Conformational analysis, X-ray crystallographic, FT-IR, FT-Raman, DFT, MEP and molecular docking studies on 1-(1-(3-methoxyphenyl) ethylidene) thiosemicarbazide

Article abstract of DOI:10.1016/j.saa.2014.12.026

Conformational analysis, X-ray crystallographic, FT-IR, FT-Raman, DFT, MEP and molecular docking studies on 1-(1-(3-methoxyphenyl) ethylidene) thiosemicarbazide (MPET) are investigated. From conformational analysis the examination of the positions of a mo

Full text of DOI:10.1016/j.saa.2014.12.026

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 139 (2015) 321–328
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Conformational analysis, X-ray crystallographic, FT-IR, FT-Raman, DFT,
MEP and molecular docking studies on 1-(1-(3-methoxyphenyl)
ethylidene) thiosemicarbazide
R.R. Saravanan a, , S. Seshadri , S. Gunasekaran , R. Mendoza-Meroño , S. Garcia-Granda
⇑
b
c
d
d
a
Department of Physics, Misrimal Navajee Munoth Jain Engineering College, Thoraipakkam, Chennai 600 097, India
Department of Physics, L.N. Govt. Arts College, Ponneri, Thiruvallur 601 001, India
Research & Development, St. Peter’s University, Avadi, Chennai 600 054, India
Faculty of Chemistry, Department of Physical and Analytical Chemistry, University Oviedo, C/ Julian Claveria, 8, 33006 Oviedo, Asturias, Spain
b
c
d
h i g h l i g h t s
g r a p h i c a l a b s t r a c t
ꢀ
ꢀ
ꢀ
The FT-IR, FT-Raman studies were
carried out for synthesized MPET.
MEP plays an important role in
determining the stability of the MPET.
Structures of MPET have been studied
by spectroscopic and X-ray diffraction
method.
ꢀ
Conformational analysis used to
examine the positions of a MPET
molecule.
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 July 2014
Received in revised form 22 November 2014
Accepted 10 December 2014
Available online 30 December 2014
Conformational analysis, X-ray crystallographic, FT-IR, FT-Raman, DFT, MEP and molecular docking stud-
ies on 1-(1-(3-methoxyphenyl) ethylidene) thiosemicarbazide (MPET) are investigated. From conforma-
tional analysis the examination of the positions of a molecule taken and the energy changes is observed.
The docking studies of the ligand MPET with target protein showed that this is a good molecule which
docks well with target related to HMG-CoA. Hence MPET can be considered for developing into a potent
anti-cholesterol drug. MEP assists in optimization of electrostatic interactions between the protein and
the ligand. The MEP surface displays the molecular shape, size and electrostatic potential values. The
optimized geometry of the compound was calculated from the DFT–B3LYP gradient calculations employ-
ing 6-31G (d, p) basis set and calculated vibrational frequencies are evaluated via comparison with exper-
imental values.
Keywords:
MPET
FT-IR
FT-Raman
Docking
Crystallography
Ó 2014 Elsevier B.V. All rights reserved.
Introduction
first reports on their medical applications began to appear in the
Fifties as drugs against tuberculosis and leprosy [1,2]. Thiosemicar-
Thiosemicarbazones are compounds that have been studied for
a considerable period of time for their biological properties. Traces
of interest date back to the beginning of the 20th century, but the
bazones are a class of small molecules that has been evaluated over
the last 50 years as antivirals [3,4] and as anticancer therapeutics,
[5] as well as for their parasiticidal action against Plasmodium fal-
ciparum [6] and Trypanosoma cruzi [7,8] which are the causative
agents of malaria and Chagas’s disease, respectively. Brockman
et al. first showed that 2-formylpyridine thiosemicarbazone
⇑
Corresponding author. Mobile: +91 99940 31849.
E-mail address: saravapj@gmail.com (R.R. Saravanan).
http://dx.doi.org/10.1016/j.saa.2014.12.026
386-1425/Ó 2014 Elsevier B.V. All rights reserved.
1

3
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R.R. Saravanan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 139 (2015) 321–328
Table 1
possesses anti-leukemic activity in mice bearing leukemic cells [9].
