Polyhedron 34 (2012) 1–12

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Polyhedron
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Synthesis, structural characterisation and cytotoxicity of new iron(III)

complexes with pyrazolyl thiosemicabazones
Nitis Chandra Saha a,⇑, Chinmoy Biswas a,c, Atanu Ghorai b, Utpal Ghosh b, Saikat Kumar Seth d,e,
Tanusree Kar d
a
Department of Chemistry, University of Kalyani, Kalyani 741235, Nadia, West Bengal, India
b
Department of Biochemistry & Biophysics, University of Kalyani, Kalyani 741235, Nadia, West Bengal, India
c
Department of Chemistry, Rishi Bankim Chandra College, Naihati, 743165, 24 PGS (N), West Bengal, India
d
Department of Materials Science, Indian Association for the Cultivation of Science, Kolkata-700032, India
e
Department of Physics, M.G. Mahavidyalaya, Bhupatinagar, Midnapore (East) 721425, West Bengal, India

a r t i c l e i n f o a b s t r a c t

Article history: New iron(III) complexes of 5-methyl-3-formylpyrazole-N(4)-dimethylthiosemicarbazone (HMPZNMe2)

Received 19 June 2011 (I) and 5-methyl-3-formylpyrazole-N(4)-diethylthiosemicarbazone (HMPZNEt2) (III), [Fe(MPZNMe2)2]-
Accepted 24 October 2011 NO3
H2O (II) and [Fe(MPZNEt2)2]NO3
H2O (IV), respectively, have been synthesised for the first time
Available online 9 November 2011
and physico-chemically characterised by magnetic measurements (polycrystalline state), electronic
and IR spectra. Both are cationic complexes containing two monodeprotonated tridentate ligands with
Keywords: NNS donor sites and an anionic counterpart; the complex species behave as 1:1 electrolytes in MeOH.
Synthesis
IR spectra (4000–200 cm 1) indicate coordination to iron(III) centre via the pyrazolyl (tertiary) ring nitro-
Iron(III)
Pyrazolylthiosemicarbazone
gen, azomethine nitrogen and thiolato sulfur atom. X-ray crystallographic data of (II) (monoclinic, C2/c)
 triclinic) have authenticated the FeN4S2 octahedral coordination in both complex ions, as
and (IV) (P1,
X-ray crystallography
Cytotoxicity envisaged from the spectral data. In both species, the two azomethine nitrogen atoms are trans to each
other, while the pyrazolyl ring nitrogen and the thiolato sulfurs atoms are in cis positions. We further
observed that both the ligands and their corresponding complexes were capable of killing HeLa cells in
culture, but the cytotoxicity of the complexes was found to be greater than their corresponding ligands.
Complex (II) does not have any role in cell-cycle progression, but complex (IV) arrests the M-phase to
prevent cell-cycle progression.
Ó 2011 Elsevier Ltd. All rights reserved.

1. Introduction pyrazolyl thiosemicarbazones, the present communication intends

A number of heterocyclic thiosemicarbazones and their metal
ion complexes have attracted considerable attention in chemistry
and biology owing to their potentially beneficial biological activi-
ties (antitumoral, antibacterial, antimalarial, antiviral, etc.) over
the years and such activities have often been related to their chela-
tion phenomenon with one or more essential trace metal ions
[1–10]. It is documented that iron(III) complexes of thiosemicarba-
zones have been shown to be more active in cell destruction, as well
as in the inhibition of DNA synthesis, than the uncomplexed thio-
semicarbazones [11]. The success in therapeutic applications of
several heterocyclic thiosemicarbazones [3,12–14] for removing
excess iron from iron-loaded mice through chelation therapy is also
remarkable. These findings have initiated further research on this
specific area. In continuation of our earlier reports on iron(III) com-
plexes and related publications [15–20] on metal ion complexes of
⇑ Corresponding author. Fax: +91 33 25828282.
E-mail address: nitis.saha@gmail.com (N.C. Saha).
to report the synthesis, structural characterisation and cytotoxic
activities of two new iron(III) complexes with the title ligands.
2. Experimental
Hoechst dye, propidium iodide and RNase A were purchased
from Sigma Chemicals (USA). Culture media MEM and serum were
purchased from HiMedia, India. All other reagents were of AR
grade/molecular biology grade and were obtained from commer-
cial sources and used without further purification. Spectrograde
solvents were used for spectral and conductance measurements.
2.1. Preparation of HMPZNMe2 (I) and HMPZNEt2 (III)
Both the title ligands, 5-methyl-3-formylpyrazole-N(4)-dimeth-
ylthiosemicarbazone (HMPZNMe2) and 5-methyl-3-formylpyraz-
ole-N(4)-diethylthiosemicarbazone (HMPZNEt2) (Fig. 1) have been
synthesized by a method similar to that reported earlier [21], but
appropriately modified, followed by the final transamination [22]

0277-5387/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.poly.2011.10.033
2 N.C. Saha et al. / Polyhedron 34 (2012) 1–12

Fig. 1. Schematic structural formulation of the ligands (I) and (III).

of the S-methyldithiocarbazate of 5-methyl-3-formylpyrazole
(HMPZSMe) with dimethylamine for HMPZNMe2 and diethylamine
for HMPZNEt2. For both the cases, white crystallised products (from
ethanol) were obtained in a yield of ca. 60–70%. HMPZNMe2 (M.P.
182–184 °C). Anal. Calc. for C8H13N5S: C, 45.5; H, 6.2; N, 33.2.
Found: C, 45.5; H, 6.0; N, 32.7%. 1H NMR d(DMSO-d6): 2.25 (3H,
s), 6.24 (1H, s), 8.06 (1H, s), 10.79 (1H, s), 3.26 (6H, s). m/z: 211
(M+, 82%).
For HMPzNEt2 (M.P. 160–162 °C). Anal. Calc. for C10H17N5S: C,
50.2; H, 7.1; N, 29.3. Found: C, 50.3; H, 7.1; N, 29.5%. 1H NMR
d(CHCl3-d): 2.29 (3H, s), 6.22 (1H, s), 7.39 (1H, s), 10.71 (1H, s),
3.80 (4H, m), 1.28 (6H, t). m/z: 239 (M+, 86%).
2.2. Synthesis of [Fe(MPZNMe2)2]NO3
H2O (II) and [Fe(MPZNEt2)2]
NO3. H2O (IV)
each reaction. Aqueous NH3 was added dropwise until the solution
was strongly ammoniacal. The resulting precipitate of Fe2O3
xH2O
was filtered off and washed with H2O until Cl free. The precipitate
was then dissolved in a minimum quantity of dilute HNO3 and the
resulting solution was added to a hot 1.05 mmol EtOH solution of
HMPZNMe2 (0.2215 g) for (II) and HMPZNEt2 (0.251 g) for (IV). The
resulting dark brown solution, in each case, was heated to reflux
for about 30 min, then the solvent was allowed to evaporate at
room temperature. The dark brown solids thus obtained were fil-
tered off, washed with cold ethanol and dried over anhydrous
CaCl2. The yield, in each case was 75–80%. Brown black (II) and
dark brown (IV) needle shaped crystals were found to be suitable
for X-ray diffraction.
2.3. Physical measurements

