Synthesis, spectroscopic characterization and biological activity on newly synthesized copper(II) and nickel(II) complexes incorporating bidentate oxygen-nitrogen hydrazone ligands

Article abstract of DOI:10.1016/j.ica.2009.08.004

We report the synthesis of the hydrazone ligands, 1-(phenyl-hydrazono)-propan-2-one (PHP), 1-(p-tolyl-hydrazono)-propan-2-one (THP), 1-[(4-chloro-hydrazono)]-propan-2-one (CHP), and their Ni(II) and Cu(II) metal complexes. The structure of the ligands and

Full text of DOI:10.1016/j.ica.2009.08.004

Inorganica Chimica Acta 362 (2009) 4991–5000
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Inorganica Chimica Acta
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Synthesis, spectroscopic characterization and biological activity on newly
synthesized copper(II) and nickel(II) complexes incorporating bidentate
oxygen–nitrogen hydrazone ligands
Ahmed A. El-Sherif
Department of Chemistry, Faculty of Science, Cairo University, Cairo, Egypt
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 May 2009
Received in revised form 28 July 2009
Accepted 3 August 2009
Available online 8 August 2009
We report the synthesis of the hydrazone ligands, 1-(phenyl-hydrazono)-propan-2-one (PHP), 1-(p-tolyl-
hydrazono)-propan-2-one (THP), 1-[(4-chloro-hydrazono)]-propan-2-one (CHP), and their Ni(II) and
Cu(II) metal complexes. The structure of the ligands and their complexes were investigated using ele-
mental analysis, magnetic susceptibility, molar conductance and spectral (IR, UV, and EPR) measure-
ments. IR spectra indicate that the free ligands exist in the hydrazo-ketone rather than azo-enol form
in the solid state. Also, the hydrazo-NH exists as hydrogen bonded to the keto-oxygen either as intra
or as intermolecular hydrogen bonding. In all the studied complexes, all ligands behave as a neutral
bidentate ligands with coordination involving the hydrazone-nitrogen and the keto-oxygen atoms. The
magnetic and spectral data indicate a square planar geometry for Cu2+ complexes and an octahedral
geometry for Ni2+ complexes. The ligands and their metal chelates have been screened for their antimi-
crobial activities using the disc diffusion method against the selected bacteria and fungi. They were found
to be more active against Gram-positive than Gram-negative bacteria. It may be concluded that the anti-
microbial activity of the compounds is related to cell wall structure of bacteria.
Keywords:
Hydrazone
Copper(II)
Nickel(II)
EPR spectra
IR spectra
Equilibrium studies
Biological activity
Protonation constant of (PHP) ligand and stability constants of its Cu2+ and Ni2+ complexes were deter-
mined by potentiometric titration method in aqueous solution at ionic strength of 0.1 M sodium nitrate.
It has been observed that the hydrazone ligand (PHP) titrated here has one protonation constant. The
divalent metal ions Cu2+ and Ni2+ form with (PHP) 1:1 and 1:2 complexes. The insolubility of (THP)
and (CHP) ligands in aqueous medium does not permit the determination of their protonation constants
and formation constants of the corresponding complexes in aqueous solution.
Ó 2009 Elsevier B.V. All rights reserved.
1. Introduction
nation chemistry of metal complexes of hydrazones [5] has gained
a special attraction due to their biological activity and their ability
The preparation of a new ligand was perhaps the most impor-
tant step in the development of metal complexes which exhibit un-
ique properties and novel reactivity. Since the electron donor and
electron acceptor properties of the ligands, structural functional
groups and the position of the ligand in the coordination sphere to-
gether with the reactivity of coordination compounds may be the
factor for different studies [1,2]. Hydrazones were important class
of ligands, such ligands have interesting ligation properties due to
presence of several coordination sites [3]. Hydrazone ligands create
an environment similar to biological systems by usually making
coordination through oxygen and nitrogen atoms. Hydrazones
were widely applied in the field of insecticides, medicines and ana-
lytical reagents for their excellent bioactivity properties [4]. Coordi-
to act as potential inhibitors for many enzymes [6,7]. Hydrazone
derivatives possessing anti-inflammatory, analgesic [8–10], antipy-
retic [11], antibacterial [12] and antitumor [13] activities are also
reported in the literature. In view of the above facts and the interest
in studying the ligating behavior of such compounds [14–16], it is
necessary to synthesize and characterize Cu2+ and Ni2+ solid com-
plexes of the newly coordinating ligands, Scheme 1. The study also
includes biological activity of the synthesized complexes.
2. Experimental
2.1. Materials and reagents
CuCl2ꢀ2H2O, NiCl2ꢀ6H2O, HCl and KOH were provided by BDH.
Aniline, P-chloro aniline, P-methyl aniline, ethyl acetoacetate and
sodium nitrite were obtained from Sigma Chem. Company.
Abbreviations: PHP, 1-(phenyl-hydrazono)-propan-2-one; THP, 1-(p-tolyl-
hydrazono)-propan-2-one; CHP, 1-[(4-chloro-hydrazono)]-propan-2-one.
E-mail address: aelsherif72@yahoo.com
0020-1693/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2009.08.004

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A.A. El-Sherif / Inorganica Chimica Acta 362 (2009) 4991–5000
(as Gram-positive bacteria) and Pseudomonas aereuguinosa and
H
N
CH3
Escherichia coli (as Gram-negative bacteria) and also for their anti-
fungal activity against Candida albican and Candida lypolytica using
the disc diffusion method [18]. Moreover, some of the commercial-
ized antibiotics are evaluated for their antibacterial activity and a
comparison with the synthesized complexes present in this inves-
tigation was drawn.
