Synthesis, characterization, antioxidant evaluation, molecular docking and density functional theory studies of phenyl and naphthyl based esters

Article abstract of DOI:10.1016/j.molstruc.2020.127812

Two phenol based esters phenyl benzoate (OE₁) and 1-naphthyl benzoate (OE₂) were synthesized from phenol/1-naphthol and benzoyl chloride respectively. The structural elucidation of the synthesized compounds was accomplished by spectroscopic studies (FTIR, ¹H NMR & GC-MS) and single crystal X-ray diffraction analysis. DPPH (2, 2-diphenyl-1-picryl-hydrazyl-hydrate) free radical and hydrogen peroxide activities were performed to evaluate the antioxidant capabilities of the synthesized esters. The compounds (OE₁ & OE₂) showed DPPH scavenging activity in concentration dependent manner with IC₅₀ values 605.6 μM and 1138.7 μM correspondingly. Similarly, in hydrogen peroxide assay, OE₁ and OE₂ exhibited moderate activity with IC₅₀ values 1510.2 μM and 1069.4 μM respectively. Molecular docking of the compounds was carried out to predict their antioxidant binding mechanism against target protein using the MOE suite. The structure?activity relationship analysis showed that replacing the phenyl ring by naphthyl significantly influences their activity. Geometrical studies of the compounds have been performed by both semi-empirical and DFT methods; results reveal an excellent convergence of experimental and theoretical structural parameters. A detailed bonding investigation of each compound has been performed by NBO and Bader's AIM analysis to obtain inter and intramolecular interactions.

Full text of DOI:10.1016/j.molstruc.2020.127812

Journal of Molecular Structure 1207 (2020) 127812
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
Synthesis, characterization, antioxidant evaluation, molecular docking
and density functional theory studies of phenyl and naphthyl based
esters
,
Zaib-un-Nisa a, Muhammad Shabbir a, Zareen Akhter a *, Muhammad Adeel Asghar a,
Vickie Mckee b, Asma Sani a, Faroha Liaqat a, Saima Kalsoom c, Shaista Sabir a,
Hammad Ismail d
a Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan
b School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland
c Center for Interdisciplinary Research in Basic Sciences (CIRBS), International Islamic University, Islamabad, Pakistan
d Department of Biochemistry & Biotechnology, University of Gujrat, 50700, Gujrat, Pakistan
a r t i c l e i n f o
a b s t r a c t
Article history:
Two phenol based esters phenyl benzoate (OE1) and 1-naphthyl benzoate (OE2) were synthesized from
phenol/1-naphthol and benzoyl chloride respectively. The structural elucidation of the synthesized
compounds was accomplished by spectroscopic studies (FTIR, 1H NMR & GC-MS) and single crystal X-ray
diffraction analysis. DPPH (2, 2-diphenyl-1-picryl-hydrazyl-hydrate) free radical and hydrogen peroxide
activities were performed to evaluate the antioxidant capabilities of the synthesized esters. The com-
pounds (OE1 & OE2) showed DPPH scavenging activity in concentration dependent manner with IC50
Received 22 September 2019
Received in revised form
26 January 2020
Accepted 28 January 2020
Available online 4 February 2020
values 605.6
exhibited moderate activity with IC50 values 1510.2
m
M and 1138.7
m
M correspondingly. Similarly, in hydrogen peroxide assay, OE1 and OE2
M and 1069.4 M respectively. Molecular docking of
Keywords:
Esters
m
m
the compounds was carried out to predict their antioxidant binding mechanism against target protein
using the MOE suite. The structureꢀactivity relationship analysis showed that replacing the phenyl ring
by naphthyl significantly influences their activity. Geometrical studies of the compounds have been
performed by both semi-empirical and DFT methods; results reveal an excellent convergence of
experimental and theoretical structural parameters. A detailed bonding investigation of each compound
has been performed by NBO and Bader’s AIM analysis to obtain inter and intramolecular interactions.
© 2020 Published by Elsevier B.V.
