Microwave-Assisted Synthesis of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) Complexes of Tridentate Schiff Base N-(2-hydroxyphenyl) 2-hydroxy-5- bromobenzaldimine: Characterization, DNA Interaction, Antioxidant, and in Vitro Antimicrobial Studies

Article abstract of DOI:10.1080/15533174.2013.799202

Five mononuclear complexes of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) with the Schiff base N-(2-hydroxyphenyl) 2-hydroxy-5-bromobenzaldimine were synthesized under microwave irradiation. The microwave irradiation method was found remarkably successful

Full text of DOI:10.1080/15533174.2013.799202

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Synthesis and Reactivity in Inorganic, Metal-Organic,
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Microwave-Assisted Synthesis of Mn(II), Co(II), Ni(II),
Cu(II), and Zn(II) Complexes of Tridentate Schiff Base
N-(2-hydroxyphenyl) 2-hydroxy-5-bromobenzaldimine:
Characterization, DNA Interaction, Antioxidant, and In
Vitro Antimicrobial Studies
a b
Ayman A. Abdel Aziz
a
Chemistry Department, Faculty of Science , Ain Shams University , Cairo , Egypt
b
Chemistry Department, Faculty of Science , University of Tabuk , Tabuk , Saudi Arabia
Accepted author version posted online: 17 Dec 2013.Published online: 26 Mar 2014.
To cite this article: Ayman A. Abdel Aziz (2014) Microwave-Assisted Synthesis of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II)
Complexes of Tridentate Schiff Base N-(2-hydroxyphenyl) 2-hydroxy-5-bromobenzaldimine: Characterization, DNA Interaction,
Antioxidant, and In Vitro Antimicrobial Studies, Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal
Chemistry, 44:8, 1137-1153, DOI: 10.1080/15533174.2013.799202
To link to this article: http://dx.doi.org/10.1080/15533174.2013.799202
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Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 44:1137–1153, 2014
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1553-3174 print / 1553-3182 online
DOI: 10.1080/15533174.2013.799202
Microwave-Assisted Synthesis of Mn(II), Co(II), Ni(II),
Cu(II), and Zn(II) Complexes of Tridentate Schiff Base
N-(2-hydroxyphenyl) 2-hydroxy-5-bromobenzaldimine:
Characterization, DNA Interaction, Antioxidant, and In
Vitro Antimicrobial Studies
Ayman A. Abdel Aziz
Chemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
Chemistry Department, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
mechanism has not yet been entirely understood[1,2]. The medic-
Five mononuclear complexes of Mn(II), Co(II), Ni(II), Cu(II), inal properties of metal complexes depend on the nature of
and Zn(II) with the Schiff base N-(2-hydroxyphenyl) 2-hydroxy-
-bromobenzaldimine were synthesized under microwave irradi-
[3]
the metal ions and the ligands . It is well known that metal
5
ions present in the complexes are not only accelerating the
drug action but also increase the effectiveness of the organic
ligands .
A great number of chemotherapeutic anticancer drugs are
those compounds interacting with DNA directly or preventing
the proper relaxation of DNA. Also, over production of acti-
vated oxygen species in the forms of superoxide anion (O2
ation. The microwave irradiation method was found remarkably
successful and gave higher yield at a less reaction time. The com-
[
4]
1
plexes were fully characterized by elemental analyses, FT-IR, H
NMR, EPR, FAB mass spectra, electronic spectra, molar conduc-
tivity, magnetic susceptibility measurements, and thermogravimet-
ric analyses (TGA). Structural compositions were assigned by mass
spectral studies. Four-coordinate geometry has been assigned to
these complexes tentatively. The interaction of the complexes with
calf thymus DNA (CT-DNA) was investigated by absorption spec-
·−
)
·
and hydroxyl radical (HO ), generated by normal metabolic pro-
troscopy, emission spectroscopy, and viscosity measurements. The cess, is considered to be the main contributor to oxidative dam-
experimental evidences indicated that the binding strength follow
the order Cu(II) > Mn(II) > Co(II) > Ni(II) >Zn (II). More-
over, the complexes were examined for their antioxidant activities
ages to biomolecules such as DNA, lipids, and proteins, thus
accelerating cancer, aging, inflammation, cardiovascular, and
neurodegenerative diseases .
[
5]
·
−
·
against reactive oxygen species (O
2
and HO radicals). Addi-
In this connection,studies of interaction between DNA and
tionally, the ligand and its complexes were screened in vitro for
their antibacterial and antifungal activities. Preliminary informa- Schiff base metal complexes of multidentate aromatic ligands
tion obtained from the present work would help in the development
of nucleic acid molecular probes and new therapeutic reagents for
diseases.
have been of current interest in the field of medicinal research
and in the development of new therapeutic agents, mainly due
to the fact that they exhibit novel electronic and/or magnetic
properties with fascinating structural features, as well as the
ability of these ligands to be modulated to DNA binding and
Keywords antimicrobial activity, antioxidant activity, characteriza-
tion, complexes, DNA binding, microwave synthesis,
[6]
∩
∩
cleaving abilities .
O N O donor Schiff base
In the present work, the tridentate Schiff base ligand N-(2-
hydroxyphenyl) 2-hydroxy-5-bromobenzaldimine (LH2) and its
Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes were syn-
thesized by microwave-assisted synthesis as a powerful syn-
thetic tool. In order to investigate the coordination mode of
ligand, the complexes have been fully characterized by FT-
INTRODUCTION
Transition metal complexes have been widely applied in
the field of medicine for centuries, although their molecular
1
IR, H NMR, FAB-mass UV–VIS, magnetic measurements,
Received 26 March 2013; accepted 17 April 2013.
Author correspondence to Ayman A. Abdel Aziz, Department of
Chemistry, Faculty of Science, Ain Shams, 11566 Cairo, Egypt. E-mail:
aabdelaziz@ut.edu.sa
Color versions of one or more of the figures in the article can be
found online at www.tandfonline.com/lsrt.
and EPR studies. The DNA binding properties of the com-
plexes have been investigated by absorption, fluorescence, and
viscosity measurements. Moreover, the ligand and its com-
plexes are also tested for their antioxidant in vitro antimicrobial
activities.
1137

