Syntheses, spectroscopic investigation and electronic properties of two sulfonamide derivatives: A combined experimental and quantum chemical approach

Article abstract of DOI:10.1016/j.molstruc.2015.12.039

Two sulfonamides derivatives, N-phenethyl-4-methylbenzenesulfonamide (1) and N-(4-hydroxyphenethyl)-4-methylbenzenesulfonamide (2), were successfully synthesized and fully characterized using ¹H NMR, ¹³C NMR, FT-IR spectroscopies and

Full text of DOI:10.1016/j.molstruc.2015.12.039

Journal of Molecular Structure 1108 (2016) 496e507
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
Syntheses, spectroscopic investigation and electronic properties of
two sulfonamide derivatives: A combined experimental and quantum
chemical approach
,
Ayyaz Mahmood a *, Tehmina Akram b, Edna Barboza de Lima c
a
ꢀ
Departamento de Química Fundamental, Universidade Federal de Pernambuco, Cidade Universitaria, Recife, 50740-560, PE, Brazil
b Department of Chemistry, Government College University, Lahore, 54000, Pakistan
c
~
Departamento de Química, Universidade Federal Rural de Pernambuco, Rua Dom Manuel de Medeiros, S/N, Dois Irmao, Recife, 52171-900, PE, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
Two
sulfonamides
derivatives,
N-phenethyl-4-methylbenzenesulfonamide
(1)
and
N-(4-
Received 1 December 2015
Received in revised form
14 December 2015
Accepted 14 December 2015
Available online 18 December 2015
hydroxyphenethyl)-4-methylbenzenesulfonamide (2), were successfully synthesized and fully charac-
terized using 1H NMR, 13C NMR, FTeIR spectroscopies and elemental analysis. The molecular and elec-
tronic structures of the compounds were further investigated using density functional theory calculation
at B3LYP and B3PW91 functionals using 6e311þþG(d,p) basis set to provide structural and spectroscopic
information and guide spectral assignments. The experimental and simulated 1H NMR, 13C NMR and FT
eIR spectra were compared and the accuracy was discussed. The conformational analysis was performed
in order to find the most stable molecular structure of the compounds. Molecular quantities such as
ionization potential, electron affinity, electronegativity, electrophilicity index and chemical hardness and
softness were calculated and used as an additional molecular characteristic to predict the stability of the
molecules. Electronic properties such Mullikan atomic charges, HOMO, LUMO and HOMOeLUMO energy
gaps and molecular electrostatic potential maps predict the large intramolecular charge transfer within
the molecules and significant substitution effects.
Keywords:
Sulfonamides
Spectroscopic properties
DFT
Spectra
Electronic properties
HOMOeLUMO
© 2015 Elsevier B.V. All rights reserved.
1. Introduction
and our current understanding of this relationship. Numerous
studies on the bioactivity and the structure activity relationship of
The relationship between chemical structure of the medicinal
agents and their biological activity i.e. structureeactivity relation-
ship (SAR) is one of the long standing problems in medicinal and
structural chemistry. Based on the assumption that the similar
compounds have similar physical and biological properties, the
biological effects of a new chemical compound can be predicted
without the cost of performing the traditional toxicology studies
and/or in vitro/in vivo assays. As a result, many efforts have been
made to elucidate this relationship and along with the experi-
mental determination of the bioactivity of the compounds with
different structural characters, several computations based tech-
niques such as quantum chemical approaches have been employed
to predict the chemical structure and electronic properties [1e8]
The sulfonamides have played a leading role in the determination
sulfonamides have been published [9e17].
Sulfonamides are of great chemical interest as they show
distinct physical, chemical and pharmaceutical properties. They are
the first antibacterial drugs [18] commonly known as sulfa drugs
which were introduced clinically in 1934. Sulfonamides are active
against gram-positive and gram-negative bacteria and are used in
the treatment of diseases like tonsillitis, urinary tract infections etc.
Aromatic sulfonamides were reported to inhibit the growth of tu-
mor cells [19]. The heterocyclic sulfonamide derivatives have been
reported to show substantial in vitro and in vivo, anticancer, anti-
tumor, anti-HIV, antimicrobial, antimalarial, anticonvulsant, anal-
gesic and anti-inflammatory activities [18e29]. Because of the wide
variety of the biological importance of the sulfonamides, the syn-
thesis of several substituted sulfonamides, the study of their mo-
lecular structure and physical, chemical, biochemical and electronic
properties has become interesting field in research. The studied
compounds are such organic compound that belongs to the sul-
fonamide family.
* Corresponding author.
E-mail address: ayyazcmc@gmail.com (A. Mahmood).
http://dx.doi.org/10.1016/j.molstruc.2015.12.039
0022-2860/© 2015 Elsevier B.V. All rights reserved.

A. Mahmood et al. / Journal of Molecular Structure 1108 (2016) 496e507
497
Density functional theory (DFT) [30,31] is a dominating method
for the investigation of electronic structures and properties of
medium-to large-size molecules. It is among the well-known and
versatile methods available in computational chemistry and
computational physics to study the electronic structures and
microscopic properties of the wide variety of compounds [32e41].
DFT have been used to study the electronic structures and molec-
ular properties of sulfonamide derivatives, including their molec-
ular, electronic (HOMOeLUMO, natural bond orbital (NBO) analysis,
dipole moment and electrostatic potential, etc.), and spectroscopic
properties (NMR, mass fragmentation, electronic, vibrational, etc.)
[42e55]. The study of microscopic properties of energetic materials
such as electronic structure and interatomic forces remains to be a
challenging task for the theoretical researchers. Theoretical calcu-
lations play an important role in investigating the physical and
chemical properties of energetic materials at atomic level and to
establish the structure-property relationship. Most of these studies
involved the comparison of DFT (mainly B3LYP, B3PW91, and
PBE1PBE) calculated results with those calculated experimentally.
Thus, one of the goals of the presents study is to determine the
reliability of these functionals to predict the molecular structure as
well as the spectroscopic properties of the studied and other sys-
tems relevant to medicinal chemistry.
characterized using spectroscopic techniques and were further
optimized using DFT functionals at two different theoretical levels.
A conformational stability study was performed to find the most
stable structures. The protone and 13C NMR and Infrared (IR)
spectra were calculated and compared with those obtained
experimentally. The highest occupied molecular orbital (HOMO)
and lowest unoccupied molecular orbital (LUMO), and HOMO-
eLUMO energy gaps were computed to predict the charge transfer
within the molecules and other related electronic properties. Mo-
lecular electrostatic potential (MEP) analysis was performed to
predict the reactive sites of the studied molecules.
2. Experimental
2.1. Material and measurements
2-Phenethylamine (CAS No.: 64-04-0), 2-(4-Hydroxyphenyl)
ethylamine (CAS NO.: 51-67-2) and p-Toluenesulfonyl chloride
(CAS No.: 98-59-9) were purchased from SigmaeAldrich. All other
reagents and solvents were obtained from common commercial
sources and used without further purification. FTeIR spectra over
the range 4000e400 cmꢀ1 were obtained with a Thermo Nicolet
FTeIRe200 (USA) spectrometer using KBr pellets. Melting points
were determined in open capillary tubes on Gallenkamp melting
point apparatus. Elemental analysis for N, C and H were performed
on Vario Micro Cube, Elementar, Germany. 1H NMR and 13C NMR
spectra were recorded on Bruker 300 MHz spectrometer at room
temperature. Chemical shifts values are reported in parts per
million (ppm) from tetramethylsilane (TMS).
In our previous study, we published the crystal structure of
several sulfonamide derivatives and performed a DFT computa-
tional study of the structural, spectroscopic and electronic prop-
erties [32,33,56,57]. Thus, in continuation to this contribution, we
here
describe
our
results
on
N-phenethyl-4-
methylbenzenesulfonamide (1) and N-(4-hydroxyphenethyl)-4-
methylbenzene-sulfonamide (2) concerning the synthesis, elec-
tronic structure, 1H NMR, 13C NMR, vibrational and charge transfer
analysis. The two compounds were previously synthesized [58,59],
however, no further studies were performed on molecular and
electronic structure and spectroscopic properties. We followed the
procedure used in Ref. [59] with some modifications to synthesize
the compounds. To the best of our knowledge, no computational
study has yet been performed on the compounds presented in this
article. We believe that the potential sulfonamide derivatives
deserve more detailed and systematic theoretical study of the
molecular and electronic structure and spectroscopic and charge
transfer properties using the advance computational methods for
understanding its chemical and biological properties. The purpose
of this study is thus to investigate the molecular and electronic
structure, NMR and vibrational spectroscopy (experimentally and
theoretically) and electronic properties (reactivity and stability
through the calculations of HOMO, LUMO and HOMOeLUMO en-
ergy gap, ionization potential, electron affinity, electronegativity,
electrophilicity index and chemical hardness and softness) of 1 and
2 and the effect of presence of hydroxyl group on these properties.
This study can be regarded as an effort towards understanding and
predicting molecular structure and electronic and spectroscopic
properties of this class of molecules that are relevant to medicinal
chemistry.
2.2. Synthesis of N-phenethyl-4-methylbenzenesulfonamide (1)
2-Phenylethanamine (0.232 g, 1 mmol) was dissolved in anhy-
drous acetone (10 mL) and triethyamine (10 mL) was added. Sub-
sequently, p-Toluenesulfonyl chloride in the stoichiometric ratio
(0.227 g, 1 mmol) was added drop-wise with continuous stirring.
The resulting reaction mixture was stirred for 4 h under nitrogen
atmosphere at room temperature (Scheme 1). By means of TLC, the
consumption of p-Toluenesulfonyl chloride was monitored. When
the reaction was completed, the reaction mixture was washed us-
ing 3M HCl and further with distilled water. The solvent was
evaporated under reduced pressure. The obtained product was
further purified by crystallization from methanol solution by slow
evaporation. Yield of the reaction was 79% (0.54 g); m.p.165e172 ꢁC.
1H NMR (Chloroform, 300 MHz)
d: 2.42 (s, 3H, CH3), 2.75 (t, 2H,
CH2), 3.21 (t, 2H, CH2), 4.46 (br. s, 1H, NH), 7.07 (d, 2H, AreH), 7.26
(m, 5H, AreH), 7.70 (d, 2H, AreH). FTeIR (KBr, cmꢀ1): 3262.6 (NeH
str.), 3020.0 (CeHaromatic asymm. str.), 2910.0 (CeH(CH2/CH3) asymm.
str.), 2810.0 (CeH(CH2/CH3) symm. str.), 1598.1 (CeC]C symm. str.),
1380.0 (NeH out-of-plane bending), 1155.6 (S]O asymm. str.),
1095.6 (SeC str.). Elemental analysis: calculated (%) for C15H17NO2S:
C, 65.43; H, 6.22; N, 5.09; O, 11.62; S, 11.64; found (%): C, 64.57; H,
6.04; N, 4.96; O, 10.84; S, 11.12.
The structures of the synthesized compounds were
Scheme 1. Synthetic pathway to N-phenethyl-4-methylbenzenesulfonamide.

