Sulfonamide-derived hydrazone compounds and their Pd (II) complexes: Synthesis, spectroscopic characterization, X-ray structure determination, in vitro antibacterial activity and computational studies

Article abstract of DOI:10.1016/j.molstruc.2019.07.016

A new sulfonamide-derived prophane sulfonyl hydrazone compounds: 2-hydroxy- acetophenoneprophanesulfonylhydrazone (afpsh), 5-Cl-2-hydroxyacetophenoneprophane sulfonylhydrazone (5-Clafpsh), 3,5-di-tert-butyl-2-hydroxybenzaldehydeprophanesulfonyl hydrazone

Full text of DOI:10.1016/j.molstruc.2019.07.016

Journal of Molecular Structure 1196 (2019) 707e719
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
Sulfonamide-derived hydrazone compounds and their Pd (II)
complexes: Synthesis, spectroscopic characterization, X-ray structure
determination, in vitro antibacterial activity and computational
studies
a,
*
b
b
c
€
€
€
Neslihan Ozbek , Ümmühan Ozmen Ozdemir , Ahmet Fazıl Altun , Ertan S¸ ahin
a Department of Mathematics and Science Education, Ahi Evran University, 40100, Kırsehir, Turkey
b Department of Chemistry, Faculty of Science, Gazi University, Teknikokullar, Ankara, 06500, Turkey
c Department of Chemistry, Faculty of Science, Ataturk University, 25240, Erzurum, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
A new sulfonamide-derived prophane sulfonyl hydrazone compounds: 2-hydroxy- acetophenonepro-
phanesulfonylhydrazone (afpsh), 5-Cl-2-hydroxyacetophenoneprophane sulfonylhydrazone (5-Clafpsh),
3,5-di-tert-butyl-2-hydroxybenzaldehydeprophanesulfonyl hydrazone (3,5tbsalpsh) and their Pd(II)
Received 9 April 2019
Received in revised form
3 July 2019
Accepted 4 July 2019
Available online 5 July 2019
complexes were synthesized. The characterization of all compounds was characterized by 1H NMR, 13
C
NMR, FT-IR, Mass spectral data, elemental analysis and magnetic susceptibility measurements. The
crystal structure of afpsh was determined by single crystal X-ray diffraction methods. 1H and 13C
shielding tensors of afpsh were calculated with GIAO/DFT/B3LYP/6e311þþG(d,p) methods in DMSO.
Molecular electrostatic potential surface and frontier orbital analysis were also carried out. HOMO-LUMO
energy gap was calculated which allowed the calculation of relative reactivity descriptors like chemical
hardness, chemical inertness, chemical potential, nucleophilicity and electrophilicity index of all com-
pounds. It has been observed that the calculated band gaps for Pd (II) complexes are much smaller than
ligands. The microbiological effect of ligands and Pd(II) complexes were tested against six human
pathogenic bacteria (three Gram-positive and three Gram-negative strains) by using microdilution (as
MICs) and disc diffusion (as mm zone) methods. It was found that all compounds, in particular Pd (II)
complexes, were more active than sulfonyl hydrazones.
Keywords:
Sulfonamide-derived sulfonyl hydrazones
Pd(II) complexes
Antimicrobial activity
Computational studies
© 2019 Published by Elsevier B.V.
1. Introduction
[7], hypoglycemic [8], anti-protease [9] properties. They are also
used in the treatment for diabetes (eg acetohexamide) [10].
Sulfonamide was first drug to treat bacterial infections. Its dis-
covery in 1932 was the most profound revolution in medicinal
chemistry. The invention of sulfonamide triggered the discovery of
other anti-bacterial members derived from this chemical group,
such as sulfadiazine and sulfadoxine [1]. Sulfonamides have a broad
spectrum of antimicrobial activity against a range of bacterial
species, both Gram-positive and Gram-negative. Sulfonamide-
based molecules are of great importance in the preparation of
various biological active compounds [2] as they possess anti
convulsant (e.g., topiramate) [3], anti-inflammatory (.eg., valde-
coxib) [4] antibacterial [5], antitumor [6], anti-carbonic anhydrase
Sulfonamides are also used in coordination chemistry as ligands
in the synthesis of metal complexes with structural [11e13],
analytical [14] and biological applications [15e17]. In this regard, a
series of sulfonamides have been coordinated and evaluated
against cancer [18], tuberculosis [19] and malaria [20]. In 2008,
Chohan and Supuran have been synthesized Co(II), Cu(II), Ni (II) and
Zn(II) sulfonamide complexes and evaluated their biological ac-
tivity. These complexes are found to be more active than the free
ligands [21]. In recent years, palladium-containing sulfonamides
have started to be synthesized and have been investigated anti-
bacterial activity of their complexes. In 1998, Otter et al. described
the synthesis of palladium sulfonamide complex, however they
were no biological evaluated [22]. Alyar and Adem have reported
that Pd(II) complexes containing salicilaldehyde-N-methyl p-
* Corresponding author.
€
E-mail address: nozbek@ahievran.edu.tr (N. Ozbek).
https://doi.org/10.1016/j.molstruc.2019.07.016
0022-2860/© 2019 Published by Elsevier B.V.

