Synthesis, thermal and antitumour studies of Th(IV) complexes with furan-2-carboxaldehyde4-phenyl-3-thiosemicarbazone

Article abstract of DOI:10.2298/JSC090729048R

Thorium(IV) complexes with the Schiff base furan-2-carboxaldehyde4phenyl-3- thiosemicarbazone (L) were synthesised and characterized. The composition and structure of the metal complexes were proposed based on elemental analysis, molar conductivity measur

Full text of DOI:10.2298/JSC090729048R

J. Serb. Chem. Soc. 75 (6) 749–761 (2010)
JSCS–4004
UDC 546.795.4+547.72’828’288.3:
543.57:615.277–188
Original scientific paper
Synthesis, thermal and antitumour studies of Th(IV) complexes
with furan-2-carboxaldehyde4-phenyl-3-thiosemicarbazone
1
1
GANGADHARAN RAJENDRAN *, CHIRAKUZHI S. AMRITHA ,
2
2
RUBY JOHN ANTO and VINO T. CHERIYAN
1
Department of Chemistry, University College, Thiruvananthapuram-695034, Kerala
2
and Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology,
Thiruvananthapuram-695014, Kerala, India
(
Received 29 July 2009, revised 2 February 2010)
Abstract: Thorium(IV) complexes with the Schiff base furan-2-carboxaldehyde4-
phenyl-3-thiosemicarbazone (L) were synthesised and characterized. The
composition and structure of the metal complexes were proposed based on
elemental analysis, molar conductivity measurements, FTIR and 1H-NMR
spectroscopy. The Schiff base behaves as a neutral bidentate ligand
coordinating through the azomethine N and the thioketo S atoms. From various
studies, complexes were ascertained the general formula [ThL X ] and
2
4
–
–
–
–
[
ThL Y ], where X represents NO , NCS , CH COO , CH CHOHCOO ,
ClO4 and Y SO4 and C O . The thermal behaviour of the nitrato and
2
–
2
3
3
3
2–
2–
2
4
oxalato complexes was studied and kinetic and thermodynamic parameters
were calculated using the Coats-Redfern Equation. The ligand and a repre-
sentative complex [ThL (NO ) ] were screened in vitro for their antitumour
2
3 4
activity against the human cervical cancer cell line (HeLa).
Keywords: thorium(IV) complexes; furan-2-carboxaldehyde4-phenyl-3-
thiosemicarbazone; antitumour activity; thermal analysis.
INTRODUCTION
Complexes of thiosemicarbazones have been explored for a variety of rea-
sons, such as variable bonding properties, presence of several donor sites, struc-
1
tural diversity and pharmacological aspects. They present a variety of biological
2
–4
activities, including anticancer and anti-inflammatory activities.
Metal thiose-
micarbazonate complexes are emerging as a new class of experimental anticancer
and chemotherapeutic agents which exhibit inhibitory activities against most can-
cer through inhibition of a crucial enzyme obligatory for DNA biosynthesis and
5
cell division, viz. ribonucleotide diphosphate reductase (RDR). Some thiosemi-
*
Corresponding author. E-mail: drrajendranetal@gmail.com
doi: 10.2298/JSC090729048R
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RAJENDRAN et al.
carbazones even increase their antitumour activity by their ability to form chela-
6
tes with specific metal ions. It was reported that the anticancer activities of
thiosemicarbazones were closely related to the parent aldehyde or ketone group,
metal chelation ability and terminal amino substitution. Among them, the parent
aldehyde or ketone group was considered critical for the anticancer activity of
thiosemicarbazones. Heterocyclic thiosemicarbazone showed higher activity com-
7
pared with aromatic thiosemicarbazones. Heterocyclic thiosemicarbazones and
their metal complexes are among the most widely studied compounds for their
potential therapeutic uses, such as antitumoural, fungicidal, bactericidal or anti-
8
viral activity. The activity of these compounds is dependent on the nature of the
hetroaromatic ring and the position of attachment of the ring as well as on the
9
form of the thiosemicarbazone moiety. There were several studies involving
1
0–13
thiosemicarbazones with different metal ions.
