Synthesis, crystal structure investigation, spectroscopic characterizations and DFT computations on a novel 1-(2-chloro-4-phenylquinolin-3-yl)ethanone

Article abstract of DOI:10.1016/j.molstruc.2016.05.095

The title compound 1-(2-chloro-4-phenylquinolin-3-yl)ethanone (CPQE) was synthesised effectively by chlorination of 3-acetyl-4-phenylquinolin-2(1H)-one (APQ) using POCl₃ reagent. Structural and vibrational spectroscopic studies were performed b

Full text of DOI:10.1016/j.molstruc.2016.05.095

Accepted Manuscript
Synthesis, crystal structure investigation, spectroscopic characterizations and DFT
computations on a novel 1-(2-chloro-4-phenylquinolin-3-yl)ethanone
S. Murugavel, C.S. Jacob Prasanna Stephen, R. Subashini, H. Raveendranatha
Reddy, Dhanabalan AnanthaKrishnan
PII:
S0022-2860(16)30565-8
10.1016/j.molstruc.2016.05.095
MOLSTR 22609
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 2 February 2016
Revised Date: 25 May 2016
Accepted Date: 27 May 2016
Please cite this article as: S. Murugavel, C.S.J.P. Stephen, R. Subashini, H.R. Reddy, D.
AnanthaKrishnan, Synthesis, crystal structure investigation, spectroscopic characterizations and DFT
computations on a novel 1-(2-chloro-4-phenylquinolin-3-yl)ethanone, Journal of Molecular Structure
(2016), doi: 10.1016/j.molstruc.2016.05.095.
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ACCEPTED MANUSCRIPT

Synthesis, crystal structure investigation, spectroscopic characterizations and
DFT computations on a novel 1-(2-chloro-4-phenylquinolin-3-yl)ethanone
ACCEPTED MANUSCRIPT
S. Murugavela*, C. S. Jacob Prasanna Stephenb, R. Subashinic, H. Raveendranatha Reddyc,
Dhanabalan AnanthaKrishnand
aDepartment of Physics, Thanthai Periyar Government Institute of Technology, Vellore-632 002,
Tamilnadu, India
bDepartment of Physics, Global Institute of Engineering and Technology, Melvisharam, Vellore-632
509, Tamilnadu, India
cDepartment of Chemistry, Arignar Anna Government Arts College for women, Walajapet, Vellore,
Tamilnadu, India
dBioinformatics infrastructure facility, University of Madras, Guindy campus, Chennai-600 025,
Tamilnadu, India
ABSTRACT
The title compound 1-(2-chloro-4-phenylquinolin-3-yl)ethanone (CPQE) was synthesised
effectively by chlorination of 3-acetyl-4-phenylquinolin-2(1H)-one (APQ) using POCl3 reagent.
Structural and vibrational spectroscopic studies were performed by utilizing single crystal X-ray
diffraction, FTIR and NMR spectral analysis along with DFT method utilizing GAUSSIAN’ 03
software. Veda program has been employed to perform a detailed interpretation of vibrational
spectra. Mulliken population analyses on atomic charges, MEP, HOMO-LUMO, NBO, Global
chemical reactivity descriptors and thermodynamic properties have been examined by (DFT/B3LYP)
method with the 6-311G(d,p) basis set level.
Key Words: Quinoline, Crystal structure, Spectroscopy, DFT.
*Corresponding author. Tel.: +919790084145. Email address: smurugavel27@gmail.com
(S.Murugavel)
1. Introduction
Various studies in medicinal chemistry research have exposed that the existence of halogens in
organic molecules often progresses their biological activities. An extensive variety of halogenated
compounds with diverse biological activities are known till date, for example anticancer [1], antiviral
[2], antituberculosis [3], antimalarial [4,5], antifungal agents [6] and antidiabetic agents [7]. A
noticeable example is chloroquine (and several of its derivatives) used in malaria treatment, as it
comprises of a chlorine atom at the 7-position of the quinoline crux. For testing anticancer activity in
vitro and immunosuppressive properties, quinolines are been probed as inhibitors of topoisomerase,
gyrase and IMPDH. Therefore, the evolvement of facile approaches for the synthesis of highly
functionalized quinoline derivatives represents a challenge in medicinal chemistry [8,9].
Furthermore, quinoline drugs primarily target type II topoisomerases or DNA gyrase in
Gramnegative bacteria to strengthen the cleavage complex at precise sites on DNA, then block DNA
replication and lastly lead to a lethal abrasion [10,11]. However, in present years the occurrence and
spread of genitourinary infections, which have developed the means of resistance to quinolines, have
become one of the major chief public health threats. A developing medical concern on methods of
resistance to quinolines has drawn much notice and much work are focused on this topic [12]. Some
researchers [13] show that the confrontation to quinolines is mainly due to mutations in whichever
ParC breakage-reunion or ParE TOPRIM areas of topo IV (topoisomerase IV) and in the analogous
gyrase domains. In addition structure activity relationship (SAR) discloses that the groups at N-1
position of quinolines are in close proximity to the preserved ParC helix a4 remains Ser79 and Asp83
in the topo IVeDNA complex [14]. Literature survey reveals that so for there is no synthesis and
characterization studies for CPQE. In recent years, density functional theory (DFT) has become a
progressively beneficial tool for theoretical studies. The success of DFT is mainly due to the point
that it expresses about small molecules more reliably than Hartree-Fock theory and also

computationally less challenging than wave function based methods with enclosure of electron
correlation [15, 16]. Thus, in order to characterize the relationship between molecular structure and
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macroscopic properties in the synthesised compound, it seems to be essential to take on a detailed
relative study of the isolated molecule and the solid state unit. In this paper, a combined approach by
X-ray crystallography and DFT calculation was handled, which takes advantage of both the high
interpretative influence of the theoretical studies and the accuracy and reliability of the experimental
technique.
In this paper, we report the synthesis, crystal structure, spectral and DFT studies of 1-(2-chloro-4-
phenylquinolin-3-yl)ethanone (C17H12ClNO). Here the molecular and selected electronic structure
properties of the title compound were studied experimentally and is compared theoretically using the
DFT. Thus, owing to the industrial and biological significance of substituted
quinolines, an extensive spectroscopic study on CPQE was accomplished using Fourier
transform infrared (FTIR) and 1H and 13C NMR. The density functional theory is a
popular post-HF method for the calculation of molecular structures, vibrational
frequencies and energies of molecules [17].The DFT calculations with the hybrid
exchange-correlation functional B3LYP (Becke’s three parameter (B3) exchange in
conjunction with the Lee–Yang–Parr’s (LYP) correlation functional) which are
specifically significant in systems comprising of extensive electron conjugation
and/or electron lone pairs [18-21]. Therefore the present investigation has been
undertaken to study the vibrational spectra of this molecule entirely and to classify
the various modes with greater wave number accuracy. Density Functional Theory
(DFT) calculation has been executed to compute the vibrational wave number [20].
Also, chemical reactivity values such as chemical hardness, chemical potential electronegativity
and electrophilicity index. HOMO, LUMO analysis have been used to reveal information regarding
charge transfer within the molecule to understand the biological activity of the CPQE. The change in
electron density (ED) in the antibonding orbital’s and stabilization energies E(2) of the molecule have
been calculated by natural bond orbital (NBO) analysis to give clear evidence of stabilization.
2. Experimental and Computational Methods
2.1. Materials and instruments
All the chemicals and reagents were purchased from commercially available suppliers and used
without further purification. Thin-layer chromatography (TLC) was carried out on aluminium backed
sheets of silica gel F254 (0.2 mm, Merck) and visualized under UV chamber. Elchem Microprocessor
based DT apparatus was used to determine the melting point for the synthesized compound on an
open capillary tube and the values are uncorrected. A Shimadzu affinity-1 FT-IR spectrophotometer
1
13
was used to record FT-IR spectra. H and C NMR spectra were recorded on 400 MHz Bruker
advance III instrument using CDCl3 as solvent. The chemical shifts are rendered as δ values in parts
per million (ppm) related to tetramethylsilane, with J values in Hertz. Mass spectra were obtained on
Perkin Elmer GC-MS [GC model: Clarus 680, MS model: Clarus 600 (EI)]. The emission spectra
were recorded on Hitachi F-7000 FL Spectrofluorimeter. The single-crystal XRD data was recorded
on a Bruker AXS Kapppa Apex II single crystal X-ray diffractometer at 296K.
2.2 Synthesis of 1-(2-chloro-4-phenylquinolin-3-yl)ethanone
Scheme 1. Synthesis of 1-(2-chloro-4-phenylquinolin-3-yl)ethanone