Following this report, various aliphatic, aromatic, and heteroaro-
matic carbaldehyde thiosemicarbazones were synthesized and
evaluated for antitumor activity against a wide spectrum of trans-
planted murine neoplasms [10]. Vibrational spectroscopy has the
potential to yield valuable structural and conformational informa-
tion of organic compounds if used in conjugation with accurate
quantum chemical calculations. [11].
During the last few years, a variety of experimental methods
developed by physicists and biologists allowed direct monitoring
of ligand-receptor interaction at the single molecule level. The con-
tinual progress within the field of crystallography, spectroscopy
and Bioinformatics made available the structure of many ligand–
receptor complexes with angstrom resolution. In this paper, we
present, the conformational stability, synthesis, X-ray crystallo-
graphic, molecular structure, spectroscopic characterization and
molecular docking studies of 1-(1-(3-methoxyphenyl) ethylidene)
thiosemicarbazide (MPET). The optimized geometry and vibra-
tional wavenumbers for conformers of MPET were calculated at
the B3LYP level of theory with the 6-31G basis set. In order to pro-
vide templates for molecular modeling studies, experimental
results obtained from X-crystallography and those from B3LYP
methods were compared. The possible stable conformers of (MPET)
were searched. Molecular docking studies for MPET also performed
to find the interaction with anti cholesterol target.
Details of the experimental diffraction data collections and refinements.
I
Empirical formula
Formula weight
Color, shape
Temperature (K)
Crystal size (mm)
Crystal system
Space group
10 13 3
C H N OS
223.29
Colorless
293
0.20 0.17 0.11
Monoclinic
1
P2 /c
Lattice constants
a (Å)
b (Å)
c (Å)
6.9460(1)
8.4300(2)
19.6150(2)
90.00
99.722(2)
90.00
1140.7(3)
4
1.5418
1.300
4.53–73.03
2.350
472
4538
2201 [R(int) = 0.0140]
188
1.061
R1 = 0.0327
wR2 = 0.0908
R1 = 0.0340
wR2 = 0.0923
0.188 and ꢁ0.182
a
(°)
b (°)
(°)
c
3
Volume (Å )
Z
k (Å)
Calculated density,
ꢁ
q
(g cm 3
)
h rang for data collection (°)
Absorption coefficient (mm 1)
ꢁ
F(000)
Reflections collected
Independent reflections
Parameters
Goodness-of-fit on F2
Final R indices [I > 2
r
(I)]
R indices (all data)
Experimental
Largest
D
F peak and hole (e Åꢁ3)
Sample preparation
Table 2
0
A solution of 1-(3-methoxyphenyl) ethanone (3.003 g 0.02 mol)
and thiosemicarbazide (1.82 g, 0.02 mol) in absolute methanol
(80 ml) was refluxed for 2 h in the presence of p-toluenesulfonic
acid as a catalyst, with continuous stirring. On cooling to room
temperature the precipitate was filtered off, washed with copious
cold methanol and dried in air. Colorless single crystals of MPET
were obtained after recrystallization from a solution in methanol.
Hydrogen-bond geometry ( AÅ , °).
D–HꢂꢂꢂA
D–H (Å)
HꢂꢂꢂA (Å)
2.68(2)
2.48(2)
2.27(2)
DꢂꢂꢂA (Å)
3.526(2)
3.344(2)
3.071(2)
D–HꢂꢂꢂA (°)
162.1(2)
160.4(2)
149.1(2)
N(2)–H(10)ꢂꢂꢂS(1) (i)
N(3)–H(11a)ꢂꢂꢂS(1)(ii)
N(3)–H(11b)ꢂꢂꢂO(1)(iii)
0.88(2)
0.90(2)
0.90(2)
Symmetry Codes (i) ꢁx, 1/2+y, 1/2ꢁz (ii) ꢁx, ꢁ1/2+y, 1/2ꢁz (iii) 1ꢁx, 2ꢁy, ꢁz.
1
3
H-RMN (DMSO-d6): r (ppm) 2.28 (s 3H, CH ) 3.806 (s 3H,
Fig. 1. The various possible stable conformers of MPET.