N
X
O
Scheme 1. X = H (PHP); CH3 (THP); Cl(CHP).
2.2. Synthesis
2.4. Instruments
2.2.1. Synthesis of ligands
Potentiometric measurements were made using a Metrohm 686
titroprocessor equipped with a 665 Dosimat (Switzerland-Heri-
sau). A thermostatted glass-cell equipped with a magnetic stirring
system, a Metrohm glass electrode, a thermometric probe, a micro-
buret delivery tube and a salt bridge connected with the reference
cell filled with 0.1 M KCl solution in which saturated calomel elec-
trode was dipped are used. The titroprocessor and electrode were
calibrated with standard buffer solutions prepared according to
NBS specifications at 25.0 0.1 °C [19] and I = 0.1 mol dmꢁ3, potas-
sium hydrogen phthalate (pH 4.008) and a mixture of KH2PO4 and
Na2HPO4 (pH 6.865). The microchemical analysis of the separated
solid chelates for C, H and N was performed in the microanalytical
Center, Cairo University. The analyses were performed twice to
check the accuracy of the analytical data. Infrared spectra were re-
corded on a 8001-PC FTIR Shimadzu spectrophotometer using KBr
pellets. The solid reflectance spectra were measured on a schi-
madzu 3101 pc spectrophotometer. The molar conductance of
the complexes was measured for 1.00 ꢂ 10ꢁ3 M DMSO solutions
at 25 1 °C using a systronic conductivity bridge type 305. The
magnetic susceptibility measurements for the complexes were
determined by the Gouy balance using Hg[Co(NCS)4] as a calibrant
at room temperature.
The ligands were synthesized according to the method reported
in the literature [17] as follows: in a 4-l beaker equipped with a
mechanical stirrer, 65 g (64 ml, 0.5 mole) of ethyl acetoacetate
was added to 35 g (0.53 mole) of 85% potassium hydroxide in
1120 ml of water. The mixture is allowed to stand at room temper-
ature for 24 h.
Forty-seven grams (48 ml, 0.5 mole) of aniline is dissolved in
200 ml of aqueous HCl (prepared from equal volumes of concen-
trated acid and water) in a 2-l beaker. The beaker is equipped with
a mechanical stirrer and immersed in an ice-salt bath. After the
solution has cooled to 0–5 °C, 36 g. (0.52 mole) of sodium nitrite
dissolved in 1 liter of water is added slowly, with stirring, from a
separatory funnel. The tip of the stem of the seperatory funnel
dipped well below the surface of the liquid. The rate of addition
is adjusted to maintain the temperature between 0 and 5 °C. A drop
of the reaction mixture is tested from time to time with starch-io-
dide paper until nitrous acid persists in the solution during a 5-min
interval.
The solution of potassium acetoacetate is cooled to 0 °C, and
45 ml of concentrated HCl in 150 ml of ice water is added slowly
with stirring. The diazonium salt solution is then added over a per-
iod of 20 min, and the mixture is made basic by the addition of 82 g
of sodium acetate dissolved in 300 ml of water. The temperature of
the reaction mixture is raised slowly to 50 °C and maintained at
this temperature for 2 h; the separated solid is collected on a filter
and dried. The yield of crude product is 72–77 g (89–95%). Purifica-
tion can be effected by recrystallization from 200 ml of toluene.
The purified product weighs 59–66 g (82%); m.p. 148–150 °C. The
same method was applied for the preparation of THP and CHP ex-
cept, P-methyl aniline and P-chloro aniline were used instead of
aniline. Chemical equations for preparations are shown in Scheme
2.
The room temperature X-band ESR spectra were recorded uti-
lizing ECS 106 ESR spectrometer in the presence of DPPH as a
standard.
2.5. Potentiometric titrations
Potentiometric titrations were carried out at constant tempera-
ture and in an inert atmosphere of nitrogen with CO2-free stan-
dardized 0.05 mol dmꢁ3 NaOH as titrant in a 50.0 ml solution at
constant ionic strength 0.1 mol dmꢁ3, (adjusted with NaNO3). The
proton association constant of the ligand (PHP) was determined
potentiometrically by titration (1.0 ꢂ 10ꢁ3 M) of the ligand solu-
tion (50 cm3). The stability constants of the binary complexes were
determined using potentiometric data obtained from mixtures
(50 cm3) of CuCl2ꢀ2H2O/NiCl2ꢀ6H2O (1.0 ꢂ 10ꢁ3 M): PHP in a con-
centration ratio 1:1 and 1:2 at ionic strength of (0.1 M) NaNO3.
The pH meter readings were converted into hydrogen ion concen-
tration by titrating a standard acid solution (0.05 mol dmꢁ3), the
ionic strength of which was adjusted to 0.1 mol dmꢁ3, with stan-
dard base solution (0.05 mol dmꢁ3) at 25 °C. The pH is plotted
against p[H]. The relationship pH ꢁ p[H] = 0.05 was observed.
[OHꢁ] value was calculated using a pKw value of 13.997 [20]. For
the variable temperature studies the following values of pKw were
employed at 20 °C (pKw = 14.146), at 30 °C (pKw = 13.833), at 35 °C
(pKw = 13.680) and at 40 °C (pKw = 13.535). The ionic strength was
adjusted to 0.1 mol dmꢁ3 by using NaNO3. The equilibrium con-
stants evaluated from the titration data (summarized in Table 1)
are defined by Eqs. (1) and (2), where M, L and H stand for the
Cu2+/Ni2+ ion, (PHP) and proton, respectively,
2.2.2. Synthesis of metal complexes
For the preparation of Cu(II) and Ni(II) complexes, the appropri-
ate quantity of the hydrazone ligand (2 mmol) was dissolved in
absolute EtOH (30 ml). To this solution an ethanolic solution of
(1 mmol) of CuCl2ꢀ2H2O or NiCl2ꢀ6H2O was added dropwise [1:2
molar ratio, M:L]. The resultant solution was refluxed for 4–5 h
at 90 °C. The precipitated complexes were then filtered off, washed
with petroleum ether and dried overnight in a vacuum desiccator.