1138
A. A. ABDEL AZIZ
EXPERIMENTAL
Materials
Synthesis of Complexes
All the new Schiff base complexes were prepared by the
same general procedure with stoichiometric amount of ligand:
hydrated metal nitrate in a 1:1 mole ratio were mixed in a
grinder. The reaction mixture was then irradiated in the mi-
crowave oven using 3–4 mL ethanol. The reaction was com-
pleted in ∼ 6 min. The mixture was cooled to room temperature
and poured into ice chilled ethanol, filtered, washed several
2-hydroxy-5-bromobenzaldehyde
(5-Br-salicylaldehyde)
was supplied from Merck, 2-aminophenol, Mn(NO3)2.4H2O,
Co(NO3)2.6H2O, Ni(NO3)2.6H2O, and Cu(NO3)2.3H2O and
Zn(NO3)2.6H2O were supplied from Sigma–Aldrich. All
solvents were of analytical grade.
◦
times with hot petroleum ether (60–80 C) and dried in vacuum
Instruments
−1
over P O .
2
5
FT-IR spectra in KBr pellets (4000–400 cm ) were car-
ried out on a Unicam-Mattson 1000 FT-IR. Elemental analyses
were carried out on a JEOL JMS-AX500 Mass Spectrometer. H
Synthetic route of N-(2-hydroxyphenyl) 2-hydroxy-5-
brormobenzaldimine and its M(II) complexes is shown in
Scheme 1.
1
NMR measurements were performed on a Spectrospin-Bruker
AC 300 MHz spectrometer using DMSO-d6 as a solvent and
TMS as an internal reference. Fast atomic bombardment mass
spectra (FAB-MS) were recorded with a VGZAB-HS spec-
trometer in a 3-nitrobenzylalcohol matrix. Molar conductivi-
Determination of the Metal Content of the Complexes
Thirty milligram of the different chelates was transferred to
Kjeldahl flask. 5.0 mL concentrated nitric acid (1.0 M) was
added initially to the powdered chelates, to start the fast wet ox-
idation digestion. This mixture had been digested by a gradual
heating with dropping of H2O2 solution. This treatment was con-
ducted until most of the powdered complexes were diminished
and the remaining solution had the color of the corresponding
metal salt. This solution was diluted up to 50 mL by deion-
−3
ties of 1 × 10 M DMSO complex solutions were measured
by using Jenway 4010 conductivity meter. Magnetic moments
were determined on a Sherwood Scientific magnetic moment
◦
balance (Model N0: MK1) at room temperature (25 C) using
Hg[Co(SCN)4] as a calibrant. Corrections for diamagnetism of
[
7]
the constituents were made using Pascal constants . Thermo-
gravimetric analyses (TGA) were carried out using a Shimadzu
DT-50 thermal analyzer under nitrogen atmosphere with a heat-
ized water and the metal content was determined by analytical
methods described in the literature[
8–10]
.
◦
ing rate of 10 C/min. Electron spin resonance (ESR) measure-
CT-DNA Interaction Studies
ments of solid complexes were recorded at room temperature
on Bruker EPR spectrometer at 9.706 GHz (X-band), the mi-
crowave power was (1.0 mW) with 4.0 G modulation ampli-
tude, using 2,2-diphenylpyridylhydrazone (DPPH) as standard
All experimental involving CT-DNA were performed in
HCl/NaCl (5:50 mM) buffer solution (pH = 7.24). Tris-HCl
was prepared using deionized and sonicated triple distilled wa-
◦
ter and kept at 4 C for 3 days. The absorption ratio of CT-DNA
(
g = 2.0037). Electronic spectra were recorded on a Shimadzu
solutions A260/A280 was 1.9:1, indicating that the DNA was suffi-
ciently free from protein[ . The DNA concentration was deter-
mined via absorption spectroscopy using the molar absorption
UV 1800 spectrophotometer, equipped with a PC, using UV
Probe software, version 2. Fluorescence spectra were recorded
on a Jenway6270Flourimeter at room temperature. Microwave-
assisted synthesis was performed in an open glass vessel on a
modified microwave oven model 2001 ETB with rotating tray
and a power source 230 V, microwave energy output 800 W, and
microwave frequency 2450 MHz.
11]
−1
−1
[12]
coefficient of 6600 M cm (260 nm) for CT-DNA
.
Stock solutions of metal complexes were prepared by dis-
solving them in dimethyl sulfoxide (DMSO) and suitably dilut-
ing them with the corresponding buffer to the required concen-
trations for all experiments. The extent of DMSO in the final
concentration did not exceed 0.1% in the tested solutions. At
Microwave-Assisted Syntheses
The use of microwave heating for the synthesis of the Schiff this concentration, DMSO was not found to have any effect on
base ligand and its complexes allows a drastic reduction of DNA conformation.
the reaction times required by conventional heating and affords
comparable or better yields.
Absorption titration experiments were carried out by varying
the DNA concentration in the range of (0–10 μM) and main-
taining the complex concentration constant at (50 μM). Upon
measuring the absorption spectra, equal amount of DNA was
added to both the complex solution and the reference solution
Synthesis of N-(2-hydroxyphenyl)
2-hydroxy-5-brormobenzaldimine (LH2)
0.1 mol of 2-amiophenol and 0.1 mol of 5-bromo-2- to eliminate the absorbance of DNA itself. The reference solu-
hydroxybenzaldehyde(5-Br-salicylaldehyde) were mixed well tion was the corresponding buffer solution. Absorbance values
in a 50 mL Pyrex beaker and the mixture was irradiated in a were recorded after each successive addition of DNA solution
microwave oven for 2 min. The reaction was monitored by thin and equilibration for ∼ 10 min. Each sample was measured three
layer chromatography (TLC). After completion of the reaction, times and an average value was calculated. The absorption data
the reaction mixture was allowed to attain room temperature and were analyzed for an evaluation of the intrinsic binding constant
the yellow product obtained was recrystallized from ethanol.
Kb of the complexes with CT-DNA.