An equimolar mixture of o-amino ketone and ethylacetoacetate were mixed in presence of
ACCEPTED MANUSCRIPT
minimum amount (2-3 drops) of piperidine and reaction mixture was refluxed in an oil bath, at about
1600C for 6 h. Completion of the reaction was monitored by checking TLC. After completion of
reaction, the compound was washed with hexane to remove the unreacted product to give a desired
off-white product of 3-acetyl-4-phenylquinolin-2(1H)-one. To the 2.5 g of 3-acetyl-4-phenylquinolin-
2(1H)-one, POCl3 was mixed for chlorination and was refluxed at 900C for 4 h. When the reaction
was considered complete as determined by TLC analysis, the reaction was permuted to cool to room
temperature. The reaction was quenched with ice to get off-white compound of 1-(2-chloro-4-
phenylquinolin-3-yl)ethanone with 84% yield. The compound was recrystallized from ethanol
solution by slow evaporation at room temperature and solid colourless single crystal was collected.
The synthesized compound was characterized by FT-IR, 1H NMR, 13C NMR, mass spectra and single
crystal X-ray diffraction studies.
1
FT-IR (KBr pellets, cm-1): 3111.18, 1710.86, 1612.49, 750.3. H NMR (400MHz, CDCl3): δ=
2.21 (3H, s, -CH3), 7.35.-7.37 (2H, m, -CH), 7.51-7.54 (4H, m, -CH), 7.60-7.62 (1H, d, J = 8 Hz, -
CH), 7.77-7.81 (1H, t, -CH), 8.09-8.11 (1H, d, J = 8 Hz, -CH). 13C NMR (100MHz, CDCl3): δ= 31.8,
125.9, 126.5, 127.6, 2×128.6, 128.7, 129.0, 129.3, 129.7, 131.1, 2×133.9, 144.6, 147.2, 147.4, 201.8.
GC-MS (EI): 281.21. Mol. formula: C17H12ClNO, Exact Mass: 281.09, Mol. Wt.: 281.06, yield 84%,
M.pt. 202-204 ºC.
2.3 X-ray Crystallography
A Crystal of CPQE with approximate dimension of 0.35×0.30×0.30 mm3 was mounted on a glass
fiber using cyanoacrylate adhesive. The crystal measurement were made on a Bruker AXS Kapppa
Apex II single crystal X-ray diffractometer using graphite mono-chromated MoKα (λ = 0.71071 Å)
radiation and CCD detector. Diffraction data were collected at room temperature by the ω-scan
mode. A least-squares fit of several high angle reflections in the ranges 2.48 o < θ < 28.20o was used
to obtain the accurate unit cell parameters and orientation matrix for the title compound. The unit cell
parameters were determined for 36 frames measured (0.5ophi-scan) from three various
crystallographic zones and by means of the method of difference vectors. The intensity data was
obtained from an average four-fold redundancy per reflection and optimum resolution (0.75 Å). The
SAINT-NT (version 7.06a) software was utilized to perform the intensity data collection, frames
integration, Lorentz-polarization correction and decay correction. SADABS [22] program was used
to execute the empirical absorption correction (multi-scan). SHELXS-97 implemented in WinGX
[23] program suit was used to solve the structure by direct methods. The refinement was done by full-
matrix least-square method on the positional and anisotropic temperature parameters of the non-
hydrogen atoms, using SHELXL-97 [24]. Entire H atoms were located geometrically and constrained
to ride on their parent atom with C—H = 0.93–0.96 Å and with Uiso(H) = 1.5 Ueq for methyl H atoms
and 1.2Ueq(C) for other H atoms. The general-purpose crystallography tool PLATON [25], ORTEP
[26] and MERCURY [27] were used for structure analysis and presentation of the results.
2.4 Computational Details
2.4.1 DFT
The density functional theory DFT (B3LYP) [28, 29] method with the 6-311G (d, p) [30] basis set
was used to optimize the molecular structure of the compound in ground state . Without specifying
any symmetry for the title molecule all calculation were performed by using GaussView molecular
visualization program [31] and Gaussian 03 program package [32]. Gaussian 03W package was used
to calculate the optimized geometrical parameters, energy, atomic charges and dipole moments. The
optimized molecular geometry, Mullikan charges, HOMO, LUMO energy distributions and HOMO-
LUMO energy gap [33, 34] were constructed using GaussView 03 program. To describe all

stationary points as minima, the optimised structural parameters are carried out in the
vibrational frequency calculations at the DFT levels. Then vibrational averaged nuclear
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positions of CPQE are used for harmonic vibrational frequency calculations resulting in
IR frequency with intensity. Reciprocating to the complexity of the molecule, the
Potential Energy Distribution (PED) is performed to obtain overall information of the
molecular motions implicated in the normal modes of the compound. The
experimentally observed spectral data of CPQE is found to be in good accordance with
the spectral data obtained by quantum chemical calculations.
The vibrational modes are assigned on the foundation of PED (Potential Energy
Distribution) analysis using VEDA (Vibrational Energy Distribution Analysis) program
[35]. In order to figure out how the calculated data are in agreement with those of the
experimental ones. The scaling factor 0.961 [36] was used to scale down the
calculated vibrational frequencies to balance the systematic error produced by ignoring
anharmonicity and electron density. The NBO calculations [37] were executed using NBO 3.1
program as carried out in the Gaussian03W [32] package to understand the intra-molecular
delocalization or hyperconjugation.
The isotropic chemical shifts are frequently used as assistance in identification of organic
compounds and accurate predictions of molecular geometries are essential for reliable studies of
magnetic properties. The nuclear magnetic resonance (NMR) chemical shifts calculation were
calculated using Gauge-Included Atomic Orbital (GIAO) method [38,39] with the optimised
parameters obtained from B3LYP level with 6-311G(d,p) basis set. The B3LYP – GIAO is one of the
best methods for including electron correlation and allows calculating the nuclear magnetic shielding
1
tensor with accuracy [40, 41]. The H and 13C isotropic chemical shifts were referenced to the
respected values for TMS, which was calculated at the same level of theory.
3. Results and Discussion
3.1 Description of Crystal structure
The displacement ellipsoid plot and theoretical geometry structure with the atom-numbering
scheme for CPQE is shown in Fig.1. The structure of compound 1 comprises of a quinoline ring to
which a benzene ring is attached to C3, Chlorine atom attached to C1 and acetaldehyde group
attached to C2.
Fig.1. (a) View of CPQE showing the atom-numbering scheme. Displacement ellipsoids for the
non-H atoms are drawn at the 30% probability level. The H atoms are presented with spheres with
arbitrary radii. (b) The theoretical geometric structure of CPQE (B3LYP/6-311G(d,p) level).
The compound crystallized as a colourless solid in monoclinic system with space group P21/n and
cell constants: a = 9.8404(7) Å, b = 10.2907(7) Å, c = 14.3406(8) Å, α = 90˚, β = 107.503(4) ˚, γ =
90˚, V = 1384.96(16)Å3 and Z = 4. Details of the data collection, crystal parameters and refinement
process of title compound are given in Table 1. The supplementary information in the CIF form is
available from Cambridge Crystallographic Database Centre, No. CCDC 1448726.

