Synthesis, characterization, molecular modeling and antioxidant activity of (1E,5E)-1,5-bis(1-(pyridin-2-yl)ethylidene)carbonohydrazide (H2APC) and its zinc(II), cadmium(II) and mercury(II) complexes

Article abstract of DOI:10.1016/j.molstruc.2012.04.029

A new series of Zn(II), Cd(II) and Hg(II) complexes of (1E,5E)-1,5-bis(1- (pyridin-2-yl)ethylidene)carbonohydrazide (H₂APC) have been prepared and characterized by elemental analyses, spectral (IR, UV-visible, mass and ¹H NMR) as well as magnetic and thermal measurements. The data revealed that the ligand acts a monobasic hexadentate, neutral tri- and monodentate in Zn(II), Cd(II) and Hg(II) complexes, respectively. An octahedral geometry is proposed for Zn(II) complex, a trigonal bi-pyramid for Cd(II) complex and a tetrahedral one for Hg(II) complex. The bond length, bond angle, HOMO, LUMO and charges on the atoms have been calculated to confirm the geometry of the ligand and the investigated complexes using material studio program. Kinetic parameters were determined for each thermal degradation stage of some complexes using Coats-Redfern and Horowitz-Metzger methods. The antioxidant, anti-hemolytic, and cytotoxic activities of the compounds have been screened. H₂APC showed moderate antioxidant activity using ABTS and DPPH methods. With respect to erythrocyte hemolysis and in vitro Ehrlich ascites assay, H₂APC exhibited the potent antioxidative activity followed by Cd(II) and Zn(II) complexes while Hg(II) complex showed very weak activity.

Full text of DOI:10.1016/j.molstruc.2012.04.029

Journal of Molecular Structure 1020 (2012) 6–15
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis, characterization, molecular modeling and antioxidant activity
of (1E,5E)-1,5-bis(1-(pyridin-2-yl)ethylidene)carbonohydrazide (H2APC)
and its zinc(II), cadmium(II) and mercury(II) complexes
⇑
O.A. El-Gammal , G.M. Abu El-Reash, S.E. Ghazy, A.H. Radwan
Department of Chemistry, Faculty of Science, Mansoura University, P.O. Box 70, Mansoura, Egypt
a r t i c l e i n f o
a b s t r a c t
Article history:
A new series of Zn(II), Cd(II) and Hg(II) complexes of (1E,5E)-1,5-bis(1-(pyridin-2-yl)ethylidene)carbon-
ohydrazide (H2APC) have been prepared and characterized by elemental analyses, spectral (IR, UV–
visible, mass and 1H NMR) as well as magnetic and thermal measurements. The data revealed that the
ligand acts a monobasic hexadentate, neutral tri- and monodentate in Zn(II), Cd(II) and Hg(II) complexes,
respectively. An octahedral geometry is proposed for Zn(II) complex, a trigonal bi-pyramid for Cd(II) com-
plex and a tetrahedral one for Hg(II) complex. The bond length, bond angle, HOMO, LUMO and charges on
the atoms have been calculated to confirm the geometry of the ligand and the investigated complexes
using material studio program. Kinetic parameters were determined for each thermal degradation stage
of some complexes using Coats–Redfern and Horowitz–Metzger methods. The antioxidant, anti-hemo-
lytic, and cytotoxic activities of the compounds have been screened. H2APC showed moderate antioxidant
activity using ABTS and DPPH methods. With respect to erythrocyte hemolysis and in vitro Ehrlich ascites
assay, H2APC exhibited the potent antioxidative activity followed by Cd(II) and Zn(II) complexes while
Hg(II) complex showed very weak activity.
Received 25 March 2012
Accepted 10 April 2012
Available online 18 April 2012
Keywords:
Carbohydrazone
Spectral characterization
Thermal analysis
DFT and ABTS
DPPH-activity
Ó 2012 Elsevier B.V. All rights reserved.
1. Introduction
and Hg(II) metal ions in more details, including structural elucida-
tion, thermal behavior and molecular modeling of both ligand and
Carbohydrazones have been found to be one of the most fasci-
nating subjects in the field of coordination chemistry due to their
well known physiological activity, coordinative capability and
applications in analytical chemistry [1–4]. Ligands derived from
substituted carbohydrazone have played an important part in
revealing the preferred coordination geometries of metal com-
plexes and have valuable contribution in the coordination chemis-
try due to their preparative accessibility, diversity and structural
variability. The carbohydrazones and their complexes with transi-
tion metal ions have been well documented in the literature as
good therapeutic, antimicrobial, anticonvulsant, pharmacological
and catalytic agents [5–7]. The ligands that contain an amidic bond
are capable of keto–enol tautomerism and coordinated to a metal
ion in neutral or deprotonated form as quinquedentates, via pyri-
dine nitrogen, hydrazone nitrogen and carbonyl oxygen atoms.
However, the coordination behavior of ligands depends on the
metal ion, the pH of the medium, the reaction conditions and the
nature of the hydrazones [8–14]. The present work aims to inves-
tigate the chelating properties of (1E,5E)-1,5-bis(1-(pyridin-2-
yl)ethylidene)carbonohydrazide (H2APC) towards Zn(II), Cd(II)
its complexes. Also, the antioxidant activity evaluated using DPPHÅ
(2,20-diphenyl-1-picrylhydrazyl radical), ABTS (2-azino-bis(3-eth-
ylbenzthiazoline)-6-sulfonic acid) and anti-hemolytic as well as
cytotoxic activities of the compounds have been discussed.
