Molecular structure interpretation, spectroscopic (FT-IR, FT-Raman), electronic solvation (UV–Vis, HOMO-LUMO and NLO) properties and biological evaluation of (2E)-3-(biphenyl-4-yl)-1-(4-bromophenyl)prop-2-en-1-one: Experimental and computational modeling

Article abstract of DOI:10.1016/j.saa.2019.117609

In this present work, a molecule (2E)-3-(biphenyl-4-yl)-1-(4-bromophenyl) prop-2-en-1-one (3BPO) was synthesized and the structure has been characterized by using spectroscopic techniques. The most stable conformational structure of title compound has bee

Full text of DOI:10.1016/j.saa.2019.117609

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 226 (2020) 117609
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Molecular structure interpretation, spectroscopic (FT-IR, FT-Raman),
electronic solvation (UVeVis, HOMO-LUMO and NLO) properties and
biological evaluation of (2E)-3-(biphenyl-4-yl)-1-(4-bromophenyl)
prop-2-en-1-one: Experimental and computational modeling
approach
,
,
A. Thamarai a b, R. Vadamalar a, M. Raja b, S. Muthu c *, B. Narayana d, P. Ramesh b,
R. Raj Muhamed e, S. Sevvanthi c, S. Aayisha f
,
g
a Department of Physics, Muthurangam Govt. Arts College, Vellore, 632002, Tamilnadu, India
b Department of Physics, Govt. Thirumagal Mills College, Gudiyattam, 632602, Vellore, Tamilnadu, India
c Department of Physics, Arignar Anna Govt. Arts College, Cheyyar, 604 407, Tamilnadu, India
d Department of Chemistry, Mangalore University, Mangalagangotri, 574 199, Karnataka, India
e Department of Physics, Jamal Mohamed College, Tiruchirappalli, 620 020, Tamilnadu, India
f Research and Development Centre, Bharathiar University, Coimbatore, 641046, Tamilnadu, India
g Department of Physics, Meenakshi College for Women, Chennai, 600024, Tamilnadu, India
a r t i c l e i n f o
a b s t r a c t
Article history:
In this present work, a molecule (2E)-3-(biphenyl-4-yl)-1-(4-bromophenyl) prop-2-en-1-one (3BPO) was
synthesized and the structure has been characterized by using spectroscopic techniques. The most stable
conformational structure of title compound has been calculated using HF-6-31G(d,p) basis set. DFT
method were used through B3LYP/6e311þþG(d,p) basis set to optimize the structure of the title com-
pound. The geometrical parameters, vibrational wavenumbers and electronic properties have also been
performed. The electronic properties for HOMO-LUMO, UVeVis and MEP maps were contemplated by
IEFPCM model with various solvation impacts which depends on TD-DFT ((M062X for UV and B3LYP for
HOMO-LUMO, MEP)/6e311þþG(d,p)) strategies. The NLO activity of title compound has been examined
by solvation DFT/B3LYP technique with 6e311þþG(d,p) premise set. Mean while, lone pair of donor-
acceptor interactions and H bond donor/acceptor surface has been obtained by which a charge trans-
fer mechanism can be explained. Molecular docking has been explored to comprehend the coupling
transportation of the examined ligand with human folate receptor alpha in complex with folic corrosive
protein (4LRH).
Received 7 April 2019
Received in revised form
18 July 2019
Accepted 6 October 2019
Available online 7 October 2019
Keywords:
PES scan
FT-IR and FT-Raman
Solvational electronic properties
Molecular docking
H bond donor/acceptors surface
Thermodynamic parameters
© 2019 Elsevier B.V. All rights reserved.
1. Introduction
compounds are usually utilized for a unique biological activities
such as anti-inflammatory, antibacterial, anticancer, antitubercu-
Chalcones derivatives are merely known intermediates for
synthesis in most of the heterocyclic compounds. Chalcones
possess an important class of pharmacological active and highly
natural products due to their tiny structures [1e4]. These de-
rivatives are not only attracted towards synthesis but also influ-
enced by extensive interesting applications for pesticides, photo-
protectors in plastics, medical field, etc. These groups of
losis, antidiabetic, antioxidant activity, antimicrobial, antiviral,
antimalarial activity, neuroprotective effects. In recent years, many
chalcones derivatives have been reported for their cytotoxic, anti-
cancer, antiviral, chemoprevenive, insecticidal and enzyme inhibi-
tory properties [5e10].
Present study reports the DFT calculations in order to under-
stand the spectroscopic characterization in detail, molecular
structural elucidation and reactive site analysis of (2E)-3-(biphenyl-
4-yl)-1-(4-bromophenyl)prop-2-en-1-one (3BPO) compound. The
molecular formula for 3BPO is C21H15BrO and the molecular weight
is 363.259 g/mol. It has a system of monoclinic at where the
* Corresponding author.