Elemental analysis data and yield are given in Table 1.
2.3. Antimicrobial activity
The hydrazone ligands and their metal complexes were evalu-
ated for their antibacterial activity against Staphylococcus aureus
CH3COCH2CO2C2H5 + KOH → CH3COCH2CO2K + C2H5OH
CH3COCH2CO2K + HCl → CH3COCH2CO2H + KCl
CH3COCH2CO2H + P-C6H5N=NCl → P-C6H5NH-N=CHCOCH3 +CO2 +HCl
Scheme 2.
pM þ qL þ rH ꢀ MpLqHr
ð1Þ
½MpLqHrꢃ
bpqr
¼
ð2Þ
p
q
r
½Mꢃ ½Lꢃ ½Hꢃ

A.A. El-Sherif / Inorganica Chimica Acta 362 (2009) 4991–5000
4993
Table 1
Analytical data of ligand and their complexes.
Compound
Yield %
M.wt.
Found% (Calcd.)
C
H
N
Cl
PHP:C9H10N2O
82%
77%
72%
69%
67%
60%
70%
65%
61%
162
176
66.68(66.66)
68.20(68.18)
54.99(54.96)
45.35(45.33)
45.94(45.93)
40.97(40.94)
45.81(45.79)
48.04(48.03)
41.35(41.32)
6.18(6.17)
6.83(6.82)
4.59(4.58)
4.62(4.61)
5.38(5.35)
3.81(3.79)
4.67(4.66)
5.22(5.20)
3.46(3.44)
17.26(17.28)
15.92(15.91)
14.29(14.24)
11.79(11.75)
10.78(10.71)
10.65(10.61)
11.90(11.87)
11.22(11.20)
10.74(10.71)
THP:C10H12N2O
CHP:C9H9N2OCl
[(PHP)2Cu]Cl2ꢀH2O
[(THP)2Cu]Cl2ꢀ2H2O
[(CHP)2Cu]Cl2ꢀH2O
[(PHP)2NiCl2]ꢀH2O
[(THP)2NiCl2] ꢀH2O
[(CHP)2NiCl2]
196.5
476.5
522.5
527.5
471.69
499.69
522.69
18.11(18.06)
14.93(14.90)
13.61(13.58)
13.50(13.45)
15.08(15.05)
14.28(14.21)
13.61(13.58)
Table 2
Tentative assignment of the important infrared bands of ligands and their complexes.
Compound
tNH
mH
tC@O
tC@N
tM–N
tM–O
2O
PHP
THP
CHP
3251 ms, 3446 mbr
3249 ms, 3446 mbr
3228 ms, 3444 mbr
3210
3205
3190
3301
3315
3305
1651 s
1653 s
1651 s
1632 m
1635 m
1629 m
1620 s
1618 s
1619 s
1602 s
1599 s
1600 s
1579 m
1580 m
1590 m
1533 m
1626 m
1520 m
[Cu(PHP)2]Cl2ꢀH2O
[Cu(THP)2]Cl2ꢀ2H2O
[Cu(CHP)2]Cl2ꢀH2O
[Ni(PHP)2Cl2]ꢀH2O
[Ni(THP)2Cl2]ꢀH2O
[Ni(CHP)2Cl2]
3510 mbr
3500 mbr
3520 mbr
3505 mbr
3498 mbr
420 w
425 w
415 w
465 w
470 w
468 w
528 w
518 w
510 w
508 w
517 w
510 w
Note: s, strong; w, weak; m, medium; br, broad; ms, medium strong; mbr, medium broad.
The calculations were obtained from ca. 100 data points in each
titration using the computer program MINIQUAD-75 [21]. The stoi-
chiometry and stability constants of the complexes formed were
determined by trying various possible composition models. The
model selected gave the best statistical fit and was chemically con-
sistent with the titration data without giving any systematic drifts
in the magnitudes of various residuals, as described elsewhere
[21]. The fitted model was tested by comparing the experimental
titration data points and the theoretical curve calculated from
the values of the acid dissociation constant of the ligand and the
formation constants of the corresponding complexes. The results
are summarized in Tables 1 and 2. The species distribution dia-
grams were obtained using the program SPECIES [22] under the
experimental conditions employed. All measurements were car-
ried out in our laboratory in Cairo University.
3.2. Infrared spectra
In absence of a powerful technique such as X-ray crystallogra-
phy, IR spectra has proven to be the most suitable technique to give
enough information to elucidate the way of bonding of the ligands
to the metal ions. The main IR spectral bands with their tentative
assignments for the free ligands and their metal (II) complexes
are given in Table 2 revealing the following features.
(1) The spectra of all ligands display sharp medium absorption
band in the range 3228–3251 cmꢁ1 range and broad med-
ium band centered at 3444–3446 cmꢁ1. The medium band
centered at 3228–3251 cmꢁ1 range is due to the different
vibrational modes of –NH– of the hydrazo moiety whereas
the broad band at ca. 3444–3446 cmꢁ1 could be taken as
an evidence for the involvement of the –NH– proton in the
formation of hydrogen bonding of the –NHꢀ ꢀ ꢀO– type [25].