DPPH free radical activity
Hydrogen peroxide activity
Molecular docking
Density functional theory
AIM analysis
1. Introduction
[6,7].Due to efficacious biological worth of aromatic esters, phenyl
benzoate (OE1) and 1-naphthyl benzoate (OE2) were synthesized
Esters, an important class of organic compounds, possess
numerous biological and industrial applications. Natural esters
form backbone of DNA molecules and are found in pheromones,
fats and oils [1]. Synthetic esters have several therapeutic appli-
cations like methyl phenidate as nervous system stimulant whereas
salicylic acid acetate and phenyl salicylate as analgesics [2e4].
Moreover, they are applied for the preparation of cosmetics, per-
fumes, surfactants, plastics and as solvents for oils, fats, gums,
resins, cellulose, paints and varnishes [5]. In addition, esters have
shown significant antioxidant and free radical scavenging activities
from phenol, 1-naphthol and benzoyl chloride.
The bioactive nature of these organic esters was evaluated by
performing DPPH and hydrogen peroxide activities. Antioxidant
behavior of these compounds was investigated computationally
through molecular docking to predict the binding orientation of
small drug candidates to a target complex, thereby playing an
important role in understanding the binding pattern of docked
compounds in the active site of target protein [8]. Since the NO free
radicals have an important role to play in the immune and nervous
systems, their production needs to be regulated [9]. Nitric oxide
synthases (NOS) produces nitric oxide (NO) from
L-arginine.
Various isoforms of NOS have recently been selected as a target for
anti-cancer inhibitors [10].
* Corresponding author.
Density Functional studies have been carried out to understand
E-mail addresses: zareenakhter@yahoo.com, zareen_a@qau.edu.pk (Z. Akhter).
https://doi.org/10.1016/j.molstruc.2020.127812
0022-2860/© 2020 Published by Elsevier B.V.

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Zaib-un-Nisa et al. / Journal of Molecular Structure 1207 (2020) 127812
Scheme 1. Synthesis of phenolic esters OE1 and OE2.
the physical properties of the compounds and more importantly,
their quantitative structure-activity relationship [11,12]. The reac-
of significant antioxidant target protein. Ten conformations were
generated for each docked compound.
tivity of each compound is dependent on its electron density (
r
)
The software package of Gaussian 03 and Turbomole (2018) has
been used to optimize the ground state geometry and evaluation of
structural parameters of the compounds OE1 and OE2. The basis
sets used for the quantum mechanical calculations are B3LYP-321 G
and MO6/def2-TZVPP in Gaussian and Turbomole, respectively. DFT
studies act as a supportive tool to experimentally observed values
of bond lengths and bond angles. The energies of the frontier or-
bitals, HOMO and LUMO, have also been computed. Bader’s AIM
analysis and NBO analysis have been carried out to obtain bond
topological parameters and gauge the strength of inter and intra
molecular interactions.
and the density distribution, Laplacian of the electron density and
electrostatic potential [13].By using Natural Bond Order (NBO)
analysis and Quantum Theory of Atoms in Molecules (QTAIM), we
have attempted to understand the nature of the chemical bonds in
our systems and correlate it to their activity [14]. Bader’s AIM
theory has been utilized to find topological parameters at bond
critical points (BCP) to predict the strength of various interactions
in the organic esters under investigation.
2. Experimental
2.1. Materials and methods
2.2. Synthesis of organic esters
Sodium hydroxide, phenol, 1-Napthol were purchased from
Fluka, Switzerland, Benzoyl chloride from Panreac, Spain and were
used without further purification. Melting points were determined
using Gallen Kamp apparatus. Infrared measurements
(4000e400 cmꢀ1) were performed on thermoscientific NICOLET
6700 FTIR spectrophotometer. 1H NMR spectra were recorded on
Bruker ARX 300 MHz in solution using tetramethylsilane (TMS) as
internal reference at room temperature. MS spectra were recorded
on Agilent-6210-LC/TOF. The single crystal X-ray analysis data for
the compounds was collected at 150(2)K on a Bruker Apex II CCD
2.35g phenol (0.025 mol) for OE1 and 3.61 g of 1-naphthol
(0.025 mol) for OE2 was added to 20 ml of 5% NaOH solution in
separate flasks. 0.75 g decolorizing carbon was added in each flask
and was filtered off. Solutions were separately poured into 100 ml
two necked flasks and 7.0 g of benzoyl chloride (2.9 ml, 0.025 mol))
Table 1
Crystal data and structure refinements for compounds OE1 and OE2.