E-mail address: mutgee@gmail.com (S. Muthu).
https://doi.org/10.1016/j.saa.2019.117609
1386-1425/© 2019 Elsevier B.V. All rights reserved.

2
A. Thamarai et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 226 (2020) 117609
intercepts (a, b and c) are different and one of the interfacial angles
is not equal to 90ꢀ. The enhanced literature survey reports that
there is no report on combined experimental and theoretical
spectroscopic investigations on the 3BPO compound. The quantum
chemical calculation is planned and executed in this work to
calculate the molecular structural properties through different
solvent phases using different DFT methods. Recently, B3LYP and
M062X methods have become the significant and highly used
quantum mechanical modeling methods to examine the electronic
structure of the molecule. The premise calculations using utilizing
various methods in DFT always give accurate results due to the
exact coincidence of additional types of precise theoretical
methods which have been taken for the studies. The study includes
the experimental FT-IR and FT-Raman spectra analyses which have
been compared theoretically on the account of Potential Energy
Distribution (PED). Generally, the internal coordinates are
depending upon the basis of the potential energy distribution (PED)
which is used to assign the vibrational mode assignments.
Furthermore, thermodynamic properties have also been performed
by the versatile B3LYP method.
The electronic transitions within the molecule and molecular
reactivity parameters such as HOMOeLUMO orbitals, MEP surface
analysis, and first order hyperpolarizability have been examined
through DFT/B3LYP and UVeVisible has been examined through
DFT/M062X by using various solvation effects. The reactive sites of
headline molecule have been investigated by analysing NBO and H
bond donor/acceptor surface. Molecular docking simulation has
been performed to understand and predict the molecular mecha-
nism and biological activity of 3BPO molecule.
has also been investigated by autodock software [13] by using
Autodock tools 1.2.6 and hence the protein-ligand complex has
been visualized by Pymol software.
3. Results and discussion
3.1. Molecular structural analysis
3.1.1. PES scan
PES scan coordinates were determined and visualized to know
the conformation stability for the title molecule at where HF/6-
31G(d,p) basis set have been utilized. The minimum and
maximum energy conformer PES plot of title molecule is shown in
Fig. 1. The calculated dihedral angle is at H29eC8eC9eO10 bonded
atoms. The dihedral angle is rotated between ꢁ180 and 180ꢀ. Here
present 36 conformer, the value (360ꢀ) has been divided into 36
steps at where each step has 10ꢀ of freedom. The present molecule
intra molecule interaction for each conformer identified stability for
the molecule. The most stable conformation for the title molecule is
obtained at rotational angle (ꢁ180ꢀ,-19.99ꢀ, 180ꢀ) values with the
local and global minimum energy (E ¼ ꢁ3448.75881, ꢁ3.448.75563,
3448.75881 Hartree) and saddle point rotational angle (ꢁ89.99ꢀ,
90.00ꢀ) values with the local and global maximum energy
(ꢁ3.448.74993, 3448.74992 Hartree) the structure is illustrated in
Fig. 2.
3.1.2. Geometrical parameters
Density functional theory is used to get optimized structure
with bond length and bond angle values. The optimized geomet-
rical parameters (bond angles, bond lengths) of the synthesized
compound has been calculated by DFTeB3LYP functional method
with 6e311þþG(d,p) basis set. The detail survey says that there are
no theoretical investigations on the title molecule performed. A.
Fischer, H.S. Yathirajan et al. [14] reported the single crystal XRD of
title compound. The optimized geometrical parameters were
compared with experimental XRD data of investigated molecule.
The atoms in 3BPO have 40 bond length values and 63 bond angle
values to form the structure. Various groups of bond lengths(CeC,
CeH, CeO, and CeBr) which were presented in the title compound
have been listed in Table S1. The Experimental and theoretical
superimposing (comparative) molecular structures of title com-
pound have been obtained as shown in Fig. 3. Table S1 and Fig. 3
shows the correlated evaluation between experimental and
calculated bond lengths, bond angles at where the high coherence
presence. M. Elanthiraiyan et al. [15] reported the bond length
(which is small) for the atoms in molecule which reports the
strongest nature of that bond. The strongest bonds of 3BPO have
been observed between C and H. The title molecule has sixteen
CeH bonds with the unique values exp- 0.930 Å/theo- 1.082 to
1.089 Å, at where the lowest bond length values have been obtained
while compared with other bonds.
