Synthesis, spectroscopic, cytotoxic aspects and computational study of N-(pyridine-2-ylmethylene)benzo[d]thiazol-2-amine Schiff base and some of its transition metal complexes

Article abstract of DOI:10.1016/j.molstruc.2013.05.051

N-(pyridine-2-ylmethylene)benzo[d]thiazol-2-amine Schiff base (L) and its Cu(II), Fe(III), Co(II), Ni(II) and Zn(II) complexes were synthesized and characterized by a set of chemical and spectroscopic measurements using elemental analysis, electrical conductance, mass spectra, magnetic susceptibility and spectral techniques (IR, UV-Vis, ¹H NMR). Elemental and mass spectrometric data are consistent with the proposed formula. IR spectra confirm the bidentate nature of the Schiff base ligand. The octahedral geometry around Cu(II), Fe(III), Ni(II) and Zn(II) as well as tetrahedral geometry around Co(II) were suggested by UV-Vis spectra and magnetic moment data. The thermal degradation behavior of the Schiff base and its complexes was investigated by thermogravimetric analysis. The structure of the Schiff base and its transition metal complexes was also theoretically studied using molecular mechanics (MM+). The obtained structures were minimized with a semi-empirical (PM3) method. The in vitro antitumor activity of the synthesized compounds was studied. The Zn-complex exhibits significant decrease in surviving fraction of breast carcinoma (MCF 7), liver carcinoma (HEPG2), colon carcinoma (HCT116) and larynx carcinoma (HEP2) cell lines human cancer.

Full text of DOI:10.1016/j.molstruc.2013.05.051

Journal of Molecular Structure 1048 (2013) 487–499
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis, spectroscopic, cytotoxic aspects and computational study of
N-(pyridine-2-ylmethylene)benzo[d]thiazol-2-amine Schiff base and
some of its transition metal complexes
⇑
⇑
Dina M. Abd El-Aziz , Safaa Eldin H. Etaiw , Elham A. Ali
Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt
h i g h l i g h t s
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
N-(pyridine-2-ylmethylene)benzo[d]thiazol-2-amine interacts in a bidentate manner.
Octahedral geometry around Cu(II), Fe(III), Ni(II) and Zn(II).
Tetrahedral geometry around Co(II).
Geometrical optimizations are performed using PM3 semiempirical method.
Zn-complex exhibits significant decrease in surviving fraction of human cancer cells.
a r t i c l e i n f o
a b s t r a c t
Article history:
N-(pyridine-2-ylmethylene)benzo[d]thiazol-2-amine Schiff base (L) and its Cu(II), Fe(III), Co(II), Ni(II) and
Zn(II) complexes were synthesized and characterized by a set of chemical and spectroscopic measure-
ments using elemental analysis, electrical conductance, mass spectra, magnetic susceptibility and spec-
tral techniques (IR, UV–Vis, 1H NMR). Elemental and mass spectrometric data are consistent with the
proposed formula. IR spectra confirm the bidentate nature of the Schiff base ligand. The octahedral geom-
etry around Cu(II), Fe(III), Ni(II) and Zn(II) as well as tetrahedral geometry around Co(II) were suggested
by UV–Vis spectra and magnetic moment data. The thermal degradation behavior of the Schiff base and
its complexes was investigated by thermogravimetric analysis. The structure of the Schiff base and its
transition metal complexes was also theoretically studied using molecular mechanics (MM+). The
obtained structures were minimized with a semi-empirical (PM3) method. The in vitro antitumor activity
of the synthesized compounds was studied. The Zn-complex exhibits significant decrease in surviving
fraction of breast carcinoma (MCF 7), liver carcinoma (HEPG2), colon carcinoma (HCT116) and larynx
carcinoma (HEP2) cell lines human cancer.
Received 17 February 2013
Received in revised form 21 May 2013
Accepted 22 May 2013
Available online 12 June 2013
Keywords:
Schiff base
Benzothiazole
Pyridenecarboxaldehyde
Molecular modeling
Cytotoxicity
In vitro antitumor activity
Ó 2013 Elsevier B.V. All rights reserved.
1. Introduction
promising materials for their use as efficient catalysts [4], optical
materials [5,6], biological sensors [7,8], antibacterial, antifungal,
Schiff bases still evoke much current interest and are used in a
variety of applications [1]. Schiff bases are considered as privileged
ligands because they are easily prepared by condensation of alde-
hydes or ketones with amines and are able to stabilize different
metals in various oxidation states [2]. The facile synthesis, wide
applications and accessibility of diverse structural modifications
of the metal complexes of Schiff bases reflect their ubiquitous
[3]. Schiff base complexes are of great interests especially for inor-
ganic and bioinorganic chemistry. This class of complexes obtained
from transition and non-transition metals has emerged as very
antiviral, herbicidal and also as anticancer agents [9–12]. It was
seen that the Schiff bases become more bactelostatic and carcino-
static chelation with metal ion [13,14]. Various heterocycles, espe-
cially thiazoles and benzothiazole derivatives, occupy an important
place owing to their versatile bioactivities due to the presence of
multifunctional groups [15–19]. On the other hand, the coordina-
tion chemistry of Schiff bases, derived from 2-pyridiene carboxade-
hyde, has received much attention during the last decade and plays
a fundamental role in inorganic chemistry [20–22]. In this context
a Schiff base, derived from 2-aminobenzothiazole and 2-pyridine
carboxaldehyde, and its Cu(II), Fe(III), Co(II), Ni(II) and Zn(II) com-
plexes have been synthesized and characterized. The antitumor
activities of the complexes were tested in vitro.
⇑
Corresponding authors. Tel.: +20 1149442423; fax: +20 403350804.
E-mail addresses: drdinamoh@yahoo.com, dina.mohamed2@science.tanta.
edu.eg (D.M. Abd El-Aziz), safaaetaiw@hotmail.com (S.E.H. Etaiw).
0022-2860/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molstruc.2013.05.051

