Synthesis and characterization of heteroleptic Schiff base transition metal complexes: a study of anticancer, antimicrobial, DNA cleavage and anti-TB activity

Article abstract of DOI:10.1080/00958972.2017.1421951

In search of effective bioactive compounds, we have synthesized the new Co(II), Ni(II), and Cu(II) complexes of the Schiff base derived from 8-formyl-7-hydroxy-4-methylcoumarin and 2-hydrazino benzothiazole and characterized by analytical, spectroscopic (IR, NMR, UV–vis, Mass), magnetic, powder X-ray diffraction data (PXRD) and TGA studies. Elemental analysis suggests the stoichiometry of the synthesized complexes and the solution electronic spectral study revealed the octahedral geometry of the compounds. Thermal analysis shows the presence of water molecule outside the coordination sphere and powder-XRD patterns have been studied to test the degree of crystallinity of the complexes and unit cell calculations were made. All the synthesized compounds were tested against human ovarian cancer cell line (PA-1). The synthesized metal complexes exhibited enhanced activity against the tested bacterial (Staphylococcus aureus and Escherichia Coli) and fungal strains (Candida albicans and Aspergillus fumigatus) as compared to free ligand (LH). The results of the DNA-cleavage activity suggest that the ligand and its metal complexes can cleave CT-DNA at different degrees. Further, anti-tuberculosis activity was done using microplate almar blue assay. Among all these synthesized compounds, the Cu(II) complex exhibits good cleaving ability compared to other newly synthesized metal complexes.

Full text of DOI:10.1080/00958972.2017.1421951

Journal of Coordination Chemistry
ISSN: 0095-8972 (Print) 1029-0389 (Online) Journal homepage: http://www.tandfonline.com/loi/gcoo20
Synthesis and characterization of heteroleptic
Schiff base transition metal complexes: A study of
anticancer, antimicrobial, DNA cleavage and anti-
TB activity
Shailaja S. Jawoor, Sangamesh A. Patil & Shivakumar S. Toragalmath
To cite this article: Shailaja S. Jawoor, Sangamesh A. Patil & Shivakumar S. Toragalmath (2017):
Synthesis and characterization of heteroleptic Schiff base transition metal complexes: A study of
anticancer, antimicrobial, DNA cleavage and anti-TB activity, Journal of Coordination Chemistry,
DOI: 10.1080/00958972.2017.1421951
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Date: 02 January 2018, At: 18:47

Publisher: Taylor & Francis
Journal: Journal of Coordination Chemistry
DOI: http://doi.org/10.1080/00958972.2017.1421951
Synthesis and characterization of heteroleptic Schiff base transition metal
complexes: A study of anticancer, antimicrobial, DNA cleavage and
anti-TB activity
SHAILAJA S. JAWOOR, SANGAMESH A. PATIL* and SHIVAKUMAR S. TORAGALMATH
P.G. Dept. of Studies in Chemistry, Karnatak University, Dharwad, Karnataka, INDIA-580003
In search of effective bioactive compounds, we have synthesized the new Co(II), Ni(II) and
Cu(II) complexes of the Schiff base derived from 8-formyl-7-hydroxy-4-methylcoumarin and
2
-hydrazino benzothiazole and characterized by analytical, spectroscopic (IR, NMR, UV-vis,
Mass), magnetic, powder X-ray diffraction data (PXRD) and TGA studies. Elemental analysis
suggests the stoichiometry of the synthesized complexes and the solution electronic spectral
study revealed the octahedral geometry of the compounds. Thermal analysis shows the presence
of water molecule outside the coordination sphere and powder-XRD patterns have been studied
to test the degree of crystallinity of the complexes and unit cell calculations were made. All the
synthesized compounds were tested against human ovarian cancer cell line (PA-1). The
synthesized metal complexes exhibited enhanced activity against the tested bacterial (S. aureus
and E. Coli) and fungal strains (Candida albicans and Aspergillus fumigatus) as compared to
free ligand (LH). The results of the DNA-cleavage activity suggest that the ligand and its metal
complexes can cleave CT-DNA at different degrees. Further, anti-tuberculosis activity was done
by using microplate almar blue assay. Among all these synthesized compounds, the Cu(II)
complex exhibits good cleaving ability compared to other newly-synthesized metal complexes.
Keywords: Coumarin; Metal complexes; Powder XRD; PA-1 Cell line; DNA Cleavage
1
. Introduction
Nowadays chemists focus their efforts on targeting DNA synthesis and cell division. Basically,
*
Corresponding author. Email: patil1956@rediffmail.com
1

