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Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 105 (2013) 532–538

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Spectrochimica Acta Part A: Molecular and


Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa

Homodinuclear lanthanide complexes of phenylthiopropionic acid: Synthesis,


characterization, cytotoxicity, DNA cleavage, and antimicrobial activity
C. Shiju a, D. Arish b, S. Kumaresan a,⇑
a
Department of Chemistry, Manonmaniam Sundaranar University, Tirunelveli 627 012, Tamilnadu, India
b
Center for Scientific and Applied Research, PSN College of Engineering and Technology, Tirunelveli 627 152, Tamilnadu, India

h i g h l i g h t s g r a p h i c a l a b s t r a c t

" New lanthanide complexes have


been synthesized and characterized.
" The spectral results show that the
lanthanide complexes are
homodinuclear in nature.
" In vitro antimicrobial and DNA
cleavage activity of the metal
complexes were studied.
" In vitro anticancer activities have
been studied towards HeLa and
HCT116 cancer cells.

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

Article history: Lanthanide complexes of La(III), Pr(III), Nd(III), Sm(III), and Ho(III) with phenylthiopropionic acid were
Received 22 October 2012 synthesized and characterized by elemental analysis, mass, IR, electronic spectra, molar conductance,
Received in revised form 6 December 2012 TGA, and powder XRD. The results show that the lanthanide complexes are homodinuclear in nature.
Accepted 10 December 2012
The two lanthanide ions are bridged by eight oxygen atoms from four carboxylate groups. Thermal
Available online 2 January 2013
decomposition profiles are consistent with the proposed formulations. Powder XRD studies show that
all the complexes are amorphous in nature. Antimicrobial studies indicate that these complexes exhibit
Keywords:
more activity than the ligand itself. The DNA cleavage activity of the ligand and its complexes were
Lanthanide complexes
Phenylthiopropionic acid
assayed on Escherichia coli DNA using gel electrophoresis in the presence of H2O2. The result shows that
Antimicrobial the Pr(III) and Nd(III) complexes have completely cleaved the DNA. The anticancer activities of the com-
DNA cleavage plexes have also been studied towards human cervical cancer cell line (HeLa) and colon cancer cells
Anticancer (HCT116) and it was found that the La(III) and Nd(III) complexes are more active than the corresponding
Pr(III), Sm(III), Ho(III) complexes, and the free ligand on both the cancer cells.
Ó 2013 Elsevier B.V. All rights reserved.

Introduction ties as well as anti-inflammation-, antitumor-, and antithrombo-


genic properties because of their electron configuration [8–10].
Rare earth complexes attract considerable interest in bioinor- Because of special, photophysical and biological properties, lantha-
ganic and coordination chemistry [1,2]. Some of the lanthanide nide complexes are used as biological probes in the areas of clinical
complexes are used in biomedical analysis as MRI contrast agents chemistry and molecular biology [11]. Some lanthanide complexes
[3] and also as effective catalysts for the hydrolytic cleavage of have a potential role in the treatment of tumor cell lines [12]. Be-
phosphate ester bonds [4]. Lanthanide complexes with organic li- cause of their special electronic configuration, lanthanide com-
gands have a great interest, not only because of their structures, plexes have inspired many efforts on the design and synthesis as
but also of potential applications of their luminescent properties potential anticancer and antibacterial agents [13–22]. The lantha-
[5–7]. These complexes have good physical and chemical proper- nide complexes have an ability to interact with DNA directly or
prevent the proper relaxation of DNA through the inhibition of
⇑ Corresponding author. Tel.: +91 94431 82502. topoisomerases [23,24]. Recently, aromatic carboxylate coordina-
E-mail address: skumarmsu@yahoo.com (S. Kumaresan). tion complexes that exhibit unique photophysical properties and

