Preparation, characterization, antimicrobial and anticancer activities of Schiff base mixed ligand complexes

Article abstract of DOI:10.1007/s10973-017-6491-1

A new Schiff base ligand (HL) derived from quinoline-2-carboxaldehyde with 2-aminophenol (1:1 molar ratio) and its mixed ligand complexes, viz. 2,2′-bipyridine (1:1:1 molar ratio), have been synthesized and characterized by elemental analysis, spectroscopic studies, X-ray diffraction, ESR, magnetic and thermal analysis. The molar conductance measurement of mixed ligand complexes in DMF showed that Zn(II) and Cd(II) complexes were nonelectrolytes; however, Cr(III), Mn(II), Fe(III), Co(II), Ni(II) and Cu(II) complexes were electrolytes. The transition metal complexes had octahedral geometry with a general molecular formulae [M(L)(2,2′-bipy)(H₂O)]Cl_x·nH₂O (M?=?Cr(III) (x?=?n?=?2), Mn(II) and Co(II) (x?=?1, n?=?0), Ni(II) and Cu(II) (x?=?n?=?1) and [M(L)(2,2′-bipy)Cl]Cl_x·nH₂O (M?=?Fe(III) (x?=?1, n?=?3), Zn(II) (x?=?0, n?=?1) and Cd(II) (x?=?0, n?=?2)). Also, Schiff base ligand and its mixed ligand complexes were screened against Gram-positive bacteria (Streptococcus pneumoniae, Bacillus subtilis), Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli) and fungal species (Aspergillus fumigatus, Candida albicans). Gentamicin, ampicillin and amphotericin B were used as standard drugs for Gram positive, Gram negative and antifungal activity, respectively. The results showed that all mixed ligand complexes have antimicrobial activity higher than free Schiff base ligand. In addition, anticancer activity of Schiff base ligand and its mixed ligand metal complexes were also tested against breast cancer cell line (MCF-7) and colon cancer cell line (HCT-116). Cd(II) complex showed the highest IC₅₀ against two cell lines.

Full text of DOI:10.1007/s10973-017-6491-1

J Therm Anal Calorim
DOI 10.1007/s10973-017-6491-1
Preparation, characterization, antimicrobial and anticancer
activities of Schiff base mixed ligand complexes
1
2
3
H. F. Abd El-Halim
•
M. M. Omar
•
Mahmoud N. Anwar
Received: 20 October 2016 / Accepted: 22 May 2017
Ó Akad e´ miai Kiad o´ , Budapest, Hungary 2017
Abstract A new Schiff base ligand (HL) derived from
quinoline-2-carboxaldehyde with 2-aminophenol (1:1
respectively. The results showed that all mixed ligand
complexes have antimicrobial activity higher than free
Schiff base ligand. In addition, anticancer activity of Schiff
base ligand and its mixed ligand metal complexes were
also tested against breast cancer cell line (MCF-7) and
colon cancer cell line (HCT-116). Cd(II) complex showed
the highest IC50 against two cell lines.
0
molar ratio) and its mixed ligand complexes, viz. 2,2 -
bipyridine (1:1:1 molar ratio), have been synthesized and
characterized by elemental analysis, spectroscopic studies,
X-ray diffraction, ESR, magnetic and thermal analysis. The
molar conductance measurement of mixed ligand com-
plexes in DMF showed that Zn(II) and Cd(II) complexes
were nonelectrolytes; however, Cr(III), Mn(II), Fe(III),
Co(II), Ni(II) and Cu(II) complexes were electrolytes. The
transition metal complexes had octahedral geometry with a
Keywords Mixed ligand complexes Á Schiff base Á
0
Quinoline Á (2,2 -Bipy) Á Antibacterial activity Á Anticancer
activity
0
general molecular formulae [M(L)(2,2 -bipy)(H O)]Cl Á
2
x
nH O (M = Cr(III) (x = n = 2), Mn(II) and Co(II) (x =
2
0
1
, n = 0), Ni(II) and Cu(II) (x = n = 1) and [M(L)(2,2 -
Introduction
bipy)Cl]Cl ÁnH O (M = Fe(III) (x = 1, n = 3), Zn(II)
x
2
(
x = 0, n = 1) and Cd(II) (x = 0, n = 2)). Also, Schiff
Mixed ligand complexes of Schiff base which have nitrogen,
oxygen and sulfur donor atoms in their backbones play an
important role in biological process as exemplified by many
instances in which enzymes were known to be activated by
metal ions [1–3]. Among mixed ligand complexes derived
from quinoline and quinoline derivative [4–6], quinolinones
are the most important class of heterocyclic compounds and
a part of the alkaloid family [7]. Quinolines have emerged as
potential therapeutic agents because of their conformational
rigidity and improved physical properties, such as charge
density or lipophilicity, and pharmacological advantages
such as metabolic stability and oral bioavailability [7, 8].
Quinolines, considered as the backbone for most natural
products, were used for the design of many synthetic com-
pounds having diverse pharmacological applications such as
antibacterial, antifungal [9, 10], anticancer [11], antimalarial
and antiviral [12], antiproliferative [13], antiplasmodial [14],
anti-inflammatory [15], anticonvulsant, antihypertensive
base ligand and its mixed ligand complexes were screened
against Gram-positive bacteria (Streptococcus pneumo-
niae, Bacillus subtilis), Gram-negative bacteria (Pseu-
domonas aeruginosa, Escherichia coli) and fungal species
(
Aspergillus fumigatus, Candida albicans). Gentamicin,
ampicillin and amphotericin B were used as standard drugs
for Gram positive, Gram negative and antifungal activity,
Electronic supplementary material The online version of this
article (doi:10.1007/s10973-017-6491-1) contains supplementary
material, which is available to authorized users.
&
H. F. Abd El-Halim
Hanan.Farouk2@yahoo.com
1
2
3
Pharmaceutical Chemistry Department, Faculty of Pharmacy,
Misr International University, Cairo, Egypt
Chemistry Department, Faculty of Science, Cairo University,
Giza, Egypt
[16], analgesic, vasorelaxing [17], immunosuppressive [18],
El-Nasr Co. for Intermediate Chemicals (NCIC), Giza, Egypt
and as a basis of development of many medicinal drugs used
123

