Synthesis, characterization, anticancer and antibacterial evaluation of Schiff base ligands derived from hydrazone and their transition metal complexes

Article abstract of DOI:10.1016/j.ica.2018.09.022

Copper(II), Nickel(II) and Cobalt(III) complexes with Schiff base ligands derived from hydrazone, (HL¹ = (E)-N′-(pyridin-2-ylmethylene)benzohydrazide, H₂L² = (E)-2-(2-hydroxybenzylidene)hydrazine-1-carboxamide and HL³

Full text of DOI:10.1016/j.ica.2018.09.022

Accepted Manuscript
Research paper
Synthesis, characterization, anticancer and antibacterial evaluation of Schiff
base ligands derived from hydrazone and their transition metal complexes
Roghayeh Fekri, Mehdi Salehi, Asadollah Asadi, Maciej Kubicki
PII:
S0020-1693(18)30782-5
https://doi.org/10.1016/j.ica.2018.09.022
ICA 18480
DOI:
Reference:
Inorganica Chimica Acta
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Received Date:
Revised Date:
Accepted Date:
19 May 2018
16 August 2018
8 September 2018
Please cite this article as: R. Fekri, M. Salehi, A. Asadi, M. Kubicki, Synthesis, characterization, anticancer and
antibacterial evaluation of Schiff base ligands derived from hydrazone and their transition metal complexes,
Inorganica Chimica Acta (2018), doi: https://doi.org/10.1016/j.ica.2018.09.022
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Synthesis, characterization, anticancer and antibacterial
evaluation of Schiff base ligands derived from hydrazone
and their transition metal complexes
Roghayeh Fekria, Mehdi Salehia,*, Asadollah Asadib, Maciej Kubickic
a Department of Chemistry, College of Science, Semnan University, Semnan, Iran
bDepartment of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran
cFaculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznan, Poland
Correspondence:Email: msalehi@semnan.ac.ir
Abstract
Copper(II), Nickel(II) and Cobalt(III) complexes with Schiff base ligands derived from
hydrazone, (HL1 = (E)-N'-(pyridin-2-ylmethylene)benzohydrazide, H2L2 = (E)-2-(2-
hydroxybenzylidene)hydrazine-1-carboxamide
and
HL3
=
(E)-2-(pyridin-2-
ylmethylene)hydrazine-1-carboxamide, were synthesized and spectroscopically characterized
1
by FT-IR, H NMR, UV-Vis spectroscopy, X-ray crystallography and cyclic voltammetry.
The synthesized compounds have been screened for their antibacterial activities against the
bacterial species E. coli, K. pneumonia (Gram-negative) and S. aureus, B. subtilis (Gram-
positive) by minimum inhibitory concentration (MIC) and minimum bactericidal
concentration (MBC) methods. In vitro anticancer studies of the ligands and coordination
compounds (1-3) using MTT assay was also done. Results show that the complexes (1-3)
have higher antibacterial and anticancer activities than the respective free ligands.
Keywords: Hydrazone, Spectral properties, Crystal Structure, Antibacterial study,
Anticancer activity.
1. Introduction
Schiff base complexes have continued to play the role of one of the most important
stereochemical models in transition metal coordination chemistry due to their structural
versatility associated with various applications [1-4]. In analytical chemistry, hydrazones are
prepared by the reaction of aldehydes with hydrazines. They can act as multidentate ligands
with transition metals and show many applications [5]. Hydrazone compounds bearing ONO
and NNO donor atoms have been introduced to coordination chemistry [6-7]. Hydrazones
have physiological and biological activities such as anticancer [8], antibacterial [9],
antioxidant [10], antifungal [11], anti-tubercular [12] and anti-inflammatory [13]. There has

been considerable interest in copper, cobalt and nickel Schiff base complexes derived from
hydrazones [14-19]. Base on today studies, the design and synthesis of new metal-based
cancer chemotherapeutic agents, is in the most important part of the research area in
inorganic medicinal chemistry. Several recent articles have summarized the anticancer
activity of metal complexes derived from hydrazones such as cobalt, nickel and copper
complexes. Moreover, a series of hydrazone derivatives were synthesized and screened for
antibacterial activity against Gram-positive and Gram-negative bacteria [20-25, 27]. In this
paper, metal chelates of Schiff base derived from hydrazones have been prepared (Scheme 1).
Schiff base ligands were synthesized and identified as described before [26-28]. Single
crystal X-ray crystallography studies confirm that the Schiff bases act as tridentate ligands.
The free ligands and their complexes (1-3) are screened for their antibacterial activities
against Gram-positive and Gram-negative bacteria. Further, the cytotoxic effect of the
compounds examined on AGS and SW742 cancer cell lines. The purpose of this study is to
compare the biological activities of the synthesized compounds (1-3) and their respective
ligands.
Scheme 1.
complexes (1-3).
2. Experimental

