Synthesis, characterization and preliminary in vitro antibacterial screening activity of metal complexes derivatives of 2-{[5-(4-nitrophenyl)-1,3, 4-thiadiazol-2-ylimino]methyl}phenol

Article abstract of DOI:10.14233/ajchem.2013.13901

A total of five new metal complexes derivatives of 2-{[5-(4-nitrophenyl)-1, 3,4-thiadiazol-2-ylimino]methyl}phenol (HL) with the metal ions [Ni(II), Cu(II), Zn(II), Cd(II) and Sn(II)] have been successfully prepared in alcoholic medium. The complexes obtained are characterized quantitatively and qualitatively by using microelemental analysis, FTIR spectroscopy, UV-visible spectroscopy, mass spectroscopy, 1H and ¹³C NMR, magnetic susceptibility and conductivity measurements. From the spectral study, all the complexes obtained as monomeric structure and the metals centre moieties are four-coordinated with distorted tetrahedral geometry except Cu(II) complex which existed as a distorted square planar geometry. The preliminary in vitro antibacterial screening activity revealed that complexes 1-5 showed moderate activity against tested bacterial strains and slightly higher compared to the parent ligand.

Full text of DOI:10.14233/ajchem.2013.13901

Asian Journal of Chemistry; Vol. 25, No. 8 (2013), 4203-4206
http://dx.doi.org/10.14233/ajchem.2013.13901
Synthesis, Characterization and Preliminary in vitro Antibacterial Screening Activity of Metal
Complexes Derivatives of 2-{[5-(4-Nitrophenyl)-1,3,4-thiadiazol-2-ylimino]methyl}phenol
1,*
2,*
1
2
YIP-FOO WIN , EMAD YOUSIF , SIE-TIONG HA and AHMED MAJEED
1Department of Chemical Science, Faculty of Science, Universiti TunkuAbdul Rahman, Perak Campus, Jalan Universiti, Bandar Barat, 31900
Kampar, Perak, Malaysia
2Department of Chemistry, College of Science, Al-Nahrain University, Baghdad, Iraq
*Corresponding author: Fax: +605 4661676; Tel: +605 4688888; E-mail: williamyfw@yahoo.com
(Received: 13 April 2012;
Accepted: 4 February 2013)
AJC-12927
A total of five new metal complexes derivatives of 2-{[5-(4-nitrophenyl)-1,3,4-thiadiazol-2-ylimino]methyl}phenol (HL) with the metal
ions [Ni(II), Cu(II), Zn(II), Cd(II) and Sn(II)] have been successfully prepared in alcoholic medium. The complexes obtained are
characterized quantitatively and qualitatively by using microelemental analysis, FTIR spectroscopy, UV-visible spectroscopy, mass
1
spectroscopy, H and 13C NMR, magnetic susceptibility and conductivity measurements. From the spectral study, all the complexes
obtained as monomeric structure and the metals centre moieties are four-coordinated with distorted tetrahedral geometry except Cu(II)
complex which existed as a distorted square planar geometry. The preliminary in vitro antibacterial screening activity revealed that
complexes 1-5 showed moderate activity against tested bacterial strains and slightly higher compared to the parent ligand.
Key Words: 1,3,4-Thiadiazole derivatives, Metal complexes, In vitro antibacterial activity.
cation. The melting points were recorded on a hot stage Gallen
Kamp melting point apparatus. Elemental C, H, N and S
analysis were carried out on a Fison EA 1108 analyzer. The
Infrared (FTIR) spectra were recorded by using FTIR.8300
Shimadzu spectrophotometer by using CsI disc in the
frequency range of 4000-200 cm-1. The ultraviolet-visible (UV-
VIS) spectra were recorded by using Shimadzu UV-VIS. 160
A-Ultra-violet spectrophotometer in the range of 200-1100
nm. The magnetic susceptibility values were obtained at room
temperature using Magnetic Susceptibility Balance Bruke
Magnet B.M.6. Conductivity measurements were carried out
by using WTW conductivity meter, atomic absorption measu-
rements were obtained by using Shimadzu 680cc-flame. The
INTRODUCTION
The synthesized and structural study of 1,3,4-thiadiazoles
derivatives are a class of heterocyclic compound which has
attracted significant interest in medicinal chemistry and have
a wide range of pharmaceutical and biological activities
including antimicrobial, antifungal, antiinflammatory and
antihypertensive1-7. Up-to-date, numerous studies have been
carried out to synthesis various type of new 1,3,4-thiadiazoles
derivatives by extending the thiadiazoles ring with some active
organic compounds to form new Schiff bases compounds1-8.