H. F. Abd El-Halim et al.
as potential application as DNA-targeted chemotherapeutics
19] and antioxidant [20]. In chemistry, quinolines can be
EDTA solution [25–27]. FT-IR spectra were recorded on a
-1
[
Perkin-Elmer 1650 spectrometer 4000–400 cm in KBr
1
pellets. H-NMR spectra, as a solution in DMSO-d , were
used as corrosion inhibitor [21], detector [22], catalytic
activity [23] and sensor [24].
6
recorded on Varian-Oxford Mercury 300 MHz ‘‘NMR 300’’
at room temperature using TMS as an internal standard. Mass
spectra were carried out by the EI technique at 70 eV using
MS-5988 GS-MS Hewlett–Packard instrument at the
Microanalytical Center, National Center for Research, Egypt.
In the present work, a new Schiff base (HL) ligand
derived from the condensation of quinoline-2-carboxalde-
hyde with 2-aminophenol and its mixed ligand complexes,
0
viz. 2,2 -bipyridine with a series of transition metal ions of
-3
Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and
Cd(II), have been synthesized. The Schiff base ligand and
its mixed ligand complexes were characterized by using
Molar conductivities of 10 M solutions of the solid com-
plexes in DMF were measured using Jenway 4010 conduc-
tivity meter. Melting points were measured by Stuart melting
point—SMP 30 UK. The molar magnetic susceptibility was
measured on powdered samples using the Faraday method,
the diamagnetic corrections were made by Pascal’s constant,
1
elemental analysis, IR spectra, HNMR, mass spectrum,
UV–visible analysis, conductivity measurement, magnetic
behavior and electronic spectra, solid reflectance, ESR,
thermal analysis and X-ray diffraction. The antimicrobial
activities of Schiff base ligand and the mixed ligand
complexes were tested. In addition, anticancer activity of
Schiff base ligand and its mixed ligand metal complexes
were tested against breast cancer cell line (MCF-7) and
colon cancer cell line (HCT-116).
and Hg[Co(SCN) ] was used as a calibrant. UV–visible
4
spectra were carried out on UV mini-1240, UV–Vis spec-
trophotometer Shimadzu. The thermogravimetric analysis
(TG and DTG) of the solid complexes was carried out using
Shimadzu TGA-50H thermal analyzer, flow rate of
-1
10 °C min atmosphere and nitrogen with flow rate of
-
1
2
0 mL min , from 25 to 1000 °C. The X-ray powder
diffraction analyses were carried out using Philips Analytical
X-ray BV, diffractometer type PW 1840. Radiation was
provided by copper target (Cu anode 2000 W) high-intensity
X-ray tube operated at 40 kV and 30 mA. Divergence and
the receiving slits were 1 and 0.15 mm, respectively. Elec-
tron spin resonance spectra were also recorded by JES-
FE2XG ESR spectrophotometer at atomic energy commis-
sion. Antibacterial, antifungal and anticancer activities were
carried out at the Regional Center for Mycology and
Biotechnology, AL-Azhar University, Egypt.
Experimental
Materials
All chemicals were purchased and used without further
purification. Quinoline-2-carboxaldehyde, 2-aminophenol
0
and 2,2 -bipyridine were supplied from Arcos organic—
USA, Combrain chemical and Fluka Chemie, respectively.
Metal chloride salts including CrCl Á6H O, MnCl Á2H O
3
2
2
2
(
Sigma), FeCl Á6H O (Prolabo), CoCl Á6H O, NiCl Á6H O,
3
2
2
2
2
2
CuCl Á2H O, ZnCl Á2H O and CdCl (BDH) were also
Synthesis of Schiff base ligand (HL)
2
2
2
2
2
used. Dimethylformamide (DMF) 97% and ethanol (99%,
5%) (Adwic) have been used as organic solvents.
9
Quinoline-2-carboxaldehyde (2.5 g, 3.18 mmol) dissolved
in 50 mL of DMF was added to 2-aminophenol (1.59 g,
3.18 mmol) and dissolved in 50 mL of ethanol, in a molar
ratio 1:1. The mixture was refluxed for 2 h. A dark brown
solid was precipitated, filtered, washed with ethanol and
weighed. The yield was 79%. Scheme 1 shows the gen-
eral reaction of synthesis and structure of Schiff base
ligand.
Physical measurements and analytical techniques
Microanalysis of carbon, hydrogen and nitrogen was carried
out at the Microanalytical Center, Cairo University, Egypt,
using CHNS-932 (LECO) Vario Elemental Analyzer. Metal
ions have been determined by titration against standard
NH2
HO
EtOH\ DMF
2hr Reflux
+
N
N
N
CHO
HO
Quinoline-2-carboxaldhyde
2-aminophenol
Schiff base (HL)
Scheme 1 The general reaction for the synthesis of Schiff base ligand (HL)
1
23

Preparation, characterization, antimicrobial and anticancer activities of Schiff base mixed…
Synthesis of mixed ligand metal complexes
An ethanolic solution of metal chloride of Cr(III), Mn(II),
Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) (0.374,
0
.227, 0.379, 0.335, 0.239, 0.242 and 0.334, 0.306 g
(
1.4 mmol)) was added to a mixture of (0.35 g, 1.4 mmol)
Schiff base ligand, HL dissolved in 50 mL DMF and
0
(
0.225 g, 1.4 mmol) of 2,2 -bipyridine dissolved in 20 mL
of EtOH, in a molar ratio 1:1:1. The mixture was refluxed
for 2 h. The solid precipitates of metal complexes were
filtered and washed with small portion of ethanol, then air-
dried and weighed. The percent yield of mixed ligand
complexes is mentioned in Table 1. The general reaction
for synthesis of mixed ligand complexes and their general
structure is represented in Scheme 2.
Biological testing
Antibacterial and antifungal
Antimicrobial tests were carried out using the agar well-
diffusion method [28]. The free Schiff base ligand (HL)
and the mixed ligand complexes were tested in vitro for
their antibacterial activity against the Gram-positive bac-
teria (Streptococcus pneumoniae (RCMB010010), Bacillis
subtilis (RCMB 010067)) and Gram-negative bacteria
(
Pseudomonas aeruginosa (RCMB 010043), Escherichia
coli (RCMB 010052)). Antifungal activity was carried out
against Aspergillus fumigatus (RCMB 02568) and Candida
albicans (RCMB 05036) using Sabouraud dextrose agar
medium. Gentamicin, ampicillin and amphotericin B were
used as standard drugs for Gram positive, Gram negative
and antifungal activity, respectively. DMSO was used as
solvent control. The compounds were tested at a concen-
-
1
tration of (5 mg mL ) against both bacterial and fungal
strains. The sterilized media were poured onto the steril-
ized petri dishes (20 mL, each petri dish) and allowed to
solidify. Wells of 6 mm diameter were made in the
solidified media with the help of sterile borer. A sterile
swab was used to evenly distribute microbial suspension
over the surface of solidified media and solution, and the
tested samples were added to each well with the help of
micropipette. The plates were incubated at 37 °C for 24 h
in case of antimicrobial activity and at 25 °C for 48 h for
antifungal activity. These tests were carried out in tripli-
cate, and zone of inhabitation was measured in mm scale.
Anticancer activity
The cytotoxicity evaluation was carried out using viability
assay. The free Schiff base ligand and its mixed ligand
complexes were tested against breast cell line (MCF-7) and
colon cell line (HCT-116). The cells were propagated in
123

H. F. Abd El-Halim et al.
Scheme 2 Synthesis of mixed
ligand metal complexes of
Schiff base (HL) with (2,2 -
Bipy), a M = Cr(III)
0
N
N
N
N
+
+
MCl /MCl
2
3
(
(
x = n = 2), Mn(II) and Co(II)
x = 1, n = 0), Ni(II) and
HO
EtOH\ DMF
2h Reflux
Cu(II) (x = n = 1) and
b M = Fe(III) (x = 1, n = 3),
Zn(II) (x = 0, n = 1), Cd(II)
HL
(
x = 0, n = 2)
N
N
N
H O
N
Cl
2
M
M
N
O
N
O
Cl .nH O
Cl .nH O
x
2
x
2
N
N
(b)
(a)
Dulbecco’s modified Eagle’s medium (DMEM) supple-
mented with 10% heated-inactivated fetal bovine serum, 1%
for at least 30 min. The stain was removed and the plates
were rinsed using tap water until all excess stain is removed.
Glacial acetic acid (30%) was then added to all wells and
mixed thoroughly, and then, absorbance of the plates was
measured after gently shaken on Microplate reader (TECAN,
Inc), using a test wavelength of 490 nm. All results were
corrected for background absorbance detected in wells
without added stain. Treated samples were compared with
the cell control in the absence of the tested compounds. All
experiments were carried out in triplicate. The cell cytotoxic
effect of each tested compound was calculated [29].
-1
L-glutamine, HEPES buffer and 50 lg mL gentamycin.
All cells maintained at 37 °C in a humidified atmosphere
with 5% CO and were subcultured two times a week. For
2
cytotoxicity assay, the cells were seeded in 96-well plate at a
4
cell concentration of 1 9 10 cells per well in 100 lL of
growth medium. Fresh medium containing different con-
centration of the tested sample was added after 24 h of
seeding. Serial twofold dilution of the tested chemical
compound was added to confluent cell monolayers into
9
6-well, flat-bottomed microtiter plates (Falcon, NJ, USA)
using a multichannel pipette. The microtiter plates were
incubated at 37 °C in a humidified incubator with 5% CO2
for a period of 48 h. Three wells were used for each con-
centration of the test sample. Control cells were incubated
without test sample and without DMSO. The little percentage
of DMSO present in the wells (maximal 0.1%) was found not
to affect the experiment. After incubator of wells for 24 h at
Results and discussion
Elemental analyses
The results of elemental analyses with suggested molecular
formula and physical properties of Schiff base ligand and
its mixed ligand complexes are shown in Table 1. The
Schiff base and its mixed ligand complexes were insoluble
in most common organic solvents except DMF and DMSO.
3
7 °C, various concentrations of sample (50, 25, 12.5, 6.25,
.125 and 1.56 lg) were added, and the incubation was
3
continued for 48 h and viable cells yield was determined by a
colorimetric method. The 50% inhibitory concentration
(
IC ), the concentration required to causes toxic effects in
50
Molar conductance measurements
5
0% of the cells, was estimated from graphic plots. In brief,
after the end of the incubation period, media were aspirated
and the crystal violet solution (1%) was added to each well
The molar conductance values of the synthesized com-
-
plexes obtained in DMF as a solvent with (1 9 10 M)
3
1
23