2. Experimental
2.1. Instrumentation and materials
All the chemicals were purchased from Aldrich and Fluka and
used without further purification. Elemental analyses (C, H, N) were
performed with a Perkin–Elmer 2400 series II analyzer. Molar con-
ductance values (10ꢀ3 mol lꢀ1) of the complexes in DMF were mea-
sured using a Tacussel conductivity bridge model CD6NG. IR spectra
(4000–400 cmꢀ1) for KBr discs were recorded on a Mattson 5000
FTIR spectrophotometer. Electronic spectra were recorded on a Uni-
cam UV–Vis spectrophotometer UV2. Magnetic susceptibilities
were measured with a Sherwood scientific magnetic susceptibility
balance at 298 K. 1H NMR measurements in d6-DMSO at room tem-
perature were carried out on a Varian Gemini WM-300 MHz
spectrometer at the Microanalytical Unit, Cairo University. Thermo-
gravimetric measurements (TGA, DTA, 20–1000 °C) were recorded
⇑
Corresponding author. Tel.: +20 126712958.
E-mail address: olaelgammal@hotmail.com (O.A. El-Gammal).
0022-2860/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molstruc.2012.04.029

O.A. El-Gammal et al. / Journal of Molecular Structure 1020 (2012) 6–15
7
on a DTG-50 Shimadzu thermogravimetric analyzer at a heating
rate of 15 °C/min and nitrogen flow rate of 20 ml/min.
2.4.1.1. Antioxidant activity screening assay DPPH method. The
hydrogen atom or electron donation ability of the corresponding
compounds was measured from the bleaching of purple colored
of the methanolic solution of DPPH. This spectrophotometric assay
uses the stable radical diphenylpicrylhydrazyl (DPPH) as a reagent
[16,17]. Different concentrations of the chemical compounds were
dissolved in methanol to obtain final concentration ranged from
6.25 to 200 mg/ml to determine IC50 (concentration make 50%
inhibition of DPPH color). Fifty microliters of various sample con-
centrations were added to 5 ml of 0.004% methanolic solution of
DPPH. After 60 min of incubation at dark, the absorbance was read
against a blank at 517 nm.
2.2. Synthesis of (1E,5E)-1,5-bis(1-(pyridin-2-l)ethylidene)
carbonohydrazide (H2APC)
The carbohydrazone was synthesized by refluxing 2-acetylpyr-
idine (0.30 ml, 2.7 mmol) and carbonohydrazide (0.10 g, 1.1 mmol)
in 2:1 M ratio in hot ethanol with adding few drops of glacial acetic
acid to the reaction mixture. The solution was heated for 4 h and
on cooling a white solid was precipitated. The product was recrys-
tallized from absolute ethanol as colorless needles, yield 80%. The
compound was checked by its m.p., (decomp. at 186 °C), TLC, IR
and 1H NMR spectra.
2.4.1.2. Antioxidant activity screening assay ABTS method. The reac-
tion mixture (negative control) consists of 2 ml of 2,20-azino-bis-
(3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) solution (60 ll)
2.3. Synthesis of complexes
and 3 ml of MnO2 solution (25 mg/ml), all prepared in phosphate
buffer (pH = 7) [18–20]. The mixture was shaken, centrifuged and
filtered to remove the excess oxide. The absorbance (Acontrol) of
the resulting green–blue solution (ABTS+ radical solution) was re-
corded at kmax = 734 nm. The absorbance (Atest) was measured upon
2.3.1. Synthesis of Cd(II), Hg(II) complexes
A hot ethanolic solution of the respective metal chloride
(1.0 mmol) was added to hot ethanolic solution of (H2APC)
(0.296 g, 1.0 mmol). The resultant mixture was heated under reflux
for 6 h. Pale yellow precipitates that formed were filtered off,
washed with ethanol followed by diethyl ether and dried in a vac-
uum desiccator over anhydrous CaCl2. The complexes are stable in
air. Hg(II) complex is insoluble in either polar or non-polar solvents
and vice versa in case of Cd(II) complex which is readily soluble.
the addition of 20
investigation in spectroscopic grade MeOH/buffer (1:1 v/v) to the
ABTS solution. Ascorbic acid 20 l (2 ml) solution was used as stan-
ll of 1 mg/ml solution of the test sample under
l
dard antioxidant (positive control). Blank sample was run using sol-
vent without ABTS. The decrease in absorbance is expressed as %
inhibition.