2. Material and methods
2.1. Synthesis procedure of 3BPO
4-Bromoacetophenone (1.99 g, 0.01 mol) in methanol (20 ml)
was mixed with biphenyl-4-carbaldehyde (1.82 g, 0.01 mol) and the
mixture was treated with a 30% potassium hydroxide solution
(3 ml) at 278 K. The reactive mixture has been magnetically stirred
for 3hrs. A flocculants precipitate has been formed and seen.
Further, the precipitate was filtered and washed with cold water.
2.2. Experimental methods
FT-IR (4000e400 cmꢁ1) and FT-Raman (4000-100 cmꢁ1) spectra
of the synthesized compound was recorded in solid state mode at
room temperature, and the spectral data have been collected at
Sophisticated Analytical Instruments Facility Indian Institute of
Technology (Madras) at Chennai, India. The precise ultraviolet ab-
sorption spectrum has been obtained for the sample in the range
250e600 nm by UV-1700 series recording spectrometer.
2.3. Methods of calculation
As it is evident from the bond lengths which are reported in
Table S1, there was a very good agreement between experimental
and theoretical values. The higher values in bond length have been
observed in halogen substitution C14 eBr17 at exp/theo: 1.905/
1.915 Å. The RMSD values of the bond lengths are 0.09453 Å and
bond angles are 0.4220ꢀ shows that there is a similarity between
the two structures.
The theoretical calculations of title compound were done using
Gaussian 09 W and Gauss View 5.0 software package [11,12]. The
potential energy surface scan coordinates have been estimated by
HF-6-31G(d,p) basis set. Furthermore, the geometry of the struc-
ture has been optimized by B3LYP method with 6e311þþG(d,p)
origin using DFT technique. Vibrational assignments of each and
every mode are precisely analyzed by VEDA4 program package.
Theoretical wavenumbers which were computed at the DFT level is
identified with logical errors and hence scaling factor value has
been added as 0.961 for B3LYP method. TD-DFT has been used to
calculate HOMO-LUMO orbital analysis, MEP analysis and
UVeVisible spectral analysis through dissimilar solvent (DMSO,
chloroform, water) phases. The biological activity of the molecule
3.2. Spectral analysis
The title molecule possesses 38 atoms, so that it has 108 normal
modes of vibrations. The vibrational spectral assignments were
initially attempted through PEDs using VEDA4 program package to
compare the values visually. Furthermore, the systematic errors of
theoretical wavenumbers have been identified and reduced for the

A. Thamarai et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 226 (2020) 117609
3
Fig. 1. Potential energy curves of 3BPO as a function of the positions of its nuclei to find minimum energy conformer.
Fig. 2. Structures of minimum and maximum energy conformers of 3BPO.
title compound by using a scaling factor 0.961 for B3LYP. The
comparative (experimental and theoretical) FTeIR and FT-Raman
spectrums of title molecule have been precisely shown in Figs. S1
and S2. The scaled frequencies, IR intensity, Raman activity and
PEDs which were estimated have been shown in Table S2.
values between 3100 and 3000 cmꢁ1 [16]. For the title molecule,
the estimated CeH (stretching) bands were obtained from 3091 to
3024 cmꢁ1 [mode nos 1e15] using B3LYP/6e311þþG(d, p) basis set
technique. The experimental FTeRaman bands (CeH) are merely
observed at 3099(w), 3076(s), 3068(vs), 3045(w), 3031(w),
3022(w) cmꢁ1 and the FTeIR bands are observed at 3088(w),
3058(m), 3034(m), 3001(m) cmꢁ1. The equivalent PED values of
investigated molecule are obtained with the best value of 98%
which is shown in Table S2.
3.2.1. CeH vibrations
Usually, the CeH stretching vibrations of aromatic compounds
are obtained as multiple weak and strong bands with different

4
A. Thamarai et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 226 (2020) 117609
Fig. 4. The theoretical (using TD-DFT/M062X method with different solvation effects)
and experimental UVeVis spectra of 3BCPO.
vibration which belongs to the band between the ring and bromine
atom is highly important at where the number of combinations of
vibrations are possible which indicates the presence of heavy atom
[22]. In this study, the CeBr vibrations for title compound were
obtained at 1040/1049/1060 cmꢁ1 by using B3LYP/6e311þþG(d,p).
The FT-IR and FT-Raman vibrations have been observed at 1031(s),
1033(s) and 453(w) cmꢁ1. The corresponding PED contributions are
35 and 35%.
Fig. 3. Experimental and Optimized geometric structure of the 3BPO using DFT/B3LYP
with 6e311þþG(d,p) basis set (experimental (stick) structures are superimposed on
theoretical (ball) structures).