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N. Ozbek et al. / Journal of Molecular Structure 1196 (2019) 707e719
toluenesulfonylhydrazone ligand binds and evaluated antibacterial
activity [23].
2-hydroxyacetophenoneprophanesulfonylhydrazone
(afpsh;
C
11H16N2SO3): Yield 50%; mp:115e116 ꢁC. Elemental analysis: Calcd
In our previous studies, we synthesized bissulfonamides and
tested antibacterial activity [6,24]. We also have reported spectro-
scopic properties and conformation analysis of aliphatic/aromatic
sulfonic acid hydrazide, sulfonic acid 1-methylhydrazide and some
sulfonylhydrazone derivatives [25e27], as well as their metal
complexes [28,29]. This study describes the synthesis of 2-
hydroxyacetophenoneprophanesulfonylhydrazone (afpsh),5-Cl-2-
for C,51.56; H,6.25; N,10.93; S,12.5. Found: C,50.87; H,5.97; N,10.07;
S,11.98.
5-chlorine-2-hydroxyaceto
phenoneprophanesulfonylhy-
drazone (5-Clafpsh; C11H15N2SO3Cl): Yield 47%; mp:138e139 ꢁC.
Elemental analysis: Calcd for C,45.43; H,5.16; N,9.63; S,11.01. Found:
C,45.38; H,5.06; N,9.27; S,10.75.
3,5-di-tert-butyl-2-
hydroxyacetophenoneprophanesulfonylhydrazone
3,5-di-tert-butyl-2-hydroxy benzaldehydeprophanesulfonylhy-
(5-Clafpsh),
hydroxybenzaldehydeprophanesulfonylhydrazone
C
(3,5tbsalpsh;
18H30N2SO3): Yield 55%; mp:183e185 ꢁC. Elemental analysis:
drazone (3,5tbsalpsh) and their Pd(II) complexes, their character-
ization using elemental analyses, spectrometric methods (FT-IR, 1H
eNMR, 13C NMR, LC-MS, UV-Vis), magnetic susceptibility and
conductivity measurements and evaluation of their antimicrobial
activities. 1H and 13C shielding tensors for crystal structure of li-
gands were calculated with GIAO/DFT/B3LYP/6e311þþG(d,p)
methods in DMSO. The frontier molecular orbitals (FMOs) and
molecular electrostatic potential maps (MEP) of sulphonyl hydra-
zine have been investigated by B3LYP/6e311þþG(d,p) and B3LYP/
LanL2DZ level of theory. The antibacterial activities of all com-
pounds were studied against Gram positive species; S.aureus ATCC
25923, E. faecalis ATCC 23212, S. epidermidis ATCC 34384 and Gram
negative species; K. pneumoniae ATCC 70063, P. aeruginosa ATCC
27853, E. coli ATCC 25922 by using microdilution (as MICs) and disc
diffusion (as mm zone) methods. Biological studies of Pd(II) com-
plexes with emphasis on its possible application as a novel anti-
bacterial agent are also present in this manuscript.
Calcd for C,61.01; H,8.47; N,7.91; S,9.03. Found: C,60.97; H,7.98;
N,7.47; S,9.00.
2.3. Synthesis of the Pd (II) complexes
All complexes are prepared by the following general method
(Fig. 1): A sample of anhydrous 0,10 mmol Na2PdCl4, was dissolved
in acetonitrile (5 mL) and a solution of afpsh (0.2 mmol) in a
mixture of acetonitrile (10.0 mL) and NaOH solution in methanol
(0.2 mmol) was added. The reaction mixture was heated at 60 ꢁC for
1 h. The complexes precipitated quickly after stirring the mixture at
room temperature and filtered off, dried in a desiccator over CaCl2.
Pd(afpsh)2 (C22H30N4S2O6 Pd): Yield 50%; mp:148e150 ꢁC.
Elemental analysis: Calcd for C,42.85; H,4.87; N,9.09; S,10.38.
Found: C,41.62; H,4.49; N,8.54; S,10.22.
Pd(5-Clafpsh)2 (C22H28N4S2O6Cl2Pd): Yield 50%; mp:168e170 ꢁC.
Elemental analysis: Calcd for C,38.54; H,4.08; N,8.17; S,9.34. Found:
C,37.07; H,3.97; N,7.81; S,9.03.
2. Experimental
Pd(3,5tbsalpsh)2 (C36H58N4S2O6 Pd): Yield 55%; mp:196e198 ꢁC.
Elemental analysis: Calcd for C,53.20; H,7.14; N,6.89; S,7.88. Found:
C,51.92; H,6.89; N,6.01; S, 7.32.
2.1. Materials and physical measurements
Propane sulfonyl chloride, hydrazine hydrate, Na2PdCl4, 2-
hydroxyacetophenone, 50-chloro-20-hydroxyacetophenone, 3,5-di-
tert-butyl-2-hydroxybenzaldehyde, ethanol, methanol, diethyl
ether, ethyl acetate, acetonitrile, dimethyl sulfoxide and tetrahy-
drofuran (all from Sigma-Aldrich) and solvents (all from Merck)
were used without further purification. All chemicals and solvents
used in synthesis were of analytical grade.
The elemental analyses (C, H, N and S) were performed on a
LECO CHNS 9320 type elemental analyzer. 1H -NMR and 13C -NMR
spectra were recorded on a Agilent Spectrospin Avance VNMRS
-500 Ultra-Shıeld. TMS was used as internal standard and deu-
teriated DMSO as solvent. The IR spectra (4000-400 cmꢀ1) were
recorded on a Mattson 1000 FT-IR Spectrophotometer with sam-
ples prepared as KBr pellets. LC/MS-APCI was recorded on an Wa-
ters 2695 Alliance Micromass ZQ Spectrometer. The melting points
were measured using an Opti Melt apparatus. TLC was conducted
on 0.25 mm silica gel plates (60F254, Merck). The molar magnetic
susceptibilities were measured on powdered samples using Gouy
method. The molar conductance measurements were carried out
using a Siemens WPA CM 35 conductometer.
2.4. Single crystal X-Ray crystallography
For the crystal structure determination, single-crystal of the
compound afpsh was used for data collection on a four-circle
Rigaku R-AXIS RAPID-S diffractometer (equipped with a two-
dimensional area IP detector). Graphite-monochromated Mo-Ka
radiation (
D
l
¼ 0.71073 Å) and oscillation scans technique with
w ¼ 5ꢁ for one image were used for data collection. The lattice
parameters were determined by the least-squares methods on the
basis of all reflections with F2 > 2 (F2). Integration of the intensities,
s
correction for Lorentz and polarization effects and cell refinement
were performed using CrystalClear (Rigaku/MSC Inc.,2005) soft-
ware [31]. The structure was solved by direct methods using
SHELXS-97 [32] and non-hydrogen atoms were refined using
anisotropic displacement parameters by full-matrix least-squares
procedure using the program SHELXL-97 [32]. H atoms were
positioned geometrically and refined using a riding model. The final
difference Fourier maps showed no peaks of chemical significance.
Crystal data for afpsh: C11H16N2O3S, crystal system, space group:
monoclinic, P21/a; (no:14); unit cell dimensions: a ¼ 7.351(2),
b ¼ 18.123(5), c ¼ 9.838(4) Å,
a
¼ 90,
b
¼ 105.698(6),
g
¼ 90ꢁ; vol-
2.2. General procedure for the synthesis of sulfonyl hydrazones
ume; 1261.8(7) Å3, Z ¼ 4; calculated density: 1.35 g/cm3; absorption
coefficient: 0.255 mmꢀ1; F(000): 544;
q-range for data collection
The reaction of the hydrazine hydrate with propane sulfonyl
chloride was carried out propane sulfonic acid hydrazide (psh) as
procedure [30]. The sulfonyl hydrazones were synthesized ac-
cording to the following general procedure (Fig. 1).
The solution of propane sulfonic acid hydrazide (0.01 mol) in of
ethanol was mixed with hot solution of the corresponding aromatic
aldehydes (0.015 mol) in ethanol and stirred for 1 h. Upon cooling,
crystalline precipitates were filtered, washed with ethanoleether,
recrystallized from water and dried in vacuo over P2O5.
2.1e30.7ꢁ; refinement method: full matrix least-square on F2; data/
parameters: 3871/161; goodness-of-fit on F2: 1.023; final R-indices
[I > 2
s
(I)]: R1 ¼0.06, wR2 ¼ 0.181; largest diff. peak and hole: 0.344
and ꢀ0.397 e Åꢀ3
.
2.5. Theoretical calculations
Because of the effective bioactivities of sulfonyl hydrazine
compounds, the three dimensional conformation analysis was

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N. Ozbek et al. / Journal of Molecular Structure 1196 (2019) 707e719
709
Fig. 1. General synthesis method of the sulfonyl hydrazones and related Pd (II) complexes.
performed to obtain important previews about molecular behavior
in gas and solution forms. To determine the most stable structures,
all the possible conformations of 5-Clafpsh and 3,5-tbsalpsh com-
pounds were obtained by potential energy scan. One-dimensional
potential energy scans were performed for seven torsion angles-
in DMSO using the GIAO method. The geometry optimizations of Pd
(II)esulfonyhydrazone complexes having square planer geometry
were applied to confirm the structure as minimum points in energy
by B3LYP/LanL2DZ quantum set in Gaussian 09 software program.
The 1H and 13C NMR absolute shielding constants were converted
t
1 C8 (H)eC7eN1eN2,
t
2 C7eN1eN2eS,
t
3 N1eN2eC9eC10,
t
t
4
7
to the
d chemical shifts using following equation that s (TMS) and
N2eSeC9eC10, 5 SeC9eC10eC11,
t
t6 C10eC9eSeO2 and
s(Xi) are the magnetic shielding constants of reference [36,37] and
N1eN2eSeO2 in the full range of 0e3600 by DFT method. DFT
calculations were performed using Becke's three parameter hybrid
exchange functional [33]. B3 combined with both the Lee-Yang-Par
gradient-corrected correlation functional (LYP) [34]. In the
mentioned conformational analysis of afpsh, the molecular geom-
etry optimizations was compared with the Gaussian 03W software
package by using DFT approaches in addition to the determination
of crystal structure (Fig. 2) [35]. The split valence 6e311þþG (d, p)
basis set was used for the expansion of the molecular orbital. The
1H and 13C NMR chemical shifts of the compounds were calculated
sample, respectively. NMR calculations were performed in solution
phase using the polarizable continuum model (PCM) for DMSO
[38]. d cal(Xi) ¼
s (TMS) e s (Xi).
In this study, the molecular properties such as ionization po-
tential, electron affinity electronegativity, chemical potential,
chemical hardness, softness, electrophilicity index (Equations
(1)e(6)) have been deduced from HOMO-LUMO (HOMO-1, HOMO,
LUMO, LUMOþ1) analysis employing B3LYP/6e311þþG(d,p)
method. The molecular electrostatic potential maps (MEP) of sul-
phonyl hydrazine were performed using B3LYP/6e311þþG(d,p)
Fig. 2. Bond lengths (Å) and selected bond angles (o) of afpsh.