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D.M. Abd El-Aziz et al. / Journal of Molecular Structure 1048 (2013) 487–499
KBr pellets. Electronic absorption spectra in the visible and ultravi-
2. Experimental
olet regions were measured on a Shimadzu 3101 PC spectropho-
tometer as a Nujol mull matrix. The magnetic susceptibility was
determined with a Magnetic susceptibility balance 436 Devon Park
Drive (USA) using Hg[Co(SCN)4] as calibrant. Thermogravimetric
analysis (TGA) was performed on Shimadzu AT-50 thermal ana-
lyzer under nitrogen atmosphere from 25 °C to 800 °C at heating
rate 10 °C/min.
2.1. Materials and instrumentation
All chemicals were purchased from Aldrich, reagent grade and
used without further purification. Elemental analysis was per-
formed on a Perkin–Elmer 2400 automatic elemental analyzer.
Mass spectra were recorded using Finnigan MAT 8200 mass spec-
trophotometer at 70 eV. Nuclear magnetic resonance spectra were
carried out on a Bruker DPX 200 spectrometer, using deuterated
dimethylsulfoxide (DMSO-d6) as a solvent and tetramethylsilane
(TMS) as an internal standard. Molar conductance in DMF
(10ꢁ3 °M) was measured at room temperature using a Hanna
8733 conductivity meter. Infrared spectra were carried out on a
Perkin–Elmer 1430 IR spectrophotometer (4000–400 cmꢁ1) using
2.2. Synthesis of N-(pyridine-2-ylmethylene)benzo[d]thiazol-2-amine
Schiff base
Schiff base ligand (Scheme 1) was prepared by condensation
reaction of 2-aminobenzothiazole (0.15 g; 1 mmol) and 2-pyridin-
ecarboxaldhyde (0.12 g; 1.1 mmol), dissolved in 30 mL absolute
Scheme 1. Chemical structure of the synthesized Schiff base (L).
Table 1
Analytical and physical data for the Schiff base and its complexes.
Compounds
Empirical formula
Color
Elemental analysis found (Calc.)%
%C
%H
%N
leff (BM)
m Oꢁ1 molꢁ1 cm2
L
C13H9N3S
Brown
Green
Black
Green
Green
Brown
65.40 (65.19)
48.35(48.11)
38.45(38.70)
41.56(41.59)
51.88 (52.11)
54.20 (54.43)
4.11 (3.79)
3.23 (3.42)
3.41(3.68)
3.14(3.96)
3.72 (4.08)
3.50 (3.65)
17.00 (17.56)
12.91 (12.95)
9.32 (9.03)
9.76 (9.70)
12.21 (12.15)
12.20 (12.69)
–
–
[CuL2 (H2O)2]Cl2
[FeLCl2(EtOH) (H2O)]Cl
[CoLCl(EtOH)] (H2O)Cl
[NiL2(OAc)2] 2H2O
[ZnL2 (OAc)2]
CuC12H14N2S2O3Cl2
FeC15H17N3SO2Cl3
CoC15H17N3SO2Cl2
NiC30H28N6S2O6
ZnC30H24N6S2O4
1.79
4.17
4.69
2.75
–
52.5
36.7
32.5
6.4
6.8
Fig. 1. Mass spectrum of L.

