DNA cleavage, in vitro antimicrobial and electrochemical studies of Co(II), Ni(II), and Cu(II) complexes with m-substituted thiosemicarbazide schiff bases

Article abstract of DOI:10.1080/00958971003602269

Co(II), Ni(II), and Cu(II) complexes, ML₂ · 2H₂O have been synthesized with Schiff bases derived from m-substituted thiosemicarbazides and 2-methoxy benzaldehyde. The complexes are soluble in DMF/DMSO and non-electrolytes. From analy

Full text of DOI:10.1080/00958971003602269

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DNA cleavage,in vitro antimicrobial and
electrochemical studies of Co(II), Ni(II),
and Cu(II) complexes withm-substituted
thiosemicarbazide Schiff bases
Sangamesh A. Patil a , Vinod H. Naik a , Ajaykumar D. Kulkarni
a , Udaykumar Kamble a , Gangadhar B. Bagihalli a & Prema S.
Badami b
a P.G. Department of Chemistry , Karnatak University , Dharwad
580 003, Karnataka, India
b Department of Chemistry , Shri Sharanabasaveswar College of
Science , Gulbarga 585102, Karnataka, India
Published online: 16 Feb 2010.
To cite this article: Sangamesh A. Patil , Vinod H. Naik , Ajaykumar D. Kulkarni , Udaykumar
Kamble , Gangadhar B. Bagihalli & Prema S. Badami (2010) DNA cleavage,in vitro antimicrobial and
electrochemical studies of Co(II), Ni(II), and Cu(II) complexes withm-substituted thiosemicarbazide
Schiff bases, Journal of Coordination Chemistry, 63:4, 688-699, DOI: 10.1080/00958971003602269
To link to this article: http://dx.doi.org/10.1080/00958971003602269
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Journal of Coordination Chemistry
Vol. 63, No. 4, 20 February 2010, 688–699
DNA cleavage, in vitro antimicrobial and electrochemical
studies of Co(II), Ni(II), and Cu(II) complexes with
m-substituted thiosemicarbazide Schiff bases
SANGAMESH A. PATIL*y, VINOD H. NAIKy,
AJAYKUMAR D. KULKARNIy, UDAYKUMAR KAMBLEy,
GANGADHAR B. BAGIHALLIy and PREMA S. BADAMIz
yP.G. Department of Chemistry, Karnatak University, Dharwad 580 003, Karnataka, India
zDepartment of Chemistry, Shri Sharanabasaveswar College of Science,
Gulbarga 585102, Karnataka, India
(Received 12 July 2009; in final form 30 September 2009)
Co(II), Ni(II), and Cu(II) complexes, ML2 ꢀ 2H2O have been synthesized with Schiff bases
derived from m-substituted thiosemicarbazides and 2-methoxy benzaldehyde. The complexes
are soluble in DMF/DMSO and non-electrolytes. From analytical, spectral (IR, UV-Vis,
ESR, and FAB-mass), magnetic and thermal studies octahedral geometry is proposed for the
complexes. The redox behavior of the complexes was investigated using cyclic voltammetry.
The Schiff bases and their metal complexes have been screened for antibacterial (Escherichia
coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella typhi) and antifungal
activities (Aspergillus niger, Aspergillus flavus, and Cladosporium) by Minimum Inhibitory
Concentration method. DNA cleavage is studied by agarose gel electrophoresis method.
Keywords: Antimicrobial; DNA; Electrochemical; Spectral characterization
1. Introduction
Thiosemicarbazide-based compounds have been extensively studied [1–3]. Various
Schiff bases of thiosemicarbazide (thiosemicarbazones) and their corresponding
complexes have wide biological activities such as antitumor [4], antibacterial [5],
and antifungal activities [6]. Thiosemicarbazones represent an important class of
compounds utilized as starting materials in the synthesis of industrial products [7].
Cu and Ni complexes with Schiff base derived from N-methylthiosemicarbazone were
studied spectroscopically [8]. Sharma et al. [9] have studied 16 ring-substituted 4-phenyl
thiosemicarbazones. Transition metal complexes with tetradentate Schiff bases have
been investigated as catalysts for a number of redox reactions and electrochemical
reduction processes. Cyclic voltammetry is useful to investigate the mechanisms of
catalysis by Schiff-base metal complexes as well as to study structure–reactivity
relationships in these compounds [10–12]. Very recently, Adel et al. reported the
*Corresponding author. Email: patil1956@rediffmail.com
Journal of Coordination Chemistry
ISSN 0095-8972 print/ISSN 1029-0389 online ß 2010 Taylor & Francis
DOI: 10.1080/00958971003602269