Table 1 Crystal and experimental data for CPQE.
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Empirical formula
Formula weight
C17H12ClNO
281.73
Temperature (K)
296(2)
Wavelength (Å)
Crystal system
Space group
0.71073
Monoclinic
P21/n
Unit cell dimensions(Å, ˚)
a
b
c
β
9.8404(7)
10.2907(7)
14.3406(8)
107.503(4)
3
1384.96(16)
Volume (Å )
Z
4
3
1.351
Calculated density (Mg/m )
-1
0.269
Absorption coefficient (mm )
F(000)
584
3
0.35 x 0.30 x 0.26
Crystal size (mm )
Theta range for data collection (°)
Index ranges
2.94 to 28.20.
-13<=h<=9, -12<=k<=13, -19<=l<=18
Reflections collected
10197
Independent reflections
Completeness to theta = 28.20°
3358 [R(int) = 0.0224]
98.4 %
2
Refinement method
Full-matrix least-squares on F
Data / restraints / parameters
3358 / 0 / 183
2
1.05
Goodness-of-fit on F
Final R indices [I > 2σ(I)]
R indices (all data)
R1 = 0.0409, wR2 = 0.1155
R1 = 0.0575, wR2 = 0.1271
-3
0.24 and -0.22.
Largest diff. peak and hole (e.Å )
The quinoline (N1/C1-C9) ring is essentially planar [maximum deviation = 0.034(2) Å for the C1
atom] and forms dihedral angle of 60.4 (1)º with the benzene ring. The chlorine atom Cl is deviated
by 0.110 (1) Å from the attached quinoline ring. The bond distances N1—C1, C9—N1, C1—Cl1,
C16—O1, C2—C16, and C3—C15 are 1.291(2), 1.372(2), 1.753(2), 1.206(2), 1.509(2) and 1.494(2)
Å, respectively, which agrees with the bond distances, C—N, C—C, C—Cl, C—O of quinoline
derivatives as shown in literature [42,43]. In pyridine ring the N—C bond lengths [1.291(2) —
1.372(2) Å] and bond angles C1–N1–C9 [116.78(1)°] are found close to the reported values for
similar quinoline derivatives [44].
The hydrogen bond geometry for CPQE is presented in Table 2. In the crystal, inversion dimers
2
are linked by pairs of C14-H14…O1i [i=1-x, 1-y, 1-z] hydrogen bonds, forming R2 (14) ring motifs.
This dimer is further linked by intermolecular C-Cl-π interactions between a chlorine atom Cl1 and a
neighbouring molecule of the pyridine ring (N1/C1-C4/C9) as an acceptor, with Cl1…centroid
(Cg1ii) [ii=1/2-x,1/2+y,3/2-z] distance of 3.744(1)Å and a C1-Cl1…Cg1ii angle of 137.7(1)° and
intermolecular π-π interactions with Cg1…Cg2iii = Cg2…Cg1iii = 3.706(1)Å [iii = -x,1-y,1-z; Cg1
and Cg2 are the centroids of the pyridine and benzene(C4-C9) rings, respectively] forming a three
dimensional supramolecular network (Table 2 and Fig. 2).
Table 2 Hydrogen bonding geometry for CPQE (Å, °)
D–H...A
C14–H14…O1i
D–H
d(H...A)
d(D...A)
3.206(2)
<(DHA)
132
0.93
2.51
Symmetry code : (i) 1-x,1- y,1-z.

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Fig. 2. View of three-dimensional supramolecular network. The C-H…O, C-Cl…π and π-π
interactions are shown as magenta, red and blue dotted lines, respectively. Cg1 and Cg2 are the
centroids of N1/C1-C4/C9 pyridine and C4–C9 benzene rings, respectively[ Symmetry codes : (i) 1-
x,1- y,1-z; (ii) 1/2-x,1/2+y,3/2-z ; (iii) -x,1-y,1-z]. Hydrogen atoms which are not included in the
hydrogen bonding are omitted for clarity.
3.2 DFT Calculations
Determining the optimized geometry of CPQE is the main task among the computational work.
The starting coordinates were taken from X-ray structure determination. The optimized parameters
(bond lengths, bond angles) of CPQE were obtained using (DFT/B3LYP) method with 6-311G(d,p)
basis set. The results are listed in Table 3 and compared with the experimental data for CPQE. As
seen from Table 3, the agreement between the experimentally obtained and the theoretically
calculated structure parameters for CPQE are very good. In assessment of the bond lengths in
Table 3, most predicted values are longer than experimental ones. We note that the theoretical
calculations are for the gas phase and the experimental results are for the solid phase. In the solid
state, the presence of a crystal field along with the intermolecular interactions connect the molecules
together, which results in the variance in bond parameters between the calculated and experimental
values [45]. When the X-ray structure of CPQE is related with its optimized counterpart (Fig. 1),
conformational differences are observed for B3LYP/6-311G (d,p) level.
Table 3 Selected structural parameters by X-ray diffraction and DFT calculations for CPQE.
Parameters
Bond lengths (Å)
C1-N1
C1-Cl1
C2-C3
C2-C16
C3-C15
C9-N1
C16-Ol
C16-C17
C13-C14
C14-C15
Bond angles (°)
N1-C1-C2
N1-C1-Cl1
C2-C1-Cl1
C3-C2-C16
C2-C3-C15
X-ray
DFT
1.291(2)
1.753(2)
1.379(2)
1.509(2)
1.494(2)
1.372(2)
1.206(2)
1.489(3)
1.383(2)
1.390(2)
1.291
1.773
1.384
1.522
1.493
1.364
1.208
1.510
1.393
1.400
126.70(2)
115.71(1)
117.59(1)
122.14(1)
120.04(1)
125.99
116.31
117.69
121.95
120.85