498
A. Mahmood et al. / Journal of Molecular Structure 1108 (2016) 496e507
2.3. Synthesis of N-(4-hydroxyphenethyl)-4-
methylbenzenesulfonamide (2)
0000109999) to the keyword line). 1H and 13C NMR chemical shifts
were then calculated as, diso rTMS riso, where diso riso and rTMS are
¼
ꢀ
,
chemical shift, absolute shielding and the absolute shielding of
TMS, respectively. The solvent effects (chloroform) were simulated
by polarizable continuum model (PCM) [67]. The electronic prop-
erties such as the co-efficient of highest occupied molecular or-
bitals (HOMO), co-efficient of lowest unoccupied molecular orbitals
(LUMO) and HOMOeLUMO band gaps were calculated at B3LYP
and B3PW91 methods and were used further to calculate the mo-
lecular quantities such as, ionization potential, electron affinity,
electronegativity, chemical hardness and softness and electrophi-
licity index using the Equations (1e6). The band gap is calculated as
the difference of HOMO and LUMO energies.
4-hydroxyphenethylamine (Tyramine) (137.179 g/mol) (0.137 g,
1 mmol) was dissolved in anhydrous acetone (10 mL) and triethy-
amine (10 mL) was added. Subsequently, p-Toluenesulfonyl chlo-
ride (190.65 g/mol) in the stoichiometric ratio (0.191 g,1 mmol) was
added drop-wise with continuous stirring. The resulting reaction
mixture was stirred for 4 h under nitrogen atmosphere at room
temperature (Scheme 2). By means of TLC, the consumption of p-
Toluenesulfonyl chloride was monitored. When the reaction was
completed, the reaction mixture was washed using 3M HCl. The
solvent was evaporated under reduced pressure. The obtained
concentrated liquor was poured into 40 mL of cold distilled water to
get the precipitates of the product. The obtained product was
further purified by crystallization from methanol solution by slow
evaporation. Yield of the reaction was 72% (0.21 g); m.p.176e180 ꢁC.
Ionization potential ðI:PÞ ¼ ꢀEHOMO ðeVÞ
Electron affinity ðE:AÞ ¼ ꢀELUMO ðeVÞ
Electronegativity ðcÞ ¼ ðI:P þ E:AÞ=2 ðeVÞ
Chemical hardness ðhÞ ¼ ðI:P ꢀ cÞ=2 ðeVÞ
(1)
(3)
(2)
(4)
1H NMR (Chloroform, 300 MHz)
d: 2.43 (s, 3H, CH3), 2.74 (t, 2H,
CH2), 3.16 (t, 2H, CH2), 4.35 (br. s, 1H, NH), 6.88 (d, 2H, AreH), 7.10
(d, 2H, AreH), 7.58 (m, 4H, AreH). FTeIR (KBr, cme1): 3270.0 (NeH
str.), 3058.6 (CeHaromatic str.), 2933.6 (CeH(CH2/CH3) asymm. str.),
2860.0 (CeH(CH2/CH3) str.), 1598.4 (CeC]C symm. str.), 1369.8 (NeH
out-of-plane bending), 1164.0 (OeH out-of-plane bending), 1095.6
(SeC str.). 1029.5 (S]O symm. str.). Elemental analysis: calculated
(%) for C15H17NO3S: C, 61.83; H, 5.88; N, 4.81; O, 16.47; S, 11.01;
found (%):C, 60.86; H, 5.47; N, 4.44; O,15.97; S, 10.56.
Softness ðsÞ ¼ 1=2h ðeVÞꢀ1
(5)
Scheme 2. Synthetic pathway to the N-(4-hydroxyphenethyl)-4-methylbenzenesulfonamide.
.
2.4. Computational procedures
Electrophilicity index ðjÞ ¼ c2 2h
(6)
All the calculations in the present study were performed by
Gaussian 09 program using its default criteria [60]. All the equi-
librium structures were fully optimized without any symmetry
constraints in gas phase by DFT methods at B3LYP [61,62] and
B3PW91 [61,63e65] levels of the theory using 6e311þþG(d,p)
basis sets. we have used the gradient corrected density functional
theory [31] with three parameter hybrid functional (B3) [61] for the
exchange part combined with Lee-Yang-Parr (LYP) [62] and Perdew
and Wang (PW91) correlation function [63e65] which is a widely
accepted as cost effective method to calculate the molecular
structures, vibrational frequencies and energetics of the structures
of medium-to large-size. The lowest energy structures of the 1 and
2 were obtained by performing a conformational analysis around
Gauss view [68] and Chemcraft [69] programs were be used to
visualize the output files and to assign the vibrational frequencies.
The calculated 1H and 13C NMR and FTeIR spectra were compared
with those obtained experimentally.
3. Results and discussion
3.1. Conformational stability and molecular geometry
The precise determination of geometrical distortions is a useful
technique to investigate the nature of intra- and intermolecular
interactions. The conformational stability study can be used to
predict and explain the selectivity, reactivity, mechanisms and rate
of reactions [70]. The different conformations of a compound are
correlated with many of the physical, chemical and medicinal
properties. Since sulfonamides show a variety of biological activ-
ities, therefore, the investigation of the different conformational
structures of sulfonamides is important for drug design and to
understand the several medicinal effects. In order to describe the
possible conformations of the two compounds, detailed one
dimensional potential energy scans were performed around the
dihedral
angles
D(C4eN7eS9eC10)
for
1
and
D(C14eN17eS19eC20) for 2, at B3LYP/6e311þþG(d,p). The mini-
mum energy structures were then fully optimized at the same
method i.e. B3LYP/6e311þþG(d,p). The optimized structures were
confirmed by force constants calculations, where all positive force
constants (no imaginary frequency) confirm the attainment of a
true minimum. The calculated results of most stable structure of 1
and 2 were compared with those obtained experimentally. The 1H
and 13C NMR chemical shifts were predicted by calculating isotropic
chemical shielding constants. The constants were calculated using
GIAO approach at WP04/6e311þþG(d,p) [66] in chloroform sol-
vent using tetramethylsilane (TMS) as standard (In Gaussian, the
WP04 functional is invoked by specifying the BLYP keyword and
dihedral
angles
D(C4eN7eS9eC10)
of
1
and
D(C14eN17eS19eC20) of 2 using B3LYP/6e311þþG(d,p) method.
These scans were carried out by relaxed PES scanning calculations
in all the geometrical parameters by varying the torsional angles for
each 10ꢁ rotation from 0ꢁ to 360ꢁ around the selected dihedral
adding
iop
(3/76)1000001189,
3/77)0961409999,
3/78)

