Synthesis, characterization, thermal and antibacterial study of a novel sulfonamide derivative, N-[(E)-pyridin-3-ylmethylidene]benzenesulfonamide, and its Co(II), Cu(II) and Zn(II) complexes

Article abstract of DOI:10.4067/S0717-97072013000100026

The novel aromatic sulfonamide ligand, N-[(E)-pyridin-3-ylmethylidene] benzenesulfonamide (PMBS) was synthesized along with its Cu(II), Co(II) and Zn(II) complexes of MLCl2 type. The characterization of the complexes and the ligand was done by physical methods like elemental analysis, UV-VIS spectra, 1H-NMR, IR and conductance studies. Additionally, the thermal degradation pattern was examined by TG/DT analysis. Antimicrobial activities are studied with both gram negative Pseudomonas aeruginosa, Salmonella typhi, Eschericia coli and gram positive bacteria Bacillus subtilus, Staphylococcus aureus, Staphylococcus epidermis, Streptococcus pneumonia.

Full text of DOI:10.4067/S0717-97072013000100026

J. Chil. Chem. Soc., 58, Nº 1 (2013)
SYNTHESIS, CHARACTERIZATION, THERMAL AND ANTIBACTERIAL STUDY OF A NOVEL SULFONAMIDE
DERIVATIVE, N-[(E)-PYRIDIN-3-YLMETHYLIDENE]BENZENESULFONAMIDE,
AND ITS CO(II), CU(II) AND ZN(II) COMPLEXES
*SAEED-UR-REHMAN, aALIA FAIZ AND bROBILA NAWAZ
Institute of Chemical Sciences, University of Peshawar, Pakistan
(Received: March 1, 2012 - Accepted: November 15, 2012)
ABSTRACT
The novel aromatic sulfonamide ligand, N-[(E)-pyridin-3-ylmethylidene]benzenesulfonamide (PMBS) was synthesized along with its Cu(II), Co(II) and
Zn(II) complexes of MLCl2 type. The characterization of the complexes and the ligand was done by physical methods like elemental analysis, UV-VIS spectra,
1H-NMR, IR and conductance studies. Additionally, the thermal degradation pattern was examined by TG/DT analysis. Antimicrobial activities are studied
with both gram negative Pseudomonas aeruginosa, Salmonella typhi, Eschericia coli and gram positive bacteria Bacillus subtilus, Staphylococcus aureus,
Staphylococcus epidermis, Streptococcus pneumonia.
Key Words: N-[(E)-pyridin-3-ylmethylidene]benzenesulfonamide (PMBS), Escherichia coli, Salmonella typhi, Bacillus subtilus, Staphylococcus aureus.
gram negative bacteria. Imipenem was used as a standard drug. It belongs
to the carbapenem class of compounds, which are used as a last shot against
many infectious bacteria8. The activity was measured by comparing the zones
of inhibition. Zones of inhibition correspond to the area where bacteria were
killed by using the standard drug, the ligand and the respective complexes.
They were measured in diameter (mm). A concentration of 1mg/6µL was used
to carry out the different antibacterial activities.
INTRODUCTION
Sulfonamide derivatives form a scaffold in a number of pharmacologically
active compounds. Their toxicity is attributed to SO2NH moiety. Among
the pharmacological properties, antibacterial is the most important one.
Sulfonamides inhibit the biosynthesis of tetrahydrofolate in the bacteria,
which is a co-factor for the bacterial DNA and RNA synthesis. Deficiency of
tetrahydrofolate, decreases the production of new DNA and RNA, ultimately
resulting in the bacterial decay. Sulfonamides mimic the substrate for the
enzymes and thus block their active sites by reacting with them first instead
of the substrate1 . Human carbonic anhydrase inhibitors which are potential
antitumor agents, are characterized by the sulfonamide units2. They are
classified as chemotherapeutic agents.
