Synthesis, DNA binding, antioxidant and cytotoxic activities of ruthenium(II) complexes of a Schiff base ligand

Article abstract of DOI:10.1007/s11243-013-9690-z

Three ruthenium(II) complexes, [Ru(CO)Cl(PPh₃)L], [Ru(CO)Cl(AsPh₃)L] and [Ru(CO)Cl(Py)L], were synthesized from the reactions of 2-(benzothiazol-2-yliminomethyl)-phenol (HL) with [RuHCl(CO)B(EPh₃)₂], where B = P

Full text of DOI:10.1007/s11243-013-9690-z

Transition Met Chem (2013) 38:291–298
DOI 10.1007/s11243-013-9690-z
Synthesis, DNA binding, antioxidant and cytotoxic activities
of ruthenium(II) complexes of a Schiff base ligand
Subbaiyan Sathiyaraj
•
•
Krishnan Sampath
Ray J. Butcher Chinnasamy Jayabalakrishnan
•
Received: 31 October 2012 / Accepted: 3 January 2013 / Published online: 24 January 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract Three ruthenium(II) complexes, [Ru(CO)Cl(PPh )L],
3
DNA strands. In the case of cancer genes, cleavage of the
[
Ru(CO)Cl(AsPh )L] and [Ru(CO)Cl(Py)L], were synthe-
3
DNA double strands can destroy their replication ability.
Ruthenium complexes are presently the objective of a great
deal of attention in the field of medicinal chemistry, as
potential antitumor agents with selective antimetastatic
properties and low systemic toxicity [3]. Ruthenium com-
plexes appear to penetrate reasonably well into tumor cells
and bind effectively to DNA [4].
sized from the reactions of 2-(benzothiazol-2-ylimino-
methyl)-phenol (HL) with [RuHCl(CO)B(EPh ) ], where
3
2
B = PPh , AsPh or pyridine, and E = P or As. All the
3
3
complexes have been characterized by physicochemical
and spectroscopic methods. The structure of the free ligand
HL was determined by single crystal X-ray diffraction. The
binding of the free ligand and its complexes with CT-DNA
was studied using electronic absorption spectroscopy. In
addition, the free ligand and its complexes were subjected
to antioxidant activity tests, which showed that they all
possess significant scavenging effects against DPPH and
OH radicals. The in vitro cytotoxicities of the compounds
were assessed using tumor (HeLa and MCF-7) cell lines.
Over recent years, a number of bisbenzimidazoles [5],
arybenzothiazoles [6] and 2-aminobenzothiazoles have been
found to possess bioorganic and medicinal applications in
drug discovery, including potent antitumour activity. From
modeling studies, they appear to act as minor groove binding
agents, spanning a number of base pairs which allows
sequence specificity to be included in the ligand design.
Based on the above facts, we herein report on the syn-
thesis and characterization of ruthenium(II) Schiff base
complexes containing 2-(benzothiazol-2-yliminomethyl)-
phenol (HL) as ligand. The single crystal X-ray structure of
the free ligand has been determined. DNA-binding abilities
of the free ligand and its ruthenium(II) complexes were
investigated with calf-thymus DNA (CT-DNA). We have
also investigated the relationship between co-ligand struc-
ture and the cytotoxicities of these complexes for two
cancer cell (HeLa and MCF-7) lines. Furthermore, their
antioxidant effects were evaluated in vitro by their abilities
to scavenge DPPH and hydroxyl radicals.
Introduction
In recent years, researchers have focused their curiosity on
metal containing drugs and their interactions with DNA [1].