OE1
OE2
diffractometer using MoK radiation (
l
¼ 0.71073 Å). The structures
Empirical formula
Formula weight
Crystal system
Space group
Unit cell
C13 H10 O2
198.21
Monoclinic
P21/c
C17 H12 O2
248.27
Monoclinic
P21/c
were solved by direct methods and refined on F2 using all the re-
flections [15]. DPPH free radical and hydrogen peroxide scavenging
activities were performed to evaluate the scavenging ability of the
synthesized esters, according to the methods reported in the
literature with slight modifications [16,17]. Data was analyzed by
two-way ANOVA followed by Tukey’s multiple comparison tests
using GraphPad Prism 7.0 software. Results are represented as
mean SD and p < 0.05 is considered to be significant.
a (Å)
b (Å)
5.6354(5)
14.5076(12)
12.2589(10)
100.8530(10)ꢁ
984.31(14)
4
1.338
0.090
416
0.33 ꢂ 0.26 ꢂ 0.21
colorless block
9998
2466 (0.0300)
1.065
8.6286(7)
15.0538(12)
10.3888(8)
108.1510(10)ꢁ
1282.29(18)
4
1.286
0.084
520
0.29 ꢂ 0.21 ꢂ 0.14
colorless block
11303
2636 (0.0310)
1.039
c (Å)
b
(ꢁ)
Volume (Å3)
Z
D (calc) (Mg/m3)
Abs. coeff. (mmꢀ1
F(000)
The crystal structures of the target protein nitric oxide synthase
NOS, PDB id: 5FVP [8] was fetched from Protein Data Bank (www.
rcsb.org/pdb). The protein was prepared, protonated and mini-
mized via the MOE 2016 suite. The chemical structures of synthe-
sized compounds were built and saved in their 3D conformations
by the Builder tool incorporated in MOE 2016. Further protonation,
minimization, charge application and atom-type corrections were
also carried out. Before docking, the efficiency of the procedure was
validated by redocking the crystallized ligand back into the pocket
)
Crystal size (mm3)
Crystal description
Reflections collected
Independent refl. (Rint
Goodness on F2
)
R1, wR2 [I > 2
s
(I)]
0.0396, 0.0872
0.0504, 0.0930
0.0357, 0.0767
0.0536, 0.0846
R1, wR2 (all data)

Zaib-un-Nisa et al. / Journal of Molecular Structure 1207 (2020) 127812
3
was added in each flask while stirring vigorously for 10e15 min
NMR & GC-MS) as well as by single crystal structure analyses.
until odor of benzoyl chloride disappeared. Solid products obtained
were filtered off using Buckner funnel followed by washing with
cold water. The products were then recrystallized from 30 ml
rectified spirit. White crystals appeared which were removed from
mother liquor by filtration and dried in the air (Scheme 1) [18].
3.1. Spectral characterization
The FTIR spectra of the synthesized esters provided evidence for
the presence of all the expected functional groups. The formation of
products was confirmed by the appearance of an intense band of
carbonyl group (C]O) at 1724-1727 cmꢀ1. The aromatic moieties in
the compounds were identified by their characteristic bands. The
band at 3057-3064 cmꢀ1 was due to the aromatic CeH stretch. The
aromatic C]C stretch in each spectrum was confirmed by bands in
a region of 1590e1597 cmꢀ1. The presence of an ester (COeO)
linkage was indicated by its absorption band at 1553-1257 cmꢀ1
[19] (Fig. S1).