metal complexes enhance the biological activity when they are in ligation with the respective
ligands; a new approach in this mission is to survey the transition metal complexes which are
pertinent to biological activities [1-5]. Transition metal complexes derived from
hydrazine/hydrazones have an eminent role in the area of bioinorganic chemistry due to their
chelation property. Moreover, hydrazide derivatives are the most used drugs in the treatment of
anti-tuberculosis [6, 7]. In this aspect, benzothiazole-anchored hydrazides have very interesting
features in ligation due to the presence of donor atoms, viz. nitrogen, sulfur, etc. Conversely,
biological activities of benzothiazoles enhance the activity of metal complexes. In addition,
coumarins gained extensive interest of researchers due to many structural modifications that have
been made at different positions of the coumarin ring to experience pharmaceutically active
coumarin derivatives [8-10]. There are number of drugs which are used in medicine; syntheses of
some new coumarin incorporated thiazole derivatives with good biological activity are also
known [11].
The paucity of literature [12, 13] promoted us to synthesize and biologically evaluate the
transition metal viz. Co(II), Ni(II) and Cu(II)) complexes of ligand derived from the
condensation of 8-formyl-7-hydroxy-4-methylcoumarin and 2-hydrazinobenzothiazole which are
characterized by spectral (IR, mass, NMR, UV-Vis), thermal, PXRD and molar conductivities.
Furthermore, anticancer, antimicrobial, DNA cleavage and anti-tuberculosis activities were
studied.
2
2
. Experimental
.1. Materials and physical measurements
All reagents were commercially available (SD-Fine Chemicals, India) and used as supplied.
Metal determination and purification of solvents were done by standard procedures. The
compound 2-hydrazinobenzothiazole was prepared as per the literature [14]. Infrared spectra of
-1
the ligand and its metal complexes were recorded in KBr discs from 4000-400 cm with a
Nicolet 170 SX FT-IR spectrometer. Magnetic susceptibility measurements were made using a
Faraday balance at room temperature using Hg[Co(SCN) ] as a calibrant. Elemental analyses
4
were done using a Thermo Quest Elemental Analyzer. Electronic spectra of the ligand and its
complexes were recorded on a Hitachi 150-20 spectrophotometer from 1000-200 nm. Thermal
analysis of the metal complexes was carried out with an SDT Q600 analyzer by keeping the final
2

1
13
temperature at 1000 °C and the heating rate was maintained at 10 °C/min. H and C NMR
spectra were recorded in DMSO-d solvent on a Bruker 400 mHz spectrometer at room
6
temperature using TMS as reference compound. The molar conductivity measurements were
made on an ELICO-CM-82 Conductivity Bridge. Electron impact (EI) mass spectra were
recorded on the JEOL GCMATE II GC-MS with data system having a high resolution and
double focusing instrument. Powder X-ray patterns were recorded on a Bruker AXS D8 Advance
instrument.
2
2
.2. Synthesis of compounds
.2.1. Synthesis of 8-formyl-7-hydroxy-4-methylcoumarin [15]. A mixture of 7-hydroxy-4-
methylcoumarin (0.03 mol) [16] and hexamine (0.07 mol) in 50 mL glacial acetic acid was
heated for 4-5 h, then 75 mL of 20% HCl were added and heated for 45 min. Resulting mixture
was cooled and extracted with ether. Ether was evaporated and the remaining solution was
poured onto ice with constant stirring. Pale yellow solid of 8-formyl-7-hydroxy-4-
methylcoumarin obtained was filtered and recrystallized from hot ethanol. Yield: 20.0%; melting
point: 176-178 °C; color: light yellow.
2
.2.2. Synthesis of ligand (LH). 2-Hydrazinobenzothiazole in ethanol (1 mmol) was added
dropwise to a solution of 8-formyl-7-hydroxy-4-methylcoumarin (1 mmol) in ethanol and the
mixture was stirred for 5 h at room temperature. The completion of the reaction was monitored
through TLC. The yellow product formed was filtered, washed with cold ethanol and then dried
in vacuo for 1 h. Schematic representation for the synthesis of ligand is given in scheme 1. Yield:
7
5%; color: yellow; melting point: 118-120 °C.
3