DNA cleavage
689
interaction of transition/inner transition metals with Schiff bases of thiosemicarbazide
ligands [13] and NS donor ligands of thiosemicarbazide [14]. From our laboratories,
a number of transition metal complexes with various Schiff bases have been reported
which have been physicochemically characterized and studied for their antibacterial
and antifungal activity [15–18]. Interactions of transition metal complexes with DNA
have been extensively studied for their usage as probes for DNA structure and their
potential application in chemotherapy. Very recently, Cu(II) complexes have been
reported to be active in DNA strand scission [19–21].
The present work synthesizes and characterizes Co(II), Ni(II), and Cu(II) complexes
with Schiff bases derived from m-chloro/nitro substituted thiosemicarbazides and
2-methoxy benzaldehyde possessing sulfur and azomethine nitrogen donors. The
electrochemistry of the Schiff bases and their complexes is investigated by cyclic
voltammetry. The Schiff bases and their metal complexes are screened for their
antimicrobial activity and DNA cleavage of the complexes is also studied.
2. Experimental
2.1. Physical measurements
Carbon, hydrogen, and nitrogen were estimated by using an Elemental Analyzer Carlo
Erba EA1108 analyzer. The IR spectra of the Schiff bases and their complexes were
recorded on a HITACHI-270 IR spectrophotometer from 4000 to 250 cmꢁ1 in KBr
disks. The electronic spectra of the complexes were measured in HPLC grade DMF on
1
a VARIAN CARY 50-BIO UV-spectrophotometer from 200 to 1100 nm. H-NMR
spectra of ligands were recorded in D6-DMSO on a BRUKER 300 MHz spectrometer
at room temperature using TMS as an internal reference. FAB-mass spectra were
recorded on a JEOL SX 102/DA-6000 mass spectrometer/data system using Argon/
Xenon (6 kV, 10 Am) as the FAB gas. The accelerating voltage was 10 kV and spectra
were recorded at room temperature with m-nitrobenzyl alcohol as the matrix. The mass
spectrometer was operated in the þve ion mode. Electrochemistry of all the complexes
was recorded on a CHI1110A-electrochemical analyzer (made in USA) in DMF
containing 0.05 M n-Bu4NClO4 as the supporting electrolyte. The ESR spectrum was
recorded on a Varian-E-4X-band EPR spectrometer with 3000 G at modulation
frequency of 100 kHz under liquid nitrogen temperature using TCNE as g marker.
Thermogravimetric analyses were measured from room temperature to 1000ꢂC at a
heating rate of 10ꢂC minꢁ1 on a PERKIN-ELMER DIAMOND TG/DTA instrument.
Molar conductivity measurements were recorded on an ELICO-CM-82 T conductivity
bridge with a cell having cell constant 0.51 and magnetic moment was measured by
using a Faraday balance.
2.2. Methods
All chemicals used were of reagent grade.
2.3. Synthesis of m-substituted thiosemicarbazide
Freshly distilled m-chloroaniline/m-nitroaniline (12.7 g/13.8 g) was dissolved in ammo-
nia (20 mL) and carbon disulfide (8 mL) was added gradually with stirring in an