A. Mahmood et al. / Journal of Molecular Structure 1108 (2016) 496e507
499
angles. The obtained potential energy surfaces are illustrated in
Fig. 1.
C26, C10) that are on the most downfield and iii) those appearing in
the midway for aromatic carbons. Since the C27 and C28, C29 and
C31, C11 and C12, C13 and C15 are equivalent carbons; therefore,
they give rise to larger peaks at same ppm due to the symmetry.
In 2, we observe almost a similar pattern of the 1H and 13C NMR
chemical shift. In 1H NMR, the methylene protons appear at 2.74
and 3.16 ppm as triplet peaks. The methyl protons appear at
2.43 ppm as a singlet peak. In 13C NMR spectrum, C6, bearing an
electronegative hydroxyl group, is observed to be deshielded. Ar-
omatic carbons appear in a range of 122e150 ppm.
As can be seen from Fig. 1, molecule 1 shows two high energy
domains at dihedral angles 227.75ꢁ and 377.75ꢁ with
energies ꢀ1185.3987 and ꢀ1185.3949 Hartree, respectively. The
system shows three low energy domains at 97.75ꢁ, 267.75ꢁ and
447.75ꢁ with energies ꢀ1185.4041, ꢀ1185.4053 and ꢀ1185.4050
Hartree. The minimum at 267.75ꢁ is calculated to be the most stable
conformer of compound 1. The barrier to this rotation (0.0104
Hartree, 27.31 kJ/mol) is calculated as the energy difference be-
tween the most stable conformer and the transition state (structure
at 377.75ꢁ).
To predict the chemical shift theoretically, a variety of func-
tionals combined with medium to large basis sets have been
shown to provide results in good agreement with the experi-
mental data, but recently Rupal proposed parameterized WP04
[66] functional which gave the improved results over other
different methods. Thus, we used his proposed method to
compute the 1H NMR and 13C NMR chemical shifts. The calcu-
lations were carried out using GIAO approach at WP04/
6e311þþG(d,p) in chloroform solvent using tetramethylsilane
(TMS) as standard. The computed chemical shifts were in good
agreement with observed chemical shift values with an average
error of 0.2536. A comparison of experimental and theoretically
calculated 1H and 13C NMR chemical shifts along with isotropic
magnetic shielding tensors for the studied systems are listed in
Table 1. The atomic positions listed are according to Fig. 2.
IR spectrum is one of the basic properties and an effective tool
to identify and analyze the compounds. The FTeIR spectra of the
studied compounds were computed using harmonic force field
calculations at B3LYP functional using 6e311þþG** basis set. The
absence of imaginary frequency confirms that the optimized
structures are true minima on the potential energy surface.
The bands appearing in the FTeIR spectra were assigned with
the help of calculated frequencies, intensities and visualization of
the vibrational modes. The experimental and calculated fre-
quencies, their assignments and the intensities are presented in
Table 2. The scaling factors, 0.958 for the calculated frequencies
in the ranges from 4000 to 1700 cmꢀ1 and 0.983 for frequencies
lower than 1700 cmꢀ1, were used [71]. A comparison between
simulated and experimental IR spectra of the two systems is
shown in Fig. 3. Since the systems have large number of vibra-
tional degrees of freedom, a large number of vibrational bands
have been observed. We shall discuss below only the prominent
bands.
The molecule 2 shows a PES quite similar to that of 1 (Fig. 1). The
scan shows two high energy barriers at dihedral angles 227.71ꢁ and
377.71ꢁ with energies ꢀ1260.6456 and ꢀ1260.640 Hartree. The
molecule shows three stable conformers at angles 97.71ꢁ, 267.71ꢁ
and
427.71ꢁ
with
energies
ꢀ1260.6511,
ꢀ1260.6523
and ꢀ1260.6508 Hartree where the most stable conformer is the
one found at dihedral angle 267.71ꢁ. The barrier to this rotation is
calculated to be (0.0123 Hartree, 32.29 kJ/mol). The stability of the
most stable conformers can fairly be related to presence of
hydrogen bonding between SO2 oxygen atoms and adjacent NH and
aromatic protons (Fig. 2). The total energies of two systems are
listed in Table 3.
The obtained minimum energy structures were optimized and
used for further calculations of spectroscopic and electronic prop-
erties at B3LYP and B3PW91 functional using 6e311þþG(d,p) basis.
The optimized geometries of the most stable conformers of 1 and 2
with labeling of atoms and selected bond distances are presented in
Fig. 2. The energies of most stable conformers of 1 and 2 were found
to be ꢀ1185.404 and ꢀ1260.651 Hartree, respectively.
3.2. Experimental and calculated 1H NMR 13C NMR and IR spectral
analyses
In the 1H NMR spectrum of 1, two triplet peaks at 2.75 and
3.21 ppm observed were assigned to methylene protons, that is,
C1H2 and C4H2, respectively. The protons on nucleus C4 are
deshielded due to the attached electronegative nitrogen atom. A
broad singlet peak observed at 4.46 ppm is assigned to the N7H8
(NH) proton. A singlet peak at 2.42 ppm was assigned to methyl
protons. The CeHaromatic protons appear in the range of
7.07e7.70 ppm.
The 13C NMR spectrum of 1 shows peaks in three major regions,
that is, i) peaks for methyl and methylene carbons (C22, C1 and C4)
that are the most shielded, ii) peaks for quaternary carbons (C17,
The studied systems consists of CeC, C]C, eCH3, eCH2, NeH,
SO2 and OeH groups. In general, the characteristic IR frequencies
due to CeH vibrations appear in the region of 3000e2800 cmꢀ1
Fig. 1. (left) Potential energy scan of 1 for rotations around the selected torsional angle D(C4eN7eS9eC10), (right) potential energy scan of 2 for rotations around the selected
torsional angle D(C14eN17eS19eC20).