2.4.1.3. Antioxidant activity screening assay for erythrocyte hemoly-
sis. The blood was obtained from rats by cardiac puncture and col-
lected in heparinized tubes. Erythrocytes were separated from
plasma and the buffy coat was washed three times with 10 vol-
umes of 0.15 M NaCl. During the last wash, the erythrocytes were
centrifuged at 2500 rev./min for 10 min to obtain a constantly
packed cell preparation. Erythrocyte hemolysis was mediated by
peroxyl radicals in this assay system [21]. A 10% suspension of
erythrocytes in phosphate buffered saline pH 7.4 (PBS) was added
to the same volume of 200 mM AAPH solution in PBS containing
samples to be tested at different concentrations. The reaction mix-
ture was shaken gently while being incubated at 37 °C for 2 h. The
reaction mixture was then removed, diluted with eight volumes of
PBS and centrifuged at 1500g for 10 min. The absorbance of the
supernatant was read at 540 nm. Similarly, the reaction mixture
was treated with eight volumes of distilled water to achieve com-
plete hemolysis, and the absorbance of the supernatant obtained
after centrifugation was measured at 540 nm. The data percentage
2.3.2. Synthesis of Zn(II) complex
A hot ethanolic solution of the zinc acetate (1.0 mmol) was
added to hot ethanolic solution of (H2APC) (0.296 g, 1.0 mmol).
The resultant mixture was heated under reflux for 8 h. The deep
red solution that obtained was evaporated to quarter of the volume
and treated with diethyl ether forming orange precipitate. The
product was dried in a vacuum desiccator over anhydrous CaCl2.
The complex is stable and readily soluble in polar and non-polar
solvents.
2.4. Biological studies
2.4.1. Anti-oxidant activity screening
The antioxidant activity assay [15] employed is a technique
depending on measuring the consumption of stable free radicals
i.e. evaluate the free radical scavenging activity of the investigated
component. The methodology assumes that the consumption of
the stable free radical (X0) will be determined by reactions as
follows:
hemolysis was expressed as mean standard deviation.
acid was used as a positive control.
L-ascorbic
X0 þ YH ! XH þ Y0
2.4.2. Cytotoxic activity
2.4.2.1. Ehrlich cells. Ehrlich cells (Ehrlich ascites Carcinoma, EAC)
were derived from ascetic fluid from diseased mouse (the cells were
purchased from National Cancer Institute, Cairo, Egypt which is a
certified institute by National Medical Research Ethics Committee).
DNA (Calf Thymus type1), bleomycin sulfate, butylatedhydroxyani-
sole (BHA), thiobarbituric acid (TBA), ethylenediaminetetraacetic
acid (EDTA) and ascorbic acid were obtained from sigma. 2,20-
azo-bis-(2-amidinopropane) dihydrochlorid (AAPH), 2,20-azino-
bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) were purchased
from Wako Co., USA.
The rate and/or the extent of the process measured in terms of the
decrease in X0 concentration, would be related to the ability of the
added compounds to trap free radicals. The decrease in color inten-
sity of the free radical solution due to scavenging of the free radical
by the antioxidant material is measured colorimetry at a specific
wavelength. The assay employs the radical cation derived from
2,20-azino-bis(3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) or
diphenylpicrylhydrazyl (DPPH) as stable free radicals to assess anti-
oxidant and extracts. The Inhibition percent of the free radical DPPH
or ABTS was calculated according to the equation:
2.4.2.2. Antitumor activity using Ehrlich ascites in vitro assay. Differ-
ent concentrations of the tested compounds were prepared (100,
50 and 25 ml from 1 mg/ml in DMSO (<00.05%, v/v) and RPMI-
1640 medium). The ascites fluid from the peritoneal cavity of the
diseased mouse (contains Ehrlich cells) was aseptically aspirated.
I% ¼ ðAblank ꢀ AsampleÞ=ðAblankÞ ꢁ 100
where Ablank is the absorbance of the control reaction (containing all
reagents except the test compound), and Asample is the absorbance
of the test sample.

8
O.A. El-Gammal et al. / Journal of Molecular Structure 1020 (2012) 6–15
The cells were grown partly floating and partly attached in a sus-
pension culture in RPMI-1640 medium, supplemented with 10% fe-
tal bovine serum. They were maintained at 37 °C in a humidified
atmosphere with 5% CO2 for 2 h. The viability of the cells deter-
mined by the microscopical examination using a hemocytometer
and using trypan blue stain (stains only the dead cells) [22,23].
4. The bond angles of the hydrazine moiety of H2APC are altered
somewhat upon coordination; the largest change affects
C(2)AN(3)AN(6) and O(4)AC(2)AN(3) angles which are
reduced or increased on complex formation as a consequence
of bonding [31].
5. The C(2)AN(3)AN(6) angle changes from 117.9° to 112.2° or
116.6° in [Zn2(HAPC)(OAc)3(H2O)3]ꢂ3H2O and [Cd(H2APC)Cl2]
complexes due to the formation of the N(13)AZnAO(22) and
N (8)ACdAO(25) chelate ring [32].
2.5. Molecular modeling
We performed cluster calculations using DMOL3 program [24] in
Materials Studio package [25], which is designed for the realization
of large scale density functional theory (DFT) calculations. DFT
semi-core pseudopods calculations (dspp) were performed with
the double numerica basis sets plus polarization functional (DNP).
The DNP basis sets are of comparable quality to 6-31G Gaussian ba-
sis sets [26]. Delley et al. showed that the DNP basis sets are more
accurate than Gaussian basis sets of the same size [25]. The RPBE
functional [27] is so far the best exchange–correlation functional
[28], based on the generalized gradient approximation (GGA), is
employed to take account of the exchange and correlation effects
of electrons. The geometric optimization is performed without
any symmetry restriction.