(2) Hydrogen bonding may be intermolecular or intramolecular
between the –NH– of the hydrazo group (Brönsted acid) and
the carbonyl oxygen (Brönsted base), which means that
there may be a possibility of a proton between these two
groups [25]. Furthermore, the presence of proton donors
and proton acceptors is prevalent in biological systems.
Thus, Scheme 3, could be assumed for the ligands in the solid
state.
3. Results and discussion
The interaction of hydrazone ligands with MCl2 [M = Cu2+ or
Ni2+] in a molar ratio 1:2 [M:L] under reflux conditions gave the
products presented in Table 1. The formulation of these complexes
based on the elemental analysis, IR, EPR, UV–Vis and electrical
conductivity.
(3) The spectra of the free ligands display bands at 1651–1653
3.1. Conductivity measurements
and 1599–1602 cmꢁ1 due to
m(C@O) and m(C@N), respec-
tively. The spectra of complexes showed that these two
bands of the free ligands were not observed at the same fre-
quencies and the same intensities. They shift to lower fre-
quencies and, at the same time, their intensities are
lowered. These results indicate that the ligands act as neu-
tral bidentate bonded to the metal through the azome-
thine-nitrogen and the keto-oxygen atoms.
The molar conductivity values for freshly prepared DMSO solu-
tions of the complexes indicated that Cu(II) complexes are electro-
lytes while Ni(II) complexes are nonelectrloytes. This is in
accordance with the fact that conductivity values for a nonelectro-
lyte are below 50
X
ꢁ1 cm2 molꢁ1 in DMSO solution [23,24]. The
nonelectrolytic nature of the Ni(II)-complexes implies the contri-
bution of chloride ions to the coordination sphere in the complexes
under investigation. Spectral methods and elemental analysis
identified complexes as [Cu(HL)2]Cl2ꢀnH2O and [Ni(HL)2Cl2]ꢀnH2O.
(4) Further proof for the involvement of both azomethine-nitro-
gen and the keto-oxygen atoms in complexation is the
appearance of weak bands in the far IR region of complexes

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A.A. El-Sherif / Inorganica Chimica Acta 362 (2009) 4991–5000
CH3
CH3
N
N
H
O
N
N
O
X
O
N
X
H
H
N
N
(I)
X
H3C
(II)
Scheme 3. Intramolecular (I) and Intermolecular hydrogen bonding (II).
at (428–470) and (508–530) cmꢁ1 due to
(M–O), respectively [27] which are absent in the free
ligands.
(5) The appearance of
m
(M–N) [26] and
acteristic of octahedral geometry [30,31]. The ligand field parame-
ter Do (splitting parameter), B0 (Racah parameter of interelectronic
ratio) for the nickel(II) complexes are calculated using the follow-
ing equations:
m
m
(C@O) and the disappearance of fre-
quency bands of the azo group in the free ligands suggest
that there is no hydrazo-azo transformation; this is similar
to that reported in the literature [28].
Do
¼
t
1
ð3Þ
ð4Þ
ð5Þ
B0 ¼ t2
þ
t3 ꢁ 3
t1=15
b ¼ B0=B0
(6) From the above-mentioned points (4) and (5), the ligands,
act as neutral bidentate chelating agents coordinated to
the metal via the azomethine-nitrogen and carbonyl oxygen
atoms forming the more stable five membered chelate rings.
(7) The OH stretching frequency appears in the spectra of metal
complexes around 3450 cmꢁ1 is attributed to the presence
of water of hydration. Also, according to Stefov et al. [29],
coordinated water should exhibit frequencies at 825, 575
and 500 cmꢁ1. The absence of spectral bands in these regions
in the spectra of complexes indicates that the water mole-
cules in these complexes are not coordinated but are present
as lattice water.
where B0 = 1041 cmꢁ1 for the free Ni2+ ion. The values of Dq for the
nickel(II) complexes (Table 4) are found to be in the range 1005–
1012 cmꢁ1 range, indicating the intermediate ligand field position
of the ligands in the nephlauxetic series. The values of transition ra-
tio t2/t
1 and Dq/B0 lies in the range 1.56–1.61 and 1.60–1.67, respec-
tively, providing further evidence for octahedral geometry for
nickel(II) complexes. The interelectronic repulsion parameter B0
was calculated and found to be 601–632 cmꢁ1 for Ni(II) complexes.
These values are lower than that for the free Ni2+ ion (1041 cmꢁ1
)
which was attributed to orbital overlap and delocalization of the
electrons over the molecular orbital that encompasses both the me-
tal and the ligands. Furthermore, the values of B’ showed that the
3.3. Magnetic and spectral data
eg-electrons are
the ligand. The t2g-electrons may become
r
-antibonding and spend some of their time on
-bonding or antibonding
p
3.3.1. Ni(II) complexes
and spend more of their time on the ligand. Such delocalization
leads to increase in the mean distance between the d-electrons
and therefore increases the interelectronic repulsion parameter B0.
The nephlauxetic ratio b = B0/B0 for the complexes (Table 4) are less
than unity suggesting the presence of electron delocalization over
The electronic spectra of Ni(II) complexes displayed three bands
at 10 050–10 116 cmꢁ1 1), 15 715–16 290 cm-1
(t (t2) and 23 450–
23 580 cmꢁ1
(t
3) (Table 3) corresponding to T1g(F) ? 4T2g(F),
4
4
4T1g(F) ? 4A2g and T1g(F) ? 4T1g(P) transitions, respectively, char-
Table 3
Molar conductance, magnetic moment and electronic spectral data of the complexes.
kmax (cmꢁ1
)
a
Complex
KM
Veff (B.M.)
n ? p*
p
?
p*
d–d transition
Assignment
PHP
THP
CHP
340
342
341
315
320
322
337
284
282
281
235
237
240
280
[Cu(PHP)2]Cl2ꢀH2O
[Cu(THP)2]Cl2ꢀ2H2O
[Cu(CHP)2]Cl2ꢀH2O
[Ni(PHP)2Cl2]ꢀH2O
77.2
72.2
69.3
6.76
1.68
1.72
1.76
2.92
15 625
15 723
15 873
10 050
15 715
23 450
10 100
15 940
23 550
10 116
16 290
23 580
2B1g
2B1g
2B1g
?