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N. Ozbek et al. / Journal of Molecular Structure 1196 (2019) 707e719
basis set. The MEP surfaces have been mapped with a rainbow color
scheme with red representing the highest negative potential region
while blue representing the highest positive potential region.
prophane sulfonic acid hydrazide (psh) and then synthesized a new
sulfonyl hydrazone and their Palladium complexes (Fig. 1). The
analytical and spectrophotometric results are consistent with the
expected structure of the general formula [ML2].
Ionization potentialðI:PÞ ¼ ꢀ EHOMOðeVÞ
Electron affinityðE:AÞ ¼ ꢀ ELUMOðeVÞ
(1)
(2)
(3)
(4)
3.1. Crystal structure of afpsh
Electronegativityð
cÞ ¼ ðI:P þ E:AÞ=2ðeVÞ
Solid-state structure of N'-[1-(2-hydroxyphenyl)ethylidene]
propane-1-sulfonohydrazide was confirmed through X-ray
diffraction analyses whose molecular diagrams are depicted in
Fig. 3a. Molecules of afpsh form centrosymmetric dimers con-
nected by N2eH/O2 [D … A ¼ 2.968(3)Å] hydrogen bonds. There is
an intramolecular hydrogen bond between the phenolic OH group
and the iminic nitrogen, as evidenced by short O1/N1 distances
[d(O/N) ¼ 2.548(3)Å]. Thus, the length of the C1eO1 bond is
1.364 Å, which is consistent with a single bond; while the C1¼C7
bond distance is 1.284 Å. The mean plane of the heterocyclic ring is
approximately coplanar with the phenyl fragment. The bond
lengths between sulphur and oxygen S1eO2 ¼ 1.431(3) Å and
SeO3 ¼ 1.423(3) Å falls within the double bond range. The geom-
etry around S atom is significantly deviated from that of regular
tetrahedral. The maximum and minimum angles around S are
119.2(3) and 104.5(3), respectively. In all essential details, the ge-
ometry of the molecule regarding bond lengths and angles of the
compound are in good agreement with the values observed in
similar structures [41,42]. Unit cell content with the stacking motif
of the molecule is given in Fig. 3b. The list of important bond
lengths and bond angles are given in Table 1.
Chemical hardnessð
h
Þ ¼ ðI:P ꢀ Þ=2ðeVÞ
c
SoftnessðsÞ ¼ 1=2
h
ðeVÞꢀ1
(5)
(6)
.
Electrophilicity indexð
j
Þ ¼ c2
2h
2.6. Procedure for antibacterial activity
Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC
23212, Staphylococcus epidermidis ATCC 34384, Klebsiella pneumo-
niae ATCC 70063, Pseudomonos aeruginosa ATCC 27853, Escherichia
coli ATCC 25922 cultures were obtained from Gazi University,
Department of Biology and bacterial strains were cultured over-
night at 310 K in a nutrient broth. During the survey, these stock
cultures were stored in the dark at 277 K. The inocula of microor-
ganisms were prepared from broth cultures and suspensions were
adjusted to 0,5 McFarland standart turbidity.
The Sulfonamide-derived hydrazones and their Pd(II) com-
plexes were dissolved in dimethylsulfoxide (15% DMSO) to a final
concentration of 3.0 mg mLꢀ1 and sterilized by filtration with
0,45 mm millipore filters. Antimicrobial tests were then carried out
by the disc diffusion method using 100 mL of suspension containing
108 CFU mLꢀ1 bacteria which was spread on nutrient agar (NA)
medium. The discs (6 mm in diameter) were impregnated with
35
3.0 mg mLꢀ1 and placed on the inoculated agar. DMSO impregnated
discs were used as negative control. Sulfisoxazole (300 g/disc)
mL of each compound (105 mg/disc) at the concentration of
m
were used as positive control to determine the sensitivity of one
strain/isolate in each microbial species tested [39]. The inoculated
plates were incubated at 37 ꢁC for 24 h for bacterial strains isolates.
Antimicrobial activity in the disc diffusion assay was evaluated by
measuring the zone of inhibition against the test organisms. Each
assay in this experiment was repeated twice. Percentage of inhi-
bition was calculated by comparing the distance of the sample to
the distance of Sulfisoxazole as standard.
The minimum inhibitory concentration (MIC) values of the
sulfonamide derivatives and their complexes were determined
using modification of the micro well dilution assay method. 100
of the test compounds, initially prepared at 3000
g mLꢀ1 con-
centration, were added into the first wells. Then, 100 L of the serial
mL
m
m
dilutions was transferred into nine consecutive wells. The contents
of the wells were mixed and the micro plates were incubated at
37 ꢁC for 24 h. The compounds were tested against each microor-
ganism twice. The values obtained are average of the two results.
The MIC values were determined from visual examinations as the
lowest concentration of the extracts in the wells with no bacterial
growth [40].
3. Results and discussion
Fig. 3. a) Dimeric structure of the afpsh molecule b) Unit cell content with the
stacking motif of the molecule. Thermal ellipsoids are drawn at the 40% probability
level.
We initiated this work by synthesizing
a multifunctional