However, only a few reports
described studies on thorium thiosemicarbazone complexes. Hence as part of on-
1
4,15
going research regarding thiosemicarbazone complexes of thorium
, the syn-
thesis, characterization and antitumour activity of Th(IV) complexes with furan-
-
2-carboxaldehyde4-phenyl-3-thiosemicarbazone (Fig. 1) are reported herein.
Fig. 1. Schematic view of the ligand.
EXPERIMENTAL
Materials and analytical methods
All employed chemicals were of analytical grade purchased from Merck, Sisco (India),
etc. Commercial solvents were distilled and used for synthesis, but for the physicochemical
studies, they were purified by standard methods.
The IR spectral studies were performed using KBr discs on a Schimadzu 8201 PC FT in-
1
frared spectrophotometer. The H-NMR spectra were recorded on a Bruker DRX-300 FT NMR
spectrophotometer employing TMS as the internal reference and DMSO-d as the solvent.
6
X-Ray diffraction studies were realized using a Philips X-ray PW 1710 diffractometer using
K-α1 radiation of wavelength 1.54056 Å. Molar conductance measurements of 10- M solu-
tions in CH CN and C H NO were performed at room temperature using a direct reading Eli-
3
3
6
5
2
co conductivity bridge. TG and DTG curves were recorded on a Mettler Toledo 850 C simul-
taneous TG/DTA thermal analyzer system in dynamic air at a heating rate of 10 °C/min. The TG
data was analyzed using the Coats-Redfern Equation for calculating the kinetic and thermody-
namic parameters. Elemental analyses were realized using an Elementar Vario EL III Carlo
Erba 1108 elemental analyzer at the Central Drug Research Institute, Lucknow, India.
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Th(IV) COMPLEXES WITH PHENYLTHIOSEMICARBAZONE
751
The metal content was estimated gravimetrically by the oxalate–oxide method.16 Stan-
dard gravimetric procedures were adopted for the estimation of the anions in the prepared com-
plexes.17 The sulphate and thiocyanate present in the complexes were estimated gravimetri-
cally as BaSO and AgNCS, respectively, while the perchlorate content was determined by the
4
Kurz method.1 The nitrate, oxalate, acetate and lactate contents were indirectly fixed by per-
8
forming elemental analysis for carbon, hydrogen and nitrogen by micro analytical methods.
Synthesis of ligand
The ligand, furan-2-carboxaldehyde4-phenyl-3-thiosemicarbazone, was prepared by the
following method. Furan-2-carboxaldehyde (0.010 mol) in methanol (10 ml) was added
dropwise to a hot solution of 4-phenyl-3-thiosemicarbazide (0.010 mol) in methanol (30 ml)
under constant stirring. The resulting mixture was heated on a water bath for 3 h, concentrated
and allowed to cool. The formed dark brown crystals of the ligand were washed, dried and
recrystallized from ethanol. Yield: 84 %; m.p. 120 °C ; Anal. Calcd. for C H N OS: C,
1
2 11 3
5
8.77; H, 4.49; N, 17.14; S, 13.06 %. Found: C, 58.56; H, 4.54; N, 17.63; S, 13.21 %. IR
-
1
(
KBr, cm ): 3256, (m, –NH), 1623 (vs, C=N), 1526 (m, C–O furan ring), 1060 (m, (N–N),
68 (s, C=S).
8
Synthesis of metal complex
The metal complexes were prepared by refluxing a methanolic solution of the metal salt
and the ligand in the stoichiometric ratio 1:2. For the preparation of the nitrato complex, the
appropriate amount of the metal salt (0.0020 mol) dissolved in a minimum quantity of metha-
nol (10 ml) was added to a solution of the ligand (0.0040 mol, 0.10 g) dissolved in methanol
(
25 ml). The pH of the solution was raised to 7 and refluxed on a water bath for about 5 h. It
was then concentrated and left standing over night. The separated complex was filtered, wash-
ed with a methanol–water mixture (50 % v/v) and then with ether and dried over P O in
4
10
vacuo. The other anionic complexes were prepared from the nitrato complex by the substi-
tution method19 by refluxing stoichiometric amounts of the nitrato complex with the respec-
tive anionic salts of lithium.
Antitumour screening
The in vitro antitumour activities of the ligand and a representative complex were exa-
mined by the MTT assay method2
0,21
against human cervical cancer cell line (HeLa).