500
A. Mahmood et al. / Journal of Molecular Structure 1108 (2016) 496e507
Fig. 2. The optimized structure of 1 (left) and 2 (right) at B3LYP/6e311þþG** with atomic labeling and numbering and selected bond distances. Bond distance values in Angstrom
(Å).
1 and at 1501.1 cmꢀ1 in 2 are assigned to CeHaromatic rocking (in-
plane asymmetric bending) vibrations.
Table 1
Experimental and theoretical 1H and13C NMR isotropic chemical shifts (diso/ppm)
and isotropic magnetic shielding tensors (siso/ppm) of 1 and 2.
The peaks due to C]C stretching vibrations normally occurs
with medium intensity in the region of 1680 to 1620 cmꢀ1 in the IR
spectra [72]. In our study, bands observed at 1598.1 cmꢀ1 in 1 and
1598.4 cmꢀ1 in 2 are assigned to these vibrations.
Atom
1
Atom 2
(
siso
)
Calc. (diso
)
Exp. (diso
)
(
siso
)
Calc. (diso
)
Exp. (diso)
C1
C4
135.60
126.49
39.57
48.68
35.74
44.16
137.70
127.12
126.98
129.92
129.40
147.36
21.61
136.85
128.95
128.71
128.38
128.43
126.40
2.75
2.75
3.21
3.21
4.46
7.70
7.70
7.07
7.07
C1
C2
C3
C4
C5
C6
C11
C14
C20
C21
C22
C23
C25
C27
C34
H7
58.46 116.72
42.86 132.32
41.78 133.40
44.00 131.17
60.89 114.29
16.61 158.56
122.81
129.86
143.53
129.76
122.50
148.33
35.22
43.96
145.39
127.11
126.99
128.41
129.71
145.37
21.47
6.88
7.10
7.10
6.88
2.74
2.74
3.16
3.16
4.35
Bands involving the CeH out-of-plane bending (wagging and
twisting) vibrations appear in the range 1000e675 cmꢀ1 [72]. The
FTeIR shows bands in the region 781.0 to 947.0 cmꢀ1 both is 1 and 2
that are assigned to CeH out-of-plane bending vibrations.
The NeH group gives rise to three internal modes of vibrations
that is stretching and in-plane and out-of-plane bending vibrations.
The NeH stretching modes are observed to be at 3260.0 in 1 and
3270.0 cmꢀ1 in 2. The NeH out-of-plane bending vibrations are
observed at 1380 cmꢀ1 and 1369.8 cmꢀ1 in 1 and 2, respectively.
The computed values of these vibrational frequencies are in good
agreement with experimental one.
C10
C11
C12
C13
C15
C17
C22
C26
C27
C28
C29
C31
C33
H2
29.41 145.76
46.62 128.55
46.89 128.28
44.99 130.19
43.30 131.88
27.40 147.77
136.75
126.76
38.42
48.42
155.54
19.63
29.97 145.21
46.24 128.94
46.37 128.80
45.14 130.04
43.94 131.24
26.83 148.35
33.87 141.30
44.15 131.03
44.47 130.70
46.38 128.80
45.82 129.36
47.16 128.02
155.29
25.28
25.03
25.16
25.68
28.91
29.74
29.54
29.63
28.08
24.31
24.54
24.93
24.75
27.71
29.60
29.75
30.09
19.89
6.73
6.98
6.85
6.33
3.11
2.27
2.47
2.38
3.93
7.70
7.47
7.08
7.26
4.30
2.42
2.27
1.92
The S]O asymmetric stretching band frequency in sulfones, in
25 cmꢀ1 and that of symmetric
28.82
29.62
29.38
29.48
28.15
24.24
24.42
24.93
24.72
30.08
29.74
29.80
24.84
24.86
24.89
24.81
24.84
3.19
2.39
2.63
2.53
3.86
7.70
7.59
7.08
7.29
1.93
2.27
2.21
7.17
7.16
7.13
7.20
7.17
general, appear around 1325
H3
H5
H6
H8
H8
H9
stretching appears near 1140 20 cmꢀ1 [72]. A strong band due to
S]O asymmetric stretching vibrations are observed at 1155.6 cmꢀ1
in 1 while the S]O symmetric stretching bands are observed at
1062.9 and 1029.5 cmꢀ1 in 1 and 2, respectively. The redshift in the
observed frequency may be due the presence of hydrogen bonds
between the oxygen of the SO2 and the hydrogen of the adjacent
NH and benzene ring. A band due to SeC stretching vibration ap-
pears at 1095.6 cmꢀ1 in 1. The band due to OeH out-of-plane
bending vibrations in 2 is observed at 1164.0 cmꢀ1. As can be
seen from linear correlation graphics presented in Fig. 4, the
simulated vibrational frequencies are in excellent agreement with
the experimental one. The R2 values of the frequencies were
calculated to be 0.9983 for both systems. The linear correlation
H10
H12
H13
H15
H16
H18
H24
H26
H28
H29
H31
H35
H36
H37
H14
H16
H18
H19
H23
H24
H25
H30
H32
H34
H35
H36
2.42
2.42
2.42
7.26
7.26
7.26
7.26
7.26
7.58
7.58
7.58
7.58
e
2.43
2.43
2.43
equations
Vcalc¼ 1.012Vexpþ0.978 for 2.
are;
Vcalc
¼
1.025Vexpꢀ3.243
for
1
and
disoH and disoC were calculated as described in computational section.
with medium to strong intensity [72]. The attached electronegative
atoms in general causes a blueshift in the CeH absorption fre-
quencies [72]. The strong bands with some shoulders appearing at
3020.0 and 3058.6 cmꢀ1 in FTeIR spectrum of 1 and 2, respectively,
are assigned to CeHaromatic stretching vibrations. The bands
appearing at 2910.0 and 2810.0 in 1 and 2933.6 and 2860.0 cmꢀ1 in
2 are assigned to CeH(CH3) and CeH(CH2) asymmetric and sym-
metric stretching vibrations, respectively. The calculated fre-
quencies corresponding to these vibrations are in close proximity to
the experimental values. It can be observed that the calculated
frequencies for these vibrational modes in 2 are blueshifted than in
1 which can be due to the electron releasing (ring activating) hy-
droxyl substituent on the benzene ring in 2.
4. Electronic properties
4.1. Molecular orbital analysis
An electronic absorption is basically a transition of one or more
electrons from ground state to first excited state. It is generally
described as a transition from highest occupied molecular orbital
(HOMO) to lowest unoccupied orbital (LUMO). Therefore, the HO-
MOs are the orbitals that have ability to donate an electron and
LUMOs are the one that can accept an electron. They are often
referred to as frontier molecular orbitals. According to the Koop-
mans theorem, the energy of the HOMO is related to the ionization
potential, while the energy of LUMO is related to the electron af-
finity [73]. HOMOe1 and LUMOþ1, represents one energy state
below and above these levels, respectively. Both highest occupied
molecular orbitals (HOMOs) and lowest unoccupied orbitals
(LUMOs) are major orbital that determine the stability or the
reactivity of a molecule. The energy gap between HOMOs and
The eCH2 scissoring (in-plane symmetric bending) vibrational
bands appear in the region of 1490e1440 cmꢀ1 [72]. In FTeIR
spectra of
1 and 2, weak bands appearing at 1425.0 and
1430.0 cmꢀ1 are assigned to CeH(CH2) and CeH(CH3) in-plane
bending vibrations. Vibrational bands observed at 1491.1 cmꢀ1 in

A. Mahmood et al. / Journal of Molecular Structure 1108 (2016) 496e507
501
Table 2
Calculated vibrational wavenumbers (unscaled and scaled) along with IR intensity at B3LYP/6e311þþG(d,p), measured infrared bands positions and assignments.
System 1
System 2
B3LYP (cmꢀ1
)
B3LYP (cmꢀ1
)
Unscaled
Scaled
IR intensity
FT-IR
Assignment
Unscaled
Scaled
IR intensity
FT-IR
Assignment
3550.4
3204.1
3198.4
3188.2
3176.5
3168.5
3167.3
3164.3
3155.8
3152.3
3108.4
3096.8
3077.5
3073.8
3047.3
3037.2
3027.2
1644.2
1637.2
1622.3
1614.6
1526.0
1524.8
1500.8
1495.3
1487.0
1484.7
1482.5
1428.7
1425.4
1415.3
1389.6
1361.5
1343.7
1334.5
1332.3
1330.1
1312.5
1275.8
1228.5
1225.1
1219.3
1205.3
1202.6
1181.5
1136.6
1119.7
1112.3
1075.7
1071.9
1061.4
1049.5
1034.1
1031.3
1017.2
1016.4
1006.7
1000.6
991.8
3393.5
3062.4
3057.0
3047.2
3036.1
3028.5
3027.4
3024.4
3016.3
3013.0
2971.0
2959.9
2941.5
2937.9
2912.7
2903.0
2893.4
1616.2
1609.4
1594.7
1587.1
1500.1
1498.9
1475.3
1469.9
1461.7
1459.5
1457.3
1404.4
1401.1
1391.2
1366.0
1338.3
1320.9
1311.9
1309.7
1307.5
1290.2
1254.1
1207.6
1204.2
1198.5
1184.8
1182.2
1161.4
1117.3
1100.7
1093.4
1057.4
1053.7
1043.3
1031.7
1016.6
1013.8
999.9
46.4
2.2
1.1
16.4
27.7
10.2
5.9
10.5
3.8
3262.6
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
r
r
d
d
d
d
y
u
u
u
g
t
u
r
t
r
u
y
NeH
3836.3
3550.8
3204.2
3198.1
3193.1
3169.2
3165.1
3163.6
3161.2
3146.4
3108.4
3095.5
3077.1
3071.7
3046.2
3036.3
3027.4
1654.8
1637.2
1630.2
1614.3
1544.0
1524.6
1500.0
1495.7
1486.8
1484.0
1465.9
1428.7
1425.7
1416.0
1390.5
1359.9
1352.1
1336.1
1333.7
1330.2
1314.1
1277.7
1276.3
1228.3
1226.8
1220.9
1205.3
1194.7
1187.2
1136.8
1129.6
1119.7
1077.7
1072.7
1061.6
1037.2
1033.6
1028.6
1015.2
1007.0
991.2
3666.7
3393.8
3062.5
3056.8
3051.9
3029.2
3025.2
3023.7
3021.5
3007.3
2971.0
2958.6
2941.1
2935.9
2911.6
2902.1
2893.6
1626.6
1609.4
1602.5
1586.9
1517.7
1498.7
1474.5
1470.3
1461.5
1458.8
1441.0
1404.4
1401.4
1392.0
1366.8
1336.8
1329.1
1313.3
1311.0
1307.6
1291.8
1255.9
1254.6
1207.4
1206.0
1200.1
1184.8
1174.4
1167.0
1117.5
1110.4
1100.7
1059.4
1054.5
1043.6
1019.5
1016.0
1011.1
998.0
73.0
45.9
2.2
1.1
4.4
10.3
11.0
10.5
11.0
19.1
14.5
15.1
12.2
2.1
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
r
r
d
d
d
d
y
y
u
u
g
r
t
u
u
r
u
y
y
y
OeH
NeH
(s) CeHaromatic
(s) CeHaromatic
(s) CeHaromatic
(as) CeHaromatic
(s) CeHaromatic
(as) CeHaromatic
(as) CeHaromatic
(as) CeHaromatic
(as) CeHaromatic
(as) CeH(CH3)
(as) CeH(CH2)
(as) CeH(CH3)
(as) CeH(CH2)
(s) CeH(CH2)
3270.0
(s) CeHaromatic
(s) CeHaromatic
(s) CeHaromatic
(as) CeHaromatic
(s) CeHaromatic
(as) CeHaromatic
(as) CeHaromatic
(as) CeHaromatic
(as) CeH(CH3)
(as) CeH(CH2)
(as) CeH(CH3)
(as) CeH(CH2)
(s) CeH(CH2)
(s) CeH(CH2)
(s) CeH(CH3)
3020.0
8.4
3058.6
2933.6
14.3
14.8
12.3
1.6
46.6
2.1
24.0
7.4
19.4
1.2
0.5
12.8
9.9
7.3
15.2
7.7
0.5
4.9
6.3
3.4
1.8
50.3
0.5
0.3
1.4
2910.0
2810.0
51.8
1.0
2860.0
1598.4
(s) CeH(CH2)
(s) CeH(CH3)
24.3
46.6
19.3
12.3
0.5
118.3
9.8
7.0
14.9
7.7
0.4
17.9
6.3
3.6
(s) CeC]C þ
(s) CeC]C þ
(s) CeC]C þ
b
b
b
CeC]C
CeC]C
CeC]C
(s) CeC]C þ
(s) CeC]C þ
(s) CeC]C þ
b
b
b
CeC]C
CeC]C
CeC]C
1598.1
1491.1
1425.2
(as) CeC]C þ
CeHaromatic
CeHaromatic
CeH(CH2)
b
CeC]C
(as) CeC]C þ
CeHaromatic
CeHaromatic
CeH(CH2)
b CeC]C
1501.1
1430.0
CeH(CH3)
CeH(CH3)
CeH(CH2)
CeH(CH3)
CeH(CH3)
CeH(CH2)
þ
g
NeH
þ
g NeH
CeCaromatic
CeH(CH2)
CeH(CH2)
CeH(CH3)
NeH
CeH(CH2)
CeH(CH2)
CeHaromatic
CeH(CH2)
CeHaromatic
CeH(CH2)
(as) S]O
CeCaromatic
CeCaromatic
CH2(CH2)
CeH(CH3)
NeH
CeHaromatic
CeH(CH2)
CeH(CH2)
CeH(CH2)
CeHaromatic
CeH(CH2)
CeO
1.8
1380.0
1319.0
47.5
26.6
3.1
2.2
0.6
1369.8
1323.1
0.3
0.5
27.8
147.6
1.7
3.6
2.6
2.0
0.0
0.6
27.3
137.2
135.0
1.9
4.4
2.3
1155.6
C
y
aromaticeCmethyl
(as) S]O
C
C
aromaticeC(CH2)
aromaticeC(CH2)
CaromaticeCmethyl
y
CaromaticeC(CH2)
u
d
d
g
d
d
y
y
y
t
t
b
b
y
t
t
t
t
u
u
d
d
y
d
y
y
t
y
y
t
y
y
t
t
t
CeH(CH2)
CeH(CH2)
CeHaromatic
CeHaromatic
CeH(CH2)
CeHaromatic
CeHaromatic
OeH
CeHaromatic
CeHaromatic
1.8
4.4
0.0
12.2
151.0
6.8
19.0
147.4
5.3
5.2
16.2
7.9
0.2
47.7
1.9
0.9
0.5
176.6
13.6
12.0
149.5
38.9
147.7
4.0
6.2
12.8
0.4
54.8
1.9
0.5
0.9
0.1
2.8
16.2
3.7
10.0
116.3
29.9
21.4
19.9
20.5
84.7
1164.0
1029.5
1095.6
1062.9
SeC þ
y
(s) S]O
CeHaromatic
CeN
SeC þ
y (s) S]O
(s) S]O
CeH(CH3)
CeN
(s) S]O
CeH(CH3)
CeH(CH2)
CeC]C
CeC]C
(s) CeC]C þ
(s) CeC]C þ
CeH(CH2)
(s) CeC]C þ
(s) NeCeC
CeH(CH3)
CeHaromatic
CeHaromatic
CeHaromatic
CeHaromatic
CeHaromatic
CeHaromatic
CeHaromatic
CeHaromatic
CeHaromatic
CeHaromatic
CeH(CH2)
b
b
CeC]C
CeC]C
b
CeC]C
999.1
989.6
983.6
975.0
967.5
952.2
908.1
842.4
836.5
825.9
816.2
809.2
792.0
752.4
701.5
(s) NeCeC
CeH(CH3)
944.0
989.9
974.4
956.1
951.5
921.9
847.6
835.9
831.3
816.0
808.7
801.6
792.6
775.4
745.6
947.3
CeHaromatic
CeHaromatic
CeHaromatic
CeHaromatic
CeHaromatic
CeHaromatic
CeHaromatic
CeHaromatic
CeHaromatic
CeHaromatic
CeH(CH2)
972.6
968.0
937.8
862.2
850.3
845.7
830.1
822.7
815.5
806.3
788.8
758.5
984.2
968.6
923.8
857.0
851.0
840.2
830.3
823.2
0.0
0.2
3.7
0.4
t
t
t
t
864.4
824.5
u
u
u
u
u
u
r
r
r
u
u
u
u
u
r
r
u
3.2
10.4
98.7
27.4
14.1
15.8
40.8
810.5
781.0
805.7
765.4
713.7
781.0
705.1
705.1
697.1
CeH(CH2)
CeHaromatic
CeH(CH2)
CeH(CH2)
y
ꢀ Stretching,
b
ꢀ in-plane bending,
g
ꢀ out-of-plane bending,
d
ꢀ scissoring,
r
ꢀ rocking,
u
ꢀ wagging,
t
ꢀ twisting, s ꢀ symmetric, asꢀ asymmetric.