1386-1425/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.saa.2012.12.066
C. Shiju et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 105 (2013) 532–538 533

intriguing structural features have attracted considerable interest DNA cleavage analysis
[25,26]. Potential applications and fascinating properties of lantha-
nide complexes with carboxylic acids mooted us to synthesize and Cleavage reactions were run between the metal complexes and
characterize a new series of lanthanide complexes with phenyl- E. coli DNA, and the solutions were diluted with loading dye using
thiopropionic acid ligand and study their biological activity. 1% agarose gel. Then 3 mL of ethidium bromide (0.5 mg mL1) was
added to the above solution and mixed well. The warmed agarose
was poured and clamped immediately with a comb to form sample
Experimental wells. The gel was mounted onto an electrophoretic tank and en-
ough electrophoretic buffers were added to cover the gel to a depth
Materials of about 1 mm. The DNA sample (30 mmol L1), 50 mmol L1 metal
complex, and 500 mmol L1 H2O2 in 50 mmol L1 tris–HCl buffer
Thiophenol and 3-chloropropionic acid were purchased from (pH 7.1) were mixed with loading dye and loaded into the well
Sigma–Aldrich. The human cervical cancer cell line (HeLa) and co- of the submerged gel using a micropipette. Electric current
lon cancer cells (HCT116) were obtained from National Centre for (50 mA) was passed into running buffer. After 1–2 h, the gel was
Cell Science (NCCS), Pune. The lanthanide nitrate salts were taken from the buffer. After electrophoresis, the gel was photo-
purchased from Sigma–Aldrich and Merck. All other reagents and graphed under a UV transilluminator (280 nm) and documented.
solvents were obtained from commercial sources and were of ana-
lytical grade. The ligand phenylthiopropionic acid (PTPA) was pre- In vitro anti cancer activity
pared according to the literature method [27].
The human cervical cancer cell line (HeLa) and Colon Cancer
Cells (HCT116) were grown in Eagles Minimum Essential Medium
Synthesis of the metal complexes (EMEM) containing 10% fetal bovine serum (FBS). The cells were
maintained at 37 °C, 5% CO2, 95% air, and 100% relative humidity.
The ligand (PTPA) (3 mmol) in 20 mL of water was taken in a Maintenance cultures were passaged weekly, and the culture med-
100 mL RB flask. A solution of NaOH (3 mmol) in 10 mL of water, ium was changed twice a week. The monolayer cells were de-
was then added and stirred well until the ligand completely dis- tached with trypsin–ethylenediaminetetraacetic acid (EDTA) to
solved. The metal nitrate (1 mmol) in 10 mL of water was added make single cell suspension and viable cells were counted using
dropwise to the flask and the reaction mixture was stirred for a hemocytometer and diluted with a medium containing 5% FBS
5 h. The precipitate formed was filtered off, washed several times to give a final density of 1  105 cells/mL. One hundred microliters
with water and with a little cold chloroform, and then dried in va- per well of cell suspension were seeded into 96-well plates at a
cuo over anhydrous CaCl2. The yield was found to be 62–68%. plating density of 10,000 cells/well and incubated to allow for cell
attachment at 37 °C, 5% CO2, 95% air and 100% relative humidity.
After 24 h, the cells were treated with serial concentrations of
Physical measurements the test samples. They were initially dissolved in neat dimethyl-
sulfoxide (DMSO) to prepare the stock (200 mM) and stored frozen
Elemental analysis was done using a Perkin-Elmer elemental prior to use. At the time of sample addition, an aliquot of frozen
analyzer. The metal contents in the complexes were determined concentrate was thawed and diluted to twice the desired final
by standard EDTA titration using xylenol-orange as an indicator maximum test concentration with serum free medium. Additional
[28]. Molar conductance of the complexes was measured in DMF three, 2-fold serial dilutions were made to provide a total of five
(103 M) solutions using a Coronation Digital Conductivity Meter. sample concentrations. Aliquots of 100 lL of these different sam-
The mass spectra were recorded on a JEOL JMS600H mass spec- ple dilutions were added to the appropriate wells already contain-
trometer. IR(KBr) spectra were recorded on a JASCO FT/IR-410 ing 100 lL of medium, resulting in the required final sample
spectrometer in the 4000–400 cm1 region. The electronic spectra concentrations. Following sample addition, the plates were incu-
were recorded on a Perkin Elmer Lambda-25 UV–VIS spectrometer. bated for an additional 48 h at 37 °C, 5% CO2, 95% air, and 100% rel-
Thermal analysis was carried out on SDT Q 600/V8.3 build 101 ative humidity. The medium without samples were served as
thermal analyzer with a heating rate of 20 °C/min using nitrogen control and a triplicate was maintained for all concentrations [30].
atmosphere.
MTT assay

