Nickel(II) complex of p-[N,N-bis(2-chloroethyl)amino]benzaldehyde-4-methyl thiosemicarbazone: Synthesis, structural characterization and biological application

Article abstract of DOI:10.1016/j.poly.2012.11.006

New complex of Ni(II) with p-[N,N-bis(2-chloroethyl)amino]benzaldehyde-4- methyl thiosemicarbazone (CEAB-4-MTSC) have been synthesized and characterized by elemental analysis, IR, electronic, ¹H NMR spectroscopy. The crystal structure of the fr

Full text of DOI:10.1016/j.poly.2012.11.006

Polyhedron 50 (2013) 264–269
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Polyhedron
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Nickel(II) complex of p-[N,N-bis(2-chloroethyl)amino]benzaldehyde-4-methyl
thiosemicarbazone: Synthesis, structural characterization and biological application
b
c
Anitha Sankaraperumal a, J. Karthikeyan a, , A. Nityananda Shetty , R. Lakshmisundaram
⇑
a Department of Chemistry, Sathyabama University, Chennai 600 119, India
b Department of Chemistry, National Institute of Technology Karnataka, Mangalore 575 025, India
c Central Research Facility, Sri Ramachandra University, Chennai 600116, India
a r t i c l e i n f o
a b s t r a c t
Article history:
New complex of Ni(II) with p-[N,N-bis(2-chloroethyl)amino]benzaldehyde-4-methyl thiosemicarbazone
(CEAB-4-MTSC) have been synthesized and characterized by elemental analysis, IR, electronic, 1H NMR
spectroscopy. The crystal structure of the free ligand and complex has been determined by single crystal
X-ray diffraction technique. In the complex, thiosemicarbazone ligand is coordinated to nickel through
Received 6 August 2012
Accepted 2 November 2012
Available online 28 November 2012
ꢀ
(1:2 complex) SNNS mode. The complex crystallizes in the triclinic with space group P1. The complex
Keywords:
Ni(II) complex
Square planar complex
Thiosemicarbazone
SNNS donor type complex
has been tested for their antibacterial activity against various pathogenic bacteria. From this study, it
was found out that the activity of complex reaches the effectiveness of the conventional bacteriocide
Streptomycin compared to simple ligand.
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
themselves, based on that new Ni(II) complex have been screened
for their antibacterial activity against various pathogenic bacteria.
Thiosemicabazone {R1R2C@N3–N2H–C(@S)–NR3R} possess NNS
donor atom and generally bind to metal via N2, S or N3, S donor
atom forming four or five member ring, respectively. Thiosemicar-
bazones (TSC), as well as their metal complex, has been the subject
of great interest of many researchers for a number of years. Apart
from their diverse chemical and structural characteristics, the
interest on these compounds also stems from their wide spectrum
of biological activity. Their biological importance is evidenced by a
wide range of antibacterial, antimalarial, antiviral, antineoplastic
and antileprotic activities [1,2]. Such pharmacological activities
are due to the strong chelating ability of this ligand with biologi-
cally important metal ions such as Fe, Cu, Ni and their reductive
capacities [3–8]. Though the versatility of thiosemicarbazone li-
gand for binding to the metal ion has been well established else-
where, there remains an ambiguity in predicting the actual
coordination mode of thiosemicarbazone. As a part of continuing
interest in this area of research, we have investigated coordination
behaviour of square planar nickel(II) complex of thiosemicarba-
zone. The complex have been characterized by spectral and X-ray
crystallography. With our keen interest in microbiological studies,
based on the fact that metal complex are systematically more
active to control pathogenic bacteria than the simple ligand by
The proposed metal complex contain aldehyde (nitrogen mustard–
anticancer agent)–thiosemicarbazone (chemotherapeutic agent)–
nickel (biologically important) metal link, so we are sure that the
new synthetic compound will have a synergic effect to control
pathogenic bacteria. These types of new therapeutic approach are
rapidly emerging and further research may help in designing more
specific chelates. Moreover, this complex is going to be a member
of new larger family of complex with nickel(II) ion. This type of
nickel(II)–thiosemicarbazone complex afford a wide variety of
structure with associated conducting and magnetic properties
and such complex has potential for use as building block in the
preparation of novel molecular material with interesting conduct-
ing or magnetic properties [9,10]. The general reaction scheme
(Scheme 1) for the preparation of the ligand in the present work
is given below.
2. Experimental
2.1. Materials
All reagents and reactant were of analytical grade. The starting
material p-[N,N-bis(2-chloroethyl)amino]benzaldehyde prepared
by the reported procedure [11]. The purity of the compound
checked by the elemental analysis and by melting point. 4-Methyl
thiosemicarbazide, nickel salt was purchased from Aldrich and
Merck respectively and were used as received.