2.1 Materials and instrumentation
All solvents and chemicals were purchased from commercial sources and used without
purification. FT-IR spectra (KBR disks) were recorded on a Bruker spectrophotometer.
Shimadzu UV-1650PC spectrophotometer was used to record the electronic spectra of
compounds. 1HNMR measurements were carried out on BRUKER AVANCE DR X400 (400
MHz) spectrometer at room temperature. Cyclic voltammetric measurements have been
performed on metrohm 757 VA computerace. RPMI 1640 and fetal bovine serum (FBS) were
obtained from Gibco. Phosphate-buffered saline (PBS), dimethylsulfoxide (DMSO),
dimethylformamide (DMF) and other chemicals were purchased from Sigma-Aldrich.
2.2 Synthesis of HL1
A mixture of an ethanolic solution of benzohydrazide (10 mmol) and pyridinecarbaldehyde
(10 mmol) was refluxed for 3 h. Then, the yellow precipitate was filtered and washed with
cold ethanol [26]. Yield: 85%. M. P. = 183 ºC. FT-IR: ѵmax cm-1 (KBr): 1621 (C=O), 1603
(C=N). UV-Vis: λmax (nm) (ε, M-1 cm-1) (Methanol): 282 (3980), 328 (3040).
2.3 Synthesis of H2L2
An ethanol solution of hydrazinecarboxamide (10 mmol) was added to an ethanol solution of
salicylaldehyde (10 mmol) and the mixture was refluxed for 4h. The resulting light yellow
precipitate was filtered off and washed with cooled ethanol [27]. Yield: 75%. M. P. = 161 ºC.
FT-IR: ѵmax cm-1 (KBr): 1681 (C=O), 1612 (C=N). UV-Vis: λmax (nm) (ε, M-1 cm-1)
(Methanol): 303 (4410), 329 (5480).
2.4 Synthesis of HL3
The synthesis of HL3 was performed using the same procedure for H2L2 with
pyridinecarbaldehyde instead of salicylaldehyde. The white precipitate of the ligand was
obtained [28]. Yield: 70%. M. P. = 172 ºC. FT-IR: ѵmax cm-1 (KBr) 1689 (C=O), 1667 (C=N).
UV-Vis: λmax (nm) (ε, M-1 cm-1) (Methanol): 287 (3680), 307 (3850).
2.5 Synthesis of complexes (1-3)
2.5.1 Synthesis of [CuII(L1)(SCN)2]n (1)
The (E)-N'-(pyridin-2-ylmethylene)benzohydrazide ligand, HL1, (0.5 mmol) was dissolved in
methanol (10 ml) and after adding of Cu(CH3COO)2.H2O (0.5 mmol) and NH4SCN (1
mmol), the resulting solution was refluxed for 4 h. After 4 days, crystals of the complex were

appeared, filtered off, washed with methanol and air dried. Yield: 54%. FT-IR: ѵmax cm-1
(KBr) 1591 (C=N). UV-Vis: λmax (nm) (ε, M-1 cm-1) (Methanol): 353 (4300).
2.5.2 Synthesis of [NiII (L2)2(Py)4].2ClO4 (2)
2
Ni(ClO4)2.6H2O (0.5 mmol) in 10 ml of methanol was added to a stirred solution of (E)-2-(2-
hydroxybenzylidene)hydrazine-1-carboxamide, H2L2, (0.5 mmol) in 10 ml of methanol.
Then, to this solution pyridine (1 ml) was added and the mixture was refluxed for 3h. The
crystals were obtained after 5 days. Yield: 64%. FT-IR: ѵmax cm-1 (KBr) 1596 (C=N). UV-
1
Vis: λmax (nm) (ε, M-1 cm-1) (Methanol): 373 (1920). H-NMR (DMSO-d6, 400 MHz): 7.56,
7.76 (s, 2H, CH=N), 7.90-8.37 (s, 4H, H2N), 6.55-7.42 (m, 31H, ArH).
2.5.3 Synthesis of [CoIII(L3)2].ClO4 (3)
To a stirring solution of Co(ClO4)2.6H2O (0.5 mmol) in methanol (20 ml) an equimolar
amount of (E)-2-(pyridin-2-ylmethylene)hydrazine-1-carboxamide, HL3, was added. To this
solution pyridine (1 ml) was added and the air was bubbled through the reaction and refluxed
for 4 h. The crystals of 3 suitable for X-ray crystallography were obtained after 3 days. Yield:
68%. FT-IR: ѵmax cm-1 (KBr): 1603 (C=N). UV-Vis: λmax (nm) (ε, M-1 cm-1) (Methanol): 314
(3660). 1H-NMR (DMSO-d6, 400 MHz): 7.91, 7.92 (s, 2H, CH=N), 8.01-9.92 (s, 4H, H2N),
6.77-11.38 (m, 8H, ArH).
2.6 X-ray crystallography
Diffraction data were collected by the ω-scan technique at 130(1) K (1, 3) on Rigaku
SuperNova four-circle diffractometer with Atlas CCD detector and mirror-monochromated
CuKα radiation (λ=1.54178 Å) and at 100(1) K (2), on Rigaku Xcalibur four-circle
diffractometers with Eos CCD detector and graphite-monochromated MoKα radiation
(λ=0.71069 Å). The data were corrected for Lorentzian and polarization as well as for
absorption effects [29]. Precise unit-cell parameters were determined by a least-squares fit of
4026 (1), 4770 (2), and 4689 (3) reflections of the highest intensity, chosen from the whole
experiment. The structures were solved with SHELXT-2013 and refined with the full-matrix
least-squares procedure on F2 by SHELXL-2013 [30]. All non-hydrogen atoms were refined
anisotropically, hydrogen atoms were placed in idealized positions and refined as ‘riding
model’ with isotropic displacement parameters set at 1.2 times Ueq of appropriate carrier
atoms. Table 1 lists the relevant experimental data and refinement details.