R.R. Saravanan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 139 (2015) 321–328
323
Table 3
Total energies of different conformations of MPET calculated at the B3LYP/6-31G (d, p) level of theory.
S. No.
Conformer
Energy (Hartree)
kJ/mol
Energy difference (kJ/mol)
1.
2.
3.
4.
C2
C1
C3
C4
ꢁ1026.53914423
ꢁ1026.52692861
ꢁ1026.49678837
ꢁ1026.49440378
ꢁ2695178.72848369
ꢁ2695146.65637094
ꢁ2695067.52316479
ꢁ2695061.26242327
0.000
32.072
111.205
117.466
Fig. 4. MEP of MPET.
Fig. 2. The structure of the title compound showing 50% probability displacement
ellipsoids and the atom-numbering scheme.
diffractometer equipped with CuK
a
radiation (k = 1.5418 Å). The
OCH
H, Ar-H) 7.44 (s 1H, Ar-H), 7.93 (s 1H, NH
s, –CNH-N). 13C-RMN (DMSO-d ): (ppm) 14.45 (1C, –CH
1C, –OCH
1C, aromatic) 129.47 (1C, aromatic) 139.36 (1C, aromatic)
47.95 (1C, aromatic) 159.55 (1C, –C@N) 179.12 (1C, C@S).
3
) 6.95–6.98 (d 1H, Ar-H) 7.28–7.32 (t 1H, Ar-H) 7.44–7.47 (d
data were processed with CrysAlis software and Empirical absorp-
tion correction using spherical harmonics, were implemented with
SCALE3 ABSPACK scaling algorithm [12]. The crystallographic data,
the data collection parameters, and the refinement parameters for
each structure are summarized in Table 1. The Hydrogen Bond
geometry of MPET is given in Table 2.
1
2
) 8.27 (s 1H, NH
2
) 10.19
) 55.41
(
(
(
6
r
3
3
) 112.05 (1C, aromatic) 115.20 (1C, aromatic) 119.36
1
Crystal structure was solved by direct methods using Sir2008
Single crystal X-ray structure determination
[13] and refined by full-matrix least-square calculations against
2
F
using SHELXL [14]. All non-hydrogen atoms were refined with
The diffraction data from a selected single crystal was collected
at room temperature on Oxford Diffraction Xcalibur Gemini S
anisotropic displacement parameters. All the hydrogen atoms were
located at the difference Fourier map in isotropically refined. The
Fig. 3. Intermolecular interactions in the crystal packing along bc plane.

3
24
R.R. Saravanan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 139 (2015) 321–328
figures were produced using ORTEP-3 [15] MERCURY [16]. The
software used for the preparation of the materials for publication:
WinGX [17], PLATON [18], PARST [19].
physical and chemical properties. The various possible stable con-
formers of MPET were shown in Fig. 1. From B3LYP/6-31G (d, p)
calculation the conformer C2 is predicted more stable from
3
2.072 to 117. 466 kJ/mol than the other MPET conformers. When
comparing C2 with C4 the positional change of atoms like S and
NH . This change makes the structure C2 has more energy than
C4. When comparing C3 and C4 the orientation of both CH and
NH group are changed, but this makes very small change in the
Computational method
The combination of spectroscopic methods with DFT calcula-
tions are powerful tools for understanding the fundamental vibra-
tional properties and the electronic structure of the compounds
2
3
2
[
20]. The entire calculations carried out in the present work were
energy. The total energies obtained for these conformers were
shown in Table 3. It is clear from Table 3 that the conformer C2
has produced the global energy minimum.
performed at B3LYP levels included in the Gaussian 03W [21]
package program with the 6-31G (d, p) basis set functions of the
DFT utilizing gradient geometry optimization [22]. All the geome-
tries were optimized using the 6-31G (d, p) basis set using DFT [23]
employing Becke’s three parameter hybrid functional [24] com-
bined with the Lee–Yang–Parr correlation [25] functional (B3LYP)
method. By combining the results of the Gaussview program [26]
with symmetry considerations, vibrational band assignments were
made with a high degree of accuracy. In order to find the most opti-
mized geometry, the energy calculations were carried out using
the B3LYP method with 6-31G (d, p) basis set for 4 different possi-
ble conformers.