⇑
Corresponding author. Tel.: +91 44 22422776.
E-mail addresses: dr.j.karthikeyan@gmail.com, jkarthik_chem@rediffmail.com
(J. Karthikeyan).
0277-5387/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.poly.2012.11.006

A. Sankaraperumal et al. / Polyhedron 50 (2013) 264–269
265
Scheme 1.
2.2. Measurements
position with refined site occupancies of 0.696(5) and 0.304(5),
respectively. Similarly for [Ni(CEAB-4-MTSC)2], the positional
disordered 2-chloroethylamino group were refined to a site occu-
pancies of 0.711(6) and 0.289(6) for C10C11Cl1 and 0.721(2) and
0.283(2) for C12C13Cl2, respectively. In both structure, bond distance
of the minor component were made similar to the major compo-
nents using certain similarity restraints with a standard of uncer-
tainty of 0.01 and 0.02 Å, respectively. The positions of the entire
hydrogen atom were identified from the differential electron den-
sity map and were allowed to ride on the parent atom.
Infrared spectral measurement were done on a Shimadzu DR
8001 series FTIR instrument using KBr pellets for spectra in the
region 4000–400 cmꢀ1, and far IR spectra were recorded using
polyethylene pellets in the 500–100 cmꢀ1 region on a Nicolet mag-
na 550 FTIR instrument. An ocean optics SD 2000 fiber optic spec-
trometer was used to measure solid-state reflectance spectra in the
range 200–900 nm. 1H NMR spectra were recorded using AMX
400 MHz FT-NMR Spectrometer with DMSO as solvent. EPR spec-
tral measurements were carried out on a Varian E-112 X-band
spectrometer using TCNE as standard. The magnetic susceptibility
measurement were made using a simple Gouy balance at room
2.5. Preparation of CEAB-4-MTSC ligand
temperature
Hg[Co(NCS)4] as calibrant.
using
mercury
tetrathiocyanatocobaltate(II),
The
p-[N,N-bis(2-chloroethyl)amino]benzaldehyde-4-methyl
thiosemicarbazone (CEAB-4-MTSC) was prepared by refluxing eth-
anol solution of p-[N,N-bis(2-chloroethyl)amino]benzaldehyde
(20 mL) with 4-methylthiosemicarbazide (20 mL) in presence of
hydrochloric acid (35%, 0.5 mL) taken into a 250 mL round bottom
2.3. Unit cell determination of the complex
X ray diffraction study was carried out using a Brukeraxs kappa
Apx II single crystal CCD diffractometer equipped with Mo K
(k = 0.7107 Å) radiation. The goniometer equipped with the diffrac-
tometer is four circle goniometer with and 2h axes by which
a
Table 1
Crystal data and structure refinement of CEAB-4-MTSC and Ni (CEAB-4-MTSC)2.
u, v, x
the crystal is rotated. A crystal specimen of size 0.30 ꢁ 0.25
ꢁ 0.20 mm was cut and mounted on a glass fiber using cyano acry-
late. The unit cell parameters were determined by collecting the dif-
fracted intensities from 36 frames measured in three different
crystallographic zones and using the method of difference vectors
Parameters
CEAB-4-MTSC
CCDC 817418
Ni (CEAB-4-MTSC)2
CCDC
Empirical formula
Formula weight
T (K)
CCDC 840170
C26H34Cl4N8NiS2
723.24
C13H18Cl2N4S
333.27
293(2)
0.71073
293(2)
k (Å)
0.71073
triclinic, P1
followed by data collection at 293 K using
x–u scan modes.
ꢀ
ꢀ
Crystal system, space
triclinic, P1
group
Unit cell dimensions
2.4. Structure solution and refinement of the complex
a (Å)
b (Å)
c (Å)
9.6538(4)
7.5947(5)
9.8404(4)
8.8875(8)
The structure was solved by direct method using the program
SHELXS 97[12], which revealed the position of all non-hydrogen
atoms, and refined on F2 by a full matrix least squares procedure
using SHELXL 97. The non hydrogen atoms were refined anisotropi-
cally and the hydrogen atoms were allowed to ride over their parent
atoms. The final cycle of refinement converged to R1 = 0.0392 and
wR2 = 0.1056 for the observed reflections. The maximum and min-
imum heights in the final difference Fourier map were found to be
0.388 and ꢀ0.441 e Åꢀ3, respectively. Least squares planes and
asymmetry calculations were done using the program PARST 97.