Preparation, characterization, antimicrobial and anticancer activities of Schiff base mixed…
-
1
concentration at room temperature are listed in Table 1.
The low molar conductance values of Zn(II) and Cd(II)
complexes showed non-electrolytic nature. However, the
molar conductance values of Cr(III), Mn(II), Fe(III),
Co(II), Ni(II) and Cu(II) complexes showed that these
chelates were ionic in nature.
spectrum also showed a band at 29,411 cm which may
be attributed to ligand-to-metal charge transfer. The mag-
netic momentum value was found to be 5.44 BM which
was assigned to an octahedral geometry [30, 31]. In Ni(II)
-
1
complex, three bands at 21,594, 17,301 and 15,873 cm
were shown, respectively. The bands were corresponding
3
to A g(F) ? T g(P), A g(F) ? T g(F) and A2g
(F) ? T g transitions. The spectrum showed band at
3
3
3
3
2
3
1
2
1
UV–Vis studies
1
-1
2
5,000 cm
that may be attributed to ligand-to-metal
Absorption spectral data of the free Schiff base ligand (HL)
and its mixed ligand complexes were carried out in DMF.
UV–Vis spectra were recorded for these complexes with
charge transfer. The magnetic momentum value was 3.13
BM which was assigned to an octahedral geometry
[30, 31]. The diffused reflectance spectrum of Cu(II)
-1
-
4
(
1 9 10 M) solutions in the range of 200–700 nm. A
showed two bands at 15,822 and 21,321 cm
2
corre-
2
2
2
band at 267 nm may be attributed to p–p* transition of the
aromatic ring. The second band observed at 310 nm can be
attributed to n–p* electronic transition of azomethine
group in the free Schiff base ligand [30]. In the spectra of
the mixed ligand complexes, the two bands were shifted to
higher frequencies (bathochromic shift) where the p–p*
and n–p* transition bands were observed at 269–282 and
sponding to Eg ? T g(D) and B g ? A g transitions.
-1
2
1
1
The spectrum showed band at 29,199 cm which may be
attributed to ligand–metal charge transfer. The magnetic
momentum value was 1.92 BM which was assigned to the
octahedral geometry [30, 31]. The Zn(II) and Cd(II) com-
plexes were diamagnetic and have octahedral geometry
according to the suggested empirical formula listed in
Table 1.
3
15–351 nm, respectively, due to the metals chelation
(
Supplementary Table 2). The spectra of Cr(III), Mn(II),
Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes
showed absorption bands at 440, 481, 425, 420, 510, 430,
Mass spectrum
4
45 and 430 nm, respectively, which may be assigned to
The electron impact mass spectrum of Schiff base ligand
(HL) was recorded and investigated at 70 eV of electron
energy. The mass spectra of the studied Schiff base ligand
splitting of d–d orbital of metal ions. The Co(II), Ni(II) and
Cu(II) complexes showed band at 333, 331 and 330 nm,
respectively, which may be assigned to ligand-to-metal
charge transfer.
0
(Scheme 3a) and [Cr(L)(2,2 -bipy)(H O)]Cl Á2H O (Sche-
2
2
2
me 3b) complex were characterized by moderate to high
relative intensity molecular ion peaks. The abundance of the
molecular ion depends mainly on the structure. The molec-
ular ion peak was found at m/z = 246 amu and at m/z = 580
amu for ligand and Cr(III) complex, respectively.
Electronic spectra and magnetic measurements
The electronic spectra of metal complexes showed differ-
ent bands at different wavelengths. The diffused reflectance
spectrum of Cr(III) complex showed three bands at 28,571,
IR spectra
-
1
2
5,000 and 12,626 cm
, respectively, which were
4
4
4
assigned to the three
4
T g(F) and A g(F) ? T g(P) transitions. The magnetic
susceptibility leff value was 4.47 BM which indicated the
octahedral geometry [30, 31]. The diffused reflectance
spectrum of Mn(II) complex showed three bands at 25,000,
A g ? T g(F),
A g ?
The data of the IR spectra of Schiff base ligand (HL) and
the mixed ligand complexes are listed in Table 2. The IR
spectra of the complexes were compared with those of the
free ligand in order to determine the coordination sites that
may be involved in chelation. There were some guide
peaks, in the spectra of the ligand, which were of good help
for achieving this goal. The position and/or the intensities
of peaks were expected to be changed upon chelation. New
peaks also appeared due to chelation. The IR spectra of
2
2
2
4
4
1
2
1
-
1
2
2,727 and 15,873 cm , respectively, which correspond
4
4
6
4
6
6
to T g ? A g, T g(G) ? A g and T g(D) ? A g
1
1
2
1
1
1
transitions. The complex had leff value 5.72 BM, which
suggested an octahedral geometry [30–32]. The diffused
reflectance spectrum of Fe(III) complex showed two bands
-
1
Schiff base ligand showed strong band at 1662 cm which
-
1
at 21,978 and 17,699 cm
6
A g ? T g(G), A ? T g transitions. The magnetic
which were assigned to
may be attributed to t(CH=N) of azomethine group. The
band was shifted by 5–22 cm to lower wavenumbers in
6
5
-1
1
2
1
1
momentum value was found to be 5.38 BM which was
assigned to an octahedral geometry [31]. Co(II) complex
most complexes or disappeared as in Cu(II) and Cd(II)
complexes, indicating its involvement in the coordination
-1
-
1
showed three bands at 23,923, 17,035 and 15,873 cm
4
,
[7, 32]. A broad band at 3440 cm was assigned to the
4
respectively, which were assigned to T g ? T g(F),
presence of t(OH) of phenolic group [7, 33]. A medium-
1
2
4
4
4
4
-1
T g ? A g(F) and T g(F) ? T g(P) transitions. The
intensity band was shown at 1282 cm
which was
1
2
1
1
123

