Three novel Ni(II), VO(II) and Cr(III) mononuclear complexes encompassing potentially tridentate imine ligand: Synthesis, structural characterization, DNA interaction, antimicrobial evaluation and anticancer activity

Article abstract of DOI:10.1002/aoc.3750

Three novel Cr(III),VO(II) and Ni(II) imine complexes derived from the condensation of 2-aminophenol (AP) with 2-hydroxynaphthaldehyde (HN) were synthesized. The prepared HNAP imine ligand and its complexes were investigated via various physicochemical tools. The results suggest that the parent ligand behaves as a dibasic tridentate ONO ligand, when coordinated to Cr(III) in octahedral and to Ni(II) in tetrahedral geometry. In the case of VO(II), it coordinates in distorted square pyramidal geometry. Also, the prepared compounds were screened for their antimicrobial activities against pathogenic bacteria, Escherichia coli (?ve), Bacillus subtilis (+ve) and Staphylococcus aureus (+ve), and some types of fungi, Aspergillus niger, Candida glabrata and Trichophyton rubrum. The results indicate that the complexes show a stronger antimicrobial efficiency compared to the pro-ligand. The interaction of the prepared complexes with calf thymus DNA was investigated using spectral, viscosity and gel electrophoresis measurements. The obtained results clearly demonstrate that the binding affinity with calf thymus DNA follows the order HNAPCr > HNAPV > HNAPNi. The cytotoxic activity of the prepared compounds on human colon carcinoma cells (HCT-116 cell line), hepatic cellular carcinoma cells (HepG-2cell line) and breast carcinoma cells (MCF-7cell line) was examined. From these results it is found that the investigated complexes have potent cytotoxicity against growth of carcinoma cells compared to the corresponding imine pro-ligand.

Full text of DOI:10.1002/aoc.3750

Received: 25 November 2016
DOI 10.1002/aoc.3750
Revised: 30 December 2016
Accepted: 9 January 2017
F U L L PA P E R
Three novel Ni(II), VO(II) and Cr(III) mononuclear complexes
encompassing potentially tridentate imine ligand: Synthesis,
structural characterization, DNA interaction, antimicrobial
evaluation and anticancer activity
Laila H. Abdel‐Rahman1 | Ahmed M. Abu‐Dief1
Azza A. Hassan Abdel‐Mawgoud1
| Maram Basha2 |
1 Chemistry Department, Faculty of Science,
Sohag University, 82524 Sohag, Egypt
2 Department of Chemistry, Faculty of
Science, Alfaisaliah Campus, King
Three novel Cr(III),VO(II) and Ni(II) imine complexes derived from the condensa-
tion of 2‐aminophenol (AP) with 2‐hydroxynaphthaldehyde (HN) were synthesized.
The prepared HNAP imine ligand and its complexes were investigated via various
physicochemical tools. The results suggest that the parent ligand behaves as a diba-
sic tridentate ONO ligand, when coordinated to Cr(III) in octahedral and to Ni(II) in
tetrahedral geometry. In the case of VO(II), it coordinates in distorted square pyra-
midal geometry. Also, the prepared compounds were screened for their antimicro-
bial activities against pathogenic bacteria, Escherichia coli (−ve), Bacillus subtilis
(+ve) and Staphylococcus aureus (+ve), and some types of fungi, Aspergillus niger,
Candida glabrata and Trichophyton rubrum. The results indicate that the complexes
show a stronger antimicrobial efficiency compared to the pro‐ligand. The interaction
of the prepared complexes with calf thymus DNA was investigated using spectral,
viscosity and gel electrophoresis measurements. The obtained results clearly demon-
strate that the binding affinity with calf thymus DNA follows the order HNAPCr >
HNAPV > HNAPNi. The cytotoxic activity of the prepared compounds on human
colon carcinoma cells (HCT‐116 cell line), hepatic cellular carcinoma cells
(HepG‐2cell line) and breast carcinoma cells (MCF‐7cell line) was examined. From
these results it is found that the investigated complexes have potent cytotoxicity
against growth of carcinoma cells compared to the corresponding imine pro‐ligand.
Abdulaziz University, Jeddah, Saudi Arabia
Correspondence
Ahmed M. Abu‐Dief, Chemistry
Department, Faculty of Science, Sohag
University, 82524 Sohag, Egypt.
Email: ahmed_benzoic@yahoo.com
KEYWORDS
anticancer activity, antimicrobial activity, DNA interaction, imine ligand, thermal analyses, Vo(ii)
1 | INTRODUCTION
nitrogen) and stability have made them the preferred ligand
systems in catalysis, biological modelling, design of molecu-
Imine ligands are considered privileged ligands, because they
are easily prepared by a simple one‐pot condensation of alde-
hydes and primary amines in an alcohol solvent. Their ease of
synthesis, multi‐denticity (from monodentate to hexadentate),
combination of donor atoms (complexion usually through the
imine nitrogen and other atoms like oxygen, sulfur or
lar ferromagnets, liquid crystals,[1–3] medical imaging[4] and
optical materials.[5] Moreover, imine ligands are able to
coordinate many different metals,[6–9] and to stabilize them
in various oxidation states. Furthermore, imine complexes
have been used as drugs and they have a wide variety of anti-
microbial activities against bacteria and fungi, and activity
Appl Organometal Chem. 2017;e3750.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
1 of 14
https://doi.org/10.1002/aoc.3750