The thermal ellipsoid plot and packing were done using ORTEP and
PLATON, respectively [13,14]. Non bonded interaction graphics were
created using the program PLATON. The crystallographic data and
methods of data collection, solution and refinement are shown in
Table 1 and selected bond distances and angles in Table 2. The
atomic coordinates and equivalent isotropic displacement coeffi-
cients are included in the deposited material (CCDC – 817418 for
ligand and 840170 for complex) as a complete list of bond distance
and angle. In both the crystal structure of CEAB-4-MTSC and
[Ni(CEAB-4-MTSC)2], all the 2-chloroethylamino group is disor-
dered and is treated well during refinement. In CEAB-4-MTSC the
2-chloroethylamino group is positional disordered over two
10.3659(4)
94.306(2)
107.195(2)
115.192(2)
2
12.9688(8)
80.987(4)
80.934(4)
65.842(4)
2
a
b (°)
c
Z
(°)
(°)
Dcalc (Mg/m3)
Crystal size (mm)
F(000)
1.337
1.531
0.30 ꢁ 0.25 ꢁ 0.20
0.30 ꢁ 0.25 ꢁ 0.20
348
374
h (°)
Limiting indices
2.11–24.99
ꢀ11 6 h 6 11,
ꢀ11 6 k 6 11,
ꢀ12 6 l 6 12
15128/2911 (0.0295)
2.52–29.38
ꢀ10 6 h 6 10,
ꢀ11 6 k 6 12,
ꢀ17 6 l 6 17
18489/4293 (0.0287)
Reflections collected/
unique (Rint
)
Refinement method
full-matrix least-
squares on F2
2911/7/211
full-matrix least-
squares on F2
4293/9/250
Data/restraints/
parameters
Goodness-of-fit (GOF) on
1.045
1.006
F2
Final R-indices [I > 2
r
(I)]
R1 = 0.0539,
wR2 = 0.1442
R1 = 0.0766,
wR2 = 0.1642
0.388 and ꢀ0.441
R1 = 0.0392,
wR2 = 0.1056
R1 = 0.0611,
wR2 = 0.1210
0.537 and ꢀ0.260
R-indices (all data)
Largest diff. peak and
hole (e Åꢀ3
)

266
A. Sankaraperumal et al. / Polyhedron 50 (2013) 264–269
Table 2
(MRSA-methicillin resistant, clinical pathogen) were used. Candida
albicans MTCC 227, Malassesia pachydermatis and Trichophyton
mentagrophytes 66/01 were used for antifungal activities. The ref-
erence cultures were obtained from Institute of Microbial Technol-
ogy (IMTECH – CSIR), Chandigarh, India 160 036. All the cultures
were obtained from the Department of Microbiology, Christian
Medical College, Vellore, Tamil Nadu, India. Bacterial inoculums
were prepared by growing cells in Mueller Hinton broth (MHB)
(Himedia) for 24 h at 37 °C. The filamentous fungi were grown
on sabouraud dextrose agar (SDA) slants at 28 °C for 10 days and
the spores were collected using sterile doubled distilled water
and homogenized. Yeast was grown on sabouraud dextrose broth
(SDB) at 28 °C for 48 h.
Selected bond lengths (Å) and angles (°) of CEAB-4-MTSC and Ni (CEAB-4-MTSC)2.
Bond length
CEAB-4-MTSC Bond length
Ni (CEAB-4-MTSC)2
C(1)–C(2)
C(2)–N(4)
N(4)–C(5)
N(4)–C(3)
C(3)–C(4)
C(5)–C(10)
C(5)–C(6)
C(6)–C(7)
C(7)–C(8)
C(8)–C(9)
C(9)–C(10)
C(8)–C(11)
C(11)–N(1)
C(12)–N(3)
C(12)–N(2)
C(12)–S(1)
C(13)–N(3)
N(1)–N(2)
1.498(6)
1.439(6)
1.391(5)
1.464(5)
1.473(6)
1.392(4)
1.400(4)
1.362(4)
1.388(4)
1.386(4)
1.370(4)
1.450(4)
1.271(4)
1.320(4)
1.344(4)
1.683(3)
1.452(4)
1.380(3)
C(1)–N(2)
C(1)–N(3)
C(1)–S(1)
C(2)–N(3)
C(3)–N(1)
C(3)–C(4)
C(4)–C(5)
C(4)–C(9)
C(5)–C(6)
C(6)–C(7)
C(7)–N(4)
C(7)–C(8)
C(8)–C(9)
N(1)–N(2)
N(1)–Ni(1)
N(4)–C(10)
N(4)–C(12)
S(1)–Ni(1)
Ni(1)–N(1)#
Ni(1)–S(1)#
C(12)–C(13)
C(10)–C(11)
1.297(3)
1.350(3)
1.732(2)
1.436(3)
1.298(3)
1.448(3)
1.387(3)
1.399(3)
1.373(3)
1.393(3)
1.379(3)
1.401(3)
1.369(3)
1.401(2)
1.9195(16)
1.440(9)
1.487(4)
2.1771(6)
1.9195(16)
2.1771(6)
1.499(5)
1.493(10)
2.8. Antimicrobial assay
Antibacterial and antifungal activity was carried out using disc-
diffusion method [15]. Petri plates were prepared with 20 mL of
sterile Mueller Hinton Agar (MHA) (Hi-media, Mumbai). The test