An understanding of the interaction between metal com-
plexes and DNA at the molecular level is important for the
design of new drugs and probes that can recognize specific
DNA sequences and structural motifs [2]. Moreover, certain
metal complexes have been shown to be capable of cleaving
S. Sathiyaraj ꢀ K. Sampath ꢀ C. Jayabalakrishnan (&)
Post Graduate and Research Department of Chemistry,
Sri Ramakrishna Mission Vidyalaya College of Arts
and Science, Coimbatore 641 020, Tamil Nadu, India
e-mail: drcjbstar@gmail.com
Experimental
Materials and instrumentation
R. J. Butcher
Department of Chemistry, Howard University,
Washington, DC 20059, USA
Reagent grade chemicals were used without further puri-
fication in all the synthetic work. Solvents were purified by
123

2
92
Transition Met Chem (2013) 38:291–298
standard methods [7]. Salicylaldehyde and 2-aminobenzo-
Table 1 Crystal and structure refinement data for Schiff base ligand
(
HL)
thiazole were purchased from Sigma-Aldrich. RuCl ꢀ3H O,
3
2
PPh and AsPh were purchased from Himedia. CT-DNA
3
3
Empirical formula
Formula weight
Temperature
C14 H10 N O S
2
was purchased from Bangalore Genei, Bangalore, India.
Infrared spectra were recorded on an FTIR Perkin Elmer
spectrophotometer RXI model as KBr pellets in the range
254.30
273(2) K
0.71073 A
Orthorhombic
Pbca
Wavelength
-
1
of 4,000–400 cm . Elemental analyses were obtained
with a model Vario ELIII CHNS at the Sophisticated Test
and Instrumentation Centre (STIC), Cochin University,
Kerala. Electronic spectra were recorded in DMSO solu-
tion in a Systronics 2202 double beam spectrophotometer
Crystal system
Space group
Unit cell dimensions
˚
a (A)
12.1518(5)
8.9528(5)
22.0200
90
˚
b (A)
1
13
31
in the range of 800–200 nm. H, C and P NMR spectra
were recorded on a Bruker WM DCX 500 MHz instrument
using TMS and orthophosphoric acid as internal standards
at SAIF, Indian Institute of Technology, Chennai. Anti-
oxidant and anticancer studies were carried out at the
Kovai Medical Centre and Hospital Pharmacy College,
Coimbatore, Tamil Nadu. The metal precursors [RuHCl(CO)
˚
c (A)
a (°)
b (°)
90
c (°)
Volume
90
3
˚
2,395.6(2) A
Z
8
3
Density (calculated)
Crystal size
8.1.410 mg/m
(
PPh ) ] [8], [RuHCl(CO)(AsPh ) ] [9] and [RuHCl(CO)
3 3 3 3
0.30 9 0.20 9 0.20 mm
2.50°–25.00°
-14 B h B 14
(
PPh ) (py)] [10] were prepared according to the reported
3
2
Theta range for data collection
Limiting indices
Reflections collected
Data/restraints/parameters
literature procedures.
-10 B k B 7
Crystal structure determination
-25 B l B 26
2
Goodness-of-fit on F
1.066
Single crystals of HL were grown by slow evaporation of a
solution of the ligand in chloroform. Selected crystal data
are given in Tables 1 and 2, and Fig. 1. The X-ray dif-
fraction data were collected on a Bruker Kappa APEXII
CCD diffraction instrument using graphite-monochromated
Final R indices [I [ 2 sigma(I)]
R indices (all data)
R1 = 0.0317, wR2 = 0.0832
R1 = 0.0479, wR2 = 0.0945
˚
Mo Ka radiation (k = 0.71073 A) by / and x scans. X-ray
data reduction, structure solution and refinement were
performed using the SHELXS-97 and SHELXL-97 pack-
ages [11]. The structure was solved by direct methods.