Crystallographic data for the structural analysis has been deposited with the Cambridge
Crystallographic Data Centre, Nos. CCDC-1811093 (1), CCDC-1811094 (2), and CCDC-
1811095 (3). Copies of this information may be obtained free of charge from: The Director,
CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK. Fax: +44(1223)336-033, E-mail:
deposit@ccdc.cam.ac.uk, or www.ccdc.cam.ac.uk.
“TABLE 1”
2.7 Cyclic voltammetry
Cyclic voltammetric measurements were performed using a three-electrode system (Ag/AgCl
as reference electrode, glassy carbon as working electrode, platinum wire as an auxiliary
electrode ) under a nitrogen atmosphere at 25 °C and using tetrabutylammonium
hexafluorophosphate as supporting electrolyte (complex concentrations of about 1×10-3 M in
DMF solution).
2.8 In vitro antibacterial efficiency
The Schiff base ligands and compounds (1-3) were tested against four different bacteria
species: Escherichia coli (PTCC-1270), Klebsiella pneumonia (PTCC-1053) as Gram-
Negative bacteria and Staphylococcus aureus (PTCC-1112) and Bacillus subtilis (PTCC-
1254) as Gram-Positive bacteria. The antibacterial activities of (1-3) were compared with
their respective ligands. The minimal inhibitory concentration (MIC) and the minimum
bactericidal concentration (MBC) data of the synthesized compounds were given in Table 4.
The Broth macro-dilution method was used to measure the MIC by a LB broth. The contents
in the tubes were mixed thoroughly and incubated overnight at 37°C. The MIC is the lowest
concentration of compound that produces inhibition of bacterial growth and MBC is the
lowest concentration of antibiotic required to kill a particular bacterium. It determined from
broth dilution minimum inhibitory concentration (MIC) tests by sub culturing to Mueller-
Hinton agar plates and incubated at 37 °C for overnight [31-33]-. Kanamycin and Co-
trimoxazole were of standard antibacterial agents included in the test [34-35].
2.9 In vitro anticancer activity
Anticancer effect of compounds were assayed by MTT assay against human gastric cancer
(AGS) and human colon cancer (SW742) cell lines. The cytotoxicity of compounds (1-3) was
compared with the ligands. The assay is based on the reduction of soluble yellow tetrazolium

salt to insoluble purple formazan crystals in the presence of enzyme in the mitochondria of
the live cells. For this assay, cells were seeded into a 96 well plates at a density of 1× 105
cells per ml in 0.2 mL of culture medium (RPMI 1640 with 10% fetal bovine serum (FBS)),
then incubated at 37 °C. After 24h the culture medium was replaced by RPMI 1640 medium
with different concentrations of the HL1, H2L2, HL3, 1, 2, and 3 (0.125, 0.25, 0.5, 1 and 2
mg/ml) and incubated at 37 °C for 24 h. Percentage cell viability was determined by MTT
assay [36-39].
3. Result and Discussion
3.1 Synthesis and characterization
Three new complexes (1-3) of copper, nickel and cobalt have been synthesized. All the
synthesized compounds were characterized on the basis of spectral data and X-ray
crystallography data suggest that the 1, 2 and 3 complexes are polymer-coordinated,
binuclear and mononuclear Schiff base complexes, respectively.
3.2 IR spectra
Some important infrared absorption frequencies of the ligands and complexes (1-3) are
presented here. All the free Schiff base ligands show characteristic azomethine at 1603 cm-1
for HL1, 1612 cm-1 for H2L2 and 1667 cm-1 for HL3. The former shifts towards the lower
frequency in the spectra of complexes at 1591, 1596 and 1603 cm-1 for 1, 2 and 3,
respectively, are due to involvement of the N atom of the -C=N- group in coordination.
Strong band at 2002 cm-1 is due to the SCN group for 1. The appearance of some new bands
in the FT-IR spectra of (1-3) in the regions 606-641 and 621-751 cm-1 are probably due to M-
N and M-O bands, respectively.
3.3 Electronic spectra
The electronic absorption spectra of methanolic solution (1×10-4 M) of ligands and
complexes (1-3) were recorded at 200-800 nm wavelength range and at 298 K. The bands at
228, 227 and 254 nm are attributable to intraligand π→ π* transitions of the benzene ring in
HL1, H2L2 and HL3, respectively. HL1, H2L2 and HL3 ligands show intensity bands at 282,
303 and 287 nm, respectively, which are assigned as π→ π* transition of the C=N and these
bands in the electronic spectra of (1-3), are shifted as a result of coordination and appeared at
353 nm for 1, 373 nm for 2 and 314 nm for 3. Also, the electronic spectrum of ligands

