Synthesis, characterization, structural study and antibacterial activity of the Schiff bases derived from sulfanilamides and related copper(II) complexes

Article abstract of DOI:10.1016/j.ica.2016.07.028

In the present work, a series of new Schiff base ligands from acetylacetone and salicylaldehyde with sulfonamides derivatives were synthesized and characterized by spectral and analytical techniques. The molecular structures of ligands, N-({4-[(E)-(2-hydr

Full text of DOI:10.1016/j.ica.2016.07.028

Accepted Manuscript
Synthesis, characterization, structural study and antibacterial activity of the
Schiff bases derived from sulfanilamides and related copper(II) complexes
Mehdi Salehi, Fateme Ghasemi, Maciej Kubicki, Asadollah Asadi, Mahdi
Behzad Mohammad Hadi Ghasemi, Ahmad Gholizadeh
PII:
S0020-1693(16)30406-6
http://dx.doi.org/10.1016/j.ica.2016.07.028
ICA 17163
DOI:
Reference:
Inorganica Chimica Acta
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Received Date:
Revised Date:
Accepted Date:
22 June 2016
17 July 2016
18 July 2016
Please cite this article as: M. Salehi, F. Ghasemi, M. Kubicki, A. Asadi, M.B.M. Ghasemi, A. Gholizadeh, Synthesis,
characterization, structural study and antibacterial activity of the Schiff bases derived from sulfanilamides and
related copper(II) complexes, Inorganica Chimica Acta (2016), doi: http://dx.doi.org/10.1016/j.ica.2016.07.028
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Synthesis, characterization, structural study and antibacterial
activity of the Schiff bases derived from sulfanilamides and
related copper(II) complexes
c
Mehdi Salehia,*, Fateme Ghasemia, Maciej Kubickib, Asadollah Asadi , Mahdi Behzad
Mohammad Hadi Ghasemid , Ahmad Gholizadehe
aDepartment of Chemistry, College of Science, Semnan University, Semnan, Iran
bFaculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznan, Poland
cDepartment of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran
dApplied Chemistry Research Group, Acecr-Tehran branch, P.O. Box: 13145-186, Tehran, Iran.
eSchool of Physics, Damghan University (DU), Damghan, Iran
Abstract
In the present work, a series of new Schiff base ligands from acetylacetone and
salicylaldehyde with sulfonamides derivatives were synthesized and characterized by
spectral and analytical techniques. The molecular structures of ligands,
(HL1),
N
-({4-[(E)-(2-
hydroxybenzylidene)amino]phenyl}sulfonyle)acetamide
N-({4-[(E)-(2-
hydroxybenxiliden)amino]phenyl}sulfonyle)benzamide (HL2) and 4-((4-oxopentan-
2ylidene)amino)benzenesulfonamide (HL3) were also determined by the method of X-
ray diffraction. Also, new copper(ІІ) complexes [CuLx](x = 1 for 1, x = 2 for 2, x = 3 for 3)
constructed from HLx were synthesized and characterized by FT-IR, UV-Vis spectroscopy
and XRD. The copper(II) complexes were screened for their antimicrobial activities
against the selected bacteria and compared to the free ligands, using the disc diffusion
method.
Keywords: Antibacterial activity, Sulfonamides, Crystal structures, Schiff base, Rietveld
analysis.
1

1. Introduction
Sulfonamide derived Schiff bases are potential class of compounds, which have been found
to possess a wide range of medicinal properties [1]. Schiff bases of aromatic or heterocyclic
sulfonamides have been used as anti-infectious agents [2,3] and have led to potent inhibitors
[4] of several physiologically relevant CA isozymes [5]. They are a potential class of
compounds which have been found to possess a wide range of medicinal properties [6,7].
Systems containing both azomethine and sulfanilamide groups are related to biological and
pharmaceutical class of compounds which display anticancer [8], antifungal [9], anti-
tubercular [10], diuretic [11], anti-inflammatory[1, anti-microbial [13-15] and several other
activities [16,17]. The coordination chemistry of sulphonamide imine complexes has
undergone noticeable development in recent years, due to their interesting properties. Some
drugs, like sulfamethoxazole, prevent the formation of dihydrofolic acid, a compound
synthesized by bacteria for their survival [18,19]. However, not all synthesis of these
complexes with different ligands have been reported. There exist only few works on the
structure and the applications of sulfanilamide ligands and their related complexes, so, this
facilitated the present study [20-23]. In this work, we describe the characterization and
applications, as well as the structures of new such ligands. Additionally, the related
complexes have been investigated as well. Therefore, the objectives include the synthesis of
some new sulfanilamide Schiff base ligands obtained by the condensation of ketone and
aldehyde derivations with sulfonamides derivatives, and related copper complexes (Scheme
1). The molecular structures of ligands were determined by X-ray diffraction method and
complexes by XRD. The Schiff Bases and the related copper complexes were also tested for
their antibacterial activities.
2