D.M. Abd El-Aziz et al. / Journal of Molecular Structure 1048 (2013) 487–499
489
Scheme 2. Proposed fragmentation routes of Schiff base L.
EtOH, in the presence of few drops of piperidine. The resulting mix-
ture was stirred well and refluxed for 7 h. The mixture was concen-
trated to its half volume then left to cool. Petroleum ether was
added to the reaction mixture dropwise until a product began to
precipitate. The formed product was filtered off, washed several
times with EtOH and recrystalized from EtOH.
ꢂ4H2O and Zn(AcO)2, in the solid state and melted in oil bath for 6–
8 h. After cooling, the solids were finely grinded and washed with
diethyl ether.
2.4. Molecular modeling studies
The geometries of the Schiff base and metal complexes were
optimized using HyperChem program 8. The geometry was ener-
getically optimized through molecular mechanics by applying
MM+ force field in vacuum with the polka Ribiere (conjugated gra-
dient) algorithm and RMS gradient 0.001 kcal molꢁ1 followed by
molecular dynamics. The optimization was performed without con-
straints allowing all atoms, bonds, and dihedral angles to change
simultaneously. The dynamic was done up to 2000 K followed by
molecular mechanics calculations.The same process was repeated
five times to obtain the minimum energy. A bath of relaxation time
of 0.1 ps and a step size of 0.001 ps were used for dynamics simula-
2.3. Synthesis of metal complexes
Cu(II), Fe(III) and Co(II) complexes were prepared by mixing an
ethanolic solution (20 mL) of the Schiff base (2 mmol) with metal
salts (1 mmol), namely, CuCl2ꢂ2H2O, FeCl3ꢂ6H2O and CoCl2ꢂ2H2O
in 10 mL EtOH. The mixture was stirred and heated to reflux for
6–8 h. The solution was concentrated. The resultant products were
collected by filteration, washed with cold ethanol and dried in vac-
uum. Ni(II) and Zn(II) complexes were prepared by mixing the
Schiff base (2 mmol) with metal salts (1 mmol), namely, Ni(AcO)2-