The human cervical cancer cell line (HeLa) was obtained from the National Centre for Cell
Science Pune, India. The cells were grown in Dulbecco’s modified eagles medium (DMEM)
containing 10 % foetal bovine serum (FBS), streptomycin (100 μg/ml), penicillin (100 units/ml)
and amphotericin B (2.5 μg/ml). The cells were incubated at 37 °C in a 5 % CO incubator in
2
a humid condition and harvested using trypsin–ethylene diamine tetraacetic acid.
The test samples were dissolved in DMSO and diluted to the required concentration for
the biological experiments. Studies were undertaken with the test compounds in the concen-
tration range from 10 to 100 μg/ml.
For the determination of the cytotoxic effects, cells harvested from the exponential phase
were seeded equivalently (5000 cells/well) in a 96-well plate and incubated for 24 h. Test so-
lutions of different concentrations were added in triplicate to the well plates. Six well plates were
maintained in a drug free medium to determine the control, cell survival and the percentage of
live cells after culture. Cells with various concentrations of the test samples were incubated at
3
7 °C for 72 h.
To determine the numbers of live cells, the dye 3-(4,5-dimethylthiazol-2yl)-2,5-
diphenyltetrazolium bromide (MTT) was added to the cells, which were then incubated for 2 h
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RAJENDRAN et al.
at 37 °C. MTT is metabolized in the presence of the pyridine cofactors NADH and NADPH,
to give blue insoluble crystals. The cells were solubilised with 0.1 ml of extraction buffer (20
%
sodium dodecyl sulphate in 50 % dimethylformamide) and then incubated for 4 h at 37 °C.
Following the solubilisation of the cells, the colour intensity was read at 570 nm using an
Elisa plate reader (Bio-Rad). The percentage viability of the cells or cell survival (CS) was ex-
pressed as mean optical density (drug exposed cell) divided by mean optical intensity (control).
RESULTS AND DISCUSSION
All the prepared complexes were brown coloured, non-hygroscopic solids
stable at room temperature. They were soluble in DMSO and DMF but insoluble
in water and common organic solvents. The room temperature molar
–
3
conductivities of 10 M solutions of the complexes in CH CN and C H NO
3
6
5
2
2
2
corresponded to those of non-electrolytes. The analytical data revealed that all
complexes possessed 1:2 metal to ligand stoichiometry. Based on elemental
analysis, the complexes were assigned the composition shown in Table I.
TABLE I. Molar conductance at room temperature and elemental analyses data of the com-
plexes (L = C H N OS)
1
2
11
3
Molar conductance
Found (Calcd.), %
2
-1
Complex
S cm mol
Metal
23.85
C
29.63
H
2.16
N
14.53
S
6.79
C6H5NO2 CH3CN
[
[
[
[
[
[
[
ThL2(NO3)4] (1)
ThL2(SO4)2] (2)
ThL2(NCS)4] (3)
5.7
7.5
8.8
6.9
7.1
7.9
12.9
13.8
12.1
10.8
9.6
(
(
(
(
(
(
(
23.92) (29.69) (2.26) (14.43) (6.59)
25.25
25.38) (31.51) (2.41) (9.19)
24.21 35.12 2.51 14.47
24.32) (35.22) (2.31) (14.67) (20.13)
25.64 37.22 2.15 9.55 7.03
25.84) (37.42) (2.45) (9.35) (7.13)
24.30 40.02 3.25 8.17 6.28
24.22) (40.08) (3.55) (8.77) (6.68)
21.27 40.26 3.87 7.81 5.73
21.52) (40.07) (3.89) (7.79) (5.93)
31.45
2.30
9.09
14.15
(14)
20.21
ThL2(C2O4)2] (4)
ThL2(CH3COO)4] (5)
ThL2(C3H5O3)4] (6)
ThL2(ClO4)4] (7)
11.1
13.6
17.1
20.67
25.76
1.50
7.63
(7.5)
5.49
(5.71)
20.71) (25.71) (1.96)
Spectral studies
The IR spectrum of the ligand showed a strong absorption band at 1623 cm
which was assigned to the azomethine group, ν(C=N). In principle, the ligand
can exhibit thione–thiol tautomerism owing to the presence of a thioamide
–1
2
3
–
NH–C=S functionality (Fig. 2). The possibility of thione–thiol tautomerism in
–
1
the ligand was ruled out as no band around 2700–2500 cm , characteristic of the
thiol group, was observed in the IR spectrum (Fig. 3). The strong band ob-
served at 868 cm in the spectrum was due to the stretching vibrations of
2
4
–
1
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Th(IV) COMPLEXES WITH PHENYLTHIOSEMICARBAZONE
753
C=S.7,25 The bands observed at 3256 and 3423 cm–1 were assigned to N–H vib-
rations. This further indicates that the ligand remained in the thione form.