690
S.A. Patil et al.
ice bath. Ethanol (30 mL) was added gradually with constant stirring in an ice bath
until carbon disulfide was completely dissolved. The reaction mixture was then allowed
to stand for 2–3 h. An aqueous sodium chloroacetate (0.1 M) solution was added,
followed by hydrazine hydrate (10 mL). The reaction mixture was stirred for 2–3 h and
allowed to stand overnight. The crystals that separated were filtered, washed with cold
ethanol, and recrystallized from hot ethanol. The IUPAC names of the synthesized
thiosemicarbazones are 4-(m-chlorophenyl) thiosemicarbazide and 4-(m-nitrophenyl)
thiosemicarbazide.
2.4. Synthesis of Schiff bases [I and II]
The synthesis of Schiff bases (schematically presented in scheme 1) is synthesized by
refluxing hot ethanolic solution (30 mL) of m-substituted thiosemicarbazide (0.01 M)
and hot ethanolic solution (30 mL) of 2-methoxy benzaldehyde (0.01 M) for 4–5 h with
addition of a few drops of hydrochloric acid. The precipitate formed during reflux was
filtered, washed with cold EtOH, and recrystallized from hot EtOH.
2.5. Synthesis of Co(II), Ni(II), and Cu(II) complexes [(1)–(6)]
An ethanol solution (45 mL) of Schiff base (2 mM) was mixed with an ethanol solution
(5 mL) of 1 mM of CoCl2 ꢀ 6H2O/NiCl2 ꢀ 6H2O/CuCl2 ꢀ 2H2O and refluxed in a water bath
for 2 h. Then, to the reaction mixture, 2 mM (in 15 mL solution) of sodium acetate was
added and the reflux was continued for 3 h. The separated complex was filtered, washed
thoroughly with water, ethanol, ether, and finally dried in a vacuum over fused CaCl2.
3. Pharmacology
3.1. DNA cleavage experiment
3.1.1. Preparation of culture media. DNA cleavage experiments were done according
to the literature [22]. Nutrient broth [peptone, 10; yeast extract, 5; NaCl, 10; in (g Lꢁ1)]
was used for culturing of Escherichia coli and potato dextrose broth [potato, 250;
X
X
CHO
S
OCH3
S
EtOH
reflux
+
C
C
N
NH2
4
5h
N
N
N
N
H
H
H
H
CH
OCH3
X = Cl, NO2
Schiff base
I
II
X
Cl
NO2
Molecular formula
C15H14N3OSCl
C15H14N4O3S
Scheme 1. Synthesis of Schiff bases.

DNA cleavage
691
dextrose, 20; in (g Lꢁ1)] was used for the culture of Aspergillus niger. The 50 mL media
was prepared, autoclaved for 15 min at 121ꢂC under 15 lb pressure. The autoclaved
media were inoculated with the seed culture. E. coli was incubated for 24 h and A. niger
for 48 h at 37ꢂC.
3.1.2. Isolation of DNA. The fresh bacterial culture (1.5 mL) is centrifuged to obtain
the pellet which is then dissolved in 0.5 mL of lysis buffer (100 mM tris pH 8.0, 50 mM
EDTA, 10% SDS). To this, 0.5 mL of saturated phenol was added and incubated
at 55ꢂC for 10 min, centrifuged at 10,000 rpm for 10 min. To the supernatant, equal
volume of chloroform : isoamyl alcohol (24 : 1) and 1/20th volume of 3 M sodium
acetate (pH 4.8) was added. After centrifuging at 10,000 rpm for 10 min, three volumes
of chilled absolute alcohol was added to the supernatant. The precipitated DNA was
separated by centrifuging and the pellet was dried and dissolved in TAE buffer (10 mM
tris pH 8.0, 1 mM EDTA) and stored cold.
3.1.3. Agarose gel electrophoresis. Cleavage products were analyzed by agarose gel
electrophoresis [22]. Test samples (1 mg mLꢁ1) were prepared in DMF and added
(25 mg) to the isolated DNA of E. coli and A. niger. The samples were incubated for 2 h
at 37 ꢂC and then 20 mL of DNA sample (mixed with bromophenol blue dye in 1 : 1
ratio) was loaded carefully into the electrophoresis chamber wells along with standard
DNA marker containing TAE buffer (4.84 g tris base, pH 8.0, and 0.5 M EDTA/1 L),
and finally loaded on agarose gel with 50 V for 30 min. Removing the gel and staining
with 10.0 mg mLꢁ1 ethidium bromide for 10–15 min gave bands under Vilberlourmate
Gel documentation system and photographed to determine the extent of DNA cleavage
as compared with standard DNA marker.
3.1.4. In vitro antibacterial and antifungal assay. The biological activities of the Schiff
bases and their complexes have been studied for antibacterial and antifungal activities
by agar and potato dextrose agar diffusion methods, respectively. The antibacterial
and antifungal activities were done at 10, 30, 50, and 100 mg mLꢁ1 concentrations
in DMF solvent using four bacteria (E. coli, Staphylococcus aureus, Pseudomonas
aeruginosa, and Salmonella typhi) and three fungi (A. niger, A. flavus, and cladosporium)
by the MIC method [23]. These bacterial strains were incubated for 24 h at 37ꢂC and
fungal strains for 48 h at 37ꢂC. Standard antibacterial (Gentamycin) and antifungal
drug (Flucanozole) was used for comparison under similar conditions.
4. Results and discussion
The Schiff bases (I and II) form complexes (1–6) with CoCl2 ꢀ 6H2O, NiCl2 ꢀ 6H2O,
and CuCl2 ꢀ 2H2O in ethanol. The complexes are colored, stable, non-hygroscopic, and
insoluble in common organic solvents but soluble in DMF and DMSO. Elemental
analyses showed 1 : 2 stoichiometry of the type ML2 ꢀ 2H2O, where L stands for a
deprotonated ligand which exhibits thiol–thione tautomerism. The structure of I is
presented in figure 1. The molar conductance values indicate non-electrolytic nature
of the complexes in DMF (table 1).