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D.M. Abd El-Aziz et al. / Journal of Molecular Structure 1048 (2013) 487–499
Fig. 2. 1H NMR spectra of: (a) L and (b) [Zn(L)2(OAc)2].
tion. The obtained structure was minimized with a semiempirical
method. Semiempirical method is another tool to determine the
stability of molecule by incorporating quantum mechanical param-
eters into the calculation. PM3 method was used for the semiempir-
ical calculation.
goes three major fragmentation pathways (Scheme 2). The first
one includes the elimination of HÅ to give ion-peak at m/z = 238
(41%). This fragment ion undergoes cleavage to give ion-peak at
m/z = 135 (22%) which can be attributed to benzothiazole moiety.
This fragment ion undergoes further fragmentation to give ion
peak at m/z 78 (base peak) followed by fragmentation due to elim-
ination of CHÅ3 radical to give fragment ion radical
[HC„CAC„CACH2]+Å at m/z = 63 (25%). The second fragmentation
pathway includes cleavage occurring on ANACA and ACACA
bonds by elimination of the azomethine (ACH@NA) group to give
ion-peak at m/z = 213 (5%). This fragment undergoes further frag-
mentation by elimination of benzothiazole moiety to give ion peak
at m/z = 79 (15%), corresponding to pyridine radical ion. This frag-
ment ion undergoes further cleavage to give ion peaks at m/z = 52
(27%) and 51 (53%). The third fragmentation pathway includes
cleavage occurring on ANACA bond by elimination of benzothia-
zole moiety to give ion-peak at m/z = 105 (47%). By elimination
of azomethine group, pyridine radical ion is formed with ion peak
at m/z = 79 (15%). Analysis by mass spectroscopy for the metal
complexes gave the molecular ion peaks for [CuL2(H2O)2]++, [FeL-
Cl2(EtOH)(H2O)]+, [CoLCl(EtOH)]+, [NiL2(OAc)2]+Å and [ZnL2
(OAc)2]+Å at the desired positions: m/z = 361, 431, 380, 655. The
fragmentation occurs mainly via initial loss of chlorine atoms
and solvent molecules followed by losing the metal ion. By losing
the metal, the ligand molecular ion peak appeared at m/z = 239.
This fragment undergoes further fragmentation to give ion peaks
at m/z = 150 (base peak) and at m/z = 79, which are attributed to
aminobenzothiazle and pyridine moiety, respectively.
2.5. Antitumor activity
In vitro Potential cytotoxicity of the complexes was tested using
the method of Skehan et al. [23]. Cells were plated in 96-multiwell
plate (104 cells/well) for 24 h before treatment with the complexes
to allow attachment of cell to the wall of the plate. Different con-
centrations of the compounds under test (0, 1, 2.5, 5, 10, 15, 20
and 50 lg/mL) were added to the cell monolayer. Triplicate wells
were prepared for each individual dose. Monolayer cells were incu-
bated with the compounds for 48 h at 37 °C in 5% CO2 atmosphere.
After 48 h, cells were fixed, washed and stained with Sulfo-Rhoda-
mine-B stain. Excess stain was washed with acetic acid and at-
tached stain was recovered with Tris EDTA buffer. Color intensity
was measured in an ELISA reader. The relation between surviving
fraction and drug concentration is plotted to get the survival curve
of each tumor cell line.
3. Results and discussion
The level of the purity of the current Schiff base ligand was
checked by running TLC on a silica gel coated plate using EtOAc-
EtOH (6:4 v/v) as the eluent. The elemental analysis data of the
Schiff base and its metal complexes (Table 1) agree well with the
proposed composition of the Schiff base and its metal complexes.
3.2. 1H NMR
The 1H NMR spectrum of the Schiff base ligand showed sharp
singlet at 10.03 ppm, corresponding to the azomethine proton.
The multi signals within the range of 7–8 ppm are assigned to
the aromatic protons of benzothiazole and pyridine rings. The 1H
NMR spectrum of the Zn(II) complex was compared with that of
3.1. Mass spectra
The mass spectrum of the Schiff base (Fig. 1) shows the molec-
ular ion peak [M+] at m/z = 239 (76%). This molecular ion under-

D.M. Abd El-Aziz et al. / Journal of Molecular Structure 1048 (2013) 487–499
491
Fig. 3. IR spectra of L and their metal complexes. (a) L, (b) [Cu(L)2(H2O)2]Cl2, (c) [FeLCl2(EtOH) (H2O)]Cl, (d) [CoLCl(EtOH)]ClꢂH2O, (e) [Ni(L)2 (OAc)2]ꢂ2H2O, (f) [Zn(L)2 (OAc)2].
the parent Schiff base (Fig. 2). The shift of ACH@NA proton to
9.95 ppm with dramatic decrease in intensity suggests that azome-
thine nitrogen is involved in coordination with Zn(II) in the com-
plex. The signal at 1.8 ppm is assigned to the protons of the
acetate groups in the complex. The signals within the range of
2.4–2.5 ppm are assigned to the protons of DMSO.
3.3. Molar conductivity measurements
The molar conductivities of 10ꢁ3 M solutions of the metal com-
plexes in DFM were measured at 25 °C. Table 1 shows the molar
conductance (m) values of the metal complexes. The Cu(II), Fe(III)
and Co(II) complexes have molar conductance values of 52.5, 36.7