exhibited bands at 328, 329 and 307 nm which assigned to * for HL1, H2L2 and HL3,
respectively and these bands disappeared upon chelation. For the all the synthesized compounds
(1-3), d-d transitions probably appeared in the area under the charge transfer.
3.4 X-Ray studies
The polymeric structure (1) and structure of complexes (2-3) are shown in Figs. (1-6). The
polymeric structure (1) is a second polymorphic form of this compound; the first one was
published recently [40]. The first one was published recently. Both forms are P21 monoclinic,
and the monomer look quite similarly in both cases (Fig. 1a), but the conformation of
polymeric chain is different [40]. In published structure the subsequent monomers are almost
perpendicular while in (1) they are parallel (Fig. 1b). This difference is a consequence of
different construction of the polymer: in XIQLIT consecutive monomers are related by 21
screw axis, which in (1) – by unit-cell translation along x. Cu cation is 5-coordinated in
square-pyramid environment (Table 2, Fig. 2). N1A, N8A, O10A and N1B atoms are
approximately coplanar (max deviation 0.046(10Å), S1B(-1+x,y,z) is 2.8278(11)Å above this
plane and Cu1 is slightly, by 0.1476(10) Å, displaced towards S atom. The ligand molecule is
almost planar, Table 2 lists the dihedral angles between the approximately planar fragments.
In the crystal structure, the neighbouring polymeric chains are connected – besides van der
Waals interactions - only by weak C-H···S hydrogen bond contacts (H···S distance 2.87Å).
In 2 a dication Ni2L2(Py)4 (bridged by the oxygen atoms of ligand molecule, Fig. 3) is Ci-
symmetrical, occupying the special position on the inversion center in the space group I2/a.
The Ni atoms are six-coordinated in quite regular octahedral fashion. In the crystal structure
the perchlorate anions neutralize the cation charge and take part in the hydrogen bond system,
which involves also NH groups and C2-symmetrical water molecule (Table 3 lists the details
of hydrogen bonds). It can be noted, that the second hydrogen atom from NH2 group, not
involved in intermolecular N-H···O hydrogen bond system, strengthens the supramolecular
architecture by taking part in relatively short and directional intermolecular N-H···π
hydrogen bond (Fig. 4, Table 3). Complex (3) contains monocation CoL2 and perchlorate
counterion. Co ion is six-coordinated, again in octahedral geometry (Fig. 5, Table 2). The N-
H···N and N-H···O hydrogen bonds connect molecules into infinite chains connected by
centrosymmetric dimers created by R2 (8) and R4 (12) hydrogen-bond motifs (Fig. 6, Table
2
4
3).

“Fig. 1”
“Fig. 2”
“Fig. 3”
“Fig. 4”
“Fig. 5”
“Fig. 6”
“TABLE 2”
“TABLE 3”
3.5 Electrochemical studies
Cyclic voltammetry analysis of complexes was recorded in DMF solution. As shown in Fig. 7
(a), tow redox peaks emerge at -0.65V attributed to the cathodic and at 0.36 V attributed to
the anodic peak, corresponding to the transfer of Cu(II)/Cu(I) and Cu(I)/Cu(II) states for (1),
respectively. Fig. 7 (b) describes the cyclic voltammetric behavior of complex (2). The cyclic
voltammogram of this complex presented reduction peaks in the potential of -0.77 and -0.65
V that are assigned to Ni(II)/Ni(I) and there is not any clear oxidative peak for (2). Also the
voltammetric response in Fig. 7 (c), for complex (3), is attributed to redox process include a
cathodic peak at -0.45V and an anodic peak at 0.40 V, corresponding to the transfer of
Co(III)/Co(II) and Co(II)/Co(III)
.
“Fig. 7”
3.6 1H NMR
Further evidence for the presence of coordinated Schiff base ligands in the new complexes is
provided by the 1H NMR spectra of the complexes. In complexes (2) and (3) the signals due
to the azomethine proton (CH=N) appeared as a singlet at 7.56 and 7.76 ppm and 7.91, 7.92
ppm, respectively. Signals appeared in the 6.55-7.42 ppm region for (2) and 6.77-11.38 ppm
for (3) has been assigned to the phenyl ring and pyridine protons. Also in the complexes (2)
and (3) NH2 protons appeared between 7.90-8.37 ppm and 8.01-9.92 ppm, respectively.
3.7 Antibacterial activity