In addition, the chemistry and the applications of these new
Schiff bases thiadiazoles derivatives could be extensively study
by coordinating to various metal ion moieties. As a result, the
structural-activity relationship study of 1,3,4-thiadiazoles
could be expanded in the near future.
1
13
spectra of H and C NMR spectra were recorded on a Jeol
400 MHz spectrometer using deuterated DMSO-d6 as the
solvent and tetramethylsilane, TMS as the internal standard.
Mass spectra were recorded on a Micromass UK PLATFORM
II LC-MS spectrometer.
As the continuation interest of our study of transition metal
complexes9-14, here we present the synthesis and characterization
of new complexes derivatives of 2-{[5-(4-nitrophenyl)-1,3,4-
thiadiazol-2-ylimino]methyl}phenol. Moreover, the preliminary
in vitro antibacterial screening activities of the complexes
obtained are carried out and the results are reported herein.
Preparation of 2-{[5-(4-nitrophenyl)-1,3,4-thiadiazol-
2-ylimino]methyl}phenol, HL: A mixture of 4-nitrobenzoic
acid (0.01 mol), thiosemicarbazide (0.01 mol) and phosphorus
oxychloride (5 mL) was heating under reflux for 3 h. Upon
cooling, distilled water (50 mL) was added to the mixture and
the heating under reflux was carried out for another 4 h. The
obtained filtrate was neutralized with potassium hydroxide.
EXPERIMENTAL
All the reagents, starting materials as well as solvents were
purchased commercially and used without any further purifi-

4204 Win et al.
Asian J. Chem.
Then, the precipitate was filtered and washed with cold distilled
water and finally recrystallized by using ethanol-water solvent
mixture to obtain 5-(4-nitrophenyl)-1,3,4-thiadiazol-2-amine.
In the next reaction, 5-(4-nitrophenyl)-1,3,4-thiadiazol-2-
amine (0.01 mol) and salicyladehyde (0.01 mol) was heating
under reflux for 3 h to obtained the yellow precipitate. The
precipitated obtained was filtered and crystallized from ethanol
to give the respective 2-{[5-(4-nitrophenyl)-1,3,4-thiadiazol-
2-ylimino]methyl}phenol, HL ligand for the further complex-
ation with metal ion. The stepwise preparation of the ligand
(HL) is shown in Fig. 1.
Preparation of complexes: An ethanolic solution of the
corresponding metal(II) compounds [nickel(II) chloride
hexahydrate, tin(II) chloride, copper(II) chloride dihydrate,
cadmium(II) chloride dihydrate and zinc(II) chloride] was
added to ethanolic solution of 2-{[5-(4-nitrophenyl)-1,3,4-
thiadiazol-2-ylimino] methyl}phenol (HL) in 1:2 (metal:
ligand) molar ratio. Then, the mixture was heating under
reflux for 0.5 h and coloured precipitates were obtained. Later,
the precipitates were filtered out, washed with distilled water
and finally recrystallized from ethanol.
RESULTS AND DISCUSSION
In general, the complexes obtained by heating under
reflux of respective metal salts with ligand (HL) in 1:2 molar
ratio. The purity of the ligand (HL) and its metal complexes
1-5 obtained were checked by TLC using silica gel-G as
adsorbent. Complexes 1-5 gave a sharp melting point indicated
the isolation of fairly pure complexes. The micro-elemental
analysis for C, H, N and S as well as the molecular weight of
the complexes obtained were in agreement with the predicted
formula for complexes 1-5. An outline of the proposed struc-
ture for complexes 1-5 and ligand (HL) are depicted in Fig. 1.
The melting point, micro-elemental analysis and m/z data are
given in Table-1.