?
?
2B2g
2B2g
2B2g
4T1g(F) ? 4T2g(F)
4T1g(F) ? 4A2g
4T1g(F) ? 4T1g(P)
4T1g(F) ? 4T2g(F)
4T1g(F) ? 4A2g
[Ni(THP)2Cl2]ꢀH2O
5.23
4.01
3.10
2.98
332
327
275
270
4T1g(F) ? 4T1g(P)
4T1g(F) ? 4T2g(F)
4T1g(F) ? 4A2g
[Ni(CHP)2Cl2]
4T1g(F) ? 4T1g(P)
a
Molar conductance measured for 10ꢁ3 M DMSO solution,
X .
ꢁ1 cm2 molꢁ1

A.A. El-Sherif / Inorganica Chimica Acta 362 (2009) 4991–5000
4995
Table 4
Electronic spectral parameters for the octahedral nickel(II) complexes.
Complex
t1
t2
t3
t2/
t1
Dq
B0
b
Dq/B0
[Ni(PHP)2Cl2]ꢀH2O
[Ni(THP)2Cl2]ꢀH2O
[Ni(CHP)2Cl2]
10 050
10 100
10 116
15 715
15 940
16 240
23 450
23 550
23 590
1.56
1.58
1.61
1005
1010
1012
601
613
632
0.58
0.59
0.61
1.67
1.65
1.60
observed for copper(II) complexes indicates that the unpaired elec-
Table 5
Electron spin resonance data.
tron is localized in ðdx2 Þ orbital [38] of the Cu(II) ion (spectro-
ꢁy2
2
scopic state B1g) and the spectral features are characteristics of
Complex
g||
g\
gavg
G
axial symmetry [39]. The values of gav were calculated according
to the equation gav = 1/3[g|| + 2g\] and the results are given in Table
5. g|| is a moderately sensitive function for M–L bond nature. Kivel-
son and Neiman [40] have reported the g|| value <2.3 for covalent
character of metal–ligand bond and g|| value >2.3 for ionic charac-
ter. By applying this criterion, the g|| values (Table 5) are less than
2.3 is an indication of significant covalent bonding in copper(II)
complexes. Based on elemental analysis, IR, electronic spectra
and ESR data, all complexes have a square planar structure.
The geometric parameter G, which is a measure of the exchange
interaction between copper centers in the polycrystalline com-
pound, is calculated using Hathway expression (G = g|| ꢁ 2.0023/
g\ ꢁ 2.0023) [41,42]. According to Hathway, if the value of G > 4,
the exchange interaction is negligible in solid complexes but
G < 4 indicates considerable interaction in solid complexes. In the
complexes reported in this paper the ‘G’ values (3.70–3.81) < 4,
indicating some weak exchange interaction between the copper(II)
centers in the solid phase.
[Cu(PHP)2]Cl2ꢀH2O
[Cu(THP)2]Cl2ꢀ2H2O
[Cu(CHP)2]Cl2ꢀH2O
2.188
2.180
2.168
2.051
2.052
2.047
2.09
2.11
2.08
3.81
3.57
3.70
all the molecular orbitals and therefore a covalent character of nick-
el(II)–ligand bonds. It is well known that magnetic susceptibility
measurements provide information to characterize the structure
of the complexes. The room temperature magnetic moment of nick-
el(II) complexes lies in the range 2.92–3.10 B.M., corresponding to
three unpaired electrons and in the range of an octahedral Ni(II)
complexes [32,33].
3.3.2. Cu(II) complexes
In general, due to Jahn–Teller distortion Cu(II) complexes give
absorption band between 16 667 and 14 286 cmꢁ1. The electronic
spectra of copper(II) complexes show absorption band in the range
15 625–15 873 cmꢁ1 assignable to 2B1g ? 2B2g transition of square
planar geometry [30,34,35]. No absorption bands are observed be-
low 10 000 cmꢁ1 in any complex under study which rules out the
possibility of tetrahedral geometry [36,37]. Copper (II) complexes
are paramagnetic and the room temperature magnetic moment
values ranging from 1.68 to 1.76 B.M. are close to the spin only va-
lue of 1.70 B.M. indicate the presence of one unpaired electron and
demonstrate that these complexes are monomeric in nature and
the absence of metal–metal interaction.
3.4. Structural interpretation
From all of the above observation and according to the data re-
ported in this paper based on the IR, molar conductivity, spec-
tral(solid reflectance) and magnetic measurements, the structure
of these complexes is given as shown in Scheme 4. The structure
proposed for Cu(II)-complexes is square planar while for Ni(II)-
complexes is octahedral. This indicates that, the ligand behaves
as bidentate chelating ligand and both azomethine nitrogen and
keto oxygen are the two sites of coordination.
3.3.2.1. EPR spectra. The X-band ESR spectra of the isolated cop-
per(II) solid complexes recorded at room temperature provides
information about the square planar geometry of the copper(II)
complexes. The spectra are anisotropic and exhibit axial type sig-
nals with two ‘‘g” values corresponding to g|| and g\ (Table 5).