H. F. Abd El-Halim et al.
Scheme 3 a Mass
fragmentation pattern of Schiff
base ligand (HL). b Mass
fragmentation pattern of
(a)
N
N
0
[Cr(L)(2,2 -bipy)H
complex
2
O]Cl
2
Á2H
2
O
HO
m/z = 246, (f = 248; RI = 27%)
+
N
+
N
m/z = 156, (f = 155; RI = 100%)
N
HO
m/z = 220, (f = 221; RI = 2%)
+
N
+
m/z = 128, (f = 129; RI = 54%)
N
+
m/z = 91, (f = 91; RI = 4%)
+
m/z = 78, (f = 78; RI = 34%)
N
m/z = 79, (f = 79; RI = 34%)
+
m/z = 64, (f = 66; RI = 11%)
+
C H
4
4
m/z = 52, (f = 52; RI = 14%)
-
1
corresponding to the presence of phenolic t(C–O) group. It
higher wavenumbers (2–7 cm ) indicating the involve-
ment of the nitrogen atom of pyridine into the coordination
sphere. The in-plane bending vibration of the pyridyl ring
-
1
was shifted to higher wavenumbers by (27–35 cm
)
during the complexation, indicating the coordination of
metal ions with deprotonated phenolic group confirmed by
the disappearance of the stretching phenolic band [7]. The
IR spectrum of the ligand showed a sharp and strong band
-
1
of the ligand d(C=N) band was observed at 620 cm and
-
1
for the complexes at 628–658 cm which further support
the coordination via pyridyl nitrogen [34]. Upon chelation
of bipy, the stretching vibration of the C=N functional
-
1
at 1592 cm , which could be attributed to the vibration
-
1
t(C=N) of the pyridyl ring [34]. The band was shifted to
group of free bipy at 1528 cm was found to be shifted to
1
23

Preparation, characterization, antimicrobial and anticancer activities of Schiff base mixed…
(b)
N
H O
N
2
H O
2
Cr
Cr
O
.2H
Cl2 2O
N
N
Cl
N
N
m/z = 580, (f = 580; R.I. = 24%)
m/z = 264, (f = 262; R.I. = 26%)
N
N
H O
2
Cl .H O
2
2
+
Cr
Cr
O
N
N
N
Cl
H O
2
N
m/z = 406, (f = 406; R.I. = 10%)
Cr
O
N
N
m/z = 246, (f = 244; R.I. =100%)
+
m/z = 473,(f = 473; R.I. = 3%)
+
N
H O
N
2
N
Cr
.Cl
N
H O
2
O
+
Cr
O
N
m/z = 355, (f = 353; R.I. = 14%)
m/z = 317,(f = 317; R.I. = 6%)
N
Cr
N
+
N
N
+
N
.Cl
m/z = 439, (f = 439; R.I. = 3%)
Cr
N
O
N
Cr
O
m/z = 338, (f = 335; R.I. = 2%)
m/z = 299,(f = 299; R.I. = 10%)
+
Cr
+
N
N
N
N
+
m/z = 204, (f = 208; R.I. = 9%)
Cr
N
+
m/z = 283, (f = 283; R.I. =3%)
Cr
m/z = 180, (f = 181; R.I. = 2%)
Cr
O
m/z = 143, (f = 145; R.I. = 8%)
+
+
N
N
Cr
Cr
m/z = 130, (f = 131; R.I. = 5%)
m/z = 258, (f = 257; R.I. = 2%)
Scheme 3 continued
-
1
-1
-1
higher wavenumbers (1566–585 cm ) [35, 36]. The
characteristic out-of-plane bending modes of free bipy at
(836–840 cm ) and (630–653 cm ) in the complexes,
respectively [35, 36]. Broad absorption bands were existing
in spectra of metal complexes in the region from 3414 to
-
48 and 656 cm were shifted to lower wavenumbers
1
8
123

H. F. Abd El-Halim et al.
-1
Table 2 Characteristic IR bands (cm ) for Schiff base ligand (HL) and its mixed ligand complexes
Compound
t(H
2
O)
t(OH)
t(CH=N)
t(C–O)
t(C=N)
of bipy
t(C=N)/pyridyl
ring of quinoline
t(M–N)
t(M–O)
HL
–
–
3440 b
1662 s
1282 m
–
–-
1592 m
–
–
–
0
2
,2 -Bipy
–
–
–
–
–
–
–
–
–
–
1528 w
1566 w
1580 w
1579 w
1569 w
1581 w
1575 w
1571 w
1585 w
–
–
0
[
[
[
[
[
[
[
[
Cr(L)(2,2 -bipy)(H
0
2
O)]Cl
2
Á2H
2
O
3414 b/h
3431 b/w
3428 b/h
3427 b/w
3426 b/h
3431 b/m
3430 b/w
3420 b/w
1644 s
1312 m
1314 m
1311 m
1309 m
1313 w
1312 m
1315 m
1317 m
1600 m
1595 m
1599 m
1597 m
1598 m
1598 m
1599 m
1599 m
450 w
479 w
448 w
447 w
425 w
466 w
412 w
431 w
526 w
540 w
505 w
522 w
520 w
540 w
530 w
525 w
Mn(L)(2,2 -bipy)(H
0
2
O)]Cl
1657 w
1657 h
1653 w
1640 w
Disappeared
1655 w
Disappeared
Fe(L)(2,2 -bipy)Cl]ClÁ3H
2
O
0
Co(L)(2,2 -bipy)(H
0
2
O)]Cl
O)]ClÁH
O)]ClÁH
Ni(L)(2,2 -bipy)(H
0
2
2
O
Cu(L)(2,2 -bipy)(H
0
2
2
O
Zn(L)(2,2 -bipy)Cl]ÁH
2
O
0
Cd(L)(2,2 -bipy)Cl]Á2H
2
O
b broad, w weak, m medium, s sharp
-
431 cm which may be assigned to stretching vibration
1
3
temperature range from 150 to 700 °C with total mass loss
of 100% (calcd. 100%). The first step of decomposition
range (150–465 °C) involved mass loss of 37.50% (calcd.
37.90%) which was corresponding to loss of C H O
of t(OH) of hydrated or coordinated water molecules
which were accompanied with characteristic bending band
-
from 833 to 844 cm [1, 7, 31]. New bands appeared in
1
6
6
-
1
region 412–479 and 505–540 cm corresponding to the
metal coordination through N (M–N) and O (M–O) atoms,
respectively [1, 31].
molecule. Second step of decomposition within the range
of 465–700 °C with mass loss of 62.50% (calcd. 62.09%)
corresponds to the loss of C H N molecule.
1
0 6 2
Thermogravimetric analysis TG of Cr(III) complex
showed its decomposition in three steps within the temper-
ature range derived from 30 to 700 °C and a total mass loss of
1
H NMR spectra
7
8.77% (calcd. 78.49%). The first decomposition step
1
The H NMR spectrum of the free Schiff base ligand (HL)
occurred within the temperature range 30–150 °C with mass
loss of 4.66% (calcd. 4.65%) corresponding to the loss of
hydrated and coordinated water molecules. Second decom-
position step occurred within the temperature range
(150–400 °C) with 17.51% (calcd. 15.52%) corresponding
was characterized by singlet proton of azomethine (CH=N)
at d = 8.65 ppm (s, 1H), multiple signals at d = 6.38–
8
.13 ppm (m, 10H) referring to the aromatic ring and
quinoline and characteristic singlet signal of phenolic OH
1
proton at d = 10.80 ppm (s, 1H). The H NMR spectra of
Zn(II) and Cd(II) complexes were characterized by signifi-
to the loss of 2NH and 2HCl molecules. Third decomposi-
3
tion step occurred within the temperature range 400–700 °C
with mass loss of 58.60% (calcd. 58.62%) corresponding to
the loss of C H N O molecule. Finally, 21.23% (calcd.
cant down-field shifts in the peak position of azomethine
(
CH=N) proton at d = 8.69 and 8.73 ppm, respectively,
2
2 18 2
indicating the complexation through azomethine group. The
absence of phenolic proton signal supported its involvement
in the chelation through proton displacement. Also, the res-
onance of aromatic protons had been shiftedto 6.48–8.56and
21.51%) metallic residue remained in a form of metal oxide
1/2(Cr O ) residue contaminated with carbon.
2
3
Mn(II) complex showed a decomposition in two steps
within the temperature range derived from 50 to 700 °C
with total mass loss of 81.33% (calcd. 81.59%). The first
decomposition step occurred within the temperature range
50–500 °C with mass loss of 51.13% (calcd. 51.23%)
which was corresponding to the loss of coordinated water
and C H N molecules. Second decomposition step
6
.47–8.70 ppm (m, 18H), respectively, as a result of the
0
coordination of metal ions with quinoline and (2,2 -bipy)
nitrogen atoms [37]. Signals at d = 3.33 ppm (s, 2H) and
d = 3.28 ppm (s, 4H) had been appeared, respectively, due
to the presence of hydrated water in Zn(II) and Cd(II) com-
plexes [31].
1
4 12 2
occurred within the temperature range 500–700 °C with
mass loss of 30.20% (calcd. 30.36%) which was corre-
sponding to loss of HCl and C H N molecules. Finally,
Thermal analysis
1
0 6 2
18.67% (calcd. 18.41%) MnO remained as residue con-
Thermogravimetric analysis TG curve of Schiff base ligand
taminated with carbon.
(
HL) and mixed ligand complexes is given in Table 3. The
Fe(III) complex showed a decomposition in three steps
within the temperature range derived from 45 to 700 °C
Schiff base ligand was decomposed in two steps within the
1
23