X-ray of the crystal structures
1
The compound crystallizes in the monoclinic lattice with P2 /c
symmetry. The ORTEP diagram of MPET is shown in Fig 2, displace-
ment ellipsoids are drawn at 50% probability level. The molecular
conformation in the crystal the C9–C8/N1/N2/S1 plane form a
dihedral angle of 42.73 (5)° with the benzene ring (C1–C6). The
C@N bond length [1.280 (2) Å] and C@S bond length [1.6916
(
2) Å] are in agreement with those values observed before (Wang
et al. [27]).
The crystal packing is established by typical intermolecular N–
HꢂꢂꢂS hydrogen-bond interactions of thiosemicarbazone moiety,
forming sheets along the 2 axes. The methoxy group is involved
stacking
interactions [Cg1 (C1?C6)ꢂꢂꢂCg1 (iv) = 4.3934 (2) Å, offset = 25.52°
for [iv: 1ꢁx, 1ꢁy, ꢁz] are present in the crystal contributing to
stabilize chains. The Details of the experimental diffraction data
collections and refinements are shown in Table 1.
Results and discussion
Conformational analysis
1
Conformational analysis is the examination of the positions a
molecule takes and the energy changes it undergoes as it converts
among its different conformations. Because each of the various
conformations of a molecule has different properties, the confor-
mation the molecule normally adopts has a deep influence on its
in N–HꢂꢂꢂO strong hydrogen bond Fig 3. Additionally
p–p
Fig. 5. Theoretical and experimental FT-IR spectra of MPET.

R.R. Saravanan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 139 (2015) 321–328
325
Molecular electrostatic potential (MEP)
Vibrational assignments
N–H vibrations
Molecular electrostatic potential (MEP) mapping is very useful
in the investigation of the molecular structure with its physio-
chemical property relationships [28–31]. Molecular electrostatic
potential surfaces are important in computer-aided drug design
as a result of them assisting in optimization of electrostatic inter-
actions between the protein and the ligand. These surfaces
are accustomed compare different inhibitors with substrates or
transition states of the reaction. Electrostatic potential surfaces
are either displayed as isocontour surfaces or mapped onto the
molecular electron density. The later are more widely used because
they maintain the sense of underlying chemical structure better
than isocontour plots. The MEP surface displays the molecular
shape, size and electrostatic potential values. The color scheme
for the MEP surface is partially negative charge or red-electron
rich; partially positive charge or blue-electron deficient; yellow-
slightly electron rich region; light blue-slightly electron deficient
region, respectively. Potential increases in the order
red < orange < yellow < green < blue. The MEP diagram of MPET is
shown in Fig. 4. The MPET molecule must present atoms either
with positive potential isosurface and atoms with negative poten-
tial isosurface. The MEP of MPET clearly indicates the electron rich
centers of sulfur and the positive potential isosurface centers of N1,
O1 and H11B.
The N-H stretching vibrations give rise to a weak band at 3500–
3300 cm . Saravanan et al. [32] have observed the N–H stretching
ꢁ1
ꢁ
1
ꢁ1
band at 3393 cm in FT-IR and 3395 cm in FT Raman spectra of
(E) -1-[1-(4-Chlorophenyl) ethylidene] thiosemicarbazide). In the
experimental FTIR spectrum of MPET observed at 3441,
ꢁ1
ꢁ1
3455 cm and in FT Raman 3445, 3453 cm is assigned to sym-
metric N–H stretching vibration with PEDs 99% and 99% respec-
tively. The symmetric stretching mode calculated at 3443,
3456 cm by B3LYP/6-31G (d, p). Fig. 5 shows that the comparison
of theoretical and experimental FT-IR spectra of MPET. Fig. 6 shows
that the comparison of theoretical and experimental FT-Raman
spectra of MPET.