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711
Table 1
Table 4
Selected bond lengths (Å) and bond angles (o) for afpsh.
The experimental and theoretical 1H and13C NMR chemical shifts
d(ppm) for the
sulfonylhydrazones.
Assig.
Exp.
Calc.
Assig.
Exp
Calc.
Assignment Afpsh
Exp.
5-Clafpsh
Exp.
3,5-tbsalpsh
Exp.
The Bond lengths (Å)
S e O(2)
1.431(2)
1.463
1.818
1.372
1.408
1.511
1.391
1.088
1.533
1.713
S e O(3)
1.423(2)
1.388(5)
1.521(5)
1.387(4)
1.400(4)
1.373(5)
1.364(4)
1.284(4)
1.482(4)
1.454
1.393
1.529
1.397
1.401
1.390
1.369
1.283
1.487
Calc.
Calc.
Calc.
S e C(9)
1.764(3)
1.385(4)
1.409(4)
1.493(4)
1.371(5)
0.930(3)
1.509(6)
0.93
C(3)eC(4)
C(9)eC(10)
C(1)eC(2)
C(6)eC(5)
C(2)eC(3)
O(1)eC(1)
N(1)eC(7)
C(7)eC(6)
C10
C9
C8
C7
C6
C5
C4
C3
C2
C1
128.41 128.2 127.34 127.93 125.96
118.41 117.8 131.52 139.80 141.36
125.98 127.9 123.79 125.82 127.49
117.79 113.0 119.35 110.31 138.99
153.75 153.5 155.83 155.81 154.49
126.44
138.92
127.48
138.77
149.89
121.39
149.32
55.29
N(2)eN(1)
C(1)eC(6)
C(7)eC(8)
C(5)eC(4)
C(3)eH(3)
C(11)eC(10)
S e N(2)
125.1
125.8 119.87 119.21 115.99
156.55 147.6 156.96 149.55 155.15
53.39
14.42
11.91
e
57.3
12.4
53.45
13.35
11.82 12.85
56.27
13.31
12.24
53.04
17.10
12.88
The bond angles (o)
16.54
12.76
O(2)-S-O(3)
119,2(2)
121.2
103.1
120.7
123.3
117.8
122.1
120.7
119.9
108.327
108.3
115.2
O(2)-S-C(9)
N(2)-S-C(9)
110,2(2)
106,0(2)
123,1(3)
115,9(3)
121,7(3)
114,5(3)
119,3(3)
120,7(3)
121,7(3)
120,1(3)
120,7(3)
113,9(3)
110.1
104.5
119.1
117.1
122.5
111.3
119.2
119.6
119.7
118.2
120.2
111.5
O(3)-S-N(2)
107,1(2)
116,2(3)
123,4(3)
116,6(3)
122,7(3)
120,7(3)
119,9(3)
104,6(2)
108,8(2)
114,1(2)
R
1 (CeCH3)
e
e
34.10e29.39 35.1e24.88
35.13e31.40 36.02e29.72
e
O(1)-C(1)-C(2)
N(1)-C(7)-C(8)
C(1)-C(6)-C(5)
C(6)-C(5)-C(4)
C(1)-C(2)-C(3)
C(2)-C(3)-C(4)
O(2)-S-N(2)
O(1)-C(1)-C(6)
N(1)-C(7)-C(6)
C(1)-C(6)-C(7)
C(9)-C(10)-C(11)
C(5)-C(4)-C(3)
C(6)-C(7)-C(8)
C(7)-C(6)-C(5)
N(2)-N(1)-C(7)
C(6)-C(1)-C(2)
SeC(9)-C(10)
R2 (CeCH3)
e
e
e
R
3 (CH3)
.
17.09
7.39
e
10.0
7.44
e
H10
H9
H8
H7
H3
H2
H1
7.3
6.8
6.8
7.7
3.19
1.75
1.02
e
6.6
6.4
6.1
6.6
3.2
0.97
0.81
e
7.41
e
7.46
e
7.25
6.92
3.24
1.90
1.07
e
7.31
6.74
3.26
1.71
0.92
7.03
e
7.23
e
3.24
1.91
1.10
1.30
1.43
8.07
e
3.41
1.74
0.98
1.14
1.33
8.21
O(3)-S-C(9)
SeN(2)-N(1)
R
1 (CH3)
R2(CH3)
R3(CH3)
OH
e
e
e
2.30
11.71
10.61
1.9
2.29
2.08
10.85
e
11.27 11.45
10.37
3.2. The characterization of compounds
3.2.1. Experimental FT-IR spectroscopy
NH
e
10.47
10.17
s
d
Transform into using equations given in Ref. [42];
d
13C ¼ 175.7e0.963
s
13C and
1H ¼ 31.0e0.970
s
1H.
Table 2 shows the assignment of the main bands in the FT-IR
spectra of free ligands and complexes, based on some general ref-
erences and previous studies on complexes with sulfonamides [43].
NH vibrations in ligands are observed between 3177 and 3225 cmꢀ1
as strong bands. In the FT-IR spectrum of ligands two bands in the
between 1617 and 1622 cmꢀ1 and 1500-1540 cmꢀ1 regions corre-
spond to the ʋ(C]N) stretching while in the complexes these bands
shifted to lower wavelengths (1583, 1586 and 1611 cmꢀ1, respec-
tively). This behavior, observed in other cases, indicated that the
sulfonamide is involved in the coordination [7,44]. On the other
hand, the free ligands presented band at between 1248 and
1253 cmꢀ1 assigned to ʋ (CeO) while in the complexes these bands
shifted to higher wavenumbers (1270, 1257 and 1251 cmꢀ1
,
respectively) in accordance with the coordination through this
group. This is confirmed by the appearance of the new bands at
548-574 cmꢀ1 and 441-466 cmꢀ1 due to ʋ (M ꢀ O) and ʋ (M ꢀ N)
stretching modes in the Pd(II) complexes respectively. The low-
frequency skeletal vibrations due to ʋ (M ꢀ O) and ʋ (M ꢀ N)
Table 2
FT- IR main bands (in cmꢀ1) of sulfonylhydrazones and their Pd(II) complexes.
Ligands/complexes
n
(C]N)
n(CO)
n(NH)/
d
(NH)
nas (SO2)/
ns (SO2)
n(CH)Ar
Afpsh
Pd(afpsh)2
5-Clafpsh
Pd(5-Clafpsh)2
3,5tbsalpsh
Pd(3,5tbsalpsh)2
1622 (m)
1583 (m)
1617 (m)
1586 (m)
1622 (m)
1611 (m)
1253 (s)
1270(s)
1251(s)
1257(s)
1248(s)
1251(s)
3218 (s)/709 (m)
3177 (s)/713(m)
3216 (s)/760 (m)
3130 (s)/743 (m)
3225 (s)/710 (m)
3219 (s)/718 (m)
1330 (s)/1166 (s)
1324 (s)/1158 (m)
1343 (s)/1160 (s)
1318 (s)/1161 (s)
1311 (s)/1150 (s)
1327 (s)/1158 (s)
3052 (w) 3024 (w)
3033 (w) 3056 (w)
3048 (w) 2972 (w)
3051 (m) 2977 (w)
3006 (w) 3041 (w)
3215 (m) 3419 (w)
s ¼ strong, m ¼ medium, w ¼ weak.
Table 3
The mass spectral data of sulfonyl hydrazones and their Pd(II) complexes.
Compounds
Relative intensities of the major ions (m/z, %) and assignment
afpsh
[MþH]þ ¼ 257.2 (100%). Me(C3H7SO2)eC8H6N) ¼ 150.0 (47%).
[M]þ ¼ 290.78 (100%). M ꢀ (C3H8SO2NN-C6H5) ¼ 154.0 (53%).
[MþH]þ ¼ 355.2 (100%). M ꢀ (C3H8S)eC8H6N) ¼ 279.0 (22.4%).
[M þ Na þ CH3CN]þ(680.1,%33.94), [MþNa]þ(641.1,%100),
Clafpsh
tbsalpsh
Pd(afpsh)2
[M-2(CH3)eCH2eCH2eCH3]þ(540.4,%17,74), [M-L-H]þ(359.5, %21,10) [M-2(CH3)e
(CH2eCH2eCH3)e(SO2eCH2eCH2eCH3)]þ (437.5, %13.94),
Pd(Clafpsh)2
Pd(tbsalpsh)2
[M þ NH4]þ(704.0230,%18.87), [M-(SO2eC3H7)eCl]þ(543.1473,%14.54),
[L þ Pdþ3H] þ(391.28.41, %9.04), [L þ PdeC3H7]þ(355.2057,%64.85),
[Le(CH3)eCl] þ(239.2256, %30.90), [L-2(CH3)eCl]þ(224.0094, %5,5)
[MeC3H7e2(C(CH3)3)]þ(654, %19,85), [M ꢀ C3H7eC(CH3)3)]þ(710,%5,03),
[M-C(CH3)3]þ (753, %4.85), [L]þ(355, %100), [L- C(CH3)3eC2H5]þ(267, %14.91),
[L-C2H5]þ (324, %9.78), [L þ PdeC3H7]þ (416, %14,83).

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N. Ozbek et al. / Journal of Molecular Structure 1196 (2019) 707e719
stretching provided direct evidence for Pd(II) complexations. This
behavior agrees with data in the literature [45]. In the spectra of
ligands vibrational bands observed 1311-1343 cmꢀ1 and 1150-
1166 cmꢀ1 are assigned to asymmetric and symmetric SO2
stretching modes, respectively. No shifting of asymmetric and
symmetric SO2 modes in the complexes is attributed to not
participating in coordination. This behavior is observed in other
compounds [46].
3.2.2. Mass spectra
The mass spectrum of the Sulfonamide-derived hydrazones and
Pd(II) complexes is in good agreement with the proposed molecular
structure. LCeMS data of aromatic sulfonyl hydrazones and Pd(II)
complexes are summarized in Table 3. Mass spectra of afpsh gives
the molecular ion [MþH]þ peak at m/z (intensity %) ¼ 257.2 (100%).
By the removal of propane sulfonyl grup (C3H7SO2), phenyl amide
group is observed at 150.0 (47%). Pd(afpsh)2 gives molecular ion,
Fig. 4. The experimental 1H NMR spectra of the sulfonylhydrazones.

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713
[Pd(afpsh)2 þ Na]þ at (641.1, 100%). Pd(afpsh)2 gives the following
fragmentation peaks: 540.4 (17.74%) which occurs by losing of two
tert-butyl, 359.5 (21.10%) which occurs by losing of afpsh.
5-Clafpsh gives the molecular ion [M]þ peak at 290.78 (100%). By
the removal of propane sulfonyl hydrazine (C3H8SO2NN), phenyl
group is observed at 154.0 (53%). Pd(5-Clafpsh)2 gives molecular
ion, [Pd(5-Clafpsh)2þNH4]þ at 704.02 (18.87,%). The other fragment
with separation of SO2eC3H7eCl group is observed at 543.15
(14.54%)
observed in all complexes are assigned to
p
/
p
*transitions of the
azomethine (C]N). The magnetic moments of complexes (as B.M)
were measured at room temperature. From magnetic measure-
ments, all complexes are founded to be diamagnetic which sup-
ports the square planer geometry [12,47].
3.3. Theoretical calculations
3.3.1. Experimental and theoretical 1H and 13C NMR spectra of
afpsh, 5-Clafpsh and 3,5tbsalpsh
3,5-tbsalpsh gives the molecular ion [MþH]þ peak at 355.2
(100%). By the removal of propane sulfonyl (C3H8S), phenyl hy-
drazine group is observed at 279.0 (22.4%). Pd(3,5tbsalpsh)2 gives
the following fragmentation peaks: 654.0 (19.85%) which occurs by
losing propyl and two tert-butyl groups, 355.2 (100%) belongs to
3,5-tbsalpsh.
Experimental 1H NMR and 13C NMR spectra of afpsh, 5-Clafpsh
and 3,5tbsalpsh were measured and interpreted in DMSO‑d6 sol-
vent. In order to facilitate the interpretation of the NMR spectra,
quantum-chemical calculations were performed using B3LYP/6-
311Gþþ(d, p) basis set of the compounds in DMSO phase. For the
B3LYP/6- 311Gþþ(d, p) method, the chemical shift value tetrame-
3.2.3. Electronic spectra and magnetic behavior
thylsilane
d
(TMS)
d
13C ¼ 175.7e0.963
s
13C
ppm
and
The complexes Pd(afpsh)2, Pd(5-Clafpsh)2 and Pd(3,5tbsalpsh)2 in
DMSO solution showed two bands characteristic of square-planar
geometry in the 14658-14879 cmꢀ1 and 21104-22886 cmꢀ1 region
assigned to 1A1g/1A2g and 1A1g/1B1g, respectively. The two bands
1H ¼ 31.0e0.970
s
1H ppm was obtained [42].
The chemical shift values of the compounds are summarized in
Table 4. In the 1H NMR spectra of afpsh (Fig. 4), H1, H2 and H3
protons were observed as triplets at 1.02 ppm, 3.19 ppm and
Fig. 5. Plot of the calculated vs. the experimental 1H NMR chemical shifts
d(ppm) for the sulfonylhydrazones.