6. The bond angles, N(10)AM(7)ACl(23), N(10)AM(7)ACl(24),
O(25)AM(7)AN(10) and O(25)AM(7)AN(8) of 142.8, 106.1,
60.77 and 61.29 in [Cd(H2APC)Cl2] complex indicate that the
complex adopts a trigonal bipyramidal arrangement. On the
other hand the bond angles in [Zn2(HAPC)(OAc)3(H2O)3]ꢂ3H2O
[Hg2(H2APC)2Cl4] complexes are quite near to an octahedral
and tetrahedral geometries, respectively predicting sp3 d2 and
sp3 hybridization.
7. The complexes can be arranged according to MANazomethine and
MAO bond lengths as follows: Zn(23)AN(13), Zn(31)AN(12) >
Cd(7)AN(10), Cd(7)AN(8) and HgAO > ZnAO > CdAO reflecting
the great strength of the ZnAN and HgAO bonds.
8. The lower HOMO energy values show that molecules donating
electron ability is the weaker. On contrary, the higher HOMO
energy implies that the molecule is a good electron donor.
LUMO energy presents the ability of a molecule receiving elec-
tron [33].
9. The bond angles within the hydrazone backbone do not change
significantly but the angles around the metal undergo apprecia-
ble variations upon changing the metal center [34].
3. Results and discussion
The data of elemental analysis together with some physical
properties of the complexes are summarized in Table 1. The stoi-
chiometries of the coordination adducts established by elemental
analysis are confirmed by weight loss determination. The values
of molar conductivity of all complexes lie in the range (1–
17
X
ꢀ1 cm2 molꢀ1) indicating their non-electrolytic nature [29].
3.2. IR spectra
3.1. Molecular modeling
The principle IR bands of H2APC and its metal complexes are
represented in Table 2. The IR spectrum of H2APC (Structure 1)
showed two bands at 1698 and 1679 cmꢀ1 attributable to stretch-
ing vibration mode of (C@O) group [35] suggesting the existence of
the ligand in syn and anti-conforms (b, c). The band observed at
The molecular structure along with atom numbering of (H2APC)
and its metal complexes are shown in structures 1–4. Analysis of
the data in Tables 1S–8S including the bond lengths and bond an-
gles, one can conclude the following remarks:
1626 cmꢀ1 is assignable to
m
(C@N) vibration and shifted to lower
wavenumber upon complexation. The ligand showed bands at
1,579,989,651 and 410 cmꢀ1 are attributable to
(C@N) pyridine
1. The N(3)AN(6), N(3)AC(2) and N(6)AC(7)azomethine bond lengths
become slightly longer in complexes as the coordination takes
place via N atoms of AC@NAC@NA group that is formed on
deprotonation of OH group in [Zn2(HAPC)(OAc)3(H2O)3]ꢂ3H2O
complex [30].
2. The C(2)AO(4) bond distance in all complexes becomes longer
due to the formation of the MAO bond which makes the CAO
bond weaker [31].
3. In [Zn2(HAPC)(OAc)3(H2O)3]ꢂ3H2O complex, C(8)AN(10) and
C(17)AN(22) bond distances of the two pyridine rings pyridine
are enlonged. This is referred to the formation of the MAO bond
which makes the CAO bond weaker and forming a double bond
character [32].
m
stretching [36], pyridine ring breathing, in-plane-bending and
out-of plane ring vibration modes [37–39], respectively. Also, the
medium intensity band at 1045 cmꢀ1 is attributable to
m
(NAN)
stretching vibration [40,41] while the band at 3207 cmꢀ1 is as-
signed to the (NH) vibrational mode. The bands 3207,
3351 cmꢀ1assigned to (NHa) and (NHb), respectively. The
(NHb) appeared at higher wavenumber because the hydrogen
m
m
m
m
bond with N atom of pyridine ring (Structure 1a).
Comparison of the IR spectra of H2APC and its metal complexes
(Table 2) showed that H2APC has two modes of coordination.
Firstly, as monobasic hexadentate in [Zn2(HAPC)(OAc)3(H2O)3]ꢂ
3H2O complex (Structure 2) via the carbonyl oxygen (C@O) in
Table 1
Analytical and physical data of H2APC and its metal complexes.
Compound
Color
m.p. (°C)
% Found (Calcd.)
Yield (%)
Empirical formula
(F.Wt)
M
–
Cl
–
C
H
(H2APC)
White
186 (decomp)
270
60.9 (60.80)
5.46 (5.44)
80
84
88
89
C
15H16N6O
Cd(H2APC)Cl2
15H16CdCl2N6O
[Hg2(H2APC)2Cl4]
30H32Cl4Hg2N12O2
[Zn2(HAPC)(OAc)3(H2O)3](H2O)3
21H36N6O13Zn2
(296.33)
(479.64)
(1135.7)
(711.33)
Pale yellow
Pale yellow
Orange
23.44
(23.6)
35.5
(35.33)
18.38
(18.5)
14.93
(14.78)
12.52
(12.49)
–
37.63
(37.56)
31.79
(31.73)
35.12
(35.46)
3.42
(3.36)
2.88
(2.84)
4.96
(5.1)
C
232
C
>300
C

O.A. El-Gammal et al. / Journal of Molecular Structure 1020 (2012) 6–15
9
Table 2
Most important IR spectral bands of H2APC and its metal complexes.