2 of 14
ABDEL‐RAHMAN ET AL.
against certain types of tumours.[10–12] Some drugs have
increased activity when administered as metal chelates and
inhibit the growth of tumours.[12,13]
The interest in vanadium coordination chemistry is
promoted by the presence of this element in biological
systems,[14,15] and by the catalytic[16] and medicinal[17] prop-
erties of its compounds. The potential catalytic abilities of
vanadium compounds have led to a great interest in vanadium
coordination chemistry in recent years.[9] Thus, in the present
paper, we report the synthesis of a tridentate imine ligand of
2‐aminophenol (AP) and 2‐hydroxynaphthaldehyde (HN).
The structure of the prepared HNAP imine ligand was
checked using1H NMR, 13C NMR, infrared (IR) and
UV–visible spectroscopies. Then its Cr(III), VO(II) and
Ni(II) complexes were prepared and the spectral and thermal
properties of these complexes were studied in detail. Also the
kinetic parameters for the degradation steps in thermograms
of these complexes were calculated. The biological activity
of the pro‐ligand and its complexes was determined against
selected kinds of bacteria and fungi. Moreover, the interac-
tion of the complexes with calf thymus DNA (CT‐DNA)
was studied. Furthermore, the anticancer activity of the
prepared imine complexes was investigated.
SCHEME 1 Synthetic strategy for preparation of investigated
complexes and suggested structures
120.31, 120.15, 118.31, 116.60, 108.35 for carbons of
aromatic rings (Figure S2).
2.3 | Preparation of HNAPCr, HNAPNi and
2 | EXPERIMENTAL
2.1 | Reagents
HNAPV imine complexes
Cr(III), VO(II) and Ni(II) imine complexes were obtained
according to a general procedure: 10 mmol (2.63 g) of HNAP
pro‐ligand was dissolved in ethanol and 10 mmol of metal
salt (4.00 g of Cr(III), 2.98 g of Ni(II) or 2.65 g of VO(II))
was dissolved in an aqueous ethanolic mixture. The two solu-
tions were mixed together and refluxed for 2 h at 85 °C. After
evaporation the solvent, the precipitated solid was filtered off
from the reaction mixture, thoroughly washed with ethanol to
remove any traces of unreacted starting materials, and dried
under vacuum. The purity of the complexes was checked by
TLC (Scheme 1).
All of the solvents and chemicals used for our study were of
commercially available reagent grade and used without puri-
fication. HN, AP, vanadyl acetylacetonate (VO(C5H7O2)2),
chromium nitrate (Cr(NO3)3⋅6H2O) and nickel nitrate
(Ni(NO3)2⋅6H2O) were obtained from Sigma‐Aldrich. All
reagents and solvents were commercially acquired from
Merck, Aldrich or Fluka. CT‐DNA, tris(hydroxymethyl)
aminomethane (Tris), bromophenol blue dye and ethidium
bromide were obtained from Sigma‐Aldrich Chemie
(Germany).
2.4 | Characterization of prepared HNAP
imine pro‐ligand and its complexes
2.2 | Preparation of HNAP imine pro‐ligand
An amount of 5 mmol (0.861 g) of HN was dissolved in
ethanol and mixed with an ethanolic solution of 5 mmol
(0.545 g) of AP. Then the mixture was refluxed and stirred
for 2 h at 85 °C and s yellow precipitate was formed. The
completion of the reaction mixture was monitored by TLC.
The product was gathered by filtration, washed with ethanol
and dried over anhydrous CaCl2 (Scheme 1).
Melting point for the prepared imine ligand and decomposi-
tion temperatures of its complexes were measured with a
melting point device (Gallenkamp, UK). IR spectra were
recorded as KBr pellets using a Shimadzu FTIR‐8300 spec-
trophotometer. 1H NMR and 13C NMR spectra were
obtained in deuterated dimethylsulfoxide (DMSO) solutions
with a Bruker Avance DPX‐500 spectrometer. All of the
scanning UV–visible spectra in DMF were recorded using
10 mm matched quartz cells with a PG spectrophotometer
model T + 80. Elemental analyses were conducted at the
main laboratory of Cairo University using an elemental
analyser (PerkinElmer 240c). Magnetic susceptibility was
1H NMR (DMSO, δ, ppm): 15.65 (s, OH), 10.15 (s, OH),
8.36–6.83 (m, 9H, aromatic), 9.49 (s, 1H, CH═N), 8.36
(s, 1H, CHposition10) (Figure S1). 13C NMR (DMSO, δ,
ppm): 177.17 (N═CH), 150.46, 149.11, 138.11, 134.36,
129.64, 129.41, 128.50, 127.19, 126.46, 125.21, 123.48,

ABDEL‐RAHMAN ET AL.
3 of 14
measured using a Gouy balance and diamagnetic correc-
tions were executed by Pascal”s constants. Molar conductiv-
ity measurements were performed using a JENWAY 4510
conductivity meter. Thermogravimetric analysis was con-
ducted under nitrogen with a heating rate 10 °C min−1 with
a Shimadzu 60H analyser. The values of absorbance of
5 × 10−3 M of each complex were determined at various
pH levels. The pH levels were checked using a series of
Britton universal buffers.[11] An ADWA AD1000 and
AD1020 pH meter at 298 K equipped with a CL‐51B com-
bined electrode was utilized for pH measurements, cali-
brated against standard buffers (pH 4.02 and 9.18) before
measurements.
the decomposition of the metal complexes was determined
employing the following equation:
ꢀ
ꢁ
ꢀ
ꢂ
ꢃꢁ
logðw∞=ðw∞−wÞÞ
AR
ϕEꢀ
2RT
Eꢀ
Eꢀ
2:303RT
log
¼ log
1−
−
(2)
T2
where w∞ is the mass loss at the completion of the decompo-
sition reaction, w is the mass loss at temperature T, R is the
universal gas constant and φ is the heating rate. Since
1 − 2RT/E* ≈ 1, a plot of the left‐hand side of equation (1)
against 1/T gives a slope from which E* was calculated and
A was determined from the intercept. The other kinetic
parameters, the entropy of activation (ΔS*), enthalpy of acti-
vation ( H*) and activation free energy change ( G*), were
calculated using the following expressions:[11,12,19,21]
2.5 | Evaluation of stoichiometry of prepared
imine complexes
Ah
KBT
ΔSꢀ ¼ 2:303R log
(3)
The molar ratio[10–12,18] and continuous variation[10–12,19,20]
methods were used. Metal salt and ligand solutions were
mixed, stirred and allowed to equilibrate and the absorbance
was read at λmax up to 2 h. The sum of the metal ion concen-
tration and HNAP imine pro‐ligand concentration was
1 × 10−3 M for each solution. Ten volumetric flasks of
10.0 ml were used for the investigation. The initial concentra-
tions of metal salt and HNAP pro‐ligand were 1 mM. The
absorbance of each solution was measured and plotted
against the mole fraction of metal ion or mole fraction of
the pro‐ligand.
ΔHꢀ ¼ Eꢀ−RT
(4)
(5)
ΔGꢀ ¼ Hꢀ−TΔSꢀ
where KB and h are Boltzmann”s and Planck”s constants,
respectively.
2.8 | Antibacterial and antifungal activities of
prepared compounds
The in vitro biological activities of the HNAP imine pro‐
ligand and its complexes were examined against various types
of bacteria (Bacillus subtilis (+ve), Escherichia coli (−ve) and
Staphylococcus aureus (+ve)) by the well diffusion method
using nutrient agar as the environment.[10–12,18–20] The
antifungal activities of the compounds were also checked by
the well diffusion method against various types of fungi
(Aspergillus niger, Candida glabrata and Trichophyton
rubrum) on potato dextrose agar as environment. The investi-
gated compounds were dissolved in DMSO and solutions
with concentrations of 10 and 20 mg ml−1 were prepared
separately. In a typical method, a well was made on the agar
medium vaccinated with microorganism.[11,12,18,22] Wells
supplemented with DMSO and reference antibacterial drug
served as negative and positive controls, respectively. The
well filled with the test solution using a micropipette and the
plate was incubated for 24 h at 37 °C for bacteria or 72 h at
35 °C for fungi. After incubation, the diameter of the obtained
zone of inhibition around the sample was taken as a criterion
of the inhibitory power of the sample against the particular
test microbe as measured with a zone reader (Hi Antibiotic
zone scale). The standard antibacterial drug gentamycin and
antifungal drug fluconazol were also screened under similar
conditions for comparison. In order to clarify the effect of
2.6 | Estimation of apparent formation
constants of prepared complexes
The formation constants (Kf) of the studied imine complexes
formed in solutions were obtained from spectrophotometric
measurements using the continuous variation method.[10–
12,18–20]
according to the following relation:
A=Am
Kf ¼
(1)
2
ð1−A=AmÞ C
where Am is the absorbance at the maximum formation of the
complex, A is arbitrarily selected absorbance values on either
side of the absorbance peak and C is the initial molar concen-
tration of the metal. Also, the free energy change, ΔG*, of the
complexes was determined using ΔG* = −RT ln Kf, at 25 °C,
where Kf is the formation constant, R is the gas constant and
T is the temperature in kelvin.
2.7 | Kinetic studies
The kinetic parameters of the decomposition process for the
metal complexes were determined using the Coats–Redfern
integral method.[11,12,19,21] The energy of activation (E*) for