0.17 g, 1.05 mmol anhydrous FeCl3 was dissolved in aqueous Elemental analyses (C, H and N) were done with a Perkin-El-
EtOH (10 cm3) containing 2 N HCl (0.5 cm3) in a small beaker for mer 2400 CHNS/O analyser and the iron content of the complexes

Table 1
Crystal data and structure refinement parameters for C8H13N5S1 (I), C32H56Fe2N23O13S4 (II), C10H17N5S1(III), and C20H34Fe1N11O4S2(IV).

Crystal data (I) (II) (III) (IV)

Empirical formula C8H13N5S1 C32H56Fe2N23O13S4 C10H17N5S1 C20H34Fe1N11O4S2
Formula weight 211.29 1210.94 239.35 612.55
T (K) 150(2) 150(2) 150(2) 150(2)
k (Å) 0.71073 0.71073 0.71073 0.71073
Crystal system monoclinic monoclinic orthorhombic triclinic
Unit cell dimensions
Space group P21 C2/c Pccn 
P1
a (Å) 11.986(3) 26.7009(11) 21.929(3) 13.145(2)
b (Å) 7.3218(18) 13.4698(4) 9.6397(10) 13.662(2)
c (Å) 12.172(3) 17.4483(9) 12.0354(13) 8.531(3)
a (°) 90 90 90 104.86(3)
b (°) 100.768(5) 125.542(2) 90 95.08(3)
c (°) 90 90 90 86.56(2)
V (Å3) 1049.4(4) 5106.2(4) 2544.2(5) 1473.9(6)
DCalc (mg/m3) 4, 1.337 4, 1.575 8, 1.250 2, 1.380
1
Absorption coefficient (mm ) 0.278 0.813 0.238 0.699
F(0 0 0) 448 2516 1024 642
Crystal size (mm) 0.32  0.26  0.22 0.28  0.23  0.18 0.42  0.34  0.22 0.30  0.28  0.24
h ranges (°) 1.70 to 25.96 1.78 to 25.00 1.86 to 24.99 3.02 to 25.00
Limiting indices 14 6 h 6 14 31 6 h 6 31 26 6 h 6 26, 15 6 h 6 15
86k68 16 6 k 6 15 11 6 k 6 11, 16 6 k 6 15
14 6 l 6 14 20 6 l 6 20 13 6 l 6 14 0 6 l 6 10
Reflections collected 9642 23 676 22 210 5186
Unique reflections 3683 [Rint = 0.0532] 4498 [Rint = 0.0549] 2246 [Rint = 0.0251] 5186[Rint = 0.0000]
Completeness to theta (%) 99.2 100.0 100.0 99.8
Refinement method full-matrix least full-matrix least full-matrix least full-matrix least
squares on F2 squares on F2 squares on F2 squares on F2
Observed reflections [I > 2r (I)] 3173 3619 2069 2272
Data/parameters 3683/259 4498/351 2246/148 5186/349
Goodness-of-fit (GOF) on F2 1.105 1.074 1.069 0.914
Final R indices [I > 2r (I)] R1 = 0.0407 R1 = 0.0554 R1 = 0.0313 R1 = 0.0704
wR2 = 0.0913 wR2 = 0.1623 wR2 = 0.0834 wR2 = 0.1450
R indices (all data) R1 = 0.0549 R1 = 0.0702 R1 = 0.0338 R1 = 0.1827
wR2 = 0.0981 wR2 = 0.1742 wR2 = 0.0852 wR2 = 0.1846
3
Largest difference peak, hole (e Å ) 0.289 and 0.395 1.101 and 1.375 0.259 and 0.234 0.979 and 0.473
 N.C. Saha et al. / Polyhedron 34 (2012) 1–12 3

Table 2
Selected bond lengths (Å), bond angles and torsion angles (°) of C8H13N5S1 (I), C32H56Fe2N23O13S4 (II), C10H17N5S1 (III) and C20H34Fe1N11O4S2 (IV).

(I) (II) (III) (IV)