Fig. 2. Tautomeric forms of the ligand.
Fig. 3. IR spectrum of furan-2-aldehyde-N-phenylthiosemicarbazone.
The diagnostic IR spectral bands of the complexes are presented in Table II,
together with their tentative assignments. In the spectra of all the complexes, the
band due to the azomethine moiety (C=N) was shifted to a lower frequency by
–
1
≈
20–30 cm , indicating its involvement in coordination with metal ion. The
–
1
ν(C=S) stretching frequency was lowered by ≈20–40 cm in the spectra of the
complexes, indicating the involvement of the thioketo sulphur in the coordina-
tion. These findings are further supported by the appearance of new bands in the
far IR region at 495–505 and 359–370 cm , which are assignable to ν(Th–N)
and ν(Th–S) vibrations, respectively.
–
1
The IR spectra of the complexes differed among themselves due to the va-
rious coordinating anions and possessed additional non-ligand bands characteris-
tic of the anion present. The spectrum of the complex 1 showed three bands at
–
1
1
495, 1373 and 1033 cm , assignable to the ν , ν and ν modes of the coordi-
4 1 2
nated nitrate ions. The magnitude of the separation between the split bands (ν
4
–
1
26
and ν ) was 120 cm , indicating monodentate coordination of the nitrate ion
1
–
to the metal. In the spectra of complexes 5 and 6, ν (COO ) was observed at
a
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RAJENDRAN et al.
–
–
1
–1
598 and 1596 cm , respectively, and ν (COO ) at 1362 and 1352 cm , res-
s
pectively, apart from the skeletal vibrations of the ligand. The separation between
the two frequencies adequately supports the monodentate coordination of the ace-
tate and lactate group. The spectrum of complex 4 showed additional bands at
2
7
–
1
1
665 and 1361 cm , which were assigned to ν (COO) and ν (COO) modes of
a s
2
8
the bidentately coordinated dicarboxylate ion. The IR spectrum of complex 3
–1
had additional non-ligand bands at 2072, 777 and 493 cm , assignable to ν(C–N),
2
9
ν(C–S) and δ(NCS) of thiocyanate. The presence of these bands revealed the
2
9
N-coordinated nature of the thiocyanate ion. The spectrum of complex 2 exhi-
–
1
bited additional non-ligand bands at 1248, 1177 and 1085 cm , and the values
showed the bridging bidentate coordination of the sulphate group. For complex
7
coordination of the perchlorate group. The nature of the bonding of the various
anions is further supported by the non-electrolytic nature of all the complexes.
30
–
1
, the spectral bands at 1110, 1071 and 627 cm indicated the monodentate
31
-1
TABLE II. IR spectral data of the complexes (cm )
ν(C–O)
Furan ring
Compound
ν(N–H) ν(C=N)
ν(N–N) ν(C=S) ν(Th–N) ν(Th–S)
[
[
[
[
[
[
[
ThL
ThL
ThL (NCS) ] (3)
2
2
(NO
(SO
3
)
4
] (1)
] (2)
3255 m 1598 vs
3256 m 1601 vs
3252 m 1590 vs
3524 m 1597 vs
1520 m
1522 m
1521 m
1522 m
1524 m
1527 m
1523 m
1064 m 827 s 503 m
1066 m 823 s 506 m
1062 m 834 s 507 m
364 m
368 m
363 m
369 m
362 m
360 m
359 m
4
)
2
2
2
4
ThL
(C
2
O
4
)
2
] (4)
1066 m 846 s
504 s
ThL (CH COO) ] (5) 3253 m 1593 vs
ThL (C H O ) ] (6)
ThL
1068 m 848 s 508 m
1067 m 848 s 506 m
2
3
4
2
2
3
5
3 4
3256 m 1596 vs
3257 m 1591 vs
(ClO
4
)
4
] (7)
1061 m 846 s
498 s
1
The H-NMR spectrum of the ligand recorded in DMSO-d showed no peak
6
8
at 4 ppm attributable to SH protons but showed a peak at 9.87 ppm, which was
attributed to the N–H group, indicating that the ligand was in the thione form,
which is in conformity with the IR spectrum. A significant azomethine proton
signal due to CH=N was observed at 8.98 ppm, while that due to aromatic pro-
tons were observed in the region 7.21–7.36 ppm. Signals for the furan ring pro-
tons were observed at 6.57, 7.38 and 7.41 ppm.