2.2.1. Phenyl benzoate (OE1)
Yield 89%; m.p. 67e71 ꢁC; FTIR: (
y
/cmꢀ1): 3057 (CeH), 1724 (C]
ppm):
O), 1590 (C]C), 1257 (CeOeC); 1H NMR (300 MHz, CDCl3,
d
aromatic protons 7.5e8.3 (m, 5H), aromatic protons (-OCO) 6.7e8.2
(m, 5H); MS (m/z): 198(M þ).
2.2.2. 1-Napthyl benzoate (OE2)
Yield 86%; m.p. 55e57 ꢁC; FTIR: (
y
/cmꢀ1): 3064 (CeH), 1727 (C]
ppm):
The 1H NMR spectra of organic esters were also consistent with
the proposed structures. The aromatic ring attached directly to the
carbonyl group of ester linkage depicted multiplets in the range of
7.5e8.3 ppm (m, 5H) for both the compounds. Attachment of aro-
matic rings (phenyl/naphthyl) directly linked to the oxygen atom of
the ester moiety was confirmed by their characteristic signals in the
range of 6.7e8.2 ppm (m, 5H for OE1 and m, 7H for OE2) as dis-
played in Fig. S2.
O), 1597 (C]C), 1253 (CeOeC); 1H NMR (300 MHz, CDCl3,
d
aromatic protons 7.5e8.3 (m, 5H), aromatic protons(-OCO) 6.7e8.2
(m, 7H); MS (m/z): 248(M þ).
3. Results and discussion
The condensation of phenols with benzoyl chloride yielded ar-
omatic esters (OE1 & OE2) (Scheme 1). Both the compounds were
isolated as crystalline and characterized by spectroscopic (FTIR, 1H
The mass spectral data of the organic esters confirmed their
formation with molecular ion peaks at (m/z) 198 for OE1 and 248 for
Fig. 1. Perspective views OE1 (a) and OE2 (b) showing 50% probability ellipsoids. Hydrogen atoms are shown as sticks.

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Zaib-un-Nisa et al. / Journal of Molecular Structure 1207 (2020) 127812
OE2 respectively which is consistent to their molecular formula
masses (Fig. S3).
3.2. Single crystal X-Ray analysis
Single crystal X-ray analyses reveal their monoclinic crystal
systems with space groups P21/c. All the non-hydrogen atoms were
refined using anisotropic atomic displacement parameters and
hydrogen atoms were inserted at calculated positions using a riding
model. Parameters for data collection and refinement are summa-
rized in Table 1.
The perspective views of the molecules are shown in Fig. 1. In
compound OE1, the two ring systems are inclined at an angle of
Fig. 3. DPPH free radical scavenging activity of OE1 and OE2 at 50, 100 and 200 ppm.
Statistically significant values expressed as ***p < 0.001, and Mean SD in comparison
with ascorbic acid.
54.89(4)ꢁ to each other. Surprisingly, there are no
p-p interactions
in the structure and the most important intermolecular in-
teractions appear to be CH …. O hydrogen bonds. In OE2 the two ring
systems are inclined at an angle of 72.59(4)ꢁ to each other. The
main intermolecular interaction is
p-p stacking of pairs of
anthracene groups (under symmetry operation 2-x, -y, 1-z). There
is also an edge-to-edge interaction between phenyl rings (under -x,
-y, -z) again linking them in pairs (Fig. 2).
3.3. Biological studies
3.3.1. DPPH free radical scavenging activity
The antioxidant potential of synthesized compounds was eval-
uated by DPPH free radical scavenging assay and the results are
presented in Fig. 3 in the form of percentage scavenging. The
experiment was performed on three different concentrations (50,
100, 200 ppm) in triplicate and ascorbic acid was used as positive
control with IC50 value 75 mM. The compound OE1 showed signif-
icant activity with IC50 value 605.6
shown by OE2 with IC50 value 1138.7
m
m
M while weak activity was
M.
3.3.2. Hydrogen peroxide scavenging activity
Fig. 4. Hydrogen peroxide scavenging activity of OE1 and OE2 at 50, 100 and 200 ppm.