Moiety A Moiety B Ligand A Ligand B Ligand A Ligand B
Bond lengths
Fe1–N2 1.973(4) 1.956(4) 1.986(6) 1.962(6)
Fe1–N3 1.927(4) 1.925(4) 1.931(6) 1.928(6)
Fe1–S1 2.2186(12) 2.2237(13) 2.233(2) 2.220(3)
N1–C2 1.360(4) 1.358(4) 1.354(6) 1.352(6) 1.353(2) 1.363(1) 1.344(1)
N2–N1 1.360(3) 1.360(3) 1.345(5) 1.350(5) 1.346(2) 1.334(8) 1.361(8)
N2–C4 1.364(4) 1.360(4) 1.341(6) 1.346(6) 1.347(2) 1.334(9) 1.348(9)
N3–C5 1.292(4) 1.286(4) 1.292(6) 1.300(6) 1.284(2) 1.269(9) 1.300(9)
N4–N3 1.381(3) 1.379(3) 1.371(5) 1.382(5) 1.370(2) 1.381(8) 1.372(8)
N4–C6 1.361(4) 1.358(4) 1.331(6) 1.329(6) 1.375(2) 1.319(1) 1.318(1)
N5–C6 1.351(3) 1.352(4) 1.340(6) 1.344(6) 1.339(2) 1.371(1) 1.379(1)
S1–C6 1.687(3) 1.694(3) 1.760(5) 1.748(5) 1.683(2) 1.756(9) 1.729(9)
Bond angles
N2–Fe–N3 80.53(15) 80.66(15) 79.9(3) 80.0(3)
N2–Fe–S1 165.39(11) 164.90(11) 163.9(2) 163.9(2)
N3–Fe–S1 85.03(11) 85.01(11) 84.8(2) 84.5(2)
N1–N2–C4 103.5(2) 103.4(2) 106.1(4) 106.2(4) 104.22(11) 106.6(6) 105.9(6)
N2–C4–C5 122.9(3) 122.0(3) 113.9(4) 114.1(4) 122.28(13) 114.3(7) 113.3(7)
N3–C5–C4 130.5(3) 130.7(3) 114.2(4) 113.6(4) 130.64(13) 114.4(7) 115.1(7)
C5–N3–N4 115.9(2) 116.0(2) 118.5(4) 118.8(4) 117.44(12) 118.5(7) 119.1(7)
N3–N4–C6 120.2(2) 119.9(2) 111.6(4) 111.5(3) 119.29(12) 112.6(7) 110.9(7)
N5–C6–N4 114.7(2) 114.3(2) 117.8(4) 118.2(4) 114.63(12) 115.1(8) 117.0(8)
N4–C6–S1 122.0(2) 122.4(2) 123.3(3) 123.7(3) 121.51(11) 123.1(7) 124.7(7)
N5–C6–S1 123.3(2) 123.3(2) 118.9(4) 118.1(3) 123.87(11) 121.8(7) 118.3(7)
Torsion angles
N1–N2–C4–C5 179.8(3) 180.0(3) 174.9(4) 175.5(4) 177.7(2) 175.9(7) 179.7(6)
N2–C4–C5–N3 1.7(5) 0.9(5) 5.0(6) 1.2(6) 4.1(2) 0.7(1) 0.5(1)
N4–N3–C5–C4 2.3(5) 1.0(5) 176.4(4) 178.8(4) 3.1(2) 177.4(7) 179.9(7)
C6–N4–N3–C5 179.1(3) 175.3(3) 178.8(4) 175.8(4) 165.9(2) 176.4(9) 179.5(8)
N3–N4–C6–N5 177.3(2) 172.5(2) 179.0(4) 176.3(4) 172.0(2) 176.3(8) 178.6(8)
N3–N4–C6–S1 3.3(4) 6.7(4) 1.5(6) 0.6(5) 8.3(2) 1.0(1) 0.7(1)
S1–C6–N5–C7 177.3(2) 176.7(2) 176.7(4) 173.6(4) 169.3(2) 2.2(1) 9.8(1)
Bond angles involving both ligands (A and B) around the Fe atom in complexes(II) and (IV)
(II) (IV) (II) (IV)
N3B–Fe1–N2A 100.55(15) 100.7(3) N3A–Fe1–N2B 98.71(15) 100.5(3)
N2A–Fe1–S1B 88.62(11) 91.0(2) N2B–Fe1–S1A 90.63(11) 90.4(2)
N3B–Fe1–S1A 93.86(11) 94.7(2) N3A–Fe1–S1B 95.71(12) 95.1(2)
N2B–Fe1–N2A 89.34(15) 87.7(3) S1B–Fe1–S1A 95.08(5) 95.2(1)

Table 3
Analytical data and other pertinent physico-chemical properties of the complexes.
1
Complex (colour) Elemental analyses Conductivity at 30 °C in MeOH (X cm2 mol 1
) leff (BM) at 298 K
Found (calc.)
%C %H %N %Fe
[Fe(MPzNMe2)2]NO3
H2O 34.2 5.2 27.3 9.9 110 1.95
(Brown black) (34.5) (5.1) (27.7) (10.0)
[Fe(MPzNEt2)2]NO3
H2O 39.0 5.1 25.4 9.0 106 2.05
(Dark brown) (39.2) (5.2) (25.2) (9.1)

was determined titrimetrically. The molar conductance of the
complexes in methanol solutions was measured with a Systronics
304 digital conductivity meter. Magnetic susceptibilities were
measured in the polycrystalline state on a PAR 155 sample
vibrating magnetometer. 1H NMR spectra for the ligands were re-
corded in DMSO-d6/CDCl3 with a Bruker AM 300L (300 MHz)
superconducting FT NMR spectrometer. Mass spectroscopy of
the ligands was done with a Jeol JMS-D300 mass spectrometer.
The electronic spectra and the diffuse reflectance spectra were
recorded on a Hitachi U-3501 spectrophotometer. IR spectra
(4000–200 cm 1) were recorded on a Jasco FT/IR-420 spectropho-
tometer with KBr pellets.

Table 4
1
IR assignments (cm ) for the ligands and the complexes pertaining to the coordination sites.

Compound m(CH@N) (azomethine) m(C@N) (pyrazole) m(C@S) m(Fe–N) (azomethine) m(Fe–N) (pyrazole) m(Fe–S)
HMPzNMe2 (I) 1611 1503 864
[Fe(MPzNMe2)2]NO3
H2O (II) 1598 1520 785 482 287 375
HMPzNEt2 (III) 1620 1510 865
[Fe(MPzNEt2)2]NO3
H2O (IV) 1600 1525 780 478 280 381
4 N.C. Saha et al. / Polyhedron 34 (2012) 1–12