cultures were swabbed on the top of the solidified media and
allowed to dry for 10 min and a specific amount (25 lL from the
40 mg/mL) of compound was added to each disc. The loaded discs
were placed on the surface of the medium and left for 30 min at
room temperature for compound diffusion. Negative control was
Bond angles
Bond angles
C(2)–C(1)–Cl(1)
N(4)–C(2)–C(1)
C(5)–N(4)–C(2)
C(5)–N(4)–C(3)
C(2)–N(4)–C(3)
N(4)–C(3)–N(4’)
N(3)–C(12)–N(2) 116.3(3)
N(3)–C(12)–S(1)
N(2)–C(12)–S(1)
105.2(4)
112.4(4)
122.4(4)
120.6(3)
116.7(4)
23.6(4)
N(2)–C(1)–N(3)
N(2)–C(1)–S(1)
N(3)–C(1)–S(1)
N(1)–C(3)–C(4)
C(5)–C(4)–C(9)
C(5)–C(4)–C(3)
C(1)–S(1)–Ni(1)
119.10(19)
123.65(16)
117.25(16)
132.6(2)
116.36(19)
117.33(19)
95.46(7)
prepared using respective solvents. Streptomycin (10 lg/disc)
was used as positive control. The plates were incubated for 24 h
at 37 °C for bacteria and for 48 h at 28 °C for fungi. Zones of inhibi-
tion were recorded in milli meters and the experiment was
repeated twice.
124.1(2)
119.6(2)
N(1)#–Ni(1)–N(1) 179.999(2)
N(1)#–Ni(1)–S(1)
N(1)–Ni(1)–S(1)
N(1)–Ni(1)–S(1)#
94.40(5)
85.60(5)
94.40(5)
C(12)–N(2)–N(1) 120.0(3)
C(11)–N(1)–N(2) 116.0(3)
2.9. Minimum inhibitory concentration (MIC)
Minimum inhibitory concentration studies of synthesis com-
pound were performed according to the standard reference meth-
od for bacteria [16], for filamentous fungi (CLSI, 2008) and yeasts
(NCCLS/CLSI, 2002). The required concentrations (1000, 500, 250,
flask. The mixture was refluxed for around 2 h and cooled, after
cooling, a yellow precipitate appeared, filtered, washed with etha-
nol followed by ether. The compound is recrystallized using small
amount of ethanol to get pure shiny yellow crystals suitable for
X-ray crystallography. [Analysis results for C13H18Cl2N4S. Found,
125, 62.5, 31.25 and 15.62 lg/mL) of the compound and fractions
were dissolved in DMSO (2%), and diluted to give serial twofold
dilutions that were added to each medium in 96 well plates. An
inoculum of 100 from each well was inoculated. The antifungal
agents Ketoconazole for fungi and Streptomycin for bacteria were
included in the assays as positive controls. For fungi, the plates
were incubated for 48–72 h at 28 °C and for bacteria the plates
were incubated for 24 h at 37 °C. The MIC for fungi was defined
as the lowest extract concentration, showing no visible fungal
FT-IR (KBr): 3375 cmꢀ1 N–H), 1604 cmꢀ1 C@N), 813 cmꢀ1
(m (m (mC@S).
The 1H NMR data for compound show that the N–H and azome-
thine (–CH@N–) protons are observed as singlet 11.26 and
7.92 ppm, respectively. While the phenyl protons of the compound
gave a multiplet at d = 6.76–7.62 ppm. The signals due to the –
CH2–CH2– protons are gave a multiplet at d = 3.00–3.80 ppm].
growth after incubation time. 5 lL of tested broth was placed on
the sterile MHA plates for bacteria and incubated at respective
temperature. The MIC for bacteria was determined as the lowest
concentration of the compound inhibiting the visual growth of
the test cultures on the agar plate.
2.6. Preparation of new [Ni(CEAB-4-MTSC)2] complex
A mixture of NiCl2ꢂ6H2O (1 mmol) and CEAB-4-MTSC (2 mmol)
in ethanol was stirred for around 4 h using magnetic stirrer at
room temperature, after which it was set aside, overnight when
an dark brown crystalline product separated out, which was fil-
tered, washed with cold ethanol and dried in vacuo. Dark brown
crystals suitable for X-ray diffraction study were obtained for the
nickel complex by slow evaporation of its DMSO solution.