Statistically significant values expressed as ***p < 0.001, and Mean SD in comparison
with ascorbic acid.
Hydrogen peroxide assay was performed to determine the
scavenging activity of newly synthesized compounds and the re-
sults are shown in Fig. 4. The assay was performed in triplicate with
the same three different concentrations. Both the compounds (OE1
& OE2) showed weak activity in concentration dependent way with
IC50 values 1510.2
served as positive control which showed significant activity with
IC50 value 55 M.
mM and 1069.4 mM respectively. Ascorbic acid
m
Fig. 5. 3D structure of target complex nitric oxide synthase NOS, PDB id: 5FVP.
Fig. 2. Edge-edge
p interactions in OE2, distances in Å.

Zaib-un-Nisa et al. / Journal of Molecular Structure 1207 (2020) 127812
5
interaction. The binding energy values for OE1 and OE2 are ꢀ6.67
and ꢀ3.46 kcal/mol, respectively. The carbonyl oxygen of OE1
shows strong hydrogen bonding with the hydroxyl of Ser457 at a
distance of 3.02 Å (energy value of 1.9 kcal/mol) in addition to a
strong
p
-
p
interaction with Trp409. Similarly, the OE2 docked
interactions with
complex has both hydrogen bonding and
p-p
Ser457 and Trp409 respectively, as shown in Fig. 9. Comparatively
lower antioxidant behavior of OE2 may be due to the presence of
steric clashes of naphthalene rings in the proximity contour of
target protein. Both organic esters bind in the same vicinity of
target complex when compared to ascorbic acid (Fig. 7). The high
antioxidant activity of ascorbic acid is due to the major number of
strong hydrogen bonds with the key contributing amino acids,
Asp597 and Glu592.
3.5. Quantum mechanical studies
Density functional studies were carried out on the compounds
OE1 and OE2 using Gaussian 03 [20] and Turbomole software
package [21]. The hybrid exchange density functional with Becke’s
three parameter (B3LYP) and 3e21 G basis set has been used to
obtain the optimized ground state geometry of each compound
(Fig. S4). The AIM analysis and NBO population analysis have been
performed with a basis set of MO6/def2-TZVPP in the Turbomole
package. The compounds were also studied by the AM1 semi-
empirical methods in Gaussian 03 and the results were compared
to those obtained from DFT studies.
A comparison of the theoretically computed and experimental
bond lengths is presented in Tables S1 and S3, while the correlation
for bond angles can be found in Tables S2 and S4 for OE1 and OE2
respectively. It can be observed that an excellent convergence of
structural parameters is observed for both compounds using
experimental and theoretical means.
The energy of the highest occupied molecular orbital (HOMO)
and the lowest unoccupied molecular orbital (LUMO) has been
computed using the DZ basis set of the density functional model
(presented in Table 2). The HOMO-LUMO energy gap signifies the
chemical reactivity of the studied compounds, as HOMO indicates
an electron donation capacity and the LUMO level is associated
with the electron affinity of molecules [22]. A schematic of the
frontier energy orbitals is depicted for compounds OE1 and OE2 in
Figs. S5 and S6 respectively.
Fig. 6. Superimposition of the docked pose of compound OE1 & OE2 (yellow color) and
standard ascorbic acid (blue color).
3.4. Molecular docking
The most suitable targets and inhibition mechanisms for the
antioxidant activity of the newly synthesized ester can be predicted
in MOE 2016 software package. The organic esters and the refer-
ence compound (ascorbic acid) were docked in the active site of
antioxidant target complex, (PDB ID: 5FVP), as shown in Figs. 5 and
6. Ten conformations were generated for each compound and the
lowest energy conformation was selected to determine the binding
mode of each complex. Root Mean Square Deviation (RMSD) values
of these compounds range from 0.12 to 1.60 Å.