The synthesized ligands and synthesized compounds (1-3) were tested for in vitro
antimicrobial activity. They are tested against the bacteria; Escherichia coli, Klebsiella
pneumonia, (Gram-Negative bacteria) and Staphylococcus aureus, Bacillus subtilis, (Gram-
Positive bacteria). The minimum inhibitory concentration (MIC) and the minimum
bactericidal concentration (MBC) values of the compounds against bacteria are summarized
in Table 4. A comparative study of MIC and MBC values of ligands and compounds (1-3)
indicate that the synthesized compounds (1-3) exhibit higher antimicrobial activity than the
respective free ligands against Gram-Positive bacteria [41]. Increased activity of compounds
can be illustrated on the basis of the Tweedy’s chelation theory [42]. The reduction in polarity
increases the lipophilic character of the chelates. This may cause the formation of hydrogen
bonded interaction through the coordinated anions and azomethine group with the active
centers. These properties may be used in metal transport across the bacterial membranes or to
attach to the bacterial cells at a specific site from which it can interfere their growth. Thus,
based on obtained results, the antimicrobial activity of the compounds (1-3) shows greater
activity compared to their respective ligands [43].
“TABLE 4”
3.8 Cytotoxicity assay
In vitro anticancer activities of the synthesized Schiff base ligands and compounds (1-3) were
tested by MTT assay against AGS and SW742 cell lines. The AGS and SW742 cells were
incubated in the presence of increasing concentrations of the synthesized compounds. The
results of these experiments were shown in Figs. 8 and 9. The absorbance was measured at
570 nm and the cell viability (%) was calculated according to the following equation:
Cell viability (%) =
×100
Where OD570(sample) and OD570(control) represent the absorbance values of the cells treated and
control cells, respectively. From the results, it can be seen that all the synthesized compounds
(1-3) have higher activities than the respective free ligands due to the presence of metal
moieties and chelation in the compounds [44-45]. Figs. 8 and 9 show relationship between AGS
and SW741 cells viability (%) and the reciprocal concentration of ligands and their metal
compounds. Based on the results, upon increasing the concentration of test compounds, all
the compounds have a good increase in cytotoxic potencies. The activity of the synthesized
compounds (1-3) and their respective ligands show that all compounds (1-3) have better
activity than respective ligands against AGS and SW174 cancer cell lines. The increase in

biological activities of the metal chelates such as anticancer and antibacterial may be due to
the effect of the metal ion on the normal cell process. A possible mode of toxicity increase
may be considered in the light of Tweedy, s chelation theory [46]. Chelation considerably
reduces the polarity of the metal ion because of partial sharing of its positive charge with the
donor group and possible -electron delocalization within the whole chelate ring system that
is formed during coordination. Such chelation could enhance the lipophilic character of the
central metal atom and hence increase the hydrophobic character and liposolubility of the
complex favoring its permeation through the lipid layers of the cell membrane.
“Fig. 8”
“Fig. 9”
3.9 Conclusion
Three novel complexes of copper, nickel and cobalt obtained by hydrazone Schiff base
1
ligands. Ligands and their metal compounds have been characterized with FT-IR, HNMR
and UV-Vis spectroscopy. Electrochemical studies of the compounds (1-3) indicate that
metal compounds show redox behavior. Single crystal X-Ray analysis reveals that the
compounds 1, 2, and 3 belongs to polymer-coordinated, binuclear and mononuclear,
respectively and all Schiff base ligands act as tridentate ligands. In vitro antibacterial study of
compounds indicates that metal chelates have higher activity than respective ligands against
Gram-Positive bacteria. Anticancer activity of compounds reveals that all metal compounds
show better activity than respective ligands against AGS and SW174 cancer cell line and
might be due to chelation theory.
References
[1] S. Yamada, Coordination Chemistry Reviews, 1 (1966) 415-437.
[2] L. H. A. Rahman, R. M. E. Khatib, L. A. E. Nassr, A. M. A. Dief, F. E. Lashin,
Spectrochim. Acta A, 111 (2013) 266.
[3] L. H. A. Rahman, R. M. E. Khatib, L. A. E. Nassr, A. M. A. Dief, A. A. Seleem,
Spectrochim. Acta A, 117 (2014) 366.
[4] X. G. Ran, L. Y. Wang, Y. C. Lin, J. Hao, D. R. Cao, Appl. Organometal. Chem., 24
(2010) 741.
[5] O. Pouralimardan, A. Ch. Chamayou, Ch. Janiak, H. H. Monfared, Inorganica Chimica
Acta, 360 (2007) 1599-1608.
[6] R. Bikas, M. Ghorbanloo, R. Sasani, I. Pantenburg, G. Meyer, Journal of Coordination
Chemistry, 70 (2017) 819-830.