3.2.4. CeO vibrations
Generally C]O stretching vibrations dominantly occur in the
region 1870 - 1540 cmꢁ1 at where the location of C]O stretching
vibrations are aligned according to the physical parameters, elec-
tronic state analysis and mass effects phenomena of nearest sub-
stituent’s, conjugation effects, inter and intramolecular action of
hydrogen bonding [23]. The present study reports C]O stretching
vibrations at 1648/1666/1668 cmꢁ1 theoretically. The FT-IR and FT-
Raman experimental vibrations have been observed at 1655(vs)
1656(w) cmꢁ1. The PED of C]O stretching vibration has been noted
as 55%
The aromatic in-plane bending of CeH vibrations are generally
present in 1300e1000 cmꢁ1 [16]. The HeCeC in-plane bending vi-
brationsforthetitlecompoundhavebeenobservedexperimentallyin
FT-IR spectrum as 1328, 1317, 1176, 1068, and 1031 cmꢁ1 and in FT-
Raman as 1320,1293,1184,1161, and 1033 cmꢁ1. These experimental
values have good agreement with theoretical values with maximum
PED values (70% for FT-IR and 62% for FT-Raman). The intensity of
these bending vibrations has very strong to very weak values and
these vibrations are combined with some stretching mode vibrations.
Theout-of-planebendingvibrationsareusuallyappearedintherange
1000e750 cmꢁ1. The title compound has these vibrations at 976 and
661 cmꢁ1 for FT-IR and 770 cmꢁ1 for FT-Raman. These values are
almost equal to the theoretical values with good PED values.
3.3. UVevisible analysis
Theoretical UVeVisible exploration for each transitions can be
obtained by solvation TD-DFT/M062X [24,25] method with unique
6e311þþG(d,p) basis set. UVeVis Spectra calculation is a signifi-
cant branch in theoretical modeling at where high-level compu-
tational methods can be calculated for the spectra which can be
analyzed directly.
In this present investigation, the electronic transition for the
headline compound has been calculated by M062X technique with
the application of various solvents (DMSO, chloroform, water) us-
ing 6e311þþG(d,p) basis set. The experimental UVeVisible ab-
sorption spectrum was recorded in the range 250e600 nm using
DMSO solvent. The electronic transition with lmax of experimental
and theoretical absorption maximum and their subsequent band
gap energies have been reported in Table S3. Furthermore, calcu-
lated transition energy, oscillator strength, and assignments which
were obtained theoretically have been reported in Table S3. The
comparative analysis has been made for experimental and theo-
retical UVeVis spectra of title molecule and shown in Fig. 4.
3.2.2. CeC vibrations
The CeC stretching vibrations of aromatic compounds are sup-
posed to be in the range 1650e800 cmꢁ1 [17e19]. Similarly, the
theoretical values of the title molecule were also identified in the
range 1670e1150 cmꢁ1 through B3LYP/6e311þþG(d,p) method.
Different frequencies with wavenumbers have been observed from
1655(vs) to 976(vs) cmꢁ1 in FTeIR and FTeRaman bands have been
presented from 1656(w) to 1002(m) cmꢁ1. The experimentally
observed and theoretically calculated CeC stretching vibration
values of the headline molecule are in well agreement with the
literature values [20].
3.2.3. CeBr vibrations
Many number of aromatic bromo compounds have CeBr
stretching vibrations in the region 650e395 cmꢁ1 [21]. The

A. Thamarai et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 226 (2020) 117609
5
Table 1
M062X technique has been taken to estimate the theoretical
Calculated energy values of 3BPO by TD-B3LYP/6e311þþG(d,p) method.
values which are highly coherent to the experimental values. The
experimental absorption maximum value while using DMSO as a
Parameters
TD-B3LYP/6e311þþG(d,p)
solvent has been observed at 336 nm due to n to
p* electronic
DMSO
Chloroform
Water
transition and the corresponding theoretical band gap energy has
been noted as 3.700 eV. The results for the absorption maxima
peak/band gap/oscillator strength using various solvents and their
corresponding values have been reported as 339 nm/3.667 eV/
0.668 (DMSO), 338 nm/3.678 eV/1.200 (chloroform), 338 nm/
3.678 eV/1.188 (water) in Fig. 4. The HOMO-LUMO assignment
value using UV analysis has been noted in percentage as 90%.
