Synthesis, characterization and biological investigation of glycine-based sulfonamide derivative and its complex: Vibration assignment, HOMO – LUMO analysis, MEP and molecular docking

Article abstract of DOI:10.1016/j.molstruc.2018.12.067

A combined experimental and theoretical investigation has been reported on N-(glycine)-para styrene sulfonamide (abbreviated as GSS). The GSS and its complex were synthesized for first time in two steps. The GSS was synthesized from the reaction of para styrene sulfonyl chloride and glycine in the mild condition. The palladium complex was prepared from the reaction of PdCl₂, CH₃CN and GSS as a ligand. The GSS and its complex was confirmed using FT-IR and ¹H-NMR spectra. The data obtained from wave number calculations are used to assign vibrational bands obtained in infrared and Raman spectra recorded. Potential energy distribution was done using GAR2PED program. HOMO-LUMO analysis, and Molecular Electrostatic Potential studies of the GSS and its complex have been investigated using DFT method. The GSS is investigated against Staphylococcus aureus and Escherichia coli. Molecular Docking study of GSS is also reported.

Full text of DOI:10.1016/j.molstruc.2018.12.067

Accepted Manuscript
Synthesis, characterization and Biological Investigation of glycine- based
sulfonamide derivative and its complex: vibration assignment, HOMO – LUMO
analysis, MEP and molecular docking
Parvaneh Shafieyoon, Ebrahim Mehdipour, Y. Sheena Mary
PII:
S0022-2860(18)31500-X
10.1016/j.molstruc.2018.12.067
MOLSTR 26004
DOI:
Reference:
To appear in:
Journal of Molecular Structure
Received Date:
Accepted Date:
08 September 2018
16 December 2018
Please cite this article as: Parvaneh Shafieyoon, Ebrahim Mehdipour, Y. Sheena Mary, Synthesis,
characterization and Biological Investigation of glycine- based sulfonamide derivative and its
complex: vibration assignment, HOMO – LUMO analysis, MEP and molecular docking, Journal of
Molecular Structure (2018), doi: 10.1016/j.molstruc.2018.12.067
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ACCEPTED MANUSCRIPT

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Synthesis, characterization and Biological Investigation of glycine- based sulfonamide
derivative and its complex: vibration assignment, HOMO – LUMO analysis, MEP and
molecular docking
a
a
Parvaneh Shafieyoon, Ebrahim Mehdipour,* Y. Sheena Mary
b
aDepartment of Chemistry, Faculty of Science, Lorestan University, Khorramabad, Iran.
bDepartment of Physics, Fatima Mata National College, Kollam, Kerala, India.
aCorresponding author: Tell: +98-06633120618
E-mail: e_mehdipour@yahoo.com, mehdipour.e@lu.ac.ir
E-mail: parva127@yahoo.com , shafieyoon.pa@fs.lu.ac.ir
E-mail: ysheena@rediffmail.com (Y.S. Mary), sypanicker@rediffmail.com

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ABSTRACT
A combined experimental and theoretical investigation has been reported on N-(glycine)-para
styrene sulfonamide (abbreviated as GSS).The GSS and its complex were synthesized for first time
in two steps. The GSS was synthesized from the reaction of para styrene sulfonyl chloride and
glycine in the mild condition. The palladium complex was prepared from the reaction of PdCl2,
1
CH CN and GSS as a ligand. The GSS and its complex was confirmed using FT-IR and H-NMR
3
spectra. The data obtained from wave number calculations are used to assign vibrational bands
obtained in infrared and Raman spectra recorded. Potential energy distribution was done using
GAR2PED program. HOMO-LUMO analysis, and Molecular Electrostatic Potential studies of the
GSS and its complex have been investigated using DFT method. The GSS is investigated against
Staphylococcus aureus and Escherichia coli. Molecular Docking study of GSS is also reported.
Keywords: N-(glycine) -para styrene sulfonamide; DNA; BSA; HSA; Molecular docking; MEP;
PED.
Introduction
Sulfonamide compounds, as antibacterial agents, are extensively applied in the world due to their
low toxicity and excellent activity against bacterial diseases[1, 2]. These materials are widely used
to prevent the growth of bacteria in the body. Some sulfonamide derivatives in pharmaceutical as
antibacterial agents such amino acid, imidazole[3]. In the overall, antimicrobial properties of
Sulfonamide derivatives are well known. Therefore, the clinical and medicinal properties of
sulfonamide derivatives as antibacterial agent, in a group of commercial pharmaceutical
compound have been known. The number of sulfonamide derivatives as an inhibitor to prevent of
generation and progression of cancer cells was applied such as tetrahydroquinoline [4]and