Sulfonamides are used in the treatment of the diseases like glaucoma,
epilepsy, congestive heart failure, mountain sickness, gastric and duodenal
ulcers2. Its derivatives are used as antifungal, anti-inflammatory and
hypoglycemic agents3. Ligands based on the sulfonamides are used as
asymmetric catalysts4. Metal complexes modify the pharmacology and
toxicology of the sulfonamide based ligands5.
Preparation of ligand
0.02 moles of pyridine-3-carbaldehyde dissolved in methanol were
mixed with a methanolic solution of 0.02 moles of benzene sulfonamide at
room temperature. The product appeared after 2 minutes. The reaction was
monitored by TLC. The precipitate formed was separated through a sintered
glass crucible, washed with dichloromethane and then dried in a vacuum oven.
M.P.100-112oC, Color=Yellowish white, Yield=33%.
(PMBS)
The present work is based on the antibacterial properties of a novel
aromatic sulfonamide derivative i.e N-[(E)-pyridin-3-ylmethylidene]
benzenesulfonamide (PMBS) and its corresponding first row transition metal
complexes i.e Cu(II), Co(II) and Zn(II).
Scheme I: Preparation of PMBS
Preparation of complexes
EXPERIMENTAL
The complexes were prepared by the following general method. 0.01
moles of the corresponding metal (II) chloride was dissolved in a minimum
amount of dry ethanol. The moisture was removed by stirring with 2,
2-dimethoxypropane for one hour, followed by the addition of an ethanolic
ligand solution (0.01mole). The mixture was stirred for one hour. Crystals were
separated by evaporating the solvent under vacuum. Recrystallization was
carried out with dichloromethane. The general synthetic procedure is described
on scheme II.
Materials and methods
Solvents used were of analytical grade. Common solvents were distilled
twice before use. Metal (II) chlorides used were obtained from Riedel-de-
Haen, Germany. The pyridine-3-carbaldehyde and benzene sulfonamide were
of analytical grade obtained from Acros Organics, USA and used without
further purification.
Instrumentation
The compounds weight was determined on Ohaus, AR 2140(USA), digital
balance. Melting points were recorded on a Gallen kamp (UK) apparatus.
Conductivity meter type AGB 1000 was used to measure the complexes
conductivities6. The magnetic moments of the solid complexes were determined
by the Gouy,s method at room temperature using Hg[Co(SCN)4] as a standard7.
Ultraviolet and visible absorption spectra of the complexes in the range
300-1000 nm in different solvents were obtained on a BMS UV-1602. The
Infrared spectra of the ligands and solid complexes were run on a Shimadzu
FTIR spectrophotometer. Proton NMR spectra of the ligand was recorded on a
Bruker (AM400) spectrometer. The spectra were measured in DMSO-d6.
Biological studies
Scheme II: Complex(s) Preparation
M=Co(II), Cu(II), Zn(II)
RESULT AND DISCUSSION
The1H NMR spectra of only the Schiff base was determined in DMSO-d .
The ligand exhibited signals that have been identified from the integratio6n
curve and found to be equivalent to the total number of protons deduced from
its proposed structures. Peak at 10.01 ppm is assigned to azomethine hydrogen
H10. Peak at 8.90ppm is assigned to the H1, peak at 9.1 shows H4, small peaks
The ligand and its complexes were tested against both gram positive
and gram negative bacteria. Gram positive included Bacillus subtilus,
Staphylococcus aureus, Staphylococcus epidermis, Streptococcus pneumonia
while Pseudomonas aeruginosa, Salmonella typhi, Eschericia coli represented
e-mail: srachem@yahoo.com
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J. Chil. Chem. Soc., 58, Nº 1 (2013)
in the range of 8.30-8.40 ppm are assigned to H9 and the peaks in the range of 7.40-7.90 ppm reveals information about the presence of H8, H7 and H2Fig1.