2.4. Structure determination

Single crystal X-ray diffraction intensity data of the free ligand 5-

methyl-3-formylpyrazole-N(4)-dimethylthiosemicarbazone (HMPZ
NMe2) (I), which was crystallized with two independent molecules
per asymmetric unit, its metal complex [Fe(MPZNMe2)2]NO3
H2O
(II), which has been represented crystallographically as 2[Fe(MPZN-
Me2)2](NO3)3
4H2O, another free ligand 5-methyl-3-formylpyraz-
ole-N(4)-diethylthiosemicarbazone (HMPZNEt2) (III) and its metal
complex [Fe(MPZNEt2)2]NO3
H2O (IV) were collected at 150(2) K
using a Bruker APEX-II CCD diffractometer equipped with graphite
monochromated Mo Ka radiation (k = 0.71073 Å). Data reduction
was carried out using the program Bruker SAINT [23]. Because of the
very small values of the absorption coefficients, no absorption cor-
rection was applied. The structures of the compounds were solved
by direct methods and refined by the full-matrix least-square tech-
nique on F2 with anisotropic thermal parameters to describe the
thermal motions of all non-hydrogen atoms using the programs
SHELXS 97 and SHELXL 97 [24]. All calculations were carried out using
the WinGX system Ver-1.64 [25]. In the complexes delu, simu and
isor constraints were applied for a few atoms. In the free ligands (I)
and (III), the hydrogen atoms were located from a difference Fourier
map and were treated as riding, whereas in the complexes, the
hydrogen atoms were located at geometrically calculated positions
and were treated by a mixture of independent and constraint refine-
ment. The refinements were based on F2 for all reflections except
those with non-reliable F2 values. In compound (II), one of the ni-
trate anions is disordered over two positions with occupancies of
1:2.5, and the water molecules of crystallization are also disordered,
Fig. 2. (a) An ORTEP diagram of the two independent molecules of the free ligand
for which the H-atoms could not be located. The crystal of compound (I) with the atom numbering scheme. Thermal ellipsoids are drawn at the 30%
(IV) diffracted weakly, less than half of the reflections were consid- probability level. (b) Packing diagram for (I), viewed down the b-axis. Hydrogen
ered to be observed, and the atoms in the –CH2CH3 substituents and bonds are indicated by dotted lines.
the nitrate anion all undergo considerable thermal motion. A sum-
mary of the crystal data and relevant refinement parameters are gi-
ven in Table 1. Selected bond-lengths, bond angles and torsion cells were examined by a fluorescence microscope (Carl Zeiss)
angles of both the ligands and the complexes are given in Table 2. using the appropriate filter. Apoptotic cells were distinguished by
nuclear fragmentation and chromatin condensation. The apoptotic
2.5. Effect of the synthesized product in cultured HeLa cells cells were randomly counted and the percentage of the apoptotic
cells was calculated at each dose. The mean percentage of apopto-
2.5.1. Cell killing activity tic cells with a standard deviation was calculated from four inde-
The human cervical cancer cell line HeLa was obtained from the pendent experiments.
National Centre for Cell Sciences, Pune, India. HeLa cells were
grown in MEM supplemented with 10% bovine serum (complete
2.5.3. Cell cycle analysis
medium) at 37 °C in a humidified atmosphere containing 5% CO2
After 18 h treatment, the cells were trypsinized, washed twice
medium [26]. After inoculation in a fresh medium, the HeLa cells
with cold phosphate buffered saline (PBS), fixed with 70% ethanol
were incubated overnight and then treated with different concen-
in PBS for 2 h at 4 °C, and then stained with a propidium iodide (PI)
trations of the synthesized products under investigation (0–50 lM)
solution (10 lg/ml) containing DNase-free RNase (100 lg/ml) and
for 13 h. After the treatment, the cells were harvested by trypsin-
0.1% (v/v) Triton X-100 in the dark for 30 min at room temperature
ization and suspended in PBS buffer. After washing twice, the cells
before flow cytometric analysis. The samples were detected with
were incubated with 0.1% tryphan blue for 5 min at room temper-
FACS Calibur (BD Bioscience, USA). A minimum of 20,000 cells, ana-
ature and counted using a hemocytometer under a light micro-
lyzed in each sample, served to determine the percentages of cells
scope. The dead cells appeared to be blue, whereas the viable
in each phase of the cell cycle using ModFit LT software [28].
cells were colourless. Each experiment was repeated four times
and the mean of the percentage viable cells at each dose was com-
pared with the mean of the untreated control using one way ANO- 3. Results and discussion
VA with a post hoc test such as the Tukey’s test and Dunnett’s test.
The number of viable cells in the untreated control was considered 3.1. Spectroscopic characterisation of HMPZNMe2 (I) and HMPZ
as 100% and the viable cell number at different doses were normal- NEt2 (III)
ized accordingly.
The title ligands, HMPZNMe2 and HMPZNEt2, have been charac-
2.5.2. Induction of apoptosis as detected by nuclear fragmentation terised by elemental analyses (C, H and N), IR, 1H NMR and mass
Detection of nuclear fragmentation was done as reported earlier spectra. The characteristic IR bands (cm 1) at 3300–3200 (mNH),
[27]. In summary, after 24 h, the treatment cells were harvested in 1615–1611 (mCH@N), 1510–1505 (mC@N), 1040–1020 (mN–NPZ) and
PBS buffer and fixed with 70% ethanol for 45 min at 4 °C. Then the 867–865 (mC@S) are in good agreement with the structure in
cells were suspended in PBS buffer, stained with Hoechst (5 lM), Fig. 1(a). Both the ligand molecules have a proton adjacent to the
incubated for 5 min in the dark, and washed twice with PBS. The thiocarbonyl group and consequently can exhibit thione–thiol
 N.C. Saha et al. / Polyhedron 34 (2012) 1–12
tautomerism. The IR spectra of the free ligands do not show any
(mSH) band in the region 2600–2200 cm 1, indicating that the thiol
tautomer is absent in the solid state [29,30], but exhibit (mNH)
bands in the region 3300–3200 cm 1, indicating the existence of
only the thioketo tautomer Fig. 1(a). The 1H NMR spectra of the
free ligands in DMSO-d6 give singlets at d 2.48–2.41 (3H), d 6.20–
6.17 (1H) assigned to C5–CH3 and C4–H of the pyrazole rings,
respectively. One-proton singlets at d 8.09–7.29, ascribed to CH@N,
indicate the existence of hydrogen bonded stabilized forms of the
ligands as shown in Fig. 1(b). The 1H NMR spectra also show signal