The g|| and g\ values are computed from the spectrum using DPPH
free radical as ‘‘g” marker. The ordering of g values (g|| > g\ > 2.003)
3.5. Equilibrium studies
The proton association constant corresponding to NH group of
(PHP) is determined (Table 6). The PHP ligand titration curve in
X
X
NH
NH
Cl
H3C
H3C
N
N
O
O
nH2O
Cl2. nH2O
Ni
Cu
O
O
N
CH3
N
CH3
Cl
NH
NH
X
X
Scheme 4. X = H (PHP); CH3 (THP) and Cl (CHP).

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A.A. El-Sherif / Inorganica Chimica Acta 362 (2009) 4991–5000
Table 6
Thermodynamic parameters for the protonation of PHP ligand in aqueous solution at I = 0.1 mol dmꢁ3 NaNO3.
T (°C)
log K
D
G0 (kJ molꢁ1
)
D
H0
ꢁ8.45 0.6
D
S0
20
25
30
35
40
11.23( 0.02)
10.98( 0.01)
10.78( 0.01)
10.51( 0.02)
10.26( 0.02)
ꢁ63.00 1.7
ꢁ62.65 1.4
ꢁ62.54 1.3
ꢁ61.98 1.4
ꢁ61.49 1.1
178.5 3.4
Standard deviations are given in parentheses.
Table 7
Stepwise stability constants for the complexes of PHP with Cu(II) and Ni(II) metal ions in aqueous solution at I = 0.1 mol dmꢁ3 NaNO3.
a
T (°C)
log K1(
r
)
log K2(
r)
log K1 ꢁ log K2
CuL
NiL
CuL2
NiL2
Cu(II) complex
Ni(II) complex
20
25
30
35
40
6.99( 0.01)
6.89( 0.02)
6.79( 0.01)
6.70( 0.01)
6.63( 0.01)
5.24( 0.02)
5.17( 0.01)
5.10( 0.01)
5.04( 0.01)
4.97( 0.02)
6.41( 0.02)
6.32( 0.01)
6.24( 0.01)
6.16( 0.07)
6.08( 0.01)
4.36( 0.03)
4.31( 0.02)
4.25( 0.01)
4.20( 0.01)
4.16( 0.02)
0.58
0.57
0.55
0.54
0.55
0.88
0.86
0.85
0.84
0.81
a
(r) is the standard deviation; L = PHP.
presence and absence of metal ion (Cu2+ or Ni2+) are compared. The
metal–ligand titration curves lie below the curve of the ligand,
which can be attributed to the liberation of proton(s) through dis-
placement by the metal ions during complex formation. The poten-
tiometric data of the divalent metal ions with PHP provide a good
fit assuming the formation of M(PHP) (1 1 0) and M(PHP)2 (1 2 0)
species. Table 7 shows that (log K1 ꢁ log K2) values are usually po-
sitive, since the coordination sites of the metal ions are more freely
available for binding of the first ligand than the second. The mag-
nitude of stability constants of Cu(II) complexes with PHP is great-
er than those of Ni(II) complexes. The greater stability of Cu2+
complexes is produced by the well-known Jahn–Teller effect.
and T is the absolute temperature. The calculated thermodynamic
functions are recorded in Table 8 and can be interpreted as follows:
(1) The protonation reaction of PHP can be represented by Eq.
(9) as follows:
L
ꢁ þ HþꢁLH:
ð9Þ
The thermodynamic processes accompanying the proton-
ation reaction are:
a. The neutralization reaction, which is an exothermic process;
b. Desolvation of ions, which is an endothermic process;
c. The change in the configuration and the arrangements of the
hydrogen bonds around the free and protonated ligands.
(2) The log KH value decrease with increasing temperature
revealing that its acidity increases with increasing tempera-
ture [43].
3.5.1. Species distribution curves
Estimation of equilibrium concentrations of Cu(II) and Ni(II)
complexes with hydrazone ligands as a function of pH provides a
useful picture of metal(II) binding in the biological system. The
concentration distribution diagram of Ni(II) with (PHP) as a repre-
sentative example of metal complexes is shown in Fig. 1. Ni(PHP)2
complex starts to form at pH 5 in the acidic pH range and reaches a
constant concentration of 97% starting from pH 9.0.
(3) A negative value of
D
H0 for the protonation process of PHP
ligand indicates that its association process is accompanied
by a release of heat and the process is exothermic.
(4) The protonation reaction of hydrazone ligand has positive
entropy; this may be due to increased disorder as a result
of desolvation processes and the breaking of hydrogen
bonds.
3.5.2. Effect of temperature
The values obtained for
D D D
H0, S0 and G0 associated with pro-
The stepwise stability constants of the complexes formed at dif-
ferent temperatures were calculated and the average values are in-
cluded in Table 8. Examination of these values reveals that:
tonation of hydrazone ligands and their complex formation with
divalent Cu(II) and Ni(II) ions were calculated from the tempera-
ture dependence of the data in Tables 6 and 7. The enthalpy change
(DH) for the protonation of ligand or complexation process was
calculated from the slope of the plot (log K versus 1/T) (Figs. 2–4)
using Van’t Hoff equation (6):
1. The stepwise stability constants (log K1 and log K2) for the
complexes decrease with increasing temperature, i.e. their
stabilities decrease with increasing temperature and com-
plexation process is more favorable at lower temperatures
[44].
log K ¼ ꢁð
D
H0=2:303RÞð1=TÞ þ
D
S0=R
G) and (
ð6Þ
2. All values of
spontaneity of the coordination process.