4 of 14
ABDEL‐RAHMAN ET AL.
solvent (DMSO) on the biological screening, DMSO alone
was used as control, and it showed no activity against micro-
bial strains. The measurements were made in triplicate for
each compound and their average values are reported.
2.9.3 | Hydrodynamic measurements for DNA
interaction
Viscosity measurements were executed using an Oswald
micro‐viscometer, maintained at constant temperature of
25 °C. The fluidity times were recorded for various concen-
trations of the complexes (5–50 μM), maintaining the con-
centration of CT‐DNA constant (260 μM). Mixing of the
solution was achieved by bubbling nitrogen gas through the
viscometer. The mean value of three measures was used to
determine the viscosity of the samples. The buffer fluidity
time in seconds was registered as t°. The relative viscosities
for DNA in the presence (η) and absence (η°) of the com-
plexes were evaluated using the relation η = (t − t°)/t°, where
t is the observed fluidity time in seconds and the relative
viscosity (η/η°) was determined against 1/R (R = [DNA]/
[complex]).[18,19,21]
2.9 | DNA binding study
2.9.1 | DNA binding propensity
All the tests including the interaction of the complexes with
DNA were conducted in Tris–HCl buffer (60 mM, pH = 7.1).
CT‐DNA was purified by centrifugal dialysis before use. A
solution of CT‐DNA in the buffer gave a ratio of UV absorp-
tion at 260 and 280 nm of greater than about 1.85, suggesting
that the DNA was sufficiently free from protein contamina-
tion.[11,12,18,22] The concentration of DNA per nucleotide
was evaluated by monitoring the UV absorbance at 260 nm
utilizing ε260 = 6600 mol−1 cm2. The stock solution was
stored at 4 °C and used within only one day.
2.9.4 | Agarose gel electrophoresis
measurements
2.9.2 | Electronic spectra for interaction of
The DNA binding studies were conducted using the agarose
gel electrophoresis method.[19] Stock solutions of complexes
were prepared by dissolving 20 mg of the prepared com-
plexes in 20 ml of DMF. The sample (25 μg ml−1) was added
to CT‐DNA and incubated for 1 h at 37 ꢂ 1 °C. Then 30 μl of
DNA sample (mixed with bromophenol blue dye at a 1:1
ratio) was transferred to the electrophoresis chamber wells
along with a standard DNA marker in TBE buffer (50 mM
Tris base, pH = 7.2; 1 mM EDTA/1 L) and then loaded onto
the agarose gel. Then a constant vloyage (60 V) was used for
about 45 min. Finally, the gel was removed and stained with
20 μg ml−1 ethidium bromide for 10–20 min. The bands
acquired was spotted under UV light using a transilluminator
followed by photography with a DMC‐LZ5 Lumix digital
camera to determine the extent of DNA binding compared
with the standard DNA marker.[18–21]
prepared complexes with DNA
All the tests including the interaction of the complexes with
DNA were carried out in Tris–HCl buffer (60 mM, pH = 7.1).
Spectrophotometric scan test was performed by keeping the
complex concentration constant while changing the nucleic
acid concentration in the surrounding conditions. The
absorption due to free CT‐DNA was removed by adding equi-
molar CT‐DNA to clear buffer solution in the reference com-
partment and the spectra obtained were considered to result
from the complexes and the DNA–metal complex aggrega-
tion.[12,18,22] From the absorption data, the intrinsic binding
constant (Kb) was determined by plotting [DNA]/(εa − εf)
versus [DNA] according to the following equation:
½DNAꢁ
½DNAꢁ
1
¼
þ
(6)
ðεa−εfÞ ðεb−εfÞ ½Kbðεb−εfÞꢁ
2.10 | Anticancer activity
where [DNA] is the molar concentration of DNA in base
pairs, εa, εf and εb are the apparent, free and fully bound
complex extinction coefficients, respectively. Particularly,
εf was evaluated from the calibration curve of the isolated
metal complex, verifying Beer”s law. εa was evaluated as
the ratio between the determined absorbance and the M(II)
complex concentration, Aobs/[complex]. The data conformed
to the above equation with a slope equal to 1/(εb − εf) and y‐
intercept equal to 1/Kb(εb − εf) and Kb was obtained from
the ratio of slope to intercept. The standard Gibb”s free
energy for DNA binding was evaluated from the following
relation:[11,12,18,21]
The anticancer activity was evaluated at the National Cancer
Institute, Cancer Biology Department, Pharmacology
Department, Cairo University. The absorbance or optical den-
sity (OD) of each well was measured spectrophotometrically
at 564 nm with an ELISA microplate reader (Σ960, Meter
Tech, USA). Evaluation of the cytotoxic activity of the pre-
pared pro‐ligand and its complexes was carried out against
human colon carcinoma cells (HCT‐116 cell line), hepatic
cellular carcinoma cells (HepG‐2 cell line) and breast carci-
noma cells (MCF‐7 cell line). The evaluation process was
carried out in vitro using sulforhodamine B stain.[12,23–25]
Cells were placed in a 96‐multiwell plate (104 cells per well)
for 24 h before adding the complexes to allow attachment of
ΔGꢀb ¼ −RT lnKb
(7)