3. Results and discussion
3.1. Spectral and magnetic measurements
IR spectrum of the complex was compared with those of the li-
gand in order to find out the point of attachment of the ligand to
the metal ion in the complex. The IR spectrum of the free Schiff base
ligand showed a strong absorption at around 1622–1595 cmꢀ1 due
2.7. Bacterial strains
The following bacteria and fungi were used for the experiment.
Staphylococcus aureus MTCC 96, Micrococcus, Shigella flexneri MTCC
1457, Staphylococcus epidermidis MTCC 3615, Proteus vulgaris MTCC
1771, Pseudomonas aeruginosa MTCC 741, Klebsiellap neumonia
MTCC 109, Salmonella typhimurium MTCC 1251, Bacillus subtilis
MTCC 441, Salmonella paratyphi-B and Staphylococcus aureus
to the azomethine m(C@N) group. This absorption has been shifted
to lower frequency in the complex indicating the coordination of
the azomethine nitrogen to nickel ion [17,18]. The presence of a
new band in the region 440–450 cmꢀ1 due to
m
(Ni–N) is another
indication nitrogen of azomethine group in coordination. The
(C–S) band that appeared at around 815 cmꢀ1 in the free Schiff
m

A. Sankaraperumal et al. / Polyhedron 50 (2013) 264–269
267
Scheme 2.
bases disappeared completely and a new band appeared in the re-
gion 738–756 cmꢀ1 attributed to the enolisation of NH–C@S group
and subsequent coordination through the sulphur atom due to
metal complex.
moiety is 13.12° and 6.90°, respectively, strongly confirming that
the atom N(1) is in sp2 hybridized state and the both group are lie
in the same plane, due to the presence of hetero p–electron delocal-
ization in the entire molecule [33]. The bond length of C5–C6, C5–
C10, C7–C8, and C8–C9 in CEAB-4-MTSC molecule are 1.400(4),
1.392(4), 1.388(4) and 1.386(4) Å, respectively, these length are
considerably higher than the normal value of 1.37 Å. These bond
length variation are attributed to the resonance character of the
methyl amine, phenyl ring and also that of imine nitrogen. In the
title compound, bis(2-chloroethyl) amino moiety is disordered over
two positions. The atoms N4–C2–C1–Cl1 and its disordered compo-
nent N04–C02–C01–Cl01 exist in two position with percentage of occu-
pancy 70% and 30%, respectively, whereas the position of the atom
The 1H NMR data for parent ligand shows singlet at 11.26 ppm
due to the hydrazide N–H group. Absence of this signal in the spec-
tra of the metal complexes confirms deprotonation of the thiosem-
icarbazone chain and subsequent coordination through the
thiolato form. Azomethine (–CH@N–) proton are observed as dou-
blet at 7.99 and 8.00 ppm, respectively. While the phenyl proton of
the compound gave a multiplets at d = 6.60–7.24 ppm. The signals
due to the –CH2–CH2– proton are gave a multiplets at d = 3.00–
3.80 ppm. There is no sign of a signal from thiol (–SH) group, which
would be expected around 4 ppm [19] strongly confirm thione
form.
0
Cl2 and its disordered component Cl2 has the percentage of occu-
pancy 67% and 33%, respectively. The Ortep diagram of the title
compound with 40% ellipsoid probability showing the disordered
component in Fig. 1.
The UV–Vis absorption spectrum of the brown colour Ni(II)
complex in DMSO medium in the region around 200–900 nm dis-
played mainly three bands in the region 265 nm (37735 cmꢀ1),
375 nm (26666 cmꢀ1) and at 460 nm (21739 cmꢀ1). These bands
may be assigned to three spin allowed transitions 1A1g?1Eg,
1A1g?1A2g and 1A1g?1B1g, respectively. The bands in the region
around 26000 cmꢀ1 are due to S?Ni(II) charge transfer transition
(LMCT) and are primarily responsible for brown color of the Ni(II)
complex. Absence of bands below 10000 cmꢀ1 confirms square-
planar nature of the complex, consistent with low spin and dia-
3.2.2. Crystal structure of the complex [Ni(CEAB-4-MTSC)2]
On the basis of the charge balance, bond distance and geometry
of the ligand, the crystal structure of the complex indicate that the
thiosemicarbazone ligand has lost a proton from its tautometric
thiol form and act as a single negatively charged bidentate ligand
coordinating to the nickel ion via the mercapto sulfur and b-nitrogen
atom. The geometry around Ni(II) is almost square-planar with two
equivalent Ni–N and two equivalent Ni–S bond, consists of neutral
molecule [Ni(CEAB-4-MTSC)2], with nickel at the centre of symme-
try. Crystal structure of the complex is shown in Fig. 2. The Ni–S
bond length is 217.71 pm, while the Ni–N bond length is
191.95 pm with the coordination sphere approaching a square pla-
nar configuration, which involves the thiolato sulfur atom and the
imine nitrogen atom N1 of the two ligand in trans-configuration. In
the free ligand, however, these centres are in trans configuration,
indicating that the complexation occurs after a 180° rotation
around the C1–N2 bond. As the ligand is deprotonated on N2 atom,
a negative charge appears and is delocalized along the thiosemicar-
bazone moiety. This fact is confirmed by the difference between
the bond distance in the deprotonated ligand of nickel complex
magnetic (leff = 0.00 BM) nature [20–26].