at d 13.40–13.10, indicating the presence of a hydrogen bonded
proton [31]. The mass fragmentation data are compatible with
the proposed molecular formulae. The strongest molecular ion
peak appears at m/z 211 (M+ 58%) for HMPZNMe2 and m/z 239
(M+ 86%) for HMPzNEt2.
3.2. Characterisation of the Fe(III) complexes
Both the Fe(III) complexes give satisfactory C, H, N and Fe anal-
yses and conform to the compositions [Fe(MPzNMe2)2]NO3
H2O
and [Fe(MPzNEt2)2]NO3
H2O. The molar conductance values in
MeOH (30 °C) classify them as 1:1 electrolytes [32] and the com-
plexes are paramagnetic (at 25 °C), as expected for a low spin d5
ion (Table 3).
Fig. 3. (a) An ORTEP diagram of complex (II) with the atom numbering scheme. (b) One-dimensional chain propagating along the (1 0 0) direction. (c) Packing diagram of (II)
displaying the two-dimensional framework.
5
3.2.1. IR spectra
The characteristic IR bands (4000–200 cm 1) for the free li-
gands, when compared with those of its Fe(III) complexes, provide
meaningful information regarding the bonding sites of the primary
ligand molecules (Table 4) A negative shift in the m(CH@N) bands
(1620–1611 cm 1) in the spectra of the free ligands to a lower va-
lue (1600–1598 cm 1) in their complexes are consistent with coor-
dination of the azomethine nitrogen to the central Fe(III) ion. The
IR bands at 482-478 cm 1 in the complexes are assignable to
m(Fe–N) [32]. Intense bands at 865 cm 1 in the free ligand spectra,
assigned to m(C@S), have been found to shift to lower frequency re-
gions (785–780 cm 1) in the complexes, indicating the coordina-
tion of the thiol sulfur to Fe(III); moreover, the appearance of
new bands in the region (381–375 cm 1) in the complexes are
assignable to m(Fe–S) [33]. IR bands at 1510–1503 and 615–
597 cm 1 in the free ligand spectra, assignable to m(C@N) (pyrazole
ring) and the in-plane deformation of the pyrazole ring, have been
shifted to the higher frequency region, indicating that the tertiary
ring nitrogen atom (2N) is a possible bonding site [34–36]. The
appearance of bands around 287–280 cm 1 in the complexes are
clearly assignable to m(Fe-N) (pyrazole ring) [33].
3.2.2. Electronic spectra
The diffuse reflectance spectral data of the iron(III) com-
plexes appear as three main bands in the regions 19 802–19 760,
6 N.C. Saha et al. / Polyhedron 34 (2012) 1–12
16 393–16 050 and 10 830–10 753 cm 1. The absorption bands can
be tentatively assigned to a 2T2 ground state for iron(III). The in-
tense bands at ca. 19 802–19 760 cm 1 and ca. 16 393–16 050
cm 1 may be assigned to CT transitions arising from the d ? p⁄
transition. The d–d transition is located at ca. 10,830–10,753
cm 1, which might correspond to a 2T2 ? 2T1 transition [37,38].
The electronic spectra of the complexes in methanol exhibit three
bands in the regions 20 800–20 325, 16 313–16 100 and 10 910–
10 858 cm 1. The bands which are found between 20 800 and
16 100 cm 1 are likely due to d ? p⁄ metal to ligand bands as well
as a sulfur to Fe(III) transition [39,40]. The bands at ca. 10 910–
10 858 cm 1 can be assigned to d-d transitions of spin paired d5
species with a distorted octahedral structure [41,42].
3.3. Structural description
The molecular views [43] of the free ligand HMPZNMe2 (I), its me-
tal complex 2[Fe(MPZNMe2)2](NO3)3
4H2O (II), the other free ligand
HMPZNEt2 (III) and its metal complex [Fe(MPZNEt2)2]NO3
H2O (IV),
together with the atom numbering scheme, are shown in Figs. 2a,
3a, 4a and 5a, respectively. The crystallographic asymmetric units
in the ligands (I) and (III) comprise of HMPZNMe2 and HMPZNEt2
molecular moieties, respectively, while that in the complexes com-
prises of a [Fe(MPZNMe2)2]+ cation for (II) and a [Fe(MPZNEt2)2]+ cat-
ion for (IV), NO3- counter ions and solvent water of crystallization. In
both complexes (II) and (IV), the Fe(III) centre has a distorted octa-
hedral coordination where a pair of mono-deprotonated ligands,
(MPZNMe2 ) and (MPZNEt2 ), respectively, coordinate the Fe(III)
ion through the thiolato sulfurs (S1A, S1B), pyrazolyl (tertiary) ring
nitrogens (N2A, N2B) and the hydrazinic chain nitrogens (N3A,
Fig. 4. (a) An ORTEP diagram of free ligand (III) with the atom numbering scheme. The thermal ellipsoids are drawn at the 30% probability level. (b) One-dimensional zigzag
chain propagating along the (0 0 1) direction. (c) Packing diagram of (III) viewed along the (0 0 1) direction.
N3B). Due to this octahedral coordination four five-membered che-
late rings [Fe–S(1A)–C(6A)–N(4A)–N(3A), Fe–S(1B)–C(6B)–N(4B)–
N(3B), Fe–N(2A)–C(4A)–C(5A)–N(3A), and Fe–N(2B)–C(4B)–C
(5B)–N(3B)] were formed. In both the complex species, the two azo-
methine nitrogen atoms [N(3A) and N(3B)] coordinate the Fe ion in a
trans orientation, while the pyrazolyl ring nitrogen atoms [N(2A)
and N(2B)] and the thiol sulfur atoms [S(1A) and S(1B)] are in cis-
coordination. This coordination is analogous to that observed in
the crystal structures of similar metal complexes [15–18].
The bond length and bond angles for the non-hydrogen atoms of
the compounds are given in Table 2. The bond lengths of the hydra-
zinic, pyrazolyl and thiol sulfur atoms to the Fe(III) ion agree well
with the corresponding values reported earlier [15,16]. As expected,
the S(1)–C(6) double bond distances of 1.687(3) and 1.694(3) Å in
moiety A and B, respectively in the free ligand (I) are lengthened
to 1.760(5) and 1.748(5) Å in complex (II), with a shortening of the
N4–C6 bond from 1.361(4) and 1.358(4) Å to 1.331(6) and
1.329(6) Å, respectively (Table 2). A similar distortion has been ob-
served in (III) and (IV), where the S(1)–C(6) double bond distance
of 1.683(2) Å in the free ligand (III) is lengthened to 1.756(9) and
1.729(9) Å in molecules A and B, respectively in complex (IV), with
a shortening of the N4–C6 bond from 1.375(2) Å in the free ligand
(III) to 1.319(1) [molecule A] and 1.318(1) Å [molecule B] in the
Fe(III) complex (IV) (Table 2). These bond distances do not vary
significantly in the structures despite the different intermolecular
interaction patterns observed in the ligand and the metal complex
[18]. The S(1)–C(6), C(6)–N(4) and C(5)–N(3) bond distances in (II)
and (IV) show partial double bond character. In (II) and (IV), the
partial double bond character of C(4)–C(5) in both molecules (A
and B) favour the conjugation of the delocalized p-electrons of the
 N.C. Saha et al. / Polyhedron 34 (2012) 1–12 7