Fig.1 1H NMR Spectra of PMBS in DMSO-d6
The ligand shows prominent peaks at 1473 cm-1 (Py-N), 1635 cm-1(C=N), 1319 cm-1 (O=S=O). [Co(PMBS)Cl2]shows a shift in the peaks of Py-N (1446 cm-1)
and C=N (1645 cm-1) Table 2. reflecting that the ligand coordinated through nitrogen atoms of the pyridine and azomethine. The data for the rest of complexes is
also given in Table 2,
Table 1 Analytical Data of PMBS Ligand and its Metal (II) Complexes.
% C
Found
% H
Found
% N
Found
% Cation
% Anion
S. No
Compound
Color
M.P oC
Cal
Cal
Cal
Cal
Found
Cal
Found
Yellowish
white
1
PMBS
100-112
58.52
58.49
4.09
4.06
11.37
11.21
-
-
-
-
2
3
4
[Co(PMBS)Cl2]
[Cu(PMBS)Cl2]
[Zn(PMBS)Cl2]
Violet
Green
White
194-200
160-165
120-122
38.32
37.86
37.67
38.31
37.77
37.61
2.68
2.65
2.63
2.66
2.56
2.59
7.45
7.36
7.32
7.50
7.24
7.26
15.67
16.69
17.10
15.47
16.52
17.07
18.85
18.62
18.53
18.81
18.48
18.50
Table 2 IR Data of Ligand PMBS and its Metal (II) Complexes.
S.No
Compound
PMBS
(Py-N) ν cm-1
1473
(C=N) ν cm-1
1635
(O=S=O)ν cm-1
1319
1
2
3
4
[Co(PMBS)Cl2]
[Cu(PMBS)Cl2]
[Zn(PMBS)Cl2]
1446
1645
1330
1429
1680
1325
1444
1610
1334
Table 3 Conductance, Magnetic andSpectral Data for Complexes of PMBS.
Molar conductance
Solvent
µeff (B.M)
λmax
Energy
(cm-1)
(mS) mol-1
S. No
Complex
(nm)
601
670
16638
14925
1
2
3
[Co(PMBS)]Cl2
[Cu(PMBS)]Cl2
[Zn(PMBS)Cl2]
DMF
DMF
29.7
0.75
4.28
4. 1
1.2
622
16077
DMF
Diamagnetic
The close agreement between the calculated and found values of the
elemental analysis results shows the formation of PMBS, Table 1. In the same
Table 1 the analytical data of the complexes are shown, corroborating the
general formula of M(PMBS)Cl2. for all of them. % anion and cations were
calculated using standard volumetric method9.
The molar conductance of Co(II), Cu(II) and Zn(II) complexes are
reported in Table 3. The molar conductance values indicate that they are
all non-electrolytic in nature. In non-electrolytic complexes the anion is
bonded to the metal and therefore is present within the coordination sphere
while in electrolytic complexes the anion remains outside the coordination
sphere10,11,12,13 Table 3.
Zn(II) complex has no magnetic moment indicating a diamagnetic character
Table 3.
[Co(PMBS)Cl2] exhibited well resolved peak at 16638 cm-1 (601 nm)
4
4
and assigned to A2 →4T1(F) and at 14925 cm-1 (670 nm) is assigned to A2
→4T1(P)14.These values supports the tetrahedral geometry for Co(II) complex.
In [Cu(PMBS)Cl2]the peak is at 16077 cm-1 (622 nm) Fig.3 and is assigned
2
to the transition B2→2A1. The low absorption value is because of the dilute
solution that we used to carry out the spectra. These observations support the
tetrahedral geometry of Cu(II) complex. The [Zn(PMBCl2] is diamagnetic and
is suggested to have tetrahedral geometry15,16 Table 3.
The magnetic moment value for Co(II) complex is 4.1 B.M, indicating the
presence of three unpaired electrons. The magnetic moment value of Cu(II)
complex is 1.2 B.M, which show the presence of one unpaired electron. The
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J. Chil. Chem. Soc., 58, Nº 1 (2013)
Fig.2 UV-Vis Spectrum for Co(PMBS)Cl2 in DMF.