1
The H-NMR spectrum of the complex [ThL (NO ) ] recorded in DMSO-d
6
2
3 4
showed proton signals in the expected regions but showed slight shifts compared
to the ligand spectrum. In the spectrum of the complex, an azomethine proton
signal was observed at 9.12 ppm; the N–H proton signal was observed at 9.98
ppm, the aromatic and furan ring proton signals were observed as multiplets in
the region 6.5 to 7.52 ppm. These data are consistent with the IR spectral data.
Based on spectral evidence, the proposed geometry for the complex is given in
Fig. 4.
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Th(IV) COMPLEXES WITH PHENYLTHIOSEMICARBAZONE
755
X-Ray diffraction study
The structure of [ThL (NO ) ] evaluated using powder X-ray diffraction in-
2
3 4
dicated the amorphous nature of the complex. The X-ray diffraction pattern is
given in Fig. 5.
Fig. 4. Proposed geometry of the complexes.
Fig. 5. XRD Pattern of the [ThL (NO ) ] complex.
2
3 4
Thermal studies
The thermal behaviour of [ThL (NO ) ] and [ThL
2
3 4
2
(C O ) ] were investi-
2 4 2
gated by the TG and DTG techniques under non-isothermal conditions.
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RAJENDRAN et al.
The [ThL (NO ) ] complex showed a single stage decomposition, as shown
2
3 4
by the DTG curve. The TG curve showed the absence of water or any other sol-
vent molecules, as the complex was stable up to 190 °C (Fig. 6). Decomposition
started at 190 °C and ended at 270 °C with a peak temperature of 247 °C, indi-
cating the loss of the ligand and nitrate group. The residue 27.57 % (calcd. 27.82 %)
showed that the final product formed was ThO , which is in agreement with the
2
analytical result for the metal content.
Fig. 6. TG and DTG curves of [ThL (NO ) ].
2
3 4
For the complex [ThL (C O ) ], the TG plateau up to 220 °C showed the
2
2 4 2
absence of coordinated water or any other solvent molecules and the stability of
complex (Fig. 7). Decomposition began at 220 °C and ended at 310 °C. The peak
temperature for the decomposition was 265 °C. The complex showed a single
stage decomposition, as evident from the DTG curve, and the decomposition oc-
curred with the loss of both ligand and oxalate molecules. The final product
formed was ThO and the residue obtained 29.55 % (calcd. 29.40 %) agreed well
2
with the analytical result obtained by an independent pyrolysis experiment.
Kinetic aspects
A kinetic evaluation of the thermal decomposition data of complexes was
carried out. The kinetic parameters, viz., the activation energy, E, and the pre-ex-
3
2
ponential factor, A, were calculated using the Coats-Redfern Equation. Compu-
tational data for the evaluation of kinetic parameters are given in Tables III and
2
IV. Here the ln g(α)/T vs. 1000/T plots (Figs. 8 and 9) gave straight lines, from
the slope and intercept of which were calculated the kinetic parameters by the
least square method. The goodness of fit was tested by evaluating the correlation
coefficient. The entropy of activation ΔS was calculated using the equation:
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Th(IV) COMPLEXES WITH PHENYLTHIOSEMICARBAZONE
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(1)
∆
S = R ln (Ah/kTs)
where R is the gas constant, A is the pre-exponential factor, k is the Boltzmann
constant, T is the DTG peak temperature and h is the Planck constant.
s
Fig. 7. TG and DTG curves of [ThL (C O4) ].