O2N
COOH
4-nitrobenzoic acid
thiosemicarbazide, POCl3
reflux 3 hrs
N
N
O2N
NH3+Cl-
S
5-(4-nitrophenyl)-1,3,4-thiadiazol-2-aminium chloride
KOH
The infrared spectrum of ligand (HL) showed some charac-
teristic stretching bands at 1635 and 1116 cm-1 assigned to
ν(C=N) and ν(C-O), respectively which could be found in
complexes 1-5. The exceptional case is that the ν(C=N) of
complexes 1-5 were found to be shifted to a lower wavelength
number compared to the ligand, HL signifying that the coordi-
nation took place via the nitrogen atom of the ligand (HL)15.
In addition, the stretching of metal-oxygen and metal-nitrogen
bands of the complexes appeared in the lower wavelength
region in the range of 556-500 and 488-432 cm-1 also signifies
the complexation through nitrogen and oxygen atoms from
the ligand16. The important infrared data of the ligand, HL
and complexes 1-5 are given in Table-2.
N
N
O2N
NH2
S
5-(4-nitrophenyl)-1,3,4-thiadiazol-2-amine
salicyladehyde
reflux 3 hrs
HO
N
N
O2N
N
C
H
S
2-{[5-(4-nitrophenyl)-1,3,4-thiadiazol-2-ylimino]methyl}phenol
The ultraviolet visible electronic spectrum of the ligand,
HL and complexes 1-5 in ethanol solution are given in Table-3.
The acid showed three bands at 210, 254 and 346 nm attributed
to π → π*, π → π* and n → π* electronic transition, respec-
tively. From Table-3, complexes 1, 4 and 5 also showed the
similar electronic transition as observed in the ligand, HL. For
complexes 2 and 3, the electronic transitions of the metal d
orbitals (d-d electronic transition) observed in the Ni(II) and
Cu(II) located in the visible region as an extra information. In
Ni(II), d-d electronic transition appeared at 728 and 1322
H
S
C
N
NO2
N
N
O
M
O
N
N
O2N
N
C
S
H
Fig. 1. Structure of acid (HL) and the proposed structure of complexes
1-5 (M = Ni, Cu, Zn, Cd or Sn)
TABLE-1
MELTING POINTS, ELEMENTAL ANALYTICAL DATA (%) AND m/z VALUE OF HL AND COMPLEXES 1-5
Elemental (%)
Physical
appearance
Compounds
m.p. (ºC)
m/z
C
H
N
S
M
HL
Yellow
Blue
113-115
140-142
160-162
129-131
111-114
135-137
55.44 (55.04)
25.25 (25.33)
25.33 (25.15)
24.89 (25.09)
23.12 (23.55)
23.02 (23.35)
3.33 (3.36)
1.34 (1.55)
1.22 (1.54)
1.33 (1.53)
1.32 (1.44)
1.09 (1.42)
17.32 (17.12)
7.55 (7.88)
7.90 (7.82)
7.55 (7.81)
7.55 (7.32)
7.55 (7.26)
9.99 (9.78)
4.44 (4.50)
4.34 (4.47)
4.33 (4.46)
4.33 (4.18)
4.20 (4.15)
–
327.0
710.7
715.5
717.4
764.4
770.69
8.45 (8.26)
9.02 (8.88)
8.98 (9.11)
14.44 (14.70)
15.56 (15.40)
Ni(L)2, 1
Cu(L)2, 2
Zn(L)2, 3
Cd(L)2, 4
Sn(L)2, 5
Green
Yellow
Yellow
Yellow
Calculated value are given in parentheses.

Vol. 25, No. 8 (2013) Synthesis andAntibacterialActivity of Metal Complexes Derivatives of 1,3,4-Thiadiazol-2-ylimino]methyl}phenol 4205
samples obtained. The 1H and 13C NMR spectra data of ligand,
TABLE-2
KEY INFRARED DATA OF HL AND COMPLEXES 1-5
HL and complexes 1-5 are given in Table-4.