3. The negative values of
H0 show that the coordination process
D
G0 for complexation are negative, indicating the
From the free energy change (
D
D
H) values one can de-
duce the entropy change (
D
S) using the well-known relationships
D
(7) and (8):
is exothermic, indicating that the complexation reactions are
favored at low temperatures.
4. It is generally noted that
D
D
G0 ¼ ꢁ2:303RT log K
ð7Þ
ð8Þ
D D
G0 and H0 values for the 1:1 com-
S0 ¼ ð
D
H0 ꢁ
D
G0Þ=T
plexes are more negative than those corresponding to the 1:2
complexes, Table 8. This may be attributed to the steric hin-
drance produced by the entrance of a second ligand.
where the gas constant R = 8.314 J Kꢁ1 molꢁ1, K is the protonation
constant for the ligand or the stability constant of the complex,

A.A. El-Sherif / Inorganica Chimica Acta 362 (2009) 4991–5000
4997
100
90
80
70
60
50
40
30
20
10
0
Ni(PHP)2
Ni(II)
Ni(OH)2
Ni(OH)
6
7
8
9
10
11
12
pH
Fig. 1. Concentration distributions of various species as a function of pH of Ni(II)–PHP system at concentration of 1.0 ꢂ 10ꢁ3 mol dmꢁ3, for Ni(II) and 2.0 ꢂ 10ꢁ3 mol dmꢁ3 for
PHP, I = 0.1 mol dmꢁ3 at 25 °C.
11.4
11.2
11
10.8
10.6
10.4
10.2
0.00315
0.0032
0.00325
0.0033
1/T
0.00335
0.0034
0.00345
Fig. 2. Van’t Hoff plot of log Kprotonation of PHP ligand.
5. The
D
S0 values for all investigated complexes are positive, indi-
pounds, we used more than one test organism to increase the
chance of detecting antibiotic principles in tested materials. The
results of the antimicrobial activity of the synthesized compounds
are recorded in Table 9. The data obtained reflect the following
results:
cating that the increase in entropy by the release of bound sol-
vent molecules on coordination is greater than the decrease
resulting from the coordination process itself. It occurs because
the solvent molecules arranged in an orderly fashion around the
ligand and the metal ion has acquired a more random configu-
ration on coordination [44].
1. The synthesized complexes were found to be more toxic com-
pared with their parent free ligands against the same micro-
organism and under the identical experimental conditions.
The increase in biological activity of the metal chelates may
be due to the effect of the metal ion on the normal cell process.
A possible mode of toxicity increase may be considered in the
light of Tweedy’s chelation theory [45]. Chelation considerably
reduces the polarity of the metal ion because of partial sharing
3.6. Antimicrobial activity
The question about the involvement of the metal complexes in
medical treatment is of special interest. To assess the biological po-
tential of the synthesized compounds, the hydrazone ligands and
their metal complexes were tested against different species of bac-
teria and fungi. In testing the antimicrobial activity of these com-
of its positive charge with the donor group and possible
p-elec-
tron delocalization within the whole chelate ring system that is

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A.A. El-Sherif / Inorganica Chimica Acta 362 (2009) 4991–5000
7.5
7
Cu(L)
6.5
6
Ni(L)
5.5
5
4.5
4
0.00315
0.0032
0.00325
0.0033
1/T
0.00335
0.0034
0.00345
Fig. 3. Van’t Hoff plot of log K1 of Cu(II) and Ni(II) complexes with PHP.
7
6.5
6
Cu(L)2
5.5
5
Ni(L)2
4.5
4
0.00315
0.0032
0.00325
0.0033
1/T
0.00335
0.0034
0.00345
Fig. 4. Van’t Hoff plot of log K2 of Cu(II) and Ni(II) complexes with PHP.
Table 8
Thermodynamic parametersa for Cu(II) and Ni(II) complexes of PHP in aqueous solution at I = 0.1 mol dmꢁ3 NaNO3.
ꢁD
G01 (kJ molꢁ1
)
ꢁ
D
G02 (kJ molꢁ1
)
ꢁ
D
H01 (kJ molꢁ1
)
ꢁ
D
H02 (kJ molꢁ1
)
D
S01 (J Kꢁ1 molꢁ1
)
D
S02 (J Kꢁ1 molꢁ1
)
T (°C)
CuL
NiL
CuL2
NiL2
CuL
NiL
CuL2
NiL2
17.92
CuL
NiL
18.8
CuL2
24.4
NiL2
22.2
20
25
30
35
40
39.21
39.31
39.39
39.51
39.67
29.39
29.50
29.58
29.72
29.79
35.96
36.06
36.20
36.33
36.44
24.46
24.59
24.67
24.77
24.93
32.67
23.89
28.80
22.2
G01 ꢄ ð0:29 ꢁ 0:85Þ; ꢁ
D
G02 ꢄ ð0:51 ꢁ 0:95Þ; ꢁ
D
H01 ꢄ ð0:49 ꢁ 0:93Þ;
D
H02 ꢄ ð0:78 ꢁ 1:12Þ;
D
S01 ꢄ ð0:99 ꢁ 1:43Þ;
D
S02 ꢄ ð0:83 ꢁ 1:28Þ; L = PHP.
a
Standard deviations, ꢁ
D
formed during coordination. Such chelation could enhance the
lipophilic character of the central metal atom and hence
increase the hydrophobic character and liposolubility of the
complex favoring its permeation through the lipid layers of
the cell membrane. This enhances the rate of uptake/entrance
and thus the antimicrobial activity of the testing compounds.

A.A. El-Sherif / Inorganica Chimica Acta 362 (2009) 4991–5000
4999
Table 9
Antimicrobial activity of the free ligands and isolated complexes.