O1-C16-C17
O1-C16-C2
122.45(2)
120.87(2)
116.67(2)
116.78(1)
119.70(1)
123.31
120.24
116.45
117.87
120.84
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C17-C16-C2
C1-N1-C9
C14-C15-C3
Torsion angles (°)
N1-C1-C2-C3
Cl1-C1-C2-C3
N1-C1-C2-C16
Cl1-C1-C2-C16
C3-C2-C16-O1
C1-C2-C16-O1
C3-C2-C16-C17
1.6(2)
-178.76(1)
-176.49(2)
3.11(2)
108.61(2)
-73.4(2)
-0.1
179.3
179.4
-1.1
87.4
-92.1
-91.7
-72.70(2)
As shown from Table 3, the difference between X-ray and calculated values for the bond lengths
C1-Cl1, C2-C16, C16-C17, C13-C14 and C14-C15 are 0.020 Å, 0.013 Å, 0.021 Å, 0.010 Å and
0.010 Å respectively. Similarly, the difference between the bond angles for C1–N1–C9, N1–C1–Cl1,
N1–C1–C2, C3-C2-C16 and O1-C16-C17 are 1.09°, 0.60°, 0.71°, 0.19° and 0.86° respectively. This
difference is more not only because of intermolecular C14–H14…O1 hydrogen bond but also due to
intermolecular C1-Cl1…π and π-π interactions. According to experimental and computed values, the
dihedral angles amongst the quinoline and benzeine rings for the title compound are 60.4 (1)º and
66.5°, respectively.
The optimized structure from theoretical calculation is superimposed with the molecular skeleton
from X-ray diffraction, giving a RMSD of 0.147 Å (Fig. 3). From the obtained results, it may be
concluded that the B3LYP calculation well reproduce the geometry of CPQE.
Fig. 3. Atom-by-atom superimposition of the calculated structure (red) and the X-ray
structure (blue) for CPQE.
3.3 Vibrational assignments
The full vibrational assignments of fundamental modes of 1-(2-chloro-4-phenylquinolin-3-
yl)ethanone along with the PED are given in Table S1. The molecule consists of 32 atoms and
expected to have 90 normal modes. Normal coordinate analyses were performed to provide the entire
assignment of fundamental vibrational wavenumbers of the molecule. DFT force fields which were
calculated theoretically was transformed to the final set of vibrational coordinates and applied in all
succeeding calculations. Potential energy distribution (PED) was calculated for each normal mode
among the symmetry coordinates of the molecule. Based on the calculated PED values and FT-IR
band intensities a detailed assignment of the fundamentals was proposed. The unscaled vibrational
wavenumbers are generally larger than the experimental value. Since the theoretical calculations
were made for a free molecule in vacuum and the experimental calculations were performed for
liquid sample, there is the disagreement between calculated and observed vibrational wavenumbers.
The reason is also relatively due to the neglecting of anharmonicity and partly due to approximate
nature of the quantum mechanical methods. However, for dependable information on the vibrational
properties the use of selective scaling is necessary. The calculated wavenumbers are scaled using the
scaling factor 0.961 [36].

The experimental and theoretical FT-IR spectra are shown in Fig. 4 for comparative purposes, in
which the calculated intensity and activity are plotted against the harmonic vibrational frequencies.
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The experimental wavenumbers, calculated wavenumbers and IR intensities are given in Table S1
along with detailed assignments. The vibrational spectral analysis is performed on the
basis of the characteristic vibrations of quioniline ring, phenly ring, carbonyl group
and methyl group.
3.3.1 Carbon–Hydrogen ring vibrations
The C–H stretching wavenumbers, for aromatic compounds occur in the range 3000–3100 cm-1,
and the for C–H in-plane and out-of-plane bending vibrations it occurs in the range 1000–1300 and
750–1000 cm-1, respectively [46, 47]. This is the distinctive region for the identification of C–H
stretching vibration. In this region the bands are not altered significantly by the nature of the
substitutions. Accordingly, in the present study, the nine adjacent hydrogen atoms left around the
rings of CPQE give rise to nine C–H stretching vibrations, which correspond to stretching modes of
C5– H5, C6–H6, C7–H7, C8–H8, C10-H10, C11-H11, C12-H12, C13-H13 and C14–H14 units
respectively. The aromatic C–H stretching of the compound give bands at 3111, 3070, 3055 and 3035
cm-1 in the FT-IR spectrum. Due to a decrease in the dipole moment instigated by reduction of
negative charge on the carbon atom, all the aromatic C–H stretching bands are found to be weak.
This reduction of negative charge on the carbon atom takes place because of the electron withdrawal
by the substituent, which in turn initiates the increase in the chain length of the substituent [48]. As
expected, these nine modes are pure stretching modes and is evident from PED column of Table 4,
which almost contribute 95%
In aromatic compounds the C–H in-plane bending vibrations are viewed in the region 1300–850
cm-1 and are generally weak. The C–H out of plane bending modes [49-51] usually medium intensity
arises in the region 950–600 cm-1 .The C–H in-plane bending vibration observed at 1298, 1244, 1137,
1102, 1060, 1012 and 1003 cm-1 by the present method shows excellent agreement with FT-IR bands
at 1271, 1202, 1157, 1118, 1080, 1030 and 1012 cm-1. The aromatic C–H out-of-plane bending
vibrations occur at the region below 1000 cm-1. In the present study, the bands 971, 969, 949, 945,
907, 828, 787, 770, 754 and 689 cm-1 assigned to the calculated spectrum fits with the C–H out-of-
pane vibrations. These vibrations are observed at 997, 964, 935, 922, 899, 804, 787, 770, 750, 718,
708 and 673 cm-1 in the FT-IR spectrum. The calculated results are in well agreement with the
observed data [52, 53].
Fig. 4. Experimental FT-IR and simulated spectra for CPQE

3.3.2 Carbon–Carbon ring vibrations
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In the spectrum of aromatic compounds the ring stretching vibrations are most essential and are
exceedingly specific of the aromatic ring itself. The peaks in fingerprint region are difficult to assign
for empirical assignments of the vibrational modes. The ring carbon–carbon stretching vibrations
occur in the region of 1625–1430 cm_1. In general, the bands are of varying intensities and are
observed at 1625–1590, 1590–1575, 1540– 1470, 1460–1430 and 1380–1280 cm_1 from the
wavenumber ranges given by Varsanyi et al. [54] for the five bands in the fingerprint region. With
heavy substituents, the bonds have a tendency to to shift to somewhat lower wavenumber and greater
the number of substituents on the ring, broader the absorption regions.
In the current study, the CH in-plane bending vibrations are mixed with C-C stretching mode of
the phenyl ring. The wavenumbers observed at 1612, 1562, 1550, 1496, 1485, 1390, 1357, 1327,
1301, 1271, 1217, 1202, 1157 and 1030 cm-1 are assigned to C–C stretching vibrations. The
calculated bands at 1589, 1578, 1553, 1524, 1426, 1415, 1358, 1339, 1304, 1274, 1257, 1244, 1173,
1159 and 1060 cm-1 for the C-C stretching vibrations and are in good agreement with the
observations in the experimental FT-IR spectra. The C-C in-plane and out-of-plane bending
vibrations modes has smaller force constants than the stretching modes, hence assigned to lower
frequencies. The frequencies of the out-of-plane deformation vibrations are lower than the in-plane
deformations. Shimanouchi et al. [55] gave the frequency information for these vibrations for
different benzene derivatives as a result of normal coordinate analysis. The aromatic ring
deformation vibrations occur in the region of 625-605 cm-1 for mono substituted ring and 475-425
cm-1 for the tri substituted ring. The bands observed at 663, 640, 613, 592, 573, 554, 480 and 424 cm-
1
in FT-IR and the calculated bands by the present method are at 642, 625, 604, 599, 577, 560, 468
and 420 cm-1 are assigned to the C-C ring deformation. Even though some modes are missing in the
experimental spectra, the calculated CCC in-plane and out-of-plane bending modes are found to be
reliable with the recorded spectral values.
3.3.3 Methyl group vibrations
In the aromatic ring system the methyl group vibrations are normally discussed as electron
donating substituent. The CPQE molecule possesses only one methyl group. The C-H stretching
vibrations of the methyl group lie in the region 2975-2840 cm-1 [56, 57]. In general, there are nine
fundamentals can be accompanied to the CH3 group [58], namely the symmetrical stretching and
asymmetrical stretching, symmetrical and asymmetrical deformation modes, in-plane stretching
modes, in-plane and out-of-plane twisting and rocking modes. For the asymmetric stretching of CH3
mode the two C-H bonds of the methyl group are expanding while the third one is contracting and for
the symmetric stretching all the three C-H bonds expand and contract in phase. The asymmetric
stretching for the CH3 has magnitude higher than the symmetric stretching [56,57,59].The
asymmetric stretching of CH3 observed in FT-IR at 3001and 2945 cm-1 are in good agreement with
the calculated values at 3013 and 2970 cm-1. The PED of this mode is 98%. The methyl symmetric
stretching mode is calculated theoretically at 2911cm-1 which is observed at 2918 cm-1 in
experimental FT-IR. The PED of this mode is 98%. The deformation of the CH3 group is generally
noticed in the range 1450-1400 cm-1 for methyl substitution aromatic rings [57, 60]. In this title
molecule the calculated peaks at 1460, 1413, 1403, 1339 and 1328 cm-1 are assigned to CH3 in-plane
scissoring modes, which are in close agreement with the observed values at 1444, 1390, 1357 and
1327 cm-1 in FT-IR. The band observed at 996 cm-1 is CH3 out-of-plane bending mode.
3.3.4 Carbonyl group vibrations
The carbonyl group stretching vibrations impart characteristic bands in IR. The carbonyl group
vibration is observed in the region 1760–1730 cm-1 [61, 62]. The strong band observed at 1710 cm-1
in IR is assigned to carbonyl C16–O1 stretching mode and calculated at 1720 cm-1 in the present
method. The chelate effect of carbonyl group with other nucleophile which includes both intra and
intermolecular hydrogen bonding in the crystal, results with red shift in C=O stretching vibrational