2
2
2
TABLE III. Computational data for the thermal decomposition of [ThL (NO ) ] (n = 2;
2
3 4
r = 0.99295)
-
3
-1
2
t / °C m / mg T/ K T / 10 K
Weight loss, %
α
g(α)
ln (g(α)/T)
2
2
2
2
2
2
2
2
2
00
10
20
30
40
50
60
70
80
3.33
3.30
3.08
2.24
1.58
1.03
0.96
0.93
0.91
473
483
493
503
513
523
533
543
553
–
0
0
0
–
2.07039
2.02840
1.98807
1.94932
1.91205
1.87617
1.84162
1.80832
0.03
0.25
1.09
1.75
2.30
2.37
2.40
2.42
0.01240 0.01255
0.10331 0.11521
0.45041 0.81955
0.72314 2.61194
0.95041 19.1667
0.97934
0.99174
1
–16.73788
–14.56204
–12.64018
–11.52046
–9.56599
–8.69842
–7.80673
–
47.4
120
–
TABLE IV. Computational data for the thermal decomposition of [ThL
(C
2 2
O
4
)
2
] (n = 1.7;
r = 0.99566)
-
3
-1
2
t / °C
m / mg T/ K T / 10 K
Weight loss, %
α
g(α)
ln (g(α)/T)
2
2
2
2
2
2
2
2
3
3
20
30
40
50
60
70
80
90
00
10
3.45
3.42
3.35
3.25
2.70
1.76
1.21
1.08
1.05
1.03
493
503
513
523
533
543
553
563
573
583
2.0284
1.98807
1.94932
1.91205
1.87617
1.84162
1.80832
1.77620
1.74520
1.71527
0
0
0
–-
0.03
0.10
0.20
0.75
1.69
2.24
2.37
2.40
2.42
0.01240 0.01253
0.04132 0.04283
0.08264 0.08892
0.30992 0.42356
–16.82091
–15.63107
–14.93921
–13.41611
–11.96454
–10.63201
–9.66269
–9.02350
–
0.69835
1.8770
0.92562 7.37952
0.97934 20.16347
0.99174 39.57784
1
–
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RAJENDRAN et al.
The kinetic parameters determined for the thermal decomposition are listed
in Table V. The positive value of the entropy of activation in both cases indicates
3
3
that the activated state was less ordered than the reactants.
Fig. 8. Coats-Redfern plot for [ThL (NO ) ]. Fig. 9. Coats-Redfern plot for [ThL (C O ) ].
2
3 4
2
2 4 2
TABLE V. Kinetic parameters for the thermal decomposition of the complexes
Pre-
Peak
temp.
ts/ °C
Activation
energy
Entropy of
activation
ΔS / J K mol
Correlation Order
exponential
term
Complex
coefficient
n
-1
-1
-1
E / kJ mol
-1
A / s
31
[
[
ThL
ThL
2
2
(NO
(C
3
)
4
]
247
265
0.99295
0.99566
2
325
282
8.6×102
362
241
5
2
O
4
)
2
]
1.7
4.4×10
Antitumour activity
The cell viability over the untreated control was determined using the MTT
assay, which is a very convenient method for assessing drug sensitivity even through
it does not discriminate between apoptosis and necrosis. The results showed that
both the ligand and complex possessed antitumour activity. The results are sum-
marized in Table VI.
The pharmacological properties of the metal complex must primarily be at-
tributed to the thiosemicarbazone ligand since the metal complex shows an acti-
vity of the same order of magnitude as that of the ligand. Ribonucleotide reduc-
tase, RR, the enzyme that catalyzes the conversion of ribonucleotides to deoxyri-
bonucleotides, is produced as a prerequisite for DNA replication and is highly
3
4
expressed in tumour cells. A strong positive correlation was established be-
3
5,36
tween RR activity and the rate of replication of tumour cells.
The inhibition
of RR prevents the production of deoxyribonucleotides. As a consequence these
3
7
compounds interfere with DNA synthesis thus decreasing the rate of replication
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Th(IV) COMPLEXES WITH PHENYLTHIOSEMICARBAZONE
759
of tumour cells and inhibiting tumour growth. The antitumour activity seems to
be due to an inhibition of DNA synthesis in cancer cells produced by modifica-
3
8
tion in reductive conversion of ribonucleotides to deoxyribonucleotides.
