Spectroscopic studies and biological activity of some transition metal complexes of unusual Schiff base

Article abstract of DOI:10.1016/j.saa.2012.12.008

Unusual Schiff base ligand, 4-ethanimidoyl-6-[(1E)-N-(2-hydroxy-4- methylphenyl)ethanimidoyl]benzene-1,3-diol, L, was synthesized via catalytic process involving the interaction of some metal ions with a macrocyclic Schiff base (MSB). The transition metal derivatives [ML(H₂O) ₄](NO₃)₃, M = Cr(III) and Fe(III), [NiL(H ₂O)₄](NO₃)₂, [ML(H ₂O)₂](NO₃)₂, M = Zn(II) and Cd(II), [Cl₂Pd(μ-Cl)₂PdL], [PtL(Cl)₂] and [PtL(Cl)₄] were also synthesized from the corresponding metal species with L. The Schiff bases and complexes were characterized by elemental analysis, mass spectrometry, IR and ¹H NMR spectroscopy. The crystal structure of L was determined by X-ray analysis. The spectroscopic studies revealed a variety of structure arrangements for the complexes. The biological activities of L and metal complexes against the Escherchia coli as Gram-negative bacteria and Staphylococcus aureus as Gram-positive bacteria, and the two fungus Aspergillus flavus and Candida albicans were screened. The cytotoxicity of [PtL(Cl)₂] complex, a cis-platin analogous, was checked as an antitumor agent on two breast cancer cell lines (MCF7 and T47D) and human liver carcinoma cell line (HepG2).

Full text of DOI:10.1016/j.saa.2012.12.008

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 105 (2013) 14–19
Contents lists available at SciVerse ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Spectroscopic studies and biological activity of some transition metal complexes
of unusual Schiff base
⇑
Ahmad K. Abu Al-Nasr, Ramadan M. Ramadan
Applied Chemistry Department, Faculty of Applied Science, Taibah University, Almadinah Almunawrah, Saudi Arabia
g r a p h i c a l a b s t r a c t
h i g h l i g h t s
Unusual Schiff base ligand, 4-ethanimidoyl-6-[(1E)-N-(2-hydroxy-4-methylphenyl)ethanimidoyl]ben-
zene-1,3-diol, L, was synthesized via catalytic process. Some transition metal derivatives were also
synthesized from the corresponding metal species with L. The biological activities of L and metal
complexes were screened.
"
"
"
"
"
Synthesis and analysis of unusual
Schiff base from a macrocycle Schiff
base (L).
Synthesis and spectroscopic of some
transition metal complexes derived
from L.
Crystal structure of L was
determined through X-ray single
crystal analysis.
Biological activity of L and
complexes against bacteria and
fungus were screened.
Cytotoxicity of [PtIIL(Cl)2] complex
was checked as an antitumor agent.
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 June 2012
Received in revised form 19 November 2012
Accepted 5 December 2012
Available online 27 December 2012
Unusual Schiff base ligand, 4-ethanimidoyl-6-[(1E)-N-(2-hydroxy-4-methylphenyl)ethanimidoyl]
benzene-1,3-diol, L, was synthesized via catalytic process involving the interaction of some metal ions
with a macrocyclic Schiff base (MSB). The transition metal derivatives [ML(H2O)4](NO3)3, M = Cr(III)
and Fe(III), [NiL(H2O)4](NO3)2, [ML(H2O)2](NO3)2, M = Zn(II) and Cd(II), [Cl2Pd(l-Cl)2PdL], [PtL(Cl)2] and
[PtL(Cl)4] were also synthesized from the corresponding metal species with L. The Schiff bases and com-
plexes were characterized by elemental analysis, mass spectrometry, IR and 1H NMR spectroscopy. The
crystal structure of L was determined by X-ray analysis. The spectroscopic studies revealed a variety of
structure arrangements for the complexes. The biological activities of L and metal complexes against
the Escherchia coli as Gram-negative bacteria and Staphylococcus aureus as Gram-positive bacteria, and
the two fungus Aspergillus flavus and Candida albicans were screened. The cytotoxicity of [PtL(Cl)2] com-
plex, a cis-platin analogous, was checked as an antitumor agent on two breast cancer cell lines (MCF7 and
T47D) and human liver carcinoma cell line (HepG2).