ABDEL‐RAHMAN ET AL.
5 of 14
cells to the walls of the plate. Various concentrations of the
compounds under test in DMSO (0, 1, 2.5, 5 and 10 μM) were
added to the cell monolayer. Monolayer cells were incubated
with the complexes for 48 h at 37 °C and in an atmosphere
of 5% CO2. After 48 h, cells were fixed, rinsed and stained
with sulforhodamine B stain.[12,23] Excess stain was washed
with acetic acid and attached stain was treated with
Tris–EDTA buffer. Colour intensity was measured in an
ELISA reader. IC50 was evaluated and potency was calculated
with regard to percentage change of vistabline standard.[12,23]
The inhibitory concentration percent (IC %) was esti-
mated[12,23–25] according to the equation:
The signals observed in the region 150.46–108.35 ppm are
assigned to phenyl carbons.
3.1.2 | Elemental analysis and electrical con-
ductivity measurements
All the prepared complexes are coloured, solid, stable at
room temperature and non‐hygroscopic in nature.
The elemental analysis results for the imine pro‐ligand
and its complexes are recorded in Table 1 and suggest that
HNAP imine pro‐ligand acts as a tridentate ligand and forms
complexes with VO(II), Cr(III) and Ni(II) in metal‐to‐ligand
ratio of 1:1 (Scheme 1). The molar conductance of all the pre-
pared complexes was measured at room temperature in DMF
as a solvent and the results are recorded in Table 1. The molar
conductance values of all prepared complexes at room tem-
perature fall in the range 2.1–9.4 Ω−1 cm2 mol−1 indicating
their non‐ electrolytic nature.[11,12,18–22,27]
ðControl ODÞ−ðligand ODÞ
IC ð%Þ ¼
×100
(8)
Control OD
3 | RESULTS AND DISCUSSION
3.1.3 | IR spectra
3.1 | Physicochemical properties of HNAP
imine pro‐ligand and its complexes
The bonding of the prepared HNAP imine pro‐ligand to the
metal ions was judged by a careful comparison of the IR
spectra of the metal complexes with that of the free ligand.
The characteristic IR frequencies of the HNAP pro‐ligand
and its complexes along with their assignments are summa-
rized in Table 2. Bands due to ─OH and ─CH═N are
distinguishable and offer proof regarding the structure of
the pro‐ligand and its bonding with metals. A band at
1632 cm−1 in the HNAP pro‐ligand spectrum is due to
─C═N stretching vibration. On complexation, this band is
displaced to a lower frequency (1597–1623 cm−1). The
negative shift of this band is an obvious indication of the
involvement of the azomethine nitrogen atoms in complex
formation.[10,26] This is supported by the appearance of bands
at 561–670 cm−1 corresponding to the stretching vibration of
M─N bond. Bands at 460–573 cm−1 correspond to M─O
stretching vibrations. Band at 3448 cm−1 observed in the
pro‐ligand spectrum is due to stretching vibrations of free
3.1.1 | 1H NMR and13C NMR spectra of
HNAP imine pro‐ligand
The formation of the prepared HNAP imine pro‐ligand was
1
further supported by the NMR spectral study. The H NMR
and 13C NMR spectral data of the prepared pro‐ligand are
1
recorded in Section 1 (Figures S1 and S2). The H NMR
spectrum of HNAP imine pro‐ligand shows two singlet
signals at 15.65 and 9.50 ppm that are assigned to the two
phenolic ─OH. Also, it shows a singlet signal at 9.49 ppm
which is characteristic for azomethine (CH═N) proton of
the pro‐ligand.[26] Moreover, it shows multiplet signals at
8.36–6.83 ppm for aromatic CH (9) protons. Furthermore, it
shows one proton doublet at position 10. The 13C NMR
spectrum of HNAP imine pro‐ligand exhibits a signal at
177.17 ppm which may be assigned to azomethine carbon.
TABLE 1 Analytical and physical data of HNAP imine pro‐ligand and its complexes
Analysis (%)
Found (calcd)
Λm
Compound
(molecular formula)
Molecular
weight
Colour
(yield, %)
(Ω−1 cm2
μeff
(BM)
M.p. And Dec.
temp. (°C)
Mol−1
)
C
H
N
HNAP
(C17H13NO2)
263.09
447.00
346.70
345.94
Yellow
(88)
‐
‐
140
77.41
(77.52)
4.91
(4.98)
5.28
(5.32)
HNAPCr
(C17H19N2CrO9)
Orange
(86)
9.40
6.30
2.10
3.70
2.65
1.78
( 220)
(280)
(180)
45.53
(45.64)
4.28
(4.25)
6.31
(6.26)
HNAPNi
(C17H14NNiO3.5
Bright green
(87)
58.79
(58.84)
4.07
(4.04)
4.10
(4.04)
)
HNAPV
(C17H13NO4V)
Brown
(89)
58.85
(58.97)
3.80
(3.76)
4.01
(4.05)

6 of 14
ABDEL‐RAHMAN ET AL.
TABLE 2 Characteristic IR bands (cm−1) of HNAP imine pro‐ligand and its complexes
Bands due to (NO3)
Compound
υ(oh)/H2O
υ(CH)ar
υ(C═N)
υ(C─O)ph
υ(NO2)as
υ(NO2)sy
υ(no)
ν(M—N)
ν(M─O)
HNAP
3448 (s)
3529
3120
3321
3060
3053
1632
1623
1620
1597
1240
1212
1211
1206
—
1470
—
—
1356
—
—
858
—
—
—
HNAPCr
HNAPNi
HNAPV
567
561
670
460
506
573
3422
3423
—
—
—
vs = very strong, s = strong, m = medium, b = broad, w = weak, ar = aromatic, py = pyridine, ph = phenolic, asy = asymmetric, sy = symmetric.
─OH. For the complexes, the recorded IR spectra show broad
bands at 3422–3529 cm−1 which correspond to ν(OH)
stretching vibration of crystalized water molecules, in accor-
dance with the findings of the elemental analysis listed in
Table 1. A band at 968–976 cm−1 (OH rocking) suggests
the presence of coordinated water in all three complexes. In
the low‐frequency region, the HNAP imine pro‐ligand shows
an absorption band at 1240 cm−1 which can result from the
stretching vibration of the phenolic (C─O) group. The
shifting of that band to lower wavenumber on coordination
shows that the oxygen atoms of the phenolic groups are
coordinated to the metal ion. The characteristic frequencies
of the coordinated nitrate group in HNAPCr complex possess
three non‐degenerate modes at 1470 cm−1 ν(NO2)asy
,
1356 cm−1 ν(NO2)sy and 858 cm−1 ν(NO).[28]
FIGURE 2 Job”s plots for determining the stoichiometry of the
prepared complexes in aqueous ethanolic medium at
[HNAPCr] = [HNAPNi] = [HNAPV] = 10−3 M and 298 K
3.1.4 | Electronic spectra
Molecular electronic absorption spectra are often very signif-
icant in the evaluation of results furnished by other methods
of investigation. The values of the maximum absorption
wavelength (λmax) and the molar absorptivity (εmax) are listed
in Table S1 and the spectra are presented in Figure 1. The
electronic spectral measurements were used for assigning
the stereochemistry of metal ions in the complexes relying
on the sites and number of d–d transition peaks.[29] The elec-
tronic absorption spectra of pro‐ligand and its complexes
were recorded in the wavelength range 200–800 nm and
298 K. The pro‐ligand presents absorption bands in the
UV–visible region around 400 nm which is assigned to
n → π* transition originating from the imine function of the
pro‐ligand.[30] The absorption bands of complexes at
λmax = 318–472 nm are assigned to charge transfer within
HNAP imine pro‐ligand to the metal ion. Furthermore, there
is a long and a broad band lying in the region 504–524 nm
(εmax= 230–570 mol−1 cm2). This band could mainly
correspond to the d → d transition in the structure of the
complexes (Table S1).[31]
3.1.5 | Magnetic moment measurements
Magnetic susceptibility measurements offer information
concerning the geometric structure of the compounds. The
observed magnetic moments for complexes are generally
diagnostic of the coordination geometry about the metal ion
(Table1). HNAPCr complex shows magnetic moment corre-
sponding to three unpaired electrons, i.e. 3.7 BM, as expected
FIGURE 1 Molecular electronic spectra of HNAPCr complex and its
components in DMF at 298 K