TABLE VI. Antitumour activity of the ligand and complex
-1
Compound
L
Concentration, μg ml
Relative cell viability, %
10
88.2
85.5
89.4
83.3
85.64
80.6
86.78
82.8
2
5
5
0
1
00
[
2 3 4
ThL (NO ) ]
10
2
5
5
0
1
00
CONCLUSIONS
The coordination sites of the ligand and the coordination number of the me-
tal in the prepared complexes were confirmed by physicochemical studies. Spec-
tral analysis showed that the ligand in the thioketo tatutomer form acts as neutral
bidentate with N and S atoms as the coordination sites. All the complexes were
neutral, amorphous solids stable at room temperature. From the research fin-
dings, the composition of the complexes can be ascertained as [ThL X ] and
2
4
–
–
–
–
[
ThL Y ], where X represents NO , NCS , CH COO , CH CHOHCOO and
2 2 3 3 3
–
2–
2–
ClO , and Y SO
and C O . A coordination number of 8 is proposed in all
2 4
4
4
these complexes. Antitumour studies indicated that complexation of the thiosemi-
carbazone with the metal ion lead to an enhancement of the activity of the thio-
semicarbazone.
И З В О Д
СИНТЕЗА, ТЕРМИЧКА И АНТИТУМОРСКА ПРОУЧАВАЊА Th(IV) КОМПЛЕКСА СА
ФУРАН-2-КАРБОКСАЛДЕХИД-4-ФЕНИЛ-3-ТИОСЕМИКАРБАЗОНОМ
1
1
2
2
G. RAJENDRAN , C. S. AMRITHA , RUBY JOHN ANTO и VINO T. CHERIYAN
1
2
Department of Chemistry, University College, Thiruvananthapuram-695034, Kerala, India, Molecular
medicine and Cancer research division, Rajiv Gandhi Centre for Biotechnology,
Thiruvananthapuram-695014, Kerala, India
Добијени су и окарактерисани комплекси торијума(IV) са Шифовом базом фуран-2-
карбоксалдехид-4-фенил-3-тиосемикарбазоном (L). Састав и структура металних комплекса
1
су предложени на основу елементалне анализе, мерења моларне проводљивости, FT-IR и H-
NMR спектара. Шифова база се понаша као неутрални бидентатни лиганд координујући се
преко азометинског N и тиокето S атома. Из различитих студија комплексима су
–
–
–
установљене опште формуле [ThL2X4] и [ThL2Y2], где X представља NO , NCS , CH COO ,
3
3
–
–
2–
2–
CH CHOHCOO и ClO , a Y SO и C O . Проучавано је термичко понашање нитрато и
3
4
4
2 4
оксалато комплекса, а кинетички и термодинамички параметри су израчунати применом
Coats–Redfern-ове једначине. Лиганд и одабрани комплекс [ThL2(NO3)4] су тестирани in vitro
на антитуморску активноост према ћелијским линијама рака грлића материце (HeLa).
(Примљено 29. јула 2009, ревидирано 2. фебруара 2010)
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60
RAJENDRAN et al.
REFERENCES
1. T. S. Lobana, Rekha, R. J. Butcher, A. Castineiras, C. Bermejo, P. V. Bharatam, Inorg.
Chem. 45 (2006) 1535
2
3
. M. Ruan, Y. Ye, Y. Song, Q. Mauricio, F. Erben, C. O. D. Vedova, Spectrochim. Acta 72
A (2009) 26
. P. I. Das, M. F. Fernando, R. Pavan, C. Q. F. Leite, F. D. Sousa, A. A. Batista, O. R. As-
cimento, J. E. Eduardo, E. Castellano, E. Niquet, V. M. Deflon, Polyhedron 28 (2009) 205
. Z. H. Chohan, Transition Met. Chem. 34 (2009) 153
4
5
6
7
8
. D. P. Saha, S. Padhye, E. Sinn, C. Newton, Indian J. Chem. 41A (2002) 279
. A. G. Quiroga, C. N. Ranninger, Coord. Chem. Rev. 248 ( 2004) 119
. H. Zhang, R. Thomas, D. Oupicky, F. Peng, J. Biol. Inorg. Chem. 13 (2008) 47
. E. M. Jouad, G. Larcher, M. Allain, A. Riou, G. M. Bouet, A. M. Khan, X. D. Thanh, J.