bands. The C–O in-plane bending is assigned at 521 cm-1 experimentally and 509 cm-1 in the
computed method
.
ACCEPTED MANUSCRIPT
3.3.5 Carbon–Chlorine vibrations
It is worth to discuss that the C-Cl vibrations belong to the bond between the ring and chlorine
atoms, due to the lowering of the molecular symmetry mixing of vibrations is possible and the heavy
atoms exist on the periphery of the molecule [63]. Balachandran et al. [64] assigned vibrations of
C-X group (X = F, Cl and Br) in the frequency range 1292-485 cm-1. Normally strong bands in the
region 710–505 cm-1 are seen in the C–Cl stretching vibrations. Regularly for simple organic chlorine
compounds, C–Cl absorptions are in the region 750–700 cm-1 [65]. The C-Cl deformations are
expected around 460–175 cm-1 [57]. Based on the above literature values, in this work, the band
observed at 573 cm-1 in FT-IR spectrum is assigned as C–Cl stretching vibration, which highly
coupled with in-plane and out-of-plane C–C bending vibrations. The theoretically computed
wavenumbers are assigned at 577 cm-1 and 348 cm-1 for C–Cl stretching and deformation bands,
respectively, showing good agreement with experimental observation.
3.3.6 Carbon–nitrogen vibrations
Since mixing of vibrations is possible due to lowering of molecular symmetry, the identification
of C–N stretching vibrations is a very difficult task. The C=N stretching skeletal bands [66-68]
occurs in the region 1627–1566 cm-1. For CPQE the band spotted at 1549 cm-1 in FT-IR spectrum
and calculated wavenumber at 1537 cm-1 are assigned to the C=N stretching mode. The ring C–N
stretching vibration occurs in the region 1310–1290 cm-1 [69].The FT-IR band observed
at 1271 cm-1 in the spectrum is assigned to the ring C–N stretching mode of vibration and the
calculated values at 1185 and 1094 cm-1 agree with the observed experimental value for the
corresponding mode of vibration. In the present study the theoretically computed wavenumber for the
C–N bending is at 981 cm-1. The PED of this mode is 12%. The low PED value of
this mode suggests that this is a mixed mode.
The comparison of theoretical observations with the experimental observation is given as the
correlation graph in Fig. S1 based on the calculation. As can be seen from the correlation graph, the
correlation coefficient (CC) R2 is 0.999 for B3LYP/6-311G (d,p).
3.4 NMR spectral studies
Since NMR involves rich information on the electronic structure of molecules, the characterization
1
of CPQE was further enhanced by use of H and 13C NMR spectroscopy. Precise prediction of
molecular geometry measurement is necessary for reliable computations of magnetic properties,
hence after performing the full geometry optimization of CPQE using DFT at B3LYP/6-311G(d,p)
method the Gauge-Independent Atomic Orbital (GIAO) procedure which is considered to be an
advanced method which is an extension of the basis set used, was performed to calculate the
chemical shift theoretically for CQPE under the same technique. The isotropic shielding values were
utilized to calculate the isotropic chemical shifts δ relating to tetra methyl silane (TMS)
TMS
iso
X
1
13
TMS
iso
(
δisXo
=
σ
−
σ iso
)
. For H and C NMR spectra, the value of
σ
are 31.99 and 184.79 ppm,
1
13
respectively. The chemical shifts were determined in chloroform (CDCl3). The H and C NMR
spectra of CPQE by means of chloroform (CDCl3) are shown in Figures S2 and S3, respectively
(Supporting information). The H and 13C experimental and theoretical chemical shifts, isotropic
1
shielding tensors and the assignments of CPQE are given in Table 4. 1H atom is mostly localised on
periphery of the molecules and their chemical shifts would be more inclined to intermolecular
interactions. Aromatic carbons give signals with chemical shift values from 100 to 200 ppm [70, 71].
In our present investigation, the experimental and theoretical 13C NMR chemical shift values of
aromatic carbons are in the range 31.85–201.26 ppm and 35.03–210.63 ppm, respectively. The
oxygen in carbonyl group reduces the electron density of the carbon atom C16, therefore the
13
calculated C NMR chemical shift value of C16 bonded to carbonyl group is the most high one,
observed at 201.26 ppm while which was calculated at 210.63 ppm using B3LYP/6-311(d,p). It is