ABDEL‐RAHMAN ET AL.
7 of 14
for octahedral Cr(III) complexes.[32] The magnetic moment
values of the Ni(II) complex is 2.65 BM, indicating the pres-
ence of two unpaired electrons per Ni(II) ion and suggesting
this complex to have tetrahedral geometry.[33] The HNAPV
complex has a magnetic moment value of 1.78 BM, which
is close to the spin‐only value for d1 and in agreement with
the reported values for square pyramidal and distorted
octahedral complexes of VO(II).[34]
to the loss of nitrate group (NO3)with a net weight loss of
13.78% (calcd 13.77%). Also, the HNAPCr complex shows
mass loss within the temperature ranges 287–399 and
401–567 °C, which are due to removal of part of the pro‐
ligand (C10H6O) and (C7H5NO) with mass losses of
31.65% (calcd 31.77%) and 26. 52% (calcd 26.6%), respec-
tively. Finally metallic residue is the final product of thermal
decomposition with mass loss of 11.70% (calcd 11.63%).[35]
The thermal analysis curve of the HNAPNi complex shows
four stages of decomposition within the temperature range
40–595 °C. The first stage at 40–115 °C corresponds to
the elimination of half a water molecule of hydration, with
a mass loss of 2.75% (calcd 2.6%). The second step at
116–222 °C corresponds to the removal of one coordinated
water molecules with mass loss of 5.00% (calcd 5.19%). The
third stage of decomposition occurs in the temperature range
223–381 °C with a net weight loss of 34.37% (calcd
34.32%) which is consistent with the removal of part of
the pro‐ligand (C7H5NO) molecule. The fourth step involves
the loss of the other part of the pro‐ligand to give finally Ni
as a residue. The final product explained from a horizontal
curve being obtained suggesting formation of metal prod-
uct.[36] HNAPV complex exhibits no mass loss up to
137 °C, indicating the absence of hydrated water molecules.
The first step of decomposition within the temperature range
137–180 °C corresponds to the loss of one coordinated
water molecule, with a mass loss of 5.07% (calcd
5.20%).[37] The third and fourth steps within the temperature
range 182–552 °C involve removal of organic ligand moiety
to give finally VO residue with a net weight loss of 19.33%
(calcd 19.35%).
3.1.6 | Thermal analysis
Thermal analysis of metal chelates is an important tool for
(i) obtaining information about the thermal stability of these
complexes and (ii) indicating if the water molecules (if pres-
ent) are inside or outside the interior coordination sphere of
the central metal ion. The thermograms of the prepared
imine complexes indicate the presence of one molecule of
coordinated water in the case of HNAPV and HNAPNi
complexes and two coordinated water molecules in the case
HNAPCr complex (Scheme 1).[33] The thermal behaviour of
the metal complexes shows dehydration of water molecules
in the first step; then loss of coordinated water molecules
with degradation of the pro‐ligand molecule in the next
steps as shown in Table 3. The thermogram of the HNAPCr
complex shows five degradation steps within the tempera-
ture range 35–567 °C. The first stage at 35–110 °C corre-
sponds to the elimination of two water molecules of
hydration, with a mass loss of 8.12% (calcd 8.05%). The
second step at 112–211 °C corresponds to the removal of
two coordinated water molecules with mass loss of 8.22%
(calcd 8.05%). The third step at 213–285 °C corresponds
TABLE 3 Thermal degradation steps, mass losses, proposed lost segments, final residue and thermo‐kinetic activation parameters of each
decomposition step for the prepared complexes
Mass loss (%)
Dec.temp.
(°C)
ΔH*
ΔG*
ΔS*
Complex
Found
(calcd)
Proposedsegment
E*(kJ Mol−1
)
A(s−1
)
(kJ Mol−1
)
(kJ Mol−1
)
(J Mol−1 K−1
)
HNAPCr
35–110
110–211
211–285
285–399
399–567
8.12
8.22
13.78
31.65
26.52
(8.05)
(8.05)
(13.87)
(31.77)
(26.60)
2H2O
2H2O
NO3
C10H6O
C7H5NO
78.30
0.096
77.8
78.3
76.0
75.5
74.2
93.6
−251.55
−259.52
−262.97
−265.50
−268.57
119.7
141.7
165.8
205.8
Residue
>567
11.70
(11.63)
Cr
—
—
—
HNAPNi
40–115
116–222
223–381
384–595
2.75
5.00
34.37
41.05
(2.60)
(5.19)
(34.32)
(40.95)
0.5H2O
H2O
C7H5NO
C10H6O
32.8
0.049
0.40
32.2
31.4
30.3
28.7
49.5
76.0
111.9
163.9
−257.62
−265.30
−270.14
−274.21
Residue
HNAPV
>595
16.83
(16.93)
Ni
—
—
—
137–180
182–326
328–552
5.07
34.49
41.13
(5.20)
(34.40)
(41.05)
H2O
C7H5NO
C10H6O
135.2
134.0
133.0
131.5
174.0
196.0
246.0
−247.40
−251.14
−255.90
Residue
>552
19.33
(19.35)
VO
—
—
—

8 of 14
ABDEL‐RAHMAN ET AL.
3.1.7 | Kinetic aspects
The kinetic parameters are given in Table 3. It is evident that
G* values increase with increasing temperature. The positive
values of H* indicate that degradation processes are endother-
mic. In most thermal steps, S* values are negative suggesting
a degradation via an abnormal pathway for those steps and
the degradation processes are undesirable. The negative acti-
vation entropy values give evidence for a more ordered acti-
vated state. This can occur through the chemisorption of
oxygen and other decomposition products. The more ordered
nature can be referred to the bond polarization of the acti-
vated state which takes place through electronic transitions.
Finally, positive values of H* and G* represent the endother-
mic character for all thermal steps.[38]
FIGURE 3 Dissociation curves of prepared imine complexes in
DMF
3.1.8 | Spectrophotometric determination of
stoichiometry of complexes
obtained results of elemental analyses, molar conductance,
magnetic measurements, IR and electronic spectra, the
suggested composition of the complexes was identified.
Stoichiometry of the prepared complexes was determined
using two methods including the use of spectrophotometry,
namely continuous variations method and molar ratio
method. Based on the obtained results, the stoichiometry of
the prepared complexes is 1:1. The curves of the continuous
variation method (Figure 2).display maximum absorbance
at mole fraction Xligand = 0.5–0.6 showing the complexation
of metal ions to ligand in a molar ratio of 1:1. Moreover,
the data from the molar ratio method support the same
metal ion to ligand ratio of the prepared complexes
(Fig. S3).[11,12,18,22]
3.2 | Antimicrobial activity evaluation
The in vitro antimicrobial activities of the HNAP imine pro‐
ligand and its complexes against three selected bacteria and
three fungi were determined. Any chemotherapeutic agent
inhibits the growth of microbes by microstatic mechanisms.
All of the compounds display good biological activity against
the microorganisms. On contrasting the biological activity of
the imine pro‐ligand and its complexes with those of standard
bactericide and fungicide, it is clear that the complexes have
moderate activity as compared with the standard, but all the
complexes are more active than free pro‐ligand. The greater
inhibition zone of the transition metal complexes than those
of the pro‐ligand can be considered based on the Overtone
notion and chelation theory. Upon chelation, the polarity of
the metal ion is decreased to a great extent due to the overlap
of the ligand orbital and the fraction of the positive charge of
the metal ion participating with donor groups. Furthermore, it
increases the delocalization of the π‐electrons over the whole
chelating ring and increases the breakthrough of the com-
plexes into lipid membranes and the blocking of the metal
attachment locations in the enzymes of microorgan-
isms.[12,23,39] The conclusions of the investigations account
for the antipathogenic manner of the compounds and this
efficacy is positively changed on complexation. Data are
listed in Table 4 and shown in Figures 4 and 5. The minimum
inhibitory concentration (MIC) was estimated by the serial
dilution route and is reported in Table 5. The HNAPV com-
plex (3 mg ml−1) is found to be highly effective as its exhibits
the lowest MIC against Bacillus subtilis bacterium and A.
flavus fungus compared to the other compounds. The
3.1.9 | Determination of apparent formation
constants of complexes
The formation constants (Kf) of the studied imine complexes
formed in solution were obtained from spectrophotometric
measurements by utilizing the continuous variation method
(Table S2), where Am is the absorption at the maximum of
the complex, A is arbitrarily selected absorbance values on
either side of the absorbance peak and C is the elementary
concentration of the metal. The obtained Kf values show the
high stability of the complexes. The values of Kf for the com-
plexes decrease in the following order: HNAPCr > HNAPV
> HNAPNi. Moreover, the stability constant (pK) and Gibbs
free energy (ΔG≠) values of the complexes were calculated.
The negative values of Gibbs free energy show that the reac-
tion is spontaneous and favoured. The pH profilse (absor-
bance versus pH) depicted in Figure 3 show typical
dissociation curves and a high stability range of pH (4–9)
of tested complexes. This shows that the formation of the
complexes greatly stabilizes the prepared imine pro‐ligand.
Consequently, the desired pH range for different applications
of the tested complexes is from pH = 4 to 9. Based on the