MICROWAVE SYNTHESIS, DNA INTERACTION
1139
SCH. 1.
DNA competitive binding studies with ethidium bromide so- Antioxidant Activity
lution (EB) were carried out by keeping the concentration of EB Scavenging Measurements of Superoxide Radical
(30 μM) and DNA (200 μM) as constant and varying the con-
The superoxide radicals were generated in the test system
centration (0–50 μM) of the complexes. Before measurements,
the resulting solutions were shaken up and incubated for 30 min.
The emission spectra were recorded in the wavelength range of
using NBT/VitB2/MET and determined spectrophotometrically
[13–15]
by the nitroblue tetrazolium photo reduction method
. The
reported complexes (the final concentration: Ci (i = 1–6) =
500–700 nm at 595 nm (478 nm excitation wavelength).
5.0, 10.0, 20.0, 30.0, 40.0, 50.0 μM) were added to a solution
Viscosity measurements were carried out using an Oswald
containing [NBT (65 μM), L-MET (13 mM), VitB2 (1.5 μM),
EDTA (0.1 mM)] and the resulting solution was made up to
microviscometer, maintained at constant temperature (30 ±
◦
0
.1 C) in a thermostat water bath. The DNA concentration was
2
mL with phosphate buffer (10 mM, pH 7.0) in dark. The above
kept constant in all samples, but the ligand and its complexes
concentration were increased from 10 to 50 μM. Mixing of the
solution was achieved by bubbling the nitrogen gas through vis-
mixture was illuminated with a white fluorescence lamp (15 W)
for 15 min and the absorbance (Ai) was measured at 560 nm.
The above mixture without no metal complex was used as a
control and its absorbance was taken as Ao. All the experiments
were conducted in triplicate and the data were expressed as the
mean value. The suppression ratio was calculated by using the
following equation:
◦
cometer. The mixture was left for 10 min at 30 ± 0.1 C after
addition of each aliquot of complex. The flow time was mea-
sured with a digital stopwatch. The experiment was repeated in
triplicate to get the concurrent values. The data are presented
1/3
as (η/ηo) versus the ratio [complex]/[DNA], where η and ηo
are the specific viscosity of DNA in the presence and the ab-
sence of the complex, respectively. The values of η and η0 were
calculated by the following equation:
Ao − Ai
−
O2 · scavenging activity (%) =
× 100.
Ao
Scavenging Measurements of Hydroxyl Radical
η = (t − to) /to,
·
The hydroxyl radical (HO ) in aqueous media was gener-
ated through the Fenton reaction[ . The solutions of the tested
compounds were prepared with DMF. The reaction mixture
contained 2.5 mL 0.15 M phosphate buffer (pH = 7.4), 0.5 mL
16]
where to is the observed flow time of DNA containing solution
and t is the flow time of buffer alone. Relative viscosities for
DNA were calculated from the relation, η/ηo.
114 μM safranin, 1 mL 945 μM EDTA-Fe(II), 1 mL 3% H2O2,

1140
A. A. ABDEL AZIZ
TABLE 1
Elemental analyses, molar conductance and magnetic susceptibility data of the Schiff base ligand (LH2) and its complexes
Calculated (Found) (%)
Yield
(%)
M.P.
( C) M.Wt
◦
−1
2
−1
Compounds
Color
C
H
N
Br
M
ꢀm (ꢁ cm mol )
(
[
LH2) C13H10NBrO2
MnL(H2O)] (1)
99
92
176 292.13
Orange
53.44 (53.32) 3.45 (3.38) 4.79 (4.76) 27.35 (27.16)
—
—
7.3
>300 363.06 Pale brown 43.00 (42.89) 2.77 (2.63) 3.85 (3.66) 22.00 (21.68) 15.13 (15.02)
(
C13H10NBrO3)Mn
CoL(H2O)] (2)
C13H10NBrO3)Co
NiL(H2O)] (3)
C13H10NBrO3)Ni
CuL(H2O)] (4)
C13H10NBrO3)Cu
ZnL(H2O)] (5)
C13H10NO3)Zn
[
[
[
[
94
95
96
97
>300 367.06 Deep brown 42.53 (42.84) 2.74 (2.81) 3.81 (3.73) 21.77 (21.52) 16.05 (15.97)
16.5
9.5
6.2
(
>300 366.82
>300 371.67 Dark green 42.01 (42.09) 2.71 (2.75) 3.76 (3.66) 21.49 (21.38) 17.07 (17.00)
>300 373.52 Yellow 41.80 (41.71) 2.69 (2.66) 3.74 (3.69) 21.39 (21.26) 17.50 (17.41)
Brown
42.56 (42.48) 2.74 (2.62) 3.82 (3.77) 21.78 (21.66) 16.00 (15.96)
(
(
4.1
(
and 30 μL the tested compound solution (the final concentra- antifungal drug) were used as the positive controls. The experi-
tion: Ci (I = 1–6) = 5.0, 10.0, 20.0, 30.0, 40.0, 50.0 μM). The ments were performed in triplicate.
sample without the tested compound was used as the control.
◦
The reaction mixtures were incubated at 37 C for 1 h in a water
RESULTS AND DISCUSSION
bath. Absorbances (Ai, Ao, and Ac) at 520 nm were measured.
The suppression ratio for HO was calculated from the following
expression:
N-(2-hydroxyphenyl)
Schiff base ligand and its metal complexes were synthesized
under microwave irradiation and fully characterized by ele-
mental analyses, FT-IR, H NMR, EPR, FAB mass spectra,
electronic spectra, molar conductivity, magnetic susceptibility
measurements, and TGA. Elemental analysis data of the
complexes indicated the formation of 1:1 [M:L] ratio. All the
metal complexes were colored, stable toward air, insoluble in
water, and common solvents but soluble in DMF and DMSO,
except Zn(II) complex was soluble only in DMSO. The molar
2-hydroxy-5-bromobenzaldimine
·
1
Ao − Ao
HO · scavengingactivity (%) =
× 100,
Ac − Ao
where Ai is the absorbance in the presence of the tested com-
pound; Ao is the absorbance in the absence of the tested com-
pound; and Ac is the absorbance in the absence of the tested
compound, EDTA-Fe(II) and H2O2.
−3
conductivities (ꢀm) of 1×10 M solutions of the complexes
−1
−1
2
in DMSO fall in the range 4.1–16.5 ꢁ mol cm . These low
Screening for Antimicrobial Activity
values indicated that all of the complexes have non-electrolytic
The antibacterial and antifungal activities of the newly syn- nature[ . Elemental analyses and some physical properties of
thesized compounds were evaluated by the agar well diffusion N-(2-hydroxyphenyl) 2-hydroxy-5-bromobenzaldimine (LH2)
method[ against the bacteria: gram +ve (S. aureus and B. sub- and its reported complexes are listed in Table 1.
tilis) and gram −ve (E. coli and P. aeruginosa) and the fungi:
19]
17]
Characterization of the Complexes
A. niger, A. flavus, C. lunata, and C. albicans. All the micro-
bial cultures were adjusted to 0.5 McFarland Standard, which FT-IR Spectra
is visually comparable to a microbial suspension containing ap- The FT-IR spectra of the complexes are compared with that of
8
[18]
proximately 1.5 × 10 cfu/mL . 20 mL of agar media was the free ligand in order to determine the coordination sites which
poured into each Petri plate and the plates were swabbed with may involve in chelation. The characteristic FT-IR data of N-
100 μL inocula of the test microorganisms and kept 15 min for (2-hydroxyphenyl) 2-hydroxy-5-bromobenzaldimine (LH2) and
adsorption. Using an 8 mm-diameter sterile cork borer, wells their metal complexes listed in Table 2. The FT-IR spectra of the
were bored into the seeded agar plates and these were loaded free ligand exhibited a characteristic broad band due to υ(OH)
−
1
with 100 mL of a solution of each compound dissolved in the at 3431 cm . The broadness of the band was attributed to the
.
. . . .
[20]
DMSO at a concentration of 1.0 mg/mL. All the plates were in- presence of internal hydrogen bond OH N C . Further-
cubated for 24 h at 37 C in the case of bacteria strains and 48 h more, high intensity bands were observed at 1624 cm and
◦
−1
◦
−1
at 30 C in the case of fungi strains. The antimicrobial activity 1278 cm , which are assigned to υ(C N) and υ(C O) for the
of all the synthesized compounds was evaluated by measuring phenolic C O in the case of salicylideneanilines[
the zone of growth inhibition against the test organisms with In comparison with the free Schiff base ligand,
zone reader (Hiantibiotic zone scale). The medium with DMSO all the complexes exhibited a broadband in the range
21]
.
−1
as solvent was used as the negative control, whereas media 3384–3432 cm , which was assignable to υ(OH) of the
with Streptomycin (standard antibiotic) and Nystatin (standard coordinated water molecule associated with the complexes. The