692
S.A. Patil et al.
Cl
3′
S
2
′
′
4
′
1
C
N
′
5
2
4
N
H
N
H
3
1
6′
CH
OMe
1″
6″
2″
3″
5″
4″
Figure 1. Structure of Schiff base I.
To establish whether water present in the complexes is coordinated, the weighed
complex was heated for 2 h at 105ꢂC, cooled in a desiccator, and weighed again with no
loss in weight [24], suggesting that water present in the complexes is coordinated.
4.1. IR spectral studies
The prominent infrared spectral data of the Schiff bases and their complexes are
presented in ‘‘Supplementary material’’.
The IR spectra of the Schiff bases exhibit two characteristic bands due to ꢀ(NH) at
3270–3152 cmꢁ1 corresponding to two ꢀ(NH) groups. A strong band at 2672–2666 cmꢁ1
is ascribed to ꢀ(SH) and another band at 1199–1187 cmꢁ1 is assigned to ꢀ(C¼S) [25].
Both ꢀ(SH) and ꢀ(C¼S) bands are of equal intensity; these observations suggest that
the Schiff bases exhibit thiol–thione tautomerism with 1 : 1 ratio. High intensity bands
at 1605 and 1596 cmꢁ1 in the IR spectra of I and II are assigned to ꢀ(C¼N) [26].
In comparison with the spectra of the Schiff bases, all Co(II), Ni(II), and Cu(II)
complexes exhibit ꢀ(C¼N) at 1559–1597 cmꢁ1 shifted to lower wave numbers,
indicating that azomethine is coordinated to metal [26–28]. Deprotonation of the
thiol is indicated by the absence of a band at ꢃ2672 cmꢁ1 in all complexes, which is due
to ꢀ(S–H), indicating that the metal is coordinated through sulfur. This is further
supported by the band at 786–769 cmꢁ1 in the complexes due to ꢀ(C–S). New bands at
473–466 cmꢁ1 are assigned to stretching of M–N bonds [29]. The band at 341–338 cmꢁ1
of far IR-spectra is due M–S [30]. The presence of coordinated water in the complexes
is confirmed by a broad band at 3436–3394 cmꢁ1 and two weak bands at 750–800 and
700–720 cmꢁ1 due to ꢀ(OH2) rocking and wagging modes, respectively [31].
The IR spectral data provide strong evidence for complexation of Schiff bases with
metal(II).
4.2. 1H NMR spectral study of Schiff bases I and II
1
In the H-NMR spectra of the Schiff bases, the NH proton exhibited two singlets
at 9.98(s, 1H)/9.24 ppm (s, 1H) and 9.92(s, 1H)/9.28 ppm (s, 1H) [32]. The characteristic
signals at 8.46 ppm and 8.42 ppm (s, 1H) are assigned to –CH¼N. Sharp singlets at
3.87 ppm (s, 1H) and 3.91 ppm (s, 1H) are attributed to SH. The multiplets in the region