˚
Table 2 Selected bond lengths (A) and angles (°) for Schiff base
ligand (HL)
Bond lengths
Bond angles
Synthesis of 3-(benzothiazol-2-yliminomethyl)-phenol
S C(1)–O(1) 1.343(2)
C(1)–C(2) 1.380(3)
C(1)–C(6) 1.413(2)
C(2)–C(3) 1.376(3)
C(2)–H(2) 0.9300
C(3)–C(4) 1.377(3)
C(3)–H(3) 0.9300
C(4)–C(5) 1.364(3)
C(4)–H(4) 0.9300
C(5)–C(6) 1.396(2)
C(5)–H(5) 0.9300
C(6)–C(7) 1.430(2)
C(7)–N(1) 1.285(2)
C(7)–H(7) 0.9300
C(8)–N(2) 1.290(2)
C(8)–N(1) 1.380(2)
C(8)–S(1) 1.7688(17)
N(2)–C(10) 1.380(2)
N(1)–C(7)–C(6) 122.23(14)
N(1)–C(7)–H(7) 118.9
(
HL)
C(6)–C(7)–H(7) 118.9
A solution of salicylaldehyde (1.1 ml, 10 mmol) in ethanol
15 ml) was added to a stirred solution of 2-amino ben-
N(2)–C(8)–N(1) 121.11(15)
N(2)–C(8)–S(1) 115.65(13)
N(1)–C(8)–S(1) 123.24(13)
C(8)–N(2)–C(10) 110.80(14)
N(2)–C(10)–C(11) 125.30(16)
N(2)–C(10)–C(15) 115.36(16)
C(11)–C(10)–C(15) 119.34(17)
C(12)–C(11)–C(10) 119.66(18)
C(12)–C(11)–H(11) 120.2
C(10)–C(11)–H(11) 120.2
C(11)–C(12)–C(13) 120.7(2)
C(11)–C(12)–H(12) 119.6
C(13)–C(12)–H(12) 119.6
C(14)–C(13)–C(12) 121.0(2)
C(14)–C(13)–H(13) 119.5
(
zothiazole (1.5 g, 10 mmol) in ethanol (20 ml). The mix-
ture was stirred for 30 min and then refluxed for 6 h. After
cooling the reaction mixture to room temperature, the solid
product formed was filtered off, washed with ethanol and
dried under vacuum. This solid was recrystallized from
chloroform, yielding needle-shaped yellow crystals that
were suitable for X-ray diffraction analysis.
Synthesis of the complexes
The complexes were prepared by the following general
procedure (Scheme 1). A solution of [RuHCl(CO)B(EPh ) ]
3
2
(
0.1510–0.1904 g, 0.2 mmol) in benzene (20 ml) (B =
PPh , AsPh or pyridine (py), E = P or As) was added to a
3
3
1
23

Transition Met Chem (2013) 38:291–298
293
data were then processed with the following equation, and
the intrinsic binding constant K was calculated in each
b
case [12].
½DNAꢁ=ðea ꢂ ef Þ ¼ ½DNAꢁ=ðeb ꢂ ef Þ þ 1=Kbðeb ꢂ ef Þ
where [DNA] is the concentration of DNA in the base
pairs, and the apparent absorption coefficients e , e and e
b
a
f
correspond to Aobsd/[complex], the extinction coefficient of
the free compound and the extinction coefficient of the
compound when fully bound to DNA, respectively. In plots
of [DNA]/(e - e ) versus [DNA], K is given by the ratio
Fig. 1 Labeled ORTEP diagram of HL with thermal ellipsoid at
5
0 % probability
a
f
b
of slope to the intercept.
stirred solution of HL (0.05086 g, 0.2 mmol) in chloroform
15 ml). The mixture was refluxed for 8 h. The solvent was
(
Antioxidant studies
then evaporated under reduced pressure, and the solid mass
was filtered out and washed with petroleum ether. The purity
of the complexes was checked by thin layer chromatogra-
phy, and they were further purified by column chromatog-
raphy using 1:10 acetonitrile–benzene as an eluent and silica
gel (60–120 mesh) as stationary phase, then recrystallized
from CH Cl /n–hexane mixture. Extensive efforts to obtain
The free radical scavenging abilities of the compounds
were determined against both DPPH and hydroxyl radicals.
The DPPH radical scavenging activity of the compounds
was investigated using the method described by Elizabeth
[
13], while the hydroxyl radical scavenging activity of the
compounds was evaluated by the modified method of Yu
14]. For each of the assays, the tests were run in triplicate
2
2
single crystals of the complexes were unsuccessful.