Preparation, characterization, antimicrobial and anticancer activities of Schiff base mixed…
123

H. F. Abd El-Halim et al.
Fig. 1 ESR spectrum of
0
4.00E + 02
[Cu(L)(2,2 -bipy)(H
complex
2
O)]ClÁH
2
O
2
.00E + 02
.00E + 00
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
–
2.00E + 02
4.00E + 02
–
–6.00E + 02
–8.00E + 02
–1.00E + 03
–1.20E + 03
–1.40E + 03
data
with total mass loss 84.35% (calcd. 84.35%). The first
decomposition step occurred within the temperature range
which corresponding to the loss of C H N molecule.
16 12 2
Finally, 14.37% (calcd. 14.18%) metallic residue remained
as NiO.
45–175 °C with mass loss of 4.62% (calcd. 4.62%) corre-
sponding to the loss of hydrated water molecules. Second
Cu(II) complex showed a decomposition in three steps
within the temperature range derived from 35 to 800 °C
with total mass loss of 80.72% (calcd. 80.11%). The first
decomposition step occurred within the temperature range
35–160 °C with mass loss of 6.60% (calcd. 6.70%) which
was corresponding to loss of hydrated and coordinated
water molecules. Second decomposition step occurred
within the temperature range 160–440 °C with mass loss of
35.40% (calcd. 35.72%) which was corresponding to the
loss of C H N and HCl molecules. Third decomposition
decomposition step occurred within the temperature range
1
75–420 °C with mass loss of 35.10% (calcd. 35.10%)
corresponding to loss of 2HCl, C H N molecules. Third
9
10 2
decomposition step occurred within the temperature range
20–700 °C with mass loss of 42.63% (calcd. 42.63%)
corresponding to the loss of C H N O molecule. Finally,
4
1
6 11 2
1
1
5.81% (calcd. 15.81%) metallic residue remained as
/2(Fe O ) contaminated with carbon.
2
3
Co(II) complex showed a decomposition occurred in
three steps within the temperature range derived from 40 to
1
0 8 2
step occurred within the temperature range 440–800 °C
with mass loss of 38.68% (calcd. 38.70%) which was
corresponding to the loss of C H N molecule. Finally,
800 °C with total mass loss of 83.89% (calcd. 83.88%).
The first decomposition step occurred within the tempera-
1
4 12 2
ture range 40–240 °C with mass loss of 3.49% (calcd.
19.28% (calcd. 18.89%) metallic residue remained as CuO
contaminated with carbon.
3
.49%) corresponding to the loss of coordinated water
molecules. Second decomposition step occurred within the
Zn(II) complex showed two decomposition steps which
occurred within the temperature range derived from 70 to
700 °C with total mass loss 84.50% (calcd. 84.84%). The
first decomposition step occurred within the temperature
range 70–500 °C with mass loss of 39.98% (calcd.
40.36%) corresponding to loss of hydrated water, C H N
10 8 2
temperature range 240–495 °C with mass loss of 37.15%
(
calcd. 37.14%) corresponding to loss of HCl and C H N
10 8 2
molecules. Third decomposition step occurred within the
temperature range 495–800 °C with mass loss of 42.48%
(
calcd. 42.48%) corresponding to the loss of C H N
15 10 2
molecule. Finally, 16.89% (calcd. 16.88%) metallic residue
remained as CoO contaminated with carbon.
and HCl molecules. Second decomposition step occurred
within the temperature range 500–700 °C with mass loss of
44.52% (calcd. 44.48%) corresponding to the loss of
C H N molecule. Finally, 15.59% (calcd. 15.16%)
Ni(II) complex showed a decomposition in three steps
within the temperature range derived from 45 to 700 °C
with total mass loss 85.63% (calcd. 85.82%). The first
decomposition step occurred within the temperature range
1
6 12 2
metallic residue remained as ZnO.
Cd(II) complex showed a decomposition occurred in
two steps within the temperature range derived from 75 to
700 °C with total mass loss 76.16% (calcd. 76.46%). The
first decomposition step occurred within the temperature
range 75–425 °C with mass loss of 43.28% (calcd.
43.18%) corresponding to the loss of two hydrated water
and C H N molecules. Second decomposition step
4
5–300 °C with mass loss of 13.36% (calcd. 13.37%)
which was corresponding to loss of hydrated, coordinated
water and HCl molecules. Second decomposition step
occurred in two stages within the temperature range
3
00–490 °C with mass loss 29.50% (calcd. 29.13%) which
corresponding to loss of C H N molecule. Third
1
0
8
2
15 10 2
decomposition step occurred within the temperature range
90–700 °C with mass loss of 42.75% (calcd. 43.32%)
occurred within the temperature range 425–700 °C with
mass loss of 32.88% (calcd. 33.00%) corresponding to the
4
1
23

Preparation, characterization, antimicrobial and anticancer activities of Schiff base mixed…
Table 4 Anti-microbial activities (antibacterial and antifungal) of Schiff base ligand (HL) and its mixed ligand complexes, the mean zone of
inhibition in (mm)
-
1
Compound
Inhibition zone diameter/mm mg
Antibacterial
Antifungal
Gram (?)
Gram (-)
Streptococcus
pneumoniae
Bacillus
subtilis
Pseudomonas
aeruginosa
Escherichia
coli
Aspergillus
fumigatus
Candida
albicans
HL
17.3
9.6
13.3
12.5
14.1
17.4
15.4
12.8
10.1
12.9
15.4
12.7
32.4
–
10.3
10.3
10.8
11.6
10.2
10.7
11.3
9.7
10.9
12.9
11.1
10.9
8.8
13.4
NA
18.9
16.4
16.7
16.7
11.2
15.4
14.9
25.8
–
11.5
NA
15.4
12.7
18.2
18.1
10.5
12.9
16.1
14.3
–
0
2
,2 -Bipy
0
[
[
[
[
[
[
[
[
Cr(L)(2,2 -bipy)(H
0
2
O)]Cl
2
Á2H
2
O
15.7
18.9
19.2
16.7
11.9
19.6
18.7
11.2
23.8
–
Mn(L)(2,2 -bipy)(H
0
2
O)]Cl
Fe(L)(2,2 -bipy)Cl]ClÁ3H
2
O
0
Co(L)(2,2 -bipy)(H
0
2
O)]Cl
O)]ClÁH
O)]ClÁH
9.9
Ni(L)(2,2 -bipy)(H
0
2
2
O
9.9
Cu(L)(2,2 -bipy)(H
0
2
2
O
8.9
Zn(L)(2,2 -bipy)Cl]ÁH
2
O
11.7
9.8
10.3
11.3
–
0
Cd(L)(2,2 -bipy)Cl]Á2H
2
O
Ampicillin
–
Gentamicin
17.3
–
19.9
–
–
–
Amphotericin B
–
–
23.7
25.4
Fig. 2 Antimicrobial activity of
0
Streptococcus pneumoniae
Bacillus subꢀlis
35
30
25
20
15
10
5
0
Schiff base ligand, 2,2 -bipy and
its mixed ligand complexes
Pseudomonas aeruginosa
Escherichia coli
Aspergillus fumigatus
Candida albicans
compound
loss of HCl, C H N molecules. Finally, 23.84% (calcd.
1
that g value \ 2.3 for covalent character of the metal–
0
10
2
ll
2
3.54%) of CdO remained as residue contaminated with
ligand bond and[2.3 for ionic character. g = 2.08, which
ll
carbon. Thermoanalytical curves are provided as Supple-
mentary Figure 1.
indicated the covalent character of the metal–ligand bond.
The trend gllð2:08Þ [ g?ð2:06Þ [ geð2:0023Þ observed for
this complex showed that the unpaired electron was
localized in dx2_y2 orbital of the Cu(II) ion and the spectral
features were characteristics of the axial symmetry [40]. In
axial symmetry, the g values were related by the expression
G ¼ ðgll À 2Þ=ðg? À 2Þ ¼ 4, where G is the exchange
interaction parameter referring to Hathaway and Billing
[41]. If the G value is greater than 4, it means that the
exchange interaction between Cu(II) centers in the solid
ESR study
The solid-state ESR spectrum of Cu(II) complex exhibited
axially symmetric g-tensor parameters (Fig. 1) with
gll\g?ð2:06Þ [ 2:0023, indicating that the copper site has
a d
ground-state characteristic of octahedral stereo-
x2_y2
chemistry [1, 38]. Kivelson and Neiman [39] had reported
123