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N. Ozbek et al. / Journal of Molecular Structure 1196 (2019) 707e719
multiplet at 1.75 ppm and calculated values were 0.81 ppm,
0.97 ppm and 3.2 ppm, respectively. Aromatic protons were moni-
tored as doublets at experimentally between 6.8 ppm and 7.3 ppm
region and computed were 6.1 ppm and 6.6 ppm, respectively.
Experimental and Calculated eNH proton was monitored as singlet
at 10.61 ppm and 10.37 ppm. A signal belong to phenolic OeH
1.0211 for optimization of all sulfonylhydrazones at the B3LYP/
6e311þþG(d,p) method.
In 13C NMR spectra of afpsh; C1, C2 and C3 carbon signals are
assigned at 11.91 ppm, 14.42 ppm and 53.39 ppm (calculated
11.82 ppm, 12.4 ppm and 57.3 ppm) respectively. In 13C NMR
spectra of 5-Clafpsh; C1, C2 and C3 carbon signals are assigned at
12.85 ppm, 13.35 ppm and 53.45 ppm (calculated 12.24 ppm,
13.31 ppm and 56.27 ppm) respectively. Aromatic carbons of 5-
Clafpsh were observed between 119.87 ppm and 131.52 ppm re-
gion. In 13C NMR spectra of 3,5tbsalpsh; C1, C2 and C3 carbon signals
are assigned at 12.88 ppm, 17.10 ppm and 53.04 ppm (calculated
12.76 ppm, 16.54 ppm and 55.29 ppm) respectively. Aromatic car-
bons of 3,5tbsalpsh were observed between 121.39 ppm and
138.92 ppm region, -CH]N- carbon was monitored at 155.15
(experimental) and 149.32 ppm (theoretical). As seen in Fig. 6, In-
clusion of the GIAO model results R2 values of 0.9948, 0.9907 and
0.9934 and slops of 0.9965, 1.0136, 0.9993 for optimization of all
sulfonylhydrazones at the B3LYP/6e311þþG(d,p) method. These
values are very satisfactory at B3LYP/6e311þþG(d,p), in general,
R2 > 0.990 and slopes which deviate from the ideal values of þ1 by
no more than 0.05 are indicative of a well performing method.
According to results, 1H and 13C NMR chemical shift values show
good agreement with experimental ones in Figs. 5 and 6.
proton was observed at
d
¼ 11.71 ppm and calculated at
11.27 ppm, respectively. In the 1H NMR spectra of 5-Clafpsh (Fig. 4),
H1, H2 and H3 protons were observed as triplets at 1.07 ppm,
1.90 ppm and multiplet at 3.24 ppm and calculated values were
0.98 ppm, 1.74 ppm and 3.41 ppm, respectively. Aromatic protons
were monitored as doublets at experimentally between 6.92 ppm
and 7.39 ppm region and computed were 6.74 ppm and 7.44 ppm,
respectively. A signal belong to phenolic OeH proton was observed
at
d
¼ 11.45 ppm and calculated at 10.85 ppm, respectively. In the
1H NMR spectra of 3,5tbsalpsh (Fig. 4), H1, H2 and H3 protons were
observed as triplets at 1.10 ppm, 1.91 ppm and multiplet at
3.24 ppm and calculated values were 0.92 ppm, 1.74 ppm and
3.41 ppm, respectively. Aromatic protons were monitored as singlet
at experimentally between 7.03 ppm and 7.41 ppm region and
computed were 7.23 ppm and 7.46 ppm, respectively. Experimental
and Calculated eNH proton was monitored as singlet at 10.47 ppm
and 10.17 ppm. As seen in Fig. 5, Inclusion of the GIAO model results
R2 values of 0.9927, 0.9975 and 0.9794 and slops of 0.9875, 0.9705,
Fig. 6. Plot of the calculated vs. the experimental 13 C- NMR chemical shifts
d(ppm) for the sulfonylhydrazones.

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715
Fig. 7. Molecular electrostatic potential of afpsh, 5-Clafpsh and 3,5tbsalpsh simulated at B3LYP/6e311þþG(d,p).
3.3.2. Molecular electrostatic potential (MEP)
more reactive site for both electrophilic and nucleophilic attack
[11,48].
The MEP (Molecular electrostatic potential) was related to the
electronic density which is a very useful descriptor for determining
site for electrophilic attack and nucleophilic reactions. The MEP of
the title compounds was optimized geometry using B3LYP method
6e311þþG(d,p) was calculated. In Fig. 7, the negative (red) regions
of the MEP are related to electrophilic reactivity and positive (blue)
regions to nucleophilic reactivity.
As it was seen from Fig. 7, the negative region was distributed on
the vicinity of oxygen of SO2 and the positive regions were localized
on nitrogen, hydrogen of NeH group and OeH group, respectively.
Therefore, it would be predicted that the oxygen of SO2 group and
nitrogen and hydrogen of amide group and hydroxide group will be
3.3.3. Frontier molecular orbital analysis
The Frontier molecular orbitals play an important role in the
electric and optical properties, as well as chemical reactions [49].
The highest occupied molecular orbital (HOMO) energies, the
lowest unoccupied molecular orbital (LUMO) energies for ligand
and three Pd(II) complexes were calculated with B3LYP in 6-
311G(d,p) basis set. The results are given in Table 5 and Fig. 8. Ac-
cording to the Koopmans theorem, the energy of the HOMO is
related to the ionization potential, while the energy of LUMO is
related to the electron affinity [50]. HOMO-1 and LUMOþ1,
Table 5
Calculated energies, ionization potential, electron affinity, chemical hardness, softness. Electronegativity, electrophilicity index and dipole moment for sulfonylhydrazones and
their Pd(II) complexes.
TD-DFT/6-311Gþþ(d.p)
afpsh
5-Clafpsh
3,5tbsalpsh
Pd(afpsh)2
Pd(5-Clafpsh)2
Pd(3,5tbsalpsh)2
Etotal(Hartree)
HOMO (eV)
ELUMO (eV)
EHOMO eLUMO gap (eV)
ꢀ1162.32
ꢀ8.4459
ꢀ5.3106
ꢀ3.1353
ꢀ8.5192
ꢀ4.2565
4.2627
ꢀ1621.94
ꢀ8.2922
ꢀ4.9723
ꢀ3.3199
ꢀ8.5192
ꢀ4.2564
4.2628
ꢀ1476.91
ꢀ8.7926
ꢀ5.1005
ꢀ3.6921
ꢀ9.4332
ꢀ4.7786
4.6546
ꢀ2302.06
ꢀ4.5974
ꢀ4.5571
ꢀ0.0403
ꢀ4.7865
ꢀ4.5353
0.2512
ꢀ1701.31
ꢀ4.5065
ꢀ4.3590
ꢀ0.1475
ꢀ4.5416
ꢀ4.0777
0.4939
ꢀ1511.45
ꢀ5.6521
ꢀ5.4122
ꢀ0.2399
ꢀ5.7201
ꢀ5.1514
0.5687
E
D
E
E
D
HOMO -1(eV)
LUMO þ1(eV)
EHOMO -1 eLUMOþ1 gap (eV)
Ionization potential I.P (eV)
8.4459
8.2922
8.7926
4.5974
4.5065
5.6521
Electron affinivity E.A (eV)
5.3106
4.9723
5.1005
4.5571
4.3590
5.4122
Electronegativity
c
(eV)
(eV)
6.8783
0.7838
0.6379
30.1858
6.9935
6.6323
0.8299
0.6025
26.5016
6.9556
6.9466
0.923
0.5417
26.1404
3.3130
4.5773
4.4327
0.0369
13.5501
266.2443
5.7198
5.5321
0.0600
33.333
255.0344
4.7014
Chemical hardness
h
0.01005
49.7513
1047.58
6.1358
Softness (s) (eV)¡1
Electrophilicity index (
Dipole moment (D)
j)
m

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Fig. 8. Plots of the frontier orbitals of the sulfonylhydrazones.