DNA cleavage
693

694
S.A. Patil et al.
6.95–7.81 and 7.01–7.87 ppm (m, 8H) (m, 8H) are due to aromatic protons and singlets
at 3.47 ppm (s, 3H) and 3.46 ppm are due to OCH3. NMR results support the IR
inferences and confirm the thiol–thione tautomerism of the Schiff bases.
4.3. Electronic spectral and magnetic studies
The Co(II) complexes exhibited bands in the region 8000–10,000 cmꢁ1 and 18,000–
4
20,000 cmꢁ1 corresponding to ꢀ1 and ꢀ3 transitions attributed to 4T1g (F) ! T2g (F) (ꢀ1)
4
4
and T1g (F) ! T1g (P) (ꢀ3). The brownish Co(II) complexes showed absorption
bands at 9256–9312 and 18,965–18,952 cmꢁ1 corresponding to ꢀ1 and ꢀ3, characteristic
of high spin octahedral Co(II) complexes [31]. However, ꢀ2 is not observed because
of its proximity to the strong ꢀ3 transition. The ligand field parameters calculated
are presented in ‘‘Supplementary material’’. Magnetic measurements for the Co(II)
complexes have magnetic moment values of 4.51–4.74 which agree with octahedral
range [33] supporting the electronic spectral results.
The greenish Ni(C15H13N3OSCl)2 ꢀ 2H2O exhibited three bands at 10,363, 15,878,
3
3
3
3
3
3
and 26,334 cmꢁ1 attributed to A2g ! T2g (ꢀ1), A2g ! T1g (F) (ꢀ2), and A2g ! T1g
(P) (ꢀ3), respectively, which indicate octahedral Ni(II) [34]. The ligand field parameters
(Supplementary material) show ꢀ2/ꢀ1 to be 1.527 and the meff value to be 3.174,
suggesting octahedral Ni(II). Hence, the ligand field parameters [35] correlate to the
electronic spectral and magnetic properties.
The electronic spectra of Cu(II) complexes display two prominent bands. A low
2
2
intensity broad band at 16,582 cmꢁ1 is assignable to Eg ! T2g transition and a high
intensity band at 25,642 cmꢁ1 is due to ligand ! metal charge transfer. The electronic
spectra suggest distorted octahedral geometry around Cu(II) [36]. The Cu(II) complexes
magnetic moment (1.77–1.79 BM) is consistent with octahedral geometry [37].
4.4. FAB-mass spectral studies of Schiff bases and their metal complexes
The FAB-mass spectrum of I, depicted in ‘‘Supplementary material’’, shows a
molecular ion peak at m/z 319 equivalent to its molecular weight. Fragment peaks
observed at m/z 288, 199, and 126 are due to the cleavage of OCH3, C7H5, and CN2SH,
respectively. For II, the molecular ion peak is observed at m/z 330, ascribed to
C15H14N4O3S.
The FAB-mass spectra of Co(C15H13N3OSCl)2 ꢀ 2H2O, Ni(C15H13N3OSCl)2 ꢀ 2H2O
and Cu(C15H13N3OSCl)2 ꢀ 2H2O showed molecular ion peaks Mþ at m/z 731, 730, and
735 equivalent to their molecular weight. All [MHL ꢀ 2H2O]þ undergo demetallation to
form [L þ H]þ at m/z 319. Co(C15H13N3OSCl)2 ꢀ 2H2O complex showed a fragment
at m/z 695 ascribed to the loss of two waters. The complexes of II showed molecular
ion peaks at m/z 753, 752, and 757 equivalent of their molecular weight and undergo
demetallation to form [L þ H]þ at m/z 330.
4.5. ESR spectrum of 5
The ESR spectrum of 5 (Supplementary material) at RT shows one intense absorption
in the high field region, isotropic due to tumbling of the molecules. However, at LNT