[
at varying concentrations. The percentage activity was
DNA interaction experiments
calculated using the following formula: % activity =
[
(A - A )/A ] 9 100, where A and Ac represent the
o c o o
Experiments involving the interaction of HL and its
ruthenium(II) complexes with CT-DNA were carried out in
double distilled water with tris(hydroxymethyl)-amino-
methane (Tris, 5 mM) and sodium chloride (50 mM) and
adjusted to pH 7.2 with hydrochloric acid. A solution of
CT-DNA in the buffer gave a ratio of UV absorbance of
about 1.9 at 260 and 280 nm, indicating that the DNA was
sufficiently free of protein. The DNA concentration per
nucleotide was determined by absorption spectroscopy
using the molar extinction coefficient value of
absorbance in the absence and presence of the test com-
pounds, respectively. The 50 % activity (IC ) was calcu-
5
0
lated from the % activities.
Cytotoxicity studies
Cytotoxicity studies of the compounds were carried out on
human cervical cancer (HeLa) and human breast cancer
(
MCF-7) cell lines, which were obtained from the National
3
-1
-1
Centre for Cell Science, Pune, India. Cell viability was
assayed using the MTT assay method. The HeLa and
MCF-7 cells were grown in Eagles minimum essential
medium containing 10 % fetal bovine serum (FBS). For the
screening experiments, the cells were seeded into 96-well
plates in 100 lL of the medium containing 10 % FBS, at a
plating density of 10,000 cells/well, and incubated at
6
,600 dm mol cm at 260 nm. Electronic absorption
titration experiments were performed by maintaining the
concentration of test compound as constant (25 lM) but
with variable nucleotide concentration from 0 to 25 lM.
While measuring the absorption spectra, equal amounts of
DNA were added to both the compound and reference
solutions to eliminate the absorbance of DNA itself. The
3
7 °C, under conditions of 5 % CO , 95 % air and 100 %
2
relative humidity for 24 h prior to the addition of the test
compounds. The test compounds were dissolved in DMSO
and diluted in the medium containing 1 % FBS. After 24 h,
the medium was replaced with the medium with 1 % FBS
containing the compounds at various concentrations and
OC
Cl
O
Ru
N
B
N
N
[
RuHCl(CO)(B)(EPh3)2]
S
S
N
incubated at 37 °C under conditions of 5 % CO , 95 % air
2
OH
and 100 % relative humidity for 48 h. Experiments were
carried out in triplicate, and the medium not containing the
compounds served as the control. After 48 h, 10 lL of
MTT (5 mg/mL) in phosphate-buffered saline (PBS) was
added to each well and incubated at 37 °C for 4 h. The
Scheme 1 Formation of ruthenium(II) Schiff base complexes.
B = PPh , AsPh or py
3
3
123

2
94
Transition Met Chem (2013) 38:291–298
-
1
-1
medium with MTT was then flicked off, and the formazan
crystals were dissolved in 100 lL of DMSO. The absor-
bance was then measured at 570 nm using a micro-plate
reader. The % cell inhibition was determined using the
following formula:
1,605 cm m(C=N thiazole ring), 1,251 cm m(CO) and
-
1
-1
750 cm m(C–S–C). The m(C=N) band at 1654 cm was
-
1
shifted to lower frequency (1,618–1,614 cm ) for the
complexes, indicating bonding of the azomethine nitrogen to
-
1
the metal [16]. The phenolic m(C–O) band at 1,251 cm for
the Schiff base [16] was shifted toward higher frequencies
-
1,261–1,260 cm ) in the complexes, confirming coordi-
%
Growth inhibition ¼ 100 ꢂ Abs ðsample)=Abs ðcontrol)
ꢃ 100:
1
(
nation of the phenolic oxygen. A low frequency band at
-
1
4
5
30–470 cm
is attributed to (M–O) and one at
Nonlinear regression graphs were plotted between %
-
1
60–580 cm to (M–N) [17]. The thiazole C=N band of the
cell inhibition and Log10 concentration and used to obtain
IC50 values [15].