Compound
Gram-positive
Gram-negative
Fungi
Staphylococcus aureus
Pseudomonas aereuguinosa
Escherichia coli
Candida albican
Candida lypolytic
PHP
THP
CHP
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
++
++
++
+
+
+
+
+++
++
+++
++
+
+
+
+
+++
++
++
+++
+
ꢁ
ꢁ
ꢁ
ꢁ
[Cu(PHP)2]Cl2ꢀH2O
[Cu(THP)2]Cl2ꢀ2H2O
[Cu(CHP)2]Cl2ꢀH2O
[Ni(PHP)2Cl2]ꢀH2O
[Ni(THP)2Cl2]ꢀH2O
[Ni(CHP)2Cl2]
Amikacin
++++
++
+++
++
+
++
++
++
+
+
+
+++
R
R
+
+
+
R
+++
R
++
++
Augmantin
Septrin
Cefobid
R
R
Erythromycin
Ampicillin
+++
R
R
+ +
Note: (1) The test was done using the disc diffusion method.
(2) (ꢁ) = non-detected (resistance).
(3) Zone of inhibition as ++++ = (20–25 mm) (very active).
(4) Zone of inhibition as +++ = (15–20 mm) (highly active).
(5) Zone of inhibition as ++ = (10–15 mm) (moderately active).
(6) Zone of inhibition as + = (5–10 mm) (moderately active).
Accordingly, the antimicrobial activity of the complexes present
in this investigation can be referred to the increase of their lipo-
philic character which in turn deactivates enzymes responsible
for respiration processes and probably other cellular enzymes,
which play a vital role in various metabolic pathways of the
tested micro-organisms.
complexes. In the same connection, Augmantin, Septrin, Cefobid
and Erythromycin have resistance effect toward P. aereuguinosa
while all synthesized complexes have a greater effect.
7. Cu(II) complexes have a greater or comparable effect than the
effect of all tabled antibiotics against Gram-positive bacteria.
2. Antibacterial activity of all complexes towards Escherichia coli
are detected.
4. Conclusions
3. Structure–activity relationships evidence that the complexation
with copper enhances the antimicrobial activity of the ligands
against some of the tested organism. Since copper chelates have
an enhanced antimicrobial activity, in comparison to their anal-
ogous containing nickel(II) ion, the metal seems to play a rele-
vant role in the activity of these compounds. A similar behavior
of the increased antibacterial activity was also exhibited by
copper derivatives of 2,6-diacetylpyridine bis(2-thenoylhydraz-
one) in comparison to the corresponding Co(II), Ni(II) and Zn(II)
chelates [46].
4. The tested complexes were more active against Gram-positive
than Gram-negative bacteria, it may be concluded that the anti-
microbial activity of the compounds is related to cell wall struc-
ture of the bacteria. It is possible because the cell wall is
essential to the survival of bacteria and some antibiotics are
able to kill bacteria by inhibiting a step in the synthesis of pep-
tidoglycan. Gram-positive bacteria possess a thick cell wall con-
taining many layers of peptidoglycan and teichoic acids, but in
contrast, Gram-negative bacteria have a relatively thin cell wall
consisting of a few layers of peptidoglycan surrounded by a sec-
ond lipid membrane containing lipopolysaccharides and lipo-
proteins. These differences in cell wall structure can produce
differences in antibacterial susceptibility and some antibiotics
can kill only Gram-positive bacteria and is infective against
Gram-negative pathogens [47].
The present paper reports on the synthesis, characterization
and their electronic absorption spectra of hydrazone ligands and
their Cu(II) and Ni(II) complexes. The synthetic procedure in this
work resulted in the formation of complexes in the molar ratio
(1:2) (M:L), respectively. In these complexes the hydrazone ligand
acts as a neutral bidentate ligand and coordinated to metal ion
through the azomethine-nitrogen and keto-oxygen atoms forming
stable five membered heterocyclic rings. The present study re-
vealed octahedral geometry around Ni(II)-complexes and square
planar geometry around Cu(II)-complexes. From conductance
measurements Cu(II)-complexes are electrolytes while Ni(II)-com-
plexes are non-electrolytes. The ionization constant of the investi-
gated ligand (PHP) has been determined potentiometrically. Also,
the present investigation described the formation equilibria of
Cu(II) or Ni(II) with PHP and from the above-mentioned results it
may be concluded that:
(a) The formation of the metal complexes has been found to be
spontaneous, exothermic and entropically favorable.
(b) The values of log K1 ꢁ log K2 are positive, indicating that the
coordination of the first ligand molecule (PHP) to the metal
ion is more favorable than the bonding to the second one.
The results of antimicrobial activity show that the metal com-
plexes exhibit antimicrobial properties and it is important to note
that they show enhanced inhibitory activity compared to the par-
ent ligand under identical experimental conditions. The antibacte-
rial activity has been explained on the basis of chelation theory.
Also, the results indicated that tested complexes were more active
against Gram-positive than Gram-negative bacteria. It may be con-
cluded that antibacterial activity of the compounds is related to
cell wall structure of the bacteria. It is possible because the cell
5. The free ligands and their synthesized complexes were found to
have antifungal activity toward C. albican and C. lypolytic fungi.
6. Furthermore, some known antibiotics are tested toward S. aur-
eus (as Gram-positive) and P. aereuguinosa (as Gram negative).
The selected antibiotics are Amikacin, Augmantin, Septrin, Cefo-
bid, Ampicillin and Erythromycin. The given data in Table 9 show
that Amikacin, Septrin, Cefobid, and Ampicillin antibiotics have
resistance effect toward S. aureus in contrast to the synthesized

5000
A.A. El-Sherif / Inorganica Chimica Acta 362 (2009) 4991–5000
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