502
A. Mahmood et al. / Journal of Molecular Structure 1108 (2016) 496e507
Fig. 3. Calculated and experimental FTeIR spectra of 1 (top panel) and 2 (lower panel). Simulated spectra with Gaussian lineshape and 15 cmꢀ1 of half-width at half-height.
Fig. 4. The linear regression between experimental and calculated FTeIR frequencies for 1 (left) and 2 (right).
LUMOs is related to the biological activity of the molecule [74,75],
which is mainly due to the change in partial charge and the change
in total dipole moment [76]. A large HOMOeLUMO energy gap
represents the high kinetic stability. This is due to the reason that
the transfer of an electron from higher occupied molecular orbitals
(HOMO) to lower unoccupied molecular orbitals (LUMO) is ener-
getically unfavorable. The 3D plots of HOMOs and LUMOs of mol-
ecules under study calculated at B3LYP/6e311þþG** level of the
theory are represented in Figs. 5 and 6.
The positive and negative phases are represented in red and
green colors, respectively. Generally, the atom or fragments occu-
pied by more densities of HOMOs should have stronger ability to
detach an electron whereas; the atom with more occupation of
LUMOs should have ability to gain an electron. As can be seen from
Fig. 5, the HOMOs of 1 present a charge density localized on
methylene groups, the benzene ring system adjacent to methylene
and N atom of NH2 while the LUMOs are distributed on toluene ring
system. The HOMO e 1 and LUMO þ 1 orbitals become more
localized on the respective sites. The HOMO and LUMO energy and
HOMOeLUMO energy gap for
1
was calculated to
be ꢀ6.9126, ꢀ1.3567 and 5.5559 eV, respectively. The small
HOMOeLUMO energy gap indicates the large intramolecular
charge transfer within the systems and thus its high reactivity.
In system 2, we observe a similar pattern of distribution of
charge density (Fig. 6). The HOMOe1 state is, however, distributed
all over the molecule. The HOMO and LUMO energy and HOMO-
eLUMO energy gap for 2 were calculated to be ꢀ6.3213, ꢀ1.3431
and 4.9782 eV, respectively. Again, the small HOMOeLUMO energy
gap represents the eventual charge transfer taking place within the
molecule. The small HOMOeLUMO energy gap in 2 as compared to

A. Mahmood et al. / Journal of Molecular Structure 1108 (2016) 496e507
503
Fig. 5. The atomic orbital compositions of the frontier molecular orbital for 1 simulated at B3LYP/6e311þþG(d,p). An isovalue of 0.02 was used for drawing the orbital surfaces.
1 suggests that 2 is more reactive than 1.
as ratio of electronegativity to chemical hardness (equation. (6)).
The numerical values of above mentioned properties of the mole-
cules calculated using equations (1)e(6) at B3LYP and B3PW91
methods are listed in Table 3. A comparison of the calculated values
shows that the hydroxyl group has a significant effect on the
electronic properties of system 2. The substitution of ring activating
(electron donating) hydroxyl group is found to decrease not only
the HOMOeLUMO energy gap but also the related electronic
properties, such as, ionization potential, electronegativity, chemical
The electronic properties such as ionization potential, electron
affinity, electronegativity, chemical hardness and softness and
electrophilicity are much better indicators of chemical stability
when comparing two similar systems with different substituents.
The chemical hardness or softness of a molecule is related to the
HOMOeLUMO energy gap. Electrophilicity (j) has been proposed
as a measure of lowering of energy due to maximal electron flow
between the donor and the acceptor atoms [77]. It can be calculated
Fig. 6. The atomic orbital compositions of the frontier molecular orbital for 2 simulated at B3LYP/6e311þþG(d,p). An isovalue of 0.02 was used for drawing the orbital surfaces.