EHOMO (eV)
ELUMO (eV)
IP(eV)
ꢁ6.3035
ꢁ2.7437
6.3035
2.7437
3.5598
4.5236
ꢁ4.5236
1.7799
0.2809
5.7483
2.5415
8.2326
3.7090
ꢁ6.2926
ꢁ2.7072
6.2926
2.7072
3.5854
4.4999
ꢁ4.4999
1.7927
0.2789
5.6477
2.5101
8.1217
3.6218
ꢁ6.3043
ꢁ2.7456
6.3043
2.7456
3.5587
4.5250
ꢁ4.5250
1.7794
0.2810
5.7536
2.5430
8.2384
3.7135
EA (eV)
D
c
m
E (eV)
(eV)
(eV)
h
(eV)
s (eVꢁ1
)
u
(eV)
3.4. Molecular reactivity analyses
D
Nmax
Wþ
Wꢁ
The properties which are calculated using HOMO-LUMO are
useful in molecular reactivity analysis, especially in the spot of
organic synthesis and biomedical field [27]. In this work, HOMO-
LUMO orbital analysis of ground (stable) and first excited state
(higher state) have been ultimately investigated by different
theoretical method of B3LYP by 6e311þþG(d,p) basis set at where
each method yields the calculation using TD-DFT approach by using
different solvation process such as DMSO, chloroform and water.
HOMO-LUMO energy gap illustration using different solvation
IP-Ionization potential, EA- Electron affinity,
D
E-Energy gap (eV), c - Electronega-
tivity, - Chemical potential, h - Chemical hardness, s -Chemical softness, u -
m
Electrophilicity index,
D
Nmax - Electronic charge, Wþ - Electron accepting capa-
bility,Wꢁ- Electron donating capability.
gap values have been calculated as 3.5598eV(DMSO),
3.5854eV(chloroform) and 3.5587eV(water) based on TD-DFT
calculations.
The Ionization potential has been estimated using different
solvational methods by TD-DFT/B3LYP method and reported in
Table 1. The title molecule exhibits Ionization energy (which is
about high) and affinity (which is about low), at where the
contribution of sharing of the electrons among the neighboring
molecules and proteins might be calculated. These low energy gap
values, Electron affinities and high Ionization potential are eluci-
dating the charge transfer mechanism within the molecule which
influences its polarizability (to be high) and biological activities.
The reactivity descriptors values for the title compound can be
found by the following equations
processes were shown in Fig. 5. The energy gap (DE), HOMO and
LUMO orbital energies, other parameters like Ionization potential
(IP), Electron affinity (EA), etc [28e30] for the title molecule were
estimated by B3LYP/6e311þþG(d,p) basis set and the results have
been reported in Table 1.
Theoretically calculated HOMO energies have been mentioned
as ꢁ6.3035 eV (DMSO), ꢁ6.2926 eV (Chloroform), ꢁ6.3043 eV
(water) and LUMO energies are ꢁ2.7437 eV (DMSO), ꢁ2.7072 eV
(chloroform) and ꢁ2.7456 eV (water). Usually, the energy differ-
ence between HOMO and LUMO is called as energy gap which
provides the stability for structure of the molecule [31]. The energy
Fig. 5. Frontier molecular orbitals at various solvent effects using DFT method for 3BPO molecule.

6
A. Thamarai et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 226 (2020) 117609
I þ A
axx
þ
ayy
þ
azz
c
m
h
¼
ðElectronegativityÞ
(1)
(2)
(3)
a
¼
(9)
2
3
Components of the first hyperpolarizability can be written as
ðI þ AÞ
¼ ꢁ
ðChemical potentialÞ
X
ꢀ
ꢁ
2
bi
¼
biii
þ
bijj
þ
bjij
þ
bjji
(10)
isj
I ꢁ A
¼
ðChemical hardnessÞ
By using the x, y and z components of
first hyperpolarizability tensor can be represented by
b
, the magnitude of the
2
s ¼ 1/2
h
(chemical softness)
(4)
(5)
rffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
ꢂ
ꢃ
btot
¼
b2x þ b2y þ b2z
(11)
u
¼
m
2/2
h (Electrophilicity index)
The entire equation for reckoning the magnitude of
Gaussian program output can be is given as
b
from
ð3I þ AÞ2
16ðI ꢁ AÞ
uꢁ
¼
ðElectron donating capabilityÞ
(6)
qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
ꢀ
ꢁ
ꢀ
ꢁ
ꢀ
ꢁ
2
btot
¼
bxxx
þ
bxyy
þ
bxzz 2 þ byyy
þ
byzz
þ
bxxy 2 þ bzzz
þ
bxxz
þ
byyz
(12)
ðI þ 3AÞ2
16ðI ꢁ AÞ
The present work describes the theoretical study of NLO
uþ
¼
ðElectron accepting capabilityÞ
(7)
behavior for various solvation effects by TD-DFT/B3LYP method
with 6e311þþG(d,p) basis set. Many organic compounds can be
soluble in many solvents (polar and non polar solvants), and hence
the solvation selections play a crucial role in molecular analysis. As
a fact, the solvents do change little (increase or decrease in order) in
the fundamental molecular behavior. Various solvation methods in
quantum mechanical aspects are useful to analyze the performance
(high/low) of solvation effects.
