucidate using XRD and confirmed by DFT calculations.
•
DFT calculations at B3LYP allow a better reproduction of the experimental data.
•
The molecular docking studies of the title compound may exhibit antibacterial activity.
A R T I C L E I N F O
A B S T R A C T
Keywords:
In this study, the optimized molecular structure, Hirshfeld surface analysis, vibrational frequencies and corre-
sponding vibrational modes of a potential bioactive agent namely; 1-(adamantan-1-yl)-3-(4-fluorophenyl)
thiourea were studied experimentally and theoretically. The theoretical calculations of the title compound were
carried out using the density functional theory (DFT/B3LYP and DFT/M06-2X) quantum mechanical method
with 6-311++G(d,p) basis set and Gaussian 09W program. The vibrational assignments of the title compound
were obtained using VEDA 4 program by %10 precision with the help of potential energy distributions (PED).
The experimental (FT-IR and Laser-Raman) spectra were recorded in solid phase at 4000–400 cm−1 (FT-IR) and
4000–100 cm−1 (Laser-Raman). Additionally, the experimental and theoretical 1H and 13C NMR chemical shifts
in DMSO‑d6 and UV–Vis. Spectral analysis in DMF were studied theoretically and experimentally. The highest
occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) analyses were per-
formed. The molecular docking studies of the title compound revealed that it may exhibit antibacterial activity
via inhibition of bacterial DNA gyrase PDB: 3U2D enzyme.
Adamantane
Thiourea
Vibrational spectroscopy
Density functional theory
Molecular docking
1. Introduction
manufacturers for the discovery of more potent and safer adamantane
analogues as potential bioactive agents. As a result of this intensive
The highly lipophilic adamantane cage constitutes the core phar-
macophore of several drugs possessing chemotherapeutic activities
[1–3]. Following the discovery of amantadine as efficient antiviral drug
against influenza Viruses [4,5] and as antiparkinsonian [6] drug, ada-
mantane derivatives attracted the attention of several drug
search, several adamantane derivatives were developed and currently
used as effective therapeutic agents. Among the major biological ac-
tivities displayed by adamantane based derivatives, the antiviral
[7–11], anticancer [12–14] antibacterial and antifungal [15–19], anti-
malarial [20,21] and central nervous activities [22,23] are the most
⁎ Corresponding author.
E-mail address: yusufsert1984@gmail.com (Y. Sert).
https://doi.org/10.1016/j.cplett.2019.136762
Received 4 August 2019; Received in revised form 9 September 2019; Accepted 10 September 2019
Availableonline11September2019
0009-2614/©2019ElsevierB.V.Allrightsreserved.

Y. Sert, et al.
ChemicalPhysicsLetters735(2019)136762
important ones. On the other hand, thiourea derivatives were reported
to exhibit marked chemotherapeutic activities as anticancer [24–26]
and antimicrobial [27,28] activities. In addition, thiourea derivatives
are frequently utilized are essential building blocks for the synthesis of
biologically active compounds [29–31]. In contrary to the adamantane-
based derivatives, the insertion of the polar thiourea moieties into
biologically-active compounds greatly diminish the lipophilicity and
consequently alter the biological activities. Thus, the title compound
was synthesized as an adamantane-thiourea hybrid derivatives [32]
with reasonable lipophilicity to be evaluated as potential bioactive
agent and as a precursor for the synthesis of its related derivatives.
To the best of our knowledge, the experimental (FT-IR and Laser-
Raman, NMR) spectral studies, structural and electronic properties,
Hirshfeld surface and HOMO-LUMO analysis studies of the title mole-
cule were not previously reported. All theoretical computations were
defined based on the previous single crystal X-ray crystallography work
[32] and DFT/B3LYP and DFT/M06-2X-two different methods were
used. In addition, the interaction of the title molecule with DNA gyrase
PDB: 3U2D receptor was investigated by docking process.
0.9614 for DFT/B3LYP and 0.9489 for DFT/M06-2X in level in 6-311+
+G(d,p) basis set. The calculated vibrational frequencies and their
corresponding assignments were dissolved and clarified using the po-
tential energy distribution (PED) analysis using VEDA 4 program
[35,36].
The theoretical 1H and 13C NMR chemical shift were computed at
both the B3LYP/6-311++G(d,p) level and the M06-2X/6-311+
+G(d,p) one using IEFPCM model and GIAO method in DMSO solvent.
The HOMO-LUMO energy computations, their clouds in DMF sol-
vent, the contributions to HOMOs and LUMOs were obtained with
Chemissian software [37]. Additionally, in the next step to underpin
HOMO-LUMO results, the theoretical UV–Vis. analyses were made
using IEFPCM model and DMF solvent based on optimized molecular
structures in DMF. The GaussSum 3.0 program was used to evaluate the
results [38].
Lastly in this study, the molecular docking interactions of the title
molecule and PDB: 3U2D receptor were investigated by AutoDock Vina
program [39].
3. Results and discussion
2. Experimental and computational methods details
3.1. Molecular geometric properties
2.1. Sample and instrumentation
In the title molecule (C17H21FN2S), the mean planes of the benzene
The title compound was prepared in 88% yield via heating 1-ada-
mantylamine and 4-fluorophenyl isothiocyanate in ethanol for four
hours. The pure single crystals were obtained by slow evaporation of
the compound solution in EtOH/CHCl3 (1:1) at room temperature.
Fourier transform infrared (FT-IR) spectrum was recorded by
Perkin-Elmer Spectrum Two FT-IR Spectrometer at room temperature
ring and thiourea component form a dihedral angle of 61.93° (9). The
¯
crystal structure of our compound is triclinic and its space group is P
1
.
The crystal structure parameters are a = 6.4274 Å, b = 11.4727 Å,
c = 11.5870 Å and α = 113.510°, β = 94.721°, γ = 94.837° and its
volume is 774.39 Å3. For the title compound, the molecular density was
determined as 1.306 mg/m3 [32]. The optimized molecular structure
with atom numbering of the title compound and experimental ORTEP
structure at 50% probability level are shown in Fig. 1(a) and (b), re-
spectively.
between and 4000 cm−1 and 400 cm−1 and its resolution is 4 cm−1
.
The Laser-Raman spectrum was recorded between 4000 cm−1 and
100 cm−1 by Renishaw Invia Raman microscope spectrophotometer.
The excitation line at 785 nm has been taken from a diode laser. Both
FT-IR and Laser-Raman measurement were done in solid phase.
The optimized bond lengths, bond angles and dihedral angles of the
title compound were calculated using the B3LYP and M06-2X methods
with 6-311++G(d,p) basis set in gas phase. The theoretical and ex-
perimental structure parameters (bond lengths and bond angles) are
shown in Table 1. The differences between experimental and calculated
values are attributed to the phase situation, and this is normal and
expected. The R2 linear regression values indicated that the scaled
B3LYP is more skillful than the scaled M06-2X.
2.2. Computational details
The primary atomic coordinates for geometry optimization were
recorded using the Gauss View molecular visualization program [33]
and Gaussian 09 W package program package [34]. The molecular
structure of the title compound in the ground state (in gas phase) were
optimized by DFT/B3LYP and M06-2X methods with 6-311++G(d,p)
basis set level, and the optimized structure was used in the vibrational
frequency calculations. For the vibrational frequency computations, the
optimized structure was used and harmonic modes were multiplied by
The title molecule is composed of three groups, these are ada-
mantane, thiourea and fluorophenyl groups. The important bond
lengths and bond angles that need to be emphasized and interpreted. In
the adamantane group, the CeC bond lengths were reported between
1.514 Å and 1.537 Å in the experimental study [32]. These bond lengths
Fig. 1. The optimized molecular structure (a) and an ORTEP plot (b) of the title molecule.
2

Y. Sert, et al.
ChemicalPhysicsLetters735(2019)136762
Table 1
Experimental and calculated geometric parameters of the title compound.
Geometric parameters
Experimental values [29]
Calculated values
Bond lengths (Å)
B3LYP/6-311++G(d,p)
M06-2X/6-311++G(d,p)
C1eH2
0.930
1.370
1.381
0.930
1.350
1.360
1.364
1.380
1.420
0.930
1.380
0.930
1.350
1.345
1.687
1.524
1.533
1.473
1.535
1.514
1.533
1.537
0.980
0.970
1.526
0.970
0.980
1.530
1.524
0.980
0.970
0.970
0.970
1.526
0.980
1.527
1.514
0.970
0.970
0.970
0.970
0.860
0.860
0.970
0.970
1.084
1.392
1.400
1.083
1.386
1.354
1.386
1.401
1.420
1.083
1.393
1.083
1.382
1.351
1.687
1.546
1.546
1.483
1.545
1.542
1.541
1.542
1.095
1.096
1.542
1.095
1.095
1.542
1.540
1.090
1.096
1.097
1.098
1.541
1.095
1.541
1.541
1.096
1.096
1.096
1.096
1.009
1.011
1.096
1.090
0.9944
1.084
1.389
1.395
1.083
1.383
1.342
1.384
1.397
1.419
1.083
1.389
1.084
1.377
1.345
1.678
1.539
1.539
1.474
1.538
1.536
1.535
1.536
1.094
1.096
1.536
1.095
1.094
1.536
1.535
1.091
1.096
1.097
1.098
1.534
1.093
1.535
1.535
1.095
1.096
1.096
1.095
1.009
1.011
1.096
1.09
C1eC3
C1eC7
C3eH4
C3eC5
C5eF6
C5eC8
C7eC10
C7eN33
C8eH9
C8eC10
C10eH11
C12eN33
C12eN35
C12eS42
C13eC19
C13eC22
C13eN35
C13eC37
C14eC15
C14eC27
C14eC37
C14eH40
C15eH16
C15eC17
C15eH41
C17eH18
C17eC19
C17eC30
C19eH20
C19eH21
C22eH23
C22eH24
C22eC25
C25eH26
C25eC27
C25eC30
C27eH28
C27eH29
C30eH31
C30eH32
N33eH34
N35eH36
C37eH38
C37eH39
R2
0.9940
Bond Angles (o)
H2eC1eC3
H2eC1eC7
C3eC1eC7
C1eC3eH4
C1eC3eC5
H4eC3eC5
C3eC5eF6
C3eC5eC8
F6eC5eC8
C1eC7eC10
C1eC7eN33
C10eC7eN33
C5eC8eH9
C5eC8eC10
H9eC8eC10
C7eC10eC8
C7eC10eH11
C8eC10eH11
N33eC12eN35
N33eC12eS42
N35eC12eS42
C19eC13eC22
C19eC13eN35
C19eC13eC37
C22eC13eN35
120.7
119.7
120.5
120.7
115.5
120.7
119.4
122.7
117.8
119.4
120.3
120.3
120.7
120.2
119.9
120.2
119.9
119.9
115.4
119.6
125.0
109.2
111.5
109.9
109.2
119.9
119.4
120.7
121.5
118.6
119.9
118.9
122.1
118.9
119.2
119.4
121.3
119.8
118.8
121.4
120.5
119.6
119.9
115.5
117.7
126.9
108.4
111.9
110.1
105.9
120.3
119.2
120.5
121.8
118.5
119.6
118.9
122.3
118.7
119.6
119.5
120.8
119.6
118.6
121.7
120.3
119.3
120.4
115.2
118.1
126.8
108.5
111.8
110.3
105.5
(continued on next page)
3