ꢁ1
C–H vibrations
The C–H stretching vibrations of aromatic and hetero aromatic
ꢁ1
structures occur [33,34] in the region 3100–2900 cm for asym-
metric stretching modes of vibrations. This permits the ready iden-
tification of the structure. A medium band is observed at 2916 and
ꢁ1
2962 cm in infrared and an intense band is observed at 2920 and
ꢁ1
2961 cm in FT-Raman can be assigned to C–H stretching respec-
tively. The corresponding calculated fundamentals using B3LYP/6-
31G (d, p) are 2919 and 2962. The theoretically scaled vibrations
Fig. 6. Theoretical and experimental FT-Raman spectra of MPET.

3
26
R.R. Saravanan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 139 (2015) 321–328
Table 4
Theoretical and experimental vibrational wavenumbers (cmꢁ1) of MPET Calculated using B3LYP/6-31G (d, p).
IR cm 1
ꢁ
m
Raman cm
ꢁ1
m
ꢁ1
cal cm
IR intensity Raman activity
P
Reduced mass
Force constant
Characterisation of normal modes with PED (%)
m
2
3
6
8
6
9
4
7
4.3542
7.5068
5.9822
1.7265
3.9113
0.2783
2.3858
0.7045
7.7305
3.7119
2.7877
1.6427
0.7491
4.9905
1.6370
2.2641
2.3952
4.0996
2.8639
1.4301
3.4716
0.5755
2.4979
0.8660
3.2431
12.9384
3.9710
4.0438
1.1166
4.3139
2.5292
3.0754
0.0970
0.6858
4.4126
6.3711
2.0878
7.2100
9.7691
31.7347
1.8974
13.9415
2.7519
0.6085
0.7386
0.7007
0.7207
0.4538
0.7499
0.6963
0.3824
0.4758
0.7245
0.6685
0.4698
0.4659
0.2448
0.4019
0.2886
0.4935
0.3992
0.1939
0.7472
0.2082
0.2854
0.4978
0.5923
0.6703
0.7027
0.7316
0.7207
0.5439
0.3567
0.1791
0.3551
0.3309
0.6868
0.4316
0.2247
0.1540
0.4223
0.5589
0.4833
0.2681
0.2496
0.3343
0.7485
0.3394
0.5794
0.4438
0.3748
0.5408
0.3125
0.2578
0.7496
0.3001
0.1621
0.5921
0.1993
0.7500
0.5390
0.7107
0.3175
0.3984
0.3402
0.3380
0.3885
0.2999
0.0289
0.0069
0.7498
0.7499
0.4475
0.5383
0.5080
0.2942
0.1166
4.3542
7.5068
5.9822
3.2956
4.0950
2.1853
2.4891
2.1176
3.4792
2.1867
1.3275
1.6434
3.4617
2.9495
4.4755
5.3126
3.7885
3.5444
4.0951
1.2058
4.5765
4.0873
4.2962
1.4837
4.0140
4.0441
2.5420
2.2721
4.8040
1.4230
3.1864
1.5522
2.4989
1.7832
1.2711
2.3212
5.8763
1.5819
2.2583
4.4959
1.8048
1.6818
4.1043
1.2732
1.1265
1.3929
2.6359
1.9619
2.0929
2.9000
3.8786
1.2737
2.5009
2.3578
1.2106
1.3957
1.0471
1.1270
1.1273
1.6377
1.9879
1.6242
5.8616
5.4348
8.8243
1.0351
1.0429
1.1061
1.1006
1.0996
1.0950
1.0880
1.0930
1.0931
0.0021
0.0077
0.0163
0.0163
0.0268
0.0203
0.0332
0.0385
0.0924
0.0619
0.0557
0.0749
0.1802
0.1875
0.3164
0.5379
0.4291
0.4390
0.5191
0.1702
0.7450
0.7246
0.8590
0.3120
0.9515
0.9875
0.6372
0.6686
1.4942
0.5430
1.3579
0.6835
1.2026
0.8690
0.7203
1.3654
3.5419
1.0195
1.4889
3.0847
1.3031
1.2527
3.2479
1.0413
0.9387
1.2067
2.5173
1.9295
2.1634
3.1013
4.3231
1.5056
3.1408
2.9671
1.5824
1.8401
1.3969
1.5115
1.5296
2.2642
2.8070
2.5149
9.1719
8.7486
14.4293
5.5424
5.6501