H. F. Abd El-Halim et al.
Fig. 3 The relation between
M–O) bond strength and
inhibition zone diameter in
mm) of metal complexes
Streptococcus pneumoniae
Bacillus subꢀlis
(
30
(
Pseudomonas aeruginosa
Escherichia coli
25
20
15
10
5
0
Aspergillus fumigatus
Candida albicans
Cr(III)
Mn(II) Fe(III)
Co(II)
Ni(II)
Cu(II)
Zn(II)
Cd(II)
M-O
Compounds
Fig. 4 The relation between
M–N) bond strength and
inhibition zone diameter in
mm) of metal complexes
Streptococcus pneumoniae
Bacillus subꢀlis
(
30
(
Pseudomonas aeruginosa
Escherichia coli
25
20
15
10
5
0
Aspergillus fumigatus
Candida albicans
Cr(III)
Mn(II) Fe(III)
Co(II)
Ni(II)
Cu(II)
Zn(II)
Cd(II)
M-N
Compounds
state is negligible. However, when G is less than 4, this
means that considerable exchange interaction will be
indicated in the solid complex. The observed value for the
exchange interaction parameter was G = 2, which sug-
gested that significant exchange coupling was present.
b1/2 is the width at half maximum of the reference
diffraction peak measured in radians.
The dislocation density d indicates the number of dis-
location lines per unit area of the crystal. The value of d is
related to the average particle diameter (n) from the rela-
tion [44, 45]:
1
d ¼
ð2Þ
X-ray powder diffraction study
2
n
The XRD patterns for mixed ligand complexes showed
crystalline nature; however, it showed an amorphous nature
for Schiff base ligand. This might confirm that the presence
of metal ions change the XRD pattern of free Schiff base
ligand [42].
The value of n was calculated and found to be 38.98,
53.00, 33.75, 25.62, 35.66, 30.97, 32.00 and 27.11 nm. The
value of d was also calculated and found to be 0.00066,
0.00036, 0.00088, 0.00152, 0.00079, 0.00104,0.00098 and
-
2
0.0014 nm
for Cr(III), Mn(II), Fe(III), Co(II), Ni(II),
The average crystallite size (n) can be calculated from
the XRD pattern according to Debye–Scherrer equation
Cu(II), Zn(II) and Cd(II) complexes, respectively.
[
42, 43]:
Biological activity
Kk
n ¼ b
ð1Þ
Antibacterial activity
cos h
=2
1
0
˚
The antimicrobial activity of Schiff base ligand (HL), 2,2 -
bipy and its mixed ligand complexes is listed in Table 4
where k is the wavelength of X-ray radiation (1.542475 A),
K is a constant taken as 0.95 for organic compounds, and
1
23

Preparation, characterization, antimicrobial and anticancer activities of Schiff base mixed…
Table 5 The screening of anticancer activity of Schiff base ligand
HL) and its mixed ligand complexes using breast cell line (MCF-7)
and colon cell line (HCT-116)
the aromatic rings, this increased the lipophilic character,
(
favoring its permeation into the bacterial membrane and
hence causing the death of the organisms [31, 46, 47].
Compound
(MCF-7)
IC50 lg
(HCT-116)
IC50 lg
Antifungal activity
HL
[50
39.3
28
22.8
22.1
18.8
38.9
21.5
18.2
11.9
10.7
9.2
1
Cr(L )(2,2 -Bipy)(H
0
[
[
[
[
[
[
[
[
2
O)]Cl
2
Á2H
2
O
0
The antifungal activity of Schiff base ligand, 2,2 -bipy and
0
Mn(L)(2,2 -Bipy)(H
0
2
O)]Cl
its complexes against Aspergillus fumigatus and Candida
albicans is listed in Table 4 and presented in Fig. 2. The
results showed that the activity of all metal complexes was
higher than free ligands except Ni(II) complex which
showed less activity than free ligands. Cd(II) complex
showed activity higher than the standard. The antifungal
activity of complexes in relation to metal oxygen (M–O)
and metal nitrogen (M–N) bonds strength is presented in
Figs. 3 and 4. The activity of complexes was decreased as
(M–O) and (M–N) bond strength was increased. The results
may be due to the presence of chloride ion in complexes
which may enhance the antimicrobial activity due to the
formation of hypochlorous acid which was decomposed to
Fe(L)(2,2 -Bipy)Cl]ClÁ3H
2
O
43.3
24
0
Co(L)(2,2 -Bipy)(H
0
2
O)]Cl
O)]ClÁH
O)]ClÁH
Ni(L)(2,2 -Bipy)(H
0
2
2
O
22.7
19.9
20.9
6.02
Cu(L)(2,2 -Bipy)(H
0
2
2
O
Zn(L)(2,2 -Bipy)Cl]ÁH
2
O
0
Cd(L)(2,2 -Bipy)Cl]Á2H
2
O
and Fig. 2. The activity against Gram-positive bacteria
Streptococcus pneumoniae showed that Mn(II), Fe(III),
Cu(II) and Zn(II) complexes have higher activity than free
ligand. However, Co(II), Ni(II) and Cd(II) complexes
showed lower activity than the free ligand against Bacillus
subtilis organism. The activity against Gram-negative
bacteria Pseudomonas aeruginosa showed that Cu(II) and
Cd(II) complexes were less active than free ligand. How-
ever, Cr(III) and Cd(II) complexes showed higher activity
than free ligand against Escherichia coli. All metal com-
plexes recorded activity less than the standard drugs. The
antimicrobial activity of complexes in relation to metal
oxygen (M–O) and metal nitrogen (M–N) bond strength is
shown in Figs. 3 and 4. The activity of complexes against
Gram-positive bacteria was decreased as (M–O) bond
strength increased, while their activity was increased as
HCl acid and O . The oxygen oxidized the cellular com-
2
ponents and destroyed the microbes. The results may also
be explained due to the combination of chlorine with
membrane protein and enzyme [48, 49].
Anticancer activity
Screening the anticancer activity of Schiff base ligand,
0
2,2 -bipy and its mixed ligand complexes using breast
cancer cell line (MCF-7) and colon cancer cell line (HCT-
116) and the value of IC50 (a minimal concentration
required to inhibit 50% of cells growth) are listed in
Table 5 and plotted in Fig. 5. The results against breast
cancer cell line (MCF-7) showed that all metal complexes
have IC50 higher than free ligand. Cd(II) complex has the
highest activity of complexes. The complexes could be
ordered due to their activities as follows Cd(II) [ Cu(II) [
(
M–N) bond strength increased. The higher activity of
metal complexes could be explained on the basis of
chelation. As the polarity of the metal ion has been reduced
because of partial sharing of its positive charge with donor
groups of the ligand and the p-electron delocalization on
Fig. 5 Anticancer activity of
0
50
Schiff base ligand, 2,2 -bipy and
its mixed ligand complexes
45
40
35
30
25
20
15
10
5
0
MCF-7
HCT-116
HL
Cr(III)
Mn(II)
Fe(III)
Co(II)
Ni(II)
Cu(II)
Zn(II)
Cd(II)
2.2'-bipy
compound
123