504
A. Mahmood et al. / Journal of Molecular Structure 1108 (2016) 496e507
Table 3
. Calculated energies, ionization potential, electron affinity, chemical hardness, softness, electronegativity, electrophilicity index and dipole moment for systems 1 and 2.
TD-DFT/6-311Gþþ(d,p)
1
2
B3LYP
B3PW91
B3LYP
B3PW91
ETotal (Hartree)
EHOMO (eV)
ELUMO (eV)
ꢀ1185.404
ꢀ6.9126
ꢀ1.3567
5.5559
ꢀ1185.046
ꢀ6.9510
ꢀ1.3565
5.5945
ꢀ1260.651
ꢀ6.3213
ꢀ1.3431
4.9782
ꢀ1260.264
ꢀ6.3376
ꢀ1.3396
4.9981
D
EHOMOꢀLUMO gap(eV)
E
E
D
HOMOꢀ1 (eV)
LUMOþ1 (eV)
EHOMO ꢀ 1 ꢀ LUMO þ 1 gap (eV)
ꢀ7.1346
ꢀ0.9818
6.1529
ꢀ7.1874
ꢀ0.9633
6.2242
ꢀ7.2016
ꢀ0.9687
6.2329
ꢀ7.2288
ꢀ0.9472
6.2816
Ionization potential I.P (eV)
6.9126
6.9510
6.3213
6.3376
Electron affinity E.A (eV)
1.3567
1.3565
1.3431
1.3396
Electronegativity
c
(eV)
(eV)
4.1347
1.3890
0.6945
4.1537
1.3986
0.6993
3.8322
1.2445
0.6223
3.8386
1.2495
0.6248
Chemical hardness
h
Softness (s) (eV)ꢀ1
Electrophilicity index (
j)
11.8725
4.746
12.0655
4.703
9.1387
5.658
9.2058
5.649
Dipole moment (D)
m
hardness and softness and electrophilicity, significantly, in system
2. It can, therefore, be inferred that molecule 1 is more stable than
2. The higher dipole moment of 2 as compared to 1 also supports
the statement, while the results of two used methods converge.
charge transfer in reactions and to simulate the electrostatic po-
tential outside molecular surfaces [80]. The Mulliken charges on
atoms of systems 1 and 2 calculated at B3LYP and B3PW91 methods
using 6e311þþG(d,p) basis set are presented in Table 4 and as a
histogram in Figs. 7 and 8.
The results shows that the introduction of hydroxyl group on the
benzene ring in 2 have redistributed the electron density on the
benzene ring. The magnitudes of atomic charges on 6 carbons of the
4.2. Mulliken population analysis
The Mulliken population analysis can be useful to describe the
processes involving the electronegativity equalization [78,79] and
benzene
ring
change
from
ꢀ0.2165,
ꢀ0.1528,
0.9481, ꢀ0.4744, ꢀ0.3194 and ꢀ0.3375 in 1 to ꢀ0.0953, ꢀ0.2232,
1.0306, ꢀ0.5124, ꢀ0.0721 and ꢀ0.5219 in 2 calculated at B3LYP/
6e311þþG(d,p). The presence of hydroxyl group makes the C6
atom in 2 more negative because of its high electronegativity. The
carbons atoms adjacent to C6 bearing the hydroxyl group, that is,
C1 and C5 are calculated to be less negative due to the reason that
they lose the electron density to the C6.
All the carbons except C17 in 1 and C27 in 2, nitrogen and ox-
ygen atoms are positively charged while all the hydrogens, sulfur
atoms and C17 in 1 and C27 in 2 are positively charged. The highest
positive observed are on C26 (0.9481) in 1 and C3 (1.0306) in 2 at
B3LYP/6e311þþG(d,p) while the highest negative charges
observed are C4 (ꢀ0.7739) and C14 (ꢀ0.7717) in systems 1 and 2,
respectively.
Table 4
. Mulliken atomic charges of systems 1 and 2 calculated at different levels of the
theory.
(1)
(2)
Atoms
C31
C28
C26
C27
C29
C33
H35
H32
H30
H34
C1
H2
H3
C4
H5
H6
N7
H8
S9
O20
O21
C10
C11
C12
C13
C15
C17
H14
H16
H18
H19
C22
H23
H24
H25
H36
B3LYP
B3PW91
ꢀ0.2818
ꢀ0.1197
1.0945
ꢀ0.5597
ꢀ0.4074
ꢀ0.4604
0.2183
Atoms
C1
C2
C3
C4
C5
C6
H7
H8
B3LYP
B3PW91
ꢀ0.1193
ꢀ0.2457
1.1462
ꢀ0.5888
ꢀ0.0856
ꢀ0.7288
0.2384
ꢀ0.2165
ꢀ0.1528
0.9481
ꢀ0.4744
ꢀ0.3194
ꢀ0.3375
0.1745
0.1763
0.1520
0.1703
ꢀ0.3061
0.1371
0.1737
ꢀ0.7739
0.2502
0.1699
ꢀ0.1385
0.3199
0.2866
ꢀ0.1492
ꢀ0.1504
0.0303
ꢀ0.0118
ꢀ0.1461
ꢀ0.2869
ꢀ0.5254
0.1472
0.2346
0.2302
0.1925
0.1820
ꢀ0.6197
0.1583
0.1703
0.1508
0.1538
ꢀ0.0953
ꢀ0.2232
1.0306
ꢀ0.5124
ꢀ0.0721
ꢀ0.5219
0.1972
0.1811
0.1576
0.1396
0.2203
0.1867
0.2139
0.2271
0.1945
0.1801
H9
H10
C11
H12
H13
C14
H15
H16
N17
H18
S19
O32
O33
C20
C21
C22
C23
C25
C27
H24
H26
H28
H29
C34
H35
H36
H37
O30
H31
ꢀ0.2987
ꢀ0.3546
ꢀ0.2962
4.3. Molecular electrostatic potential
0.1667
0.1417
0.1715
0.2115
0.1722
0.2099
ꢀ0.9926
ꢀ0.7717
ꢀ0.9898
Molecular electrostatic potential (MEP) surfaces describe the
three dimensional charge distributions in a molecule. The distri-
bution of charge within molecules can help to understand how
molecules interact with each other. It is a useful property which
describes the size, shape and positive, negative and neutral regions
within a molecule in terms of color grading. The potential increases
in the order red < orange < yellow < green < blue. Therefore, one
can determine the preferred sites for nucleophilic and electrophilic
attacks in a molecule [81,82]. The equation to calculate the elec-
trostatic potential V at a point r for the system of charge qi located at
point ri is given as [83].
0.2798
0.2533
0.2828
0.2088
0.1716
0.2107
ꢀ0.1117
ꢀ0.1370
ꢀ0.1182
0.3437
0.3199
0.3423
0.2376
0.3027
0.2754
ꢀ0.1198
ꢀ0.1027
0.0701
ꢀ0.0148
ꢀ0.1796
ꢀ0.3253
ꢀ0.6341
0.2253
0.2743
0.2698
0.2391
0.2280
ꢀ0.1493
ꢀ0.1528
0.0444
ꢀ0.0414
ꢀ0.1391
ꢀ0.2510
ꢀ0.5424
0.1230
0.2331
0.2289
0.1931
0.1821
ꢀ0.1223
ꢀ0.1015
0.0810
ꢀ0.0566
ꢀ0.1753
ꢀ0.2689
ꢀ0.6582
0.1931
0.2710
0.2678
0.2404
0.2282
Z
X
qi
jri ꢀ rj
rðrˊÞdrˊ
jrˊ ꢀ rj
VðrÞ ¼
ꢀ
(7)
i
ꢀ0.8292
ꢀ0.6203
ꢀ0.8343
where r(rˊ) is the electron density function of the molecule. The
0.1819
0.1660
0.1923
first part of the equation represents the nuclear effect while the
second part represents that of electron. The two expressions in the
equation have opposite sign and hence have opposite effects.
MEP is a real physical property and can be determined by both
0.1956
0.1814
0.1904
0.1505
0.1633
0.1814
0.1867
ꢀ0.2299
ꢀ0.2003
0.2627
0.2689

A. Mahmood et al. / Journal of Molecular Structure 1108 (2016) 496e507
505
Fig. 7. (Color online) Graphical representations of atomic charges on the atoms of system 1.
Fig. 8. (Color online) Graphical representations of atomic charges on the atoms of system 2.
experimental (XRD) and computational methods [84]. In most of
the MEP's, the areas with highest electrostatic potential are shown
in blue color, which refers to the relative absence of the electrons in
that area and hence the preferred site for nucleophilic attack while
the regions with low electrostatic potential are shown in red color,
which indicates the relative abundance of electron and hence a
preferred site for electrophilic attack. The molecular electrostatic
potential maps of the compounds were calculated at B3LYP/
6e311þþG(d,p) and is shown in Fig. 9.
group and, therefore, appears to show a positive (blue) potential in
both the systems. The hydrogen of the hydroxyl group is the most
positive in the whole molecule of system 2 being attached to the
electronegative oxygen atom, which makes it the possible site for
nucleophilic attack.
5. Conclusion
The experimental and theoretical spectroscopic and electronic
properties of two synthesized sulfonamide derivatives, N-phe-
According to the MEP analysis, the regions of least potential are
located on the oxygen atoms of the SO2 group (red coded region) in
both the systems, as can be seen from Fig. 9. Therefore, the oxygen
atoms of the SO2 can be the possible sites for electrophilic attack.
The aromatic hydrogens in the benzene ring bearing the electro-
negative SO2 group appear to have increased potential and hence
the adjacent NHeCH2 moiety. The aromatic hydrogens of the other
benzene ring are observed to be less positive. The hydrogen of NH
group is involved in hydrogen bonding with the oxygen of the SO2
nethyl-4-methylbenzenesulfonamide
(1)
and
N-(4-
hydroxyphenethyl)-4-methylbenzenesulfonamide (2), were inves-
tigated by 1H NMR, 13C NMR, FTeIR spectroscopies and elemental
analysis and DFT quantum chemical methods. The simulated 1H
NMR, 13C NMR and FTeIR spectra were compared with the exper-
imental data. Indeed, the calculated chemical shifts were used in
the assignment of the studied molecules. The most stable struc-
tures were obtained by means of conformational analysis.