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chromone[5] containing sulfonamide moiety. During the past two decades, the synthesis of
sulfonamide derivatives have been developed as antibacterial and anticancer drugs [6-13].In the
recently, by changing the structural parts of sulfonamides, new drugs have been designed. These
investigations promoted us to synthesize and evaluate a sulfonamide derivative for pharmaceutical
chemistry, we have selected glycine and styrene structural parts to synthesis a new sulfonamide
structure due to these group in coordination to metals and synthesis of novel complex-based
sulfonamide drugs. In other words, the title compound have medicinal property. In our previous
research, we reported the synthesis of sulfonamide and amino acid derivatives [14-16] and
theoretical investigation about the new drug-based materials [17, 18]. In this work, the title
compound was obtained by the reaction of glycine with para styrene sulfonyl chloride. The
bioactivity of this compound for the first time was investigated in vitro against gram positive and
gram negative bacteria. Molecular docking calculations were performed to evaluate the medicinal
properties of the title compound.
2
. Material and methods
Para- styrene sulfonic acid sodium salt, PCl , sodium hydroxide, CH CN, PdCl , CHCl and
5
3
2
3
glycine were purchased from Aldrich Company and were used without further purification. Fourier
−
1
transform infrared spectra of prepared compounds were recorded at 400–4000 cm region using
1
KBr pellets on Shimadzu FT-IR 8400 spectrometer. H NMR spectrum was recorded on a Brucker
Ultrashield 300 MHz spectrometer using D O as solvent and tetramethylsilane as internal standard.
2
2
.1. Preparation of Para styrene Sulfonyl Chloride
To prepare the monomer first, Para- styrene sulfonyl chloride was synthesized as follows: 7.50 g
of PCl (36mmol) was placed in a 500-mL round-bottomed flask, equipped with magnetic stirrer,
5
5
.00 g (24mmol) of Para-styrene sulfonic acid sodium salt was added slowly with ice bath cooling.

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After 30 min. it was heated under reflux at 50-60°C for 2 hr. The product was cooled and separated
from inorganic materials by chloroform and ice water. The chloroform was evaporated from the
Para- styrene sulfonyl chloride. The product was washed 3 times with water. The solvent was
evaporated and product used without further purification. Experimental details are described in
Ref [19]
2
.2. Preparation of N-(glycine) - Para- styrene sulfonamide (GSS)
The synthetic method for the preparation of the GSS with chemical formula (C H NO S) is as
1
0
11
4
follows: In a 100 mL round-bottomed flask, equipped with magnetic stirrer, 4.86 g para vinyl
styrene sulfonyl chloride (24 mmol) in 50 mL CHCl as a solvent and 1.8 g glycine (24 mmol)
3
were placed. Then, 24 mL NaOH 1M was slowly added. The reaction mixture was stirred for 4 h
at room temperature. After the reaction time, the organic layer was separated and GSS as the
product was obtained. The obtained product was washed 3 times with CHCl and analyzed without
3
-1
further purification (Yield 4.79 g, 83.0%, m.p. 141°C). IR (KBr, Cm ): 3616(υOH), 3394(υNH),
3
1
050(υCHPh), 3009(υCH, υCH ), 2975(υCH ), 2880(υCH ), 1743(υC=O), 1570(υPh, δCHPh),
2 2 2
462(δNH, υPh), 1433(δCH ), 1320(υSO , δCH ), 1245(υCO, δCH , δNH), 1136(δCH , δOH,
2
2
2
2
2
υCN), 1082(υCN, υSO ), 1041(δCH , υPh, 1008(δCH , δCH, υPh), 910(γCC), 813(γCHPh),
2
2
2
1
7
27(τPh, γCC,γCS, γCHPh) 640(τOH, δSO , γC=O), 559(γNH, δNH). H-NMR ((D O, ppm):
2 2
2
.04(s, CH ), 3.77(NH) 5.42(CH in vinyl), 5.97(CH in vinyl), 6.81(CH in vinyl), 7.66 (CH
2
Benzene), 7.76 (CH Benzene), 9.95(COOH).
.3. Preparation of complex (PdCl L)
2
2
The synthetic method for preparation of palladium complex is as follows: 0.09 g PdCl (0.5 mmol)
2
and CH CN (50 mL) were placed in a 100-mL round-bottomed flask equipped with a reflux
3
condenser and a magnetic stirrer. The mixture was stirred and warmed to 70 °C to give a light