6.1678
6.1650
6.4352
6.4813
6.5262
6.6628
6.7086
s
s
s
s
c
c
ring (11) + CH
3
twist (17)
ring (16) + CN(27)
s
CH
CH
3
(18) +
(21)
c
CH(18)
3
1
01
120
44
168
04
CH
CH
3
(33) +
3
(26)
s
CN(25)
1
15
66
1
CNrock (41)
CNrock (36)
s
s
c
s
s
1
2
CH
CH
3
(33)
2
2
16
51
212
256
2.3260
3
(24) +
c
CS (15)
149.7140
12.3150
19.1545
4.9603
10.7059
14.4834
1.3401
4.5653
0.3528
104.6209
13.8440
3.1115
2.6713
3.8228
0.3992
4.7611
1.4329
9.3106
3.1283
28.1163
21.0770
23.7718
52.5218
35.2894
0.6533
9.1096
1.0961
1.5534
21.7532
52.0104
17.2099
9.9143
120.3939
0.6475
NH
2
(43) +
(27)
cCN (13)
2
67
286
15
CH
3
294
ring (18)
(23)
3
b CH
3
3
4
36
05
333
400
b CCH(21) + dCS (16)
b NCS (26)
b NH
b ring (37) +
b ring (32)
4
4
21
41
2
(31) +
m
CH (59)
mCN (65)
451
469
504
533
449
470
505
528
c
NH(27)
b CCC (16)
CH (15) + CH3scis(16)
b ring (26) + CO (54)
NH (22) + CO (61)
Ring breathing (65)
x
5
60
574
10
m
577
s
2
m
6
622
681
778
622
33
678
95
619
628
679
697
775
b ring (24) + CO (45)
b CNH (31) + mCS (69)
CH CH (26)
b CCH (15) + mCN (72)
c
c
c
c
6
3
opr (18) +
c
6
CH (15) + cCO (26)
CN (29) + b CNH (15)
CH twist (19) + dCO (23)
8
18
833
860
877
830
862
878
832
865
875
943
962
973
1001
1017
1035
b ring (21) + dCH
CH(43)+dCH (21)
dCH (46) + dCH(35)
b CCH(67)
3
(17)
s
3
946
1.8875
3
9
65
18.4484
78.5506
8.8515
14.9224
3.2886
22.7360
61.6583
103.0271
4.3457
39.0904
8.3031
41.2047
24.5974
14.8739
388.3666
152.4666
9.7992
9
9
74
97
dCH
dCH
3
(27) + dCH(14)
(24)+dCH(32)
3
1015
b CCC(15)
CC (16) +
CH opr (78) + dCH(31)
b CCH(32)
1
031
086
1032
c
3
sCH (26)
1
066
1082
1114
3
1
1110
CH
CH
3
opr(20) +
cCC (51)
1
134
3
opr (45) +
c
CC (32)
1151
1173
1229
1152
1171
1229
1148
1169
1225
1243
1279
8.1783
7.8691
CHipr (56) +
dCH
dCH
m
NN(77)
3
(63) + dCH (29)
200.1657
418.7783
12.9725
11.4490
19.2909
7.7079
123.2757
14.0800
189.7236
3.8316
3
(28)+ b CCH (79)
1244
dCH (47) + dCC(64)
dCH (13) + CN (69)
dCC (31) + CN (56)
(10) + dCC (73)
CC (81)
CH (19)+ dCH(13)
(21)+ CO (79)
CN (84)
1
282
1281
3
m
1
297
m
1
1
319
364
1318
1362
1321
1363
1405
406
1432
439
1448
1452
1460
1474
1490
c
m
c
CH
3
1403
70.4237
8.6845
3
1
b CH
3
t
1429
1446
1463
1492
1427
14.7229
18.1702
27.0013
19.3178
16.1730
10.4048
136.8894
183.0268
1381.9847
534.3458
702.2122
123.2235
111.8711
40.6345
46.0600
173.7227
39.1178
90.0515
169.4561
67.6353
m
CH
CH
b CH
m
m
m
m
1
3
scis (61) + dCH (37)
scis (46) + CN (82)
(31)
7.3721
3
m
1
455
478
75.2736
142.2858
335.7285
62.9492
263.4853
7.2270
121.9896
5.9833
46.4998
7.2530
41.0482
9.9206
27.9342
7.6161
11.7149
6.3808
5.9265
3
CN (78) + dCH(65)
CN (62) + dCH (26)
1
1489
CH (45) +
CC(63)
m
CC(23)
1
1
561
568
1590
1603
d CH
3
(11) +
m
CN (60)
1
1
589
604
1592
m
m
m
m
m
m
m
m
m
m
m
CO (89)
C@N (96)
C–H (98)
C–H(99)
C–H(99)
C–H(99)
2
902
2
2
916
962
2920
2961
2919