Scheme 1. Syntheses of the Schiff base ligands and related complexes.
2. Experimental
2.1. Reagents and measurements
1
All solvents and chemicals were used as received. H–NMR spectra were obtained on a
BRUKER AVANCE DR X400 (400 MHz) spectrometer, using DMSO solvent; FT-IR
spectra were obtained as KBr plates using a Bruker FT-IR instrument and UVVis spectra
were obtained on a Shimadzu UV-1650PC spectrophotometer. Melting point was measured
by a THERMO CIENTEFIC apparatus.
2.2. Procedure for synthesis of Schiff’s bases:
2.2.1 Synthesis of HL1
The Schiff base HL1 was synthesized with a method different from the one in the literature
[24], by refluxing sulfacetamide (1mmol, 0.214 g) and salicylaldehyde (1mmol, 0.122 g) in
3

about 15 ml of methanol for 3 h at ca.70 ºC, in the presence of 4 to 5 drops of conc. H2SO4.
The solid product was collected through filtration and finally air dried. Yield: 58%. M.P. =
215 ºC. Anal. Calcd. for C15H14N2O4S (%):C, 56.59; H, 4.43; N, 8.80. Found: C, 56.42; H,
4.25; N, 8.75. FT-IR (KBr, cm-1): ѵmax cm1 (KBr):1645 (s, C=N), 1715 (C=O), 1575, 1616
-1
(C=Caromatic), 1093, 1157 (SO2) 3340 (N-H). UV-Vis: λmax (nm) (ε.M cm-1) (DMSO-d6): 350
(40000), 320 (41000). 1H-NMR (DMSO-d6, 400MHz):6-8 (m, 8 H), 9 (s, 1H), 10 (s, 1H),
3(s, 3H), 11 (s, 1H).
2.2.2. Synthesis of HL2
HL2 was synthesized following the same procedure as described for HL1 except
sulfabenzamide was used instead of sulfacetamide. The precipitated ligand was filtered and
air dried. The purity of the ligand was checked by thin layered chromatography (TLC) and
melting point determination method. Yield: 60%. M.P. = 243˚C. Anal. Calcd. for
C20H16N2O4S (%):C, 63.14; H, 4.24; N, 7.36. Found: C, 62.52; H, 4.15; N, 7.20. FT-IR: ѵmax
cm-1 (KBr):1618 (s, C=N), 1699 (C=O), 1575, 1591 (C=Caromatic), 1064, 1164 (SO2)
-1
1
3228 (N-H). UV-Vis: λmax (nm) ( .M
cm-1) (DMSO): 364 (24000), 326 (27000). H-NMR
ε
(DMSO-d6, 400 MHz):7-8 (m, 13H), 9 (s, 1H), 12(s, 1H), 11 (s, 1H).
2.2.3. Synthesis of HL3
The Sulphonamide imine Schiff base ligand (HL3) was prepared by refluxing sulphanilamide
(1 mmol, 0.164 g) and acetyl acetone (1mmol, 0.100 g) in about 15 ml of ethanol for 3 h in
the presence of 1 to 2 drops of CH3COOH. The precipitated light yellow colored ligand was
filtered and air dried. Yield: 45%. M.P. = 210˚C. Anal. Calcd. For C11H4N2O3S (%):C, C,
51.95; H, 5.55; N, 11.02. Found: C, 51.65; H, 5.35; N, 10.95. FT-IR: ѵmax cm-1(KBr): 1595
(s, C=N), 1625 (C=O), 3128, 3224 (NH2), 1516, 1566 (C=Carom),1163, 1195 (SO2)., UV-Vis:
4