noted that the maximum deviance from experimental chemical shift for 13C chemical shift calculated
by B3LYP/6-311G(d,p) is for C3 at 23.44 ppm. The chemical shift value of C1 and C9 are also found
ACCEPTED MANUSCRIPT
significantly high due to the influence of electronegative nitrogen atom and chlorine atom and are
observed at 147.49 and 147.21 ppm and the corresponding calculated values are at 155.54 and
152.97ppm, respectively. The extreme downfield signal is assigned to the carbonyl carbon C16, due
to the high electronegativity of oxygen when compared to the nitrogen atom at C1 and C9. The
extreme upfield signal observed at 31.85 ppm and calculated at 35.03 ppm was assigned to methyl
carbon at C17. The other carbons lie in the range 144.64 – 125.94ppm. The experimental chemical
shift values are well agreed with the theoretical values. The strong signal at around 77 ppm belongs
to the solvent peak.
1H chemical shifts of CPQE were obtained by complete analysis of their NMR spectra and
interpreted critically in an attempt to calculate the possible different effects acting on the shielding
constant of protons. The chemical shift values of H atoms are measured in the range 2.21– 8.10 ppm
1
and calculated in the range 1.90 – 8.43 ppm. For H chemical shifts, the maximum deviance from
experimental value is calculated by B3LYP/6-311G(d,p) for H7 at 0.68 ppm. The CPQE has a
nitrogen atom on the quinoline ring which can act as donor site and on the base of its basicity, the
1
endocyclic nitrogen N1 is expected to be a good donor atom and evidenced by the H NMR
spectrum. Thus, the extreme down field signal at 8.10 ppm assigned to the H8 proton of the quinoline
ring, strongly specifies the donor nature of N1 atom. The methyl protons at C17 gave the signal
appears as singlet at 2.21 ppm. The calculated and experimental chemical shift values in Table 4
shows good agreement with each other. The correlation graph between the experimental and
13
theoretical C NMR Chemical shifts are represented in Fig. S4 based on calculations. As can be
seen from the graph, the correlation co-efficient (CC) R2 for 13C is 0.973.
1
13
Table 4 The experimental and calculated H and C isotropic chemical shifts (ppm) with respect to
TMS of CPQE
Experimental
Theoretical
δ (ppm)
Experimental
δ (ppm)
Theoretical
δ (ppm)
Assignment
Assignment
δ (ppm)
C1
C2
C3
C4
C5
C6
C7
147.49
128.76
133.97
126.54
127.66
131.15
133.94
155.54
140.51
157.41
132.53
133.17
134.01
137.51
H5
H6
H7
H8
H10
H11
H12
7.79
7.51
7.53
8.10
7.37
7.54
7.61
7.85
7.93
8.21
8.43
7.64
7.88
7.91
C8
C9
125.94
147.21
128.62
129.75
129.30
129.01
128.62
135.90
152.97
136.92
133.87
135.68
134.76
139.32
H13
H14
H17A
H17B
H17C
-
7.55
7.35
2.21
2.21
2.21
-
7.86
7.68
1.90
1.89
2.69
-
C10
C11
C12
C13
C14
-
-
-
C15
C16
C17
144.64
201.26
31.85
142.37
210.63
35.03
-
-
-
-
-
-
-
-
-
Note: The atom numbering according to Fig. 1 used in assignment of chemical shifts.
3.5. NBO analysis
The study of inter-molecular bonding, interaction among bonds, and also the investigation of
charge transfer or conjugative interactions in molecular systems are effectively analysed from the
Natural Bond Orbital (NBO) analysis [72, 73]. The natural bond orbital (NBO) calculations [37]
were executed using the NBO 3.1 program as implemented in the Gaussian 03W package in order to
understand the different second order interactions among the filled orbitals of one subsystem and
vacant orbitals of another subsystem, which is an assessment of the intermolecular delocalization or

hyperconjugation. NBO analysis provides the most accurate possible ‘natural Lewis structure’ picture
of j, because all orbital details are mathematically chosen to include the highest promising percentage
ACCEPTED MANUSCRIPT
of the electron density (ED). The significance of NBO method is that it gives validation about
interactions in both filled and virtual orbital spaces, thus improving the analysis of inter and
intramolecular interactions. To compute the donar-acceptor interactions in the NBO basis, the second
order Fock matrix was used [74]. The interactions result in a loss of occupancy from the localised
NBO of the idealized Lewis structure into an empty non-Lewis orbital. For each donor (i) and
acceptor (j) the stabilization energy E(2) associated with the delocalization i → j is determined as
E(2) = ꢀEij = qiF(i,j)2 / (εj-εi)
Where qi is the donor orbital occupancy, εi and εj are diagnol elements and F(i,j) is the off-
diagonal NBO Fock matrix element.
In NBO analysis large E(2) value shows the exhaustive interaction between electron donors
and electron acceptors and larger the extent of conjugation of the whole system. NBO analysis has
been executed on the molecule at the DFT/B3LYP/6-311G(d,p) level in order to elucidate the inter
molecular, rehybridization and delocalization of electron density within the molecule. The significant
interactions between Lewis-type and non-Lewis NBOs for CPQE are reported in Table S2. The
interaction between the doubly occupied orbitals and the unoccupied orbital is responsible for
decreasing of orbital energy, which is a suitable method to interpret the molecular structure in the
electronic point of view. Several other types of valued data, such as directionality, hybridization and
partial charges, can also be analysed from NBO results.
The strong intermolecular hyperconjugative interactions are formed by orbital overlap
between π(C-C), π*(C-C) and σ(C-C), σ*(C-C) bond orbitals, which effects in intermolecular charge
transfer, causing stabilization of the system. These interactions are noted as an increase in the
electron density(ED) in the C-C antibonding orbital that weakens the respective bonds [75]. The ED at
the conjugated σ bonds (1.96e) and σ*(0.02e) of the aromatic ring clearly demonstrates weak/strong
delocalization. The intermolecular hyperconjugation interaction is strong for the π electrons from
(C12-C13) to the π* antibonding orbitals of (C10-C11) and (C14-C15) bond shows an ED of 1.65e,
leading to the stabilization of 20.75 and 21.52 kJ/mol respectively. From Table S2, it is seen that the
interactions are viewed as increase in ED in C14-C15 anti-bonding orbital that weakens the respective
bonds. Another important hyperconjugation interaction is for the lone pair atoms, in the present study
of our molecule there is a strong intermolecular hyper-conjugative interaction of N1-C1from Cl1 of
LP (3) Cl1→π*(N1-C1) which increases ED(0.35658e) that weakens the respective bond N1-C1
(1.91668e) leading to stabilization of 14.85 kJ/mol. The hyper conjugative interaction of C2-C16
from O1 of LP (2) O1→σ*(C2-C16) which increases ED (0.07671e) that weakens the respective bond
C2-C16 (1.87899e) leading to stabilization of 21.94 kJ/mol and also the hyperconjugation of C16-
C17 from O1 of LP (2) O1→σ*(C6-C17) which increases ED (0.05683e) that weakens the respective
bonds C6-C17 (1.87899e) leading to stabilization of 19.21 kJ/mol. Then, the hyperconjugative
interaction of C1-C2 from N1 of LP (1) N1→σ*(C1-C2) which increases ED (0.04995e) weakens the
respective bond C1-C2 (1.88803e) leading to stabilization of 11.98 kJ/mol. The significant highest
energy, associated to the molecule is electron donating from π*(C4-C9) to the antibonding acceptor
π*(C5-C6) and π*(C7-C8) with stabilization energy 233.92 and 194.46 kJ/mol, respectively.
Similarly, the electron donating from π*(N1-C1) to the antibonding acceptor π*(C4-C9) and π*(C2-
C3) leads to strong delocalization of 136.02 and 81.31 kJ/mol respectively. These highest interactions
around the ring can induce large bioactivity in the compound.
3.6. Mulliken analysis
The fundamental to chemistry is the atomic charge in molecules. For instance, to describe the
processes of electronegativity equalization and charge transfer in chemical reactions atomic charge
has been used [76, 77] and also to model the electrostatic potential outside molecular surfaces [78-
80]. Mulliken atomic charges calculated at the B3LYP/6-311G(d,p) methods are collected in Table 5.
It is worthy to mention that C1, C9 and C16 atoms of title compound exhibit positive charges,