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orange solution. Then, 0.127 g ligand (0.5 mmol) and sodium hydroxide 0.5 M (2 mL) were added.
The reaction mixture refluxed for 12 h and the green solid appeared. The green solution filtered
and washed with CH CN (3 × 10 mL). The product was used without further purification.
3
-1
IR (KBr, Cm ): 3050(υCHPh), 3009(υCH), 2987(υCH ), 2880(υCH ), 1743(υC=O), 1510(υPh),
2
2
1
462(δNH, υPh),, 1433(δCH ), 1315(υSO , δCH ), 1245(υCO, δCH , δNH), 1136(δCH , δOH,
2 2 2 2 2
υCN, 1082(υCN, υSO ), 1041(δCH , υPh, 1008(δCH , δCH, υPh), 910(γCC), 813(γCHPh),
2
2
2
1
7
27(τPh, γCC, γCS, γCHPh) 640(τOH, δSO , γC=O), 559(γNH, δNH). H-NMR (D O, ppm):
2 2
2
.04(s, CH2), 5.42(CH in vinyl), 5.97(CH in vinyl), 6.81(CH in vinyl), 7.66 (CH Benzene), 7.76
(CH Benzene),
2
.4. Computational details
Calculations of the GSS were performed using Gaussian 09 software[20].These calculations
include geometry optimization(opt-freq), MEP, HOMO – LUMO analysis were performed using
density functional theory (DFT) [21, 22].The optimization (opt-freq) of compounds was carried
out using CAM-B3LYP/Aug.-cc-pVDZ level of theory. The Potential Energy Distribution (PED)
of the normal modes among the respective internal coordinates was calculated for GSS using
the GAR2PED program [27] and compared with theoretical and experimental values. PASS
(Prediction of Activity Spectra) [23]was used as an online server to predict the activity of the
ligand. Molecular docking has recently been used as a tool to get an insight into ligand – receptor
interaction and screen molecules for the binding affinities against a special receptor. Molecular
docking calculations were performed on AutoDock-Vina software[24]. The output of geometry
optimization (using CAM-B3LYP/Aug-cc-pVDZ level of theory) for title compound was used as
the input of ligand for docking processes. Lamarckian Genetic Algorithm (LGA) available in
Autodock was employed for docking, as the most popular algorithm[25, 26]. The 3D crystal

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structure of employed DNA, BSA and HSA as receptors were obtained from Protein Data Bank
(
PDB ID: 423D, 4F5S, 1AO6). The graphical representation of ligand-receptor interaction was
obtained using ligplot software [27].
.5. Antibacterial assays
2
The minimal inhibitory concentration (MIC) is determined by preparing solutions of the chemical
in vitro at increasing concentrations, incubating the solutions with the separate batches of cultured
bacteria, and measuring the results using agar solution. It is used to measure the Minimum
Inhibitory Concentration [MIC] of an antimicrobial agent, which is the lowest concentration of
antibacterial agent which will prevent the growth of bacteria .The MIC of the GSS as antibacterial
agent against Escherichia coli and Staphylococcus aureus will be reported in the next section. The
GSS was tested for its antibacterial activity against Staphylococcus aureus, as the model from
Gram-positive and Escherichia coli as Gram-negative bacteria by the disk diffusion method [28].
2
.6. Preparation of Nutrient-Agar medium
For this work, 3.80 g of Nutrient-Agar (NA) medium was dissolved in 100 mL of distilled water.
This solution was sterilized at 120 °C for 20 min in an autoclave. Then, 20 mL of this solution was
solidified in Petri plate.
3
. Result and discussion
3
.1. Synthesis and characterization
The synthetic routes for preparation of GSS and its complex, as explained in experimental
section, are schematically represented in Schemes1 and 2.

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NH2
CH2
CHCl ,NaOH
3
C
S
rt.4h
S
HO
O
O
O
O
O
NH
CH2
C
Cl
HO
O
Scheme 1. The reaction involving synthesis of GSS
reflux
Cl
Cl
N
N
C
C
CH3
CH3
PdCl2
CH CN
3
Pd
N
N
C
C
CH3
Cl
Cl
GSS, r.t.
NaOH
S
Pd
O
O
CH3
N
Cl
Pd
Cl
CH2
C
O
O
Scheme 2. Synthesis of complex
.2. Tautomeric and dynamic processes
GSS could be presented in two different tautomers (named as T , T ). This is important to know
3
1
2
about the relative stabilities of these tautomers (Fig.1).