Keywords:
Schiff bases
Complexes
Spectra
Biological activity
Cytotoxicity
Ó 2012 Elsevier B.V. All rights reserved.
⇑
Corresponding author. Address: Chemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt. Tel.: +20 966556404953; fax: +20 96648401743.
E-mail address: r_m_ramadan@yahoo.com (R.M. Ramadan).
1386-1425/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.saa.2012.12.008

A.K. Abu Al-Nasr, R.M. Ramadan / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 105 (2013) 14–19
15
and the formed yellow precipitate was isolated by filtration. The
crude was recrystallized from hot ethanol to give yellow fine crys-
tals. The compound was left to dry under vacuum for several hours
(yield 86%).
Introduction
Coordination chemistry of macrocyclic ligands has shown to be
interesting subject of current research in the last two decades [1,2].
Importance in designing new macrocyclic ligands arises mainly
from their use as models for protein-metal binding sites in a sub-
stantial array of metalloproteins in biological systems, such as
the synthetic ionophores, models for the magnetic exchange phe-
nomena, therapeutic reagents in chelate therapy for treatment of
metal intoxication and the cyclic antibiotics that retain their anti-
biotic actions to specific metal complexation [3–6]. On the other
hand, the synthesis of binuclear complexes in which a ligand struc-
ture accommodates two metal centers in close proximity but in a
different compartments separated by an intervening group repre-
sents important criteria in the study of transition-metal systems.
In such molecularly designed ligands, the aromatic rings are ex-
pected to act as a bridge and a rigid separator between the two
compartments. The interest in these complexes corresponds to
their ability to serve as simple models for multi-metal-centered
catalysts [7,8]. From these types of ligands, the macrocyclic Schiff
bases exhibited great importance in macrocyclic chemistry be-
cause they can selectively chelate certain metal ions depending
on the number, type and position of their donor atoms, the ionic
radii of the metal centers, and the coordinating property of the
counter ions [9]. Thus, the coordination chemistry of these macro-
cyclic Schiff bases was appeared in many recent reports due to
their important applications [2,10–12].
Preparation of 4-ethanimidoyl-6-[(1E)-N-(2-hydroxy-4-
methylphenyl)ethanimidoyl]-benzene-1,3-diol (L)
A mixture of MSB and FeCl3 (1:1 mol ratio) in absolute ethanol
was heated to reflux for 5 min and then left to stand at room tem-
perature for few hours. The formed yellow residue was separated
by filtration. The compound was recrystallized from hot ethanol
to give yellow crystals. The crystals were left to dry under vacuum
for several hours (yield 42%).
Preparation of complexes
A mixture of metal ion salt and 4-ethanimidoyl-6-[(1E)-N-(2-
hydroxy-4-methylphenyl) ethanimidoyl]benzene-1,3-diol ligand
(1:1 M ratio) in about 30 cm3 aqueous ethanol was heated to reflux
with stirring for ca. 2 h. The reaction mixture was cooled and solid
complexes were separated by slow evaporation. The isolated com-
plexes were recrystallized from hot ethanol (yield 68–79%). Table 1
gives the elemental analysis and mass spectrometry data for the
Schiff bases and complexes.