Antimicrobial activities MTT is a yellow water soluble tetrazolium salt [(3-(4,5-dimeth-


ylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide)]. Succinate-
Antibacterial and antifungal properties of the ligand and its dehydrogenase, a mitochondrial enzyme in living cells cleaves
complexes were tested in vitro against the bacterial species Esche- the tetrazolium ring, converting the MTT to an insoluble purple
richia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Staphylo- formazan. Thus, the amount of formazan produced is directly pro-
coccus aureus; fungal species, Aspergillus niger, Aspergillus flavus, portional to the number of viable cells. After 48 h of incubation,
and Candida albicans by the disk diffusion method. Amikacin, Oflox- 15 lL of MTT (5 mg/mL) in phosphate buffered saline (PBS) was
acin, and Ciprofloxacin were used as standards for antibacterial added to each well and incubated at 37 °C for 4 h. The medium
activity and Nystatin was used as a standard for antifungal activity. with MTT was then flicked off and formazan crystals obtained were
The test organisms were grown on nutrient agar medium in petri solubilized in 100 lL of DMSO. The absorbance at 570 nm was
plates. The compounds were prepared in DMSO and soaked in filter measured using a micro plate reader [31]. The % cell inhibition
paper disk of 5 mm diameter and 1 mm thickness. The disks were was determined using the following formula.
placed on the previously seeded plates and incubated at 37 °C and
% Cell inhibition ¼ 100  AbsðsampleÞ=AbsðcontrolÞ  100
the diameter of inhibition zone around each disk was measured
after 24 h for antibacterial and 72 h for antifungal activities. The Nonlinear regression graph was plotted between % cell inhibi-
minimum inhibitory concentration (MIC) was determined by ‘seri- tion and log10 concentration and IC50 was determined using Graph-
al dilution technique’ [29]. Pad Prism software.
534 C. Shiju et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 105 (2013) 532–538

Results and discussion Table 2


IR spectral data of the Schiff base ligand (PTPA) (L) and its complexes (cm1).

Characterization of metal complexes Compound masym.(COO) msym.(COO) m(H2O) m(M–O)