The theoretical nonlinear optical parameters on solvent phases
(DMSO, chloroform and water) are highly compatible with TD-DFT/
B3LYP technique by 6e311þþG(d,p) basis set levels. The title
molecule NLO values have been compared with the standard NLO
material (Urea) values (dipole moment, polarizability and hyper-
polarizability) and these values are mentioned in Table 2. The
3.5. MEP analysis
Molecular electrostatic potential energy surfaces usually pro-
vide extremely important parameters about the chemical stability
and reactivity of an organic compound to understand the electro-
philic and nucleophilic reaction properties. It is always a unique
and useful tool for the evaluation of physical and chemical pa-
rameters, especially for biomolecules and organic compounds [32].
MEP surfaces and contour surfaces were carried out for the com-
pounds at where DMSO, chloroform and water have been used as
the solvents using (TD-DFT)/B3LYP method by 6e311þþG(d,p)
level. MEP surfaces with contour plots of the title compound have
been shown in Fig. 6. Nucleophilic and electrophilic properties have
been investigated and mentioned by using various colors in the
region. The blue color always indicates nucleophilic potential (to be
high) and the red color indicates electrophilic potential (to be high).
The electrostatic potential generally decreases with the order as
blue < cyan < green < yellow < orange < red. Electrophilic spots
have been noted around the O10 atom and the nucleophilic po-
tentials have been noted around the hydrogen and carbon atoms
respectively.
calculated
solvation
hyperpolarizability
values
are
122.9100 ꢂ 10ꢁ30 e.s.u for DMSO, 97.2760 ꢂ 10ꢁ30 e.s.u for chloro-
form and 124.3100 ꢂ 10ꢁ30 e.s.u for water. The minimum value in
NLO activity for the two phases have been reported as wa-
ter > DMSO > Chloroform.
NLO
possesses
higher
hyper-
polarizability while water and DMSO solvents have been taken
instead of taking other solvents. The title molecule has been
identified with higher hyperpolarizability, and the corresponding
values have been noted as B3LYP/(108, 102, 108) times higher than
urea by the same level of solvations and basis set. Thus earlier re-
ports conclude that if the molecule has higher
b and lower HOMO-
LUMO energy gap then it possesses NLO activity.
3.6. Hyperpolarizability calculations
3.7. Thermodynamic properties
Quantum mechanical computation method is one of the most
excellent methods for computing molecular hyperpolarizability.
This new technical phenomena has great importance towards the
emerging application in electronic devices [34]. The total dipole
moment, mtot, induced by the field can be written as
On the account of vibrational analysis, the static thermodynamic
functions like heat capacity, entropy, enthalpy changes, Gibbs en-
ergies have been computed by the B3LYP/6e311þþG(d,p) basis set
using Perl script, THERMO.PL and those values are listed in Table 3.
The Gibbs free energy has been calculated by the following
equation,
mtot
¼
m0
þ
aijEj þ bijkEjEk þ …;
(8)
Where
a
denotes the linear polarizability, m0 denotes the per-
D
G ¼
D
H ꢁ T
D
S
(13)
manent dipole moment and bijk denotes the first hyper-
polarizability tensor components. The isotropic linear polarizability
is written as
where
ature (Kelvin).
D
S e change in entropy,
D
H- Enthalpy changes, T- Temper-

A. Thamarai et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 226 (2020) 117609
7
Fig. 6. Molecular Electrostatic Potentials (MEP) at various solvent effects using DFT methods of 3BPO molecule.
Table 2
Comparison table of theoretically calculated (at solvation phase) dipole moment
m
(D), polarizability a0 (e.s.u), first order hyperpolarizability
B3LYP/6e311þþG(d,p)
b
tot (e.s.u) with Urea for 3BPO.
Compounds
Parameters
DMSO
Chloroform
Water
3BPO
m
(D)
2.1240
20.3010
122.9100
2.1790
1.3403
1.1377
1
1.9836
19.1230
97.2760
2.0541
1.2722
0.9502
1
2.1315
20.3600
124.3100
2.1854
1.3438
1.1482
1
a0x 10ꢁ23 (e.s.u)
b
m
tot x 10ꢁ30 (e.s.u)
(D)
Urea
a0x 10ꢁ23 (e.s.u)
b
m
tot x 10ꢁ30 (e.s.u)
(D)
Comparison of 3BPO and urea (3BPO > urea (times))
a0x 10ꢁ23 (e.s.u)
15
108
15
102
15
108
b
tot x 10ꢁ30 (e.s.u)
From the results which were in Table 3, it can be observed that
the values of all the thermodynamic functions are increasing with
the increment in temperature (100e1000 K) and hence the mo-
lecular vibration intensities are also increased with temperature
increment. The parameters with different temperatures have been
fixed by quadratic equation and the corresponding fitting factors
(R2) have been estimated for the thermodynamic properties
(0.99999, 0.9987 and 0.9999). The correlation plots of those values
have been shown in Fig. 7. The thermodynamic correlation fitting
equations are as follows:
Table 3
Various thermodynamic properties of 3BPO at varying temperature by B3LYP/
6e311þþG(d,p).