Biological activity
In vitro antibacterial and antifungal activity of the ligand and
the synthesized complexes were tested against the two bacteria:
Escherchia coli as Gram-negative bacteria and Staphylococcus aureus
as Gram-positive bacteria, and the two fungus: Aspergillus flavus
and Candida albicans. The tests were carried out using paper disc
diffusion method. The nutrient agar medium (peptone, beef ex-
tract, NaCl and agar-agar) and 5 mm diameter paper discs of What-
man No.1 were used. The test compound was dissolved in DMSO in
0.1–0.4% concentrations. The paper discs was soaked in different
solutions of the compound, dried and placed in the Petri plates
(9 cm diameter) previously seeded with the test organisms. The
plates were incubated for 24–30 h at 27 1 °C and the inhibition
zones (mm) were measured around each disc. As the organism
grows, except in the region where the concentration of antibacte-
rial agent was above the minimum inhibitory concentration and a
zone of inhibition was seen. The size of the inhibition zone de-
pends upon the culture medium, incubation conditions, rate of dif-
fusion and the concentration of the antibacterial agent.
Comparison of the obtained data was carried out with the two
standards: tetracycline antibacterial agent and Amphotericin B
antifungal agent.
In this article, we report the synthesis of a molecularly designed
macrocyclic Schiff base (4,6-di[(1E)-N-(2-hydroxy-4-methyl-
phenyl)-ethanimidoyl]benzene-1,3-diol). Interaction of this com-
pound with different transition metal species showed unusual
catalytic process to yield the unusual ligand 4-ethanimidoyl-6-
[(1E)-N-(2-hydroxy-4-methylphenyl)ethanimidoyl]benzene-1,3-
diol, L, Scheme 1. The synthesis and spectroscopic studies of some
transition metal complexes of that unusual ligand are also reported.
Experimental
Reagents
4,6-Diacetylresorcinol, 2-amino-5-methylphenol and the tran-
sition metal salts were purchased from Aldrich. All the solvents
were of analytical reagent grade and were purified by standard
methods.
Instruments
IR measurements (KBr pellets) were carried out on a Unicam–
Mattson 1000 FT-IR spectrometer. NMR measurements were
performed on a Spectrospin–Bruker 300 MHz spectrometer. Sam-
ples were dissolved in (CD3)2SO and TMS was used as an internal
reference. Thermogravimetric analysis measurements were carried
out under N2 atmosphere at a heating rate of 10 °C/min using a
Shimadzu DT-50 thermal instrument. Elemental analyses were
performed on Perkin–Elmer 2400 CHN elemental analyzer. Mass
spectrometry measurements of the solid complexes (70 eV, EI)
were carried out on a Finnigan MAT SSQ 7000 spectrometer.
Cytotoxicity determination
Three human cancer cell lines were used for in vitro screening
experiments: two breast cancer cell lines (MCF7 and T47D) and hu-
man liver carcinoma cell line (HepG2). The cancer cells were ob-
tained frozen in liquid nitrogen (ꢀ180 °C) from the American
Type Culture Collection. The tumor cell lines were maintained in
the National Cancer Institute, Cairo, Egypt, by serial sub-culturing.
Cell culture cytotoxicity assays were carried out as described in lit-
erature [13]. RPMI-1640 medium (Sigma Chemical Co., St. Louis,
Mo, and USA) was used for culturing and maintenance of the hu-
man tumor cell lines. Cells were seeded in 96-well microliter plates
at a concentration of 5 ꢁ 104–105 cell/well in a fresh medium and
left to attach to the plates for 24 h. Growth inhibition of cells was
calculated spectrophotometrically using a standard method with
the protein-binding dye sulforhodamine B (SRB) [14]. The optical
density (OD) of each well was measured at 564 nm with an ELIZA
Preparation of Schiff bases
Preparation of 4,6-di[(1E)-N-(2-hydroxy-4-methylphenyl)-
ethanimidoyl]-benzene-1,3-diol (MSB)
Solutions of 4,6-diacetylresorcinol and 2-amino-5-methylphe-
nol in absolute ethanol with molar ratio 1:2 were mixed together
and heated to reflux for 1 h. The reaction mixture was then cooled

16
A.K. Abu Al-Nasr, R.M. Ramadan / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 105 (2013) 14–19
microplate reader (Meter Tech.
