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