DNA cleavage
Table 2. Thermogravimetric data of 1, 3, and 5.
695
Weight loss
(%)
Metal oxide
(%)
Decomposition
temperature
(ꢂC)
Compound
No.
Obsd Calcd Obsd Calcd
Inference
1
3
5
145–174
230–270
315–365
4.8
32.8
54.4
4.9
32.8
54.4
10.1
10.0
10.7
10.3
10.1
10.7
Loss due to coordinated water molecules
Loss due to 2-methoxy benzaldehyde
Loss due to thiosemicarbazide
140–185
215–255
300–355
4.9
32.7
54.4
4.9
32.9
54.5
Loss due to coordinated water molecules
Loss due to 2-methoxy benzaldehyde
Loss due to thiosemicarbazide
140–165
210–260
310–355
4.9
32.5
54.1
4.9
32.7
54.1
Loss due to coordinated water molecules
Loss due to 2-methoxy benzaldehyde
Loss due to thiosemicarbazide
four well-resolved peaks in low field region are observed. The g|| and gr values have
been found to be 2.1009 and 2.015, respectively. The trend g|| 4 gr4 2.0023 indicates
that the unpaired electron is localized in the dx2ꢁy2 orbital of Cu(II) and is characteristic
for axial symmetry [38]. Thus, ESR spectral data confirm that 5 possesses distorted
octahedral geometry.
4.6. Thermal studies of metal complexes
The thermal behavior of Co(II), Ni(II), and Cu(II) complexes are almost the same; only
Co(C15H13N3OSCl)2 ꢀ 2H2O, Ni(C15H13N3OSCl)2 ꢀ 2H2O, and Cu(C15H13N3OSCl)2 ꢀ2H2O
will be discussed.
The thermal decomposition of 1, 3, and 5 took place in three steps as indicated
by DTG peaks around 140–185, 210–270, and 300–365ꢂC corresponding to the loss of
coordinated water, 2-methoxy benzaldehyde and m-substituted thiosemicarbazide,
respectively. TGA studies confirm coordination of water to the metal ions. Both waters
depart in a narrow (ꢃ45 K) one step process. Finally, the metal complexes decompose
gradually with the formation of metal oxide above 365ꢂC. The TG/DTG spectrum
of 3 is presented in ‘‘Supplementary material’’. The proposed chemical change with
temperature and the percentage of metal oxide obtained are given in table 2.
4.7. Electrochemistry
All complexes were studied for their electrochemical behavior. Both Cu(II) com-
A cyclic voltammogram of
plexes exhibit similar electrochemical properties.
Cu(C15H13N3OSCl)2 ꢀ 2H2O (Supplementary material) displays a reduction peak at
Epc ¼ ꢁ1.41 V with a corresponding oxidation peak at Epa ¼ ꢁ0.79 V. The peak
separation of this couple (DEp) is 0.62 V at 0.1 V sꢁ1 and increases with the increase
in scan rate. The most significant feature of the Cu(II) complex is the Cu(II)/Cu(I)
couple. The difference between forward and backward peak potentials provides a
rough evaluation of the degree of the reversibility of one electron transfer reaction.
The analysis of cyclic voltammetric responses with scan rate varying from 50 to

696
S.A. Patil et al.
300 mV sꢁ1 gives the evidence for quasi-reversible one electron transfer. The ratio of
cathodic to anodic peak height was less than one. However, the peak current increases
with the increase of the square root of the scan rates, establishing the electrode process
as diffusion controlled [39]. The separation in peak potentials increases at higher scan
rates, consistent with quasi-reversibility of the Cu(II)/Cu(I) couple.
The cyclic voltammogram of Ni(C15H13N3OSCl)2 ꢀ 2H2O (Supplementary material)
exhibits a reduction peak at Epc ¼ ꢁ1.352 V with oxidation peak at Epa ¼ ꢁ0.682 V
corresponding to the Ni(II)/Ni(I) couple. The peak separation of this couple (DEp) is
0.67 V. This Ni(II) complex also has a quasi-reversible character as the separation
in peak potential that is higher than 59 mV and the peak currents rise with increasing
square root of the scan rates. The difference between forward and backward peak
potentials can provide a rough evaluation of the degree of the reversibility.
5. Pharmacological results
5.1. In vitro antibacterial and antifungal activity
Antibacterial studies indicated that I and II were potentially active against
P. auregenosa and S. typhi and moderately active against S. aureus. All the Co(II),
Ni(II), and Cu(II) metal complexes showed higher antibacterial activity against all
the bacterial strains (table 3) than the respective Schiff bases. For antifungal activity,
the Schiff bases and their Co(II), Ni(II), and Cu(II) complexes were highly active. All
the metal complexes possess higher antifungal activity than the Schiff bases. The metal
complexes are powerful and potent bactereostatic agents, inhibiting the growth of the
microorganisms [40–44].
The minimum inhibitory concentration (MIC) of some selected compounds, which
showed significant activity against selected bacterial and fungi species, were determined.
The results indicated that these compounds were most active in inhibiting the growth
of the tested organisms at 10 mg mLꢁ1 (table 4).
5.2. DNA cleavage activity
C15H14N3OSCl, Co(C15H13N3OSCl)2 ꢀ 2H2O, and Cu(C15H13N4O3S)2 ꢀ 2H2O were
studied for their DNA cleavage activity by agarose gel electrophoresis against DNA
of A. niger and E. coli.
DNA-binding studies are important for construction of new and more efficient drugs
targeted to DNA [45]. Most DNA interaction studies are carried out on calf thymus
DNA [46, 47]. Here we studied DNA cleavage on DNA isolated from A. niger and
E. coli. The electrophoresis clearly revealed that the Schiff base and both complexes act
on DNA as there was molecular weight difference between the control and the treated
DNA samples. The difference was observed in the bands of lanes 1–3 compared to
the control DNA of A. niger (Supplementary material) and control DNA of E. coli.
The control DNA alone does not show any apparent cleavage, whereas Schiff base
and complexes do. However, the nature of reactive intermediates involved in DNA
cleavage by the complexes is not clear. The results indicated the important role of metal
in these isolated DNA cleavage reactions. As the compound was observed to cleave