The ligand interactions of the reference compound (ascorbic
acid) can be seen in Fig. 7, while Figs. 8 and 9 show the 2D and 3D
docked maps of the organic esters OE1 and OE2 respectively. It is
found that the key contributing amino acids in the vicinity of target
complexes are Ser457, Gly586, Trp587, Gly417, Trp409, Ser585,
Leu424, Phe584, Phe704 and Val567. The antioxidant behavior of
organic ester OE1 and OE2 can be attributed to a strong binding
Fig. 7. Binding analysis (a) and ligand interactions (b) of reference ascorbic acid.

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Zaib-un-Nisa et al. / Journal of Molecular Structure 1207 (2020) 127812
Fig. 8. 2D (a) and (b) 3D docking map of organic ester OE1 in active site of target protein 5FVP.
Fig. 9. 2D (a) and 3D (b) docking map of organic ester OE2 in active site of target protein 5FVP.
ꢀ
ꢁ
3.6. Atoms in Molecules (AIM) analysis
character of bond. It is related to l1 and l2, which correspond to the
eigen values of Hessian, by the relationship: ε ¼ l1
ꢀ 1.
=
l2
Bader’s theory of Atoms in Molecules (AIM) enables one to take
advantage of the notion of an atom as the volume around the nu-
cleus with zero-flux in the electron density gradient and to predict
quantum mechanically, the nature of interactions in crystals, mol-
ecules, clusters, etc [14]. It makes use of the charge density in a
molecule, which is in turn reliant on the chemical bonding between
atoms [23]. A population analysis should therefore reflect the
qualitative results of electronegativity, where more electronegative
atoms ‘‘draw’’ more electrons to themselves than less electroneg-
ative ones. The electronic information in the bonding region is
In this study, the optimized geometries of the compounds OE1
and OE2 are analyzed with Bader’s “Atoms in Molecules” (AIM)
analysis using a DFT approach with the M-O6/def2-TZVPP basis set
in TURBOMOLE software [25]. The topological properties of the
electron density distribution, Bond Critical Points (BCPs) and Ring
Critical Points (RCP) are determined for both the compounds;
Table 2
Energy values of the frontier orbitals and band gap for compounds OE1 and OE2.
determined from the electron density
r, Laplacian of electron
Compounds
HOMO (eV)
LUMO (eV)
Energy Gap (eV)
density V, and bond critical points [24]. The ellipticity (e) at the
Bond Critical Points (BCP) is a sensitivity index to monitor the p-
OE1
OE2
ꢀ2.990
ꢀ3.911
ꢀ0.031
ꢀ0.255
ꢀ2.959
ꢀ3.656

Zaib-un-Nisa et al. / Journal of Molecular Structure 1207 (2020) 127812
7
Fig. 10. AIM analysis of OE1 (a) and OE2 (b). The Ring Critical Points (RCP) are shown in red, while the Bond Critical Points (BCP) are depicted green in color. The circles around each
atom represent charge density
Fig. 11. NBO analysis of OE1(a) and OE2(b).
Fig. 10 indicates BCPs and RCPs for the compound OE1 and OE2,
respectively. The optimized structures of the compounds were used
to obtain parameters at the BCPs such as the electron density(rBCP),
Laplacian of electron density (VBCP), electron kinetic energy density
(GBCP), total electron energy density (KBCP), estimated interaction
energy (Eint) at bond critical point (BCP). All the calculated
topological parameters are listed in Table S5 (OE1) and S6 (OE2).
3.7. Natural population analysis (NP)
In the current study, the NP analysis has been performed to
obtain atomic charges and orbital populations using the basis set,
Table 3
Second Order Perturbation Theory Analysis of Fock Matrix in NBO Basis for OE2. Stabilization energy of charge delocalization interactions (E2), Energy difference between donor
i and acceptor j NBO orbitals (E(j) e E(i), Fock matrix element between i and j NBO orbitals (Fi, j).
Donor NBO (i)
Occupancy (i)
Acceptor NBO (j)
Occupancy (j)
E2 (kcal/mol)
E(j)-E(i) (a.u.)
F (i, j) (a.u.)
