Synthesis, characterization, and antibacterial activity of the schiff bases derived from thiosemicarbazide, salicylaldehyde, 5-bromosalicylaldehyde and their copper(II) and nickel(II) complexes

Article abstract of DOI:10.1080/15533174.2010.522661

Two Schiff bases salicylidene thiosemicarbazone (SALTSC) and 5-bromosalicylidene thiosemicarbazone (5-BrSALTSC) were prepared in excellent yield via the condensation of salicylaldehyde/5-bromosalicylaldehyde and thiosemicarbazide. The copper (II) and nick

Full text of DOI:10.1080/15533174.2010.522661

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Synthesis, Characterization, and Antibacterial
Activity of the Schiff Bases Derived from
Thiosemicarbazide, Salicylaldehyde, 5-
bromosalicylaldehyde and their Copper(II) and
Nickel(II) Complexes
a
a
b
Jisha Joseph , N. L. Mary & Raja Sidambaram
a
Department of Chemistry , Stella Maris College , Chennai, India
b
Centre for Research in Science and Technology, Stella Maris College , Chennai, India
Published online: 03 Dec 2010.
To cite this article: Jisha Joseph , N. L. Mary & Raja Sidambaram (2010) Synthesis, Characterization, and Antibacterial
Activity of the Schiff Bases Derived from Thiosemicarbazide, Salicylaldehyde, 5-bromosalicylaldehyde and their Copper(II)
and Nickel(II) Complexes, Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 40:10, 930-933
To link to this article: http://dx.doi.org/10.1080/15533174.2010.522661
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Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 40:930–933, 2010
Copyright © Taylor & Francis Group, LLC
ISSN: 1553-3174 print / 1553-3182 online
DOI: 10.1080/15533174.2010.522661
Synthesis, Characterization, and Antibacterial Activity of
the Schiff Bases Derived from Thiosemicarbazide,
Salicylaldehyde, 5-bromosalicylaldehyde and their
Copper(II) and Nickel(II) Complexes
1
1
2
Jisha Joseph, N. L. Mary, and Raja Sidambaram
1
Department of Chemistry, Stella Maris College, Chennai, India
Centre for Research in Science and Technology, Stella Maris College, Chennai, India
2
the biological activities displayed by Schiff bases.[18] The com-
Two Schiff bases salicylidene thiosemicarbazone (SALTSC) and pounds having antimicrobial activity may act either by killing
5
-bromosalicylidene thiosemicarbazone (5-BrSALTSC) were pre-
the microbe or by inhibiting multiplication of the microbe by
blocking their active sites. Schiff bases derived from salicy-
pared in excellent yield via the condensation of salicylaldehyde/5-
[19]
bromosalicylaldehyde and thiosemicarbazide. The copper (II) and
nickel (II) complexes of the Schiff base ligands (CuSALTSC, 5-
BrCuSALTSC, NiSALTSC, and 5-BrNiSALTSC) were also pre-
pared. The complexes were tested against Staphylococcus aureus
gram-positive) and Escherichia coli (gram-negative) using Disc
diffusion method. Among these complexes, 5BrCuSALTSC was
laldehydes are well known as polydentate ligands, coordinating
as deprotonated or neutral forms.[
20]
In the present study we synthesized Salicylidenethiosemicar-
bazone (SALTSC) and 5-Bromosalicylidene thiosemicarbazone
(
(5-BrSALTSC) and their Cu (II) and Ni (II) complexes. The
found to be highly active against S. aureus at a concentration of
complexes were tested for their antibacterial activity.
1
5
00 µg/disc and against E. coli at a concentration of 150 µg/disc.
BrNiSALTSC was found to be highly active against E. coli at a
concentration of 150 µg.
EXPERIMENTAL
Keywords antibacterial activity, azomethine linkage, Schiff bases
Preparation of Schiff base Complexes[21,22]
A mixture of 0.735 ml of salicylaldehyde (0.01 M) dissolved
and 0.0919 g of thiosemicarbazide (0.01 M) dissolved in ethanol
INTRODUCTION
Many biologically important Schiff bases have been refluxed for two hours on a water bath till a clear solution was
[
1−7]
[8−10]
reported possessing antibacterial,
antifungal,
obtained. It was allowed to cool and the Schiff base separated
antimicrobial,[
11−13]
and anti-HIV
[14,15]
activities. Also, certain out was filtered and recrystallized from hot ethanolic solution.
◦
polymeric Schiff bases have been found to possess antitumor The melting point of this base was 203 C.
activity. The Schiff bases have the highest degree of hydrolysis
5-bromosalicylaldene thiosemicarbazone was prepared by
at pH 5, and the solubility in water is also high at this pH. using brominated salicylaldehyde (1.99 g; 0.01 M) and thiosemi-
Antitumor activity of the Schiff bases towards acidic tumors carbazide (0.01 M).
increases considerably with the slight increase in water
Salicylaldene thiosemicarbazone/ 5-bromosalicylaldene
thiosemicarbazone (0.01 M) dissolved in ethanol was mixed
solubility.[
16]
Schiff bases are important intermediates for the synthesis of with corresponding metal ion (0.01 M) in ethanol. The resulting
some bioactive compounds such as beta-lactams. The base cat- solution was refluxed for two hours. If necessary, sodium acetate
alyzed condensation of acetyl chlorides with N-arylaldimines was added to control the pH at 8.2. The refluxed solution was
occurs by initial acylation at the nitrogen atom and leads to cooled and the precipitated complex was filtered. The filtered
[17]
β-lactams of interest in penicillin chemistry. It has been sug- complex was washed with ethanol and dried over anhydrous
gested that the azomethine linkage might be responsible for calcium chloride.
Received 7 February 2010; accepted 26 July 2010.
CHARACTERIZATION STUDIES
Address correspondence to Raja Sidambaram, Technical Director,
Centre for Research in Science and Technology, Stella Maris College,
Chennai, India. E-mail: rajasidambaram@gmail.com
The complexes were characterized using FT IR spectra, mass
spectra, and NMR spectra.
930