ABDEL‐RAHMAN ET AL.
9 of 14
FIGURE
4
Histogram showing the comparative antibacterial
activities of prepared compounds (HNAP, HNAPCr, HNAPNi and
HNAPV) against E. coli bacteria
FIGURE 5 Histogram showing the comparative antifungal activities
of prepared compounds (HNAP, HNAPCr, HNAPNi and HNAPV)
against C. albicans fungus
antimicrobial studies suggest that all the complexes exhibit
promoted antimicrobial activity against microbial strains in
comparison to the free pro‐ligand. Previous studies suggested
that chelation tended to make the pro‐ligand a more powerful
and potent bacteriostatic agent,[40] thus inhibiting the growth
of microbes more than the pro‐ligand, which is similar to the
results of this study. It is suspected that factors such as solu-
bility, conductivity, dipole moment and cell permeability
influenced by the existence of metal ion might be a possible
reason for the increase in activity. The activities of the pre-
pared complexes were confirmed by calculating the potency
index (Table S3) according to the following relation:[11,12,22]
Inhibition zone of complex ðmmÞ
Activity index ðAÞ ¼
×100 (9)
Inhibition zone of standard drug ðmmÞ
The variation in the activity of the metal complexes against
different microbes depends either on the difference in the ribo-
somes of the microbial cells or on the impermeability of the
cells of the microbes. The lower activity of complexes as

10 of 14
ABDEL‐RAHMAN ET AL.
TABLE 5 Minimum inhibition concentration (MIC) for antimicrobial assay of the ligand and its complexes
Bacteria
Fungi
Compound
S. aureus
E. coli
B. subtilis
A. flavus
C. albicans
T. rubrum
HNAP
7.0
4.5
6.0
5.0
8.0
3.5
5.5
4.5
7.5
3.0
6.0
5.5
6.0
3.0
3.5
3.5
6.5
4.0
5.0
5.0
7.0
3.5
4.0
4.5
HNAPV
HNAPNi
HNAPCr
compared to others may be attributed to low lipid solubility, so
that the metal ion may not be able to reach the favourable site of
action of the cell wall to interfere with normal cell activity.
Althoughchelationitselfplaysasignificantroleindetermining
antibacterial behaviour of the complexes, concurrently various
factors such as solubility, size, dipole moment, coordinating
sites, redox potential of metal ion, solubility, bond length
between metal and ligand, geometry of complexes, steric fac-
tors, pharmacokinetics, concentration and hydrophobicity
have substantial influence on the antibacterial activity. Thus,
it is apparent from the results that enhanced antibacterial activ-
ity of the metal complexes may be due not only to chelation but
also intricate combinations of several other factors as well.[40]
3.3 | DNA binding potency
3.3.1 | Electronic spectra of interaction with
DNA
Titration with electronic absorption spectroscopy is an attrac-
tive route to investigate the binding mode of DNA with metal
complexes. The spectra were recorded as a function of the
addition of buffer solutions of pure CT‐DNA to buffer solu-
tions of the tested complexes. If the interaction mode is inter-
calation, the orbital of the inserted ligand can couple with the
orbital of the base pairs, lowering the π–π* transition energy
and leading to bathochromism. If the conjunction orbital is
partially filled by electrons, it results in reduction of the
transition probabilities and leads to hypochromism.[12,22]
The extent of hypochromism or hyperchromism in the
metal‐to‐ligand charge transfer band is commonly consistent
with the force of intercalation interaction.[11,23] The elec-
tronic absorption spectra of HNAPCr complex in the absence
and presence of various concentrations of buffered CT‐DNA
are shown in Figures 6 and S4. Addition of increasing
amounts of CT‐DNA results in a reduction of absorbance
for a complex. The spectral parameters and Kb for DNA inter-
action with the tested complexes are summarized in Table 6.
The investigated complexes can bind to DNA mainly via
FIGURE 6 Spectral scans of interaction of HNAPCr complex
(10−3 M) in 0.01 M tris buffer (pH = 7.2, 298 K) with CT‐DNA (0–
30 μM, from top to bottom)
TABLE 6 Spectral parameters for interaction of imine complexes
a
λmax, free
(nm)
λmax, bound
Type of
chromism
Binding constant, Kb
Complex
(nm)
Δn
Chromism (%)
(× 104 mol−1 dm3)
ΔG* (kJ Mol−1
−28.87
)
HNAPCr
442
464
348
444
466
356
2
2
8
26.20
15.84
164.18
Hyper
Hyper
Hyper
11.51
1.69
7.68
HNAPNi
HNAPV
447
470
236
441
463
237
6
7
1
28.70
24.43
33.00
Hypo
Hypo
Hypo
−24.12
−27.87
458
327
444
338
14
11
14.46
34.67
Hyper
Hyper
[11,12,18,22]
aChromism (%) = (Absfree − Absbound)/Absfree
.

ABDEL‐RAHMAN ET AL.
11 of 14
intercalative and replacement modes with the sequence:
HNAPCr > HNAPV > HNAPNi (Scheme 2a).
3.3.2 | Viscosity measurements
For explaining the nature of interaction between the tested
complexes and DNA, viscosity measurements were carried
out. Hydrodynamic methods such as viscosity measure-
ments which are sensitive to length increase or decrease
of DNA are regarded as the most effective routes of study-
ing the binding mode of compounds to DNA in the absence
of crystallographic structural data and NMR data. For fur-
ther explaining the binding mode, viscosity measurements
were made. Under appropriate conditions, a traditional
intercalative mode such as intercalation of drugs like
ethidium bromide leads to a significant increase in the vis-
cosity of DNA solution due to an increase in the segrega-
tion of base pairs at the intercalation site and hence an
increase in the overall DNA length. On the other hand, drug
molecules attaching exclusively to the DNA grooves lead to
less pronounced DNA solution viscosity.[22,41] A partial
intercalation of a compound may bend the DNA helix,
resulting in the reduction of its effective length and, con-
comitantly, its viscosity.[12,22,42–44] The relative viscosity
of DNA solution increases significantly as the amount of
compound increases, as shown in Figure 7. This may be
due to the admission of the aromatic ring in the imine
pro‐ligand into the DNA base pairs resulting in a distortion
in the DNA helix, and hence an increase in the segregation
of the base pairs at the intercalation place and an increase in
DNA molecular length. Moreover, the sequence of the
observed increase in the values of viscosity is related with
the binding affinity to DNA, i.e. HNAPCr complex shows
the highest binding affinity to DNA and the highest
(a)
(b)
SCHEME 2 (a) suggested mechanism for interaction of HNAPCr
complex with DNA via (a) intercalation binding and (B) replacement.
(b) suggested mechanism for interaction of HNAPCr complex with
DNA via electrostatic binding
FIGURE 7 Effect of increasing concentration of prepared complexes
on relative viscosities of DNA at [DNA] = 0.5 mM, [complex] and
[ethidium bromide] = 25–250 μM and 298 K