2962
2968
3034
3051
3071
3097
3107
2970
3038
3053
3063
3100
3102
s
CH
CH
3
(98)
(99)
s
3
3
CH (98)
a
CH
CH
3
(100)
(98)
a
3

R.R. Saravanan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 139 (2015) 321–328
327
Table 4 (continued)
IR cm 1
ꢁ
m
Raman cm
ꢁ1
m
cal cm
ꢁ1
IR intensity Raman activity
P
Reduced mass
Force constant Characterisation of normal modes with PED (%)
m
3
111
3111
3443
3456
3615
5.6715
32.7024
36.0834
109.2166
52.1374
189.4240
128.9123
58.0800
0.2443
0.2148
0.1223
0.6396
1.0888
1.0754
1.0477
1.1036
6.7000
8.1026
7.9536
9.1679
m
m
m
m
C–H(100)
NH(99)
3441
3455
3620
3445
3453
3617
s
NH
NH
2
(99)
(98)
a
2
m
: stretching; b: in-plane bending;
c: out-of-plane bending; asym: asymmetric stretching; sym: symmetric stretching; ipr: in-plane rocking; opr: out-of-plane rocking;
sRing: ring out of-plane bending; scis: scissoring; wag: wagging.
by B3LYP/6-31G (d, p) level method also show good agreement
with experiment recorded data.
The bands due to C–H in-plane bending vibrations are observed
ꢁ1
in the region 1000–1300 cm [35]. In the present study the C–H in
ꢁ1
plane bending vibrations were observed at 1173 and 1229 cm in
ꢁ1
FT-IR and at 1171 and 1229 cm in FT-Raman. The deviation is
ꢁ1
2
cm between experimental and calculated B3LYP/6-311++G (d,
p) values in MPET show better agreement with theoretical values.
The C–H out-of-plane bending vibrations appear within the region
ꢁ
1
ꢁ1
9
00–675 cm [36]. The vibrations identified at 681 cm in FT-IR
ꢁ1
and 678 cm in FT-Raman are assigned to C–H out-of-plane bend-
ing for MPET. The B3LYP level at 6–31G (d, p) gives the wavenum-
ꢁ1
ber value at 679 cm for C–H out-of-plane bending and are shown
in Table 4.
C–C vibrations
The C–C stretching modes of the phenyl group are expected in
ꢁ1
the range from 1650 to 1200 cm . The actual position of these
modes is determined not to much by the nature of the substitu-
ent’s but by the form of substitution around the ring [37]. In the
ꢁ1
present study, the bands at 1492 and 1364 cm in FT-IR spectrum
ꢁ1
and 1489 and 1362 cm in FT-Raman are assigned to C-C stretch-
ing vibration for our MPET molecule. The theoretically computed
ꢁ1
wavenumbers at 1490 and 1363 cm in B3LYP method also corre-
lated with the experimental observations. The calculated PED val-
ues corresponding to these two modes are 23% and 81%.
Fig. 7. Poseview of MPET with HMG-CoA receptor, dotted lines shows hydrogen
bonds.
C–N vibrations
Saravanan et al. [32] have observed the C–N stretching band at
site finder [www.bioinformatics.leeds.ac.uk/qsitefinder]. The small
molecule or ligand is optimized by Gaussian 03W [21] package in
the basis set B3LYP/6-31G (d, p). The ligand–protein docking sim-
ulations are carried out by Autodock tools [43] V1.5.4. and Auto-
dock V4.2. Programs.