[7] B. I. N. Mladenova, G. T. Momekov, Bulgarian Chemical Communications, 49 (2017)
83-88.
[8] J. G. Deng, Y. Gou, W. Chen, X. Fu, H. Deng, Bioorganic & Medicinal Chemistry, 24
(2016) 2190-2198.
[9] G. Gomathi, R. Gopalakrishnan, Materials Science and Engineering, 64 (2016) 133-138.
[10] Y. Harinath, D. H. K. Reddy, B. N. Kumar, Ch. Apparao, K. Seshaiah, Spectrochimica
Acta Part A: Molecular and Biomolecular Spectroscopy, 101 (2013) 264-272.
[11] A. Mahal, R. A. E. Halawa, S. A. Zabin, M. Ibrahim, M. A. Refai, T. Kaimari, Journal
of Organic Chemistry, 3 (2015) 1-8.
[12] P. Dandawate, K. Vemuri, E. M. Khan, M. Sritharan, S. Padhye, Carbohydrate
Polymers, 108 (2014) 135-134.
[13] M. A. Abdelgawad, M. B. Labib, M. A. Latif, Bioorganic Chemistry, 74 (2017) 212-
220.
[14] L. Li, Y. Zh. Zhang, E. Liu, Ch. Yang, J. A. Golen, A. L. Rheingold, G. Zhang, Journal
of Molecular Structure, 110 (2016) 180-184.
[15] S. Mondal, B. Pakhira, A. J. Blake, M. G. B. Drew, Sh. K. Chattopadhyay, Polyhedron,
117 (2016) 327-337.
[16] J. Qin, Sh. Sh. Zhao, Y. P. Liu, Zh. W. Man, P. Wang, L. N. Wang, Y. Xu, H. L. Zhu,
Bioorganic & Medicinal Chemistry Letters, 26 (2016) 4925-4929.
[17] G. Xu, B. Tang, L. Gu, P. Zhou, H. Li, Journal of Molecular Structure, 1120 (2016)
205-214.
[18] U. P. Meshram, G. B. Pethe, A. R. Yaul, B. G. Khobragade, M. L. Narwade, Journal of
Physical Chemistry A, 91 (2017) 1877-1882.
[19] E. I. Yousif, R. M. Ahmed, H. A. Hasan, A. S. A. Fahdawi, M. J. A. Jeboori, Journal of
Science and Technology, 41 (2017) 103-109.
[20] Y. Zhang, L. Zhang, L. Liu, J. Guo, D. Wu, G. Xu, X. Wang, D. Jia, Inorganica Chimica
Acta, 363 (2010) 289-293.
[21] J. G. Deng, W. Chen, H. Deng, Journal of Fluorescence, 26(2016) 1987-1996.
[22] Sh. Shen, H. Chen, T. Zhu, X. Ma, J. Xu, W. Zhu, R. Chen, J. Xie, T. Ma, L. Jia, Y.
Wang, Ch. Peng, Oncology Letters, 13 (2017) 3169-3176.
[23] Y. Du, W. Chen, X. Fu, H. Deng, J. G. Deng, Royal Society of Chemistry Advances, 6
(2016) 109718-109725.
[24] M. E. Behery, H. E. Twigry, Molecular and Biomolecular Spectroscopy, 66 (2007) 28-
36.
[25] R. Fekri, M. Salehi, A. Asadi, M. Kubicki, Polyhedron, 128 (2017) 175-187.
[26] A. Datta, N. T. Chuang, J. H. Huang, H. M. Lee, Acta Crystallographica, 65 (2009) 996.
[27] R. Fekri, M. Salehi, A. Asadi, M. Kubicki, Applied Organometallic Chemistry, (2017) 1-
17.
[28] J. Zhou, Z. F. Chen, Y. S. Tan, X. W. Wang, Y. H. Tan, H. Liang, Y. Zhang, Acta
Crystallogr. 60 (2004) 519.
[29] Agilent Technologies, Crys Alis PRO (Version 1.171.33.36d), Agilent Technologies
Ltd, (2011).
[30] G. M. Sheldrick, Acta Crystallogr., (2015), C71, 3-8.
[31] C. S. Ukesh, S. D. Patil, J. of Life Sciences, 5 (2017) 97-101.