506
A. Mahmood et al. / Journal of Molecular Structure 1108 (2016) 496e507
[4] S. Shen, X. Xu, Z. Liu, J. Liu, L. Hu, Bioorg. Med. Chem. 23 (2015) 1982.
[5] T. Nguyen, N. German, A.M. Decker, J.-X. Li, J.L. Wiley, B.F. Thomas,
T.P. Kenakin, Y. Zhang, Bioorg. Med. Chem. 23 (2015) 2195.
[6] G. Song, X. Shen, S. Li, Y. Li, Y. Liu, Y. Zheng, R. Lin, J. Fan, H. Ye, S. Liu, Eur. J.
Med. Chem. 93 (2015) 431.
[7] C. Beinat, T. Reekie, S.D. Banister, J. O'Brien-Brown, T. Xie, T.T. Olson, Y. Xiao,
A. Harvey, S. O'Connor, C. Coles, A. Grishin, P. Kolesik, J. Tsanaktsidis,
M. Kassiou, Eur. J. Med. Chem. 95 (2015) 277.
ꢀ
[8] D. Załuski, Ł. Ciesla, Z. Janeczko, Stud. Nat. Prod. Chem. (2015) 217e249.
~
~
ꢀ
[9] V. Del Solar, A. Quinones-Lombrana, S. Cabrera, J.M. Padron, C. Ríos-Luci,
ꢀ
ꢀ
A. Alvarez-Valdes, C. Navarro-Ranninger, J. Aleman, J. Inorg. Biochem. 127
(2013) 128.
[10] J. Malmstrom, J. Viklund, C. Slivo, A. Costa, M. Maudet, C. Sandelin, G. Hiller, L.-
€
€
L. Olsson, A. Aagaard, S. Geschwindner, Y. Xue, M. Vasange, Bioorg. Med.
Chem. Lett. 22 (2012) 5919.
[11] X. Zou, Z. Lin, Z. Deng, D. Yin, Y. Zhang, Chemosphere 86 (2012) 30.
[12] R.P. Wurz, L. Liu, K. Yang, N. Nishimura, Y. Bo, L.H. Pettus, S. Caenepeel,
D.J. Freeman, J.D. McCarter, E.L. Mullady, T.S. Miguel, L. Wang, N. Zhang,
K.L. Andrews, D.A. Whittington, J. Jiang, R. Subramanian, P.E. Hughes,
M.H. Norman, Bioorg. Med. Chem. Lett. 22 (2012) 5714.
[13] C.P. Holmes, X. Li, Y. Pan, C. Xu, A. Bhandari, C.M. Moody, J.A. Miguel,
S.W. Ferla, M.N. De Francisco, B.T. Frederick, S. Zhou, N. Macher, L. Jang,
J.D. Irvine, J.R. Grove, Bioorg. Med. Chem. Lett. 15 (2005) 4336.
[14] S.-A. Poulsen, L.F. Bornaghi, P.C. Healy, Bioorg. Med. Chem. Lett. 15 (2005)
5429.
[15] T.C. Johnson, T.P. Martin, R.K. Mann, M.A. Pobanz, Bioorg. Med. Chem. 17
(2009) 4230.
[16] D.L. Aubele, A.P. Truong, D.B. Dressen, G.D. Probst, S. Bowers, M.N. Mattson,
C.M. Semko, M. Sun, A.W. Garofalo, A.W. Konradi, H.L. Sham, W. Zmolek,
K. Wong, E. Goldbach, K.P. Quinn, J.-M. Sauer, E.F. Brigham, W. Wallace,
L. Nguyen, M.P. Bova, S.S. Hemphill, G. Basi, Bioorg. Med. Chem. Lett. 21 (2011)
5791.
[17] J. Lal, S.K. Gupta, D. Thavaselvam, D.D. Agarwal, Eur. J. Med. Chem. 64 (2013)
579.
[18] A. Achari, D.O. Somers, J.N. Champness, P.K. Bryant, J. Rosemond,
D.K. Stammers, Nat. Struct. Biol. 4 (1997) 490.
Fig. 9. (Color online) Molecular electrostatic potential of 1 (top) and 2 (bottom)
simulated at B3LYP/6e311þþG(d,p).
[19] C.T. Supuran, A. Scozzafava, J. Enzyme Inhib. 15 (2000) 597.
[20] M.S. Al-Said, M.M. Ghorab, S.I. Al-Qasoumi, E.M. El-Hossary, E. Noaman, Eur. J.
Med. Chem. 45 (2010) 3011.
[21] J.A. Turpin, Y. Song, J.K. Inman, M. Huang, A. Wallqvist, A. Maynard,
D.G. Covell, W.G. Rice, A. Ettore, J. Med. Chem. 42 (1999) 67.
Molecular quantities such as ionization potential, electron affinity,
electronegativity and chemical hardness and softness were calcu-
lated and used as an additional molecular characteristic to predict
the stability and reactivity of the molecules. The computed elec-
tronic properties such Mullikan atomic charges, HOMO, LUMO and
HOMOeLUMO energy gaps and molecular electrostatic potential
maps predict significant substituent effects of ring activating hy-
droxyl group, intramolecular charge transfer. The presence of hy-
droxyl group causes a blue shift in the vibrational frequencies and
decrease in the HOMOeLUMO energy gap in 2. These investigations
could be useful for understanding and predicting molecular and
electronic structure and the spectroscopic properties of this class of
molecules that are relevant to medicinal chemistry. The study also
demonstrates that scaled DFT/B3LYP calculations using a medium
size basis set are powerful approach to determine the molecular
structure and spectroscopic properties.
ꢀ
ꢁ
ꢀ
ꢀ
ꢁ
ꢀ
[22] M. Kratký, J. Vinsova, M. Volkova, V. Buchta, F. Trejtnar, J. Stolaríkova, Eur. J.
Med. Chem. 50 (2012) 433.
[23] S. Konda, S. Raparthi, K. Bhaskar, R.K. Munaganti, V. Guguloth, L. Nagarapu,
D.M. Akkewar, Bioorg. Med. Chem. Lett. 25 (2015) 1643.
[24] N. Boechat, L.C.S. Pinheiro, O.A. Santos-Filho, I.C. Silva, Molecules 16 (2011)
8083.
[25] J. Mun, A.A. Jabbar, N.S. Devi, Y. Liu, E.G. Van Meir, M.M. Goodman, Bioorg.
Med. Chem. 20 (2012) 4590.
[26] M.J. Walsh, K.R. Brimacombe, H. Veith, J.M. Bougie, T. Daniel, W. Leister,
L.C. Cantley, W.J. Israelsen, M.G. Vander Heiden, M. Shen, D.S. Auld,
C.J. Thomas, M.B. Boxer, Bioorg. Med. Chem. Lett. 21 (2011) 6322.
[27] M. Koller, K. Lingenhoehl, M. Schmutz, I.-T. Vranesic, J. Kallen, Y.P. Auberson,
D.A. Carcache, H. Mattes, S. Ofner, D. Orain, S. Urwyler, Bioorg. Med. Chem.
Lett. 21 (2011) 3358.
€
[28] A. Casini, J. Antel, F. Abbate, A. Scozzafava, S. David, H. Waldeck, S. Schafer,
C.T. Supuran, Bioorg. Med. Chem. Lett. 13 (2003) 841.
[29] H. Turkmen, M. Durgun, S. Yilmaztekin, M. Emul, A. Innocenti, D. Vullo,
A. Scozzafava, C.T. Supuran, Bioorg. Med. Chem. Lett. 15 (2005) 367.
[30] W. Koch, M.C. Holthausen, A Chemist's Guide to Density Functional Theory,
Wiley-VCH, Weinheim, 2000.
[31] P. Hohenberg, W. Kohn, Phys. Rev. 136 (1964) B864.
[32] A. Mahmood, A. Irfan, J. Comput, Electron 12 (2013) 437.
[33] A. Mahmood, I.U. Khan, R.L. Longo, A. Irfan, S.A. Shahzad, Comptes Rendus
Chim. 18 (2015) 422.
Acknowledgements
The authors acknowledge analytical center, DQF, CCEN for
providing experimental 1H and 13C NMR and FTeIR spectra for the
studied compounds.
[34] R. Anbazhagan, K.R. Sankaran, J. Mol. Struct. 1050 (2013) 73.
[35] S. Liu, L. Zhang, W. Zan, X. Yao, Y. Yang, X. Liu, Sensors Actuators B Chem. 192
(2014) 386.
[36] H. Ebrahimi, J.S. Hadi, H.S. Al-Ansari, J. Mol Struct. 1039 (2013) 37.
ꢀ
Appendix A. Supplementary data
[37] R. Jasinski, J. Fluor. Chem. 160 (2014) 29.
ꢀ
[38] A. Łapczuk-Krygier, V.Y. Korotaev, A.Y. Barkov, V.Y. Sosnovskikh, E. Jasinska,
ꢀ
R. Jasinski, J. Fluor. Chem. 168 (2014) 236.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.molstruc.2015.12.039.
[39] S. Debnath, S. Mondal, Comput. Theor. Chem. 1046 (2014) 42.
[40] M.A. Pasha, A. Siddekha, S. Mishra, S.H.S. Azzam, S. Umapathy, Spectrochim.
Acta. A. Mol. Biomol. Spectrosc. 136 (Pt B) (2015) 221.
[41] H. Tanak, J. Mol. Struct. 1090 (2015) 86.
References
[42] M. Karabacak, M. Cinar, M. Kurt, J. Mol. Struct. 968 (2010) 108.
[43] P.V. Bharatam, A. Gupta, D. Kaur, Tetrahedron 58 (2002) 1759.
[44] P. Govindasamy, S. Gunasekaran, J. Mol. Struct. 1081 (2015) 96.
[45] M.T. Tavares, K.F.M. Pasqualoto, J. van de Streek, A.K. Ferreira, R.A. Azevedo,
[1] S. Marsden-Jones, N. Colclough, I. Garrard, N. Sumner, S. Ignatova,
J. Chromatogr. A 1398 (2015) 66.
~
ꢀ
M.C.F.C.B. Damiao, C.P. Rodrigues, P.L. de-Sa-Júnior, J.A.M. Barbuto, R. Parise-
Filho, F.F. Ferreira, J. Mol. Struct. 1088 (2015) 138.
[2] H. Tan, A. Ashour, Y. Katakura, K. Shimizu, Phytomedicine 22 (2015) 498.
[3] J. Charton, M. Gauriot, J. Totobenazara, N. Hennuyer, J. Dumont, D. Bosc,
X. Marechal, J. Elbakali, A. Herledan, X. Wen, C. Ronco, H. Gras-Masse,
A. Heninot, V. Pottiez, V. Landry, B. Staels, W.G. Liang, F. Leroux, W.-J. Tang,
B. Deprez, R. Deprez-Poulain, Eur. J. Med. Chem. 90 (2015) 547.
[46] S. Muthu, G. Ramachandran, E. Isac Paulraj, T. Swaminathan, Spectrochim.
Acta. A. Mol. Biomol. Spectrosc. 128 (2014) 603.
[47] A. Chandran, H.T. Varghese, Y.S. Mary, C.Y. Panicker, T.K. Manojkumar, C. Van