Fig.3 UV-Vis Spectrum for Cu(PMBS)Cl2 in DMF.
Table 4 Thermoanalytical Data of Ligand PMBS and its Metal (II) Complexes.
Weight loss/mg
DTA Peak Temp/ TG Temp range
S. No
Compounds
Products Evolved/ Residue
Found
oC
/oC
Calc.
%Weight Loss
1
2
PMBS
150(+)
150(+)
30-890
6.1
6.2
C12H10N2 SO2 + H2O
90
30-1000
1000
6.7
1.6
6.7
1.6
C12H N2SO2+ Cl2
Co1O0 (residue)
80
19
[Co(PMBS)Cl2]
30-600
600-1000
5.4
1.3
5.8
0.7
C12H N2SO2+ Cl2
Cu1O0 (residue)
89
11
3
4
[Cu(PMBS)Cl2]
[Zn(PMBS)Cl2]
550(+)
700(-)
30-735
735-1000
6.3
1.6
7.1
0.5
C H N2SO2+ Cl2
1Z2 n1O0 (residue)
94
6
Temp = Temperature, Calc.= Calculation, (+) = Endothermic and (-) = Exothermic.
Thermoanalytical study
The ligand PMBS follows a single step degradation process after the loss
of a water molecule. The entire ligand is released in the temperature range of
30-890ºC with an endothermic DTA peak at 150ºC.
All the complexes also follow the same two steps by liberating the ligand
in the first step along with the chlorine molecule. Metal oxides (MO) were left
as residues in all the complexes, Table 4. The above degradation pattern can be
summarized in the following general equations.
PMBS→H2O+PMBS
M(PMBS)Cl → PMBS+Cl2
M+O2→MO2
Pharmacological Studies
Ligand PMBS show moderate activities against all the bacterial strains.
DMSO was used as a solvent to check their antibacterial activity against the
gram negative bacteria Escherichia coli, Salmonella typhi and Pseudomonas
aeruginosa and gram positive bacteria Bacillus subtilus, Staphylococcus
aureus, Staphylococcus epidermidis, Streptoccus pneumonia Fig. 4. The
potency of some of the coordinated compounds is higher than the one observed
for the ligand. The toxicity of the coordinated compounds can be explained
by the Chelation theory. According to this theory the polarity of the metal ion
decreases because of the following two factors.
Fig.4 Antibacterial Activities of PBMS and its Metal (II) Complexes.
CONCLUSION
1.
2.
Overlap of the ligand orbitals with the metal orbitals
Partial sharing of the positive charge of the metal ion with the donor
The novel sulfonamide derivative N-[(E)-pyridin-3-ylmethylidene]
benzenesulfonamide was synthesized and characterized by 1H-NMR, IR and
elemental analysis. Its transition metal complexes were also synthesized and
properly characterized. The thermal study that we carried out suggested that
new bonds have been formed in the complexes i.e between the ligand and
the transition elements because the degradation pattern seen in the ligand got
changed in case of the complexes. The antibacterial activity shows that zinc
complex was most active against Bacillus subtilis exhibiting more than 80%
activity. The rest of the compounds were moderately active.
groups.
These factors help in the delocalization of the n-electrons over the whole
chelate ring and thus increase the lipophilic character of the complexes.
This increased lipophilicity renders high penetration to the complexes into
the bacterial system, thus blocking the metal binding sites of the specific
enzyme17. So this chelation theory explains the high activity of the complexes
as compared to the uncomplexed ligand. Zinc complex was most active against
Bacillus subtilus, Staphylococcus epidermis, Salmonella typhi showing 80%,
58% and 60% activity. The rest of the complexes were either moderately or
weakly active.
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J. Chil. Chem. Soc., 58, Nº 1 (2013)
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