-
1
free ligand at 1,605 cm is shifted to lower frequency at
-
about 1,588–1,582 cm for the complexes, whereas the
1
-
1
m(C–S–C) band at 750 cm for the free ligand is not much
shifted for the complexes, suggesting coordination of the
thiazole through N rather than S. A strong band in the region
Results and discussion
-
1
1
,950–1,944 cm is assigned to the terminally coordinated
The molecular structure of HL, along with the atom
numbering scheme, is given in Fig. 1. The crystal data and
structural refinement parameters are given in Table 1 and
selected bond lengths and angles are given in Table 2. The
compound crystallized into an orthorhombic lattice with
carbonyl. For the complex [RuCl(CO)(py)L)], the IR spec-
-
1
trum showed a medium intensity band at 1,125 cm , which
is characteristic of the coordinated nitrogen base. For the
other complexes, characteristic bands for triphenylphos-
phine and arsine are also present in the expected regions [18].
The electronic spectra of the free Schiff base and its
complexes were recorded in DMSO (Table 4). The elec-
tronic spectrum of the free ligand showed four bands at
˚
space group Pbca. The azomethine bond, C7–N1 1.285(2) A,
is in conformity with a formal C=N double bond, and the
˚
C1–O1 bond distance of 1.343(2) A is slightly shorter than
the normal C–O single bond distance. The bond distances
˚
for C8–N2, at 1.290(2) A, and C8–S1, for thiazole group at
2
61, 296, 366 and 412 nm, assigned to the p–p* and n–p*
transitions in the aromatic ring and C=N chromophore [19].
In electronic spectra of all three complexes, five to six
bands were observed at 262–502 nm. Those at
˚
.7688(17) A, are closer to C=N double and C–S single
1
bonds, respectively. The single crystal X-ray diffraction
study unambiguously shows that this compound exits in the
imine-ol form.
2
62–366 nm may be due to intra-ligand transitions. The
charge transfer bands observed for all three complexes due
Three air stable, mononuclear octahedral ruthenium(II)
Schiff base complexes of the type [RuCl(CO)B(L)] (where
to M ? L transitions are observed in the range of
471–502 nm [20, 21]. The electronic spectra of these
B = PPh , AsPh or py; L = monobasic tridentate Schiff
3
3
complexes indicate of an octahedral coordination geome-
try, similar to other octahedral ruthenium(II) complexes
[20].
base) have been prepared by the reaction of [Ru-
HCl(CO)B(EPh ) ] (E = P or As) with the Schiff base in
3
2
1
1
:1 molar ratio in chloroform–benzene mixture. The ana-
The H NMR spectra of the free ligand and its com-
lytical data (Table 3) for the complexes agree well with the
proposed molecular formulae (Scheme 1).
plexes were recorded in DMSO-d . The spectra of HL and
6
[Ru(CO)Cl(PPh )L] are shown in Figs. 2 and 3, and the
3
The IR spectrum of the ligand was compared with those of
the ruthenium(II) complexes in order to confirm the binding
mode of the Schiff base ligand (Table 4). For the free Schiff
base, the most characteristic bands were observed at
assignments are given in Table 5. The aromatic protons for
free HL appear as a multiplet at 7.04–8.10 ppm. On
complexation, these signals show only slight variations
[
22] and cannot be distinguished from the aromatic signals
-
1
-1
3
,426 cm
m(OH), 1,654 cm
m(C=N azomethine),
of PPh3 or AsPh , due to their extensive overlap at
3
Table 3 Analytical data of ligand and ruthenium(II) complexes
Ligand/complexes
Color
Yield (%)
Melting point (°C)
Elemental analysis calculated (found)
C (%)
H (%)
N (%)
S (%)
HL
Yellow
Pink
74
67
68
61
152
178
192
186
66.12 (66.24)
58.29 (58.37)
54.75 (54.89)
48.33 (48.04)
3.96 (3.75)
3.55 (3.69)
3.33 (3.61)
2.83 (2.96)
11.02 (11.18)
4.11 (3.95)
3.86 (3.89)
8.45 (8.17)
12.61 (12.48)
4.71 (4.89)
4.42 (4.19)
6.43 (6.65)
[Ru(CO)Cl(PPh
[Ru(CO)Cl(AsPh
[Ru(CO)Cl(Py)L]
3
)L]
3
)L]
Pink
Pink
1
23

Transition Met Chem (2013) 38:291–298
295
Table 4 IR and electronic spectroscopic data of ligand and ruthenium(II) complexes
-
1
Ligand/complexes
FT-IR cm
UV–Vis
max (nm)
m(C=N)
m(Ph–CO)
m(C:O)
m(C=N) thiazole
k
HL
1,654
1,618
1,614
1,617
1,251
1,260
1,261
1,260
–
1,605
1,585
1,582
1,588
261, 296, 366, 412
[Ru(CO)Cl(PPh
[Ru(CO)Cl(AsPh
[Ru(CO)Cl(Py)L]
3
)L]
1,944
1,945
1,950
262, 293, 365, 404, 471
262, 294, 351, 397, 502
3
)L]
262, 294, 366, 428, 466, 488
6
.63–7.80 ppm [23]. The hydroxyl proton gives a singlet at
0.21 for the free Schiff base. The equivalent signal is
1
absent from the spectra of the complexes, consistent with
coordination of the hydroxyl oxygen to the metal [24]. The
signal due to the azomethine proton is considerably de-
shielded at 9.06–9.24 ppm relative to the free Schiff base
ligand at 8.62 ppm, as a consequence of electron donation
to the metal center.