Scheme 1. Synthesis of ligand LH.
2
.2.3. Synthesis of metal complexes 1-3. An ethanolic solution of ligand (2 mmol) was refluxed
with CoCl ·6H O/NiCl ·6H O/CuCl ·2H O (1 mmol) in ethanol on a water bath for 1 h. Then, to
2
2
2
2
2
2
the reaction mixture sodium acetate (2 mmol) was added and reflux was continued for 3 h, the
separated metal complexes were filtered, washed with cold ethanol and dried in vacuo.
3
3
. Pharmacology
.1. In vitro anticancer activity
Anticancer activity studies were carried out on a PA-1 cell line, which was obtained from
National Center for Cell Lines, Pune, India. Cell viability was tested using the (3,4,5-
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay [17]. In vitro growth
inhibition effect of the tested compound was assessed by spectrophotometric determination of
conversion of MTT into “Formazan blue” by living cells. The cells were maintained in a 96-well
micro titer plate containing MEM media supplemented with 10% heat inactivated fetal calf
serum (FCS) containing 5% of mixture of gentamicin (10 µg), penicillin (100 units/ml) and
streptomycin (100 µg/mL) in the presence of 5% CO at 37 C for 48-72 h. In our study, 10, 20,
2
4

2
5, 30 and 50 µL of the stock solution (10 mg/mL prepared in DMSO) were added to respective
wells containing 100 µl of the medium. Therefore, the final concentrations were 10, 20, 25, 30
and 50 µg/mL. After 48 h incubation at 37 C, stock solution of MTT was added to each well
(
20 µL, 5 mg/mL in sterile PBS) for a further 4 h incubation. Then, the supernatant carefully
aspirated, the precipitated crystals of ‘Formazan blue’ were solubilized by adding DMSO
100 µL). The absorbance was measured at 570 nm using an ELISA plate reader. Data were
(
collected for three replicates each and used to calculate the mean. Photographs of anticancer
activity of ligand and its metal complexes are given in Supplementary Data (figure S1).
3
.2. DNA Cleavage activity
DNA-cleavage activity study was carried out using calf-thymus DNA (purchased from
Bangalore Genie, Bengaluru, Cat. No. 105850) using the Agarose Gel Electrophoresis method
[18]. The synthesized ligand (LH) and its metal complexes 1-3 in DMF were prepared and these
samples were added to the CT-DNA and incubated for 2 h at 37 C. Agarose gel was prepared in
TAE buffer (4.84 g Tris base, pH 8.0, 0.5 M EDTA / 1 L). The gel was poured into a gel cassette
fitted with a comb, allowed to attain 55 °C and then kept to solidify. Later, the comb was
carefully removed and the gel was placed in the electrophoresis chamber flooded with TAE
buffer. Then, 20 mL of each incubated sample (LH and 1-3)-DNA mixtures (mixed with
bromophenol blue dye at 1:1 ratio) was loaded on the gel along with the standard DNA marker.
The electrophoresis was carried out in a dark room at constant 50 V of electricity for around
4
5 min. Agarose gel was stained with ethidium bromide solution 10 (µg/mL) for 10-15 min.
Cleaved DNA bands were visualized under UV light using a Bio-Rad Trans illuminator and
photographed by using a polaroid camera (a red filter and polaroid film were used).
3
.3. Antimicrobial activity
According to clinical and laboratory standards institute (CLSI) protocol [19, 20], minimum
inhibitory concentrations (MICs) were determined by broth microdilution method using a 96-
well plate. In each well, 100 µL of Mueller-Hinton broth (for bacterial strains) or Sabouraud
dextrose broth (for fungal strains) was placed. The serial dilutions were performed. The
5
4
inoculums were adjusted to contain approximately 10 CFU/mL of bacteria and 10 CFU/mL of
fungi. After adding 100 microliters of the inoculums, plates were incubated 24 h at 37 C for
5