MICROWAVE SYNTHESIS, DNA INTERACTION
1141
FIG. 1. FT-IR of LH2 (a) and [CuL(H2O)] complex (b).

1142
A. A. ABDEL AZIZ
TABLE 2
−1
Infrared (cm , KBr) spectral data of LH2 and its complexes
Compound
LH2
O H
C N
C O
M O
M N
3431(w, br.)
3431(s, br.)
3384(s, br.)
3618(w, br.)
3424(s, br.)
3432(m, br.)
1624(s)
1605(s)
1607(s)
1607(s)
1606(s)
1610(s)
1278(m)
1289(m)
1297(m)
1284(m)
1291(m)
1290(m)
—
—
[MnL(H2O)] (1)
[NiL(H2O)] (2)
[CoL(H2O)] (3)
[CuL(H2O)] (4)
[ZnL(H2O)] (5)
520(w)
532(w)
512(w)
511(w)
518(w)
427(w)
434 (w)
435(w)
472(w)
442(w)
Notes.
∗
s: strong, m: medium, w: weak, br: broad.
metal ions (C–O–M)[25]. The characteristic H NMR data of N-
(
its Zn(II) complex are listed in Table 3.
1
presence of one water molecule was indicated from the thermo-
gravimetric studies (vide infra). Moreover, in the FT-IR spectra
of the complexes, the band of υ(C N) is exhibited a shift to
2-hydroxyphenyl) 2-hydroxy-5-bromobenzaldimine (LH2) and
−1
lower wave numbers in the region 1605–1610 cm indicating
that the nitrogen of azomethine group is coordinated to the metal
Mass Spectral Studies
[
22]
ion . Moreover, a medium to high intensity band appeared in
The FAB-mass spectrum of Schiff base ligand (LH2) de-
picted in Figure 3a showed a molecular ion peak [M ] at
m/z 292 which is equivalent to its molecular weight corre-
sponding with formula, C13H10NBrO2. In addition, the frag-
ment peaks observed at m/z 185 and 107 were assigned to
the fragment ions [C6H5NO] and [C7H5BrO] , respectively.
The FAB-mass spectra of Mn(II), Co(II), Ni(II), Cu(II), and
Zn(II) complexes showed a molecular ion peak M corre-
sponding to m/z 363, 367, 366, 371, and 373, respectively,
consistent with monomeric nature of complexes. The FAB-
mass spectrum of Cu(II) complex (Figure 3b) showed a frag-
mentation peak at m/z 353, corresponding to the loss of
−
1
the region 1284–1297 cm due to phenolic υ(C–O), indicat-
+
ing the coordination of phenolic oxygen via deprotonation[
24]
.
Finally, the most obvious feature after the complexation was
−
−1
1
found in the region 400–600 cm . The non-ligand bands at
5
−1
11–532 cm and 427–442 cm were observed due to M–N
+
+
and M–O, which gave conclusive evidence regarding the bond-
ing of azomethine nitrogen and phenolic oxygen of the Schiff
+
[
20]
base to the metal ion . The FT-IR spectra of LH2 and its Cu(II)
complex as a representative example are shown in Figure 1.
1
H NMR Spectra of the Schiff Base and its Zinc(II) Complex
1
The H NMR spectra of N-(2-hydroxyphenyl) 2-hydroxy-5- water molecule and a fragmentation peak at m/z 308, corre-
bromobenzaldimine (LH2) and its diamagnetic Zn(II) complex sponding to demetallation of [CuL(H2O)] to form the species
+
recorded in d6-DMSO at room temperature showed a sharp sin- [L + H] . The other reported complexes showed similar pat-
glet signal at 8.67 and 8.85 ppm, respectively, which may be terns. Thus, the mass spectral data results along with el-
assigned to the azomethine hydrogen atom. The shift of the emental analyses agree with the formation of [ML(H2O)]
imine carbon proton signal to the downfield region in Zn(II) complexes with 1:1 stoichiometry.
complex in comparison with that of the free ligand inferred
coordination through the azomethine nitrogen atom of the lig- Magnetic Properties of Complexes
[
23]
and . The multiplet signal due to the aromatic protons, ex-
Magnetic measurements were recorded in order to obtain in-
ists in N-(2-hydroxyphenyl) 2-hydroxy-5-bromobenzaldimine formation about the geometry of the complexes. The magnetic
at 6.99–7.78 ppm, exhibited a small shift in Zn(II) complex at
6
.95–7.70 ppm. The small shift may be attributed to the changes
TABLE 3
1
in the electronic environment around the protons attached to the
group that contain the site of donation and involvement in com-
H NMR spectral data (δ, ppm) of LH and Zn(II) complex
2
plexation[ . Moreover, the H NMR spectrum of the parent
24]
1
Compound
LH2
δ (ppm)
Assignments
ligand showed two singlet signals at very downfield at δ 13.21
and 9.85 ppm which were attributed to two phenolic –OH pro-
tons. A comparison of H NMR spectrum of diamagnetic Zn(II)
complex (Figure 2) showed that the chemical shift observed for
the OH protons in the ligand was missed in the Zn(II) spec-
trum. The absence of –OH signals indicated deprotonation of
the hydroxyl group of the Schiff base ligand prior to coordina-
tion with Zn(II) and confirmed the bonding of oxygen to the
13.21, 9.85
(s, 2H, –OH)
(s, 1H, –CH N)
(m, 7H, ArH)
—
(s, 1H, CH N)
(m, 7 H), ArH)
,
8.67
1
6.99–7.78
—
[ZnL(H2O)] (5)
8.85
6.95–7.70
∗
s: singlet, m: multiplet.