1
λmax (nm) (ε. M-1 cm-1) (DMSO-d6): 340 (91000), 330 (22000). H-NMR (DMSO-d6, 400
MHz):12.67 (s,1H), 7-8.7 (d-d, 4H), 5.5 (s, 1H), 2.8 (s, 6H), 3.3 (s, 2H).
2.3. Procedure for synthesis of complexes (1-3):
All the copper(II) complexes were synthesized by the same general procedure from the
literature [26]. The appropriate quantity of Schiff base ligand HL1 (2mmol, 0.636 g,), HL2
(2mmol, 0.76.g) and HL3 (2mmol, 0,50g) were dissolved in 20 ml methanol. These ligands
solutions were added dropwise as separation to a 10 ml methanolic solution of
Cu(OAC)2.H2O (1mmol, 0.199g). After addition, the reaction mixture was refluxed for 3 h.
The metal complexes of Schiff base ligands were separated from the reaction mixture as
amorphous solids and washed several times with MeOH, followed by drying under reduced
pressure at room temperature. The dark brown (1), light green (2) and green solid complexes
(3) were, respectively prepared in a similar manner as described. The precipitate was filtered,
washed with methanol and dried under vacuum.
Data analytics for 1: Yield: 65%. M.P. = 400 ˚C. Anal. Calcd. for C30H26CuN4O8S2, (%): C,
51.61; H, 3.75; N, 8.02. Found: C, 51.05; H, 3.15; N, 7.95. FT-IR: ѵmax cm-1 (KBr): 1587 (s,
C=N), 1608 (C=O), 3274 (N-H), 1444, 1533 (C=Carom), 1164, 1151 (SO2). (UV-Vis: λmax
(nm) (ε, M-1cm-1) (DMSO-d6): 560 (900), 340 (51000).
For 2: Yield: 45%. M.P. = 350 ˚C. Anal. Calcd. for C40H30CuN4O8S2, (%): C, 58.42; H, 3.68;
N, 7.73. Found: C, 57.95; H, 3.25; N, 7.45. FT-IR: ѵmax cm-1 (KBr): 1552 (s, C=N), 1577
(C=O), 2921 (N-H), 1427, 1525 (C=Carom), 1247, 1018 (SO2). UV-Vis λmax (nm) (ε, M-1cm1)
(DMSO-d6): 540 (800), 343 (31000).
For 3: Yield: 50%. M.P. = 360 ˚C. Anal. Calcd. for C22H26CuN4O6S2, (%): C, 46.35; H, 4.60;
N, 9.83. Found: C, 46.38; H, 4.45; N, 9.59. C22H30CuN4O6S2, M.P. = 360˚C), FT-IR: ѵmax
5

cm-1 (KBr): 1565 (s, C=N),1577 (C=O), 3124, 3210 (NH2), 1490, 1529 (C=Carom),1163,
1108 (SO2). UV-Vis: λmax (nm) (ε, M1cm-1) (DMSO-d6): 520 (850), 345 (20500).
2.4. X-ray crystallography
X-ray diffraction data were collected at 130(1) K by the ω-scan technique on a SuperNova
(Atlas detector) Agilent Technologies four-circle diffractometer, with a mirror-
monochromatized CuKα radiation (λ = 1.54178Å). The data were corrected for
Lorentzpolarization and absorption effects [27] fit of 8394 (HL1), 3801 (HL2), and 3835
(HL3) reflections of highest intensity, chosen from the whole experiment. The structures
were solved with SIR92 [28] and refined with the full-matrix least-squares procedure on F2
by SHELXL97 [29] Scattering factors incorporated in SHELXL97 were used. All non-
hydrogen atoms were refined anisotropically, methyl hydrogen atoms were placed in the
calculated positions and refined as ‘riding model’, with the corresponding isotropic
displacement parameters set at 1.5 times the Ueq value for appropriate non-hydrogen atom,
while all other hydrogen atoms were found in the difference Fourier maps and freely refined
(only NH hydrogen atoms were fixed at the geometry found in HL2). In the HL3 structure,
the methyl group was found to be disordered between two sets of positions, s.o.f.’s were
fixed at ½ (AFIX 123 [3]). Crystallographic data (excluding structure factors) for the
structural analysis has been deposited with the Cambridge Crystallographic Data Centre,
Nos. CCDC- 1430681 (HL1), CCDC- 1430682 (HL2), and CCDC- 1430683 (HL3). Copies
of this information may be obtained free of charge from: The Director, CCDC, 12 Union
Road, Cambridge, CB2 1EZ, UK. Fax: +44(1223)336-033, e-mail: deposit@ccdc.cam.ac.uk,
or www: www.ccdc.cam.ac.uk. Relevant crystal data are listed in Table 1 together with
refinement detail.
Table 1.
6