Compound
H2APC
t
(NH)
t
(C@O)
t
(C@N)
t
(C@N)py
d(C@N)py
t
(C@Nꢃ)
t
(CAO) enolic
t
(MAO)
t
(MAN)
3207
3351
1698
1679
1616
1558
1625
1575
1540
1525
1540
1550
651
–
–
–
–
[Cd(H2APC)Cl2]
3212
3357
1662
1689
–
666
645
660
–
–
–
500
507
507
427
481
425
[Hg2(H2APC)2Cl4]
3232
3326
645
[Zn2(HAPC)(OAc)3(H2O)3](H2O)3
3310
1629
1197
t
(C@Nꢃ): New azomethine.
N
O
N
N
OH
N
N
N
N
N
N
H
N
N
N
H
H
Enol[syn]
Keto form
(a)
(b)
H3C
HN
N
N
N
N
N
OH
CH3
Enol form [anti]
(c)
Structure 1. Molecular structure of (a) H2APC (b) electron density of H2APC (c) HOMO of H2APC (d) LUMO of H2APC.
the enol form, the two azomethine nitrogens, (C@N) that already
exists and the new (C@N)ꢃ that formed on enolization and (C@N)py
groups. This mode of chelation is confirmed by the following evi-
dences: (i) the disappearance of bands due to (C@O) and (NH)
m
m

10
O.A. El-Gammal et al. / Journal of Molecular Structure 1020 (2012) 6–15
Structure 4. Molecular modeling of [Cd((H2APC)Cl2].
the band due to pyridine ring deformation shifts to higher wave-
number is an additional evidence of coordination through (C@N)
pyridine atom [42]. The broad bands observed at 1550 and
Structure 2. Molecular modeling of [Zn2(HAPC)(OAc)3(H2O)3](H2O)3.
1426 cmꢀ1 assignable to
m
asym(OCO) and
m
sym(OCO) vibrations,
respectively with frequency difference (
D
m
= 123 cmꢀ1)confirming
monodentate nature of the acetate group [43]. Secondly, H2APC
coordinates either as neutral mono-dentate as in [Hg2(H2APC)2Cl4]
complex (Structure 3) via the carbonyl oxygen (C@O) in the keto
form as illustrated by shift of its band to lower wavenumber or
as neutral tridentate manner through (C@O) and both azomethine
nitrogen atoms in case of [Cd(H2APC)Cl2] complex (Structure 4).
This mode of coordination is supported by the shift of the stretch-
ing vibrations of both azomethine groups to lower wavenumber
and shift of m(NAN) to higher wave-number [44,45]. The suggested
mode of chelation for the aforementioned complexes is also con-
firmed by the appearance of new bands at 500–507 and 420–
427 cmꢀ1 attributable to
respectively.
m (MAO) [46] and m (MAN) [47],
3.3. The 1H NMR
The 1H NMR spectrum of H2APC is displayed in DMSO-d6 solu-
tion. The signals of all hydrogen are duplicated suggesting the exis-
tence of the anti and syn configurations in solution [48]. In fact,
two signals of NH protons were observed as doublet at downfield
d10.03 (anti) and 10.13 ppm (syn) which disappear upon adding
D2O. The signals at d2.10–2.51 ppm may be equivalent to 12
protons of the four CH3 groups. The signals due to pyridine ring
protons appeared at d: {6.687 (anti), 7.33 ppm (syn) (t, 2H,
HAC12@HAC20)}, {7.36 (anti), 7.56 (syn) ppm (t, 2H, HAC13@
HAC19)}, {7.85 (anti), 8.03 ppm (syn) (d, 2H, HAC14@HAC18)}
and {8.57 (anti) 8.69 (syn) ppm (d, 2H, HAC11@HAC21)} [48,49].
Also, the signal at 14.3 ppm may be corresponding to enolic proton
of ligand in solution. This signal supported the existence of the li-
gand in keto–enol form in solution which disappears upon addition
of D2O as illustrated in Structure 1. The above assumption was
confirmed by the molecular modeling of H2APC as the two isomers
possessed the same binding energy (ꢀ4043.32, 4043.48 kcal/mol
for anti and syn isomers, respectively).
Structure 3. Molecular modeling of [Hg2(H2APC)2Cl4].
modes with simultaneous appearance of new bands at 1629 and
1197 cmꢀ1 assignable to (C@N)ꢃ and
(CAO) modes, (ii) (NAN)
m
m
m
shifts to higher wavenumber as a result of the increase in the dou-
ble bond character of NAN offsetting the loss of electron density
via donation to the metal ion and is a further evidence of coordina-
tion of the ligand through the azomethine nitrogen atom., (iii) the
bands due to
m
(C@N)azomethine
,
m
(C@N) pyridine and pyridine ring
Further evidence for deprotonation of the enolized carbonyl
breathing modes shift to lower wavenumber and (iv) moreover,
oxygen comes from the 1H NMR spectrum of the diamagnetic Zn(II)

O.A. El-Gammal et al. / Journal of Molecular Structure 1020 (2012) 6–15
11
Table 3
Decomposition steps with the temperature range and weight loss for H2APC complexes.