T(K)
D
C(J/molK)
D
S(J/molK)
D
H(kJ/mol)
-DG(KJ/mol)
100
200
298
300
400
500
600
700
800
900
1000
135.131
221.823
319.905
321.775
417.868
498.811
563.741
615.654
657.724
692.363
721.267
413.949
533.285
639.940
641.925
747.939
850.191
947.099
1038.043
1123.093
1202.626
1277.114
9.050
32.345
79.897
26.760
53.298
53.892
90.974
136.948
190.198
249.262
313.002
380.560
451.284
137.500
138.686
208.202
288.148
378.061
477.368
585.472
701.803
825.830
D
S ¼ 291.9979 þ 1.2482 Te2.6258 ꢂ 10ꢁ4T2 (R2 ¼ 0.9999)
C ¼ 6.1548 þ 1.2285 Te5.1406 ꢂ 10ꢁ4T2 (R2 ¼ 0.9987)
(14)
(15)
D

8
A. Thamarai et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 226 (2020) 117609
Fig. 8. Hydrogen bond donor-acceptor surface of 3BPO molecule.
surface indicates two colors namely green and lavender. Green
color is for H bond acceptor and lavender is for H bond donor. Two
lone pairs (O10, Br17) of H bond accepter have been observed for
the title compound as shown in Fig. 8. Stabilization energy has been
observed for O10, Br17, H bond acceptors in NBO analysis. NBO
analysis and H Bond donor/acceptor surfaces describe inter and
intra molecular transitions of 3BPO molecule which are the evi-
dence for the biological activity in the molecule.
Fig. 7. Correlation plots of different thermodynamic properties at varying tempera-
tures for 3BPO compound.
3.9. Molecular docking studies
Molecular docking plays a consistent role in drug design process
to treat many diseases. The biological parameters of title molecule
have been calculated using autodock software through autodock
tool 1.2.6. In this study, the various parameters have been
completely analyzed for the headline compound and reported in
Table 5 at where 4LRH [36] protein interacts with ligand molecule.
Auto dock software calculates the inhibition constant [29] using the
following equations,
D
H ¼ - 13.1024 þ 0.1346 T þ 3.3475 ꢂ 10ꢁ4T2 (R2 ¼ 0.9993) (16)
D
G ¼ 10.6647e0.3585 Te4.8031 ꢂ 10ꢁ4T2 (R2 ¼ 0.9999)
(17)
The thermodynamic parameters provide unique information
apparently for further investigation on the title compound. They
could be used to compute the thermodynamic energies based on
the relationship between thermodynamic functions and the eval-
uation of the directions of chemical behavior by the second law of
thermodynamics in the thermo-chemical field [28].
ꢄ
ꢅ
VG
ꢁRT
Ki ¼ e
(18)
3.8. NBO and H bond donor/acceptor surface analysis
where Ki ¼ inhibition Constant, VG ¼ Binding energy, R ¼ gas con-
stant (1.987 ꢂ 10ꢁ3 kcal molꢁ1 Kꢁ1), T e Temperature (298.15 K).
The least value in binding energy gives the inhibition constant
as Ki ¼ kd at where biological activity has been increased and a
little amount of prescription is used to the patients. The increase in
Ki values describes the increment in drug dosage which are used to
the patients and which might not induces the biological activity.
The 3BPO molecule has been selected to dock into the active region
of 4LRH receptor. 100 molecular docking conformations have been
performed for 4LRH protein at where they can be acted as human
folate receptor active like fetal neural tube defects, cardiovascular
disease and cancers inhibitors.
Natural bond orbital analyses provide intermolecular energy
transitions of donors and acceptors. In this study, the lone pair
energy transitions of title molecule was investigated by B3LYP/
6e311þþG(d,p) basis set [35]. Generally, the lone pair of atoms
gives higher electrophilic charges and higher stabilization energies.
Electrophilic charge in atoms is frequently involved in the hydrogen
bond interaction with neighboring molecules and proteins. The
investigated molecule has two lone pair (LP) atoms O11 and Br17.