[32] F. Pakdel, Sh. Ghasemi, A. Babaloo, Y. Javadzadeh, R. Momeni, M. Ghanizadeh, S. R.
Moaddab, F. Y. Fathi, J. Clin Diagn Res. 11 (2017) 16-19.
[33] R. F. M. Elshaarawy, Ch. Janiak, Journal of chemistry, 9 (2016) 825-834.
[34] A. Brezdent, M. F. Mohamed, M. Nepal, J. S. Harwood, J. Kuriakose, M. N. Seleem, J.
Chmielewski, J. Am. Chem. Soc., 138 (2016) 10945-10949.
[35] J. Duan, J. Kang, T. Han, Y. Ma, Q. Guo, Y. Song, Q. Zhao, Y. Yang, R. Zhang, Journal
of Pharmaceutical Sciences, 30 (2017) 551-553.
[36] S. Sujarani, A. Ramu, Journal of Molecular Structure, 1059 (2014) 299-308.
[37] R. Gomathi, A. Ramu, A. Murugan, Bioinorganic Chemistry and Applications, (2014)
(2014) 1-12.
[38] N. Bai, Ch. Sh. Lai, K. He, Zh. Zhou, L. Zh. Quan, N. Zhu, Q. Y. Zheng, M. H. Pan, Ch.
T. Ho, J. Nat. Prod., 69 (2006) 531-535.
[39] F. Shokri, M. Heidari, S. Gharagozloo, M. G. Khansari, Toxicology, 146 (2000) 171-
176.
[40] C. Batistakis, Y. Gan, C. J. Cardin, D. G. Paschalidis, C. A. Kavounis, Z. Kristallogr, NCS, 222
(2007) 251-252.
[41] M. Salehi, F. Rahimifar, M. Kubicki, A. Asadi, Inorganica Chimica Acta, 443 (2016)
28-35.
[42] B.G. Tweedy, Phytopathology, 55 (1964) 910.
[43] M. M. A. Aly, A. M. Salem, M. A. Sayed, A. A. A. Aziz, Molecular and Biomolecular
Spectroscopy, 136 (2015) 993-1000.
[44] G. Jiang, Y. Jiang, Y. Shen, K. H. Nam, D. Lee, Zh. Gao, International Journal of
Pharmaceutics, 365 (2009) 155-161.
[45] J. Dh. Chellaian, J. Johnson, Molecular and Biomolecular Spectroscopy, 127 (2014)
396-404.
[46] K. L. Haas, K. J. Franz, Chem. Rev. 109 (2009) 4921-4960.

(a)
(b)
Fig. 1. Comparison of (a) the monomers in (1) and XIQLIT (cf. text), and (b) polymers formed in
XIQLIT (left) and in (1) (right).
Fig. 2. A perspective view of the monomer complex in (1); ellipsoids are drawn at the 50%
probability level and hydrogen atoms are shown as spheres of arbitrary radii.

Fig. 3. A perspective view of the dimeric complex in (2); ellipsoids are drawn at the 50% probability
level, hydrogen atoms are shown as spheres of arbitrary radii. Unlabelled part is related to the labeled
one by symmetry operation 1/2-x,3/2-y,1/2-z.
Fig. 4. Fragment of the hydrogen-bonded chain in (2) as seen along x-direction; hydrogen bonds are
shown as blue dashed lines.

Fig. 5. A perspective view of the cationic complex in (3); ellipsoids are drawn at the 50% probability
level, hydrogen atoms are shown as spheres of arbitrary radii.
Fig. 6. Fragment of the hydrogen-bonded chain in (3); hydrogen bonds are shown as dashed blue
lines.

(a)
(b)

(c)
Fig. 7. Cyclic voltammograms of polymer 1 (a) and complexes of 2 (b) and 3 (c) in DMF
(1×10-3M).
(a)

(b)
Fig. 8. Effect of Schiff base ligands (a) and their metal compounds (b) at different
concentrations (0.125, 0.25, 0.5, 1 and 2 mg/ml) on the AGS cell line, (HL1), 1 (green),
(H2L2), 2 (red), (HL3), 3 (blue).
(a)

(b)
Fig. 9. Effect of Schiff base ligands (a) and their metal compounds (b) at different
concentrations (0.125, 0.25, 0.5, 1 and 2 mg/ml) on the SW742 cell line, (HL1), 1 (green),
(H2L2), 2 (red), (HL3), 3 (blue).

Table 1. Crystal data, data collection and structure refinement.
Compound
1
2
3
[C36H36N10Ni2O4]2+·2(ClO4)-
·H2O
-
[C14H14CoN8O2]+·ClO4
Formula
[C14H10CuN4OS]n
Formula
Crystal system
Space group
a(Å)
b(Å)
c(Å)
345.86
monoclinic
P21/n
5.66016(12)
14.5908(3)
16.7539(4)
90
94.970(2)
90
1378.44(5)
4
1007.08
monoclinic
I2/a
19.7348(4)
10.4539(2)
20.2919(4)
90
90.861(2)
90
4185.86(14)
4
484.71
triclinic
P-1
8.3696(5)
10.3786(5)
11.9066(6)
106.261(4)
104.568(4)
102.500(4)
914.02(9)
2
 (º)
(º)
 (º)
V(Å3)
Z
Dx(g cm-3)
F(000)
1.67
700
3.686
1.60
2072
1.104
1.76
492
9.216
(mm-1)
 range (0)
Reflections:
collected
unique
4.02 – 76.26
3.59 – 26.65
4.10 – 76.59
6506
2845 (0.020)
2610
8292
4029 (0.019)
3603
7744
3770 (0.044)
3513
with
R(F) [I>2σ(I)]
0.034
0.095
0.041
0.135
0.046
0.126
wR(F2)
R(F) [all data]
wR(F2) [all
0.037
0.098
0.046
0.141
0.049
0.129
Goodness of fit
1.08
1.11
1.08
max/min  (e
Å-3)
0.39/-0.53
2.28/-1.04
0.53/-0.56