1
3
The C NMR data were recorded in DMSO-d and the
6
assignments are given in Table 5. The spectrum of the free
Schiff base displayed a single azomethine resonance at
1
53 ppm [25], indicating only one tautomer. A signal at
67 ppm is assigned to the thiazole C=N carbon [25]. The
1
downfield shifts of these two signals in the complexes, at
62–163 and 171–173 ppm, respectively, clearly indicate
that both the C=N carbons are affected by coordination
26]. The aromatic carbons of both the free ligand and its
1
1
Fig. 3 H NMR spectrum of complex [Ru(CO)Cl(PPh )L]
3
[
complexes show signals in the region of 107–135 ppm. For
all the complexes, the terminal carbonyl group appeared in
the range of 191–194 ppm [27].
DNA-binding experiments
3
1
The P NMR spectrum of the complex [Ru(CO)Cl-
PPh )L] in DMSO-d showed a sharp singlet at 26.2 ppm,
The DNA-binding properties of both the ligand and its
complexes were investigated by UV–Vis spectral titration.
The electronic spectra of HL and the complexes upon the
addition of DNA are shown in Fig. 4. The titration results
showed that with increasing concentrations of DNA, sig-
nificant hyperchromism with a red shift was observed in all
cases. This can be attributed to a strong interaction between
DNA and the complexes. However, there were no appre-
ciable wavelength shifts in the charge transfer band. From
these results, we infer a nonintercalative mode of binding
with DNA. In general, the observation of hypochromism is
indicative of intercalative binding, along with stabilization
of the DNA double helix structure [29]. On the other hand,
the observation of hyperchromism is indicative of disrup-
tion of the secondary structure of DNA [30]. Hence, the
observation of hyperchromism and a red shift in the present
case suggests that these compounds disrupt the double
helix structure of DNA.
(
3
6
confirming the presence of only one phosphine group. The
coordination of PPh to the metal changes its chemical shift
3
by about 32 ppm [28].
The intrinsic binding constants K for these compounds
b
are given in Table 6 and Fig. 5. The constants were
determined by monitoring the changes in the absorbance of
the IL (intraligand) band at the corresponding kmax with
1
Fig. 2 H NMR spectrum of HL
123

2
96
Transition Met Chem (2013) 38:291–298
1 13
Table 5 H and C NMR data of ligand and ruthenium(II) complexes
1
13
Ligand/complexes
H NMR data (ppm)
C NMR data (ppm)
Ph–OH (s)
HC=N (s)
Aromatic (m)
Aromatic carbon
C=N imine
C:O
C=N thiazole
HL
10.21
8.62
9.24
9.06
9.12
7.40–8.10
6.90–7.80
6.63–7.80
6.94–7.78
117–134
109–135
107–134
118–134
153
163
162
163
–
167
173
171
171
[Ru(CO)Cl(PPh
[Ru(CO)Cl(AsPh
[Ru(CO)Cl(Py)L]
3
)L]
–
–
–
191
191
194
3
)L]
increasing concentrations of DNA, as given by the ratio of
Table 6 Binding constant value for interaction of the compounds
with CT-DNA
the slope to the Y intercept in plots of [DNA]/(e - e )
a
f
4
K 9 10 M
-1
versus [DNA]. From the binding constant values, it is
Compounds
b
inferred that [RuCl(CO)PPh (L)] shows the strongest
3
HL
3.56
9.49
3.65
5.15
binding to DNA. The values of K for these complexes are
b
[
Ru(CO)Cl(PPh
3
)L]
comparable to those of some polypyridyl ruthenium(II)
4 -1
complexes, at 1.0–4.8 9 10 M [31].