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N. Ozbek et al. / Journal of Molecular Structure 1196 (2019) 707e719
717
Fig. 9. Measured inhibition zone diameter (mm) of the sulfonylhydrazones, (PdII) complexes and antibiotics by disc diffusion method.
represents one enery state below and above these levels, respec-
tively. The energy gap between HOMO and LUMO is related to the
biological activity of the compounds [12,28]. The calculated en-
ergies of the HOMO levels for ligands, afpsh, 5-Clafpsh and
3,5tbsalpsh, show that 5-Clafpsh has a higher energy of the HOMO
(ꢀ8.2922 eV) than that of afpsh (ꢀ8.4459 eV) and 3,5tbsalpsh
(ꢀ8.7926 eV). The calculated energy of the LUMO levels for ligands
shows that afpsh has a lower of the LUMO (ꢀ5.3106 eV). Chemical
Pseudomonas aeruginosa, Klebsiella pneumonia) of bacterial strains
by the disc diffusion and micro dilution methods. The antibacterial
results were given in Fig. 9 by disc diffusion and Table 6 micro
dilution methods. The results were compared with those of the
standard drug sulfioxazole (Fig. 10).
The results (Fig. 9) show that Pd(3,5tbsalpsh)2 and Pd(afpsh)2
have exhibited the strong inhibition effect against most of test
bacteria whereas afpsh and 3,5tbsalpsh have weaker activity. All
complexes show the highest activities against P.aeruginosa which is
the mostly effected by Pd (3,5tbsalpsh)2 having the diameter zone of
13 mm [28].
Percentage of inhibition for the compounds showed in Fig. 10
that is expressed as excellent activity (120e200% inhibition),
good activity (90e100% inhibition), moderate activity (75e85%
inhibition), significant activity (50e60%inhibition), negligible ac-
tivity (20e30% inhibition) and no activity [43]. As seen in Fig. 10,
the ligand 3,5tbsalpsh (144,4%) and Pd(3,5tbsalpsh)2 (144.4%),
Pd(afpsh)2 (133.3%), Pd (5-Clafpsh)2 (133.3%) complexes show
excellent activity against Gram-negative bacteria P.aeruginosa. Also,
the compounds exhibit moderate or significant activity against the
other tested bacteria (Sulfisoxazole is accepted 100% inhibition).
The minimum inhibitory concentration (MIC) was determined
hardness,
h, Softness, s, are important properties to measure the
molecular stability and reactivity. The calculations indicate that
afpsh (0.6379 eV) is softer than 5-Clafpsh (0.6025 eV) and
3,5tbsalpsh (0.5417 eV), respectively. As shown in Fig. 8 and Table 5,
the difference between HOMO and LUMO energy levels of the
complexes are 3.2076, 0.1475, 0.0403 eV for Pd(afpsh)2, Pd (5-
Clafpsh)2 and Pd(3,5tbsalpsh)2, respectively. The calculated HOMO-
LUMO energy gap
(DE) of the ligands (3.1353, 3.3199 and
3.6921 eV) are lower than that of the palladium (II) complexes
(3.2076, 0.1475, 0.0403 eV). The dipole moment is important
quantity which reflects the ability of interaction of the molecules
with the surrounding environment. The dipole moment of
Pd(3,5tbsalpsh)2 complex (6.1358 D) is higher than that of
3,5tbsalpsh (3.3130 D).
for test compounds as well as reference standard in terms of mg/mL
and the antimicrobial activity data is summarized in Table 6. Ac-
cording to the MIC's results shown in Table 6, the compounds
possess a broad spectrum of activity against the tested bacteria at
3.4. Antibacterial activity results
the concentrations of 93.75e750 m
g mLꢀ1. Among the complexes,
Sulfonylhydrazones and Pd(II) complexes were investigated for
their antibacterial activities against three Gram-positive species
(Staphylococcus epidermidis, Staphylococcus aureus Enterococcus
faecalis) and three Gram-negative species (Eschericha coli,
the Pd(afpsh)2 complex has exhibited excellent activity against
P.aeruginosa strain (MIC 0,304 mM) and its activity is comparable to
Table 6
The MICs of antibacterial activity of the sulfonylhydrazones and their Pd(II) complexes.
Compounds
MIC
mg/mL (mM)
Gram- negative
Gram-positive
E coli ATCC 25922 P.aeruginosa ATCC 27853 K.pneumoniae ATCC 70063 S. aureus ATCC 25923 E.faecalis ATCC 23212 S. epidermidis ATCC 34384
afpsh
375 (1,46)
187,5 (0,304)
375 (1,29)
375 (0,547)
750 (2,11)
750 (2,92)
93.75 (0.152)
750 (2,58)
375 (0,547)
750 (2,11)
375 (0,461)
375 (1.403)
375 (1,46)
187,5 (0,304)
375 (1,29)
187,5 (0,273)
750 (2,11)
375 (0,461)
23.4 (0.088)
375 (1,46)
187,5 (0,304)
375 (1,29)
187,5 (0,273)
750 (2,11)
375 (0,461)
23.4 (0.088)
375 (1,46)
187,5 (0,304)
375 (1,29)
187,5 (0,273)
750 (2,11)
187,5 (0,231)
93.75 (0.35)
750 (2,92)
187,5 (0,304)
375 (1,29)
375 (0,547)
>1500 >(4,22)
375 (0,461)
93.75 (0.35)
Pd(afpsh)2
5-Clafpsh
Pd(5-Clafpsh)2
3,5tbsalpsh
Pd(3,5tbsalpsh)2 375 (0,461)
Sulfisoxazole 23.4 (0.088)