2.5. Biological studies
2.5.1. Determination of minimum inhibitory concentrations (MIC)
The MIC was determined by using a broth macro-dilution method, which applied LB broth
and final inoculums of 105 and 106 cfu/ml. A culture was diluted with a sterile physiological
saline solution (sodium chloride), with reference made to the 0.5 McFarland standards in
order to achieve an inoculum size of approximately 106 colony forming unit mL-1. Different
concentration of compounds was tested against four pathogenic representative Gram-
negative bacteria (E. faecalis; ATCC 29212 and E. coli; TCC 25922) and Gram-positive
bacteria (B. subtilis; ATCC 6633 and S. aureus; ATCC 25923). Sterile centrifuge tubes were
arranged in rows of sets for each bacterial inoculum to cover the different concentration of
complexes in duplicate. Volumes of 1 mL of each concentration of compounds were
transferred to the tubes accordingly, containing final inoculums of 105 cfu/mL test bacteria.
The contents in the tubes were mixed thoroughly and incubated at 37 °C overnight. The MIC
endpoint is the lowest concentration of compounds which produced inhibition of bacterial
growth [30].
2.5.2. Determination of minimal bactericidal concentration (MBC)
The MBC is the lowest concentration of antibiotic required to kill a particular bacterium. For
the MBC test, the 10 dilutions were run in duplicate. At the end of overnight incubation, at
37 °C, the tubes were read to determine the MBC by sampling all the macroscopically clear
tubes (1 dilution was used below the MIC for the levels to be assessed in the MBC assay)
and the first turbid tube in the series. Running dilutions above the known MIC permits the
detection of tolerance to normally bactericidal agents. In order to measure the MBC, 100 µL
volumes of all clear tubes from a dilution MIC test was spread on Mueller-Hinton agar plates
and incubated at 37 °C overnight. Mueller–Hinton Agar was employed for bacterial growth
7

and the organisms were purchased from Iranian Research Organization for Science and
Technology (IROST). Each organism was tested in duplicate on different days in order to
measure the reproducibility of the test [31].
3. Results and Discussion
3.1. Synthesis
In this study, three new sulfonamide Schiff bases were synthesized. The conformational
analysis was carried out for all synthesized Schiff base ligands. In addition, new Cu(ІІ)
complexes from these ligands were synthesized and characterized by elemental analysis, FT-
IR and UV-Vis spectroscopy.
3.2. FT-IR spectra
A comparative study of the FT-IR spectral data of the reported complexes with those of the
free ligand provided meaningful information regarding bonding sites of the ligand molecules.
All Schiff base ligands, HL1 to HL3, exhibited a broad band in the 3400 to 3570 cm−1 region,
characteristic of the OH group. The disappearance of this band in the FT-IR spectra of the
complexes (1-3) indicated the fact that the bidentate ligands were coordinated as anions. The
strong bands observed at 3128 to 3340 cm-1 region in the free ligands HL1 and HL2 were
assigned to ν(NH) vibrations. The IR spectra of the synthesized Schiff base ligands showed
the presence of C=N stretching bands at 1645 to 1595 cm-1. These bands were present in the
IR spectra of the complexes (1-3) and shifted by almost between 30 to 66cm-1 to lower wave
numbers after complexation. This shift indicated the coordination of the ligands through their
iminic nitrogen atoms. The coordination of azomethine nitrogen to metal ion reduces the
electron density of C=N, by back bonding from the Cu(II)) metal to the π* orbital of
azomethine group [32].
8

3.3. Electronic spectra
The UV-Vis absorption spectra of the ligands and complexes were recorded in DMSO at
room temperature. The bands at 350, 364 and 340 nm for HL1, HL2 and HL3, respectively,
correspond to the n to π*transition. These signals disappeared from the UV-Vis spectra of the
copper(II) complexes upon coordination [33]. This could be easily rationalized since the
nonbonding electrons are now incorporated in coordination to the metal center. The other
bands at around 320, 326 and 330 nm were assigned to the π to π* transitions of azomethine
groups for HL1, HL2 and HL3, respectively. These bands were red shifted by about 15 to 20
nm in the corresponding copper(II) complexes, indicating the coordination of C=N to the
metal ion [34]. A weak d-d transition existed at about 560, 545 and 525 nm for complexes 1,
2
2
→
2 and 3, respectively, which may be assigned to the A1g B1g transition and a square
planar geometry, similar to that suggested around the copper (II) ion with the sulphonamide
imine ligand as an N, O-donor [31].
3.4.1H-NMR spectra
1H-NMR spectra of Schiff base ligands were recorded in DMSO-d6, using TMS as an
internal standard. The signal at 3 ppm in the 1H-NMR spectra of the HL1 was as the result of
the protons of the methyl group. The singlet signal which corresponded to the imine group in
this ligand was observed at 9 ppm. Phenolic -OH groups, which were probably involved in
intramolecular hydrogen bonding were clearly indicated at 11 ppm. The amide proton was
exhibited in the spectra at 10 ppm. The remaining signals were recorded in the 6 to 8 ppm
range and resulted from the aromatic protons. The 1H-NMR spectrum of the HL2 exhibited a
singlet signal at 12 ppm which was assigned to the phenolic -OH group proton. The
compound exhibited a group of multiple signals which corresponded to the aromatic protons
at 7 to 8 ppm. Furthermore, a singlet signal was observed at 9 ppm due to azomethine group.
9