whereas remaining carbon atoms exhibit negative charges. All the hydrogen atoms exhibit net
positive charge. The existence of huge negative charge on N1, O1 and Cl1 atoms are due to their
ACCEPTED MANUSCRIPT
electron withdrawing nature.
Table 5 Mulliken atomic charges of CPQE.
Atoms
Cl1
O1
Atomic charges
-0.061710
-0.269418
-0.320255
0.096478
Atoms
C14
Atomic charges
-0.024031
-0.213666
0.177491
-0.283724
0.116766
0.100959
0.102508
0.107493
0.101163
0.100742
0.101565
0.104144
0.114496
0.134981
0.136166
C15
C16
C17
H5
N1
C1
C2
C3
C4
C5
C6
C7
C8
C9
C10
C11
C12
-0.078560
0.220866
H6
-0.090966
-0.061592
-0.087783
-0.083087
-0.033883
0.080861
-0.065170
-0.086109
-0.086523
H7
H8
H10
H11
H12
H13
H14
H17A
H17B
C13
-0.087597
H17C
0.137397
3.7. Molecular orbital studies
In principle, there are several ways to calculate the excitation energies. The first,
and the easiest one, comprises the variation between the highest occupied molecular
orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of a neutral
system. This technique associates to the frozen orbital approximation, as the ground
state properties are utilized to compute excitation values. The molecular orbital (MO)
theory has been broadly used by chemists. The frontier molecular orbitals play a vital role in the
optical and electronic properties, as well as in UV-VIS spectra and chemical reactions [81]. LUMO
as an electron acceptor denotes the capability to obtain an electron, while HOMO as an electron
donor gives away an electron. If the energy gap of LUMO and HOMO is small, the excitation for the
electrons of HOMO will also be easy. It is easy for HOMO to donate electrons when the energy of
HOMO is high and similarly it is easy for LUMO to accept electrons when the energy of LUMO is
low. Fig. 5 shows the frontier molecular orbital energies of the title compound.
Fig. 5. The molecular orbital and energies for the HOMO and LUMO of CPQE.

The HOMO–LUMO gap is also related to kinetic stability or chemical reactivity [82]
.
The huge value of HOMO–LUMO gap signifies to chemically stable molecules and in vice
versa the chemically reactive molecules are frequently related with less HOMO–
ACCEPTED MANUSCRIPT
LUMO gap. Further energy gap between HOMO and LUMO is a critical parameter in determining
molecular electrical conveyance properties [83, 84]. The lowest unoccupied molecular orbital
(LUMO) energy is -2.0680 eV and the highest occupied molecular orbital (HOMO) energy is -6.7484
eV. The ultimate charge transfer interaction within the molecule is explained by the energy gap of
HOMO–LUMO. The frontier orbital energy gap of CPQE is found to be -4.6804 eV which shows
that there is a transfer of electrons from HOMO to LUMO, obtained at DFT method using 6-
311G(d,p) basis set. The Eigen values of LUMO–HOMO energy gap reflect the chemical
activity of the molecule. The decrease in the HOMO and LUMO energy gap describes
the subsequent charge transfer interaction taking place within the molecule, due to the
strong electron-accepting capacity of the electron-acceptor group. It is necessary to
note that HOMOs will have a whole p bonding character together with a significant
non-bonding character and LUMOs will have an anti-bonding character. The strong
p
charge transfer interaction is accountable for the bioactivity of the compound.
3.8. Chemical reactivity
Chemical reactivity indices like chemical hardness (η), electronegativity (χ), electronic chemical
potential (ꢀ), and electrophilicity Index (ω), are calculated using DFT. Chemical hardness is related
with the stability and reactivity of a chemical system. In a molecule, it evaluates the resistance to
vary the electron distribution or charge transfer. On the base of frontier molecular orbitals, chemical
hardness links to the gap between the HOMO and LUMO. Chemical hardness is approximated using
equation η = (ELUMO− EHOMO)/2, where ELUMO and EHOMO are the LUMO and HOMO energies,
respectively.
The greater the HOMO–LUMO energy gap, the molecule will be harder, more stable and less
reactive. Table 6 (row 4) comprises the computed chemical hardness value for CPQE. The idea of
electronegativity given by Pauling [85] is defined as ‘‘the power of an atom in a molecule to attract
electrons towards itself’’. Higher the electronegativity of the type, larger is its electron accepting
power or rather the electrophilicity. Electronegativity is determined using equation χ = - (EHOMO
LUMO) /2, Table 8 (row 6) contains the computed electronegativity values for CPQE.
Electronic chemical potential is explained as the negative of electronegativity of a molecule [86]
+
E
and determined using equation ꢀ = (EHOMO + ELUMO)/2. Physically, ꢀ describes the evading tendency
of electrons from an equilibrium system [87].
Table 6 Calculated energy values of CPQE by B3LYP/6-311G(d,p)
Basis set
B3LYP/6-311G(d,p)
EHOMO (eV)
-6.7484
ELUMO (eV)
-2.0680
EHOMO - ELUMO gap (eV)
Chemical hardness (η)
Chemical potential (µ)
Electronegativity (χ)
Electrophilicity index (ω)
-4.6804
2.3402
-4.4082
4.4082
4.1518
The value of ꢀ for CPQE is presented in Table 6 (row 5). Global electrophilicity index (ω),
introduced by Parr, is determined using the electronic chemical potential and chemical hardness as
presented in equation ω = ꢀ2/2η. Electrophilicity index calculates the propensity or ability of a type to
accept electrons [88, 89]. It is a measure of the stabilization in energy once a system accepts

additional sum of electronic charge from the environment [90, 91]. The electrophilicity value of the
CPQE is presented in Table 6 (row 7).
ACCEPTED MANUSCRIPT
The HOMO and LUMO orbital energies are related to gas phase ionization energies (I) and
electron affinities (A) of the isomers according to the Koopmans’ theorem through equations A = −
E
LUMO, I = − EHOMO. Electron affinity states that the potential of a ligand will accept accurately one
electron from a donor. The chemical reactivity values obtained from Table 6 concludes that the
CPQE is biologically active with reference to the literature [92].
3.9. Molecular Electrostatic Potential
Molecular electrostatic potential (MEP) provides a signal of the total electrostatic impact
generated at that point through the total charge distribution of the molecule. It also relates with dipole
moments, electronegativity and chemical reactivity of the molecules. It offers a visual method to
recognize the relative polarity of the molecules. The size, shape, site of chemical reactivity and
charge density of the molecules is depicted by an electron density isosurface mapped by electrostatic
potential surface. It is also been used mainly for calculating sites and relative reactivity towards
electrophilic and nucleophilic [93] attack, in studies of biological identification and hydrogen
bonding interactions [94, 95]. The negative electrostatic potential and positive electrostatic potential
are related through the attraction of proton by intense electron density in the molecule (colored in
shades of red on the EPS surface) and repulsion of the proton by the atomic nuclei in regions of low
electron density (colored in shades of blue on the EPS surface), respectively. Potential increases in
the order red < orange < yellow < green < blue, where blue specifies the strongest
attraction; red indicates strongest repulsion; and green indicates neutral electrostatic
potential region [96, 97]
.
Fig. 6. Molecular electrostatic potential map of CPQE, calculated using B3LYP/6-311G(d, p) level.
Fig. 6 shows the molecular electrostatic potential (MEP), was resolved using B3LYP/6-311G(d, p)
technique. The various values of the electrostatic potential at the surface are represented by different
colors. As can be seen in Fig. 6, the negative (red) region is localized on the unprotonated atom of O1
with minimum value of -0.0463a.u. However, positive (blue) region is localized on atom C14
probably due to hydrogen, with a value of 0.0424 a.u., respectively. So, Fig. 6 proves the presence of
an intermolecular C14–H14…O1 interactions.
3.10 Thermodynamic properties
To get consistent relations between energetic, structural and reactivity characteristics of the
molecules, the thermodynamics parameters of the compound have been determined. From the
knowledge of permanent dipole moment of the molecule, the molecule conformation is obtained.