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O
O
H20
N1
N1
C
C3
C
C3
S12
C
S12
C
H2
OH
H
O
14 O13
2
OH
O14
O13
H20
T1
T2
Fig. 1. The general structures of GSS tautomers
In fact, structures of these tautomers were calculated using CAM-B3LYP/Aug.-cc-pVDZ level
of theory. Thermodynamic properties such as electronic energies, relative total energies, relative
enthalpies, and relative Gibbs free energies for two Tautomers (T and T ) shown in the Table1,
1
2
As a result, T tautomer is the more stable due to the symmetrical elements in SO .
1
2
Table 1. Kinetic and thermodynamic data of two tautomers
Tautomer
Ee
ZPE
Rel.E
Rel.H°298
Rel. G°298
-1141.6938
0.202907
-1141.475378
-1141.474433
-1141.536567
T1
-1141.1358
0.202631
-1140.917449
-1140.916504
-1140.978557
T2
All energetic data have been reported in Hartrees.
3
.3 Molecular structural
The optimized geometry (opt-freq) using (CAM-B3LYP method Aug –cc–pVDZ) of GSS was
calculated. The numbers of atoms was defined in Fig. 2.

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Fig.2.Optimized geometry T (top) and T (bottom) of GSS
1
2
3
.4. Spectroscopic characterization of GSS
The experimental FT- IR of GSS is reported in experimental section (Fig.3) The C–H stretching
-1
-1
frequencies of aromatic can be observed in the range of 3100–3000 cm is showed at 3106 cm .
-1
The aliphatic C–H stretching frequencies are also appeared below 3000 cm . The C= C stretching
-1
vibration in the range of 1650–1430 cm and the C–H bending bands are appeared in the regions
-1
-1
1
275–1000 cm (in-plane C-H bend) and 900–690 cm (out-of plane C-H bend). In addition, the
-1
stretching mode of NH group is appeared at 3234cm . The out- of –plane NH wag is assigned at
-
1
5
1
56cm in the IR spectrum. In the following discussion, Sulfonamides absorb strongly at 1370-
-1
335 and 1170-1155 cm .The stretching mode symmetrical and asymmetrical O=S=O is observed
-1
-1
at 1174cm and 1384 cm respectively.
,
NH modes

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According to literature [29, 30]the NH vibrations are expected in the following regions: stretching
-1
-1
mode: 3500-3300 cm ; deformation modes: around 1500, 1250 and 750-600 cm . For the title
-1
compound, the NH stretching modes are assigned at 3396 cm theoretically (Table 2) and the NH
-1
deformations are assigned at 1464, 1279, 561 cm theoretically. The reported values of NH modes
-1
-1
-1
are at 3462 cm in the IR spectrum, 3450 cm in the Raman spectrum, 3400 cm theoretically
-1
(
stretching modes), 1508, 1219, 655 cm (DFT) (deformation modes[31] and 1587, 1250, 650
-1
-1
cm (IR), 1580, 1227, 652 cm (DFT) (deformation modes[32].
Phenyl ring vibrations
-1
The phenyl CH stretching modes are assigned at 3079, 3076, 3061, 3049 cm theoretically. The
phenyl ring stretching modes are assigned at 1569, 1539, 1464, 1372, 1301 cm-1 theoretically[33].
The ring breathing mode of para-substituted phenyl rings with entirely different substituent are
-1
expected in the range 780-880 cm according to literature[34] and in the present case, this is
confirmed by the band at 772 cm-1 theoretically. The phenyl ring breathing mode of para
-1
-1
substituted phenyl rings was reported at 795 cm [35] at 873 cm in the IR spectrum and at 861
-1
-1
-1
cm theoretically [36]and at 753 cm in IR spectrum, 793, 759 cm theoretically[18] The in-plane
-1
CH bending modes of the phenyl rings are assigned as 1270, 1161, 1096, 989 cm (DFT) as
expected[33]. The out-of-plane CH bending modes of the phenyl rings are assigned at 956, 942,
-1
8
33, 814 cm (DFT) for PhIV.
COOH modes
For the title compound, the C=OOH modes are assigned at 3612 cm (DFT) (OH stretching mode),
-1
-
1
-1
1
6
746 cm (DFT) (C=O stretching mode), 603, 502 cm (DFT) (C=O deformation modes), 1301,
-
1
-1
37 cm (DFT) (OH in-plane and out-of-plane deformation), 1248 cm (DFT) (C-O stretching)
as expected in literature [33]. The reported values are 1680, 561(IR), 1675, 735, 555 (DFT) for