cm1 cm1 cm1 cm1
The analytical and physical characterization of Ln(III)-PTPA PTPA (L) 1697 1675 – –
complexes are given in Table 1. The analytical data show that the [La2L6(H2O)4] 1557 1438 3408(b) 474
[Pr2L6(H2O)4] 1559 1440 3440 470
metal to ligand ratio is 1:3 in all the complex systems. And also
[Nd2L6(H2O)4] 1556 1437 3409 473
all the complexes are homodinuclear in nature. The composition [Sm2L6(H2O)4] 1556 1436 3418(b) 473
of the complexes is [Ln2L6(H2O)4], where L is the phenylthioprop- [Ho2L6(H2O)4] 1558 1439 3410 475
ionic acid ligand (PTPA). The La(III), Pr(III), Nd(III), Sm(III), and
Ho(III) complexes are soluble in THF and DMSO. The mass spectra
of the La(III), Pr(III), Nd(III), Sm(III), and Ho(III) complexes show
molecular ion peaks at m/z 1437 (M + 1, 15%), 1401 (M 2H2O, of the lanthanide ion does not have a significant effect on the p–
90%), and 1364 (M 4H2O); 1441 (M + 1, 13%) and 1405 (M p transition. The molar absorption coefficient value for the com-
2H2O 18%); 1443 (M + 1, 11%), and 1370 (M 4H2O, 12%); 1463 plexes are about six times than that of the free ligand, which indi-
(M + 1, 13%) and 1408 (M 3H2O, 16%); 1489 (M + 1, 12%)], and cating the presence of six PTPA molecules in the homodinuclear
1416 (M 4H2O, 10%) respectively, which coincide with the for- lanthanide complexes [34].
mula weights of the lanthanide complexes. The low molar conduc-
tance values (Table 1) of the metal complexes reveal their non- Thermal analysis
electrolytic nature [32].
The thermal stability data of the complexes are listed in Table 3.
IR spectra The [La2L6(H2O)4], [Pr2L6(H2O)4], [Nd2L6(H2O)4], [Sm2L6(H2O)4], and
[Ho2L6(H2O)4] complexes undergo the same type of decompositions
The important IR spectral data are given in Table 2. The band at mainly in two stages. The first stage taking place in the 120–190 °C
1697 cm1 for the carboxylate group of free ligand shifted to lower range corresponds to the dehydration of four coordinated water
frequency in the range 1556–1558 cm1 in the complexes is molecules. The final decomposition step is represented by the total
indicative of the coordination of the carboxylate oxygen atom to removal of the organic ligand moiety in the 345–620 °C range with
the metal ion. On complexation, the asymmetric and symmetric the formation of the corresponding metal oxide as the final product.
stretching bands of carboxylato groups are shifted to lower fre- The TG curve of the complex [La2L6(H2O)4] shows a weight loss 6.4%
quency for all the complexes, which reveals the formation of a link- (calculated – 5.01%) in the temperature range 125–180 °C. This is
age between the metal ion and carboxylato oxygen atom. due to the loss of four coordinated water molecules. The second
Moreover, the difference (<150 cm1) between the asymmetric decomposition step of the complex is in the temperature range
and symmetric stretching modes indicates the bidentate binding 395–620 °C bringing a weight loss of 71.3% (calculated 72.50%)
of the carboxylato group in the complexes [33]. The carboxylate which correlates with the loss of coordinated organic ligand. Above
stretching frequency spectra is little broad because of the three dif- this temperature, a horizontal thermal curve has been observed due
ferent modes of coordination of the ligand to the lanthanide ions to the formation of the metal oxide. The TG curves of the complexes
[34]. The new broad band appeared at 3400 cm1 can be attrib- [Pr2L6(H2O)4] shows a weight loss 6.2% (calculated 5.0%) in the tem-
uted to the stretching vibration of the coordinated water mole- perature range 135–185 °C showing the elimination of four coordi-
cules. The spectrum of all the metal complexes show new bands nated water molecules. The second weight loss 70.9% (calculated
in 470–475 cm1 region, which may probably be due to the forma- 72.4%) in the 380–610 °C corresponds to the coordinated organic li-
tion of M–O bonds [32]. gand. Above this temperature, a horizontal curve has been observed
due to the formation of a metal oxide. The complexes [Nd2L6(H2O)4]
Electronic spectra and [Sm2L6(H2O)4] show a similar trend of two decomposition
steps. The first stage taking place in the 120–190 °C range is attrib-
The UV absorption spectra of the free ligand and the corre- uted to the expulsion of four coordinated water molecules. The sec-
sponding lanthanide complexes were measured in THF solution ond stage starts from 395 °C to 595 °C for [Nd2L6(H2O)4] and 385 °C
(c = 1  104 M) and are shown in Fig. 1. The spectrum displayed to 600 °C for [Sm2L6(H2O)4] complexes. The corresponding mass
an absorption maximum at 252 nm for the free ligand, which is loss is due to the decomposition of the organic ligand molecule
attributable to singlet–singlet p–p absorption of the aromatic and it is in agreement with the calculated mass loss. The final resi-
ring. The kmax value of the La(III), Pr(III), Nd(III), Sm(III), and Ho(III) due is qualitatively proved to be anhydrous metal oxides. The first
complexes are 254, 255, 253, 254, 254 nm respectively (Table 1) step taking place in the temperature range 130–155 °C for [Ho2L6(-
which slightly red-shifted with respect to that of the free ligand H2O)4] complex. The second stage start from 345 °C to 540 °C corre-
(252 nm). The UV bands of the lanthanide complexes spectra are sponds to the loss of organic ligand. Above this temperature a
similar to that of the free ligand, suggesting that the coordination horizontal thermal curve has been observed due to the formation

Table 1
Analytical and physical data of the ligand (PTPA) (L) and its complexes.

Compound Empirical formula Yield Elemental analysis found (calcd.) % Kc (Ohm1 cm2 mol1) kmax (nm)
C H S M
PTPA (L) C9H10O2S 70 60.52 (59.33) 4.81 (5.54) 16.36 (17.56) – 252
[La2L6(H2O)4] C54H62La2O16S6 65 42.87 (45.12) 4.32 (4.35) 12.87 (13.36) 18.35 (19.35) 4 254
[Pr2L6(H2O)4] C54H62O16Pr2S6 62 45.65 (45.05) 5.82 (4.34) 14.22 (13.36) 21.02 (19.46) 3 255
[Nd2L6(H2O)4] C54H62Nd2O16S6 68 42.98 (44.79) 4.04 (4.32) 12.78 (13.26) 18.82 (19.94) 3 253
[Sm2L6(H2O)4] C54H62O16S6Sm2 65 43.54 (44.42) 4.98 (4.28) 12.85 (13.15) 19.32 (20.61) 2 254
[Ho2L6(H2O)4] C54H62Ho2O16S6 67 34.67 (43.55) 4.09 (4.20) 11.06 (12.89) 17.16 (22.17) 2 254
C. Shiju et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 105 (2013) 532–538 535