ꢁ1
ꢁ1
1
1
296 cm in FT-IR and 1291 cm in FT-Raman spectrum of (E) -
-[1-(4-Chlorophenyl) ethylidene] thiosemicarbazide. In the pres-
ꢁ
1
ent work, the bands at 1282 and 1281 cm in the FT-IR and FT-
Raman spectrum of MPET are assigned to the C-N stretching mode
of vibrations respectively. The calculated bands at a B3LYP level in
The non bonded atoms in the target receptor like an oxygen
ꢁ1
the same region show band positions at 1279 cm
vibrations.
for C–N
atom of H
of Human reductase with HMG and CoA, is cleaned up by removing
O molecules and hydrogen atoms also added. Autodock docks a
2
O molecules that were present in the crystal structure
H
2
N–N vibrations
flexible ligand to a rigid receptor. Affinity maps for all the atom
types present as well as electrostatic map, were computed with
grid spacing of 0.375 E. Evaluation of the results was done by sort-
ing the different complexes with respect to predicted binding
energy.
Azo compounds are difficult to identify by IR spectroscopy
because no significant bands are observed for those, the azo group
being non polar in nature [38–40]. Crane et al. [41] have observed
ꢁ1
the N-N stretching band at 1151 cm and Seena et al. [42] at
ꢁ
1
ꢁ1
1
136 cm . In the present work the band appears at 1151 cm
The Autodock V4.2 software is used to simulate the binding
mode of the target receptor and ligand. The protein structure of
HMG-CoA reductase (PDB ID: 1DQ8) used as a target receptor.
Fig. 7 shows the poseview of MPET with HMG-CoA receptor. Pose-
view [44–46], a tool which displays molecular complexes incorpo-
rating a simple, easy-to-perceive arrangement of the ligand and
the amino acids towards which it forms interactions. HMG-CoA
reductase is the rate controlling enzyme of the mevalonate path-
way, the metabolic pathway that produces cholesterol and isopre-
noids. The 10 docking candidates were ranked by energy and the
one with the lowest energy was regarded as the best mimic struc-
ture. There are two hydrogen bonds joining MPET and HMG-CoA
reductase.
ꢁ1
in FT-IR and 1152 cm in FT-Raman assigned to N–N vibrations.
The theoretically computed values by B3LYP/6-31G (d, p) method
for N–N vibrations coincide with experimental values.
Molecular docking studies
The structure of the target receptor, Human reductase with
HMG-CoA (PDB id: 1DQ8) were obtained from the RCSB protein
databank [http://www.rcsb.org/pdb]. Protein retrieved from the
database was analyzed for pockets before docking studies, to
ensure the possible number of binding sites of protein and ligand.
The binding sites for the target receptor were searched from the Q-

3
28
R.R. Saravanan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 139 (2015) 321–328
The hydrogen bonds between HMG-CoA and MPET also shown
in Fig. 7. Hydrogen bonding in docking plays a significant role in
interaction studies. The hydrogen bonds formed between N1, O1
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[
and H11B with GLY806, MET655 and GLY765, the distance are
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0
9
3
.5, 3.1 and 2.2 ÅA . The energy value between binding sites of
[
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The FT-IR, FT-Raman studies were carried out for synthesized
MPET. DFT calculations at the B3LYP/6-31G (d, p) level of theory
were performed in order to analyze structural properties of MPET.
The calculated structural parameters by the DFT method closely
match with single crystal XRD data. MEP plays an important role
in determining the stability of the molecule. The energies for the
various possible conformers of the title compound was calculated
and the minimum energy structure was chosen for the computa-
tional study as well as for Docking. From the Molecular docking
studies, it shows that the positive potential isosurface of MPET
are very active and also interact with protein target. Hence this
MPET based new compound has also tested to estimate its poten-
tial against cholesterol biosynthesis.
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Acknowledgement
One of the authors, R.R. Saravanan, feels indebted to Prof. S. Gar-
cia-Granda. The authors thank Misrimal Navajee Munoth Jain Engi-
neering College Management, Thoraipakkam, Chennai 600 097,
India for their support. We thank financial support from Spanish
Ministerio de Economía y Competitividad (MAT2010-15094, Fac-
toría de Cristalización – Consolider Ingenio 2010, FEDER funds.
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