Y. Sert, et al.
ChemicalPhysicsLetters735(2019)136762
Table 1 (continued)
Geometric parameters
Bond lengths (Å)
Experimental values [29]
Calculated values
B3LYP/6-311++G(d,p)
M06-2X/6-311++G(d,p)
C22eC13eC37
N35eC13eC37
C15eC14eC27
C15eC14eC37
C15eC14eH40
C27eC14eC37
C27eC14eH40
C37eC14eH40
C14eC15eH16
C14eC15eC17
C14eC15eH41
H16eC15eC17
H16eC15eH41
C17eC15eH41
C15eC17eH18
C15eC17eH19
C15eC17eC30
H18eC17eC19
H18eC17eC30
C19eC17eC30
C13eC19eC17
C13eC19eH20
C13eC19eH21
C17eC19eH20
C17eC19eH21
H20eC19eH21
C13eC22eH23
C13eC22eH24
C13eC22eC25
H23eC22eH24
H23eC22eC25
H24eC22eC25
C22eC25eH26
C22eC25eC27
C22eC25eC30
C22eC25eH26
C22eC25eC30
C27eC25eC30
C14eC27eC25
C14eC27eH28
C14eC27eH29
C25eC27eH28
C25eC27eH29
H28eC27eH29
C17eC30eC25
C17eC30eH31
C17eC30eH32
C25eC30eH31
C25eC30eH32
H31eC30eH32
C7eN33eC12
C7eN33eH34
C12eN33eH34
C12eN35eC13
C12eN35eH36
C13eN35eH36
C13eC37eC14
C13eC37eH38
C13eC37eH39
C14eC37eH38
C14eC37eH39
H38eC37eH39
R2
108.3
112.5
109.9
109.7
109.4
109.1
109.9
109.8
109.4
109.9
109.4
109.7
108.2
109.7
109.7
109.5
109.3
108.2
109.7
109.9
109.6
109.8
109.8
109.8
109.8
108.2
109.7
109.7
110.0
108.2
109.3
109.3
109.3
109.4
109.6
109.3
109.6
109.8
108.8
109.9
109.9
109.9
109.9
108.3
109.7
109.7
109.7
109.7
109.7
108.2
125.7
117.2
117.2
131.4
114.3
114.3
109.3
109.8
109.8
109.8
109.8
108.3
108.4
111.9
109.5
109.5
109.7
109.6
109.7
108.8
110.0
109.5
110.1
110.1
107.1
110.1
109.7
109.4
109.6
108.8
109.7
109.6
109.8
109.5
109.1
110.7
110.3
107.5
109.5
109.5
110.4
107.5
109.9
109.9
108.8
109.4
109.5
109.8
109.8
109.5
109.3
110.4
110.1
109.9
110.2
106.9
109.3
110.2
110.4
110.2
109.9
106.9
129.1
117.9
112.3
130.2
115.6
113.9
109.7
109.1
109.6
110.3
110.7
107.4
0.9651
108.4
112.0
109.6
109.5
109.6
109.7
109.7
108.8
109.9
109.6
109.9
109.9
107.5
109.9
109.7
109.2
109.7
108.9
109.7
109.6
109.5
109.5
108.8
110.6
110.4
107.9
109.2
109.3
110.4
107.9
110.1
109.9
108.9
109.4
109.3
109.9
109.9
109.5
109.3
110.2
110.0
109.7
110.1
107.4
109.3
110.0
110.2
110.0
109.8
107.3
127.5
118.1
112.8
129.4
116.0
114.1
109.5
108.8
109.7
110.5
110.4
107.9
0.9618
Dihedral Angles (o)
H2eC1eC3eH4
H2eC1eC3eC5
C7eC1eC3eH4
C7eC1eC3eC5
H2eC1eC7eC10
H2eC1eC7eN33
C3eC1eC7eC10
C3eC1eC7eN33
C1eC3eC5eF6
0.5
0.6
−178.6
−179.6
1.2
−178.5
−179.6
1.2
−1.4
179.8
−2.9
−0.0
177.1
179.2
179.5
−2.3
−0.3
177.9
179.3
−2.1
177.9
−178.3
(continued on next page)
4

Y. Sert, et al.
ChemicalPhysicsLetters735(2019)136762
Table 1 (continued)
Geometric parameters
Bond lengths (Å)
Experimental values [29]
3.3
Calculated values
B3LYP/6-311++G(d,p)
M06-2X/6-311++G(d,p)
C1eC3eC5eC8
−1.0
0.1
−0.8
0.1
H4eC3eC5eF6
H4eC3eC5eC8
179.8
−178.7
−0.4
0.9
179.9
−178.9
−0.5
0.8
C3eC5eC8eH9
C3eC5eC8eC10
F6eC5eC8eH9
−1.9
179.9
3.7
F6eC5eC8eC10
179.3
−1.4
177.1
−178.5
−0.0
123.2
−46.5
−59.6
130.6
1.6
179.3
−1.1
177.9
−179.3
−0.1
116.0
−48.6
−65.8
129.5
1.5
C1eC7eC10eC8
C1eC7eC10eH11
N33eC7eC10eC8
N33eC7eC10eH11
C1eC7eN33eC12
C1eC7eN33eH34
C10eC7eN33eC12
C10eC7eN33eH34
C5eC8eC10eC7
−176.2
−117.2
62.7
−1.9
C5eC8eC10eH11
H9eC8eC10eC7
−176.9
179.9
1.4
−177.5
179.9
0.9
H9eC8eC10eC11
N35eC12eN33eC7
N35eC12eN33eH34
S42eC12eN33eC7
S42eC12eN33eH34
N33eC12eN35eC13
N33eC12eN35eH36
S42eC12eN35eC13
S42eC12eN35eH36
C22eC13eC19eC17
C22eC13eC19eH20
C22eC13eC19eH21
N35eC13eC19eC17
N35eC13eC19eH20
N35eC13eC19eH21
C37eC13eC19eC17
C37eC13eC19eH20
C37eC13eC19eH21
C19eC13eC22eH23
C19eC13eC22eH24
C19eC13eC22eC25
N35eC13eC22eH23
N35eC13eC22eH24
N35eC13eC22eC25
C37eC13eC22eH23
C37eC13eC22eH24
C37eC13eC22eC25
C19eC13eN35eC12
C19eC13eN35eH36
C22eC13eN35eC12
C22eC13eN35eH36
C37eC13eN35eC12
C37eC13eN35eH36
C19eC13eC37eC14
C19eC13eC37eH38
C19eC13eC37eH39
C22eC13eC37eC14
C22eC13eC37eH38
C22eC13eC37eH39
N35eC13eC37eC14
N35eC13eC37eH38
N35eC13eC37eH39
C27eC14eC15eH16
C27eC14eC15eH17
C27eC14eC15eH41
C37eC14eC15eH16
C37eC14eC15eC17
C37eC14eC15eH41
H40eC14eC15eH16
H40eC14eC15eC17
H40eC14eC15eH41
C15eC14eC27eC25
C15eC14eC27eH28
C15eC14eC27eH29
C37eC14eC27eC25
−0.8
178.6
176.0
−3.4
−59.0
0.7
5.8
170.9
−178.8
−8.6
−178.8
−5.7
0.7
171.1
−174.1
−8.8
−178.7
−6.3
1.2
173.8
59.8
173.6
59.8
−178.4
−61.1
176.3
−61.9
55.3
−178.7
−61.0
175.8
−62.8
55.0
−174.9
59.6
−58.5
63.2
−58.8
62.6
−179.4
179.1
61.6
−179.6
178.9
61.1
59.3
−59.6
58.8
−59.8
58.9
−58.8
−179.9
−61.4
−179.0
59.7
−58.8
−179.9
−61.2
−179.0
60.0
179.1
−60.4
−64.7
62.4
63.4
−110.7
−179.6
7.1
−109.0
−178.8
8.8
177.0
59.3
−61.6
125.1
58.4
−61.0
126.5
58.6
−58.7
179.4
−63.2
−59.8
61.0
179.4
−62.7
−60.1
60.8
60.5
178.4
−176.4
−55.4
61.9
178.6
−176.0
−55.2
62.6
176.4
61.3
61.3
−59.7
179.1
−178.4
60.5
−59.6
179.5
−178.3
60.7
−60.3
−60.6
−59.0
179.9
58.7
−60.1
−59.0
180.0
59.1
−59.5
60.9
60.0
60.0
−60.9
−178.7
−60.2
−60.7
−178.9
−60.1
(continued on next page)
5