nide–carboxylic acid complexes [36]. The antimicrobial activity of


the complexes is greater than those of the free ligand, this indicates
that the complexation to metal enhances the activity of the ligand.
This is explained on the basis of Overtone’s concept and chelation
theory [37]. Chelation tends to make the ligand a more powerful
and potent bacterial agent. A possible explanation for this increase
in the activity upon chelation is that, in a chelated complex, the po-
sitive charge of the metal is partially shared with donor atoms
present in the ligands and there is an electron delocalization over
the whole chelated ring. This, in turn, increases the lipoid layers
of the bacterial membranes. Generally, it is suggested that the che-
lated complexes deactivate various cellular enzymes, which play a
vital role in various metabolic pathways of these microorganisms.
Other factors such as solubility, conductivity, and dipole moment
that are affected by the presence of metal ions may also be the pos-
sible reasons for increasing the biological activity of the metal
complexes as compared to the ligand from which they are derived
[38].

Fig. 1. UV absorption spectra in THF (c = 1  104 M). DNA cleavage analysis

Gel electrophoresis experiments using E. coli. DNA was per-


of the metal oxide. Based on the above studies, the proposed struc- formed with the ligand and its complexes in the presence and ab-
ture of the metal complex is shown in Fig. 2. This type of structures sence of H2O2 as an oxidant. The results (Fig. 3) indicate that all the
has reported previously [35]. complexes could interact with E. coli. DNA in the presence of H2O2.
Pr(III) and Nd(III) complexes cleave DNA completely compared to
other systems. The lanthanide complexes seem to catalyze the gen-
Biological studies eration of highly reactive hydroxyl radicals from H2O2. These hy-
droxyl radicals participate in the oxidation of the deoxyribose
Antimicrobial activity moiety, followed by the hydrolytic cleavage of the sugar-phos-
phate backbone. La(III), Sm(III), and Ho(III) complexes partially
The results of the antimicrobial activities are summarized in Ta- cleave the DNA. It is observed that most cleavage cases are due
ble 4. The standard error for the experiment is ±0.001 cm and the to the metal ions reacting with H2O2 to produce diffusible hydroxyl
experiment was repeated three times under similar conditions. radicals or molecular oxygen, which may damage DNA through a
DMSO was used as a negative control and amikacin, ofloxacin, Fenton type chemistry [39]. In addition, the nuclease activity of
and ciprofloxacin were used as positive standards for antibacterial the complexes has also been investigated in the absence of the oxi-
studies. Nystatin was used as a reference for antifungal studies. dant H2O2. This experiment did not help cleaving the DNA, thus
These compounds exhibit moderate to strong antimicrobial activ- confirming the involvement of hydroxyl radicals in the cleavage
ity. Comparatively a better activity is found for the bacteria rather process.
than the fungi. The Nd(III) complex exhibits a higher activity than
the other metal complexes towards fungal species. The Nd(II) com- In vitro anti cancer activity
plex shows a good activity, especially against the Gram-negative
bacteria such as E. coli and B. subtilis. The Nd(II) complex shows The reliable criteria for judging the efficacy of any anticancer
equal or better activity compared to the negative controls such drug are prolongation of life span, improving the clinical, haemato-
as amikacin, ofloxacin, and ciprofloxacin. The La(III) and Pr(III) logical, biochemical profile, and reduction in viable tumour cell
complexes display moderate activity against the bacteria. Our count in the host [40]. In order to evaluate the biological effects
compounds show comparable activity to the mononuclear lantha- of the ligand, PTPA and its La(III), Pr(III), Nd(III), Sm(III), and Ho(III)
complexes on cancer cells, we used the compounds to treat HeLa
(Human Cervical Cancer Cells) and HCT116 (Colon Cancer Cells)
Table 3 at the concentrations of 6.25, 12.5, 25, 50, and 100 lM for 48 h
Thermogravimetric data of metal complexes. (Figs. 4a and b). The untreated cells were used as a control. Cell
Complex Temperature % Weight loss Process growth inhibition was analyzed by MTT assay and the results
range T (°C) Obs. (calcd.) showed that the complexes and the ligand exhibited an inhibitory
[La2L6(H2O)4] 125–180, 6.4(5.10), 4H2O(coord.), loss of effect on the proliferation of HeLa and HCT116 cells in a dose-
395–620, 71.3(72.5), organic moiety, La2O3 dependent manner (Table 5). Among them, La(III) and Nd(III) com-
>620 24.7(22.5) plexes showed the most potent inhibitory effect on the growth of
[Pr2L6(H2O)4] 135–185, 6.2(5.0), 4H2O(coord.), loss of
both the cells compared to the Pr(III), Sm(III), and Ho(III) com-
380–610, 70.9(72.4), organic moiety, Pr2O3
>610 24.4(22.6) plexes and the free ligand. Values for La(III), Pr(III), Nd(III), Sm(III),
[Nd2L6(H2O)4] 120–190, 6.0(4.9), 4H2O(coord.), loss of and Ho(III) complexes for HeLa cancer cells are better than some
395–595, 71.2(72.2), organic moiety, Nd2O3 previously reported values [41]. The IC50 values for our metal com-
>600 24.8(22.9)
plexes and the free ligand against HCT116 cancer cells show mod-
[Sm2L6(H2O)4] 120–175, 6.5(4.9), 4H2O(coord.), loss of
385–600, 69.4(71.0), organic moiety, Sm2O3
erate activity compared to the IC50 value of the clinically used drug
>600 25.6(23.9) such as etoposide (29.6 lM) [42]. The activity of the metal com-
[Ho2L6(H2O)4] 130–155, 6.1(4.8), 4H2O(coord.), loss of plexes and the free ligand towards HeLa cancer cells are not much
345–540, 68.8(70.0), organic moiety, Ho2O3 significant, compared to the known metal-free anticancer agents
>550 27.3(25.2)
such as estramustine (IC50 1.5 to 3.0 lM), [43] noscapine (IC50
536 C. Shiju et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 105 (2013) 532–538