MICROWAVE SYNTHESIS, DNA INTERACTION
1143
FIG. 2. 1H NMR of LH2 (a) and [ZnL (H2O)] complex (b).

1144
A. A. ABDEL AZIZ
FIG. 3. FAB-mass of LH2 (a) and [CuL(H2O)] complex (b).
moments obtained at room temperature showed paramagnetism known for most of the mononuclear Co(II) complexes in the
for Mn(II), Co(II), Ni(II), and Cu(II) complexes and dimag- tetrahedral environment[ . In the case of Mn(II) complex, the
netism for Zn(II) complex (Table 4). The magnetic susceptibil- magnetic moment value was found to be 5.23 BM, indicating
ity value of Cu(II) complex (1.80 BM) was an indicative of one the presence of Mn(II) complex in the tetrahedral structure. Fi-
unpaired electron per Cu(II) ion and suggested a square-planar nally, Zn(II) complex showed diamagnetism as expected for d10
geometry[ . The magnetic moment of Ni(II) complex 3.84 BM configuration, in analogy with those described for Zn(II) com-
was close to that of 3.0–3.5 B.M for the more distorted tetrahe- plexes containing N–O donor Schiff bases[ and according to
dral complexes[ . The Co(II) complex has a magnetic suscep- the empirical formulae, a tetrahedral geometry was proposed
tibility value of 4.74 BM which lies in the range (4.2–4.8 BM) for the Zn(II) complex.
28]
26]
29]
27]

MICROWAVE SYNTHESIS, DNA INTERACTION
1145
TABLE 4
2000
Electronic spectra and magnetic properties of LH2 and its
complexes
1000
Compound
UV–VIS (DMSO, 10 3 M) μeff. (BM)
−
0
a
b
LH2
226 , 346
—
a
b
c
c
c
c
c
[
[
[
[
[
MnL(H2O)] (1)
NiL(H2O)] (2)
CoL(H2O)] (3)
CuL(H2O)] (4)
ZnL(H2O)] (5)
238 , 270 , 440
5.23
3.84
4.74
1.80
Dia
-
1000
a
b
232 , 264 , 446
a
b
242 , 268 , 402
a
b
-2000
268 , 298 , 442
a
b
260 , 304 , 434
-
3000
Notes.
∗
∗
a: π→π ; b: n→π ; c: LMCT.
-4000
2
000
2500
3000
3500
4000
4500
5000
EPR Spectra of Cu(II) Complex
Magnetic Induction (G)
The EPR spectrum of solid Cu(II) complex (Figure 4)
recorded at room temperature (298 K) was consistent with the
FIG. 4. EPR spectrum of [CuL(H2O)] complex at 298 K.
[
30]
square-planar geometry. The “g” tensor values of the Cu(II)
[
31]
complexes could be used to obtain the ground state . The relaxation of the Mn(II), Co(II), and Ni(II) broaden the lines at
Cu(II) complex (5) exhibited gꢀ value of 2.09 and g value of higher temperatures[
36]
.
2
.02. The trend gꢀ > g > 2.0023 indicate that the unpaired
From the above arguments, the proposed structure of Cu(II)
complex and Zn(II) complex as an example of tetrahedral
[
32,33]
electron is localized in the dx2−y2 orbital of the Cu(II) ion
and characteristic of axial symmetry. The deviation of the cal- complexes is shown in Scheme 2.
culated gav value (2.07) from that of the free electron (2.0023)
[
34]
is due to the covalence property , which was supported by Thermal Analysis Studies
[
35]
[32]
Kivelson and Neiman . According to Hathaway , if the
Thermogravimetric analysis (TGA) is a very useful method
anisotropic value G > 4, the exchange interaction is negligi- for studying the thermal decompositions of solid sub-
ble, while G < 4 indicates a considerable exchange interaction stances, including simple metal salts and complex com-
in the complex. The calculated G value for Cu(II) complex was pounds[ . Thermal studies of all the complexes were per-
37]
4
.5, which suggested that the local tetragonal axis is aligned formed under nitrogen atmosphere in the temperature range
◦
parallel or slightly misaligned and consistent with dx2-y2 ground of 20–1000 C. The thermal curves of the [MnL(H2O)] (1)
state. Moreover, this result indicates that the exchange interac- and [CuL(H2O)] (4) as representative examples are given in
[
32,35]
tion between Cu(II) centers is negligible
. The EPR spectra Figure 5. Thermal analysis of the synthesized complexes con-
of the solid Mn(II), Co(II), and Ni(II) complexes at room tem- firmed the presence of a coordinated water molecule. The de-
perature do not show EPR signal because the rapid spin lattice composition mass losses were found in agreement with the
SCH. 2.