Table 7 Thermodynamical parameters of CPQE by B3LYP/6-311G(d,p)
Parameters
ACCEPTED MANUVSaCluResI(PaTt 298 K)
Total energy (Hartree)
-1245.189210
Zero point energy (K cal.mol-1)
Rotational constants (GHz)
152.07304
0.38166
0.31298
0.18744
63.878
Specific heat (Cv) (cal.mol-1K-1)
Entropy (cal.mol-1K-1)
Total
Translational
Rotational
132.074
42.798
33.928
55.347
4.9495
Vibrational
Dipole moment (Debye)
The values of thermodynamic parameters (such as zero-point vibrational energy, entropy, specific
heat capacity), rotational constants and dipole moment of CPQE by DFT method B3LYP levels 6-
311G(d,p) basis set at 298.15 K and 1 atm pressure were calculated and listed in Table 7. From this
table, the high value of dipole moment of CPQE implies high delocalization of charges, ensuing in
the creation of relatively loose structured and charge withdrawn species. On the basis of B3LYP/6-
o
o
311G(d,p) calculations, the heat capacity at constant pressure (
C
), entropy ( ) and enthalpy (
S
p,m
m
o
H
) for CPQE were obtained from the harmonic frequencies and listed in Table 8. Since the
m
molecular vibrational intensities increases with the increase in temperature, the thermodynamic
functions also increase with temperature of the range 100–700K [98]. The temperature dependence of
heat capacity, entropy and enthalpy are shown in the temperature dependence correlation graph, Fig.
7.
Table 8 Thermodynamic properties of CPQE at different temperatures at B3LYP/6-311G(d,p) level
o
p,m
( cal.mol-1K-1)
o
o
( cal.mol-1K-1)
H
(Kcal.mol-1)
C
S
m
m
Temperature (K)
100
200
298.15
300
400
500
600
700
26.048
44.240
63.878
64.249
83.261
99.300
112.210
122.555
85.077
153.663
157.161
162.461
162.580
169.975
179.131
189.730
201.487
109.978
132.074
132.482
154.198
175.004
194.656
213.066
With the help of quadratic expressions, enthalpy changes, heat capacities, entropies and
temperature of correlation equation were fitted and the related fitting factors (R2) for these
thermodynamic properties were found to be 0.999, 0.998 and 1.000, respectively.
∆Hmo = 151.3 + 0.013T + 0.8 X10-4T2
Cpom
(R2= 0.999)
(R2 = 0.998)
(R2 = 1.000)
= 1.525 + 0.241T - 10.0 X10-5T2
Smo = 60.01 + 0.259T – 0.6 X10-4T2
These equations could be used for further studies on the title compound. For example, while
studying about the interaction of CPQE with another compound, the thermodynamic properties
obtained from the above equation can be used to evaluate the change in Gibbs free energy of the
reaction, which will in turn comfort to evaluate the spontaneity of the reaction.

ACCEPTED MANUSCRIPT
Fig. 7. Variation in thermodynamic parameters with temperature for CPQE.
4. Conclusion
The compound CPQE was synthesised and had been confirmed with NMR, FTIR and single
crystal X-ray diffraction techniques. Thee equilibrium geometry parameters, vibrational assignments,
13
1H NMR and C NMR chemical shifts have been determined using DFT method with 6-311G(d,p)
as basis set and are in good conformity with experimental outcomes. In the crystal molecules are
linked by intermolecular C-H…O, C-Cl…π and π-π interactions, forming a three dimensional
supramolecular network. Using Potential Energy Distribution (PED) the vibrational modes of
experimental wave numbers are allotted. The results of NBO specify strong intermolecular
hyperconjugative interactions with the molecule and stabilization of the molecule. The small HOMO-
LUMO gap value and the chemical reactivity values show that the molecule is biologically active.
The MEP map confirms the existence of intermolecular C–H…O interactions. The correlations
between the statistical thermodynamics and temperature are also obtained. The results of the studies
discussed in this paper will upsurge the knowledge to design and synthesize quinoline derivatives
with exceptional chemical, physical and biological properties.
Acknowledgements
The authors thank Dr. Shibu M.Eapen, SAIF, Cochin University of Science and Technology, for
his help with the single-crystal XRD measurements.
Supplementary Materials
CCDC 1448726 contains the supplementary crystallographic data for this paper. This data can be
obtained free of charge at http://www.code.cam.ac.uk/data_request/cif, by e-mailing
data_request@ccdc. cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB21EZ, UK; fax: +44(0)1223–336033.
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Figure caption
Scheme 1. Synthesis of 1-(2-chloro-4-phenylquinolin-3-yl)ethanone
Fig. 1. (a) View of CPQE showing the atom-numbering scheme. Displacement ellipsoids for the non-
H atoms are drawn at the 30% probability level. The H atoms are presented with spheres with
arbitrary radii. (b) The theoretical geometric structure of CPQE (B3LYP/6-311G(d,p)level).
Fig. 2. View of three-dimensional supramolecular network. The C-H…O, C-Cl…π and π-π
interactions are shown as magenta, red and blue dotted lines, respectively. Cg1 and Cg2 are the
centroids of N1/C1-C4/C9 pyridine and C4–C9 benzene rings, respectively[ Symmetry codes : (i) 1-
x,1- y,1-z; (ii) 1/2-x,1/2+y,3/2-z ; (iii) -x,1-y,1-z]. Hydrogen atoms which are not included in the
hydrogen bonding are omitted for clarity.
Fig. 3. Atom-by-atom superimposition of the calculated structure (red) and the X-ray structure (blue)
for CPQE.
Fig. 4. Experimental FT-IR and simulated spectra for CPQE.

Fig. 5. The molecular orbital and energies for the HOMO and LUMO of CPQE.
Fig. 6. Molecular electrostatic potential f CPQ calculat using B3LYP/6-311G(d, p) level.
map o E, ed
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Fig. 7. Variation in thermodynamic parameters with temperature for CPQE.
Supplementary figure caption
Fig. S1. Correlation graph between experimental and calculated wavenumbers at B3LYP level.
Fig. S2. Experimental spectrum of 13C NMR of CPQE.
Fig. S3. Experimental spectrum of 1H NMR of CPQE.
Fig. S4. Correlation graph between the experimental and theoretical 13C NMR chemical shift values
of CPQE.
Table caption
Table 1 Crystal and experimental data for CPQE.
Table 2 Hydrogen bonding geometry for CPQE (Å, °).
Table 3 Selected structural parameters by X-ray diffraction and DFT calculations for CPQE.
Table 4 The experimental and calculated 1H and 13C isotropic chemical shifts (ppm) with respect to
TMS of CPQE.
Table 5 Mulliken atomic charges of CPQE.
Table 6 Calculated energy values of CPQE by B3LYP/6-311G(d,p).
Table 7 Thermodynamical parameters of CPQE by B3LYP/6-311G(d,p).
Table 8 Thermodynamic properties of CPQE at different temperatures at B3LYP/6-311G(d,p) level.
Supplementary table caption
Table S1 Calculated and observed vibrational frequencies for CPQE at B3LYP
method with 6-311G(d,p) basis set.
Table S2 Second order perturbation theory analysis of fock matrix in NBO basis for CPQE.

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Highlights
•
•
•
•
The title compound has been characterized by FTIR, 1H NMR and 13C NMR.
The structure has been studied by SCXRD method and DFT.
The wavenumbers were assigned using PED analysis.
NBO, HOMO-LUMO and MEP and thermodynamic properties were reported.