Fig. 2. Proposed structure of Ln(III)-PTPA complexes.

Table 4
In vitro antimicrobial activity (MIC, lg/mL) of the compounds and standard reagents.

Compound Bacterial species Fungal species


E. coli B. subtilis P. aereuguioa S. aureus A. niger A. flavus C. albicans
PTPA (L) 15 60 48 68 27 64 86
[La2L6(H2O)4] 10 35 12 26 19 23 13
[Pr2L6(H2O)4] 12 16 9 17 28 13 11
[Nd2L6(H2O)4] 05 08 18 11 10 11 05
[Sm2L6(H2O)4] 78 40 12 47 54 >100 68
[Ho2L6(H2O)4] 69 38 34 60 71 68 >100
Amikacina 05 06 05 07 – – –
Ciprofloxacinb 04 05 05 05 – – –
Ofloxacinc 10 04 04 05 – – –
Nystatind – – – – 07 05 05
a,b,c,d
Standard.

22 lM) [44] as well as metal-bound anticancer reagents such as pressing iron uptake, inhibiting ROS formation by binding to hy-
cisplatin (IC50 8 lM) [45]. From the literature we understand that dro-peroxides and preventing the activity of free radicals via
lanthanide metal complexes prevent the tumor growth by sup- magnetic interactions etc. Differences in the number of 4f electrons
C. Shiju et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 105 (2013) 532–538 537

Table 5
IC50 values of the compounds on the cancer cells.

Compound IC50 (lM)


HeLa HCT116
PTPA (L) 55.66 49.48
[La2L6(H2O)4] 43.58 42.04
[Pr2L6(H2O)4] >100 47.12
[Nd2L6(H2O)4] 39.13 28.33
[Sm2L6(H2O)4] 86.51 71.38
[Ho2L6(H2O)4] >100 79.51