1146
A. A. ABDEL AZIZ
0
0
.0005
.0000
1.8
0.0005
.0000
3
2
2
1
1
0
.0
.5
.0
.5
.0
.5
0
1.6
1.4
1.2
1.0
-
0.0005
0.0010
-
-
-
-
-
0.0005
0.0010
0.0015
0.0020
0.0025
-
-0.0015
0.0020
-0.0025
-
0.8
-
0.0030
0.0035
-0.0030
-0.0035
-
0.6
[
MnL(H O)]
[CuL(H O)]
2
2
392
400
Temp. ( C)
3
97
-0.0040
0.4
0
200
400
600
800
1000
0
200
600
800
1000
o
o
Temp. ( C)
FIG. 5. The thermal curves of [MnL(H2O)] and [CuL(H2O)] complexes.
formula weightsss of each complex proposed from the ele- observed in metal Schiff base complexes containing phenolato
mental analysis. The thermal behavior of all the complexes is ligands due to “phenolato-to-M” charge transfer[ . The absorp-
almost same. The TG data revealed that the complexes decom- tion spectra of the ligand and its complexes in the absence and
poses in one step with an endothermic peak in the DTA curves the presence of CT-DNA are given in Figure 6. In the case of
40]
◦
at around 262–669 C, corresponding to the elimination of co- the ligand, with increasing DNA concentrations, a small change
ordinated water and organic ligand moieties, leaving metallic was observed in the absorption intensity which is consistent with
oxide as the final decomposition product. The residual metal its weak external contact with the duplex. For the complexes,
oxide percentages were coincided fairly with the theoretical the well-defined LMCT band observed was used to monitor ab-
values. The nature of proposed chemical change with tem- sorption titration of the complexes with DNA solution. With
perature and the percent of metal oxide obtained are given in increasing concentration of DNA, all the complexes showed
Table 5.
hypochromicity and a redshifted charge transfer peak maxima,
indicating the complexes are actively in associating with CT-
DNA. These spectral characteristics obviously suggested that
the titled complexes most likely interact with DNA through a
mode of stacking interaction between aromatic chromophore of
the complexes and the base pairs of DNA. For the quantitative
investigation of the binding strength of the ligand and its com-
plexes to CT-DNA, the intrinsic binding constants Kb of the
DNA Binding Studies
Absorption Spectral Studies
The application of electronic absorption spectroscopy is one
of the most useful techniques to investigate the binding mode of
DNA with metal complexes . The electronic absorption spec-
tra of the investigated ligand and its complexes (1–5) consist of
two or three well-resolved bands in the range of 226–446 nm.
The high-energy absorption band appeared in the spectra of the
[
38]
complexes with CTDNA were calculated using the following
function equation[
:
41]
∗
ligand and its complexes below 400 nm are assigned π–π and
∗
[39]
n–π transitions and the band observed around 400 nm in the
[DNA]
[DNA]
1
=
+
complexes spectra may be assigned to LMCT transition, usually
(
ε − ε )
(ε − ε ) [K (ε − ε )]
a
f
b
f
b
b
f
TABLE 5
Thermogravimetric characteristics of the reported complexes
Temp.
Mass loss (%)
◦
Complex
Range ( C) Calculated (Found)
Assignment
Residue
1
[
[
[
[
[
Mn(L)(H2O)] (1) [Mn(C13H8NBrO2)(H2O)] 290–530
76.05 (75.95)
79.58 (79.18)
79.63 (78.96)
78.59 (78.54)
78.21 (78.00)
C6H4N + C7H4 + /2 Br2 +H2O MnO2
1
Co(L)(H2O)] (2) [Co(C13H8NBrO2)(H2O)]
Ni(L)(H2O)] (3) [Ni(C13H8NBrO2)(H2O)]
Cu(L)(H2O)] (4) [Cu(C13H8NBrO2)(H2O)]
Zn(L)(H2O)] (5) [Zn(C13H8NBrO2)(H2O)]
396–669
389–558
262–455
438–668
C6H4N + C7H4O + /2 Br2 +H2O CoO
1
C6H4N + C7H4O + /2 Br2 +H2O NiO
1
C6H4N + C7H4O + /2 Br2 +H2O CuO
1
C6H4N + C7H4O + /2 Br2 +H2O ZnO

MICROWAVE SYNTHESIS, DNA INTERACTION
1147
1
0
0
.0
.5
.0
2.0
(1)
(
LH )
2
1
.5
1.0
0
.5
0.0
300
2
00
(
250
300
350
400
450
500
350
400
450
500
550
600
Wavelength (nm)
Wavelength (nm)
2
1
1
0
0
.0
.5
.0
.5
.0
2.0
1.5
1.0
0.5
0.0
2)
(3)
3
00
350
400
450
500
550
600
300
350
400
450
500
550
600
Wavelength (nm)
Wavelength (nm)
2
1
1
0
0
.0
2.0
1.5
1.0
0.5
0.0
(
5)
(
4)
.5
.0
.5
.0
3
00
350
400
450
500
550
600
300
350
400
450
500
550
600
Wavelength (nm)
Wavelength (nm)
.
. .. . .
FIG. 6. Electronic absorption spectra of LH2 and complexes (50 μM, DMSO) in the absence (
) and presence (—) of increasing amounts of CT-DNA
(
0–10 μM). Arrows show the changes in absorbance with respect to an increase in the DNA concentration (Inset: Plot of [DNA] vs. [DNA]/(ea − ef)).