The LP donor, acceptor and stabilization energies are calculated and
listed in Table 4. The important interaction between them have
been shown with the electron donors from LP (2) O10 and LP (1)
Br17 to the neighboring antibonding acceptors
s
*(C8eO9),
The 4LRH active regions have been reported for the best 3 rank
conformations and have been shown in Table 5 (Fig. 9). Human
folate receptor folate deficiency always causes many diseases. 4LRH
protein has the lowest binding energy and inhibition constant out
of three conformations at ꢁ9.11/210.84, ꢁ8.82/344.60, ꢁ8.81 (kcal/
s
*(C9eO11), *(C13eC14), *(C14eC15), *(C14eC15) with the en-
s
s
p
ergies of 18.98, 20.03, 4.86, 30.77 and 75.19 KCal/mol for 3BPO.
Hydrogen bond (H bond) donor-acceptor surface clearly illus-
trates reactive site of organic molecule by color grading. H bond
Table 4
Second order perturbation theory analysis by Fock matrix in NBO basis for 3BPO.
Donor(i)
O10
Type
LP(2)
ED/e
Acceptor(i)
Type
ED/e
aE(2) (Kcal molꢁ1
)
bE(J)-E(i)(a.u.)
cF (i,j)(a.u.)
1.8938
C8 eC9
s*
s*
s*
s*
0.0562
0.0642
0.0280
0.0277
0.3859
18.98
20.03
4.86
30.77
75.19
0.71
0.67
2.08
2.03
1.33
0.105
0.105
0.090
0.224
0.314
C9 e C11
C 13 -C14
C14 eC15
C14 eC15
Br17
Br17
Br17
LP(1)
LP(1)
LP(1)
1.9931
p*
a
E(2) means energy of hyper conjugative interaction (stabilization energy).
Energy difference between donor and acceptor i and j NBO orbitals.
F(i,j) is the Fock matrix element between i and j NBO orbitals.
b
c

A. Thamarai et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 226 (2020) 117609
9
Table 5
Molecular docking energy data for 3BPO ligand and Hydrogen bonding with the human folate receptor alpha in complex with folic acid protein (4LRH).
Proteins Run R Bonded
residues
No. of hydrogen
bond
Bond distance EIC
BE (kcal/
mol)
IME (kcal/
mol)
vdW þ Hbond þ desolv
ESE (kcal/
mol)
Reference RMSD
(Å)
(Å)
(nm)
Energy
4LRH
87 1 TRP 140
32 2 TRP 140
58 3 TRP 140
1
1
1
2.7
2.6
2.2
210.84 ꢁ9.11
ꢁ10.30
ꢁ10.01
ꢁ10.01
ꢁ10.33
ꢁ10.01
ꢁ10.01
þ0.03
0.00
0.00
84.604
91.275
91.515
344.60 ꢁ8.82
346.84 ꢁ8.81
Abbreviations: R- Rank, EIC -Estimated Inhibition Constant, BE- Binding energy, IME -Intermolecular Energy, ESE-Electrostatic Energy.
Fig. 9. Docking and Hydrogen bond interactions of 3BPO with 4LRH protein.
mol)/346.84 (nm). These binding energies clearly report the bio-
logical activity of title compound.
ligand binding interactions have been performed. It has minimum
binding energy and minimum value of inhibition constant which
lead a significant biological role.
4. Conclusions
Appendix A. Supplementary data
The molecular structure has been illustrated in detail using
experimental and theoretical spectroscopic (FT-IR, FT-Raman and
UVeVis) analysis. The most stable molecular structure of 3BPO
molecule was confirmed by PES scan analysis using HF/6-31G(d,p)
basis set. The molecular structure has been optimized and hence
the theoretical geometrical parameters have been compared
instantly with experimental XRD data. The superimposing experi-
mental and theoretical 3BPO molecular structure has been noted
and high coherency is maintained. The functional groups of the title
molecule have been confirmed by theoretical and experimental
(FT-IR and FT-Raman) vibrational spectra characterization. The
electronic properties such as HOMO-LUMO, UVeVisible and NLO
activity have been estimated through solvation phases using TD-
DFT/B3LYP (for HOMO-LUMO), M062X (for UV) with IEFPCM
model. In this study, the lowest binding energy has been estimated
not only by UVeVisible spectra but also by HOMO-LUMO in the
range ~3.5eV for the title compound. Meanwhile, lowest electron
affinities and higher ionization potentials have been calculated for
the title compound. The title compound exhibits good NLO activity,
dipole moment, polarizability and first-order hyperpolarizability
than urea. The molecular surfaces were clearly described by MEP
surfaces. Inter and intramolecular interactions in lone pair atoms of
title molecule were investigated by NBO and H bond donor/
acceptor surface analyses. The molecular docking has been re-
ported at where the best 3 rank conformations for protein (4LRH) -
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.saa.2019.117609.
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