Y. Sert, et al.
ChemicalPhysicsLetters735(2019)136762
Table 1 (continued)
Geometric parameters
Bond lengths (Å)
Experimental values [29]
Calculated values
B3LYP/6-311++G(d,p)
M06-2X/6-311++G(d,p)
C37eC14eC27eH28
C37eC14eC27eH29
H40eC14eC27eC25
H40eC14eC27eH28
H40eC14eC27eH29
C15eC14eC37eC13
C15eC14eC37eH38
C15eC14eC37eH39
C27eC14eC37eC13
C27eC14eC37eH38
C27eC14eC37eH39
H40eC14eC37eC13
H40eC14eC37eH38
H40eC14eC37eH39
C14eC15eC17eH18
C14eC15eC17eH19
C14eC15eC17eC30
H16eC15eC17eH18
H16eC15eC17eH19
H16eC15eC17eC30
H41eC15eC17eH18
H41eC15eC17eH19
H41eC15eC17eC30
C15eC17eC19eC13
C15eC17eC19eH20
C15eC17eC19eH21
H18eC17eC19eC13
H18eC17eC19eH20
H18eC17eC19eH21
C30eC17eC19eC13
C30eC17eC19eH20
C30eC17eC19eH21
C15eC17eC30eC25
C15eC17eC30eH31
C15eC17eC30eH32
H18eC17eC30eC25
H18eC17eC30eH31
H18eC17eC30eH32
C19eC17eC30eC25
C19eC17eC30eH31
C19eC17eC30eH32
C13eC22eC25eH26
C13eC22eC25eC27
C13eC22eC25eC30
H23eC22eC25eH26
H23eC22eC25eC27
H23eC22eC25eC30
H24eC22eC25eH26
H24eC22eC25eC27
H24eC22eC25eC30
C22eC25eC27eC14
C22eC25eC27eH28
C22eC25eC27eH29
H26eC25eC27eC14
H26eC25eC27eH28
H26eC25eC27eH29
C30eC25eC27eC14
C30eC25eC27eH28
C30eC25eC27eH29
C22eC25eC30eC17
C22eC25eC30eH31
C22eC25eC30eH32
H26eC25eC30eC17
H26eC25eC30eH31
H26eC25eC30eH32
C27eC25eC30eC17
C27eC25eC30eH31
C27eC25eC30eH32
R2
178.9
61.0
179.2
60.9
−179.5
59.5
−179.6
59.7
−58.3
−59.4
−179.6
61.7
−58.6
−59.3
−179.1
61.6
59.0
−61.4
60.8
60.9
−59.3
−178.1
−179.3
60.5
−58.9
−178.2
−179.1
61.0
−58.2
−179.8
−60.5
59.7
−58.2
−179.9
−60.6
59.5
−59.4
−60.2
59.1
59.0
178.4
−61.4
−58.7
60.6
178.3
−61.4
−59.1
60.1
−179.1
59.3
−179.6
59.5
−61.5
179.6
179.2
58.2
−61.3
179.4
179.2
58.4
−60.6
−60.8
178.2
59.4
−60.9
−60.7
178.5
59.1
59.6
59.8
−60.0
178.8
60.9
−59.8
179.1
61.0
179.5
58.3
179.7
58.7
−59.5
60.1
−59.4
60.1
−59.8
−61.1
−178.9
179.9
−60.0
59.9
−60.9
−179.0
179.9
−59.9
59.9
60.8
−59.6
−59.1
60.9
−59.3
60.8
−179.1
59.0
−179.4
59.3
179.0
−61.0
59.5
179.5
−60.7
59.2
−60.4
−179.3
−61.7
178.9
−59.9
57.7
−179.7
−61.7
178.8
−60.2
57.8
59.9
59.6
−60.5
60.8
−60.5
60.5
178.3
−59.4
61.7
178.5
−59.4
61.5
179.3
−178.9
−57.7
59.8
179.5
−178.9
−58.0
60.0
−60.6
60.4
60.4
−178.3
−60.8
0.9995
−178.7
−60.6
0.9993
6

Y. Sert, et al.
ChemicalPhysicsLetters735(2019)136762
Fig. 2. The interaction forms in the structure.
were computed between 1.540 Å and 1.546 Å in B3LYP and 1.534 Å and
1.539 Å in M06-2X methods. Almutairi et al. reported the adamantane
CeC bond lengths for a related adamantane derivative at 1.544 Å [40].
The adamantane CeH bond were reported at between 0.97 Å and
0.98 Å in experimental study [32], these bond lengths were computed
at between 1.090 Å and 1.098 Å in B3LYP, and 1.090 Å and 1.098 Å in
M06-2X methods which agrees with the previously reported values in
the range 1.092–1.097 Å [40]. The adamantane bond angles were cal-
culated at about 109° with both methods in accordance with the re-
ported values [40].
fluorophenyl)-3-[3-(trifluoromethyl)phenyl]thiourea molecule [43]
were reported in the ranges 1.4035 Å-1.3887 Å/1.3895 Å-1.3765 Å.
Additionally, the C5-F6 bond length was calculated at 1.354 Å/1.342 Å
in B3LYP/M06-2X methods, and experimentally was determined as
1.360 Å. Meanwhile, the CeF bond was reported at 1.3392 Å/1.3474 Å
in DFT/XRD [43]. Finally, the aromatic CeCeC bond angle values were
calculated in the ranges 118.6°-122.1°/118.5°-122.3° in B3LYP/M06-2X
methods, and experimentally in the ranges 115.5°-122.7°. The C3-C5-F6
and C8-C5-F6 angles were calculated at 118.9°/118.9° and 118.9°/
118.7° in B3LYP/M06-2X methods, respectively. These calculated va-
lues were also consistent with the previously reported values [43].
In the thiourea moiety, the C12-S42, N33-H34 and N35-H36 bond
lengths were computed as 1.687 Å /1.678 Å, 1.009 Å/1.009 Å and
1.011 Å/1.011 Å with B3LYP/M062X methods and 6-311++G(d,p)
basis level, respectively. These bond lengths were reported at 1.68 Å,
1.37 Å and 1.37 Å, respectively for related thiourea molecule [41]. In
another study, the CeS bond lengths of 1,3-diphenylthiourea were
found to be 1.6636 Å with DFT/B3LYP method and 6-311++G(d,p)
basis set [42]. Mary et al. [43] reported the CeS bond length of 1-(3-
3.2. Hirshfeld surface analysis
The Hirshfeld surface analysis of the title molecule was carried out
using the Crystal Explorer 3.1 program [44] to explore the interactions
of the crystal molecules. To visualize the Hirshfeld surface, dnorm: the
normalized contact distance is used and formulized in Eq. (1).
chloro-4-fluorophenyl)-3-[3-(trifluoromethyl)phenyl]thiourea
at
di rvdw
de revdw
1.6770 Å/1.6853 Å (DFT/XRD). The N33-C12 and N35-C12 bond
lengths were calculated at 1.382 Å/1.377 Å and 1.351 Å/1.345 Å in
B3LYP/M06-2X methods and these bonds were reported at 1.350 Å and
1.345 Å in experimental study [32], respectively. The H34-N33-C12,
S42-C12-N33, S42-C12-N35, N33-C12-N35 and H36-N35-C12 bond
angles were computed at 112.3°/112.8°, 117.7°/118.1°, 126.9°/126.8°,
115.5°/115.2° and 115.6°/116.0° in B3LYP/M06-2X methods respec-
tively, and these angles experimentally were found to be 117.2°, 119.6°,
125.04°, 115.4° and 114.3°, respectively. These results were consistent
with previously reported values [42,43].
i
dnorm
=
+
rvdw
revdw
(1)
i
In here, de, di and rvwd are described as follows: de is the distance
from the Hirshfeld surface to the nearest nucleus outside the surface;
secondly di is the corresponding distance to the nearest nucleus inside
the surface; and as a thirdly rvwd is a vdw (van der Waals) radius of the
atom. Finally in Eq. (1), dnorm is a surface and visualized using a red,
white, blue colour.
The results are shown as 3D Hirshfeld surfaces (dnorm) and 2D fin-
gerprint histogram in Fig. 2 and Fig. 3, respectively. Fig. 2 shows the
intermolecular contacts over the surface and the red colors indicate the
intercontacts in the hydrogen bonds (and bond distances in hydrogen
bond). The blue regions are contact sites longer than sum of van der
In the fluorophenyl group, the aromatic CeC bond lengths were
calculated in the ranges 1.386 Å-1.401 Å/1.383 Å-1.397 Å in B3LYP/
M06-2X methods, and experimentally in the ranges 1.350 Å-1.381 Å.
The aromatic DFT/XRD CeC bond lengths of 1-(3-chloro-4-
7