R
960, USA). The sensitivity of the
and refinements. All Diagrams and calculations were performed
using maXus crystallographic software package (Nonius, Delft &
MacScience, Japan). The structure was determined by direct meth-
ods SIR 92 [15] and refined by full matrix least-squares methods
maXus [16]. The displacement factors of non-hydrogen atoms of
the compound were refined with anisotropic thermal parameters.
The hydrogen atoms were refined isotropically. The function min-
human tumor cell lines to thymoquinone was determined by the
SRB assay. The percentage of cell survival was calculated as
follows:
Survival fraction ¼ ODðtreated cellsÞ=ODðcontrol cellsÞ
The IC50 value is the concentration of thymoquinone required to
produce 50% inhibition of cell growth. The results are compared
with a similar run of cis-platin as an antitumor compound.
imized was [
R
w(|Fo| ꢀ |Fc|)2/
R
w|Fo|2]½ with w = l/d2(Fo)2 + 0.0300
(Fo)2. The final R and Rw values are given in Table 3.
X-ray structure determination
Results and discussion
All X-ray measurements were made at room temperature using
suitable crystals for data collection. Accurate lattice parameters
were determined from least squares refinements of well-centered
reflections in the ranges 2.91 6 h 6 27.49 for the compound. Dur-
ing data collection, three standard reflections were periodically ob-
served and showed no significant intensity variations. The ranges
of h, k and l are 0 6 h 6 14; 0 6 k 6 12 and ꢀ17 6 l 6 16. 5456 un-
The Schiff base 4,6-di[(1E)-N-(2-hydroxy-4-methyl-phenyl)-
ethanimidoyl]benzene-1,3-diol was prepared by the condensation
reaction of 4,6-diacetylresorcinol and 2-amino-5-methylphenol in
1–2 M ratio (Scheme 1). This Schiff base was molecularly designed
to be used as a bicompartment ligand. The IR spectrum of the com-
pound showed characteristic stretching frequencies due to the
functional groups, Table 2 [17]. Also, the presence of the OH groups
was confirmed by 1H NMR (Table 2). Direct interaction of this
Schiff base with some transition metal species such as Fe(III), Ni(II)
ique reflections were measured of which 2018 had I > 3:00r(I).
These observed reflections were used for structure determination
Table 1
Elemental analysis and mass spectrometry data of the Schiff bases and complexes.
Complex
Elemental analysis found (calc.)
Mass spectrometry
C
H
N
Cl
M.M.
m/z
MSB
L
71.20 (71.27)
68.38 (68.44)
33.56 (33.53)
33.31 (33.35)
36.83 (36.92)
38.91 (38.98)
31.22 (31.27)
35.69 (35.77)
36.10 (36.18)
32.06 (32.14)
6.03 (5.98)
6.12 (6.08)
4.35 (4.31)
4.32 (4.28)
4.85 (4.74)
4.31 (4.23)
2.84 (2.78)
4.32 (4.23)
3.35 (3.22)
2.84 (2.78)
6.88 (6.92)
9.30 (9.39)
11.48 (11.51)
11.40 (11.44)
10.05 (10.13)
10.62 (10.70)
4.22 (4.29)
9.73 (9.82)
4.91 (4.96)
4.19 (4.29)
–
–
–
–
–
–
404.47
298.34
608.41
612.27
553.11
523.77
652.95
570.79
564.34
635.24
388
299
547, 549, 552
551, 553
491, 492, 493
460, 462, 463
648, 649, 652
549, 550, 552
562, 563, 564, 565
634, 635, 636, 638, 641
[CrL(H2O)4](NO3)3
[FeL(H2O)4](NO3)3
[NiL(H2O)4](NO3)2
[ZnL(H2O)2](NO3)2
[Cl2Pd(
[CdL(H2O)2](NO3)2
[PtL(Cl)2]
l
-Cl)2PdL]
21.63 (21.72)
–
12.50 (12.57)
22.27 (22.32)
[PtL(Cl)4]
Table 2
IR and NMR data of the Schiff bases and complexes.