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D.M. Abd El-Aziz et al. / Journal of Molecular Structure 1048 (2013) 487–499
Table 2
IR spectral bands (cmꢁ1) of the Schiff base and its metal complexes.
Compounds
mCH Aromatic
mC@N thiazole
mC@C
mC@N Azomethine
cHC@N
mCASAC
mMAN
mMAO
mMACl
L
3002, 2978
3061, 2970
3062, 2971
3063
3057, 2990
3059, 2998
1562
1567
1574
1561
1572
1563
1522, 1446
1533, 1491
1532, 1474
1528, 1458
1532, 1440
1532, 1441
1608
1594
1602
1602
1602
1595
1037
1020
1020
1021
1020
1017
723
718
701
725
725
723
–
–
–
–
313
332
–
[CuL2(H2O)2]Cl2
[FeLCl2(EtOH) (H2O)]Cl
[CoLCl(EtOH)] (H2O)Cl
[NiL2(OAc)2] 2H2O
[ZnL2 (OAc)2]
537
538
539
538
560
422
421
425
428
429
–
Table 3
Thermal gravimetric analysis data for the Schiff base and its complexes.
Compound
L
Temperature (°C) Weight loss% found (Calc.) Weight of residue% found (Calc.) Assignment
27–105
105–355
355–650
No loss
56.67 (56.49)
43.33 (44.35)
Thermally stable
Decomposition of benzothiazole
Decomposition of pyridine and loss of HCN
[CuL2 (H2O)2]Cl2
27–180
No loss
Thermally stable
180–195
195–255
255–520
520–650
650–800
5.60 (5.55)
11.30 (10.94)
24.05 (24.38)
50.50 (49.99)
loss of two coordinated water
loss of Cl2
Elimination of two pyridine
Elimination of two benzothiazole moieties and 2 HCN
Residue: Cu metal
14.4 (14.7)
[FeLCl2(EtOH)(H2O)]Cl
27–180
No loss
Thermally stable
180–280
280–390
390–450
452–520
520–650
650–800
11.44 (11.49)
25.54 (25.14)
17.00 (16.99)
28.59 (29.04)
6.36 (5.80)
Loss of 1Cl and one coordinated H2O
Loss of 1 coordinated EtOH and Cl2
Loss of pyridine moiety
Loss of benzothiazole moiety
Loss of HCN
12.07 (11.99)
18.82 (17.39)
Residue: Fe metal
[CoLCl(EtOH)] (H2O)Cl 27–120
4.00 (4.16)
Loss of one crystal water
Loss of Cl2 and coordinated
EtOH Loss of pyridine moiety
Loss of benzothiazole moiety
Residue: CoO
120–380
380–525
525–610
610–800
28.19 (27.02)
18.50 (18.26)
30.486(31.20)
[NiL2(OAc)2] 2H2O
27–150
4.98 (5.21)
Loss of two crystal water
Loss of two acetate group
Loss of two pyridine moieties
Loss of two HCN
Loss of two benzothiazole moieties
Residue: Ni metal
150–240
240–405
405–475
475–600
600–800
17.14 (17.08)
22.95 (22.88)
7.50 (7.80)
40.21 (39.10)
7.22 (8.49)
[ZnL2 (OAc)2]
27–140
No loss
Thermally stable
140–260
260–475
475–650
650–800
16.18 (17.83)
22.82 (23.90)
47.20 (49.00)
Loss of two coordinated acetate group
Loss of two pyridine moieties
Loss of two benzothiazole and 2HCN
Residue: ZnS
13.80 (14.72)
and 32.5 ꢁ1 molꢁ1 cm2, respectively, indicating the ionic nature of
these complexes [24]. However, the Ni(II) and Zn(II) complexes
have molar conductance values of 6.4 and 6.8 ꢁ1 molꢁ1 cm2, respec-
tively, supporting the non-electrolytic nature.
tion) [25]. After complexation, the azomethine band is shifted to
lower frequency in all complexes, suggesting that this group takes
part in coordination. The coordination of nitrogen to the metal
atom was expected to reduce the electron density on the azome-
thine link and thus causes a shift in the C@N band [26]. It is worth
noting that there is a shift of the bands characteristic for the
absorption of the pyridine ring (out of plane and in plane ring
deformation). This is due to the coordination of pyridine nitrogen
to the metal [27,28]. In the low frequency region, the band of weak
intensity at 421–429 cmꢁ1 is attributed to mMAO while the band in
the region of 537–560 cmꢁ1 is due to mMAN [29]. The IR spectra of
Fe(III) and Co(II) complexes exhibit medium band at 313 and
332 cmꢁ1, respectively, which can be assigned to mMACl vibrations.
Extensive infrared spectral studies, reported on metal acetate com-
plexes, indicated that the acetate ligand coordinates to the metal
center in either a mono dentate, bi-dentate or bridging manner
[30]. The IR spectra of Ni and Zn complexes show bands in the re-
3.4. IR spectra
The comparative IR spectral study of the Schiff base ligand and
its complexes reveals the interesting coordination mode of the
Schiff base during complex formation (Fig. 3). The important IR
bands with their assignments are depicted in Table 2.The IR spec-
trum of the Schiff base displayed characteristic bands at 1608 and
1037 cmꢁ1 which can be attributed to mC@N and cCH@N of the azo-
methine group. The bands at 3002, 1445, 1342 and 753 cmꢁ1 are
assigned to
mCH, dCH and cCH of the aromatic system, respectively.
On the other hand, vibrations characteristic to the thiazole ring
are observed at 1562 and 723 cmꢁ1 due to
mC@N and mCASAC, respec-
tively. The bands at 1522 and 1446 cmꢁ1 are attributed to mC@C of
the aromatic system. The ring skeletal mode of pyridine ring of
2-pyridinecarboxaldehyde appears in the region of 430 cmꢁ1 (out
of plane ring deformation) and 652 cmꢁ1 (in plane ring deforma-
gion of 1598 and 1395 cmꢁ1 which can be attributed to
and sym(CO2), respectively. The separation wavenumber values
, { asy(CO2) –
sym(CO2)}, are greater than 200 cmꢁ1. This indi-
cates the mono dentate behavior of the acetate ions. All complexes,
masy(CO2)
m
D
D
=
m
m