Compound
Decomposition step
Temperature range (°C)
Removes species
wt loss
% (Calcd.)
% Found
[Cd(H2APC)Cl2]
1st
2nd
3rd
4th
264–297
354–415
441–469
555–607
607–800
A2N2
AHCl + C5H5N
AHCl
AC5H5N + C3H6
ACdO
11.68
23.88
7.60
30.06
26.80
11.90
24.10
7.63
30.30
26.07
Residue
[Zn2(HAPC)(OAc)3(H2O)3](H2O)3
1st
2nd
3rd
4th
5th
57–96
A3H2O
A3H2O
A2HOAc
A2C5H5N + N2 + HOAc
ACH3CN + HCN
Zn + ZnO + 2C
7.59
7.59
16.86
34.28
9.55
8.28
8.12
16.34
33.80
9.12
138–169
292–326
398–479
547–589
589–800
Residue
23.99
24.34
in hydrogen bonding with N of the pyridine ring and overlapped
with the signals of pyridine protons. The appearance of multiplet
at 3.57–3.41 ppm is due to the CH3CH2 protons of the acetate.
3.4. Electronic spectra
The electronic spectrum of the ligand and its complexes was dis-
played in DMF or Nujol mull. The tentative assignments of the sig-
nificant spectral absorption bands are given in Table 3. The
electronic spectra of the complexes are dominated by intense in-
tra-ligand charge transfer bands. The spectrum f the ligand shows
an intense absorption band at 36,496–35,971 cmꢀ1 region assigned
to
p ?
pꢃ transition of pyridine rings [50]. A red shift is observed for
this transition in the spectrum of [Zn2(HAPC)(OAc)3(H2O)3]ꢂ3H2O
complex as a result of coordination of the nitrogen of the pyridine
ring [49]. Another intense absorption band in the region
33,557 cmꢀ1 assigned to
p ?
pꢃ of C@N group which shifts in all
complexes toward higher frequencies, supporting the coordination
of the hydrazone via azomethine nitrogen atom. A third intense
band is observed in the 25,907–28,089 cmꢀ1 region assignable to
n ? pꢃ transition of carbonyl group [49]. In complexes, this band
is shifted by ꢄ150–409 cmꢀ1
.
Fig. 1. Thermal analysis curves (TGA, DTG) of [Cd(H2APC)Cl2].
Owing to the deep orange color of [Zn2(HAPC)(OAc)3
(H2O)3]ꢂ3H2O complex, its spectrum in Nujol mull was displayed.
The spectrum exhibited a moderately intense broad bands in the
region 24,876–19,084 cmꢀ1 may be due to L–M charge transfer. Ex-
cept this, the complex showed no appreciable absorptions in the
region below 190,84, in accordance with d10 electronic configura-
tion of Zn(II) ion.
3.5. Thermogravimetric studies
The stages of decomposition, temperature range, decomposition
product as well as the weight loss percentages of Cd(II) and Zn(II)
complexes are given in Table 3. Figs. 1 and 2 shows the TGA curves
of some metal complexes. The experimental weight loss values are
in good agreement with the calculated values. The final decompo-
sition product was identified by the conventional chemical analysis
method. [Zn2(HAPC)(OAc)3(H2O)3]ꢂ3H2O complex is chosen as a
representative example since it contains both types viz. water of
coordination and water of crystallization. In the TG thermogram
of this complex, the first stage at 57–96 °C with weight loss of
8.28 (Calcd. 7.59%) is corresponding to the loss of the three lattice
water molecules. The second step with weight loss of 8.12 (Calcd.
7.59%) at 138–169 °C is attributed to the elimination of three coor-
dinated water molecules. The third step at 292–326 °C with weight
loss of 16.34 (Calcd. 16.86%) is referring to the removal of 2HOAc
molecules. The fourth step corresponds to the elimination of
2C5H5N + N2 + HOAc fragments with weight loss of 33.80 (Calcd.
Fig. 2. Thermal analysis curves (TGA, DTG) of [Zn2(HAPC)(OAc)3(H2O)3](H2O)3.
complex, emphasizing the lack of the signals due to the first NH
proton while the second NH signal shifted to high field as involved

12
O.A. El-Gammal et al. / Journal of Molecular Structure 1020 (2012) 6–15
Table 4
Kinetic parameters evaluated by Coats–Redfern equation for H2APC complexes.
Complex
Peak
Mid temp (K)
Ea (kJ/mol)
A (Sꢀ1
)
D
Hꢃ (kJ/mol)
D
Sꢃ (kJ/mol K)
D
Gꢃ (kJ/mol)
[Zn2(HAPC)(OAc)3(H2O)3](H2O)3
1st
349.52
427.00
581.89
711.51
840.87
8.06
6.07
104.29
37.58
165.09
5.71 ꢁ 103
3.82 ꢁ 10ꢀ3
1.34 ꢁ 107
1.50 ꢁ 101
7.92 ꢁ 107
35.16
2.52
99.45
31.66
158.10
ꢀ0.1743
ꢀ0.2942
ꢀ0.1140
ꢀ0.2487
ꢀ0.1023
96.08
128.14
165.79
8.65
2nd
3rd
4th
5th
244.13
[Cd(H2APC)Cl2]
1st
170.18
94.60
141.08
202.85
170.18
94.60
141.08
202.85
1.95 ꢁ 1014
3.82 ꢁ 105
6.36 ꢁ 107
3.29 ꢁ 107
165.58
89.13
135.03
195.75
0.0235
ꢀ0.1446
ꢀ0.1029
ꢀ0.0523
152.56
184.21
209.98
240.45
2nd
3rd
4th
34.28%). This is followed by loss of C3H4N2 fragment with weight
loss of 9.12 (Calcd. 9.55%). The residual part is Zn + ZnO + 2C (found
24.34, Calcd. 23.99%). An inspection of the data represented in
Table 4 indicates that TG thermograms displayed a high residual
part for the studied complexes reflecting a higher thermal stability
owing to the existence of five membered chelate rings.