Fig. 5. (a) An ORTEP diagram of complex (IV) with the atom numbering scheme. (b) One-dimensional chain propagating along the (0 0 1) direction. Hydrogen atoms not
involved in hydrogen bonding are shown as broken-off bonds. (c) Formation of the R66(24) dimeric ring in complex (IV). (d) Formation of the supramolecular assembly
generated through the water-nitrate cluster (colour code: N, blue; O, red; H, white). Hydrogen atoms not involved in hydrogen bonding have been omitted for the sake of
clarity. (Colour online)

heterocyclic ring with the thiosemicarbazone skeleton. This conju-
gation results in near co-planarity of the pyrazolyl ring with the thi-
osemicarbazone skeleton. The pyrazole ring is therefore restricted
with respect to the thiosemicarbazone moiety due to coordination
of the pyrazolyl nitrogen atom.
The significant closing of the N(3)–C(5)–C(4) and N(2)–C(4)–
C(5) angles in both complexes compared to the corresponding
ligands, by about 15–16° and 8–9°, respectively, as indicated by
Table 2, may be attributed to geometrical necessity for coordina-
tion. The N–Fe1–N, N–Fe1–S and S–Fe1–S angular distributions

Scheme 1. Reaction mechanism showing the rotation about the azomethine double bond.
8 N.C. Saha et al. / Polyhedron 34 (2012) 1–12

indicate that the coordination polyhedron is distorted. This distor-
tion in the metal ion coordination polyhedron results from steric
interactions, and the maximum distortion from an ideal octahedral
geometry occurs for the N(3B)–Fe1–N(2B) [80.66(15)°] and N(3B)–
Fe1–N(2A) [100.5(3)°] angles in (II) and those for (IV) are 80.0(3)°
and 100.7(3)°, respectively. A similar distortion has been observed
in the literature [44]. Some selected torsion angles of the free li-
gands (I) and (III) and the metal complexes (II) and (IV) are given
in Table 2, which may establish the molecular conformation.
The ligand molecules HMPZNMe2 (I) and HMPZNEt2 (III), and the
tridentate ligands MPZNMe2 and MPZNEt2 in complexes (II) and
(IV), respectively are practically planar. In the ligand molecule (I),
the C(6A), C(2A), N(4B) and C(6B) atoms have the largest deviations
in opposite directions [C(6A): +0.0678(31) Å, C(2A): 0.0497(32) Å;
N(4B): +0.0551(28) Å, C(6B): 0.0205(27) Å], whereas in ligand
(III), the C(2) and N(4) atoms have the largest deviations in opposite
directions [C(2): +0.3819(15) Å, N(4): 0.4693(13) Å] from the least
square mean plane through S(1)–C(6)–N(4)–N(3)–C(5)–C(4)–N(2)–
N(1)–C(2)–C(3). In complex (II), the C(2A) and N(2A) atoms in li-
gand A and the N(4B) and C(4B) atoms in ligand B have the largest
deviations in opposite directions [C(2A): +0.1508(61) Å, N(2A):
0.0942(47) Å; N(4B): +0.1032(36) Å, C(4B): 0.1074(43) Å]
whereas those in (IV) are for N(4A) and N(1A), and C(5B) and
N(1B) [N(4A): +0.0582(84) Å, N(1A): 0.1762(68) Å, C(5B):
+0.0284(79) Å, N(1B): 0.1038(63) Å] in ligand A and B, respec-
tively from the least square mean planes through Fe1–S(1)–C
(6)–N(4)–N(3)–C(5)–C(4)–N(2)–N(1)–C(2)–C(3). The coordinating
ligand A and B of both complexes are orthogonal to each other;
the dihedral angle between them is 86.52(5)° in (II) and 89.75(6)°
in (IV). The three individual rings (of A and B), namely the pyrazolyl
and two five membered chelate rings, are individually almost pla-
nar, with a small dihedral angle between them. In (II), the maxi-
mum dihedral angle of 8.32(18)° is between the pyrazolyl ring
C(2A)–C(3A)–C(4A)–N(1A)–N(2A) and the chelate ring Fe1–
N(2A)–C(4A)–C(5A)–N(3A) in ligand A, and that of 5.19(7)° is be-
tween the two chelate rings Fe1–N(2B)–C(4B)–C(5B)–N(3B) and
Fe1–S(1B)–C(6B)–N(4B)–N(3B) in ligand B. In (IV), the maximum
dihedral angle of 8.47(21)° is between the pyrazolyl ring C(2A)–
C(3A)–C(4A)–N(1A)–N(2A) and the chelate ring Fe1–S(1A)–C(6A)–
N(4A)–N(3A) in ligand A, and that of 3.42(16)° is between the two
chelate rings Fe1–N(2B)–C(4B)–C(5B)–N(3B) and Fe1–S(1B)–
C(6B)–N(4B)–N(3B) in ligand B.
It is known [2,45–49] that many thiosemicarbazone ligands ex-
ist in solution as two conformers, E and Z. In the present crystallo-
graphic study, the Z-form, as indicated by the C(4)–C(5)–N(3)–N(4)
torsion angles of 2.3(5)° and 1.0(5)°, was obtained in the solid state
for the free ligand (I). In complex (II), the coordinating ligand exists
as E conformers [the C(4)–C(5)–N(3)–N(4) torsion angle is
176.4(4)° in ligand A and 178.8(4)° in ligand B], as necessitated
by the requirements of coordination. A similar observation was ob-
served for (III) and (IV), where the C(4)–C(5)–N(3)–N(4) torsion
angle in (III) is 3.1(2)° whereas those in (IV) are 177.4(7)° and
179.9(7)°. Therefore, the Z-conformers of the ligand, which could
be present in solution, must be transformed to the E-form before
complexation. A possible mechanism for this transformation, lead-
ing to an unusual rotation about the azomethine (C@N) double
bond, is shown in Scheme 1. The feasibility of this mechanism is
due to the electropositive character of the azomethine carbon,
C(5), as reported earlier [50,51]. The intermediate conversion from
a double bond to a single bond allows the rotation of the thiosem-
icarbazone moiety to bring the sulfur atom, S(1), to the cis position
with respect to the pyrazolyl nitrogen, N(2), in order to permit
complex formation.
The crystal structures adopted by (I) and (II) are quite different.
The structures of the ligand and the complex includes a combina-
tion of N–H