Compound
IR data (cmꢀ1
(OH)
)
1H NMR data (ppm)
t
t
(NH)
t
(C@N)
t
(C@C)
MSB
3379 (m)
3310 (m)
–
1615 (sh)
1593 (vs)
1530 (vs)
1460 (s)
1433 (s)
12.70 (s, 2 H, OH), 9.46 (s, 2 H, OH), 8.41, 8.25 (d, 2 H, Ph), 6.88–6.1
(m, 6 H, Ph), 2.40 (s)–2.08 (s, 12 H, CH3)
L
3431 (b)
3069 (m)
1636 (s)
1611 (s)
1592 (s)
1536 (s)
1463 (m)
1435 (m)
17.21 (s, 1H, C@NH), 12.72 (s, 1 H, OH), 9.71 (d, 2 H, OH), 8.26 (d, 2 H, Ph),
6.89–6.20 (m, 3 H, Ph), 2.65–2.25 (m, 9 H, CH3)
[CrL(H2O)4](NO3)3
[FeL(H2O)4](NO3)3
3319 (b)
2925 (m)
2928 (m)
1603 (m)
1617 (s)
1519 (s)
–
–
3388 (vs)
3209 (s)
1542 (s)
1404 (s)
[NiL(H2O)4](NO3)2
[ZnL(H2O)2](NO3)2
3426 (vs)
2923 (m)
3028 (m)
1628 (s)
1417 (m)
–
3398 (m)
3291 (m)
3162 (m)
1692 (m)
1623 (s)
1528 (m)
1484 (m)
1440 (m)
12.48 (bs, 1 H, OH), 10.23 (bs, 2 H, OH), 8.41 (bs, 2 H, OH), 7.11–6.35
(m, 5 H, Ph), 1.35–1.03 (m, 9 H, CH3)
[Cl2Pd(
l-Cl)2PdL]
3399 (vs)
3196 (vs)
1616 (s)
1565 (m)
1499 (m)
1424 (s)
12.33 (bs, 1 H, OH), 10.15 (bs, 2 H, OH), 8.80 (bs, 2 H, OH), 7.30–6.59
(m, 5 H, Ph), 1.32–1.27 (m, 9 H, CH3)
[CdL(H2O)2](NO3)2
3510 (b)
3075 (w)
2928 (w)
1612 (m)
1594 (m)
1531 (m)
1491 (m)
12.45 (bs, 1 H, OH), 10.20 (bs, 2 H, OH), 8.37 (bs, 2 H, OH), 7.10–6.10
(m, 5 H, Ph), 1.25–1.06 (m, 9 H, CH3)
[PtL(Cl)2]
[PtL(Cl)4]
3427 (b)
3216 (m)
2927 (w)
3076 (m)
1627 (m)
1654 (s)
1500 (m)
1428 (m)
12.42 (bs, 1 H, OH), 10.15 (bs, 2 H, OH), 8.02 (bs, 2 H, OH), 7.31–6.18
(m, 5 H, Ph), 1.71–1.06 (m, 9 H, CH3)
1587 (s)
1488 (m)
1425 (sh)
12.48 (bs, 1 H, OH), 10.22 (bs, 2 H, OH), 8.14 (bs, 2 H, OH), 7.27–6.37
(m, 5 H, Ph), 1.33–1.26 (m, 9 H, CH3)

A.K. Abu Al-Nasr, R.M. Ramadan / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 105 (2013) 14–19
17
Table 4
and Pd(II) in ethanol exhibited a catalytic process to give the unu-
Selected bond lengths (Å) and bond angles (°) for the ligand L.