Y. Sert, et al.
ChemicalPhysicsLetters735(2019)136762
Fig. 3. The 2D finger plots of the title molecule.
3.3.1. Adamantane cage vibrations
Waals radii with positive dnorm; and white regions correspond to the
inter-molecular distances close to van der Waals radii with dnorm equal
to zero [45,46]. The dnorm values were found to be in the range of
−0.2337 (red color) to 1.3609 (blue color) Å. In Fig. 3, the H-H in-
teractions (with 61% the contribution of intercontacts-), F-H/H-F in-
teractions (with 12.5% contribution), S-H/H-S interactions (with 12%
contribution) and CeH/H-C interactions (with 11.6% contribution)
were obtained as shown in Fig. 3(a)–(d), respectively, with included
reciprocal interactions. Both Fig. 2 and Fig. 3 were obtained by using
B3LYP/6-311++G(d,p).
The adamantane moiety of the title molecule contains six CH2 and
three CH groups attached on cage skeleton of ten carbon atoms in sp3
hybridized state. Accordingly, the adamantyl group is expected to show
the molecular vibrations corresponding mainly to scissoring, rocking,
wagging, and twisting vibrations of the CH2 groups, CeH stretching,
CeH bending, in addition to the CeC stretching, CeCeC deformation
and CeCeCeC torsion vibrations. The wavenumber of asymmetric
stretching vibration is generally found to be higher than that of the
symmetric one. In the present study, the six CH2 asymmetric were
computed at 2980/2974, 2977/2966, 2935/2931, 2928/2928, 2925/
2923 and 2917/2912 cm−1 in B3LYP/M06-2X methods and 6-311+
+G(d,p) basis level. These asymmetric modes were experimentally
observed at 2974/2974, 2934/2926, 2907/2902 cm−1 in FT-IR/Laser-
Raman spectra. The symmetric CH2 modes were calculated at 2901/
2887 cm−1, 2895/2886 cm−1, 2891/2883 cm−1, 2890/2880 cm−1 and
2880/2864 cm−1 in B3LYP/M06-2X methods and 6-311++G(d,p)
basis level. These modes were observed at 2907/2902 cm−1 and 2859/
2870 cm−1 in FT-IR/Laser-Raman spectra. The symmetric CH2 modes
in adamantane group were reported at 2999, 2983, 2966, 2956 and
2955 cm−1 with DFT/B3LYP/6-311++G(d,p) method for a related
adamantane derivative [40].
3.3. Vibrational frequencies
The title molecule with 42 atoms has 120 vibrational modes. As can
be seen from the optimized structure (Fig. 1) and output results, the
title compound is in C1 point group symmetry. Because of C1 symmetry,
all the vibrational modes are active in both IR and Raman spectra. In
this section, the harmonic vibrational frequencies were computed by
using both B3LYP and M06-2X method and 6-311++G(d,p) basis set in
gas phase. The assignments of the calculated wavenumbers were de-
termined as in terms of potential energy distribution (PED) using VEDA
4 program [35] and tabulated in Table 2. The calculated IR and Raman
spectrum were compared with the experimental FT-IR and Laser-Raman
spectra and for comparison were given Fig. 4(a and b) and Fig. 5 (a and
b), respectively.
The CH2 scissoring modes were calculated in the range 1443/
1424 cm−1-1427/1405 cm−1 in B3LYP/M06-2X methods (five scis-
soring band: ν28-ν32). The wagging modes were calculated in the range
1338/1327–1292/1281 cm−1 in B3LYP/M06-2X methods (six wagging
8

Y. Sert, et al.
ChemicalPhysicsLetters735(2019)136762
Table 2
Observed and calculated vibrational frequencies of title compound with 6-311++G(d,p) basis set.
Vibration no. Assignments
Observed frequencies
Calculated frequencies in cm−1 (IR intensities/Raman
activity)
FT-IR
Laser-Raman
B3LYP
M06-2X
ν1
υNH (1 0 0) in the N33-H34
3390
3370
3092
3092
3053
3044
2974
2974
2934
2934
2934
2934
2907
2907
2907
2907
2907
3466
3426
3081
3080
3066
3060
2980
2977
2935
2928
2925
2922
2917
2915
2913
2904
2901
2895
2891
2890
2880
1580
1567
1504
1477
1466
1460
1443
1443
1439
1430
1427
1387
1345
1343
1338
1325
1323
1319
1300
1295
1292
1281
1271
1267
1262
1260
1258
1249
1238
1213
1188
3456
3415
3061
3053
3039
3036
2974
2966
2931
2928
2923
2916
2912
2909
2909
2889
2887
2886
2883
2880
2864
1602
1589
1503
1483
1452
1446
1424
1420
1419
1407
1405
1385
1337
1335
1327
1325
1312
1311
1286
1284
1281
1280
1267
1264
1262
1258
1244
1243
1231
1226
1195
ν2
υNH (1 0 0) in the N35-H36
ν3
υCH (99) in the ring1
ν4
υCH (98) in the ring1
ν5
υCH (92) in the ring1
3069
3069
2974
2974
2926
2926
2926
2926
2902
2902
2902
2902
2902
ν6
υCH (82) in the ring1
ν7
υCH(8 1 ) asymmetric mode
ν8
υCH(8 5) asymmetric mode
ν9
υCH(8 8) asymmetric mode
ν10
ν11
ν12
ν13
ν14
ν15
ν16
ν17
ν18
ν19
ν20
ν21
ν22
ν23
ν24
ν25
ν26
ν27
ν28
ν29
ν30
ν31
ν32
ν33
ν34
ν35
ν36
ν37
ν38
ν39
ν40
ν41
ν42
ν43
ν44
ν45
ν46
ν47
ν48
ν49
ν50
ν51
ν52
υCH(7 6) asymmetric mode
υCH(6 9 ) asymmetric mode
υCH(7 3)
υCH(7 4 ) asymmetric mode
υCH(83)
υCH(89)
υCH(93)
υCH(78) symmetric mode
υCH(9 7) symmetric mode
υCH(84) symmetric mode
υCH(9 0) symmetric mode
υCH(9 6) symmetric mode
2859
1610
1548
1509
1451
1451
1451
1425
1425
1425
1425
1425
2870
1602
1540
1502
1444
1444
1444
1444
1444
1444
1416
1416
1368
1358
1358
1358
1358
1306
1306
1306
1306
1287
1284
υCC(5 5 ) in the ring1 + δHCC(18) in the ring1
υCC(6 4 ) in the ring1 + δHCC(11) in the ring1
δHNC (74) in the H36- N35-C12 + υNC(15) in the N35-C12
δHCC(45) in the ring1 + υCC(1 2 ) in the ring1
δHCH(79)
δHNC(53) in the H34-N33-C7 + υNC(11) in the N35-C12
δHCH(76) scissoring mode
δHCH(75) scissoring mode
δHCH(82) scissoring mode
δHCH(85) scissoring mode
δHCH(85) scissoring mode
υCC(3 8 ) in the ring1 + δHCC(28)
τHCCC (10) in H16-C15-C17-C19
δHCC(45)
1359
1359
1359
1359
1301
1301
1301
1301
1301
τHCCC (15) wagging mode
υNC(1 3 ) in the N35-C12 + τHCCC (10) wagging mode
τHCCC (23) wagging mode + δHCC(17) in H16-C15-C17
υNC(2 9) in the N35-C12 + δHNC(15) in the H34-N33-C7
τHCCC (59) wagging mode
τHCCC (28) wagging mode + δHCC(11) inH16-C15-C17
τHCCC (28) wagging mode
δHCC(27)
υCC(5 1 ) in the ring1
δHCC(61) in H2-C1-C3
1248
1248
1248
1248
1248
1248
1213
1253
1253
1253
1253
1253
1253
1220
1191
δHCC(24) H16-C15-C17 + υCC(11) C14-C37 + υCC(10) C22-C25
δHCC(31)
δHCC(15) + τHCCC (12) + υCC(1 0 ) in the C14-C37
δHCC(13) + τHCCC (11) + υCC(1 0)
τHCCC (24) + υCC(15) C37-C13
υCC(2 9 ) in the ring1 + υNC(2 1) in the N33-C7 + υFC(11) in the F6-C5
υFC(3 5) in the F6-C5 + δHCC(19) in the ring1 + δCCC(10) + υCC(1 0) in the 1213
ring
ν53
ν54
ν55
ν56
ν57
ν58
ν59
ν60
ν61
ν62
ν63
ν64
ν65
ν66
ν67
ν68
ν69
ν70
δHCC(24)
1169
1156
1138
1138
1103
1098
1098
1098
1098
1050
1050
1015
1015
1015
979
1153
1153
1134
1134
1100
1100
1100
1100
1100
1038
1038
1000
1000
1000
986
1169
1165
1131
1126
1104
1092
1089
1080
1079
1075
1069
1010
1008
1007
989
1159
1154
1139
1114
1110
1081
1077
1070
1068
1064
1054
1022
1021
1016
981
δHCC(39)
δHCC(42) in the ring1 + υCC(1 6 ) in the ring1 + υNC(11) in the N33-C12
δHCC(27) in the ring1 + υNC(2 3 ) in the N33-C12
υNC(2 7 ) in the N35-C13
δHCC(23) + τHCCC (16)
δHCC(39) + τHCCC (20)
τHCCC (15)
τHCCC (17)
δHCC(55) in the ring1 + υCC(2 4) in the ring
δCCC(11)
δCCC(10)
υCC(35) C37-C13
υCC(1 6) C37-C13 + υCC(11) C22-C25
δCCC(61) in the ring1 + δHCC(22) in the ring1
γCCCC (29) C19-C15-C30-C17
γCCCC (15) C19-C15-C30-C17 + δCCC(10) 14-C37-C13
γCCCC (12) + δCCC(10)
979
986
973
969
957
957
952
951
957
957
951
950
(continued on next page)
9