ANTIBACTERIAL ACTIVITY OF SOME SYNTHETIC CHEMICALS
931
Infrared Spectra
TABLE 1
The characteristic FT IR frequencies of the ligand and
complexes
SALTSC and 5-BrSALTSC exhibit a sharp band at 1610
−1
cm due to azomethine linkage. In all the complexes, this band
−1
appears at a frequency lower (approximately 20cm ) than that
on the free ligand. This clearly indicates the involvement of
nitrogen atom in coordination due to a reduction in the electron
Name of the
compound
−1
−1
−1
−1
νNH cm
νHC=N cm
νOH cm
νC−S cm
density in the azomethine linkage. Keto-enol tautomerism is SALTSC
possible for thiosemicarbazone, and the ligand can exist as keto CuSALTSC
1610
1612
1612
1622
1610
3439
3447
3445
3445
3483
754
789
766
752
762
3171
3250
3259
–
(
I) or enol (II) or as a mixture of both.
5BrCuSALTSC
NiSALTSC
S
SH
5BrNiSALTSC
2980
R=N-NH-C-NH2
I)
R=N-N=C-NH2
II)
Mass Spectra
(
(
Inthe mass spectra of the CuSALTSCcomplex, themolecular
ion peak is observed at 630 m/z. Since the compound contains
six nitrogen atoms (even number), it gives a molecular ion peak
with an even mass number (nitrogen rule). Isotopic peaks of
The SH stretching vibrations are absent in the expected re-
−1
gion. 2650–2500 cm indicate that the free ligand exists in
this keto form in the solid state. However, during the complex
formation, it might exist in the enol form. This is indicated by
the absence of the band due to νC-S of the ligand in the com-
1
3C, 15N, 33S (M + 1 peak), and 18O, 34S (M + 2 peak)
are also observed. Since the compound is a dimer, it shows
m/2 peak at m/z = 315 and corresponding isotopic peak at
m/z = 316.
−1
plexes. In the free ligand, the band appears at 754 cm . A
−1
new band arises on complexation at 704 cm , which can be
attributed to νC-S. In all these studies, the clear indication is of
the participation of sulphur atom in coordination.
The mass of the same compound has been determined with
considerable accuracy with the help of high resolution mass
spectra. The experimental mass and the calculated mass are in
good agreement in both cases. For CuSALTSC, the mass is
The free hydroxyl group in a compound has stretching mode
−1
at 3700–3450cm . The –OH band is weakened, if the group is
hydrogen bonded, and in such cases the band is broadened with
a shift to lower frequency. In salicylidene thiosemicarbazone
629.9476 and the calculated mass is 629.9478 (Figure 1).
and 5 Bromosalicylidene thiosemicarbazone, this band occurs at NMR Spectra
−
1
3
439 cm , which excludes the possibility of hydrogen bonding.
1H NMR spectra of SALTSC, BrSALTSC have been charac-
−1
It also shows two N-H stretching bands, one at 3317cm and terized by using DMSO-d6 as the solvent. The peaks between δ
−1
the other at 3171cm . These two bands also appear as sharp 6.71 and 6.95 showed the presence of azomethine (HC=N) pro-
bands indicating the absence of hydrogen bonding. tons. Singlet peaks between δ 9.3–10.1 indicated NH proton and
The bands due to νNH and νOH are retained almost at the the phenolic protons have shown peak at δ 7.1 to 7.8 ranges. 13C
same position in the case of complexes. This excludes any pos- spectra of SALTSC and CuSALTSC have also been taken. The
sible participation of the oxygen of the phenol group or nitrogen spectra showed bands attributed to C-N at δ 156.9 and 160.3,
of the NH2 group in coordination (Table 1).
respectively, aromatic carbon between δ 139 and 120, carbonyl
FIG. 1. High resolution mass spectra of CuSALTSC.