The singlet signal at 11 ppm was assigned to the amide proton. The 1H-NMR spectrum of the
Schiff base ligand HL3 exhibited multiplet signals at around 7 to 8.7 ppm which were
assigned to the aromatic protons, while 2.8 ppm signal (2s, C-H) was assigned to the methyl
group, and finally the signal at 5.5 ppm was assigned to (C-H) group protons due to keto-
enol tautomeric structures with (C=O) group. A singlet signal at 12 ppm was also
corresponded to the hydroxyl group.
3.5. X-Ray studies
Figures 1 to 3 show the perspective views of molecules HL1 to HL3, respectively; Table 2
lists some relevant geometrical data.
Fig. 1
Fig. 2
Fig. 3
Compound HL1 crystallizes with two almost identical but symmetry-independent molecules
in the asymmetric part of the unit cell (referred to as HL1A and HL1B). A comparison of both
molecules, with the central phenyl rings fitted one onto another, is shown in the supporting
material (Figure 1s).
In all three compounds, intramolecular hydrogen bonds were observed, however, the
positions of hydrogen atoms were different. In HL1 there existed O-H···N hydrogen bonds,
while in HL2 and HL3 the hydrogen atoms were located close to the nitrogen atoms, there by
forming N-H···O hydrogen bonds. An appropriate tautomeric form (keto-enol) was chosen
on the basis of the experimentally determined positions of hydrogen atoms.The locations of
hydrogen atoms were found in the difference Fourier maps (cf. Figure 4), and positions of
these atoms were freely refined. It is noteworthy at this point that the hydrogen bond in HL3,
despite apparently larger conformational freedom, was significantly longer than those in HL1
10

and HL2. The crystal architectures were mainly determined by N-H···O intermolecular
hydrogen bonds. Table 3 gives a list of the hydrogen bond data. Even though the hydrogen
bonds in HL1 and HL2 seemed identical (donor and acceptor atoms), there were observable
differences in the motifs created. In HL1, both symmetry independent molecules were lined
into homomolecular (i.e….AAA… and …BBB…) chains of hydrogen-bonded molecules
related by twofold screw axis along y-direction (Fig. 5); these chains were linked by weaker
C-H···O interactions (Figure 5).
In
HL2,
molecules
were
connected
into
centrosymmetric hydrogen-bonded dimers by similar hydrogen bonds (Figure 6), and these
dimers were further expanded into three-dimensional network by C-H···O interactions.
In HL3, two hydrogen bond donors and acceptors existed (not involved in the intramolecular
interactions), and the hydrogen bonded systems were typical for this kind of primary
sulfonamides (Figure 7).
Table 2.
Table 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
3.6. XRD Studies
Attempts to obtain single crystals for the corresponding metal complexes were unsuccessful.
Instead, attempts were made to analyze the X-ray diffraction peaks of these compounds.
Figure 8 shows the XRD patterns of the copper complexes.
Fig. 8
A comparison of the xrd patterns of the complexes revealed that only complexes 1 and 2
showed sharp peaks, therefore, complexes 1 and 2 were crystalline, while complex 3 was
amorphous. The line broadening of the diffraction peaks observed for complex 1 was more
than those for complex 2. This showed lower crystallinity of complex 1 respect to complex 2.
11