H. F. Abd El-Halim et al.
Zn(II) [ Ni(II) [ Co(II) [ Mn(II) [ Cr(III) [ Fe(III) [
6. Melinmath SP, Venkatesh KB, Rekha ND, AshaIyengar T.
Mononuclear mixed ligand transition metal complexes: synthesis,
characterization, antioxidant and antimicrobial activity along
with DNA cleavage studies. IAJPR. 2015;5:2503–11.
0
2
,2 -bipy. The results against colon cancer cell line
(
HCT-116) showed that all metal complexes have IC50
higher than free ligand and complexes ordered due to
7. Creaven BS, Devereux M, Foltyn A, McClean S, Rosair G,
Thangella VR, Walsh M. Quinolin-2(1H)-one-triazole derived
Schiff bases and their Cu(II) and Zn(II) complexes: possible new
therapeutic agents. Polyhedron. 2010;29:813–22.
their activities as follows Cd(II) [ Zn(II) [ Cu(II) [
0
Ni(II) [ Mn(II) [ Co(II) [ Cr(III) [ Fe(III) [ 2,2 -bipy.
8
. Marcaccino S, Pepino R, Pozo MC, Basurto S, Garia-valverde M,
Torroba T. One-pot synthesis of quinolin-2-(1H)-ones via tandem
Ugi-Knoevenagel condensations. Tetrahedron Lett. 2004;45:
Conclusions
3
999–4001.
9
. Kulkarni NV, Hegde GS, Kurdekar GS, Budagumpi S, Sathisha
MP, Revankar VK. Spectroscopy, electrochemistry and structure
of 3d-transition metal complexes of thiosemicarbazones with
quinoline core: evaluation of antimicrobial property. Int J Rapid
Commun. 2010;43:235–46.
The following conclusions have been drawn from the ele-
mental analysis and spectroscopic studies. New Schiff base
ligand (HL) was prepared from a condensation reaction
between quinoline-2-carboxaldehyde and 2-aminophenol in
a molar ratio 1:1. Its mixed ligand transition metal com-
1
0. Sudha N, Selvi G. Synthesis, characterization and biological
studies on Fe(II) and Zn(II) quinoline Schiff Base complexes. Int
J Chem Tech Res. 2015;8:367–74.
0
plexes, viz. 2,2 -bipy with molar ratio 1:1:1, were also
synthesized and characterized. The metal complexes
showed electrolytic nature, except Zn(II) and Cd(II) com-
plexes were nonelectrolyte. Spectroscopic studies sup-
ported the suggested structure of the complexes, whereas
the metal ion coordinated through azomethine group, two
pyridyl nitrogen and phenolic group. The metal complexes
had octahedral geometry around the metal center. XRD
studies showed that mixed ligand complexes had crystalline
nature, while Schiff base ligand had an amorphous nature.
The complexes showed higher antibacterial and antifungal
activities than free Schiff base ligand. The Cd(II) complex
showed the highest IC50 against breast cancer cell line
11. Solomon VR, Lee H. Quinoline as a privileged scaffold in cancer
drug discovery. Curr Med Chem. 2011;18:1488–508.
1
2. Bentzinger G, De SW, Mulli e´ C, Agnamey P, Dassonville-Klimpt
A, Sonnet P. Asymmetric synthesis of new antimalarial amino-
quinolines through Sharpless aminohydroxylation. Tetrahedron
Asymmetry. 2016;27:1–11.
1
3. Anantacharya R, Manjulatha K, Satyanarayan ND, Santoshkumar
S, Kaviraj MY. Antiproliferative, DNA cleavage, and ADMET
study of substituted 2-(1-benzofuran-2-yl) quinoline-4-carboxylic
acid and its esters. Cogent Chem. 2016;2:2016. doi:10.1080/
23312009.1158382.
1
4. Nkoana W, Nyoni D, Chellan P, Stringer T, Taylor D, Smith PJ,
Hutton AT, Smith GS. Heterometallic half-sandwich complexes
containing a ferrocenyl motif: synthesis, molecular structure,
electrochemistry and antiplasmodial evaluation. J Organomet
Chem. 2014;752:67–75.
(
MCF-7) and colon cancer cell line (HCT-116).
1
1
5. Maddela S, Makulaa A, Maddela R. Synthesis of isatin-quinoline
conjugates as possible biologically active agents. Toxicol Envi-
ron Chem. 2014;96:1–11.
6. Muruganantham N, Sivakumar R, Anbalagan N, Gunasekaran V,
Leonard JT. Synthesis, anticonvulsant and antihypertensive
activities of 8-substituted quinoline derivatives. Biol Pharm Bull.
2004;2:1683–7.
References
1
. Mahmoud WH, Mahmoud NF, Mohamed GG, El-Sonbati AZ, El-
Bindary AA. Synthesis, spectroscopic, thermogravimetric and
antimicrobial studies of mixed ligands complexes. J Mol Struct.
17. Shinkai H, Ito T, Ida T, Kitao Y, Yamadu H, Uchida I. 4-Ami-
noquinolines: novel nociceptin antagonists with analgesic activ-
ity. J Med Chem. 2000;43:4667–77.
2
015;1095:15–25.
2
. El-Sonbati AZ, Belal AAM, El-Gharib MS, Morgan S.
Supramolecular structure, mixed ligands and substituents effect
on the spectral studies of oxovanadium(IV) complexes of
bioinorganic and medicinal relevance. Spectrochim Acta A.
18. Papageorgion C, Matt AV, Joergensen J, Anderson E, Wagner K,
Beerli C, Than T, Borex X, Florineth A, Rihs S, Schreier MH,
Weckbecker G, Hausser C. Aromatic quinolinecarboxamides as
selective, orally active antibody production inhibitors for pre-
vention of acute xenograft rejection. J Med Chem 2001;44:
1986–92.
2
012;95:627–36.
3
4
5
. Annaraj B, Balakrishnan C, Neelakantan MA. Synthesis, struc-
ture information, DNA/BSA binding affinity and in vitro cyto-
toxic studies of mixed ligand copper(II) complexes containing a
phenylalanine derivative and diimine co-ligands. J Photochem
Photobiol B. 2016;160:278–91.
. Neelaeni R, Vasantha S, Keerthana R, Sivakolunthu S, Angeline
T. DNA cleavage activity of novel schiff base copper(II) com-
plexes with sulfur containing-ligand (2-(2-methyl-thio)
phenylimino)methylphenol, N-benzylidine-2-methylthioaniline.
Asian J Pharm Clin Res. 2016;9:277–81.
`
19. Pascual-Alvarez A, Topala T, Estevan F, Sanz F, Alzuet-Pi n˜ a G.
Photoinduced and self-activated nuclease activity of copper(II)
complexes with N-(Quinolin-8-yl)quinolin-8-sulfonamide—
DNA and bovine serum albumin binding. Eur J Inorg Chem.
2016;7:982–94.
20. Mruthyunjayasswamy BHM, Vivekanand DB, Mahenra RK.
Synthesis, characterization and DNA cleavage studies of some
transition metal complexes derived from 5-chloro-3-phenyl-
0
N (tetrazolo[1,5-a]quinolin-4-ylmethylene)-1H-indole-2-carbo-
. Kudrat-E-Zahan M, Alim Abdul M, Haque MM, Lokonuzzaman
A, Sher AM, Saiidul IM. Studies on the mixed ligand complexes
of Co(II), Ni(II) and Cu(II) with phthalimide and heterocyclic
amines. Int J Mater Sci Appl. 2015;4:120–3.
hydrazide. Res J Pharm Biol Chem Sci. 2014;5:1057–70.
21. Mistry BM, Jauhari S. Synthesis and evaluation of some quino-
line Schiff bases as a corrosion inhibitor for mild steel in 1 N
HCl. Res Chem Intermed. 2013;39:1049–68.
1
23