1148
A. A. ABDEL AZIZ
3
3
2
2
1
1
50
350
300
250
200
150
100
50
(
LH2)
(1)
00
50
00
50
00
5
0
0
5
0
500
00
550
600
650
700
550
600
650
700
Wavelength (nm)
Wavelength (nm)
3
3
2
2
1
1
50
00
50
00
50
00
350
300
250
200
150
100
50
(
2)
(3)
5
0
0
5
0
500
00
550
600
650
700
550
600
650
700
Wavelength (nm)
Wavelength (nm)
3
3
2
2
1
1
50
00
50
00
50
00
350
300
250
200
150
100
50
(
4)
(5)
5
0
0
5
0
500
00
550
600
650
700
550
600
650
700
Wavelength (nm)
Wavelength (nm)
.
. .. . .
FIG. 7. Emission spectra of DNA-bound EB in Tris buffer [EB] = 30 μM, [DNA] = 200 μM in the absence (
) and presence (—) of increasing amounts of
LH2 and complexes (0–50 μM). Arrows show the changes in emission intensity with respect to an increase complex concentration (Inset: Plot of Stern–Volmer
plot of Io/I vs. [LH2]/[DNA].and [M( complex]/[DNA].
II)

MICROWAVE SYNTHESIS, DNA INTERACTION
1149
TABLE 6
UV–VIS absorption properties of LH2 and its complexes
in the presence of CT-DNA
4
Kb × 10
%
Redshift
(nm)
−
1
a
Complex
LH2
(M )
Hyporchromism
0.933
3.078
2.276
2.261
3.569
1.999
1.8
21
15
13
26
9
0.5
12
7
5
3
[MnL(H2O)] (1)
[CoL(H2O)] (2)
[NiL(H2O)] (3)
[CuL(H2O)] (4)
[ZnL(H2O)] (5)
2
where [DNA] is the concentration of DNA in base pairs, the
apparent extinctions coefficient εa, εb, and εf correspond to
Aobs./[compound], respectively, the extinction coefficient of the
compound in the free solution and the extinction coefficient of
the compound in the fully bound form, respectively. In plots
FIG. 8. The effect of increasing concentrations of LH2 and complexes on the
viscosity of CT-DNA at 30.0 ± 0.1 C.
◦
seen that the addition of the ligand and its complexes (1–5) to
DNA pretreated with EB caused appreciable reduction in emis-
sion intensity, indicating that the complexes binds to DNA at the
sites occupied by EB. The quenching of the EB bound to DNA
[
DNA]/(εa − εf) versus [DNA] (Figure 6, inset), the intrinsic
binding constants (Kb) value, given by the ratio of the slope to
the intercept of the linear fit of data were found to be 0.933 ×
4
−1
4
−1
4
−1
4
1
0 M , 3.078 × 10 M , 2.276 × 10 M , 2.261 × 10
−
1 4 4
−1
−1
by the complex is in agreement with the linear Stern–Volmer
M , 3.569 × 10 M , and 1.999 × 10 M for LH2, Mn(II),
Co(II), Ni(II), Cu(II), and Zn(II) complexes, respectively, in-
dicating a moderate intercalation between the complexes and
CT-DNA. These (Kb) values are much smaller than the typ-
ical classical intercalators (e.g., EB-DNA, ∼10 M )
have the same level as those of some well-established inter-
equation[
:
46]
ꢀM(II)Complexꢁ
[DNA]
Io/I = 1 + KSV
6
−1 [42]
and
calation agents (∼10 )[43,44]. The Kb value (Table 6) revealed where Io and I represent the fluorescent intensities in the absence
that the comparative binding strength of the complexes with and the presence of the complex, respectively, and Ksv is the lin-
CT-DNA were in the order 4 > 1 > 2 > 3 > 5 > LH2, ear Stern–Volmer quenching constant. The Ksv value is obtained
suggesting that Cu(II) intercalates more strongly than other from the slope of the Io/I versus [M( complex]/[DNA] linear
complexes, which may be explained as in the square-planar plot (Figure 7, inset) and is found to be 0.864, 1.54, 1.17, 1.05,
complex the more extended π-area of planar aromatic ring of 1.93, and 1.01 for LH2, Mn(II), Co(II), Ni(II), Cu(II), and Zn(II)
the ligand could intercalate better between the adjacent base complexes, respectively, indicating that DNA binding affinity of
pairs of DNA than that of other complexes having tetrahedral Cu(II complex is higher than those of other complexes. Also, the
4
II)
geometries.
data revealed that DNA-bound EB can be more readily replaced
by the complexes in the order 4 > 1 > 2 > 3 > 5 > LH2, which
is consistent with the above UV–VIS observations.
Fluorescence Spectral Studies
Ethidium bromide (EB) was used to investigate the potential
DNA binding mode of the ligand and its complexes (1–5). EB Viscosity Measurements
emits intense fluorescence at 595 nm in the presence of CT-
Due to its sensitivity to the change of length of DNA, vis-
DNA due to its strong intercalation between the adjacent DNA cosity measurements may be the most effective means to study
base pairs. The addition of a second molecule which binds to the binding mode of complexes to DNA. In classical interca-
DNA more strongly than EB would quench the DNA-induced lation, the DNA helix lengthens as base pairs are separated to
EB emission[ . The extent of quenching of the fluorescence of accommodate the bound ligand leading to an increase in DNA
EB bound to DNA would reflect the extent of the DNA bind- viscosity, whereas a partial, non-classical ligand intercalation
ing of the second molecule. The ligand, complexes (1–5) and causes a bend (or kink) in DNA helix reducing its effective
DNA independently or in combination do not give luminescence length and thereby its viscosity[ . The effect of the ligand and
spectra in buffer and DMSO solutions. The emission spectra of its complexes on the viscosity of CT-DNA is shown in Fig-
DNA-bound EB in the absence and the presence of the ligand ure 8. The viscosity measurements clearly showed that as the
and its complexes (1–5) are shown in Figure 7. It was clearly amount of the ligand (LH2) and complexes (1–5), the relative
45]
47]