Conclusion

La(III), Pr(III), Nd(III), Sm(III), and Ho(III) complexes with the


phenylthiopropionic acid ligand were synthesized and character-
ized by elemental analysis, mass, IR, electronic spectra, molar con-
Fig. 3. DNA cleavage studies of ligand and its metal complexes, M – marker, C –
ductance, TGA, and powder XRD. From the IR data, the
control E. coli DNA (untreated sample), S1 – ligand + DNA, S2 – [La2L6(H2O)4] + DNA,
S3 – [Pr2L6(H2O)4] + DNA, S4 – [Nd2L6(H2O)4] + DNA, S5 – [Sm2L6(H2O)4] + DNA, S6 – coordination of the ligand to the metal atom was found to be
[Ho2L6(H2O)4] + DNA. bidentate. A two-stage process is shown in the thermogravimetric
spectra of all the complexes. Powder XRD results show that the
complexes are amorphous in nature. The antimicrobial studies re-
veal that the complexes show higher activity than the ligand. The
Nd(III) complex shows better activity against Gram negative bacte-
ria such as E. coli compared to the other complexes and the free li-
gand. DNA cleavage studies indicate that the Pr(III) and Nd(III)
complexes have completely cleaved the DNA. In vitro anticancer
activity is not significant compared to the known anticancer agents
such as estramustine, noscapine, and cisplatin [47]. The La(III) and
Nd(III) complexes are more active than the other three complexes
and the free ligand on both the cancer cells (HeLa and HCT116).

Appendix A. Supplementary material

Supplementary data associated with this article can be found, in


the online version, at http://dx.doi.org/10.1016/j.saa.2012.12.066.

References
Fig. 4a. Growth inhibition based on concentration (HeLa).
[1] Gyula Tircso, Zoltan Kovacs, A. Dean Sherry, Inorg. Chem. 45 (23) (2006) 9269–
9280.
[2] S.K. Agrawal, K.C. Gupta, Indian J. Chem. 27 (A) (1988) 1008–1009.
[3] S. Aime, S.G. Crich, E. Gianolio, G.B. Giovenzana, L. Tei, E. Terreno, Coord. Chem.
Rev. 250 (2006) 1562–1579.
[4] S.J. Franklin, Curr. Opin. Chem. Biol. 5 (2) (2001) 201–208.
[5] (a) D. Parker, R.S. Dickins, H. Puschmann, C. Crossland, J.A.K. Howard, Chem.
Rev. 102 (2002) 1977–2010;
(b) S. Petoud, S.M. Cohen, J.C.G. Bu nzli, K.N. Raymond, J. Am. Chem. Soc. 125
(2003) 13324–13325.
[6] P. Yan, W. Sun, G. LI, C. Nie, T. Gao, Z. Yue, J. Coord. Chem. 60 (2007) 1973–
1982.
[7] (a) Y.F. Li, K.Z. Tang, Y. Tang, W.S. Liu, M.Y. Tan, Spectrochim. Acta A 71 (2008)
1153–1157;
(b) Y.L. Song, Y. Tang, W.S. Liu, M.Y. Tan, Spectrochim. Acta A 64 (2006) 595–599.
[8] Z. Shen, D. Xu, N. Cheng, X. Zhou, X. Chen, Y. Xu, Q. He, J. Coord. Chem. 64
(2011) 2342–2352.
[9] Z.A. Taha, A.M. Ajlouni, K.A. Al-Hassan, A.K. Hijazi, A.B. Faiq, Spectrochim. Acta
A 81 (2011) 317–323.
[10] P. Kapoor, N. Fahmi, R.V. Singh, Spectrochim. Acta A 83 (2011) 74–81.
[11] A.L. Gassner, C. Duhot, J.C.G. Bunzli, A.S. Chauvin, Inorg. Chem. 47 (2008)
7802–7812.
[12] I. Kostova, I. Manolov, G. Momekov, Eur. J. Med. Chem. 39 (2004) 765–775.
[13] S.V. Eliseeva, J.C.G. Bunzli, Chem. Soc. Rev. 39 (2010) 189–227.
[14] M. Liu, W. Yuan, Q. Zhang, L. Yan, R. Yang, Spectrochim. Acta A 70 (2008)
1114–1119.
Fig. 4b. Growth inhibition based on concentration (HCT116).
[15] I. Kostova, T. Stefanova, J. Coord. Chem. 62 (2009) 3187–3197.
[16] Z.A. Siddiqi, M. Shahid, M. Khalid, S. Noor, S. Kumar, Spectrochim. Acta A 74
(2009) 391–397.
[17] Z.A. Taha, A.M. Ajlouni, W.A. Momani, A.A. Al-Ghzawi, Spectrochim. Acta, Part
are believed to display different biological properties [46]. From A 81 (2011) 570–577.
the IC50 values of La(III) and Nd(III) complexes on both the cancer [18] Y.T. Yang, Spectrochim. Acta, Part A 55 (1999) 1527–1533.
[19] P. Hermann, J. Kotek, V. Kubicek, I. Lukes, Dalton Trans. (2008) 3027–3047.
cells, it is understood that these complexes are more active on [20] A.L. Gassner, C. Duhot, J.C.G. Bunzli, A.S. Chauvin, Inorg. Chem. 47 (2008)
HCT116 cancer cells than on the HeLa cancer cells. 7802–7812.
538 C. Shiju et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 105 (2013) 532–538