[Ru(CO)Cl(AsPh )L]
3
[
Ru(CO)Cl(Py)L]
Antioxidant properties
117 lM, respectively, whereas the complexes [Ru(CO)Cl-
The antioxidant activities of the free Schiff base and its
complexes were evaluated in a series of in vitro assays
(PPh )L], [Ru(CO)Cl(AsPh )L] and [Ru(CO)Cl(Py)L]
3 3
gave IC50 values of 20.4, 85.4 and 65.6 lM, respectively,
for DPPH radical and 13.5, 57.3 and 29.5 lM, respectively,
for OH radical. Hence, the ruthenium(II) complexes pos-
sess higher radical scavenging activities than the free
ligand. These results are generally better than those
0
involving 2-2 -diphenyl-1-picrylhydrazyl (DPPH) and
hydroxyl radicals along with ascorbic acid as a standard
and the determination of 50 % activity (IC ) values. The
5
0
IC50 values of HL for DPPH and OH radicals are 136 and
Fig. 4 Absorption spectral traces of the ligand HL (a) and the complexes [Ru(CO)Cl(PPh
[
3 3
)L] (b), [Ru(CO)Cl(AsPh )L] (c) and
Ru(CO)Cl(py)L] (d) with increasing concentration of CT-DNA in a Tris HCl–NaCl buffer (pH 7.1)
1
23

Transition Met Chem (2013) 38:291–298
297
Conclusion
Three new mononuclear ruthenium(II) complexes con-
taining 3-(benzothiazol-2-yliminomethyl)-phenol Schiff
base ligand have been prepared and characterized by
spectroscopic techniques. The complexes show groove
binding modes with CT-DNA, with the strongest DNA
binding observed for [Ru(CO)Cl(PPh )L]. In addition,
3
[Ru(CO)Cl(PPh )L] shows significant antioxidant proper-
3
ties. The complexes [Ru(CO)Cl(PPh )L] and [Ru(CO)Cl-
3
(Py)L] show considerable cytotoxic activities against HeLa
and MCF-7 cancer cell lines, with higher inhibition of
HeLa cells compared to MCF-7 cells. From the above
results, we conclude that the complex containing triphen-
ylphosphine as co-ligand shows higher biological activity
than the other two complexes and the free ligand.
a f
Fig. 5 Plots of [DNA]/(e - e ) versus [DNA] for the titration of
compounds with CT-DNA
Supplementary data
Crystallographic data for the structural analysis have been
deposited with the Cambridge Crystallographic Data Cen-
tre, CCDC 866090. Copy of this information may be
obtained free of charge from the Director, CCDC, 12
Union Road, Cambridge, CB21 EZ, UK (fax: ?44-1223-
Table 7 The cytotoxic activity of the compounds
Compounds
IC50 values (lM)
HeLa
MCF-7
HL
178.21
27.12
54.69
44.38
184.15
32.54
58.53
46.12
336033: e-mail: deposit@ccdc.cam.ac.uk or www.ccdc.
[Ru(CO)Cl(PPh
[Ru(CO)Cl(AsPh
[Ru(CO)Cl(Py)L]
3
)L]
cam.ac.uk/deposi).
3
)L]
Acknowledgments We sincerely thank University Grants Com-
mission (UGC), New Delhi, for financial support [MRP Scheme. No.
3
8-222/2009 (SR)].
observed for ascorbic acid, which gave IC50 values of
6.8 lM for DPPH and 34.3 lM for OH radicals.
4
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