-10.6
-10.8
-11.0
-11.2
-11.4
-11.6
-11.8
-12.0
-12.2
-12.4
-12.6
lnx n=1.00
lnx n=0.66
lnx n=0.33
lnx n=0.00
lnx n=0.50
3.6. Kinetic data
The kinetic and thermodynamic parameters of thermal degra-
dation process have been calculated using Coats–Redfern and
Horowitz–Metzger models [51,52]. Coats–Redfern relation is as
follows:
ꢀ
ꢁ
ꢂ
ꢃ
lnð1 ꢀ
aÞ
AR
bE
E
RT
ln ꢀ
¼ ln
ꢀ
ð1Þ
T2
where
a represents the fraction of sample decomposed at time t,
×10-3
defined by:
2.70 2.75 2.80 2.85 2.90 2.95 3.00 3.05
1/T
wo ꢀ wt
a
¼
wo ꢀ w
1
Fig. 3. Coats–Redfern plot of first degradation step for [Zn2(HAPC)(OA-
c)3(H2O)3](H2O)3 complex.
In which wo, wt and w1 are the weight of the sample before the deg-
radation, at temperature t and after total conversion, respectively. T
is the derivative peak temperature. b is the heating rate = dT/dt, E
and A are the activation energy and the Arrhenius pre-exponential
plexes was suggested to be first order [53], therefore we assume
n = 1 for the remainder of the present text. The other thermody-
namic parameters of activation can be calculated by Eyring equa-
tion [54]:
factor, respectively. A plot of ln [ꢀln (1 ꢀ
a
)/T2] versus 1/T gives a
straight line whose slope (E/R) and the pre-exponential factor (A)
can be determined from the intercept.
The Horowitz–Metzger relation [52] used to evaluate the degra-
dation kinetics is:
D
D
D
H ¼ E ꢀ RT
ð3Þ
ð4Þ
ð5Þ
Eh
RT2s
hA
S ¼ R ln
kBT
ln ½ꢀ lnð1 ꢀ
aÞꢅ ¼
ð2Þ
where h = T ꢀ Ts, Ts is the DTG peak temperature, T is the tempera-
G ¼
D
H ꢀ T
DS
ture corresponding to weight loss wt. A straight line should be ob-
served between ln [ꢀln (1 ꢀ
a
)] and h with a slope of E=RT2s . A
Thermodynamic parameters such as activation energy (E), pre-
exponential factor (A), entropy of activation ( S), enthalpy of acti-
vation ( H) and free energy of activation ( G) of decomposition
number of pyrolysis processes can be represented as a first order
D
D
reaction. Particularly, the degradation of a series of H2APC com-
D
Table 5
Kinetic parameters evaluated by Horowitz–Metzger equation for H2APC complexes.
Complex
Peak
Mid temp (K)
Ea (kJ/mol)
A (Sꢀ1
)
D
Hꢃ (kJ/mol)
D
Sꢃ (kJ/mol K)
D
Gꢃ (kJ/mol)
[Zn2(HAPC)(OAc)3(H2O)3](H2O)3
1st
349.22
427.14
11.581
712.02
842.07
43.94
13.19
113.94
49.53
4.91 ꢁ 104
6.15 ꢁ 10ꢀ2
1.07 ꢁ 108
1.48 ꢁ 101
6.31 ꢁ 108
41.04
9.64
109.11
43.61
172.08
ꢀ0.1564
ꢀ0.2711
ꢀ0.0967
ꢀ0.2298
ꢀ0.0851
95.66
125.43
165.31
207.20
243.72
2nd
3rd
4th
5th
179.08
[Cd(H2APC)Cl2]
1st
553.37
657.46
728.06
854.14
179.53
105.99
153.13
217.57
1.55 ꢁ 1015
3.40 ꢁ 106
5.04 ꢁ 108
2.78 ꢁ 1011
174.93
100.53
147.08
210.47
0.0408
ꢀ0.1265
ꢀ0.0857
ꢀ0.0346
152.37
183.67
209.50
240.02
2nd
3rd
4th

O.A. El-Gammal et al. / Journal of Molecular Structure 1020 (2012) 6–15
13
1.2
1.0
lnx n=1.00
lnx n=0.66
lnx n=0.33
lnx n=0.00
lnx n=0.50
0.8
0.6
0.4
0.2
0.0
-0.2
-0.4
-0.6
-0.8
-1.0
-20
-10
0
10
20
T-Ts
Fig. 4. Horowitz–Metzger plot of first degradation step for [Zn2(HAPC)(OA-
c)3(H2O)3](H2O)3 complex.