O 18 - C 30
C 13 - H 16
C 1
O 18
O 18
C 3 - C 4
O 18 e C 30
C 23 - C 30
C 30 - O 31
O 31
C 1 - C 2
C 3 - C 4
O 18
1.99270
1.98408
1.99852
1.94579
1.94579
1.96346
1.99270
1.97795
1.99665
0.00093
1.97998
1.96346
0.00137
1.98064
1.63664
1.99270
C 2
1.99803
1.74020
1.99127
1.99860
1.98064
1.97999
1.99665
1.99127
0.00038
0.00038
1.98099
1.74020
1.97998
1.63664
1.99848
1.99665
1.80
2.61
0.61
0.58
48.27
264.04
1.32
2.60
2.22
18.64
187.39
264.04
27.08
54.57
0.83
2.01
1.13
10.22
11.24
0.29
0.01
0.24
0.97
2.00
1.60
0.01
0.01
0.34
0.04
0.84
0.24
0.054
0.049
0.071
0.072
0.107
0.077
0.058
0.045
0.060
0.155
0.078
0.077
0.087
0.072
0.054
0.058
C 9 - C 14
C 2 - O 18
C 20
C 30 - O 31
C 9 - C 14
C 30 - O 31
C 2 - O 18
C 30
C 30
C 5 - C 6
C 9 - C 14
C 1 - C 2
C 22 - C 23
C 23
C 30 - O 31
C 22 - C 23
O 18 e C 30
C 30 - O 31
1.32

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Zaib-un-Nisa et al. / Journal of Molecular Structure 1207 (2020) 127812
MO6/def2-TZVPP in the TURBOMOLE software. The natural anal-
ysis, as an alternative to the conventional Mulliken population
analysis, describes accurately the electron distribution in com-
pounds of high ionic character, such as those containing metal
atoms. The NP analysis for the compounds OE1 and OE2 are pro-
vided in Tables S7 and S8.In the natural bond orbital (NBO) method
developed by Weinhold, atomic population is calculated from
localized natural atomic orbitals (NAO), therefore the name, natural
population (NP) [26]. The occupied (or bond) and unoccupied (or
antibond/Rydberg) NBO’s provide an idea of the delocalization of
charge densities and charge transfer between donors and acceptors
[27,28].
docking and DFT studies. Saima Kalsoom: carried out molecular
docking and DFT studies. Shaista Sabir: carried out molecular
docking and DFT studies. Hammad Ismail: Performed the biological
activities of the compounds.
Declaration of competing interest
The authors have declared no conflict of interest.
Acknowledgements
The authors are highly grateful to Chemistry department Quaid-
i-Azam University Islamabad, Pakistan and School of Chemical
Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland for
providing technical support and laboratory facilities.
The NBO analysis translates computational solutions of
€
Schrodinger’s wave equation into familiar chemical bonding con-
cepts. Using version 3.1 of the NBO program by F. Weinhold and
coworkers [29] in Gaussian 03, the NBO analysis the wave function
into localized form, corresponding to the one-center (“lone pairs”)
and two-center (“bonds”) elements of the Lewis structure [30]. The
NBO analysis for the compounds OE1and OE2 (Fig. 11) are given in
Tables S9 and S10 respectively. Additionally, the stabilization en-
ergy of charge delocalization interactions (E2), Energy difference
between donor i and acceptor j NBO orbitals (E(j) e E(i), and the
Fock matrix element between i and j NBO orbitals (Fi, j) for OE2 are
shown in Table 3. A larger value of stabilization energy indicates an
extensive interaction between electron donors and acceptors; a
greater E2 value would therefore indicate increased conjugation in
the system [28]. For OE2, it can be seen from Table 3, that the largest
E2 values of 264 kcal/mol are obtained for C3eC4 donor NBO and
C9eC14 acceptor NBO numbering as shown in Fig. 11(b). This
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.molstruc.2020.127812.
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4. Conclusions
Two phenol-based organic esters have been synthesized and
characterized successfully. Both the compounds are crystalline in
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