sual Schiff base, 4-ethanimidoyl-6-[(1E)-N-(2-hydroxy-4-methyl-
phenyl)ethanimidoyl]-benzene-1,3-diol, L (Scheme 1). Due to the
expected unusual structure arrangement of this Schiff base with
a free azomethine group, C@NH, the crystal structure was deter-
mined by X-ray analysis. The crystallographic data are presented
in Table 3. The ORTEP representation of the compound is illus-
trated in Fig. 1. Selected bond lengths and angles are given in Table
4. The crystal analysis revealed that the compound crystallized in
the monoclinic space group P21/c with a Z value of 4. From the
structural analysis of the compound (Fig. 1), it can be noted that
it is totally unsymmetrical having the point group Cs. The frag-
ments N1AC19AC18 and N1AC19AC9 are planar which revealed
the sp2 hybridization of the N1, C19 and C18 atoms. The bond an-
gles between these atoms lie in the range of 120° (Table 4). Also,
the bond angle C19AN1AH1 of the free azomethine is linear
(179.9°). Furthermore, the bond length of C19AN1 is 1.212 Å,
which is shorter than the normal single CAN bond, indicated the
presence of double bond character [18,19]. The bond lengths in
the other azomethine (C11AN5AC13) showed the presence of con-
jugation between the CAN bonds and the two phenyl groups at-
tached to the group (1.431 and 1.324 Å). The X-ray analysis of L
also showed that it contains three OH groups attached to the phe-
nyl rings. Interestingly, the CAO bond length of the OH group at-
tached to the position para to the C@NAH group (C16AO2 =
1.281 Å) is shorter than the other CAO bonds (C6AO3 = 1.355 Å
Bond lengths (Å)
N1AC19
O2AC16
O3AC6
1.212
(5)
1.281
(4)
1.355
(4)
1.339
(5)
1.324
(5)
1.431
(5)
1.392
(5)
1.400
(5)
C7AC18
1.382
(5)
1.370
(5)
1.514
(5)
1.438
(5)
1.505
(6)
1.410
(5)
1.455
(5)
1.415
(6)
C18AC20
C20AC22
C9AC19
C10AC13
C10AC21
N1AH1
1.441
(6)
1.353
(5)
1.514
(7)
1.382
(5)
1.382
(6)
0.960
(3)
0.960
(2)
0.960
(3)
C8AC14
C11AC12
C11AC15
C14AC17
C14AC21
C15AC16
C16AC22
C18AC19
O4AC20
N5AC11
N5AC13
C6AC8
O2AH2
C6AC13
C7AC15
O3AH3
1.396
(5)
1.469
(5)
O4AH4
0.960
(3)
Bond angles (°)
C11AN5AC13 127.2
O4AC20AC18
C6AC8AC14
119.3
(3)
121.4
(3)
C6AO3AH3
179.9
(9)
(3)
O3AC6AC8
O3AC6AC13
C8AC6AC13
123.3
(3)
117.4
(3)
119.3
(3)
O4AC20AC22 119.5
(4)
179.6
(3)
117.4
(3)
C13AC10AC21 120.7
C20AO4AH4
N5AC13AC6
(3)
120.4
(3)
118.2
(3)
N5AC11AC12
N5AC11AC15
C15AC7AC18 123.4
N5AC13AC10 122.7
(3)
(3)
N1AC19AC9
119.9
(4)
C12AC11AC15 121.5
C6AC13AC10 119.6
Table 3
(3)
(3)
The crystal structure parameters for the ligand L.
N1AC19AC18 121.3
C19AN1AH1
C16AO2AH2
179.9
(7)
180.0
(2)
C8AC14AC17 121.1
(4)
C9AC19AC18 118.8
(4)
(3)
C8AC14AC21 119.0
(4)
Crystal parameters
Empirical formula
Fw
Crystal system
Space group
a (Å)
C17H18N2O3
298.34
Monoclinic
P21/c
11.4842 (3)
9.7771 (3)
13.1498 (4)
90.00°
99.988 (2)°
90.00°
1454.11 (7)
and C20AO4 = 1.339 Å). The content of one unit cell (Fig. 2)
showed that the dihydroxy phenyl moieties of every two mole-
cules are located in opposite faces and are parallel. This could be
due to a charge transfer between every two moieties with
type of interaction [20].