The XRD data were analyzed using Fullprof program as shown in Figure 9. Results of the
rietveld analysis using Fullprof program indicated that all the diffraction peaks of complex 1
could be quite well indexed to the monoclinic structure with space group P21/c. In addition,
these results for complex 2 showed the formation of the monoclinic structure with space
group P21/n. The derived lattice parameters of the complexes 1 and 2 are given in Table 4.
Looking at the results summarized in Table 4 and 1, we can observe that unit cell parameters
of complex 2 vary much more than complex 1 with respect to their free ligands.
Fig. 9
Table 4
3.7. Antibacterial Activity
In this study, all the synthesized compounds were investigated against two Gram-positive
(S.aureus and K. pneumoniae) and two Gram-Negative (E.coli and E.faecalis) growth of
bacteria. MIC and MBC values of the bacteria strains used in this study are presented in
Table 5 and Figure 10. The Schiff base ligands and their complexes, exhibited varying degree
of inhibitory results on the growth of different tested bacterial strains. The obtained results
were compared with Kanamycin as the reference standards. Dimethyl sulphoxide (DMSO)
solvent was also used as positive control. From the data, it was observed that the complexes
(1-3) showed higher activity against bacteria compared to free Schiff base ligands. Such an
increased activity of the complexes can be explained on the basis of Overtone’s concept [35]
and Tweedy’s chelation theory [36]. This was due to an increase in cell permeability. The
lipid membrane, which surrounds the cell, favors the passage of only lipid soluble materials,
in a process known as liposolubility, which is an important factor for controlling
antimicrobial activity. By complexation, the electron delocalization over the Schiff-base
molecules participate in the complex molecules which in turn increase the hydrophobic
12

character of the metal chelate, increase the liposolubility, there by favoring its permeation
through lipoid layer of microorganism. The construction of the Schiff bases derived from
sulfanilamides was carefully selected to confer different electronic environments to the
molecules. The results from antimicrobial activity suggested that sulfonamide derivatives
were remarkably influenced by various substituents on the azomethine (-HC=N-) linkage.
Some of the synthesized compounds of this series exhibited significant antibacterial activities
[9]. The antibacterial results demonstrated that complex 2 was very active at MIC values
11.4-22.8µg/mL and compares well with the data found in related complexes [24-25]. The
data revealed that Schiff base ligand and their complexes with electron withdrawing groups
like the phenyl ring remarkably enhanced the antimicrobial activity against selected
microorganisms [20]. Thus, our aim was to explore structure activity relationship (SAR) of
synthesized compounds and to develop lead molecules for further optimization. To clear that
antibacterial activity of chemical compounds influence DNA structure, interfere with
replication, transcription, translation and other biological systems need more researches.
In another experiment, copper(II) acetate was tested against the same bacterial species in
order to evaluate an individual role of the corresponding metal ion in antibacterial activity. It
was found that the metal ion showed weak activity.
Fig. 10
Table 5
4. Conclusion
A series of novel sulfonamides were synthesized and characterized by the spectral and
analytical techniques. All the crystal structures were determined by X-ray crystallography.
The related copper (II) complexes of these sulfonamides was also obtained and characterized
by FT-IR, UV-Vis spectroscopy and XRD. The antibacterial results showed the copper (II)
13

complexes to be more antibacterial than the Schiff base ligands which was as a result of the
coordination of copper (II) to the ligands. Also, the proposed three complexes exhibited
distinct differences in their biological properties.
Acknowledgements
We gratefully acknowledge the Faculty of chemistry at Semnan University for supporting
this work.
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22. R. Taherlo, M. Salehi, Inorg. Chim. Acta 418 (2014) 180-186.
23. M. Salehi, M. Hasanzadeh, Inorg. Chim. Acta 426 (2015) 6-14.
24. H. H. Freedman, J. Am. Chem. Soc. 83(1961) 2900-2905.
25. S. Zolezzi, A. Decinti, E. Spodine, Polyhedron 18 (1999) 897-904.
15

26. Y. -L. Zhang, W. -J. Ruan, X. -J. Zhao, H. -G. Wang, Z. -A. Zhu, Polyhedron 22 (2003)
1535-1545.
27. P. Knopp, K. Weighardt, B. Nuber, J. Weiss, W.S. Sheldrick, Inorg. Chem. 29 (1990)
363-371.
28. N. Dharamaraj, P. Viswanathamurthi, K. Natarajan. Transition Met. Chem. 26 (2001)
105-109.
29. Z. H. Chohan, H. A. Shad, Appl. Organometal. Chem. 25 (2011) 591-600.
30. Z. Chohan, H. A. Shad, F.-H. Nasim Appl. Organometal. Chem. 23 (2009) 319-328.
31. D. W. Bembee, S. R. K. Bhubon, J. P. Jasinski, J. A. Golen, Inorg. Chem. Comm. 21
(2012) 163-167.
32. Oxford Diffraction, CRYSALIS PRO, Version 1.171.33.36d, Oxford Diffraction Ltd.,
Yarn ton, Oxford shire (2009).
33. A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, J. Appl. Crystallogr. 26(1993)
343-350.
34. G. M. Sheldrick, Acta Crystallogr. Sect A A64 (2008) 112-122.
35. EUCAST Definitive Document E.DEF 3.1, June 2000: Determination of minimum
inhibitory concentrations (MICs) of antibacterial agents by agar dilution. Clin. Microbiol.
Infect. 6 (2000) 509-515.
36 S. Ravikumar, R. Gokulakrishnan, P. Boomi, Asian Pac. J. Trop. Dis. 2 (2012) 85-89.
16