D.M. Abd El-Aziz et al. / Journal of Molecular Structure 1048 (2013) 487–499
493
Fig. 4. TG curve of L.
Fig. 5. Nujol mull electronic spectra of L and its metal complexes (a) L, (b) [Cu(L)2(H2O)2]Cl2, (c) [FeLCl2(EtOH) (H2O)]Cl, (d) [CoLCl(EtOH)]ClꢂH2O, (e) [Ni(L)2 (OAc)2] 2H2O, (f)
[Zn(L)2(OAc)2].
except Zn(II) complex, display bands near the region 3552–
3400 cmꢁ1 which are attributed to tOH of the water or ethanol
molecules. The presence of the cH2O band in the region 802–
810 cmꢁ1 confirms the presence of the coordinated water mole-
cules in Cu(II) and Fe(III) complexes.
the suggested formulae (Table 3). Differential thermal analysis
(DTA) curve of the Schiff base (Fig. 4) shows an exothermic peak
at 45 °C. TGA curve shows no mass loss in that temperature range.
This DTA peak can be assigned to lattice or chemical rearrange-
ment of the ligand. The observed endothermic DTA peak at
138 °C, with mass loss in the temperature range 105–355 °C, can
be assigned to the decomposition of the Schiff base. The TGA curve
suggests that this decomposition takes place through the loss of
the benzothiazole moiety. The exothermic peak at 248 °C, which
was accompanied by mass loss in the TGA curve, resulted from
3.5. Thermal analysis
The mass losses of thermal gravimetric analysis (TGA) for the
Schiff base ligand and its metal complexes were calculated for