[21] R.M. Supkowski, J.P. Bolender, W.D. Smith, L.E.L. Reynolds, W.D. Horrocks, [35] S. Viswanathan, A. Bettencourt-Dias, Inorg. Chem. 45 (2006) 10138–10146.
Coord. Chem. Rev. 186 (1999) 307–319. [36] Y.F. Win, M.H. Yousif, N. Shalan, Int. J. Phys. Sci. 7 (2012) 43–47.
[22] D. Xu, Y. Xu, N. Cheng, X. Zhou, Y. Shi, Q. He, J. Coord. Chem. 63 (2010) 2360– [37] N.P. Priya, S.V. Arunachalam, N. Sathya, V. Chinnusamy, C. Jayabalakrishnan,
2369. Transit. Metal Chem. 34 (2009) 437–445.
[23] Y. Wang, Y. Wang, Z.Y. Yang, Spectrochim. Acta 66 (2007) 329–334. [38] A.A.A. Emara, Spectrochim. Acta A 77 (2010) 117–125.
[24] Y. Li, Z. Yang, J. Coord. Chem. 63 (2010) 1960–1968. [39] M.S.S. Babu, K.H. Reddy, G.K. Pitchika, Polyhedron 26 (2007) 572–580.
[25] L. Pan, M.B. Sander, X. Huang, J. Li, M. Smith, E. Bittner, B. Bockrath, J.K. [40] S.I. Mostafa, Transit. Metal Chem. 32 (2007) 769–775.
Johnson, J. Am. Chem. Soc. 126 (2004) 1308–1309. [41] J.D. Aguirre, A.M. Angeles-Boza, A. Chouai, C. Turro, J.P. Pellois, K.R. Dunbar,
[26] X.Y. Chen, Y. Bretonniere, J. Pecaut, D. Imbert, J.C.G. Bunzli, M. Mazzanti, Inorg. Dalton Trans. 48 (2009) 10806.
Chem. 46 (2007) 625–637. [42] M.A. LeBlanc, A.G. Sarrias, F.A. Beckford, P.M. barushimana, N.P. Seeram, Int. J.
[27] R. Ramasubramanian, S. Kumaresan, R. Thomas, A.D. Stephen, P. Kumaradhas, Inorg. Chem. 8 (2011).
Cryst. Res. Technol. 42 (2007) 1024–1028. [43] K.M. Nicholson, R.M. Phillips, S.D. Shnyder, M.C. Bibby, Eur. J. Cancer 38 (2002)
[28] M.F. Zhou, Q.Z. He, J. Rare Earths 26 (2008) 473–477. 194–204.
[29] Methods for Anti-Microbial Dilution and Disk Susceptibility Testing of [44] J. Zhou, K. Gupta, S. Aggarwal, R. Aneja, R. Chandra, D. Panda, C.H. Joshi, Mol.
Infrequently Isolated or Fastidious Bacteria; Approved Guideline Document Pharmacol. 63 (2003) 799–807.
M45-A 26(19). National Committee for Clinical Laboratory Standrd. NCCLS, [45] S. Ray, R. Mohan, J.K. Singh, M.K. Samantaray, M.M. Shaikh, D. Panda, P. Ghosh,
Villanova PA USA, 1999. J. Am. Chem. Soc. 129 (2007) 15042–15053.
[30] T. Mosmann, J. Immunol. Methods 65 (1983) 55–63. [46] I. Kostova, N. Trendafilova, G. Momekov, J. Trace Elem. Med. Biol. 22 (2008)
[31] A. Monks, J. Natl. Cancer Inst. 83 (1991) 757–766. 100–111.
[32] W.J. Geary, Coord. Chem. Rev. 7 (1971) 81–122. [47] D. Suresh, M.S. Balakrishna, K. Rathinasamy, D. Panda, J.T. Mague, Dalton
[33] G.B. Deacon, R.J. Phillips, Coord. Chem. Rev. 33 (1980) 227–250. Trans. (2008) 2285–2292.
[34] R. Shyni, S. Biju, M.L.P. Reddy, A.H. Cowley, M. Findlater, Inorg. Chem. 46
(2007) 11025–11030.

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