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-1
C=O group, 1321 (IR), 1318, 920 (DFT) for OH group and 1235 (IR), 1238 cm (DFT) for C-O,
for a similar derivative[37].
C=C, and CH modes
2
-1
For the title compound, C=C stretching mode is assigned at 1617 cm (DFT[38]. In the present
-1
case, the CH modes are assigned at 3102, 3025, 2974, 2879 cm (DFT) (stretching modes), 1435,
2
-1
1
405, 1318, 1201, 1134, 1040, 1007, 974 cm (DFT) (deformation modes)[39].
SO modes
2
The asymmetric and symmetric stretching vibrations of SO are reported in the range 1330 ± 60
2
-1
and 1180 ± 45 cm respectively. For the title compound, the DFT calculations give these modes
-1
at 1318 and 1179 cm . The SO deformation bands are expected in the regions 535 ± 40, 485 ±
2
-1
-1
5
0, 405 ± 65, 320 ± 40 cm . DFT calculations give SO modes at 541, 472, 383, 329 cm and
2
most of the bands are not pure but contains significant contributions from other modes also.
-1
Rodriguez et al [33] reported the SO bands in the range 1242-1394, 590-632 and 460-470 cm .
2
-1
The C-S stretching modes are assigned at 630 cm theoretically as expected[33].
Table 2. Theoretical (B3LYP/6-311G (d, p)) and experimental IR wavenumbers with PEDs (Vibrational
assignments) of the GSS
Observed IR bands
Assignments
Scaled
IR
frequency intensity
7
7
7
7
7
7
6
6
6
6
6
6
5
4
3
2
1
0
9
8
7
6
5
4
3612
3396
3102
3079
3076
3061
3049
3025
3016
2974
2879
1746
95.44
81.41
8.96
1.62
2.19
3.25
9.31
2.48
11.80
6.40
3616
3394
-
-
-
υOH(100)
υNH(100)
υCH (98)
2
υCHPh(92)
υCHPh(96)
υCHPh(99)
υCHPh(94)
-
3050
-
3009
2975
2880
1743
υCH (83),υCH (15)
2
υCH(83),υCH (16)
2
υCH (97)
2
17.96
278.00
υCH (97)
2
υC=O (80)

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6
3
1620
6.56
-
υC=C(60), δCH (15),
2
δCH(11)
6
6
6
5
5
5
5
5
5
5
5
5
5
4
4
4
4
4
4
4
4
4
4
3
3
3
3
3
3
2
1
0
9
8
7
6
5
4
3
2
1
0
9
8
7
6
5
4
3
2
1
0
9
8
7
6
5
4
1569
1539
1464
1435
1405
1397
1372
1318
1301
1279
1270
1261
1248
1201
1179
1161
1134
1096
1085
1081
1040
1007
989
15.89
4.46
6.73
16.84
2.09
9.50
20.34
224.25
3.25
1570
-
1462
1433
-
-
-
1320
-
-
-
υPh(56), δCHPh(13)
υPh(69)
δNH(59), υPh(35)
δCH (90)
2
δCH (62), δCH (17)
2
δNH(22), δCH (36), υCC(13)
2
υ Ph(42), δCHPh(22)
υSO (43), δCH (41)
2
2
δOH (40), υPh(42)
υPh(32), δNH(35)
δCHPh(53), υPh(19), υSO (10)
2.25
14.86
57.09
63.13
15.45
1.21
2
-
δCH (20), δOH (17), υSO (19)
2
2
1245
-
-
-
1136
-
-
1082
1041
1008
-
-
-
-
-
υCO(41),δCH (21), δNH (14)
2
δCH (87)
2
υSO (39),υPh(21)
2
0.76
δCHPh(71)
143.33
30.84
168.08
259.37
77.82
77.82
7.41
13.97
0.66
0.23
δCH (52), δOH(16), υCN(17)
2
δCHPh (48), υPh(24)
υCN(33), υSO (23)
2
υCN(28), υSO (21)
2
δCH (47), υPh(22)
2
δCH (62), δCH (11), υPh(11)
2
υPh(61), δCHPh (47)
987
974
956
942
911
886
δCH (49),γCH(43)
2
δCH (72), γC=O(19)
2
γCHPh(91)
γCHPh(78),τPh(18)
γCC(95)
0.03
43.07
5.40
910
-
υCC(31),δCH (18), δNH (16),
2
υSN(14)
3
3
3
3
2
3
2
1
0
9
833
814
812
772
728
25.96
21.01
91.32
5.82
-
γCHPh(65), γCC(12)
γCHPh(85)
υSN(36), υCC(25)
δPh (28), υCC(18), υPh(39)
τPh(56), γCC(12),γCS(9),
γCHPh(11)
813
-
-
0.07
727
2
2
2
2
2
2
2
2
8
7
6
5
4
3
2
1
637
630
625
620
603
561
541
516
280.98
10.66
4.26
640
-
-
-
τOH(43), δSO (16), γC=O(15)
2
τPh(32), γCH(12), υCS(38)
τOH(22), τPh(42), δPh(16)
δPh(62)
δC=O(44)
γNH(43), δNH(12)
2.42
37.89
109.15
30.31
59.56
-
559
-
-
δSO (36), δCC(21), δPh (17)
2
δSO (22), τPh(18)
2