1150
A. A. ABDEL AZIZ
FIG. 9. Scavenging activity of complexes on superoxide radical (a) and hydroxyl radical (b).
viscosity of CT-DNA increases steadily, which proved that all many diseases. Since the reported complexes exhibited good
the compounds can intercalate between adjacent DNA base DNA-binding affinity, it was considered worthwhile to study
[
48]
pairs, causing an extension in the DNA helix . The increased other potential aspects of these compounds such as antioxidant
degree of viscosity, which may depend on its affinity to DNA, activity. Figure 9 depicts the inhibitory effect of the complexes
·− ·
on O2 and hydroxyl HO . As shown in Figure 9, the inhibitory
The DNA binding studies have been described in this study effect of the complexes (1–5) on O2 and hydroxyl HO was
show that changing the metal environment can modulate the concentration dependent and the suppression ratio increased
follows the order of 4 > 1 > 2 > 3 > 5 > LH2.
·−
·
[
49]
binding property of the complex with DNA
.
with increasing of sample concentration (5–50 μM). Among
the studied complexes, Cu(II) and Mn(II) complexes showed
highest superoxide scavenging ability of 91% and 88% respec-
tively at a concentration of 50 μM. Also, Co(II), Ni(II), and
Zn(II) complexes also showed considerably high scavenging
activity of 72%, 61%, and 54%, respectively. The complexes
at the same concentration (10–50 μM) were also screened for
Antioxidant Activity
Schiff base metal complexes are known to show various
biological activities including biocidal and antioxidant activ-
[
50,51]
ities
(
. Reactive oxygen species (ROS), e.g., superoxide
·−
·
O2 ) and hydroxyl (HO ) radical are responsible for cell
·
the HO radical scavenging activity and it was evident from the
membrane disintegration, membrane protein damage, DNA mu-
tation, and further initiate or propagate the development of
results that Cu(II) and Mn(II) complexes are better scavenging
TABLE 7
Antimicrobial activity of LH2 and its complexes
Antibacterial activity of zone of inhibition (mm) Antifungal activity of zone of inhibition (mm)
Compound
LH2
S. aureus
B. subtilis
E. coli
P. aeruginosa
A. niger
A. flavus
C. lunata
C. albicans
8
9
10
17
16
16
20
13
24
—
0
10
17
16
18
20
12
24
—
0
14
18
16
17
21
13
—
21
0
13
19
17
20
22
16
—
21
0
11
19
13
23
27
16
—
22
0
14
17
18
21
25
18
—
22
0
[MnL(H2O)] (1)
[NiL(H2O)] (2)
[CoL(H2O)] (3)
[CuL(H2O)] (4)
[ZnL(H2O)] (5)
21
17
19
23
11
28
—
0
21
15
17
24
18
27
—
0
Streptomycin
Nystatin
DMSO

MICROWAVE SYNTHESIS, DNA INTERACTION
1151
FIG. 10. Biological diagram of LH2 and its complexes against bacteria strains (a) and fungi strains (b).
agents (84% and 73%) than Co(II), Ni(II), and Zn(II) which pounds possess higher antifungal activity than the antibacterial
showed 54%, 50%, and 39% scavenging activities respectively property.
at a concentration of 50 μM.
In Vitro Antimicrobial Activity
CONCLUSION
Antibacterial and antifungal activities of the N-(2-
A series of mononuclear four coordinated transition metal (II)
hydroxyphenyl) 2-hydroxy-5-bromobenzaldimine (LH2) and its complexes (M = Mn, Co, Ni, Cu, and Zn) were synthesized un-
metal complexes (1–5) were tested for their inhibitory effects der microwave conditions by the reaction hydrated metal nitrate
on the growth of bacteria: S. aureus, B. subtilis, E. coli, and salt with the tridentate ONO Schiff base N-(2-hydroxyphenyl)
P. aeruginosa and the fungi: A. niger, A. flavus, C. lunata, 2-hydroxy-5-bromobenzaldimine (LH2). The analytical, FT-IR,
and C. albicans because such organisms can achieve resis- UV–VIS, EPR, FAB-mass, magnetic and thermal studies have
tance to antibiotics through biochemical and morphological been confirmed the bonding of Schiff bases to metal ions through
modification[ . The inspection of microbial results is listed the azomethine-nitrogen and phenolic-oxygen atoms forming
in Table 7 and represented graphically in Figure 10. The re- stable four coordinated complex, where the fourth site was oc-
sults have indicated that, in comparison with the Schiff base cupied by a water molecule. Based on the characterization data
N-(2-hydroxyphenyl) 2-hydroxy-5-bromobenzaldimine (LH2), and keeping in mind the preferred geometries, the square-planar
Mn(II) and Cu(II) complexes showed good antibacterial and an- geometry was proposed for Cu(II) complex, whereas the tetra-
tifungal activity, whereas the Co(II), Ni(II), and Zn(II) showed hedral geometry was proposed for Mn(II), Co(II), Ni(II), and
moderate activity. The variation in the activity of different metal Zn(II) complexes, respectively. The interaction of the ligand
complexes against different microorganisms depends on the im- and its complexes with CT-DNA was performed with UV spec-
permeability of the cell or differences in the ribosomes in the troscopy, fluorescence study, and viscometric measurements and
microbial cells[ . Such increased activity of the metal chelates it revealed that the reported compounds can bind to CT-DNA
can be explained on the basis of chelation theory. On chelation, via intercalation mode. The binding studies have been shown
the polarity of the metal ion will be reduced to a greater extent that Cu(II) complex has stronger binding strength as compared
due to the overlap of the ligand orbital and partial sharing of the to the other complexes. Additionally, the complexes also exhib-
52]
53]
·−
·
positive charge of the metal ion with donor groups. Further, it in- ited good antioxidant (O2 and HO radical scavengers) and the
creases the delocalization of π-electrons over the whole chelate suppression ratio follow the order of Cu(II) > Mn(II) > Co(II)
ring and enhances the penetration of the complexes into lipid > Ni(II) > Zn(II) > LH2. Moreover, in vitro antimicrobial ac-
membranes and blocking of the metal binding sites in the en- tivities of the new compounds were studied against the bacteria
zymes of microorganisms. In general, metal complexes are more strains (S. aureus, B. subtilis, E. coli, and P. aeruginosa) and the
active than the ligands because metal complexes may serve as fungi strains (A. niger, A. flavus, C. lunata, and C. albicans).
a vehicle for activation of ligands as the principle cytotoxic The data have been shown that the metal complexes show en-
species[ . The studies showed that the newly synthesized com- hanced inhibitory activity compared to the parent ligand under
54]

1152
A. A. ABDEL AZIZ
identical experimental conditions. These findings clearly indi-
cated that the complexes have many potential practical appli-
cations, like the development of nucleic acid molecular probes
and new therapeutic reagents for diseases.
7. Earnshaw, A. Introduction to Magnetochemistry; Academic Press: London,
968.
1
8
. Rishi, A.K.; Garg, B.S.; Singh, R.P. Tirimetric determination of cobalt(II)
with EDTA using 1-(2-Pyridylazo)-2-phenanthrol (PAP) as a visual indica-
tor. Fresenius’ J. Anal. Chem. 1972, 259, 288–288.
9. Vogel, A.I. Text Book of Quantitative Chemical Analysis, 5th ed.; Long-
mans: London, 1998.
10. Macarovici, C.G. Inorganic Quantitative Chemical Analysis; Editura
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