3.2. X-ray crystallography
3.2.1. Crystal structure of the ligand CEAB-4-MTSC
Thiosemicarbazone exist in two tautomeric form, thione (A) and
thiol (B) (Scheme 2). The thione function as bidentate neutral
ligand and the thiol can deprotonate and act as an anionic ligand.
Due to the presence of C@N, thiosemicarbazone exist as E and Z ste-
reoisomer. Considering the thermodynamic stability, E isomer will
predominate in the mixture [27]. The crystal structure reveal that
the compound exist in the thione form and C11 and C12 are at E
configuration to each other with respect to N1–N2 bond. The thione
form in the solid state is strongly confirmed by the observed bond
length C12–S1 [1.683(3) Å], C12–N2 [1.344(4) Å] and C12–N3
[1.320(4) Å]. The C12–S1 distance of 1.683(3) Å is closer to C@S
bond length [1.62 Å] than to C–S bond length [1.81 Å], and C12–
N2, C12–N3 distance of 1.344(4) and 1.325(6) Å respectively is in
the range of 1.349(6)–1.386(4) Å for other thiosemicarbazone hav-
ing C–N single bond reported earlier [28,29]. The shorter than usual
length of C–N and longer than usual length of C@S point out the ex-
tended conjugation in the molecule, However, the N(1)–N(2)
[1.380(3) Å], N(2)–C(12) [1.344(4) Å] and C12–N3 [1.325(6) Å]
bond distance observed are intermediate between the ideal value
of corresponding single [N–N, 1.45 Å; C–N, 1.47 Å] and double bond
[N@N, 1.25 Å; C@N, 1.28 Å] which are in support of an extended ‘p’
delocalization along the thiosemicarbazone chain [30–32]. The an-
gle around the atom of N1 is 359.7° and dihedral angle between the
benzene ring to the thiourea and N,N-bis(2-chloroethyl)amino
Fig. 1. Crystal structure of CEAB-4-MTSC.

268
A. Sankaraperumal et al. / Polyhedron 50 (2013) 264–269
Fig. 2. Crystal structure of Ni(CEAB-4-MTSC)2.
Fig. 3. Crystal packing of Ni(CEAB-4-MTSC)2–H-bond contacts shown by dashed lines.
is C1–S1 = 1.732(2) Å (thiolato form); C1–N2 = 1.297(3) Å; C3–
N1 = 1.298(3) Å and the same bond distance in the free ligand is
C1–S1 = 1.683(3) Å (thione form); C1–N2 = 1.344(4) Å; C3–
N1 = 1.271(4) Å. In the crystal, molecule are linked through inter-
molecular C–Hꢂ ꢂ ꢂCl hydrogen bond, generate edge fused ring motif.
The hydrogen bonded motifs are linked to each other to form a
three dimensional network, seems to be effective in the stabiliza-
tion of the crystal structure to form chain [34]. Packing arrange-
ment shown in Fig. 3. Polar hydrogen atom on the title
thiosemicarbazone fragment, on C(130)–H(13C) participating the
hydrogen bond. Symmetry transformation used to generate
dimensions of the hydrogen bond equivalent atom x ꢀ 1, y, z,
shows that d(D–H), d(Hꢂ ꢂ ꢂA), d(Dꢂ ꢂ ꢂA), <(DHA) are 0.97, 2.69,
3.603(9) Å and 156.4°, respectively. The conformation of thiosem-
icarbazone fragment is such that the imine N atom is oriented in a
way to form an intermolecular hydrogen bond C(130)–H(13C)
ꢂ ꢂ ꢂCl(10) resulting in the formation of edge fused ring motif.
3.3. Biological activity
The antimicrobial screening data show that the compounds ex-
hibit antimicrobial properties, and it is important to note that the
nickel complex exhibit more inhibitory effect than the parent li-
gand. It is clear that the zone of inhibition is much larger for metal
complex against the Gram-positive bacteria and Gram-negative
bacteria (Table 3). The increased activity of the metal chelate can
be explained on the basis of chelation theory. It is known that che-
lation tends to make the ligand act as more powerful and potent
bactericidal agent, thus killing more of the bacteria than the ligand.