Wavelength (cm-1)
Magnetic moment measurements are widely used in
Compounds
ν(C=N)
1635
1602
1600
1610
1608
1608
ν(C-O)
1116
1122
1120
1109
1110
1121
ν(M-O)
ν(M-N)
studying transition metal complexes and the magnetic moment
of complexes 1-5 are given in Table-5. The magnetic properties
are due to the presence of unpaired electrons in the partially
filled d-orbital in the outer shell of these elements. These
magnetic measurements give an outline about the electronic
state of the metal ion in the complexes. The magnetic moment
value of complex 1 was ca. 4.33 B.M. and referred as para-
magnetic and the geometry of nickel(II) metal centre was
distorted tetrahedral. Complex 2 showed that the magnetic
moment value at 0.85 B.M. and believed that the copper(II)
metal moiety exhibited distorted square planar geometry21.
Complexes 3-5 are diamagnetic and there were no magnetic
moment recorded in this study. Based on the molar conduc-
tivity measurements study of complexes 1-5 in (Table-5), all
the prepared complexes were found to be non-electrolyte.
HL
–
–
510
504
500
510
556
488
482
432
444
480
Ni(L)2, 1
Cu(L)2, 2
Zn(L)2, 3
Cd(L)2, 4
Sn(L)2, 5
TABLE-3
ELECTRONIC SPECTRA DATA OF HL
AND COMPLEXES 1-5 IN ETHANOL
Absorption bands
(nm)
Comp.
Assigned transition
HL
210, 254, 346
π → π*, π → π*, n → π*
245, 349 728
(av.), 1322 (calc.)
Ni(L)2, 1
π → π*, n → π*,
3T1(F) → 3T1(P), 3T1(F) → 3A2(F)
π → π*, n → π*, L → Cu(C.T.),
2B1g → 1A1g, 2B1g → 2B2g, 2B1g → Eg
π → π*, n → π*
245, 348, 440
500, 680, 904
Cu(L)2, 2
TABLE-5
CONDUCTIVITY MEASUREMENTS AND MAGNETIC
MOMENT OF HL AND METAL COMPLEXES 1-5 IN DMF
252, 349
250, 350
238, 323
Zn(L)2, 3
Cd(L)2, 4
Sn(L)2, 5
π → π*, n → π*
π → π*, n → π*
Conductivity
(µS/cm)
Magnetic
moment (BM)
Proposed
structure
Compounds
calculated) nm assigned to the 3T1(F) → 3T1(P) and 3T1(F) →
3A2(F) transition, respectively17. For Cu(II), the bands appeared
at 440, 550, 680 and 904 nm were attributed to the L (ligand)
→ Cu (charge transfer, C.T.), 2B1g → 1A1g, 2B1g → 2B2g and 2B1g
HL
–
–
–
20
17
17
9
4.33
0.85
0.00
0.00
0.00
Tetrahedral
Square planar
Tetrahedral
Tetrahedral
Tetrahedral
Ni(L)2, 1
Cu(L)2, 2
Zn(L)2, 3
Cd(L)2, 4
Sn(L)2, 5
→ Eg, respectively18,19
.
20
The 1H NMR spectra of complexes 1-5 gave an additional
support for the formation of the complexation. In the 1H NMR
spectra of ligand, HL showed a sharp peaks, δ(OH) at 9.90
ppm which was absent in the spectra of the complexes 1-5
indicated deprotonation and complexation of ligand anion to
metal ions. The 1H NMR spectra of complexes 1-5 exhibited
some similarities to the ligand, HL with the occurrence of
-N=CH- and aromatic protons signals centering at δ ≈ 7.35
ppm and in the range of 8.23-9.20 ppm, respectively20. From
the 13C NMR study, all the complexes obtained also exhibited
some similarities to the ligand, HL with the occurrence of
-N=CH- carbon signals centering at δ ≈ 111.00 ppm and
thiadiazole carbons signals centering at δ ≈ 87.60 and 90.78
ppm, respectively. Moreover, the aromatic carbons signals of
both complexes 1-5 and ligand, HL were located at the
downfield region in the range of 125.42-132.61 ppm. Generally,
there is no uncharacterized peak in the 1H and 13C NMR spectra
of ligand, HL and complexes 1-5 signify the purity of the
All the complexes obtained were studied in ethanol
solution to determine the [M/L] ratio in the complex by Job's
Method22. A series of solutions were prepared with a constant
concentration (10-3 M) of the metal ion and ligand, HL. The
[M/L] ratio was determined from the relationship between the
absorption of the absorbed light and the mole ratio of [M/L].