Y. Sert, et al.
ChemicalPhysicsLetters735(2019)136762
Table 2 (continued)
Vibration no. Assignments
Observed frequencies
Calculated frequencies in cm−1 (IR intensities/Raman
activity)
FT-IR
Laser-Raman
B3LYP
M06-2X
ν71
τHCCN (90)
931
931
928
928
928
928
928
871
871
871
837
823
780
780
780
938
933
919
908
905
868
864
862
843
826
798
794
786
784
757
741
696
679
640
630
628
622
603
544
503
484
473
448
441
429
425
412
398
395
392
384
350
348
302
276
267
260
211
149
109
88
949
939
927
918
913
858
855
852
850
835
808
803
795
792
759
751
699
682
637
625
621
615
603
544
501
486
472
448
443
423
421
408
340
391
386
383
349
348
296
283
266
260
214
151
111
100
56
ν72
υCC(1 1) C14-C37
ν73
τHCCN (57) in the ring1 + τCCCC (12) in the ring1
υCC(2 4)
ν74
ν75
υCC(4 5)
ν76
τHCCC (51)
873
873
873
847
816
816
816
816
816
772
ν77
τHCCC (41) + δHCC(12)
τHCCC (25)
ν78
ν79
υCC(2 3) in the ring1
ν80
υCC(1 8) in C1-C3 + τHCCN (10)
τHCCN (45)
ν81
ν82
τHCCN (46)
ν83
υCC(39)
ν84
υCC(16) + υCC(14)
ν85
υFC(2 1 ) in the F6-C5 + δCCC(16) in the ring1
υCC(72) CeC breathing mode in adamantane ring
τCCCC (34) + γNCCC (13)
τHCCC (13) + υSC(10) in the S42-C12
υSC(14) in the S42-C12
ν86
ν87
697
694
ν88
ν89
657
631
631
631
609
547
520
481
481
446
446
428
428
656
637
637
ν90
γCCCC (14) + δCCC(11)
δCCC(10)
ν91
ν92
δCCC(51)
ν93
γSNNC (79) S42-N35-N33-C12
δCCC(10) in the ring1
598
541
527
484
484
460
460
412
412
412
ν94
ν95
γFCCC (14) + γNCCC (10) + δCCC(12) + δSCN(12)
τHNCC (68)
ν96
ν97
τHNCC (12)
ν98
τHNCC (57)
ν99
τHNCC (16) + τHCCC (13)
δCCC(24) C19-C17-C30
ν100
ν101
ν102
ν103
ν104
ν105
ν106
ν107
ν108
ν109
ν110
ν111
ν112
ν113
ν114
ν115
ν116
ν117
ν118
ν119
ν120
R2
δFCC(29) F6-C5-C8 + δCNC(11)
τCCCC (73) in the ring1
γFCCC (12) + τCCCC (10) + δFCC(10)
τCCCN (17) + δCCC(13) + τCCCC (11)
δCCC(24) + τCCCN (14)
δCCN(19) + τCCCC (18) + τHCCC (10) + τCCCN (10)
τNCCC (12) + δFCC(10)
δFCC(26) in the F6-C5-C8 + τNCCC (10)
δCCC(25) + τHCCC (15)
δSCN(11) in S42-C12-N33 + υNC(1 1) in N33-C7
τCCCN (23) + δCCN(14)
τCCCN (12) + δCNC(10)
δSCN(41) in the S42-C12-N33 + δCNC(12)
τCCCC (31) in the ring1
δCNC (28) + τCCCC (14) in the ring1
τCNCC (15) + τCNCN (11)
τCNCC (13) + τCNCN (10)
τCNCC (26) + τCNCN (16)
τCNCN (12) + τCNCC (10)
τCNCN (10) + τCNCC (10)
370
370
370
297
278
278
230
230
173
61
45
46
30
28
22
12
0.9997
0.9996
υ, stretching; δ, in-plane bending; γ, out-of-plane bending; τ, torsion. aPotential energy distribution (PED), less than 10%are not shown.
band: ν36-ν42). The CH2 scissoring and wagging modes were reported
in the range 1456–1416 cm−1 and 1341–1287 cm−1, respectively [40].
The adamantane CeC symmetric breathing mode was calculated at
741/751 cm−1 in B3LYP/M06-2X methods. This mode was not detected
in both FT-IR and Laser-Raman spectra. In the literature [40,47,48],
this mode was calculated at 736, 743 and 729 cm−1, respectively.
3570 cm−1 and 3583 cm−1 by B3LYP/6-311++G(d,p) level of theory
[41]. Additionally, these assignments were also supported by the other
related structures [42,43]. The out-of-plane τHNCC modes were com-
puted in the range 484/486–441/443 cm−1 as four modes in the
B3LYP/M06-2X methods (ν96, ν97, ν98 and ν99). These modes were ob-
served at 481/484 and 446/460 cm−1 in FT-IR/Laser-Raman spectra.
The thiourea C12-N35 stretching vibrations were computed at
3.3.2. Thiourea group vibrations
1504/1503 cm−1
,
1460/1446 cm−1
,
1325/1325 cm−1 and 1319/
The N-H stretching modes are generally observed in the range of
3500–3200 cm−1 [49]. In the present study, we determined two im-
portant N-H mode in ν1 and ν2. These modes were calculated at 3466/
3456 cm−1 and 3426/3415 cm−1 in B3LYP/M06-2X methods with
100% PED contribution, and experimentally at 3390 cm−1 and
3370 cm−1 in the FT-IR spectrum. The N-H stretching modes of 1-(4-
methoxyphenyl)-3-(pyridine-3-ylmethyl)thiourea were reported at
1311 cm−1 in the B3LYP/M06-2X methods (ν24, ν27, ν37 and ν39). These
modes were experimentally observed at 1509/1502 cm−1
, 1451/
1444 cm−1, 1359/1358 cm−1 and 1301/1306 cm−1 in FT-IR/Laser-
Raman spectra. The N33-C7(ν51), N33-C12 (ν55 and ν56) and N35-C13
(ν57) stretching modes were calculated at 1213/1226 cm−1, 1131/
1139 cm−1, 1126/1114 cm−1 and 1104/1110 cm−1 with B3LYP/M06-
2X method and 6-311++G(d,p) basis set. These assignments were also
10

Y. Sert, et al.
ChemicalPhysicsLetters735(2019)136762
Fig. 5. The experimental (a) and theoretical (b) Laser-Ra spectra of the title
Fig. 4. The experimental (a) and theoretical (b) FT-IR spectra of the title
compound.
compound.
The phenyl CeH stretching usually appears in the region
3150–2900 cm−1 regardless the nature of the aromatic substituents
[52]. In this study, the phenyl CeH stretching was calculated at 3081/
3061 cm−1, 3080/3053 cm−1, 3066/3039 cm−1 and 3060/3036 cm−1
in B3LYP/M06-2X methods and 6-311++G(d,p) basis set. These
modes were observed at 3092 cm−1 (FT-IR), 3053/3069 cm−1 (FT-IR/
Laser-Raman) and 3044/3069 cm−1 (FT-IR/Laser-Raman). The δHCC
in-plane bending modes were calculated at 1580/1602 cm−1, 1567/
supported by the literature [41–43].
The CeS stretching modes were reported in the region
930–670 cm−1 [44]. In this study, the CeS stretching modes were
calculated at 679/682 and 640/637 cm−1 in the B3LYP/M06-2X
methods. These modes were observed at 657/656 cm−1 in FT-IR/Laser-
Raman spectra. Mushtaque et al. [41] reported the thiourea CeS modes
of
1-(4-methoxyphenyl)-3-(pyridine-3-ylmethyl)thiourea
at
728.23 cm−1 experimentally and theoretically calculated at 698 and
743 cm−1. Meanwhile, Mary et al. [43] observed these modes at 887/
892 cm−1 in the IR/Raman spectra, and theoretically at 889 cm−1. The
in-plane and out-of-plane or torsion modes of thiourea group could be
controlled easily in Table 2. These CeS deformation modes are found at
lower frequencies.
1589 cm−1
,
1477/1483 cm−1
,
1387/1385 cm−1
,
1267/1264 cm−1
,
1131/1139 cm−1
,
1126/1114 cm−1
,
1075/1064 cm−1 and 989/
981 cm−1 in B3LYP/M06-2X methods and 6-311++G(d,p) basis set.
The CeH out-of-plane bending vibrations were observed in the region
650–900 cm−1 in literature [53]. In this study, the out-of-plane modes
were calculated at 938/949 cm−1
,
919/927 cm−1
,
843/850 cm−1
,
826/835 cm−1, 798/808 cm−1 and 794/803 cm−1 in B3LYP/M06-2X
methods and 6-311++G(d,p) basis set.
3.3.3. Fluorophenyl group vibrations
The aromatic CeF stretching mode generally observed at
1270–1100 cm−1. In this study, we observed two CeF stretching modes
calculated at 1213/1226 cm−1 and 1188/1195 cm−1 in B3LYP/M06-
2X methods and 6-311++G(d,p) basis set with 11% and 35% PED
contribution, respectively. These stretching modes were observed at
1213/1220 cm−1 and 1213/1191 cm−1 in FT-IR/Laser-Raman spectra.
This CeF mode of 1-(3-chloro-4-fluorophenyl)-3-[3-(trifluoromethyl)
phenyl]thiourea were reported at 1231 cm−1 with 35% PED [43].
Furthermore, these CeF modes were reported at 1227, 1225 cm−1 in
the IR spectrum and at 1239 and 1223 cm−1 theoretically [50,51].
The fundamental vibrational assignments of the experimental and
calculated frequencies (with B3LYP and M06-2X functionals) of the
other modes excluding of the aforementioned modes (the remaining
modes) were given in detailed in Table 2. These modes could be de-
termined from Fig. 4 (a and b) and Fig. 5 (a and b), respectively.
3.4. 1H and 13C NMR chemical shifts
The 1H and 13C NMR chemical shift spectra of the title compound
11