bacteria and 48 h at 30 C for fungi. 20 µL of 0.5% of TTC aqueous solution was added to
determine the antimicrobial activity of the compounds. Standard antibiotics used were penicillin
and gentamycin [21].
3
.4. Anti-tuberculosis
By using microplate Alamar Blue Assay Method (MABA) [22], all the synthesized compounds
were assessed against M. tuberculosis. This methodology is non-toxic, uses a thermally stable
reagent and shows a good correlation with proportional and BACTEC radiometric method. In
brief, 200 mL of deionized sterile water was added to all outer perimeter wells of a sterile
9
9
6-well plate to minimize the evaporation of medium in the test wells during incubation. The
6-well plate received 100 mL of the Middle brook 7H9 broth and serial dilutions of compounds
were made directly on the plate. The final drug concentrations tested were 100 to 0.2 mg/mL.
Plates were covered and sealed with parafilm and incubated at 37 °C for five days. After this,
2
5 mL of freshly prepared 1:1 mixture of Almar Blue reagent and 10% tween 80 was added to
the plate and incubated for 24 h. A blue color in the well was interpreted as no bacterial growth
and pink color was scored as growth. The MIC was defined as lowest drug concentration which
prevented the color change from blue to pink.
4
. Results and discussion
All the synthesized metal complexes 1-3 of the synthesized ligand are soluble in DMF and
DMSO; they are in the form of amorphous solid. The analytical data of the ligand and its
complexes 1-3 are given in table S1 (Supplementary Data).
4
.1. Infrared spectral studies
Some important IR frequencies of ligand and its metal complexes are systematized in table 1.
-1
The ligand shows a broad band in the region 3437 cm ascribed to v(-OH), which disappeared in
the metal complexes, indicating the coordination of -OH group to the metal ion through oxygen
-1
atom. In addition, all the complexes show a new broad band in the region of 3400 cm , which
may be due to the water molecules. However, the formation of M-O bond confirms the
-1
deprotonation of hydroxyl group [23]. A sharp intense band at 1618 cm in the ligand assigned
-1
to azomethine group v(C=N) is shifted to lower frequency in the range 1578-1573 cm in the
6

case of metal complexes. This shows the coordination through azomethine nitrogen to the metal
-1
ions [24]. The free ligand also shows a sharp band at 1553 cm assigned to v(C=N) of the
benzothiazole ring. This band is broadened and intensified in all the complexes due to the
coupling of exo-azomethine band with azomethine of benzothiazole ring showing a negative
-1
-1
shift of about 40-60 cm . The strong bands at 1288 and 1733 cm in ligand are assigned to
phenolic v(C-O) and lactonyl v(C=O), respectively. There is no drastic change in the position of
the v(C=O) in metal complexes, suggesting that lactone carbonyl oxygen is not involved in the
coordination to the metal. The phenolic v(C-O) band shows a positive shift in the complexes of
-1
-1
about 30-45 cm by appearing the band around 1319 cm ; these observations support the
-1
-1
formation of v(M-O) bond. The bands observed in the regions 485-452 cm and 541-619 cm
are assigned to v(M-N) and v(M-O) vibrations, respectively [25] (figure S2). In conclusion, the
IR data suggest a tridentate ONN-coordination of the ligand.
4
.2. NMR spectral studies
From the NMR spectral data, notable conclusions for the formation of ligand have been drawn.
1
13
The ligand is scanned in the range of 0-16 ppm for H NMR and 0-300 ppm for C NMR
1
studies. The H NMR spectrum of ligand is reproduced in figure S3.
1
In the H NMR spectrum, we observed a singlet at 12.29 ppm, 11.87 ppm and 8.7 ppm
assigned to phenolic (-OH), azomethine (-HC=N) and hydrazone N-H protons, respectively.
Another singlet at 2.39 ppm is assigned to -CH protons. The aromatic protons resonated in the
3
region 7.7 to 6.2 ppm.
1
3
In the C NMR spectrum (figure S4), (C=N) of the benzothiazole ring shows a singlet at
1
60.43 ppm and (C=O), (C-O), (C=N) of azomethine and (-CH ) carbon atoms resonated as
3
singlets at 159.14 ppm, 153.70 ppm, 152.05 ppm and 18.25 ppm. Signals at 105.97 ppm to
1
27.49 ppm are assigned to aromatic carbon atoms of the ligand.
4
.3. Mass spectral study of the ligand and its metal complexes
Formation of the ligand was further confirmed by mass spectral analysis. The mass spectrum of
the ligand exhibited a molecular ion peak at m/z 351 which corresponds to its molecular weight.
The fragmentation peak at m/z 334 is due to loss of -OH group.
The electron impact mass spectral study of the metal complexes supports the formation of
7