Inorg. Biochem. 86 (2001) 565
9. S. Chandra, M. Tyagi, M. S. Refat, J. Serb. Chem. Soc. 74 (2009) 907
1
1
1
1
1
1
1
0. M. J. M. Campbell, Coord. Chem. Rev. 15 (1975) 279
1. M. A. Ali, S. E. Livingstone, Coord. Chem. Rev. 13 (1974) 101
2. S. Padhye, G. B. Kauffman, Coord. Chem. Rev. 63 (1985) 127
3. J. S. Casas, M. S. Garcia-Tasenda, J. Sorda, Coord. Chem. Rev. 209 (2000) 197
4. G. Rajendran, C. S. Amritha, Asian J. Chem. 18 (2006) 2695
5. G. Rajendran, C. S. Amritha, Oriental, J. Chem. 22 (2006) 365
6. I. M. Kolthoff, P. J. Elving, Treatise on Analytical Chemistry, Interscience, New York,
1
963
th
1
1
1
2
2
7. A. I. Vogel, A Textbook of Quantitative Inorganic Analysis, 4 ed., ELBS, London, 1978
8. E. Kurz, G. Kober, M. Berl, Anal. Chem. 30 (1958) 1983
9. P. Indrasean, G. Rajendran, Synth. React. Inorg. Met. Org. Chem. 22 (1992) 715
0. T. Mosmann, J. Immunol. Methods 65 (1983) 55
1. A. P. Wilson, Cytotoxicity and Viability Assays in Animal Cell Culture: A Practical
rd
Approach, 3 ed., Vol. 1, Oxford University Press, Oxford, 2000
2
2
2. W. J. Geary, Coord. Chem. Rev. 7 (1971) 81
3. A. K. Sen, G. Singh, K. Singh, R. K. Noren, R. M. Handa, S. N. Dubey, Indian J. Chem.
3
6A (1977) 891
2
2
2
2
4. K. S. A. Melha, J. Enzym. Inhib. Med. Chem. 23 (2008) 493
5. P. Bindu, M. R. P. Kurup, Transition Met. Chem. 22 (1997) 578
6. S. G. Devi, P. Indrasenan, Inorg. Chim. Acta 133 (1987) 157
7. B. W. Mistry, A Hand Book of Spectroscopic Data Chemistry, 1 ed., ABD Publishers,
Jaipur, India, 2000
st
28. D. N. Sathyanarayana, Vibrational Spectroscopy, Theory and Applications, New Age In-
ternational (P) Ltd., India, 2004
2
3
9. R. K. Agarwal, P. Kumar, H. K. Rawat, Thermochim. Acta 88 (1985) 397
0. K. Nakamoto, Infrared and Raman Spectra of Inorganic and Coordination Compounds,
Wiley, New York, 1987
3
3
3
3
1. M. Viswanathan, J. Indian Chem. Soc. 82 (2005) 871
2. K. K. Aravindakshan, K. Muraleedharan, Thermochim. Acta 155 (1989) 247
3. A. A. Frost, R. G. Pearson, Kinetics and Mechanism, Wiley, New York, 1961
4. C. R. Kowol, R. Berger, R. Eichinger, A. Roller, M. A. Jakupee, P. P. Schmidt, V. B.
Arion, B. K. Keppler, J. Med. Chem. 50 (2007) 1254
Available online at www.shd.org.rs/JSCS/
______________________________________________________________________________________________________________________
_
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Th(IV) COMPLEXES WITH PHENYLTHIOSEMICARBAZONE
761
35. R. A. Finch, M. C. Liu, S. P. Grill, W. C. Rose, R. Loomis, K. M. Vasquez, Y. C. Cheng,
A. C. Sartorelli, Biochem. Pharmacol. 59 (2000) 983
3
3
6. F. A. French, J. E. Blanz, J. Med. Chem. 17 (1974) 172
7. M. B. Ferrari, F. Bisceglie, C. Casoli, S. Durot, I. M. Badarau, G. Pelosi, E. Pilotti, S.
Pinelli, P. Tarasconi, J. Med. Chem. 48 (2005) 1671
38. W. X. Hu, W. Zhou, C. Xia, X. Wen, Bioorg. Med. Chem. Lett. 16 (2006) 2213.
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