It is observed that, p–electron delocalization over the whole com-
plex increases the lipophilic character of the metal chelate and fa-
vours its permeation through the lipoid layer of the bacterial
membrane [35–38]. There are other factors which also increase
the activity, which are solubility, conductivity, and bond length be-
tween the metal and the ligand.

A. Sankaraperumal et al. / Polyhedron 50 (2013) 264–269
269
and characterized by elemental analysis, IR, electronic, 1H NMR
spectroscopy. The crystal structure of the free ligand and complex
has been determined by single crystal X-ray diffraction technique.
In the complex, thiosemicarbazone ligand is coordinated to nickel
via (1:2 complex) SNNS mode. In the crystal, molecules are linked
through intermolecular C–Hꢂ ꢂ ꢂCl hydrogen bond network, generate
edge fused ring motif that stabilizes the crystal structure. The metal
complex has shown enhanced synergic effect to control pathogenic
bacteria comparable with standard Streptomycin.
Table 3
Antimicrobial activity using the disc-diffusion method (zone of inhibition in mm).
Organism
CEAB-4-
MTSC
Ni (CEAB-4-
MTSC)2
Streptomycin
Bacteria
Staphylococcus aureus
Micrococcus
Shigella flexneri
Staphylococcus
epidermidis
9
10
9
12
18
18
11
14
26
30
14
8
Proteus vulgaris
Salmonella typhimurium
Salmonella paratyphi-B
Pseudomonas aeruginosa
Bacillus subtilis
Klebsiella pneumonia
Staphylococcus aureus
(MRSA)
Fungi
Candida albicans
Malassesia pachydermatis 10
Trichophyton
11
8
–
–
–
18
18
–
–
–
30
24
18
30
22
20
–
Appendix A. Supplementary material
CCDC 817418 and 840170 contain the supplementary crystallo-
graphic data for ligand and complex, respectively. These data can
be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/
retrieving.html, or from the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223
336 033; or e-mail: deposit@ccdc.cam.ac.uk.
10
8
17
14
Ketoconazole
8
20
19
–
28
29
30
–
mentagrophytes
Reference
(–) No activity; Streptomycin
standard antifungal agent.
–
standard antibacterial agent; Ketoconazole –
[1] D.G. Bauer (Ed.), International Encyclopedia of Pharmacology, vol. 1, Pergamon
Press, Oxford, 1972, p. 35.
[2] D.R. Williams, Chem. Rev. 72 (1972) 203.
[3] E. Sorkin, W. Roth, H. Erlenmeyer, Helv. Chim. Acta 35 (1952) 1736.
[4] J.C. Cymerman, D. Wills, S.D. Rubbo, J. Edgar, Nature 176 (1955) 34.
[5] S. Padhye, G.B. Kaufman, Coord. Chem. Rev. 63 (1985) 127.
[6] M.J.M. Cambell, Coord. Chem. Rev. 15 (1975) 279.
[7] S.K. Chattopadhyay, M. Hossain, A.K. Guha, S. Ghosh, Transition Met. Chem. 15
(1990) 473.
Table 4
Minimum inhibitory concentration (lg/mL) against the tested bacteria and fungi.
Organism
CEAB-4-
MTSC
Ni (CEAB-4-
MTSC)2
Streptomycin
[8] G.J. Palenik, D.F. Rendle, W.S. Carter, Acta Crystallogr. Sect. B 30 (1974) 2390.
[9] R. Kato, Chem. Rev. 104 (2004) 5319.
[10] N. Robertson, L. Cronin, Coord. Chem. Rev. 227 (2002) 93.
[11] R.C. Elderfield, I.S. Covey, J.B. Geiduschek, W.L. Meyer, A.B. Ross, J.H. Ross,
Potential Anticancer Agents 23 (1958) 1749.
[12] G.M. Sheldrick, Acta Crystallogr. Sect. A A64 (2008) 112.
[13] L.J. Farrugia, J. Appl. Crystallogr. 30 (1997) 565.
[14] A.L. Spek, J. Appl. Crystallogr. 36 (2003) 7.
[15] A.D. Weber, C.S. Sanders, Antimicrob. Agents Chemother. 34 (1990) 156.
[16] V. Duraipandiyan, P. Kanan, S. Ignacimuthu, Leaflets 13 (2009) 320.
[17] L.J. Baucher, J. Inorg. Nucl. Chem. 36 (1974) 531.
[18] J. Uttamachandani, R.N. Kapoor, Transition Met. Chem. 3 (1978) 79.
[19] D. Gattegno, A.M. Giuliani, Tetrahedron 30 (1974) 701.
[20] M.B. Ferrari, S. Capacchi, F. Bisceglie, G. Pelosi, P. Tarasconi, Inorg. Chim. Acta
312 (2001) 81.