1
:2 (ML ) stoichiometric ratios. The EI mass spectrum of representative Co(II) complex
2
+
(
figure S5) shows a [M ] peak at m/z 759 (100%), [M+1] and [M+2] peak at m/z 760 (38.9%)
and 761 (9.0%), respectively. In the case of Ni(II) and Cu(II) complexes, the mass spectrum
+
shows a [M ] peak at m/z 758 and 763, respectively.
4
.4. Solution electronic spectral study
The solution electronic spectra of the ligand as well as its corresponding metal complexes were
recorded over the range of 200-1000 nm in DMSO. The ligand shows the absorption band
around 270 nm due to intra-ligand π→π* and 340 nm due to n→π* transitions [26, 27]. For all
the complexes, n→π* transitions are red-shifted due to the coordination of azomethine group to
the metal ion [28].
The absorption spectrum of Co(II) complex revealed two bands in the region of 954 nm
4
4
4
4
and 501 nm of T (F)→ T (F) (ν ) and T (F)→ T (P) (ν ) transitions [29]. The electronic
1
g
2g
1
1g
1g
3
spectrum of Ni(II) complex displays d-d transition band around 912 nm and 630 nm
3
3
3
3
corresponding to A (F)→ T (F) (ν ), A (F)→ T (F) (ν ) transitions and the high energy
2
g
1g
3
2g
1g
2
peak at 380 nm may be due to the charge-transfer transition [30]. Cu(II) complex shows two
2
2
absorption bands; the broad band at 635 nm is assigned to E → T transition and, further the
g
2g
high-intensity band around 375 nm is due to symmetry-forbidden ligand-to-metal charge-transfer
transition [31]. These values support the octahedral geometry of all the synthesized complexes.
4
.5. Powder X-ray diffraction studies
The synthesized metal complexes are soluble in polar organic solvents, like DMSO and DMF.
Hence, we have failed to grow suitable crystals for single-crystal studies. Therefore, to
understand the degree of crystallinity of the metal complexes we have carried out powder X-ray
diffraction pattern in the scanning range 3-90 (θ) at a wavelength of 1.54 Å (Cu Kα). In all the
synthesized complexes, intensity of the peaks decreases from high to low indicating the
amorphous nature of the complexes.
Powder X-ray patterns of complexes 1, 2 and 3 showed nine, seven and eleven reflections
with maximum 2θ = 30.38, 41.34 and 29.28, respectively. The representative powder X-ray
diffraction spectrum is given in figure S6. The inter-planar spacing (d) has been calculated using
equation nλ = 2dsinθ (Bragg’s Equation). The calculated inter-planar d-spacing together with
8