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2
1
1
1
1
1
1
1
1
1
1
9
8
7
6
0
9
8
7
6
5
4
3
2
1
0
502
472
462
443
399
383
329
308
258
234
224
205
136
123
107
53.65
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
γC=O(38), τOH(22), δCH (11)
2
36.94
44.10
0.84
0.31
2.42
2.82
2.93
2.33
1.03
1.51
0.56
1.80
3.45
2.67
δSO (37), γNH(15), δC=O(10)
2
δCC(37), γNH(18), δC=O(15)
τPh(36),γCC(17), δSO (16)
2
τPh(81)
δSO (41), δC=O(17), δCS(15)
2
δSO (51), γCC(17), τPh(12)
2
δSO (42), δC=O(18)
2
δPh(18), δCC(12), δSO (15)
2
δSO (14), δCC(24)
2
δCH (12), δCC(18), δSO (15)
2
2
δCH (18), γCS(12), δSO (11)
2
2
δCS(49), δCC(17)
τC=O(22), γNH(14), τPh(11)
δNH(28), τNH(18), δCH (13),
2
τC=O(12), δSO (12)
2
5
77
2.63
-
τC=O(24), γCS(18),
τCH (18),τCC(11), δSO (10)
2
2
4
3
2
1
46
40
36
20
1.64
0.52
0.26
0.21
-
-
-
-
τC=O(41), τNH(35)
τCC(45), τSO (13), τPh(12)
2
τSO (50), τCC(14)
2
τCH (48)
2
Ph-phenyl ring; υ-stretching; δ-in-plane deformation; γ-out-of-plane deformation; τ-torsion
Potential energy distribution is given in brackets in the assignment column.
In order to investigate the performance of vibrational wave numbers of the title compound, the
root mean square (RMS) value between the calculated and observed wave numbers were
calculated. The RMS values of wave numbers were calculated using the following expression
2
1
푛
푐푎푙푐푢
푖
― ʋ 푒푖 푥푝
)
RMS =
∑ (ʋ
푛 ― 1
푖
The RMS errors of the observed IR bands are found to 1.55. The small differences between
experimental and calculated vibrational modes are observed. This is due to the fact that
experimental results belong to solid phase and theoretical calculations belong to gaseous phase.

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Fig. 3. The experimental FT-IR spectra of GSS (bottom) and complex (top)
1
3
.5. Observed and calculated H NMR chemical shifts
1
1
The experimental H-NMR spectrum of the compound are reported in section 2.2 (Fig.4) The H-
NMR spectrum of the GSS was recorded in D O as solvent with TMS as internal standard at 400
2
MHz

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1
Fig.4.The experimental H-NMR spectra of GSS (top) and complex (bottom)
1
Table 3. Experimental and calculational results related to H NMR of ASS
Hydrogen number exp. cal.
Hydrogen number exp. cal.
8
,9
7.66 7.42
7.76 7.72
6.81 6.69
24
22
5.42 5.32
3.77 4.18
9.95 5.46
2.04 3.01
7
,10
2
3
5
21
2
5.97 6.00
26,27
1
Observed and computed H NMR chemical shifts with their assignments.
The theoretical chemical shift values was calculated by B3LYP method using 6-311+g. The
theoretical chemical shift values was calculated by B3LYP method using 6-311+g (2d, p) basis set
GIAO model (scale number=0.9614). Then, the results showed that the predicted proton chemical
shifts were in good agreement with the experimental data for GSS which represented in Table 3.
1
The RMS error between observed and calculated H-NMR are 1.74.The small differences between