12 of 14
ABDEL‐RAHMAN ET AL.
viscosity. Moreover, HNAPCr complex could bind to DNA
via electrostatic binding as shown in Scheme 2(b). Electro-
static binding may occur due to water molecules replacing
coordinated nitrate group. Thus, HNAPCr complex will be
charged (Scheme 2b) and electrostatic interaction occurs
between the positive charge in the complex and base pairs
of DNA.
3.3.3 | Gel electrophoresis
Agarose gel electrophoresis was used for the DNA binding
studies. The prepared imine chelates were studied for their
DNA binding activity using the agarose gel electrophoresis
method (Figure 8). The gel after electrophoresis clearly
showed that the intensity of all the treated DNA samples
has partially decreased, possibly because of the interaction
with DNA. The partial binding of DNA was observed for
the prepared imine chelates. The difference is clarified in
the bands of the complexes compared to that of the control
DNA. The control DNA alone does not show any visible
cleavage whereas the complexes show cleavage.[22,44] How-
ever, the nature of reactive intermediates involved in the
DNA binding by the complexes is not obvious.[45] These
results show that the metal ions play an important role
in the interaction with isolated DNA. As the compounds
are observed to bind with DNA, it can be concluded that
the compounds reduce the growth of the pathogenic organ-
isms by interaction with the genome. The studies reveal
that there is partial binding of DNA with VO(II), Cr(III)
and Ni(II) imine complexes. The experimental results
FIGURE 9 IC50 values of HNAP imine pro‐ligand and its complexes
against HCT‐116, HepG‐2 and MCF‐7 cell lines
suggest that the complexes could bind to DNA via
intercalative mode.
3.4 | Anticancer activity
The cytotoxic potency of the prepared HNAP imine pro‐ligand
and its complexes was evaluated against HCT‐116 HepG‐2 and
MCF‐7 cell lines within the concentration range 0–10μM. The
IC50 values were evaluated for each compound and the results
are shown in Figure 9 and Table S4. As shown, most complexes
display manifestly cytotoxic potencies (which are greater than
that of the ligand) compared to vinblastine standard drug. It
seems that changing the complexation locations and the nature
of the metal ion has an impact on the biological activity.
Cytotoxicity of the complexes may be due to the focal
metal atom which was considered in Tweedy”s chelation
theory.[46,47] Cytotoxicity conclusions indicated that all tested
complexes (IC50 = 25.4 – 98.4 μg/μl) demonstrated potent
cytotoxicity against HCT‐116 cancer cells, (IC50 = 19.3 –
68.6 μg/μl) demonstrated potent cytotoxicity against HepG‐2
cancer cells and (IC50 = 14 – 55.3 μg/μl) against MCF‐7 can-
cer cells. HNAP V complex shows the highest cytotoxicity
effect with IC50 value of 14 μg μl−1, followed by HNAPNi
complex with IC50 value of 37.4 μg μl−1 and then HNAPCr
complex with IC50 value of 55.3 μg μl−1 in the case of all tested
cancer cells. It is observed also that all complexes are more
potent than the free pro‐ligand. This indicates the benefits of
the anti‐tumour potency upon coordination. The cytotoxic
potency may be explained in that the positive charge of the
metal increases the acidity of coordinated pro‐ligand that gives
protons, causing more potent hydrogen bonds which enhance
the biological activity.[22,47] It seems that changing the coordi-
nation locations and the nature of the metal ion has a clear effect
on the biological activity by modifying the binding ability to
DNA.[12,48] Gaetke and Chow reported that metal has been sug-
gested to smooth oxidative tissue damage through a free‐radical
mediated trajectory analogous to the Fenton reaction.[49]
FIGURE 8 DNA binding results of prepared imine complexes based
on gel electrophoresis. Lane 1: DNA ladder; lane 2: HNAPV + DNA;
lane 3: HNAPCr + DNA; lane 4: HNAPNi + DNA; lane5: HNAPV
complex