b (Å)
c (Å)
a
(°)
b (°)
(°)
p–
pꢂ
c
V (Å)
According to the unusual structure of the ligand L, it was
expected that its transition metal complexes may have unique
chemical and structure features. Therefore, we have prompted to
carry out the interaction of some transition metal ions ca. Cr(III),
Fe(III), Ni(II), Zn(II), Pd(II), Cd(II), Pt(II) and Pt(IV) with the L,
1:1 M ratio, in aqueous ethanol solutions. A variety of complexes
were isolated; mainly: [ML(H2O)4](NO3)3, M = Cr(III) and Fe(III),
[NiL(H2O)4](NO3)2, [ML(H2O)2](NO3)2, M = Zn(II) and Cd(II), [Cl2-
Z
T/K
4
298
1.363
0.09
0.087
0.178
0.71073
qcalc (g cmꢀ3
)
l
(cmꢀ1
)
Ra
b
Rw
(Mo K
a
) Å
a
R =
Rw = [
R
[|Fo| ꢀ |Fo|R|Fo|].
b
½
R
w(|Fo| ꢀ |Fc|)2/
R
w|Fo|2] ; w = l/d2(Fo)2 + 0.0300 (Fo)2.
Fig. 1. The ORTEP projection of L.

18
A.K. Abu Al-Nasr, R.M. Ramadan / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 105 (2013) 14–19
Fig. 2. The unit cell packing of L. Hydrogen atoms are omitted for clearance.
Pd(
l-Cl)2PdL], [PtL(Cl)2] and [PtL(Cl)4]. Table 1 gives the elemental
Antibacterial and antifungal activity
analysis and mass spectrometry data of the complexes. The frag-
mentation patterns in the mass spectra of the complexes as well
as the elemental analysis data revealed the correctness of the sug-
gested molecular formula. The numbers of water molecules in the
complexes were determined using the thermogravimetry (TG)
technique. The electrical molar conductance in DMSO at room tem-
The free ligand and its respective metal complexes were
screened against the E. coli as Gram-negative bacteria and S. aureus
as Gram-positive bacteria, and the two fungus A. flavus and C. albi-
cans to assess their potential activity relative to the two standards:
Tetracycline antibacterial agent and Amphotericin B antifungal
agent, Fig. 3. The data showed that the free ligand has the capacity
of inhibiting the metabolic growth of the investigated bacteria and
one of the fungus to different extents, which may indicate broad-
spectrum properties. The activity of this compound may be arising
from the benzene diol and free azomethine moieties. The mode of
action may involve the formation of hydrogen bonding between
the OH and C@NH groups and the active centers of the cell constit-
uents, resulting in interference with the normal cell process [24].
All the tested metal complexes showed activity against both E. coli
and S. aureus. However, although the complexes showed promising
activities against the two bacteria, their activities were less than
the standard Tetracycline. On the other hand, only the three com-
perature for the Pd and Pt complexes lies in the 23–36 lS range,
which indicates that these complexes are nonelectrolytes. The
other complexes showed higher molar conductance due to their
electrolytic characteristics.
The IR spectrum of L showed characteristic bands correspond-
ing to the t(OH), t(NH), t(C@N) and t(C@C) functional groups in
the compound [17]. The IR spectra of the complexes also exhibited
the characteristic bands of the ligand with the corresponding shifts
due to complex formation (Table 2). In addition, the IR spectra of
the chromium, iron, nickel, zinc and cadmium complexes dis-
played a broad band in the range 3510–3320 cmꢀ1, which can be
ascribed to the stretching vibrations of water molecules coordi-
nated to the metal ion in consistent with the elemental and ther-
mal analyses. Furthermore, all the spectra showed non-ligand
bands in the range 651–419 cmꢀ1 corresponding to the stretching
frequencies of MAO and MAN bonds [21–23]. The appearance of
plexes [NiL(H2O)4](NO3)2, [Cl2Pd(l-Cl)2PdL] and [PtL(Cl)2] showed
antifungal activities against the tested fungus, while the other
tested complexes were inactive. It is important to point out that
nickel complex is more toxic against the C. albicans fungus, while
palladium complex is more toxic against the A. flavus fungus com-
pared to the standard Amphotericin B antifungal agent (Fig. 3). The
the
t(NH) in all the IR spectra of the complexes indicated that
the free azomethine (C@NH) group was not involved in the coordi-
nation. The 1H NMR spectra of the diamagnetic complexes
antibacterial data revealed that the [Cl2Pd(l-Cl)2PdL] and [PtL(Cl)2]
([ZnL(H2O)2](NO3)2, [Cl2Pd(
l
-Cl)2PdL], [CdL(H2O)2](NO3)2, [PtL(Cl)2]
complexes are more bioactive than the free ligand. The enhanced
activity of the metal complexes may be retained to the increased
lipophilic nature of the complexes which arose from the chelation.