Fig. 1 A perspective view of one of symmetry-independent molecules of HL1. The ellipsoids are drawn at the
50% probability level, hydrogen atoms are shown as spheres of arbitrary radii, hydrogen bonds are drawn as
blue dashed lines.
Fig. 2 A perspective view of a molecule of HL2. The ellipsoids are drawn at the 50% probability level,
hydrogen atoms are shown as spheres of arbitrary radii, hydrogen bonds are drawn as blue dashed lines.
17

Fig. 3 A perspective view of a molecule of HL3. The ellipsoids are drawn at the 50% probability level,
hydrogen atoms are shown as spheres of arbitrary radii, hydrogen bonds are drawn as blue dashed lines.
Fig. 4 A comparison of the different Fourier maps calculated for the models without hydrogen atoms involved
in intramolecular hydrogen bonding (upper row – two molecules of HL1, lower HL2 and HL3).
18

Fig. 5 Fragment of the crystal structure of HL1. There are homomolecular chains of molecules along y-
direction, connected by C-H···O hydrogen bonds. Hydrogen bonds are shown as blue dashed lines.
Fig. 6 Hydrogen-bonded dimer in the crystal structure of HL2. Hydrogen bonds are shown as blue dashed lines.
19

Fig. 7 Crystal packing of HL3 as seen along x-direction. Hydrogen bonds are shown as blue dashed lines.
Fig. 8 X-ray diffraction pattern of complex 1 (a), 2 (b) and 3 (c).
20

Fig. 9 Rietveld analysis of XRD patterns for complexes 1 (a), 2 (b). The circle signs represent the raw data. The
solid lines represent the calculated profile. Vertical bars indicate the position of Bragg peaks for the complexes 1
(space group P21/c) and 2 (space group P21/n) with monoclinic structure. The lowest curve is the difference
between the observed and the calculated patterns.
21

(a)
(b)
Fig. 10. Histogram showing the comparative activities of the compounds.
Table 1. Crystal data, data collection and structure refinement.
HL1 HL2
C15H14N2O4S
HL3
Formula
C20H16N2O4S
380.41.78
C11H14N2O3S
254.30
Orthorhombic
Pbca
Formula weight
941318.3464
monoclinic
P21/c
Crystal system
Space group
a(Å)
monoclinic
P21/n
5.3850(3)
11.0642(2)
10.2186(2)
b(Å)
c(Å)
18.7863(3)
14.8771(3)
111.644(2)
2874.26(10)
8
10.4920(6)
30.22 50(12)
94.904(4)
1701.44(15)
4
9.9480(2)
23.1136(4)
90
2349.60(8)
8
β(º)
V(Å3)
Z
dx(g cm-3)
F(000)
µ(mm-1)
Θ range (0)
1.47
1328
2.20
3.97 – 70.00
1.49
792
0.22
2.06 – 26.53
1.44
1072
2.46
3.83 – 75.59
22