The study showed that the metal to ligand, HL ratio was [1/2]
for complexes 1-5 and found to be similar to the solid state.
Based on the spectral study, complexes 1-5 exhibited distorted
tetrahedral geometry except complex 2 (distorted square
planar). The proposed structures of complexes 1-5 are depicted
in Fig. 1.
The preliminary in vitro antibacterial screening activity
of ligand (HL) and complexes 1-5 are given in Table-6. The
synthesized complexes and ligand, HL were screened for their
in vitro antibacterial activity against Staphylococcus aureus,
TABLE-4
1H AND 13C NMR DATA OF HL AND METAL COMPLEXES 1-5 IN DMSO-d6
Chemical shift, δ (ppm)
1H NMR
13C NMR
Compounds
HL
-N=CH-
7.38 (s)
7.32 (s)
7.31 (s)
7.33 (s)
7.32 (s)
7.35 (s)
Aromatic
OH
9.90
–
-N=CH-
111.12
112.67
110.85
111.49
112.34
110.56
Thiadiazole
87.70, 90.79
87.66, 90.77
87.66, 90.80
87.64, 90.79
87.61, 90.76
87.66, 90.78
Aromatic
8.23-9.05 (m)
8.33-9.16 (m)
8.29-9.17 (m)
8.39-9.20 (m)
8.27-9.19 (m)
8.31-9.17 (m)
125.43-132.54
125.57-132.51
125.52-132.61
125.42-132.52
125.52-132.61
125.42-132.54
Ni(L)2, 1
Cu(L)2, 2
Zn(L)2, 3
Cd(L)2, 4
Sn(L)2, 5
–
–
–
–

4206 Win et al.
Asian J. Chem.
TABLE-6
PRELIMINARY IN VITRO ANTIBACTERIAL SCREENING ACTIVITY OF HL AND COMPLEXES 1-5
Inhibition zone (mm)
Comp.
Staphylococcus aureus
100 (µg/mL) 200 (µg/mL)
Salmonella typhi
Escherichia coli
100 (µg/mL)
200 (µg/mL)
100 (µg/mL)
200 (µg/mL)
HL
–
+
+
+
+
++
+
+
+
+
+
+
++
+
+
Ni(L)2, 1
Cu(L)2, 2
Zn(L)2, 3
Cd(L)2, 4
Sn(L)2, 5
++
–
+
++
++
++
++
++
++
+++
++
+
++
+
++
++
+
++
++
+
++
+ = 5-10 mm, ++ = 11-20 mm, +++ = larger than 20 mm, – = no inhibition.
Salmonella typhi and Escherishia coli bacterial strains by
inhibition zone method using agar diffusion method23,24. In
this method a standard 6.35 mm diameter sterilized filter paper
disc impregnated with the compound (200 and 100 µg/mL in
DMSO) was placed on an agar plate seeded with the test
bacterial strains. The plates were incubated for 24 h at 37 ºC.
The activity was determined by measuring the diameter of the
inhibition zone (in mm) and streptomycin was used as the
standard control. The preliminary screening results revealed
that complexes 1-5 showed a significant activity compared to
the ligand, HL. Overall, the activities of all the complexes
obtained were found to be moderate even though higher
concentration were applied. This may be due to the bulkiness
of the molecule with a complicated structure which in turn
restrict their mobility to the target cell or active site although
all the complexes obtained as a monomeric and four-coordi-
nated metal(II) moiety.
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Conclusion
The ligand 2-{[5-(4-nitrophenyl)-1,3,4-thiadiazol-2-
ylimino]methyl}phenol, HL was successfully synthesized. The
ligand, HL was coordinated to five different metal ions via
oxygen and nitrogen atoms to afford the corresponding comp-
lexes. All the complexes were four-coordinated and exhibited
distorted tetrahedral geometry except complex 2 (distorted
square planar). Preliminary in vitro antibacterial study indicated
that all the complexes obtained showed moderate activity
against the tested bacterial strains and slightly higher activity
compared to the ligand, HL.
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