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experimental and calculated vibrational modes are observed. This is due to the fact that
experimental results belong to solid phase and theoretical calculations belong to gaseous phase.
3
.6. Spectroscopic characterization of palladium complex
The FT- IR spectrum of complex are listed in experimental section. The vibrational band present
−
1
at 3396 cm is assigned to ν(N–H) for free ligand. This band disappears for the complex because
the ligand has been deprotonated. The SO group did not participate in the coordination, then
2
−
1
ν (S=O) shifted from 1320 cm−1 in the free ligand to 1315 cm in the complex due to the different
as
spatial orientation of this group in the complex, but the ν (S=O) remained almost unchanged. The
s
FT-IR spectrum of ligand showed absorption bands at 1570 cm−1 which was assigned to the
−
1
ν(C=C) vibrations, in the complex showed 1510 cm is correlated with the coordination of the
ligands (Fig 3).
1
3
.7. Observed H NMR chemical shifts of palladium complex
1
1
The experimental H-NMR spectrum of the complex is reported in section 2.3. The H-NMR
spectrum of the compound was recorded in D O as solvent with TMS as internal standard at 400
2
1
MHz. The H-NMR spectrum of the ligand showed a broad singlet at 3.77 ppm for –NH group and
9
.95 ppm for –COOH group. The absence of these signals in the spectrum of the complex, due to
deprotonation and coordination of anions to palladium and the formation of Pd–N and Pd-O bonds
Fig.4)
(

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3
.8. Molecular electrostatic potential
MEP (Molecular electrostatic potential) is as a significant tool to predict the electrophilic and
nucleophilic attacks for the biological interactions. The MEP of the title compound was optimized
geometry using b3lyp method 6-311+g (d, p) was calculated. As can be observed in Fig.5. The
different colors in this plot are indicated different values of the electrostatic potential.
Red<orange< yellow<green<blue. The blue illustrate the strongest attraction. The positive area is
located around vinyl and phenyl groups. These areas are having positive potential. The negative
area is related to C=O group. In these areas having negative potential are over the electronegative
atoms such as oxygen. The red indicates the strongest repulsion. These regions of negative
potential are associated with the lone pair of electronegative atoms. The residuals species are
surrounded by zero potential. The nitrogen of NH and oxygen of OH are as anions coordination to
palladium and the formation of complex.
Fig.5. MEP plot of N-(glycine) para styrene sulfonamide in the left and its complex in the right
3
.9. Frontier molecular orbital analysis
Investigation of the HOMO and the LUMO is important in a molecule as a ligand. The LUMO
energy explains the ability to accept an electron and the HOMO energy is related to the ability to

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donate an electron. Both the HOMO and the LUMO play a significant role in the electrical
properties and chemical activities in the compound. The HOMO and LUMO orbital energy are
important parameters to predict the chemical properties of the title compound. The HOMO and
LUMO orbital energy of GSS and its complex are calculated at the B3LYP method 6-311+g (p,d)
basis set. The energy values of the ligand and its complex are, EHOMO = - 6.601,-8.940 and ELUMO
=
- 5.059,-5.821eV, respectively. The energy difference between the HOMO and LUMO of the
ligand and its complex are 1.542 and 3.119 eV, respectively. The energy of HOMO and LUMO
orbitals of the GSS and its complex are negative that these compounds are stable and does not
decompose spontaneously into theirs elements. According to Parr et al[40]. The molecule with
small energy gap is more polarization property, low kinetic stability and is in general called as soft
molecule. These molecules can be explained as the resistance towards the deformation of electron
cloud and polarization of chemical systems during the chemical process. The chemical softness is
a useful concept for predicting the behavior of chemical systems and is related to the stability and
low reactivity of a chemical system. The chemical hardness is a useful concept for predicting the
behavior of chemical systems and is related to the stability of a chemical system By using HOMO
and LUMO orbital energies, the ionization energy and electron affinity of the ligand and its
complex can be calculated as: I = - EHOMO = 6.601,8.940 and A = - ELUMO = 5.059, 5.821eV,
respectively. The global hardness η and chemical potential µ of the ligand and its complex are
given by using the relation η = (I - A)/2 = 0.771, 1.559 eV, µ = - (I + A)/2= -5.831,-7.381 eV and
2
Electrophilicity index (ω) = µ /2η = 22.043, 17.467 eV, respectively. The calculated value
describes the catalytically and biologically activity of the title compound (GSS). The atomic orbital
components of the frontier molecular orbital are shown in Fig. 6.