Y. Sert, et al.
ChemicalPhysicsLetters735(2019)136762
Fig. 6. 1H (a) and 13C (b) NMR spectra of title compound.
12

Y. Sert, et al.
ChemicalPhysicsLetters735(2019)136762
Table 3
The experimental and computed 1H and 13C NMR isotropic chemical shifts (with respect to TMS, all values in ppm) of 1-(adamantan-1-yl)-3-(4-fluorophenyl)
thiourea.
Atoms
δexp.
δcal. (B3LYP)
δcal. (M06-2X)
Atoms
δexp.
δcal. (B3LYP)
δcal. (M06-2X)
C1
136.28
125.97–126.05
160.33
157.93
115.19–115-41
136.28
179.60
53.75
135.80
123.95
172.97
140.33
123.09
135.76
189.79
62.71
37.20
41.33
37.33
43.64
49.31
37.41
42.38
42.15
43.04
152.77
138.69
184.07
153.89
137.62
152.29
209.30
59.71
32.50
41.16
32.14
43.78
50.04
32.38
42.93
42.74
43.53
H2
7.09–7.13 and 7.43
7.41
7.44
7.41
7.58
1.68
1.79
1.75
1.76
1.66
1.71
1.95
1.88
2.05
3.53
1.35
1.67
1.44
1.58
3.80
6.85
5.58
8.07
8.15
8.18
8.18
1.63
1.82
1.67
1.94
1.84
1.62
1.61
1.63
1.69
3.55
1.29
1.59
1.30
1.60
4.04
7.28
5.79
C3
H4
C5
H9
C7
H11
H16
H41
H28
H29
H31
H32
H18
H26
H40
H20
H21
H23
H24
H38
H39
H34
H36
C8
1.64
C10
C12
C13
C14
C15
C17
C19
C22
C25
C27
C30
C37
29.50
36.46
29.50
2.05
2.23
41.32
41.32
29.50
36.46
36.46
41.42
9.24
7.22
Table 4
The UV–Vis. spectral parameters and electronic transitions measured and computed in DMF of 1-(adamantan-1-yl)-3-(4-fluorophenyl)thiourea.
The UV–Vis. spectral parameters computed with the B3LYP/6-311++G(d,p) level
Exp. λ (nm)
272
Transition
n → π*
Calc. λ (nm)
Oscillator strength
Major contributions
306.05
281.24
275.74
274.30
254.67
247.69
242.89
241.56
0.0009
0.0004
0.0773
0.2054
0.0061
0.0102
0.0695
0.1543
H → L + 1 (77%), H → L + 3 (15%)
H → L (92%)
H-1 → L (88%)
H-1 → L + 1 (88%)
H → L + 3 (83%), H → L + 1 (14%)
H-2 → L (74%), H-2 → L + 1 (11%)
H-2 → L + 1 (49%), H → L + 2 (32%)
H → L + 2 (53%), H-2 → L + 1 (31%)
The UV–Vis. spectral parameters computed with the M06-2X/6-311++G(d,p) level
Exp. λ (nm)
272
Transition
n → π*
Calc. λ (nm)
Oscillator strength
Major contributions
280.74
247.50
238.44
224.94
223.15
220.10
215.34
212.86
0.0013
0.4070
0.0253
0.0170
0.1343
0.0681
0.0089
0.0074
H → L + 1 (37%), H → L + 8 (14%), H → L + 13 (10%)
H-1 → L + 1 (50%)
H-2 → L (21%), H-1 → L (16%), H-2 → L + 2 (13%)
H → L + 5 (28%), H → L + 2 (20%), H → L (19%)
H-2 → L + 1 (23%), H-1 → L + 5 (14%)
H-1 → L (20%), H-1 → L + 5 (17%), H-1 → L + 2 (16%), H-2 → L + 1 (15%)
H → L + 1 (23%), H → L + 7 (13%), H → L + 8 (13%)
H → L (41%), H → L + 2 (28%)
were recorded in DMSO‑d6 (Fig. 6 a and b). The 1H and 13C NMR
chemical shift were calculated at both the B3LYP/6-311++G(d,p)
level and the M06-2X/6-311++G(d,p) using IEFPCM model and GIAO
method in DMSO. The computed and experimental NMR chemical shifts
are shown in Table 3.
slightly higher values. The recorded and calculated NMR chemical
shifts for these carbons were found at δ 160.33 (exp.)/172.97 (B3LYP)/
184.07 (M06-2X) and 157.93 (exp.)/140.33 (B3LYP)/153.89 (M06-2X)
ppm, respectively. The chemical shifts of aromatic carbons usually
observed in the range of δ 100–175 ppm, depending on the nature of
the substituent groups attached to these carbons [55–57]. The aromatic
carbons (C1, C3, C5, C7, C8 and C10) of the title molecule were shown
as characteristic signals in the expected region. The C1, C3, C8 and C10
carbons were shown at δ 136.28, 125.95–126.05, 115.19–115.41 and
136.28 ppm, while they were computed at 135.80, 123.95, 123.09 and
135.76 ppm with B3LYP level and 152.77, 138.69, 137.62 and
152.29 ppm with M06-2X, respectively. The aliphatic carbons give
The electronegativity, conjugation, inductive effect and nature of
the substituents influence the electron distribution in the molecules and
consequently its NMR chemical shifts [54]. In the 13C NMR spectrum,
the thiourea carbon atom (C12) was experimentally assigned at δ
179.60 ppm, and computed at δ 189.79 ppm with B3LYP level and δ
209.30 ppm with M06-2X. The C5 and C7 carbon atoms attached to the
electronegative fluorine and nitrogen atoms were normally observed at
13

Y. Sert, et al.
ChemicalPhysicsLetters735(2019)136762
1.35–3.80 ppm with B3LYP level and δ 1.29–4.04 ppm with M06-2X.
The thiourea NH protons (H34 and H36) were assigned at δ 9.24 and δ
7.22 ppm and they were calculated at δ 6.85 and 7.28 ppm with B3LYP
level and δ 5.58 and 5.79 ppm with M06-2X. This discrepancy between
NMR signals of these two NH protons could be attributed to the relative
electron withdrawing effect of the aromatic ring compared to the ali-
phatic adamantane cage.
3.5. UV–Vis. spectroscopic analysis
The TD-DFT method for B3LYP and M06-2X functionals at the 6-
311++G(d,p) basis set was used to obtain UV–Vis. spectroscopic
parameter of the title compound. The theoretical UV–Vis. parameters
such as wavelengths, oscillator strengths and excitation energies com-
puted with IEFPCM solvent model (solvent = DMF) based on optimized
molecular structures in DMF are listed in Table 4. The major con-
tributions to the electronic transitions corresponded to the computed
wavelengths were found by GaussSum 3.0 program [38]. The measured
and simulated UV–Vis. spectra at the interval of 200–500 nm in DMF
are depicted in Fig. 7 (a and b). An experimental electronic wavelength
was arisen at 272 nm and it was ascribed to n → π* electronic transi-
tion, and the obtained all theoretical values were given in detailed in
Table 4. These values computed with B3LYP and M06-2X computa-
tional levels are the most intensity values obtained of oscillator
strengths in both levels.
3.6. HOMO and LUMO analyses
The highest occupied molecular orbital (HOMO) and lowest un-
occupied molecular orbital (LUMO) are known as the frontier molecule
orbitals (FMOs). They have an important role in chemical reactivity
[59]. They provide great convenience to determine intramolecular
charge transfers and molecular electronic transitions. Additionally, they
can be used to compute many molecular electronic properties [60]. The
HOMOs can be taken as donor groups filled by electrons, whereas the
LUMOs are defined as acceptor groups unfilled by electrons [61].
The HOMOs (H and H-1) and LUMOs (L and L + 1) surfaces were
simulated by .chk file of the optimized molecular structures in DMF
with the B3LYP and M06-2X/6-311++G(d,p) levels. Fig. 8 (a and b)
shows the HOMO-1, HOMO, LUMO and LUMO + 1 simulations and
their calculated energies.
Fig. 7. The experimental (a) and theoretical (b) UV–Vis. spectra of the title
compound.
NMR signals within the region up to about 60 ppm [54]. The ada-
mantane group which is a cycloalkane compound showed the 13C NMR
chemical shift signals at the interval of δ 28.24–49.09 ppm. The NMR
chemical shifts for C13, C14, C15, C17, C19, C22, C25, C27, C30 and
The HOMO-1, HOMO, LUMO, LUMO + 1, HOMO-LUMO and
HOMO-1-LUMO + 1 energy values were calculated as −6.2428,
−6.0734, −1.1249, −1.0966 4.9485 and 5.1462 eV for the B3LYP/6-
311++G(d,p) level and −7.5966, −7.5038, −0.2316, −0.1695,
7.2722 and 7.4271 eV for the M06-2X/6-311++G(d,p) level, respec-
tively. The HOMO and LUMO analyses were performed to verify the
presence of the n → π* electronic transition corresponding to the ob-
served wavelength at 272 nm in the experimental UV–Vis. spectrum of
the compound. In this connection, we can conclude from Fig. 8 (a and
b) that the HOMO and HOMO-1 localizations obtained with both
computational levels are mostly placed on lone pairs of sulfur atom of
the thiourea group of the title molecule, whereas the LUMO and
LUMO + 1 are mainly formed from π-type anti-bonding molecular or-
bitals of phenyl ring. These localizations on HOMOs and LUMOs con-
firm electronic transition mentioned in the compound.
C37 carbons in this group were recorded in the range of
δ
29.50–53.75 ppm, while they were computed at the intervals of δ
37.20–62.71 ppm with B3LYP level and 32.14–59.71 ppm with M06-
2X. The adamantane 13C NMR chemical shifts are consistent with the
previously reported data [58].
The aromatic ring protons give chemical shift signals in the region
of δ 6.5–8.0 ppm [54–56]. The 1H NMR spectrum showed the aromatic
protons (H2, H4, H9 and H11) at δ 7.09–7.13 and 7.43 ppm. These
protons were computed at the intervals of δ 7.41–7.58 ppm with B3LYP
level and 8.07–8.18 ppm with M06-2X. The adamantane protons (15H)
were experimentally detected at three different locations in the 1H NMR
spectrum. The H16, H28, H29, H31, H32 and H41 (6 protons) and H18,
H26 and H40 (3 protons) were assigned at δ 1.64/1.66–1.79 (B3LYP)/
1.62–1.94 (M06-2X) ppm and 2.05/1.88–2.05 (B3LYP)/1.61–1.69
(M06-2X) ppm, respectively. The H20, H21, H23, H24, H38 and H39 (6
protons), which are adjacent to the electronegative nitrogen atom were
3.7. Molecular docking studies
assigned at
δ 2.23 ppm, and calculated at the intervals of δ
Protein (receptor) and ligand interactions play an important role in
14