S, N–H


N, N–H


O and O–H


O hydrogen bonding
interactions (Table 5). It is convenient to consider the substruc-
tures generated by each type of hydrogen bonds as acting individ-
ually, and then the combination of substructures build a three
dimensional framework. In ligand (I), the pyrazole ring nitrogen
N(1A) acts as a donor to the hydrazinic chain nitrogen N(3B) in
the molecules at (x, y, z) and (1 x, ½ y, 1 z). Another pyrazole
nitrogen N(1B) of moiety B acts as a donor to N(3A) at (x, y, z) and
(1 x, 1/2 + y, z). The thiolato sulfur atom of both the moieties
acts as an acceptor of N(1B) and C(1A) in the molecule at (1 x,
1/2 + y, z) and (1 x, ½ + y,1 z), respectively. The packing
view of (I) is displayed in Fig. 2b. In complex (II), the pyrazole ring
nitrogen of both moieties act as a donor to the oxygen atom of a
nitrate anion, thus forming a 1D chain which propagates along
the (1 0 0) direction (Fig. 3b). The packing view of the title complex

Table 5
Hydrogen bonding geometry of C8H13N5S1 (I), C32H56Fe2N23O13S4 (II), C10H17N5S1 (III) and C20H34Fe1N11O4S2 (IV) (Å, °).

D–H


A d(D–H) d(H


A) d(D


A) D–H


A Symmetry

Compound (I)
N1A–H1A


N3B 0.86 2.20 2.996(3) 153 1 x, ½ + y, 1 z
N1B–H1B


S1A 0.86 2.72 3.363(3) 133 1 x, ½ + y, z
N1B–H1B


N3A 0.86 2.44 3.214(3) 150 1 x, ½ + y, z
C7B–H7B3


N3A 0.96 2.57 3.480(4) 157 x, 1 + y, z
C1A–H1A3


S1B 0.96 2.83 3.637(4) 142 1 x, ½ + y, 1 z
Compound (II)
N1A–H1A


O3 0.86 1.86 2.710(9) 168 x, 1 y, ½ + z
N1B–H1B


O4 0.86 1.96 2.797(7) 164
O1W–H1W1


O2 0.87 1.85 2.627(10) 148 ½ x, ½ + y, ½ z
O1W–H1W1


O3 0.87 2.15 2.927(11) 148 ½ x, ½ + y, ½ z
O1W–H2W1


N4B 0.86 2.17 2.928(6) 148 ½ x, ½ y, 1 z
C1A–H1A1


O1 0.96 2.47 3.388(11) 159 x, 1 y, ½ + z
C7B–H7B2


O2 0.96 2.45 3.319(11) 150 1 x, y, ½ z
Compound (III)
N1–H1


S1 0.86 2.79 3.448(1) 135 ½ x, y, ½+z
N1–H1


N3 0.86 2.13 2.910(2) 151 ½ x, y, ½+z
Compound (IV)
N1A–H1A


O1W 0.86 1.95 2.803(9) 170 2 x, 1 y, 2 z
N1B–H1B


O1 0.86 2.03 2.862(10) 164
O1W–H1W1


O3 0.82 2.15 2.966(11) 178
O1W–H2W1


O2 0.83 1.99 2.815(12) 168 2 x, 1 y, 1 z
 N.C. Saha et al. / Polyhedron 34 (2012) 1–12 9

are bonded to O1 and O1W, respectively, and this generates a supra-

molecular synthon which is formed through a hydrogen bonded
water–nitrate cluster (Fig. 5d).

3.4. Cytotoxicity

3.4.1. Comparison of the cell killing effect between the ligands

and their corresponding complexes
The percentage of viable HeLa cells was decreased dose-depen-
dently with the increase in concentration of the ligand or its com-
plex, but the complex showed a significantly greater killing effect
than the corresponding ligand. For example, Fig. 6A shows the %
viability after treatment with (I) (solid square) and (II) (hollow
square). Although there was no appreciable difference in % viability
produced by (I) and (II) at 5 lM concentration, there was a signif-
icant difference in % viability at and above 20 lM concentration, as
shown in Fig. 6A. The difference in % viability by (I) and (II) was in-
creased with concentrations above 20 lM and reached a maximum
at 50 lM. Only 7% cells were viable after 50 lM of (II) treatment
where as 57% cells were viable at the same concentration of (I).
This data indicates that the metal complex (II) has a greater cell
killing effect than (I) (ligand). Similarly, both (III) and (IV) induced
cell death dose-dependently, but complex (IV) shows a greater cell
killing effect than its ligand (III). Cell death by (IV) was found to be
significantly (p = 0.000) greater than (III) at and above 4 lM (IV)
killed about 95% cells at 10 lM whereas (III) killed about 20% at
the same concentration, implicating that (IV) was observed to be
more effective in inducing cell death than (III). This result is re-
flected in a cell morphology study, as shown later. Furthermore,
LD50 of (II) and (IV) was calculated to be at 28 and 8 lM, respec-
tively from the graph. The reason for the higher cell killing effect of
the complexes over their corresponding ligands is not really
known. Possibly, bulkier groups (–CH2CH3 for (IV) and –CH3 for
(II)) may play a role to potentiate its cytotoxic effect.

Fig. 6. Cell viability. Each square represents the mean ± SD of the% Cell viability
obtained from four independent experiments and p values calculated at each
concentration of the compound with respect to the untreated control are shown
above the respective point. Solid and hollow squares represent the ligand and its
complex, respectively.

displayed in Fig. 3c is generated through several intermolecular

interactions (Table 5).
The amino N(1) atom of the pyrazolyl ring of the free ligand (III)
in the molecule at (x, y, z) acts as a donor to the thiolato sulfur atom
S(1) at ½ x, y, ½ + z, forming a one-dimensional zigzag chain
which propagates along the (0 0 1) direction (Fig. 4b). The packing
diagram of the free ligand (III) is shown in Fig. 4c, where the pyraz-
olyl nitrogen atom plays a role as a donor to the thiolato sulfur and
hydrazinic chain nitrogen. In complex (IV), the pyrazolyl N(1B) atom
in ligand B in the molecule at (x, y, z) acts as a donor to the O1 atom of
the nitrate anion. Another amino N(1A) atom of the pyrazolyl ring in
ligand A acts as a donor to the solvent water atom O1W in the mol-
ecule at x + 2, y + 1, z + 2. Again, O1W acts as a donor to the oxy-
gen atom O2 of the nitrate anion via H2W1 at x + 2, y + 1, z + 1,
forming a one dimensional chain propagating along the (0 0 1) direc-
tion (Fig. 5b). Additional reinforcement between these molecules
combine to form a dimer with a characteristic R66(24) ring
(Fig. 5c). The solvent water O1W acts as a donor to both O3 and O2
Fig. 7. Cell morphology as photographed under a light microscope (Carl Zeiss) with
atoms of the nitrate anion via H1W1 and H2W1, respectively, form-
the appropriate attachment. (a) Untreated control HeLa cells and (b) and (c) are
ing a water–nitrate cluster through O–H