[21] N.C. Kasuga, K. Sekino, C. Koumo, N. Shimala, M. Ishikawa, K. Nomiya, J. Inorg.
Biochem. 84 (2001) 55.
[22] Alessia Famengo, Dalice Pinero, Olivier Jeannin, Thierry Guizouarn, Marc
Fourmigue, Dalton Trans. 41 (2012) 1441.
Bacteria
Staphylococcus aureus
Micrococcus
Shigella flexneri
Staphylococcus
epidermidis
Proteus vulgaris
Salmonella paratyphi-B
Salmonella typhimurium
Pseudomonas aeruginosa
Bacillus subtilis
Klebsiella pneumonia
Staphylococcus aureus
(MRSA)
125
250
250
500
100
150
150
300
6.25
6.25
6.25
25
250
500
–
–
–
250
200
–
–
–
6.25
–
30
25
25
6.25
–
250
500
250
250
Fungi
Candida albicans
Malassesia pachydermatis 250
Trichophyton
Fluconazole
>100
12.5
250
250
250
–
–
25
[23] Xing Chen, Wei Qiang Chen, Lin Liang Yu, Jing Hua Lin, Dong Dong Zhou, Wen
Tao Yin, Hong Rong Zuo, Jia Rong Zhou, Le Min Yang, Chun Lin Ni, J. Mol. Struct.
1006 (2011) 419.
[24] Anant Prakash, P.K. Mukesh, K.K. Singh, J. Dev. Biol. Tissue Eng. 3 (2) (2011) 13.
[25] V.M. Leovac, L.S. Jovanovic, V. Divijakovic, A. Pevec, I. Leban, T. Armbruster,
Polyhedron 26 (2007) 49.
mentagrophytes
(–) No activity; Streptomycin and Fluconazole (standard antimicrobial agent).
[26] K.R. Krishnapriya, M. Kandasamy, Polyhedron 24 (2005) 113.
[27] D.X. West, A.E. Liberta, S.B. Pandhye, R.C. Chikate, P.B. Sonawane, A.S.
Kumbhar, R.G. Yerande, Coord. Chem. Rev. 123 (1993) 49.
[28] E. Huheey, E.A. Keiter, R.L. Keiter, Inorganic Chemistry Principles of Structure
and Reactivity, fourth ed., Harper Collins College Publishers, New York, 1993.
[29] M. Joseph, V. Suni, M.R.P. Kurup, M. Nethaji, A. Kishore, S.G. Bhat, Polyhedron
23 (2004) 3069.
[30] A. Sreekanth, S. Sivakumar, M.R.P. Kurup, J. Mol. Struct. 655 (2003) 47.
[31] E.B. Seena, M.R.P. Kurup, Polyhedron 26 (2007) 829.
[32] A. Sreekanth, H.K. Fun, M.R.P. Kurup, J. Mol. Struct. 737 (2005) 61.
[33] V. Philip, V. Suni, M.R.P. Kurup, M. Nethaji, Polyhedron 23 (2004) 1225.
[34] N. Sampath, Rita Mathews, M.N. Ponnuswamy, Lin-Woo Kang, Mol. Cryst. Liq.
Cryst. 518 (1) (2010) 151.
The results of fungicidal screening show that Ni(II) complex were
highly active than the free ligand against phytopathogenic fungi, C.
albicans, M. pachydermatis, and T. mentagrophytes (Table 4). The
mode of action may involve the formation of a bond through the
azomethane nitrogen atom with the active centres of the cell con-
stituent, resulting in interference with the normal cell process. The
variation in the effectiveness of different compound against differ-
ent organism depends either on the impermeability of the cells of
the microbes or the difference in ribosomes of microbial cells. It
has also been proposed that concentration plays a vital role in
increasing the degree of inhibition, as the concentration increases,
the activity increases. It is noteworthy that the compound is effec-
tive against fungi and bacteria make it interesting for a practical
use as antimicrobial agent.
[35] Yu.-Mei. Hao, Acta Crystallogr. Sect. E 66 (2010) 2528.
[36] S.K. Sengupta, O.P. Pandey, B.K. Srivastava, V.K. Sharma, Transition Met. Chem.
23 (4) (1998) 349.
[37] S.O. Podunavac kuzmanovic, V.M. Leovac, N.U. Perisic janjic, J. Rogan, G. Balas,
J. Serb. Chem. Soc. 64 (1999) 381.
[38] A. Wissner, D.M. Berger, D.H. Boschelli, J. Med. Chem. 43 (17) (2000) 3244.
4. Conclusion
New complex of Ni(II) with p-[N,N-bis(2-chloroethyl)amino]
benzaldehyde-4-methyl hiosemicarbazone have been synthesized