Y. Sert, et al.
ChemicalPhysicsLetters735(2019)136762
Fig. 8. Calculated HOMO-LUMO plots of the title compound with B3LYP/6-311++G(d,p) (a) and M06-2X (b)/6-311++G(d,p).
the distribution mechanism, metabolism and transport of small mole-
cules in biological systems and processes [62]. Therefore, the aim of
this section is to research molecular docking between the potential
bioactive agent 1-(adamantan-1-yl)-3-(4-fluorophenyl)-thiourea (li-
gand) and the protein DNA gyrase (PDB: 3U2D) receptor interaction
mechanism. The researched mechanism was prepared in two step:
firstly, we optimized the structure with B3LYP/6-311++ method/
basis set for most stable situation, so ligand structure was converted
into PDB format (Protein Data Bank). Later, the 3U2D-target or receptor
structure was determined and obtained from SwissTargetPrediction
[63] and Protein Data Bank (PDB) [64]. The X-ray crystal structure of
protein DNA gyrase (3U2D) was studied by Eakin et al. [65]. Both li-
gand and receptor were arranged with Discover Studio Visualizer 4.0
(DSV 4.0) software [66] for docking study using AutoDock Vina pro-
gram [39]. For docking process, the docking positions or grid box sizes
were taken as 60 × 74 × 74 Å3 and x, y, z centers were determined as
15

Y. Sert, et al.
ChemicalPhysicsLetters735(2019)136762
Table 5
adamantan-1-yl and ILE-102/ILE-86. Also, between NH and GLU-58/
ASP-81 attractive charge interactions could be observed from the Fig. 9
(a) and (b). In this section finally we computed the inhibition constant
(Ki) as 3.18024 μM from Ki = exp(ΔG/RT) equation, where ΔG, R and T
are the docking energy (binding free energy), gas constant
(1.9872036 × 10−3 kcal/mol) and room temperature (298.15 K), re-
spectively.
AutoDock Vina results of the binding affinity and RMSD values of different
poses in 3U2D receptor of the title compound.
Mode
Affinity (kcal/mol)
Distance from best mode (Å)
RMSD l.b.
RMSD u.b.
1
−7.5
−7.0
−6.5
−6.3
−6.3
−6.2
−6.2
−6.1
−6.1
−6.1
0.000
0.000
2
31.497
17.226
16.893
18.881
29.332
2.916
32.406
19.617
19.349
19.838
30.679
4.036
3
4
4. Conclusions
5
6
The vibrational analysis (FT-IR/Laser-Raman) of potential bioactive
agent namely, 1-(adamantan-1-yl)-3-(4-fluorophenyl)thiourea was stu-
died experimentally and theoretically using the DFT-B3LYP/M06-2X
methods with 6-311++G(d,p) basis set. The wavenumbers were cal-
culated theoretically using Gaussian 09 W software and the results were
analyzed with VEDA 4 program. The comparison of the observed (ex-
perimental) and the calculated outcomes indicated that the scaled
B3LYP method is more accurate than the M06-2X method for both the
vibrational frequencies and the geometric parameters. Their sum of
electronic and zero-point energies was calculated as −1267.924782 a.u
and −1267.540659 a.u, respectively, these energy values also sup-
ported the above mentioned results. Later, the 1H and 13C NMR che-
mical shift spectra recorded in DMSO‑d6 of the title compound and
these NMR chemical shift were calculated at the B3LYP/M06-2X
methods 6-311++G(d,p) basis level IEFPCM model and GIAO method
in DMSO‑d6. In addition, the molecular orbital energies and their dis-
tributions (HOMO-LUMO clouds) were obtained and experimental/
theoretical UV–Vis. analysis was performed to support the HOMO-
LUMO analysis. Finally, the molecular docking outcomes showed that
the title compound may exhibit antibacterial activity via inhibition of
bacterial DNA gyrase-3U2D enzyme.
7
8
5.093
7.669
9
13.986
29.612
16.427
30.570
10
18.276, −0.553 and 11.015, respectively. The general assumption is
that for a good docking should be 2 Å according to the RMSD analysis
[67]. In this section, 10 different modes were determined for ligand
which is within the 3U2D receptor, and the obtained docking results are
given in Table 5. The results shown in Table 5 revealed that the best
docking pose was obtained with the binding energy of −7.5 kcal/mol.
The amino acids ASP-81 which interacts with NH hydrogen atom (the
distance is 2.24 Å), ASP-81 which interacts with CS sulfur atom (the
distance is 3.70 Å), THR-173 which interacts with CS sulfur atom (the
distance is 3.52 Å) and ASN-54 which interacts with NH hydrogen atom
(the distance is 2.41 Å) as shown in Fig. 9.
In this figure, the surfaces around ligand (a) and 2D forms of mo-
lecular positions (b) could be seen. Additionally, between fluorophenyl
ring and ILE-175/ILE-86 amino acids were observed as alkyl and π-
alkyl interactions. These interactions also were observed between
Fig. 9. The molecular docking results of the title compound with 3U2D protein, surfaces around ligand (a) and 2D forms (b).
16