DNA cleavage
697
Table 3. Antimicrobial results of Schiff bases and their metal complexes.
% Inhibition against bacteria
Compound Concentration
% Inhibition against fungi
No.
(mg mLꢁ1
)
E. coli S. aureus P. aeruginosa S. typhi A. flavus Cladosporium A. niger
I
10
30
50
100
13
19
35
49
22
36
49
59
13
60
67
72
14
23
74
80
51
57
68
78
75
82
86
92
63
69
81
88
II
1
2
3
4
5
6
10
30
50
100
19
28
41
61
25
39
56
67
19
55
64
71
22
29
66
82
49
57
67
75
66
79
86
93
59
69
78
89
10
30
50
100
70
76
83
94
54
66
78
90
79
83
83
91
77
83
89
92
78
84
86
97
76
83
90
93
81
88
91
94
10
30
50
100
64
76
83
92
56
58
70
81
68
81
83
93
75
79
87
92
77
80
87
95
75
79
87
94
79
84
89
95
10
30
50
100
46
57
65
78
56
66
75
83
63
72
77
80
64
71
76
83
65
70
78
89
90
94
94
97
72
75
88
91
10
30
50
100
44
53
64
76
54
61
72
82
57
70
77
82
59
68
71
81
57
69
73
87
81
88
88
90
66
77
80
84
10
30
50
100
49
52
62
73
36
75
83
93
54
62
72
74
50
61
68
70
65
73
78
97
72
78
85
95
69
81
91
94
10
30
50
100
84
90
95
98
83
90
95
98
83
88
93
96
82
85
89
95
76
78
86
95
90
92
93
96
88
91
94
97
Gentamycin
Flucanozole
100
100
100
–
100
–
100
–
100
–
–
100
–
100
–
100
Table 4. Minimum inhibitory concentration (mg mLꢁ1).
Compound No.
E. coli
P. aeruginosa
S. typhi
A. flavus
Cladosporium
A. niger
I
25
25
10
10
10
10
25
25
10
10
10
10
10
10
4100
4100
25
25
10
25
10
10
–
25
25
10
10
10
10
25
4100
10
25
10
10
10
10
4100
4100
4100
4100
10
10
10
25
4100
4100
II
1
2
3
4
5
6
–

698
S.A. Patil et al.
Cl
H
N
N
C
S
N
H2O
CH
OMe
M
OMe
CH
N
H2O
S
C
N
H
N
Cl
M = Co(II), Ni(II) and Cu(II)
Figure 2. Structure of Co(II) 1, Ni(II) 3, and Cu(II) 5 complexes.
DNA, it can be concluded that the compound inhibits the growth of the pathogenic
organism by cleaving the genome.
6. Conclusions
The synthesized Schiff bases are bidentate ligands and exhibit thiol–thione tautomer-
ism. The metal ion is coordinated through the azomethine nitrogen and sulfur in thiol
form via deprotonation. The structures of Co(II), Ni(II), and Cu(II) complexes are
presented in figure 2. The bonding of ligand to metal ion is confirmed by analytical,
spectral, magnetic, and thermal studies. The electrochemistry of the Cu(II) and Ni(II)
metal complexes in DMF exhibit quasi-reversible one electron transfer. The Schiff bases
and their metal complexes were highly active against some of the antibacterial and
antifungal species. The activity is significantly increased on coordination. The DNA
cleavage studies reveal that the complexes showed non-specific cleavage of DNA
isolated from A. niger and E. coli.
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