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HOMO
LUMO
HOMO
LUMO
Fig.6. HOMO and LUMO plots of N-(glycine) - para -styrene sulfonamide in the up and its complex in
the down
3
.10. Molecular docking studies
We decided to perform molecular docking simulation of the title compound against the 3D crystal
structure of DNA, BSA, and HSA were obtained from Protein Data Bank (PDB ID: 423D, 4F5S,
1
AO6) respectively. Molecular docking is a significant investigation to understand the ligand-
receptor interactions. The ligand was prepared for docking by B3LYP method 6-311+g (p,d)basis
set. The active sites of the DNA and BSA were defined to include residues of the active site within
the grid box size of 36A°×28A°×20A° for DNA, 82A°×54A°×64A° for BSA and
7
0A°×54A°×72A° for HSA with a grid-point spacing of 1.00 Å were applied. Among the docked
conformations, the best scored conformation predicted by AutoDock scoring function were
visualized for ligand-DNA, ligand-BSA, and ligand-HSA interactions in Ligplot and Ligplus
software. The resulting docking in which the ligand binds into the DNA creates two hydrogen

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bonds (Fig. 7), viz. These hydrogen bonds are between the OSO2 of ligand and Dg4 and Dg22
(5.32Ȧ, 6.02Ȧ) respectively. There are hydrophobic contacts between the carbon atom of phenyl
ring and Dc6 and Dc21. The BSA creates two hydrogen bonds (Fig.9), viz. These hydrogen bonds
are between Oso of ligand with Gly327 and Asp323 (2.96 Ȧ, 3.03 Ȧ) respectively. There are
2
hydrophobic contacts between the carbon atoms and sulfur atom of ligand with Ala212, Leu326,
Leu330, Leu346, Ala349, Lys350, and Val481. The HSA creates hydrophobic contacts between
the carbon atoms and sulfur atom of ligand with Leu 238, Leu 260, Ile 264, Ile 296, Ala 261 and
-1
Ala 291. The binding free energy (∆G° in kcal mol ) -6.5 for DNA, -6.8 for BSA and =6.7 for
HAS are predicted for the best conformation of the ligand. The values of ∆G° indicate a high
binding affinity between DNA, BSA and HSA separately with the ligand (title compound).
Fig.7. The non-covalent interactions and hydrophobic forces across the binding interface of Ligand–DNA
in the left, ligand-BSA in the middle and ligand- HAS in the right (H bonds are shown by green dotted
lines).

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3
.11. The disk diffusion method
A microbial suspension (1 mL) Staphylococcus aureus and Escherichia coli were spread separately
over the surface of agar plate, which were then incubated for 24 h at 37°C in an autoclave.
Inhibitory zone values (diameter of inhibition) from disk diffusion tests and growth inhibition ring
for GSS was reported in Table 4 and Figure 8.
Table 4. Inhibitory zone values (diameter of inhibition) from disk diffusion tests.
Compound
bacteria
E.coli
Inhibition zone diameter (mm)
N-(glycine)-para-styrene sulfonamide
N-(glycine)-para-styrene sulfonamide
19
21
S.aureus
The results of this assay can be showed that both of Staphylococcus aureus and Escherichia coli
are sensitive to N-(glycine)-para-styrene sulfonamide but Staphylococcus aureus more
sensitiveness to the compounds.
Fig.8 The growth inhibition ring observed for ligand in S.aureus in the right and E.coli in the left.

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4
. Conclusion
We report the new compounds of based- glycine sulfonamide and its complex. Tautomers of
based- glycine sulfonamide were calculated using B3LYP method 6-311+g (p,d) basis set. These
calculations were shown the structure of based- glycine sulfonamide is stable. HOMO-LUMO
analysis, and Molecular Electrostatic Potential studies of the GSS and its complex have been
investigated using DFT method. Molecular electrostatic potential and Frontier molecular orbital
analysis were indicated the GSS can be designed for the new catalyst due to its properties. The
1
GSS and palladium complex were characterized using FT-IR and H NMR spectra. The Potential
Energy Distribution (PED) of the normal modes among the respective internal coordinates was
calculated for GSS using the GAR2PED program and compared with theoretical and experimental
values. These biological investigations against the Staphylococcus aureus and Escherichia coli
and docking simulation of the GSS against the 3D crystal structure of DNA, BSA, and HAS
suggest that GSS can be used for the design and synthesis of new based-drug materials
Acknowledgment
We would like to thank Lorestan University for its financial support
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1

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We report the new compounds of based- glycine sulfonamide and its complex. These biological
investigations and docking simulation of the GSS against the 3D crystal structure of DNA, BSA,
and HAS suggest that GSS can be used for the design and synthesis of new based-drug materials