932
J. JOSEPH ET AL.
TABLE 2
The antibacterial activity of the compounds
Concentration of compound-
0 µg/disc
Concentration of compound-
Concentration of compound-
5
100 µg/disc
150 µg/disc
Compound
S. aureus
E. coli
S. aureus
E. coli
S. aureus
E. coli
SALTSC
CuSALTSC
+
+
++
++
+
+
++
+ + +
+
−
+
+
−
++
+ + +
+
++
++
−
5
BrCuSALTSC
NiSALTSC
BrNiSALTSC
++
+
+ + +
+
−
5
+
+
++
++
+ + +
−
Highly active = + + + (inhibition zone >12 mm)
Moderately active = ++ (inhibition zone 9–12 mm)
Slightly active = + (inhibition zone 6–9 mm)
Inactive = − (inhibition zone <6 mm)
carbon attached to N at δ 131.6, CH ranging from δ 40.1 and around an antibiotic disc after incubation if the agent inhibits
39.9 and CH2 at δ 39.
bacterial growth.
An inoculating loop is touched to four or five isolated
colonies of the pathogen grown on nutrient agar medium and
then used to inoculate a tube of culture broth. The culture is in-
Antibacterial Studies
The Schiff base ligand and selected four Schiff base com-
plexes were screened in vitro for their antibacterial activity
against one gram-positive (Staphylococcus aureus) and two
gram-negative (Escherichia coli and Klebsiella pneumoniae)
bacterial strains by disc diffusion method and tube dilution
method.
◦
cubated for a few hours at 37 C until it becomes slightly turbid.
A sterile cotton swab is dipped into the standardized bacterial
test suspension and used to evenly inoculate the entire surface
of a Mueller-Hinton agar plate. After the agar surface has dried
for about 5 minutes, the appropriate antibiotic test discs are
placed on it with sterilized forceps or a needle. The plate is
Stock culture of bacteria was purchased from Science House,
Chennai. A sub-culture was prepared from the stock culture.
◦
immediately placed in a 37 C incubator. After 24 hours of incu-
bation, the diameter of the zones of inhibition measured to the
nearest mm.
Disc diffusion method[23]
The concentration of the prepared compound was taken as
When an antibiotic-impregnated disc is placed on agar pre-
viously inoculated with the test bacterium, the disc picks up
moisture and the antibiotic diffuses radially outward through
the agar, producing an antibiotic concentration gradient. The
antibiotic is present at high concentrations near the disc and
affects even minimally susceptible microorganisms (resistant
organism will grow up to the disc). As the distance from the
disc increases, the antibiotic concentration drops and only more
susceptible pathogens are harmed. A clear zone or ring is present
5
0 µg/disc, 100 µg/disc, and 150 µg/disc.
Tube dilution method
In broth dilution test, a series of broth tubes containing antibi-
otic concentrations in the range of 10 to 100µg/tube is prepared
and inoculated with standard numbers of test organism. The
lowest concentration of the antibiotic resulting in no growth af-
ter 16 to 20 hours of incubation is the MIC. Tryptone soya broth
and sterile saline were used in this test.
RESULTS AND DISCUSSION
TABLE 3
To determine the antibacterial activity of these compounds,
the disc-diffusion (Kirby-Bauer) method[ was carried out us-
ing DMSO as control. The prepared compounds were exam-
ined against a gram-positive (Staphylococcus aureus) and gram-
negative (Escherichia coli) bacterial strains. The test results are
given in Table 2.
The MIC of the bacterial strains
10]
Schiff
base/complex
MIC for
MIC For
MIC For
K. pneumoniae
S. aureus
E. coli
SALTSC
CuSALTSC
5
>100 µg
>100 µg
>100 µg
>100 µg
>100 µg
>100 µg
>100 µg
>100 µg
>100 µg
>100 µg
60 µg
60 µg
60 µg
-BrCuSALTSC
NiSALTSC
-BrNiSALTSC
Minimal inhibitory concentration (MIC)
The broth tube dilution method was used to determine the
minimal inhibitory concentration (MIC). The MIC is determined
60 µg
5
>100 µg

ANTIBACTERIAL ACTIVITY OF SOME SYNTHETIC CHEMICALS
933
for the growth of one gram-positive (Staphylococcus aureus)
and two gram-negative (Escherichia coli and Klebsiella pneu-
moniae) bacterial strains. The culture that shows no growth in
the presence of the lowest concentration of the complex repre-
sents the MIC of the complex against those particular bacteria.
The findings are given in Table 3.
From the data, it was observed that the antibacterial activity
of these compounds showed significant increase on coordina-
tion. This enhancement in the antibacterial activity may be due
to the possession of an additional azomethine bond. It has been
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