relative intensities with respect to most intense peak for complex 1 have been recorded and
2
2
2
depicted in table S2. From the entire important peaks and h + k + l values the unit cell
2
2
parameters have been calculated for cubic symmetry. For complex 1 the h + k2 + l are 1, 2, 3,
, 8, 9 and 13. It was observed that the absence of forbidden numbers (7, 15, 23, etc.) indicates
5
that complex 1 has cubic symmetry. The calculated lattice parameters were a = b = c = 10.63 Å.
Similar calculations were performed for complexes 2 and 3 (table S3 and table S4).
4
.6. Magnetic susceptibility studies, conductivity measurement and thermal analysis of metal
complexes
The µ values of complexes 1, 2 and 3 are 4.86, 2.90 and 1.77 BM, respectively, and are in good
eff
agreement with the reported values [32, 33]. Molar conductivity values were observed in the
-1
2
-1
range of 17.05 - 25.20 Ω cm mol indicating that the complexes are non-electrolytes. All these
data are given in table 2.
Thermal behavior of all the synthesized metal complexes is studied over the temperature
range of 25-1000 C. Thermal features of the metal complexes were almost the same.
Representative spectrum of complexes 2 and 3 (figure 1 and S7) showed thermal decomposition
in significant steps. Compound 2 shows weight loss at around 50-80 °C in the first step, which is
attributed to loss of four lattice water molecules. In the second stage, the decomposition
corresponds to a mass loss at around 375-440 °C and 440-720 C showing loss of the ligand and
finally at higher temperature the graph becomes plateau because of the formation of stable metal
oxide.
4
.7. Anticancer activity study
To investigate the anticancer effect of the synthesized compounds, human ovarian cancer cell
line (PA-1) was treated with ligand and its metal complexes. Absorbance values that are lower
than the control cells (table S5) indicate a reduction in the rate of cell proliferation. Conversely, a
higher absorbance rate indicates an increase in cell proliferation. So, we found that the
synthesized compounds showed reduction in the rate of cell proliferation [34]. Cell survival is
almost 50% after 48 h of incubation with ligand and complexes (figure 2). Cytotoxicity results of
ligand and complexes 1-3 are presented in table S5. The comparison revealed that Co(II)
complex exhibit lower cytotoxic effect than the parent ligand, whereas all the other compounds
9

exhibit moderate cytotoxic effect.
4
.8. DNA Cleavage activity study
The cleavage of CT-DNA has been monitored by using agarose gel electrophoresis method.
Figure 3 shows the cleavage activity of ligand (LH) and its metal complexes 1-3, M- standard
DNA molecular weight marker, C- control CT-DNA (untreated DNA) and LH and lanes 1-3 are
CT-DNA treated with ligand and different metal complexes, respectively. A control experiment
using DNA alone does not show any significant cleavage of DNA, even after a long exposure of
time. Further, as compared to the untreated DNA, a substantial decrease in the intensities of the
bands for the ligand and complexes bound to DNA is observed, when the genomic DNA is
allowed to interact with ligand and metal complexes 1-3. The results (figure 3) suggest that the
ligand and metal complexes can cleave CT-DNA at different degrees. Further, Cu(II) complex
shows a greater cleavage compared to other compounds. In 2011, Manjunath et al. reported the
DNA-cleavage activity for similar M(II) complexes by using agarose gel electrophoresis method
and obtained comparable results [35, 36]. Further, Mahendra Raj and Mruthyunjayaswamy also
studied the DNA-cleavage activity of 8-formyl-7-hydroxy-4-methylcoumarin containing Schiff
base metal complexes and reported that the cleavage study inhibited the growth of pathogenic
organisms [37].
4
.9. Antimicrobial activity study
The ligand (LH) and its metal complexes 1-3 were evaluated for in vitro antimicrobial activities.
MIC values for antibacterial and antifungal activity of ligand and metal complexes 1-3 are listed
in table 3, respectively. Compared to the free ligand, metal complexes show good activity against
tested strains of bacteria and fungi [38, 39]. In the case of antibacterial activity, Cu(II) complex
shows very good activity compared to other compounds, it even shows better activity compared
to standard drug Gentamicin against Staphylococcus aureus. In another case, Co(II) and Cu(II)
complexes showed a similar behavior against antifungal activity. The increase in activity of these
complexes may depend on their lipophilic nature and can be explained on the basis of Tweed’s
chelation therapy [40]. Previously, Prabhakar et al. reported the antimicrobial activity by the disc
diffusion method and their result revealed that Cu(II) complexes are more effective than the
other metal complexes [41]. Also, numerous reported methods showed that metal complexes
1
0