Table 2. Relevant geometrical parameters (Å, °) with s.u.’s in parentheses. Line “angles”
lists three largest angles around the metal center; A, B and C denote the least-squares planes
of phenyl/pyridine ring, chain, and terminal ring in case of (1).
(1)
(2)
(3)
Cu-N1A
Cu-N8A
2.031(2)
1.933(2)
Ni-O1A
Ni-O1A
2.0299(18)
2.0561(19)
Co-N1A
Co-N1B
1.914(2)
1.904(2)
(1/2-x,3/2-y, 3/2-
z)
Cu-O10A
Cu-N1B
Cu-S1B (x-
1,y,z)
1.9716(17)
1.928(2)
2.6819(7)
Ni-N8A
Ni-O11A
Ni-N1B
2.011(2)
2.0731(19)
2.122(2)
Co-N8A
Co-N8B
Co-O11A
1.860(2)
1.861(2)
1.914(2)
Ni-N1C
2.122(2)
172.98(8)
171.20(8)
169.24(7)
119.1(2)
Co-O11B
1.914(2)
176.10(10)
166.19(9)
165.92(10)
125.2(3)
Angles
173.20(9)
157.44(8)
100.83(8)
123.8(2)
C7-N8-N9
125.7(3)
N8-N9-C10
107.14(19)
115.7(2)
107.5(2)
107.4(2)
N1-C6-C7-N8
C6-C7-N8-N9
-0.3(3))
C1-C6-C7-N8
-0.8(4)
176.5(2)
177.2(2)
-1.2(4)
N1-C6-C7-N8
0.7(3)
2.1(3)
-178.8(2)
-179.193)
-179.2(2)
-175.4(3)
-174.8(3)
1.3(5)
-3.1(4)
179.4(3)
177.6(3)
C7-N8-N9-C10 -179.6(2)
N8-N9-C10-
C11
N9-C10-C11-
C12
-
N8-N9-C10-O11
177.48(19)
7.2(3)
N8-N9-C10-N12 180.0(2)
4.32(18)
A/B
0.7(2)
6.65(17)
6.40(11)
B/C
A/C
9.2(2)
8.61(12)

Table 3. Hydrogen bond data (Å, °). Ctg1 describes centroid of the N1C pyridine ring.
D
H
A
D-H
H···A
D···A
D-H···A
(2)
N9A
N12A
N12A
N12A
O1E
H9A
H12B
H12B
H12A
H1E
O1E
O2Di
O3Di
Cg1i
O1D
0.88
0.88
0.88
0.88
0.84
(3)
2.12
2.48
2.34
2.42
2.02
2.906(3)
3.166(4)
3.057(3)
3.238(3)
2.817(3)
149
135
139
154
159
N12A
N12A
N12B
N12B
H12A
H12B
H12C
H12B
O3C
O4Cii
O3Ciii
N9Biv
0.88
0.88
0.88
0.88
2.17
2.15
2.58
2.04
2.931(4)
2.999(4)
2.992(3)
2.915(4)
145
161
110
177
Symmetry codes: i ½-x,y,1-z; ii 1-x,-y,-z; iii -1+x,y,z; iv –x,1-y,1-z.
Table 4. The MIC and MBC values of the synthesized compounds (10-6 M).
Gram-Positive Bacteria Gram-Negative Bacteria
B. subtilis S. aureus
K. pneumoniae
E. coli
pound
MBC
MIC
MBC
MIC
MBC
MIC
MBC MIC
HL1
1
H2L2
444
3.5
111
1.7
444
7.0
222
0.8
444
222
28.3
558
444
444
56.6
558
56.6
56.6
558
8.0
279
4.0
558
279
558
558
15.8
63.4
63.4
1.9
15.8
304
63.4
609
129
2
HL3
3
609
304
8.0
609
304
609
129
609
129
32.3
64.7
16.1
64.7

* Three metal complexes from hydrazone Schiff base ligands were synthesized and
characterized.
* Molecular structures of the metal compounds were determined by single crystal X-ray
diffraction technique.
* The cyclic voltammetry behavior of these compounds was discussed.
* The Schiff base ligands and their metal compounds have been screened for their
antibacterial and in vitro anticancer activities.

In this paper, metal chelates of Schiff base derived from hydrazones have been prepared and
1
characterized by HNMR, IR, UV-Vis spectroscopy and cyclic voltammetry. Single crystal
X-ray crystallography studies confirm the structure of newly synthesized Schiff bases. The
Schiff bases act as tridentate ligands. The free ligands and metal compounds are screened for
their antibacterial activities against Gram-positive and Gram-negative bacteria. Further the
cytotoxic effect of the ligands and their metal compounds examined on cancer cell
lines showed that the metal compounds exhibit better activity than ligands.