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N. Ozbek et al. / Journal of Molecular Structure 1196 (2019) 707e719
Fig. 10. Percentage of inhibition of the sulfonylhydrazones, (PdII) complexes.
Sulfisoxazole against E.faecalis strain (MIC 0,35 mM). Pd(II) com-
plexes are better antibacterial agents than sulfonylhydrazones as
expected [51].
Acknowledgement
The authors would like to thank Gazi University BAP (GrantNo:
05/2019-01) for the financial support of this project.
Appendix A. Supplementary data
Crystallographic data that were deposited in CSD under CCDC-
1907542 registration number contain the supplementary crystal-
lographic data for this structure (afpsh). These data can be obtained
free of charge from the Cambridge Crystallographic Data Centre
(CCDC) via www.ccdc.cam.ac.uk/data_request/cif and are available
free of charge upon request to CCDC, 12 Union Road, Cambridge, UK
(fax: þ441223 336033, e-mail: deposit@ccdc.cam.ac.uk).
4. Conclusion
The experimental and theoretical spectroscopic and electronic
properties of three synthesized sulfonamide derivatives, 2-
Hydroxyacetophenoneprophanesulfonylhydrazone (afpsh), 5-
chlorine-2-hydroxyaceto phenoneprophanesulfonylhydrazone (5-
Clafpsh),
and
3,5-Di-tert-butyl-2-
(3,5tbsalpsh)
hydroxybenzaldehydeprophanesulfonylhydrazone
were investigated by 1H NMR, 13C NMR, FT-IR, Mass spectroscopies
and DFT quantum chemical methods. The crystal structure was
determined of afpsh by X-ray crystallography. The related palla-
dium (II) complexes of these sulfonamides were obtained and
characterized by FT-IR, Mass spectra, elemental analysis and mag-
References
[1] G. Domagk, Ein Beitrag zur Chemotherapie der bakteriellen Infektionen,
Deut.Med.Wochenschr. 61 (1935) 250e253.
[2] M. Danish, A. Bibi, K. Gilani, M.A. Raza, M. Ashfaq, M.N. Arshad, A.M. Asiri,
K. Ayub, Antiradical, antimicrobial and enzyme inhibition evaluation of sul-
fonamide derived esters; synthesis, X-Ray analysis and DFT studies, J. Mol.
Struct. 1175 (2019) 379e388.
netic susceptibility measurements. The theoretical 1H NMR and 13
C
NMR spectra were compared with the experimental data. Indeed,
the calculated chemical shifts were used in the assignment of the
studied molecules. Molecular quantities such as ionization poten-
tial, electron affinity, electronegativity and chemical hardness,
softness, electrophilicity index and dipole moment were calculated
and used to predict of the molecules. The computed electronic
properties such HOMO, LUMO and HOMO-LUMO energy gaps and
molecular electrostatic potential maps predict significant substit-
uent effects of ring activating eNH and eOH groups. The presence
of eNH and eOH groups causes a blue shift in the molecular
electrostatic potential and decrease in the HOMO-LUMO energy
gap in Pd(II) complexes. The antibacterial results showed the
palladium (II) complexes to more antibacterial than the sulfo-
nylhydrazone ligands which was as a result of coordination of
palladium (II) to the ligands.
[3] T. Tanaka, N. Yajima, T. Kiyoshi, Y. Miura, S. Iwama, N-alkyl-[1,10-biphenyl]-2-
sulfonamide derivatives as novel broad spectrum anti-epileptic drugs with
efficacy equivalent to that of sodium valproate, Bioorg. Med. Chem. Lett 27
(2017) 4118e4121.
[4] A.A.M. Abdel-Aziz, A. Angeli, A.S. El-Azab, M.E.A. Hammouda, M.A. El-Sher-
beny, C.T. Supuran, Synthesis and anti-inflammatory activity of sulfonamides
and carboxylates incorporating trimellitimides: dual cyclooxygenase/carbonic
anhydrase inhibitory actions, Bioorg. Chem. 84 (2019) 260e268.
€
ꢀ
[5] N. Ozbek, H. Katırcıoglu, N. Karacan, T. Baykal, Synthesis, characterization and
antimicrobial activity of new aliphatic sulfonamide, Bioorg. Med. Chem. 15
(2007) 5105e5109.
[6] A.C. Hangan, G. Borodi, R.L. Stan, E. Pall, M. Cenariu, L.S. Oprean, B. Sevastre,
Synthesis, crystal structure, DNA cleavage and antitumor activity of two
copper(II) complexes with N-sulfonamide ligand, Inorg. Chim. Acta 482 (2018)
884e893.
€
[7] S. Alyar, C. S¸ en, H. Alyar, S¸ . Adem, A. Kalkancı, U.O. Ozdemir, Synthesis,
characterization, antimicrobial activity, carbonic anhydrase enzyme inhibitor
effects, and computational studies on new Schiff bases of Sulfa drugs and their
Pd(II), Cu(II) complexes, J. Mol. Struct. 1171 (2018) 214e222.
[8] A.E. Boyd, Sulfonylurea receptors, ion channels, and fruit flies, 3rd Diabetes 37
(1988) 847e850.
[9] C.T. Supuran, A. Scozzafava, A. Mastrolorenzo, Bacterial proteases: current
therapeutic use and future prospects for the development of new antibiotics,
Expert Opin. Ther. Pat. 11 (2001) 221e259.
[10] N. Ghareb, N.M. El-Sayed, R. Abdelhameed, K. Yamada, M.S. Elgawish, Toward
a treatment of diabesity: rational design, synthesis and biological evaluation
of benzene-sulfonamide derivatives as a new class of PTP-1B inhibitors, Bio-
org. Chem. 86 (2019) 322e338.
As a result, if the MIC values of all compounds are examined,
Pd(afpsh)2 complex shows remarkable activity on six human bac-
teria than the other compounds. This is probably due to the fact that
the Pd complex has lower HOMOe LUMO energy gap
(
D
E ¼ ꢀ0.0403). The lower LUMOe HOMO energy gap (
DE) affects
the noncovalent binding affinities of the compounds to biological
molecules as receptor [52].