A. Mahmood et al. / Journal of Molecular Structure 1108 (2016) 496e507
507
€
Alsenoy, G. Rajendran, Spectrochim. Acta. A. Mol. Biomol. Spectrosc. 87 (2012)
29.
J.J. Dannenberg, S. Dapprich, A.D. Daniels, O. Farkas, J.B. Foresman, J.V. Ortiz,
J. Cioslowski, D.J. Fox, Gaussian, Inc., Wallingford CT, 2009.
[61] A.D. Becke, J. Chem. Phys. 98 (1993) 5648.
[48] G. Velraj, S. Soundharam, J. Mol. Struct. 1074 (2014) 475.
[49] B.A. Shainyan, N.N. Chipanina, T.N. Aksamentova, L.P. Oznobikhina,
G.N. Rosentsveig, I.B. Rosentsveig, Tetrahedron 66 (2010) 8551.
[50] K. Sarojini, H. Krishnan, C.C. Kanakam, S. Muthu, Spectrochim. Acta. A. Mol.
Biomol. Spectrosc. 108 (2013) 159.
[51] K. Sarojini, H. Krishnan, C.C. Kanakam, S. Muthu, Spectrochim. Acta. A. Mol.
Biomol. Spectrosc. 96 (2012) 657.
[52] Z. Xiang, Comput. Theor. Chem. 991 (2012) 74.
[53] A. Chandran, Y.S. Mary, H.T. Varghese, C.Y. Panicker, P. Pazdera, G. Rajendran,
Spectrochim. Acta. A. Mol. Biomol. Spectrosc. 79 (2011) 1584.
[54] C. Zhao, A. Fu, H. Li, C. Tian, Z. Wang, S. Yuan, Y. Duan, Comput. Theor. Chem.
1018 (2013) 77.
[62] C. Lee, W. Yang, R.G. Parr, Phys. Rev. B 37 (1988) 785.
[63] J.P. Perdew, J.A. Chevary, S.H. Vosko, K.A. Jackson, M.R. Pederson, D.J. Singh,
C. Fiolhais, Phys. Rev. B 48 (1993) 4978.
[64] J.P. Perdew, K.A. Jackson, M.R. Pederson, D.J. Singh, C. Fiolhais, Phys. Rev. B 46
(1992) 6671.
[65] K. Burke, J.P. Perdew, Y. Wang, in:, Plenum, New York, 1998, pp. 81e121.
[66] K.W. Wiitala, T.R. Hoye, C.J. Cramer, J. Chem. Theory Comput. 2 (2006) 1085.
[67] J. Tomasi, B. Mennucci, R. Cammi, Chem. Rev. 105 (2005) 2999.
[68] M.J. Frisch, A.B. Nielsen, A.J. Holder, Gauss View User's Manual, Gaussian Inc.,
Pittsburgh, PA, 2000.
[69] Chemcraft, http://www.chemcraftprog.com.
[55] A. Chandran, H.T. Varghese, C.Y. Panicker, C. Van Alsenoy, G. Rajendran, J. Mol.
Struct. 1001 (2011) 29.
[56] I.U. Khan, A. Mahmood, M.N. Arshad, S.A. Shahzad, Rep. Online, Acta Crys-
tallogr. Sect. E Struct. 67 (2011) o2703.
[70] D.H. Barton, Science 169 (1970) 539.
[71] A.P. Scott, L. Radom, J. Phys. Chem. 100 (1996) 16502.
[72] G. Socrates, Infrared Characteristic Group Frequencies, third ed., Wiley
Interscience Publications, New York, 1980.
[57] A. Mahmood, I.U. Khan, M.N. Arshad, J. Ahmed, Rep. Online, Acta Crystallogr.
Sect. E Struct. 67 (2011) o2140.
[58] M.K. Ghorai, A. Kumar, D.P. Tiwari, J. Org. Chem. 75 (2010) 137.
[59] Q. Gu, S.-L. You, Chem. Sci. 2 (2011) 1519.
[73] T. Koopmans, Physica 1 (1934) 104.
[74] M. Ibrahim, A.A. Mahmoud, J. Comput. Theor. Nanosci. 6 (2009) 1523.
[75] J.S. Griffith, L.E. Orgel, Q. Rev. Chem. Soc. 11 (1957) 381.
[76] M. Ibrahim, H. El Haes, Int. J. Environ. Pollut. 23 (2005) 417.
ꢀ
[60] Gaussian 09, Revision D.01 M.J. Frisch, G.W. Trucks, H.B. Schlegel,
G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci,
G.A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H.P. Hratchian, A.F. Izmaylov,
J. Bloino, G. Zheng, J.L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda,
J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven,
J.A. Montgomery Jr., J.E. Peralta, F. Ogliaro, M. Bearpark, J.J. Heyd, E. Brothers,
K.N. Kudin, V.N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari,
A. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J.M. Millam,
M. Klene, J.E. Knox, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts,
R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski,
R.L. Martin, K. Morokuma, V.G. Zakrzewski, G.A. Voth, P. Salvador,
[77] R.G. Parr, L.V. Szentpaly, S. Liu, J. Am. Chem. Soc. 121 (1999) 1922.
[78] R.S. Mulliken, J. Chem. Phys. 23 (1955) 1833.
[79] R.G. Parr, R.G. Pearson, J. Am. Chem. Soc. 105 (1983) 7512.
[80] L. Pauling, The Nature of Chemical Bond, third ed., Cornell University Press,
New York, 1960.
ꢀ
[81] F.J. Luque, J.M. Lopez, M. Orozco, Theor. Chem. Acc. 103 (2000) 343.
[82] E. Scrocco, J. Tomasi, Advances in Quantum Chemistry 11, Elsevier, 1978.
[83] P. Politzer, P.R. Laurence, K. Jayasuriya, Environ. Health Perspect. 61 (1985)
191.
[84] S.J. Grabowski, Hydrogen BondingeNew Insights, in: Challenges and Ad-
vances in Computational Chemistry and Physics, 3, Springer, 2006.