Y. Sert, et al.
ChemicalPhysicsLetters735(2019)136762
Declaration of Competing Interest
[29] H.Y. Hassan, N.A. El-Koussi, Z.S. Farghaly, Chem. Pharmaceut. Bull. 46 (1998) 863.
[30] R. Ottanà, S. Carotti, R. Maccari, I. Landini, G. Chiricosta, B. Caciagli, M.G. Vigorita,
E. Mini, Bioorg. Med. Chem. Lett. 15 (2005) 3930.
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influ-
ence the work reported in this paper.
[31] R. Ottana, R. Maccari, M.L. Barreca, G. Bruno, A. Rotondo, A. Rossi, G. Chiricosta,
R. Di Paola, L. Sautebin, S. Cuzzocrea, Bioorgan. Med. Chem. 13 (2005) 4243.
[32] G. Demirtaş, N. Dege, M.M. Al-Shehri, A.A. El-Emam, N.R. El-Brollosy,
O. Büyükgüngör, Acta Crystallog. Sect. E: Struct. Rep. Online 68 (2012) o1523.
[33] A. Frish, A. Nielsen, A. Holder, Pittsburg, PA (2001).
[34] M.J. Frisch, G. Trucks, H.B. Schlegel, G. Scuseria, M. Robb, J. Cheeseman, G.
Scalmani, V. Barone, B. Mennucci, G. Petersson, Gaussian Inc. Wallingford CT 27
(2009) 34.
Acknowledgements
This work was funded by the Deanship of Scientific Research at
Princess Nourah bint Abdulrahman University through the Research
Group Program (Grant No. RGP-1438-0010).
[35] M. Jamróz, VEDA 4 program for Vibrational Energy Distribution Analysis. Warsaw,
Poland, 2004Ā2010, 2004.
[36] M.H. Jamróz, Spectrochim. Acta Part A: Mol. Biomol. Spectrosc. 114 (2013) 220.
[37] S. Leonid, Chemissian Software, 2017.
[38] N.M. O'boyle, A.L. Tenderholt, K.M. Langner, J. Comput. Chem. 29 (2008) 839.
[39] O. Trott, A.J. Olson, J. Comput. Chem. 31 (2010) 455.
[40] M.S. Almutairi, A.M. Alanazi, E.S. Al-Abdullah, A.A. El-Emam, S.K. Pathak,
R. Srivastava, O. Prasad, L. Sinha, Spectrochim. Acta Part A: Mol. Biomol. Spectrosc.
140 (2015) 1.
References
[1] G. Lamoureux, G. Artavia, Curr. Med. Chem. 17 (2010) 2967.
[2] J. Liu, D. Obando, V. Liao, T. Lifa, R. Codd, Eur. J. Med. Chem. 46 (2011) 1949.
[3] L. Wanka, K. Iqbal, P.R. Schreiner, Chem. Rev. 113 (2013) 3516.
[4] W. Davies, R. Grunert, R. Haff, J. McGahen, E. Neumayer, M. Paulshock, J. Watts,
T. Wood, E. Hermann, C. Hoffmann, Science 144 (1964) 862.
[5] H.A. Wendel, M.T. Snyder, S. Pell, Clin. Pharmacol. Therap. 7 (1966) 38.
[6] R.S. Schwab, A.C. England, D.C. Poskanzer, R.R. Young, Jama 208 (1969) 1168.
[7] J. Balzarini, B. Orzeszko-Krzesińska, J.K. Maurin, A. Orzeszko, Eur. J. Med. Chem.
44 (2009) 303.
[41] M. Mushtaque, M. Jahan, M. Ali, M.S. Khan, M.S. Khan, P. Sahay, A. Kesarwani, J.
Mol. Struct. 1122 (2016) 164.
[42] C.Y. Panicker, H.T. Varghese, A. George, P.K.V. Thomas, Eur. J. Chem. 1 (2010)
173.
[43] Y.S. Mary, V. Aswathy, C.Y. Panicker, A. Bielenica, P. Brzózka, O. Savczenko,
S. Armaković, S.J. Armaković, C. Van Alsenoy, RSC Adv. 6 (2016) 111997.
[44] M. Turner, J. McKinnon, S. Wolff, D. Grimwood, P. Spackman, D. Jayatilaka, M.
Spackman, CrystalExplorer17. University of Western Australia, Nedlands, Western
Australia, 2017.
[8] M. Burstein, A. Serbin, T. Khakhulina, I. Alymova, L. Stotskaya, O. Bogdan,
E. Manukchina, V. Jdanov, N. Sharova, A. Bukrinskaya, Antivir. Res. 41 (1999) 135.
[9] A.A. El-Emam, O.A. Al-Deeb, M. Al-Omar, J. Lehmann, Bioorgan. Med. Chem. 12
(2004) 5107.
[45] F.L. Hirshfeld, Theoret. Chim. Acta 44 (1977) 129.
[46] M.A. Spackman, D. Jayatilaka, CrystEngComm 11 (2009) 19.
[47] A.-M.S. Al-Tamimi, A.A. El-Emam, O.A. Al-Deeb, O. Prasad, S.K. Pathak,
R. Srivastava, L. Sinha, Spectrochim. Acta Part A: Mol. Biomol. Spectrosc. 124
(2014) 108.
[10] F. Hayden, J. Gwaltney, R. Van de Castle, K. Adams, B. Giordani, Antimicrob.
Agents Chemother. 19 (1981) 226.
[11] K. Lundahl, J. Schut, J. Schlatmann, G. Paerels, A. Peters, J. Med. Chem. 15 (1972)
129.
[48] A.A. El-Emam, A.-M.S. Al-Tamimi, K.A. Al-Rashood, H.N. Misra, V. Narayan,
O. Prasad, L. Sinha, J. Mol. Struct. 1022 (2012) 49.
[12] P. Lorenzo, R. Alvarez, M.A. Ortiz, S. Alvarez, F.J. Piedrafita, A.R. de Lera, J. Med.
Chem. 51 (2008) 5431.
[49] A. Rao, J. Balzarini, A. Carbone, A. Chimirri, E. De Clercq, A.M. Monforte,
P. Monforte, C. Pannecouque, M. Zappalà, Il Farmaco 59 (2004) 33.
[50] Y.S. Mary, C.Y. Panicker, M. Sapnakumari, B. Narayana, B. Sarojini, A.A. Al-Saadi,
C. Van Alsenoy, J.A. War, Spectrochim. Acta Part A: Mol. Biomol. Spectrosc. 138
(2015) 73.
[13] J. Min, V.S. Guillen, A. Sharma, Y. Zhao, Y. Ziegler, P. Gong, C.G. Mayne,
S. Srinivasan, S.H. Kim, K.E. Carlson, J. Med. Chem. 60 (2017) 6321.
[14] S.-Y. Sun, P. Yue, R.A. Chandraratna, Y. Tesfaigzi, W.K. Hong, R. Lotan, Mol.
Pharmacol. 58 (2000) 508.
[51] Y.S. Mary, H.T. Varghese, C.Y. Panicker, T. Ertan, I. Yildiz, O. Temiz-Arpaci,
Spectrochim. Acta Part A: Mol. Biomol. Spectrosc. 71 (2008) 566.
[52] A. Teimouri, A.N. Chermahini, M. Emami, Arkivoc 12 (2008) 172.
[53] V.D. Vitnik, Ž.J. Vitnik, N.R. Banjac, N.V. Valentić, G.S. Ušćumlić, I.O. Juranić,
Spectrochim. Acta Part A: Mol. Biomol. Spectrosc. 117 (2014) 42.
[54] R.M. Silverstein, F.X. Webster, D.J. Kiemle, D.L. Bryce, Spectrometric Identification
of Organic Compounds, John wiley & sons, 2014.
[15] L. Al-Wahaibi, H. Hassan, A. Abo-Kamar, H. Ghabbour, A. El-Emam, Molecules 22
(2017) 710.
[16] E. Bogatcheva, C. Hanrahan, B. Nikonenko, G. De los Santos, V. Reddy, P. Chen,
F. Barbosa, L. Einck, C. Nacy, M. Protopopova, Bioorg. Med. Chem. Lett. 21 (2011)
5353.
[17] A.A. El-Emam, A.-M.S. Al-Tamimi, M.A. Al-Omar, K.A. Alrashood, E.E. Habib, Eur.
J. Med. Chem. 68 (2013) 96.
[55] R.J. Anderson, D.J. Bendell, P.W. Groundwater, Organic Spectroscopic Analysis,
Royal Society of Chemistry, 2004.
[18] K. Omar, A. Geronikaki, P. Zoumpoulakis, C. Camoutsis, M. Soković, A. Ćirić,
J. Glamočlija, Bioorg. Med. Chem. 18 (2010) 426.
[56] J.B. Lambert, H.F. Shurvell, D.A. Lightner, R.G. Cooks, Introduction to Organic
Spectroscopy, Macmillan Publishing Company, 1987.
[19] M. Protopopova, C. Hanrahan, B. Nikonenko, R. Samala, P. Chen, J. Gearhart,
L. Einck, C.A. Nacy, J. Antimicrob. Chemother. 56 (2005) 968.
[20] S.A. Charman, S. Arbe-Barnes, I.C. Bathurst, R. Brun, M. Campbell, W.N. Charman,
F.C. Chiu, J. Chollet, J.C. Craft, D.J. Creek, Proc. Natl. Acad. Sci. 108 (2011) 4400.
[21] Y. Dong, S. Wittlin, K. Sriraghavan, J. Chollet, S.A. Charman, W.N. Charman,
C. Scheurer, H. Urwyler, J. Santo Tomas, C. Snyder, J. Med. Chem. 53 (2009) 481.
[22] M.A. Abou-Gharbia, W.E. Childers, H. Fletcher, G. McGaughey, U. Patel,
M.B. Webb, J. Yardley, T. Andree, C. Boast, R.J. Kucharik, J. Med. Chem. 42 (1999)
5077.
[57] D. Pavia, G. Lampman, G. Kriz, J. Vyvyan, Introduction to spectroscopy; Brooks/
Cole, Cengage Learning, USA. ISBN 0-495-11478-9, 2009.
[58] T. Pehk, E. Lippmaa, V. Sevostjanova, M. Krayuschkin, A. Tarasova, Organ. Magn.
Reson/ 3 (1971) 783.
[59] K. Fukui, Science 218 (1982) 747.
[60] Y.B. Alpaslan, H. Gökce, G. Alpaslan, M. Macit, J. Mol. Struct. 1097 (2015) 171.
[61] H. Buyukuslu, M. Akdogan, G. Yildirim, C. Parlak, Spectrochim. Acta Part A: Mol.
Biomol. Spectrosc. 75 (2010) 1362.
[23] J. Bormann, Eur. J. Pharmacol. 166 (1989) 591.
[62] U. Kragh-Hansen, Pharmacol. Rev. 33 (1981) 17.
[24] X. Huang, R. Huang, Z. Liao, Y. Pan, S. Gou, H. Wang, Eur. J. Med. Chem. 108
(2016) 381.
[63] http://www.swisstargetprediction.ch/.
[64] https://www.rcsb.org/.
[25] J. Li, J.Z. Tan, L.l. Chen, J. Zhang, X. Shen, C.l. Mei, L.l. Fu, L.p. Lin, J. Ding, B.
Xiong, Acta Pharmacol. Sin. 27 (2006) 1259.
[65] A.E. Eakin, O. Green, N. Hales, G.K. Walkup, S. Bist, A. Singh, G. Mullen, J. Bryant,
K. Embrey, N. Gao, Antimicrob. Agents Chemother. 56 (2012) 1240.
[66] http://www.3dsbiovia.com/.
[26] W. Liu, J. Zhou, T. Zhang, H. Zhu, H. Qian, H. Zhang, W. Huang, R. Gust, Bioorg.
Med. Chem. Lett. 22 (2012) 2701.
[67] J.-L. Stigliani, V. Bernardes-Génisson, J. Bernadou, G. Pratviel, Organ. Biomol.
Chem. 10 (2012) 6341.
[27] K.H. Chikhalia, M.J. Patel, J. Enzyme Inhib. Med. Chem. 24 (2009) 960.
[28] S.D. Joshi, S.R. Dixit, M. Kirankumar, T.M. Aminabhavi, K. Raju, R. Narayan,
C. Lherbet, K.S. Yang, Eur. J. Med. Chem. 107 (2016) 133.
17