-11
-12
-13
-14
lnx n=1.00
lnx n=0.66
lnx n=0.33
lnx n=0.00
lnx n=0.50
Fig. 7. DPPH inhibition of H2APC and its metal complexes. (a) DPPH scavenging
capacities (IC50) of H2APC and its metal complexes. (b) DPPH scavenging activity
spectrophotometric assay of various concentration of H2APC and its complexes.
×10-3
1.75
1.80
1/T
1.85
Fig. 5. Coats–Redfern plot of first degradation step for [Cd(H2APC)Cl2] complex.
1.5
ln X n=1.00
ln X n=0.66
ln X n=0.33
ln X n=0.00
ln X n=0.50
1.0
0.5
0.0
-0.5
-1.0
-1.5
Fig. 8. Ehrlich in vitro assay for H2APC and its complexes. (a) Ehrlich scavenging
capacities (IC50) of H2APC and its metal complexes. (b) Ehrlich scavenging activity
spectrophotometric assay of various concentration of H2APC and its complexes.
steps were calculated using Coats–Redfern [50] and Horowitz–
Metzger [51] methods (Tables 4 and 5). In both methods, the lift
side of Eqs. (3) and (4) are plotted against 1/T and h, respectively
(Figs. 3–6). From the results, the following remarks can be pointed
out:
-20
-15
-10
-5
0
5
10
15
20
T-Ts
Fig. 6. Horowitz–Metzger plot of first degradation step for [Cd(H2APC)Cl2] complex.

14
O.A. El-Gammal et al. / Journal of Molecular Structure 1020 (2012) 6–15
Table 6
i. One C@O, two (C@N)azomethine, one NH and two (C@N)pyridine
groups free in the carbohydrazone, H2APC moitey. So, it
showed the potent antioxidant activity [59].
Antioxidant erythrocyte hemolysis assay for the prepared ligand and its metal
complexes.
Compound
-ascorbic acida
ABTS inhibition (%)
96.57
Erythrocyte hemolysis (%)
4.08
ii. In Cd(II) complex, there are still four donor sites free i.e. two
(C@N)pyridine and two NH groups that can donate an electron
or hydrogen radical thus be converted into a stable diamag-
netic molecule [60].
iii. In case of the binuclear Zn(II) complex, there is only one NH
group free. However its moderate activity can be referred to
the presence of three acetate groups which enhances the
scavenging activity.
L
H2APC
53.90
18.09
12.76
9.71
4.48
5.17
4.48
Zn-complex
Cd-complex
Hg-complex
31.15
a
Standard drug.
iv. In Hg(II) complex showed no activity owing to its well
known high toxicity although it most of the donor sites free
otherwise C@O group.
i) The high values of the energy of activation, Ea of the com-
plexes reveals the high stability of such chelates due to their
covalent bond character [55] and the increase of Ea on going
from Zn(II) complex to Cd(II) complex reflects the greater
thermal stability of first complex than the second one as Ea
depends on the strength of (O ? M N) and increases with
increasing the cation radius.
4. Conclusion
1,5-Bis(1-(pyridin-2-yl)ethylidene)carbonohydrazide (H2APC)
and its mono- and binuclear complexes with Zn acetate, Cd(II)
and Hg(II) chlorides were prepared. The complexes have been
characterized and assigned the formulae [Zn2(HAPC)(OA-
c)3(H2O)3]ꢂ3H2O, [Cd(H2APC)Cl2] and [Hg2(H2APC)2Cl4]. A trigonal
bipyramidal was proposed for Cd(II)complex, an octahedral for
Zn(II) complex and a tetrahedral geometries, respectively. The li-
gand and its complexes were screened for antioxidant activity
(using DPPH and ABTS+), erythrocyte hemolysis and in vitro Ehrlich
ascites assay. The relation between the structure of the studied
compounds and their activity was discussed. All the data obtained
revealed the high activity of Cd(II) and Zn(II) complexes and very
weak activity for Hg(II) complex.
ii) The positive sign of
DG for the investigated complexes
reveals that the free energy of the final residue is higher than
that of the initial compound, and all the decomposition steps
are non-spontaneous processes. Also, the values of the acti-
vation,
position stages of a given complex. This is due to increasing
the values of T S significantly from one step to another
which overrides the values of H [56–58].
iii) The negative values of S for the degradation process indi-
DG increases significantly for the subsequent decom-
D
D
D
cates more ordered activated complex than the reactants
or the reaction is slow [54].
3.7. Biological application
Appendix A. Supplementary material
3.7.1. Antioxidant activity
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.molstruc.2012.
04.029.
3.7.1.1. DPPH free radical scavenging activity. We found that most of
compounds showed considerable free radical-scavenging activities
(Fig. 7a). H2APC was the strongest radical scavenger among the
studied compounds with IC50 9.64 mg/ml comparable with ascor-
bic acid (standard antioxidant). Zn(II) and Cd(II) complexes showed
moderate scavenging activity with IC50 32.88 and 42.97 mg/ml,
respectively. On the other hand, Hg(II) complex exhibited no activ-
ity. The variation of % DPPH radical scavenging activity with con-
centration of test compounds is represented in Fig. 7b.
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