containing coumarin Schiff bases have more effective antimicrobial property [42-44].
4
.10. Anti-tuberculosis activity study
The preliminary screenings of all the synthesized compounds were analyzed for anti-tubercular
activity against mycobacterium tuberculosis using the Microplate Almar Blue Assay (MABA)
method. The data (table 4) divulge that the metal complexes show increased anti-tubercular
activity compared with the free ligand, with MIC value 0.8 µg/mL, compared to standard drug
streptomycin (MIC of 6.25 µg/mL). Many literatures show that the benzothiazole containing
compounds are more effective against bacterial diseases [45, 46].
5
. Conclusion
A tridentate heterocyclic hydrazone ligand and three of its transition metal complexes have been
synthesized and their anti-cancer, DNA cleavage studies, in vitro antibacterial and antifungal
potential was evaluated. Further, anti-tuberculosis has been conducted for the ligand and its
complexes. These synthesized compounds were characterized using physicochemical techniques
1
such as elemental analyses and H NMR, UV-vis, IR and mass spectroscopic studies. Octahedral
geometry is proposed on the basis of electronic spectra and magnetic moment data. Molar
conductivity measurements show that all the metal complexes are non-electrolytic in nature.
Metal to ligand stoichiometry is 1:2 as evident from mass spectra. TG/DTA spectrum of all the
metal complexes suggests the presence of four lattice held water molecules. Anti-cancer activity
showed that the IC value for the compounds tested is beyond the concentrations tested,
5
0
therefore the compounds appear to be nontoxic to the cell line (PA-1) against which the
cytotoxic activity has been tested. Antimicrobial results indicated that the metal complexes are
more potent than the ligand. DNA-cleavage studies reveal that the ligand and metal complexes
cleave CT-DNA to different extents. Representative structure of the metal complexes is shown in
figure 4.
Acknowledgements
Authors are thankful to University Scientific Instrumentation Centre, Karnatak University,
Dharwad, IISc Bengaluru and SAIF IIT Bombay, India for providing instrumental facilities.
1
1

Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
UGC, New Delhi for the financial support through UGC-UPE Fellowship.
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Figure 1. TGA spectrum of Ni(II) complex (2).
1
4

Figure 2. Cytotoxicity evaluation of LH and 1-3 against PA-I cell line. The cell viability was
assessed after 48 h by the MTT assay. (The experiment is carried out in triplicate under identical
conditions.)
Figure 3. DNA-cleavage activity of ligand (LH) and its complexes 1-3. Photograph of gel
electrophoresis experiment of LH series on CT-DNA. Lane M, DNA marker; lane C, treated
DNA.
1
5

Figure 4. Proposed structure of metal complexes 1-3.
-1
Table 1. Prominent FT-IR (in cm ) of ligand and its metal complexes.
Compound ν(C=O)lactonyl ν(C=N)azomethine ν(-OH) ν(C=N)benzothiazole ν(N-H)
ν(M-N)
ν(M-O)
LH
1
1733
1731
1727
1731
1618
1578
1576
1578
3437
---
1553
1501
1510
1495
3172
3175
3171
3173
---
---
484
449
452
623
541
549
2
---
3
---
1
6

Table 2. Electronic spectral, magnetic moment and conductivity data of the synthesized
compounds.
-1
2
-1
Compound
λmax (nm)
µeff (BM)
Molar conductivity (Ω cm mol )
LH
1
270, 340
---
---
501, 954
4.86
2.90
1.77
17.05
19.21
25.20
2
380, 630, 912
375, 635
3
Table 3. Results of antimicrobial screenings (MIC in µg/mL).
Antibacterial activity
Antifungal activity
Compound
Candida
Albicans
Aspergillus
fumigatus
S. aureus
E. Coli
LH
50
50
50
25
25
25
25
1
25
50
12.5
50
2
50
25
3
3.125
6.25
12.5
3.165
12.5
Gentamycin
Nystatin
3.125
6.25
1
7

Table 4. Results of anti-tubercular activity (MIC in µg/mL).
Compound
Anti-tubercular activity
LH
1.6
0.8
1.6
0.8
6.25
1
2
3
Streptomycin
Graphical Abstract
DNA Cleavage activity
Cytotoxicity
1
8