O hydrogen bonding. The HeLa cells treated with 50 lM of (I) and (II), respectively. (d) and (e) Represent cells
amino N(1A) and N(1B) atoms of the pyrazolyl ring act as a donor and treated with 10 lM of (III) and (IV), respectively.
10 N.C. Saha et al. / Polyhedron 34 (2012) 1–12

Fig. 8. Cell cycle distribution of HeLa cells treated with different concentrations of (I) and (II) in a typical experiment after analysis with ModFit LT software. DNA content (PI)
staining is shown in the X-axis (FL2-A) in all the figures. A, represents the untreated control HeLa; B, C, D, and E represents HeLa cells treated with 5, 20, 35 and 50 lM of (I),
respectively; F, G, H, and I shows HeLa cells treated with same concentrations of (II), respectively, as mentioned for (I).

The cell morphology as seen under a light microscope revealed
that cells got damaged with the increase in concentration of the
compounds. A typical picture of untreated HeLa cells (Fig. 7A),
HeLa treated with 50 lM of (I) and (II) is shown in Fig. 7B and C,
respectively. The cells are observed to be healthy (long attached)
in Fig. 7A. In Fig. 7B the cells are less damaged (smooth and round
shaped) than for Fig. 7C where the cells are short, wrinkled and
irregular in shape. Most of the cells were healthy at 10 lM of
(III), as shown in Fig. 7D, whereas almost all the cells are dead (nu-
clear portion that looks darker and a small patch is tending to sep-
arate from the cytoplasm that is a lighter big circular patch) at the
same concentration of (IV), as shown in Fig. 7E. Therefore, the
greater cytotoxicity of the complexes over their ligands was also
reflected from our morphological studies.
3.4.2. Detection of nuclear fragmentation or apoptosis
Nuclear fragmentation is one of the hallmarks of apoptotic cell
death, a special type of cell death [26,27]. We have monitored nu-
clear fragmentation of HeLa cells after treatment with various
doses (0–50 lM) of the synthesized products. We observed only
1–2% apoptotic cells after treatment with the products and this
percentage is within the background level. Therefore, this data
revealed that although the species (I), (II), (III) and (IV) exhibit a
cell-killing effect, they were not capable of inducing apoptosis. This
data implicates that the compounds under investigation put stress
on the cells resulting in shrinkage and small irregular shapes, but it
could not induce apoptosis.
3.4.3. Cell cycle analysis
The cell cycle alterations in HeLa cells induced by (I) and (II) are
shown in Fig. 8A–I whereas those by (III) and (IV) are shown in
Fig. 9A–K, after analysis by MODFIT LT software. The cell cycle
phase distribution is graphically shown in Fig. 10A [for (I) and
(II)] and Fig. 10B [for (III) and (IV)]. Each bar of a particular pattern
represented as average (denoted as ‘avg’ in the figure) values of %
G0/G1 cells, % S cells and % G2/M cells with standard deviations
after treatment with (I), (II), (III) and (IV). In the figure, ‘L’ desig-
nates ligand treatment i.e., (I) and (III), and ‘C’ is for complex treat-
ment i.e., (II) and (IV). The change of cell population at each dose in
a particular phase with respect to the untreated control was evalu-
ated to be statistically significant using Dunnett’s test. There was a
dose-dependent decrease in % G0/G1 cells and a dose-dependent
increase in % G2/M cells after treatment with (II), indicating that
this complex might be arresting cells at the M phase and thereby
prevent cell cycle progression from the M to G0 phase up to
35 lM concentration, in comparison with the control. On the con-
trary, there was a significant increase in the S phase at and above
20 lM (I), but there was no appreciable change of cell population
in the G0/G1 and G2/M phases with respect to the untreated con-
trol. This implies that (I) arrested cells in the S phase so that no cells
moved onto the subsequent G2/M or G0/G1 phases. Therefore, (II)
was capable of arresting cells at the G2/M phase while (I) can block
the cell cycle progression at the S phase. On the other hand, there
was consistently an increase of the S-phase population in a dose-
dependent manner of the ligand-(III) treated cells, implicating that
 N.C. Saha et al. / Polyhedron 34 (2012) 1–12 11

Fig. 9. Cell cycle distribution of HeLa cells treated with different concentration of (III) and (IV) in a typical experiment after analysis with ModFit LT software. DNA content
(PI) staining is shown in the X-axis (FL2-H) in all the figures. A, represents untreated control HeLa; B, C, D, E, and F represents HeLa cells treated with 1, 2, 4, 8 and 10 lM of
(III), respectively; G, H, I, J, and K shows HeLa cells treated with same concentrations of (IV), respectively, as mentioned for (III).

Fig. 10. Effect of the compounds on the cell cycle distribution in HeLa cells by fluorescence-activated cell sorting (FACS). (A) Cells treated with different concentrations of (I)
and (II); (B) cells treated with different concentrations of (III) and (IV).

(III) arrested cells at the S-phase, thereby inhibiting cells to move cells in the G2/M phase. Above 4 lM of (IV), the majority of the cells
onto the next G2/M phase. However, there was a dose-dependent were dying, as shown from the cell viability assay, and hence there
increase of the G2/M cell population of complex-(IV) treated cells was no appreciable cell population was found in the G2/M phase at
up to 4 lM concentration, indicating that (IV) might be arresting 8 or 10 lM concentrations of (IV).
12 N.C. Saha et al. / Polyhedron 34 (2012) 1–12

Acknowledgement [20] P. Bera, N.C. Saha, J. Ind. Chem. Soc. 87 (2010) 919.
[21] N. Saha, N. Mukherjee, Polyhedron 3 (1984) 1135.
[22] J.P. Scovill, Phosphorus Sulfur Silicon 60 (1991) 15.
The author, NCS, is grateful to the UGC (Government of India) [23] Bruker, SAINT (Version 6.36a) Bruker AXS Inc., Madison, Wisconsin, USA, 2002.
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[25] L.J. Farrugia, J. Appl. Crystallogr. 32 (1999) 837.
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