Preparation, characterization, antimicrobial and anticancer activities of Schiff base mixed…
2
2
2
2. Veledo MT, Pelaez-Lorenzo C, Gonzalez R, de Frutos M, Diez-
Masa JC. Protein fingerprinting of Staphylococcus species by
capillary electrophoresis with on-capillary derivatization and laser-
induced fluorescence detection. Anal Chim Acta. 2010;658:81–6.
3. Sarmah PP, Deb B, Borah BJ, Fuller AL, Slawin AMZ, Woollins
JD, Dutta DK. Rhodium(I) carbonyl complexes of quinoline
carboxaldehyde ligands and their catalytic carbonylation reaction.
J Organomet Chem. 2010;695:2603–8.
36. Reddy PR, Shilpa A. Oxidative and hydrolytic DNA cleavage by
Cu(II) complexes of salicylidene tyrosine schiff base and 1,10-
phenanthroline/bipyridine. Polyhedron. 2011;30:565–72.
37. Sheikhshoaie I, Ebrahimipour SY, Lotfi N, Mague JT, Khaleghi M.
Synthesis, spectral characterization, X-ray crystal structure and
antimicrobial activities of two cis dioxido-vanadium(V) complexes
incorporating unsymmetrical dimalonitrile-based (NNO) Schiff
base ligands. Inorg Chim Acta. 2016;442:151–7.
38. Soliman MH, Hindy AM, Mohamed GG. Thermal decomposition
and biological activity studies of some transition metal com-
plexes derived from mixed ligands sparfloxacin and glycine.
J Therm Anal Calorim. 2014;115:987–1001.
39. Kivelson D, Meiman R. ESR studies on the bonding in copper
complexes. J Chem Phys. 1961;35:149–55.
40. Chandra S, Sangeetika X. EPR, magnetic and spectral studies of
copper(II) and nickel(II) complexes of schiff base macrocyclic
ligand derived from thiosemicarbazide and glyoxal. Spectrochim
Acta Part A. 2004;60:147–53.
41. Hathaway BJ. D.E. Billing DE. The electronic properties and
stereochemistry of mono-nuclear complexes of cu(II) ion. Chem
Rev. 1970;5:143–207.
42. El-Sonbati AZ, Diab MA, El-Bindary AA, Mohamed GG, Mor-
gan SM. Thermal, spectroscopic studies and hydrogen bonding in
supramolecular assembly of azo rhodanine complexes. Inorg
Chim. 2015;430:96–107.
43. El-Ghamaz NA, El-Sonbati AZ, Diab MA, El-Bindary AA,
Mohamed GG, Morgan SM. Correlation between ionic radii and
of metal azodye complexes and electrical conductivity. Spec-
trochim Acta A. 2015;147:200–11.
44. Velumania S, Mathew X, Sebatain PJ, Narayandass SK, Mana-
glaraj D. Structural and optical properties of hot wall deposited
CdSe thin films. Sol Energy Mater Sol Cells. 2003;76:347–58.
45. Sasavaraja S, Salaji DS, Bedre MD, Raghunandan D, Swamy PM,
Venkatarmam A. Solvo-thermal synthesis and characterization of
4. Qin J, Li T, Wang B, Yang Z, Fan L. A sensor for selective
3?
detection of Al based on quinoline Schiff-base in aqueous
media. Synth Met. 2014;195:141–6.
2
2
2
2
5. Flaschka HA. EDTA titration. 2nd ed. New York: Pergamon
Press; 1964. p. 81–6.
6. Vogel AI. Textbook of quantitative inorganic analysis. 4th ed.
London: Longman; 1978.
7. West TS. Complexometry with EDTA and related reagents. 3rd
ed. Pools: DBH Ltd.; 1969.
8. Scott AC. Laboratory control of antimicrobial therapy. In: Collee
JG, et al., editors. Practical medical microbiology. 13th ed.
Edinburgh: Churchill Livingstone; 1989. p. 161–81.
2
3
9. Mosmann T. Rapid colorimetric assay for cellular growth and
survival: application to proliferation and cytotoxicity assays.
J Immunol Methods. 1993;65:55–63.
0. Abd El-Halim HF, Mohamed GG, El-Dessouky MM, Mahmoud
WH. Ligational behaviour of lomefloxacin drug towards Cr(III),
Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Th(IV) and
UO2(VI) ions: synthesis, structural characterization and biologi-
cal activity studies. Spectrochim Acta Part A. 2011;82:8–19.
1. Mahmoud WH, Mohamed GG, El-Dessouky MM. Synthesis,
characterization and in vitro biological activity of mixed transi-
tion metal complexes of lornoxicam with 1,10-phenanthroline. Int
J Electrochem Sci. 2014;9:415–38.
2. Mohamed GG, Soliman MH. Synthesis, spectroscopic and ther-
mal characterization of sulpiride complexes of iron, manganese,
copper, cobalt, nickel, and zinc salts. Antibacterial and antifungal
activity. Spectrochim Acta Part A. 2010;76:341–7.
3. Wei Q, Dong J, Zhao P, Li M, Cheng F, Kong J, Li L. DNA
binding, BSA interaction and SOD activity of two new nickel(II)
complexes with glutamine Schiff base ligands. J Photochem
Photobiol B Biol. 2016;161:355–67.
4. Abd El-Halim HF, Mohamed GG. Synthesis, spectroscopic studies,
thermal analyses, biological activity of tridentate coordinated
transition metal complexes of bi(pyridyl-2-ylmethyl)amine]ligand.
J Mol Struct. 2015;1104:91–5.
3
3
3
3
3
2 3
acicular a-Fe O nanoparticles. Bull Mater Sci. 2011;34:1313–7.
46. El-Sonbati AZ, El-Bindary AA, Mohamed GG, Morgan SM,
Hassan WM, Elkholy AK. Geometrical structures, thermal
properties and antimicrobial activity studies of azodye com-
plexes. J Mol Liquids. 2016;218:16–34.
47. Abd El-Halim HF, Nour El-Dien FA, Mohamed GG, Mohamed
NA. Synthesis, spectroscopic, thermal characterization and
antimicrobial activity of miconazole drug and its metal com-
plexes. J Therm Anal Calorim. 2012;109:883–92.
48. Pelczar MJ, Chan ECS, Krieg NR. Host–parasite interaction;
nonspecific host resistance. In: Microbiology concepts and appli-
cations, 6th ed. New York: McGraw-Hill Inc.; 1999, p. 478–9.
49. Prescott LM, Harley JP, Klien DA. Microbiology, 2nd ed. Wm.
C. Brown Communications, Inc.; 1993.
5. Meenongwa A, Brissos RF, Soikum C, Chaveerach P, Gamez P,
Trongpaniche Y, Chaveerach U. Effects of N, N-heterocyclic
ligands on the in vitro cytotoxicity and DNA interactions of
copper(II) chloride complexes from amidino-O-methylurea
ligands. New J Chem. 2016;40:5861–76.
123