hkl range
-13≤h≤9
-22≤k≤21
-18≤l≤18
-6≤h≤5
-7≤k≤12
-37≤l≤36
-7≤h≤12
-7≤k≤12
-27≤l≤28
Reflections:
collected
14805
7247
5694
unique (Rint)
5400 (0.047)
4518
0.057
0.152
0.065
0.157
1.088
0.95/-0.59
3444 (0.024)
3258
0.038
0.109
0.040
0.111
1.040
0.43/-0.42
2350 (0.025)
2218
0.041
0.108
0.043
0.110
1.069
0.56/-0.43
with I>2σ(I)
R(F) [I>2σ(I)]
wR(F2) [I>2σ(I)]
R(F) [all data]
wR(F2) [all data]
Goodness of fit
max/min ∆ρ (e·Å-3)
Table 2. Selected geometrical parameters (Å, °) with s.u.’s in parenthes.
HL1A
HL1B
HL2
HL3
C-O
C=N
C-N
C-S
1.361(3)
1.290(3)
1.415(3)
1.758(3)
1.4279(19)
1.433(2)
1.653(2)
121.4(2)
1.347(3)
1.294(4)
1.435(4)
1.757(3)
1.429(2)
1.433(2)
1.653(2)
121.9(2)
1.2950(19)
1.311(2)
1.410(2)
1.7573(15)
1.4275(11)
1.4331(11)
1.6535(12)
126.30(13)
1.252(2)
1.367(2)
1.400(2)
1.7595(17)
1.4335(14)
1.4389(14)
1.6072(16)
130.73(16)
S=O
S-N
C=N-C
Table 3. Hydrogen bond data (Å, °).
D
H
A
D-H
H···A
D···A
D-H···A
HL1
O1A
O1B
N18A
N18B
C7A
C10A
C7B
C10B
HL2
N8
N18
C7
C10
HL3
N6
H1A
H1B
H18A
H18B
H7A
H10A
H7B
H10B
N8A
0.89(5)
0.99(6)
0.85
0.81
0.95(3)
0.93(3)
0.96(3)
0.98(3)
1.74(5)
1.67(6)
2.10
2.568(3)
2.568(3)
2.911(3)
2.828(3)
3.486(3)
3.178(3)
3.396(3)
3.283(3)
152(5)
148(5)
158
N8B
O1Ai
O1Bii
2.06
158
O17Biii
O19Biv
O17Aiv
O19Aiii
2.61(3)
2.38(3)
2.45(3)
2.40(3)
154(3)
143(2)
170(3)
150(3)
H8
H18
H7
O1
0.97(3)
0.86(2)
0.97(2)
0.98(2)
1.73(3)
1.90(2)
2.41(2)
2.50(2)
2.5592(16)
2.7464(16)
3.2376(17)
3.4186(18)
141(3)
168(2)
142.6(18)
156.7(17)
O1v
O19vi
O17vii
H10
H6
H16A
O1
0.90(3)
0.89(3)
1.90(2)
2.01(3)
2.664(2)
2.899(2)
142(2)
173(3)
N16
O14viii
23

N16
H16
O15ix
0.75(3)
2.20(3)
2.935(2)
166(2)
i
Symmetry codes: 1-x,1/2+y,1/2-z; ii –x,1/2+y,3/2-z; iii –x,1-y,1-z; iv 1-x,1-y,1-z; v2-x,-y,1-z; vi 2-x,1-y,1-z; vii 3-
x,-y,1-z; viii -1/2+x,y,1/2-z; ix 1-x,1/2+y,1/2-z.
Table 4 The structure type and unit cell parameters of complexes 1 and 2.
Complex
1
2
Crystal system
monoclinic
monoclinic
Space group
a(Å)
b(Å)
c(Å)
β(º)
V(Å3)
P21/c
P21/n
11.1162(1)
21.2375(5)
15.0119(5)
110.690(8)
3315.44(9)
11.1033(6)
18.8447(5)
24.8554(5)
95.5695(5)
5176.20(3)
Table 5. MIC and MBC of synthesized compounds against growth of bacteria (µgmL-1).
Gram Negative Bacteria
E. Coli
Gram Positive Bacteria
Compound
E. Faecalis
S. Aureus
K. Pneumoniae
MBC
182.9
182.9
182.9
91.4
45.7
91.4
3.8
MIC
45.7
22.8
45.7
22.8
11.4
45.7
4.0
MBC
MIC
45.7
22.8
91.4
22.8
11.4
45.7
3.3
MBC
182.9
182.9
635.7
91.4
91.4
182.9
3.0
MIC
45.7
22.8
91.4
45.7
22.8
45.7
3.2
MBC
MIC
45.7
45.7
91.4
22.8
11.4
45.7
4.0
HL1
365.8
365.8
182.9
182.9
91.4
91.4
3.2
182.9
182.9
731.7
91.4
45.7
91.4
3.6
HL2
HL3
1
2
3
Kanamycin
DMSO
Cu(OAC)2.H2O
-
-
-
-
-
-
-
-
˃600
˃600
˃600
˃600
˃600
˃600
˃600
˃600
24

ꢀ A series of new sulfonamides and the related copper (II) complexes were synthesized
and characterized by the spectral and analytical techniques.
ꢀ The molecular structures of ligands were determined by X-ray diffraction method and
complexes by XRD.
ꢀ Their antibacterial activities against some microorganism were reported.
25

A new series of Schiff base ligands derived from sulfonamide were prepared and
1
investigated. These ligands were characterized by FT-IR, H–NMR, UV–Vis spectroscopy
and elemental analysis. The crystal structures of ligands were determined by Single-crystal
X-ray Diffraction. Also, the copper(ІІ) metal complexes of these ligands were synthesized
and characterized by FT-IR, UV-Vis spectroscopy and powder X-ray diffraction. The
copper(II) chelates have been screened for their antimicrobial activities using the disc
diffusion method against the selected bacteria compared with free Schiff base ligands.
26

27