It was also noted that the toxicity of the metal complexes increases
on increasing the metal ion concentration. This elevation is proba-
bly due to faster diffusion of the chelates as a whole through the
cell membrane. The chelated metal may block the enzymatic activ-
ity of the cell or it may catalyze the toxic reactions among cellular
constituents.
and [PtL(Cl)4]) gave more insight on the structure of the com-
plexes. All the spectra displayed signals due to the protons of
OH, phenyl and methyl groups with the corresponding shifts due
to complex formation (Table 2). Interestingly, the signal due the
C@NH group (17.21 ppm) disappeared from all the spectra of the
complexes probably due to their involvement in intermolecular
hydrogen bonding. From the spectroscopic data, it can be con-
cluded that the ligand acted as a bidentate through the two donor
sites CH3C@N and adjacent OH group. It is worth to mention that
the OH group coordinated without proton displacement in consis-
tent with 1H NMR data. Therefore, according to the elemental anal-
ysis and the spectroscopic studies, the complexes may have the
proposed structures shown in Scheme 2.
Cytotoxicity of [PtL(Cl)2] complex
To evaluate the potential usefulness of the reported platinum
complex (cis-platin analogous) as antitumor agent, three human

A.K. Abu Al-Nasr, R.M. Ramadan / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 105 (2013) 14–19
19
Fig. 3. In vitro antibacterial and antifungal activities of the ligand and the reported complexes. (Gꢀ): Gram-negative Escherchia coli bacteria; (G+): Gram-positive
Staphylococcus aureus bacteria; fungus1: Aspergillus flavus; fungus2: Candida albicans.
cell lines (two breast cancer cell lines, MCF7 and T47D, and liver
carcinoma cell line, HepG2) were treated by the compound and
compared with cis-platin. The complex showed promising activity
against the studied cell lines. The IC50 value (the concentration that
produce 50% inhibition of cell growth) of [PtL(Cl)2] and cis-platin
were determined. The IC50 values of the reported platinum com-
and the calculated and observed structure factors) are available
from the CCDC, 12 Union Road, Cambridge CB2 IEZ, UK on request,
deposition number: CCDC 821862. Schemes 1 and 2 are deposited
as journal supplementary data. Supplementary data associated
with this article can be found, in the online version, at http://
dx.doi.org/10.1016/j.saa.2012.12.008.
plex were found to be: MCF7 (12.2
(19.4 g/ml, 34.4 M) and HepG2 (20.7 g/ml, 36.7
to the IC50 values, the [PtL(Cl)2] complex is, thus, considered as
weak anticancer drug compared to cis-platin (11.9–9.9 M) [25].
However, the validity of [PtL(Cl)2] complex as an anticancer drug
requires further investigation such as in vivo study on the effect
of the compound on Ehrlich solid carcinoma induced in mice
including the study of tumor growth, apoptosis/necrosis ratio,
hematological profile, liver and kidney functions and histological
examination of the tumor cells and some organs.
l
g/ml, 21.6
lM), T47D
l
l
l
lM). According
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Appendix A. Supplementary material
Supplementary crystallographic data (Atomic positional param-
eters, all bond lengths and angles, anisotropic temperature factors