€
N. Ozbek et al. / Journal of Molecular Structure 1196 (2019) 707e719
719
[11] P. Shafieyoon, E. Mehdipour, Y.S. Mary, Synthesis, characterization and bio-
logical investigation of glycinebased sulfonamide derivative and its complex:
vibration assignment, HOMO e LUMO analysis, MEP and molecular docking,
J. Mol. Struct. 1181 (2019) 244e252.
[12] A. Bouchoucha, S. Zaater, S. Bouacida, H. Merazig, S. Djabba, Synthesis and
Characterization of new complexes of nickel (II), palladium (II) and plati-
num(II) with derived sulfonamide ligand: structure, DFT study, antibacterial
and cytotoxicity activities, J. Mol. Struct. 1161 (2018) 345e355.
[13] C.M. Sharaby, M.F. Amine, A.A. Hamed, Synthesis, structure characterization
and biological activity of selected metal complexes of sulfonamide Schiff base
as a primary ligand and some mixed ligand complexes with glycine as a
secondary ligand, J. Mol. Struct. 1134 (2017) 208e216.
[14] R.B. Hoff, G. Rübensam, L. Jank, F. Barreto, M.C.R. Peralba, T.M. Pizzolato,
M.S. Diaz eCruz, D. Barcelo, Analytical quality assurance in veterinary drug
residue analysis methods: matrix effects determination and monitoring for
sulfonamides analysis, Talanta 132 (2015) 443e450.
[32] G.M. Sheldrick, Acta Crystallogr. A64 (2008) 112.
[33] A.D. Becke, Density-functional thermochemistry. III. The role of exact ex-
change, J. Chem. Phys. 98 (1998) 5648e5652.
[34] C. Lee, W. Yang, R.G. Parr, Development of the Colle-Salvetti correlation-en-
ergy formula into a functional of the electron density, Phys. Rev. B Condens.
Matter 37 (1988) 785e789.
[35] 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. Nor-mand, 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,
J.J. Dannenberg, S. Da rich, A.D. Daniels, O. Farkas, J.B. Foresman, J.V. Ortiz,
J. Cioslowski, D.J. Fox, Gaussian 09, Revision A.02, Gaussian, Inc., Wallingford,
CT, 2009.
[36] F. Blanco, I. Alkorta, J. Elguero, Spectral assignments and reference data, Magn.
Reson. Chem. 45 (2007) 797e800, https://doi.org/10.1002/mrc.2053.
[37] A.M.S. Silva, R.M.S. Sousa, M.L. Jimeno, F. Blanco, I. Alkorta, J. Elguero,
Experimental measurements and theoretical calculations of the chemical
shifts and coupling constants of three azines (benzalazine, acetophenoneazine
and cinnamaldazine), Magn. Reson. Chem. 46 (2008) 859e864, https://
doi.org/10.1002/mrc.2272.
[15] A. Ashraf, W.A. Siddiqui, J. Akbar, G. Mustafa, H. Krautscheid, N. Ullah, B. Mirza,
M. Hanif, C.G. Hartinger, Metal complexes of benzimidazole derived sulfon-
amide: synthesis, molecular structures and antimicrobial activity, Inorg. Chim.
Acta 443 (2016) 179e185.
€
€
_
€
€
[16] Ü.O. Ozdemir, E. Aktan, F. Ilbiz, A.B. Gündüzalp, N. Ozbek, M. Sarı, O. Çelik,
S. Saydam, Characterization, antibacterial, anticarbonic anhydrase II isoen-
zyme, anticancer, electrochemical and computational studies of sulfonic acid
hydrazide derivative and its Cu(II) complex, Inorg. Chim. Acta 423 (2014)
194e203.
€
_
[17] S. Alyar, N. Ozbek, N.O. Iskeleli, N. Karacan, Synthesis, characterization, and
antimicrobial activity of copper(II) complexes with N,N0-propanediyl-bis-
benzenesulfonamide and N,N’-ethanediyl-bis-2- methylbenzenesulfonamide,
Med. Chem. Res. 22 (2013) 2051e2060.
[18] U.O. Ozdemir, N. Ozbek, Z.K. Genc, F. Ilbiz, A.B. Gündüzalp, New bioactive
silver(I) complexes: synthesis, characterization, anticancer, antibacterial and
anticarbonic anhydrase II activities, J. Mol. Struct. 1138 (2017) 55e63.
[19] M. Mondelli, F. Pavan, P.C. de Souza, C.Q. Leite, J. Ellena, O.R. Nascimento,
G. Facchin, M.H. Torre, Study of a series of cobalt(II) sulfonamide complexes:
synthesis, spectroscopic characterization, and microbiological evaluation
against M. tuberculosis. Crystal structure of [Co(sulfamethoxazole)2(H2O)2]
_H2O, J. Mol. Struct. 1036 (2013) 180e187.
[38] J. Toasi, B. Mennucci, R. Cammi, Quantum mechanical continuum salvation
models, Chem. Rev. 105 (2005) 2999e3093.
€
_
ꢀ
[39] N. Ozbek, S. Mamas¸ , T. Erdogdu, S. Alyar, K. Kaya, N. Karacan, Synthesis,
characterization, DFT studies of piperazine derivatives and its Ni(II), Cu(II)
complexes as antimicrobial agents and glutathione reductase inhibitors,
J. Mol. Struct. 1171 (2018) 834e842.
[40] A.B. Gündüzalp, N. Ozbek, N. Karacan, Synthesis, characterization, and anti-
bacterial activity of the ligands including thiophene/furan ring systems and
their Cu(II), Zn(II) complexes, Med. Chem. Res. 21 (2012) 3435e3444.
€
[41] N. Ozbek, S. Alyar, H. Alyar, E. Sahin, N. Karacan, Synthesis, characterization
[20] G.M. Fisher, S. Bua, S.D. Prete, M.A.J. Arnold, C. Capasso, C.T. Supuran,
K.T. Andrews, S.A. Poulsen, Investigating the antiplasmodial activity of pri-
mary sulfonamide compounds identified in open source malaria data, Int. J.
Parasitol.: Drugs and Drug Resis. 7 (2017) 61e70.
[21] Z.H. Chohan, C.T. Supuran, Structure and biological properties of first row d-
transition metal complexes with N-substituted sulfonamides, J. Enzym. Inhib.
Med. Chem. 23 (2008) 240e251.
[22] C.A. Otter, M. Couchman, J.C. Jeffery, K.L.V. Mann, E. Psillakis, M.D. Ward,
Complexes of a new bidentate chelating pyridylkulfonamide ligand with
copper( II), cobalt( II) and palladium( II) : crystal structures and spectroscopic
properties, Inorg. Chim. Acta 278 (1998) 178e184.
and anti-microbial evaluation of Cu(II), Ni(II), Pt(II) and Pd(II) sulfonylhy-
drazone complexes; 2D-QSAR analysis of Ni(II) complexes of sulfonylhy-
drazone derivativesSpectrochim, Acta Mol. Biomol. Spectrosc 108 (2013)
123e132.
€
[42] H. Alyar, S. Alyar, A. Ünal, N. Ozbek, E. Sahin, N. Karacan, Synthesis, charac-
terization and antimicrobial activity of m-toluenesulfonamide, N,N’-1,2-
ethanediylbis (mtsen) and [Cu(II)(phenanthroline)2]mtsen complex, J. Mol.
Struct. 1028 (2012) 116e125.
[43] U.O. Ozdemir, N. Akkaya, N. Ozbek, New Ni(II), Pd(II), Pt(II) complexes with
aromatic methanesulfonylhydrazone based ligands. Synthesis, spectroscopic
characterization and in vitro antibacterial evaluation, Inorg. Chim. Acta 400
(2013) 13e19.
[44] G. Ayyannan, M. Mohanraj, G. Raja, N. Bhuvanesh, R. Nandhakumar,
C. Jayabalakrishnan, Design, synthesis, structure and biological evaluation of
new palladium(II) hydrazone complexes, Inorg. Chim. Acta 453 (2016)
562e573.
[23] S. Alyar, S¸ . Adem, Synthesis, characterization, antimicrobial activity and car-
bonic anhydrase enzyme inhibitor effects of salicilaldehyde-N-methyl p-tol-
uenesulfonylhydrazone and its Palladium(II), Cobalt(II) complexes,
Spectrochim. Acta Mol. Biomol. Spectrosc. 131 (2014) 294e302.
€
[24] S. Alyar, N. Ozbek, K. Kuzukıran, N. Karacan, Quantitative structureeactivity
relationships studies for prediction of antimicrobial activity of synthesized
disulfonamide derivatives, Med. Chem. Res. 20 (2011) 175e183.
[25] U. Ozmen Ozdemir, A. Altuntas¸ , A. Balaban Gündüzalp, F. Arslan, F. Hamurcu,
New Aromatic/heteroaromatic propanesulfonylhydrazone compounds: syn-
thesis, physical properties and inhibition studies against carbonic anhydrase II
(CAII) enzyme, Spectrochim. Acta, Part A 128 (2014) 452e460.
[45] S. Sert, O.S. Sentürk, Ü. Ozdemir, N. Karacan, F. Ugur, Synthesis and charac-
terization of the products from reaction of metal carbonyls [M(CO)(6) (M¼
Cr,Mo, W), Re(CO)(5)Br, Mn(CO)(3)Cp] with salicylaldehyde meth-
anesulfonylhydrazone, J. Coord. Chem. 57 (2004) 183e188.
[46] M. Gaber, M.K. Awad, F.M. Atlam, Pd (II) complexes of bidentate chalcone
ligands: synthesis, spectral, thermal, antitumor, antioxidant, antimicrobial,
DFT and SAR studies, J. Mol. Struct. 1160 (2018) 348e359.
[47] M. Gaber, H.A. El-Ghamry, M.A. Mansour, Pd(II) and Pt(II) chalcone complexes.
Synthesis, spectral characterization, molecular modeling, biomolecular
docking, antimicrobial and antitumor activities, J. Photochem. Photobiol. A
Chem. 354 (2018) 163e174.
[26] S. Alyar, H. Alyar, U. Ozmen Ozdemir, O. Sahin, K. Kaya, N. Ozbek,
A.B. Gunduzalp, Synthesis, characterization, antibacterial activity and quan-
tum chemical studies of N’-Acetyl propane sulfonic acid hydrazide, J. Mol.
Struct. 1094 (2015) 237e245.
_
[27] U.O. Ozdemir, F. Ilbiz, A.B. Gunduzalp, N. Ozbek, Z.K. Genc, F. Hamurcu,
S. Tekin, Alkyl sulfonic acide hydrazides: synthesis, characterization, compu-
tational studies and anticancer, antibacterial, anticarbonic anhydrase II (hCA
II) activities, J. Mol. Struct. 1100 (2015) 464e474.
[48] G. Velraj, S. Soundharam, Structure, vibrational, electronic, NBO and NMR
analyses of 4-amino-N-[2-pyridinyl] benzene sulfonamide (sulfapyridine) by
experimental and theoretical approach, J. Mol. Struct. 1074 (2014) 475e486.
[49] I. Fleming, Frontier Orbitals and Organic Chemical Reactions, Wiley, London,
1976.
[50] T. Koopmans, Über die Zuordnung von Wellenfunktionen und Eigenwerten zu
den Einzelnen Elektronen Eines Atoms, Physica 1 (1934) 104e113.
[51] W. Al Zoubi, A.A. Salih, A. Hamdani, S.D. Ahmed, Y. Gun Ko, A new azo-Schiff
base: synthesis, characterization, biological activity and theoretical studies of
its complexes, Appl. Organomet. Chem. 32 (2018) 3895e3910.
[52] S.M. Abd El-Hamid, S.A. Sadeek, W.A. Zordok, W.H. El-Shwiniy, Synthesis,
spectroscopic studies, DFT calculations, cytotoxicity and antimicrobial activity
of some metal complexes with ofloxacin and 2,20-bipyridine, J. Mol. Struct.
1176 (2019) 422e433.
[28] N. Ozbek, S. Alyar, B.K. Memmi, A.B. Güzndüzalp, Z. Bahçeci, H. Alyar, Syn-
thesis, characterization, computational studies, antimicrobial activities and
carbonic anhydrase inhibitor effects of 2-hydroxy acetophenone-N-methyl p-
toluenesulfonylhydrazone and its Co(II), Pd(II), Pt(II) complexes, J. Mol. Struct.
1127 (2017) 437e448.
[29] U. Ozdemir, P. Güvenç, E. S¸ ahin, F. Hamurcu, Synthesis, characterization and
cobalt(II) complexes, Inorg. Chim. Acta 362 (2009) 2613e2618.
[30] U.O. Ozdemir, G. Olgun, Synthesis, characterization and antibacterial activity
of new sulfonyl hydrazone derivatives and their nickel(II) complexes, Spec-
trochim. Acta, Part A 70 (2008) 641e645.
[31] Rigaku/MSC, Inc., 9009 New Trails Drive, TheWoodlands, TX 77381.