ABDEL‐RAHMAN ET AL.
13 of 14
[15] S. Y. Ebrahimipour, I. Sheikhshoaie, A. C. Kautzb, M. Ameri, H.
Pasban‐Aliabadi, H. A. Rudbari, G. Bruno, C. Janiak, Polyhedron
2015, 93, 99.
4 | CONCLUSIONS
In this study, three innovative VO(II), Cr(III) and Ni(II) imine
complexes have been synthesized and their structures have
been characterized using physicochemical and spectral tools.
The obtained results demonstrated that the HNAP imine
pro‐ligand behaves as a dibasic tridentate ONO ligand and
coordinates to VO(II), Cr(III) and Ni(II) in a 1:1 molar ratio.
From the analytical and spectral data, it is observed that the
complexes adopted octahedral geometry in the case of Cr(III),
tetrahedral geometry in the case Ni(II) and distorted square
pyramidal geometry in the case of VO(II). The antipathogenic
screening showed that these complexes are good antimicro-
bial agents against various organisms as compared to stan-
dards. Moreover, the interaction of the complexes with CT‐
DNA has been effectively explored by electronic absorption,
viscosity measurements and gel electrophoresis. The DNA
interaction studies suggest intercalative and replacement
modes of interaction. Furthermore, the growth inhibitory
effect of the prepared compounds was tested on HepG‐2,
HCT‐116 and MCF‐7 cancer cells. Among these compounds,
HNAPV significantly decreases cell viability in time‐ and
dose‐dependent manners. These biological findings from
our study would be helpful in exploring the interaction of
DNA exposed to metal complexes and may lead to progress
in improvement of novel metal‐based therapeutic drugs.
[16] S. Rayati, A. Ghaemi, N. Sadeghzadeh, Catal. Commun. 2010, 11, 792.
[17] H. Keypour, M. Rezaeivala, L. Valencia, P. Pérez‐Lourido,
Polyhedron 2008, 27, 3172.
[18] L. H. Abdel‐Rahman, R. M. El‐Khatib, L. A. E. Nassr, A. M.
Abu‐Dief, F. E. D. Lashin, Spectrochim. Acta A 2013, 111, 266.
[19] L. H. Abdel‐Rahman, A. M. Abu‐Dief, M. Ismael, M. A. A.
Mohamed, N. A. Hashem, J. Mol. Struct. 2016, 1103, 232.
[20] A. M. Abu‐Dief, L. A. E. Nassr, J. Iran. Chem. Soc. 2015, 12, 943.
[21] L. H. Abdel Rahman, A. M. Abu‐Dief, N. A. Hashem, A. A.
Seleem, Int. J. Nano Chem. 2015, 1, 79.
[22] L. H. Abdel‐Rahman, A. M. Abu‐Dief, E. F. Newair, S. K.
Hamdan, J. Photochem. Photobiol. B 2016, 160, 18.
[23] A. M. Abu‐Dief, I. F. Nassar, W. H. Elsayed, Appl. Organometal.
Chem. 2016, 30, 917.
[24] S. S. Hindo, M. Frezza, D. Tomco, M. J. Heeg, L. Hryhorczuk, B.
R. McGarvey, Q. P. Dou, C. N. Verani, Eur. J. Med. Chem. 2009,
44, 4353.
[25] M. I. Hossain, M. Switalska, W. Peng, M. Takashima, N. Wang, M.
Kaiser, J. Wietrzyk, S. Dan, T. Yamori, T. Inokuchi, Eur. J. Med.
Chem. 2013, 69, 294.
[26] L. H. Abdel‐Rahman, A. M. Abu‐Dief, M. S. S. Adam, S. K.
Hamdan, Catal. Lett. 2016, 146, 1373.
[27] S. Chandra, S. Raizada, M. Tyagi, P. Sharma, Spectrochim. Acta A
2008, 69, 816.
[28] A. A. A. Emara, Spectrochm Acta A 2010, 77, 117.
REFERENCES
[29] R. A. Kusanur, M. Ghate, M. V. Kulkarni, J. Chem. Sci. 2004,
116, 265.
[1] L. H. Abdel‐Rahman, R. M. El‐Khatib, L. A. E. Nassr, A. M.
Abu‐Dief, Int. J. Chem. Kin. 2014, 46, 543.
[30] R. M. Silverstein, F. X. Webster, Spectrometric Identification of
Organic Compounds, 6th ed., John Wiley, New York 1997.
[2] A. M. Abu‐Dief, M. S. M. Abdelbaky, S. García‐Granda, Acta
Crystallogr. 2015, E71, 496.
[31] L. H. Abdel‐Rahman, A. M. Abu‐Dief, R. M. El‐Khatib, L. A. E.
Nassr, J. Mol. Struct. 2013, 1040, 9.
[3] L. H. Abdel‐Rahman, R. M. El‐Khatib, L. A. E. Nassr, A. M.
Abu‐Dief, Russ. J. Gen. Chem. 2014, 84, 1830.
[32] A. N. M. A. Alaghaz, M. E. Zayed, S. A. Alharbi, R. A. A. Ammar,
J. Mol. Struct. 2015, 1087, 60.
[4] J. Tisato, F. Refosco, F. Bandoli, Coord. Chem. Rev. 1994, 135, 325.
[5] J. Lacroix, Eur. J. Inorg. Chem. 2001, 2, 339.
[33] T. M. A. Ismail, A. A. Saleh, M. A. El Ghamry, Spectrochim Acta
A 2012, 86, 276.
[6] A. M. Abu‐Dief, R. Díaz‐Torres, E. C. Sañudo, L. H. Abdel‐Rahman,
N. A. Alcalde, Polyhedron 2013, 64, 203.
[34] S. Sarkar, K. Dey, S. Biswas, B. B. Bhaumik, J. Coord. Chem.
2007, 60, 1143.
[7] A. M. Abu‐Dief, I. M. A. Mohamed, J. Basic Appl. Sci. 2015, 4, 119.
[8] C. Redshaw, Dalton Trans. 2010, 39, 5595.
[35] M. Montazerozohori, S. Mojahedi Jahromi, A. Masoudiasl, P.
McArdle, Spectrochim. Acta A 2015, 138, 517.
[36] S. M. Pradeepa, H. S. B. Naik, B. V. Kumar, K. I. Priyadarsini, A.
Barik, T. R. R. Naik, M. C. Prabhakara, J. Spectrochim. Acta A
2013, 115, 12.
[9] K. Nomura, S. Zhang, Chem. Rev. 2011, 111, 2342.
[10] L. H. Abdel‐Rahman, R. M. El‐Khatib, L. A. E. Nassr, A. M.
Abu‐Dief, M. Ismael, J. Spectrochim. Acta A 2014, 117, 366.
[37] S. N. Azizi, S. E. Tilami, Micropor. Mesopor. Mater. 2013,
167, 89.
[11] L. H. Abdel‐Rahman, A. M. Abu‐Dief, S. K. Hamdan, A. A.
Seleem, Int. J. Nano Chem. 2015, 1, 65.
[38] T. A. Yousef, G. M. Abu El‐Reash, I. M. Gabr, O. A. El‐Gammal,
R. A. Bedier, J. Mol. Struct. 2012, 1029, 149.
[12] L. H. Abdel‐Rahman, A. M. Abu‐Dief, R. M. El‐Khatib, S. M.
Abdel‐Fatah, J. Photochem. Photobiol. B 2016, 162, 298.
[39] Z. Khanam, C. S. Wen, I. Ul Haq Bhat, J. King Saud Univ. 2015,
27, 23.
[13] A. Datta, N. K. Karan, S. Mitra, G. Rosair, Z. Naturforsch. 2002,
576, 999.
[40] L. P. Nitha, R. Aswathy, N. E. Mathews, B. S. Kumara, K.
[14] D. Rehder, Coord. Chem. Rev. 1999, 182, 297.
Mohanan, Spectrochim. Acta A 2014, 118, 154.

14 of 14
ABDEL‐RAHMAN ET AL.
[41] D. S. Raja, S. P. Bhuvanesh, K. Natarajan, J. Biol. Inorg. Chem.
2012, 17, 223.
SUPPORTING INFORMATION
Additional Supporting Information may be found online in
the supporting information tab for this article.
[42] L. H. Abdel‐Rahman, A. M. Abu‐Dief, N. M. Ismail, Inorg.
Nano‐Metal Chem. 2017, 47, 467.
[43] Y. Liu, W. Mei, J. Lu, H. Zhao, L. He, F. Wu, J. Coord. Chem.
2008, 61, 3213.
How to cite this article: Abdel‐Rahman LH, Abu‐
Dief AM, Basha M, Hassan Abdel‐Mawgoud AA.
Three novel Ni(II), VO(II) and Cr(III) mononuclear
complexes encompassing potentially tridentate imine
ligand: Synthesis, structural characterization, DNA
interaction, antimicrobial evaluation and anticancer
activity. Appl Organometal Chem. 2017;e3750. https://
doi.org/10.1002/aoc.3750
[44] L. H. Abdel‐Rahman, R. M. El‐Khatib, A. M. Abu‐Dief, S. M.
Abdel‐Fatah, A. A. Sleem, Int. J. Nano Chem. 2016, 2, 83.
[45] G. Yang, F. Z. Wu, L. Wang, L. Nian Fi, X. Tina, J. Inorg.
Biochem. 1997, 66, 141.
[46] B. Tweedy, Phytopathology 1964, 55, 910.
[47] L. H. Abdel‐Rahman, A. M. Abu‐Dief, R. M. El‐Khatib, S. M.
Abdel‐Fatah, Bioorg. Chem. 2016, 69, 140.
[48] G. Feng, J. C. Mareque‐Rivas, N. H. Williams, Chem. Commun.
2006, 1845.
[49] L. M. Gaetke, C. K. Chow, Toxicology 2003, 189, 147.