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D.M. Abd El-Aziz et al. / Journal of Molecular Structure 1048 (2013) 487–499
0
1000
2000
3000
4000
5000
6000
Fig. 6. X-band ESR spectrum of [Cu(L)2(H2O)2]Cl2.
Fig. 7. Optimized geometry of the Schiff base L using AM1 calculations.
the chemical changes in the Schiff base due to decomposition pro-
cess. The broad endothermic DTA peak at 508 °C, accompanied by
mass loss in the TGA curve, can be assigned to complete decompo-
sition of Schiff base through the loss of pyridine moiety and HCN.
The thermograms of the metal complexes exhibit thermal stability
from room temperature up to 180 °C for Cu(II), Fe(III) and 140 °C
for Zn(II), indicating that no water of crystallization is present in
these complexes. The water of crystallization of Co(II) and Ni(II)
complexes was lost in the temperature range of (27–120 °C) and
(27–120 °C), respectively. The final exothermic decomposition be-
gan at Ca. 250 °C for Cu(II), Ni(II) and Zn(II) complexes. However,
Fe(III) and Co(II) complexes began to decompose at Ca. 380 °C by
the elimination of pyridine moiety followed by benzothiazole moi-
ety, azomethine group and finally the formation of the residue.
3.6. Electronic spectra
The electronic spectrum of the Schiff base (Fig. 5) as Nujol mull
matrix exhibits absorption bands at ca. 215 nm (46512 cmꢁ1) and
255 nm (39216 cmꢁ1) which correspond to pꢃ transitions of the
p–
benzenoid system of benzothiazole moiety due to (1La 1A) and
Fig. 8. HOMO–LUMO representation (bottom and top, respectively).

D.M. Abd El-Aziz et al. / Journal of Molecular Structure 1048 (2013) 487–499
495
3D structure of [CuL2 (H2O)2]Cl2
3D structure of [FeLCl2 (EtOH) (H2O)]Cl
3D structure of [CoLCl(EtOH)] (H2O)Cl
Fig. 9. Optimized geometry of the metal complexes.

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D.M. Abd El-Aziz et al. / Journal of Molecular Structure 1048 (2013) 487–499
3D structure of [NiL2(OAc)2] 2H2O
3D structure of [ZnL2 (OAc)2]
Fig. 9 (continued)
(1Lb 1A) states, respectively [31]. The absorption band at 240 nm
The electronic absorption spectrum of the green Cu(II) complex
exhibits a broad band centered at 680 nm (14706 cmꢁ1) that can
be assigned to 2B1g ? 2A1g (dx2–y2–dz2). The low intensity shoulder
bands at 580 nm (17,241 cmꢁ1) and 550 nm (18182 cmꢁ1) can be
attributed to 2B1g ? 2B2g (dx2–y2–dxy) and 2B1g ? 2Eg (dx2–y2–dxz,
dyz) [33,34]. These d–d transitions are due to the 2Eg ? 2T2g transi-
tion states of the octahedral Cu(II) ion (d9) that split under the
influence of the asymmetric filling causing tetragonal distortion.
The magnetic moment value of Cu(II) complex is 1.79 BM. This va-
lue lies appreciably above the spin-only value of 1.73 BM for Cu(II)
[35]. This indicates the presence of single unpaired electron sug-
gesting the octahedral structure for the complex. The shoulder
(41,667 cmꢁ1) is due to
p–
pꢃ transitions (1Lb 1A) of the thiazole
moiety [32]. The two bands at 225 nm (44,444 cmꢁ1) and 268 nm
(37,313 cmꢁ1) are attributed to the
p–
pꢃ transitions of pyridine
moiety due to (1La 1A) and (1Lb 1A), respectively [31]. The
n–pꢃ transitions of the pyridyl ring and imine functional group
are observed as at 360 nm (27,778 cmꢁ1) [18]. The band at
445 nm (22,472 cmꢁ1) can be assigned to the transition within
the molecule, essentially an intramolecular charge transfer interac-
tion. In the spectra of the metal complexes, the band characteristic
for n–pꢃ transitions is shifted to a longer wavelength. This shift can
be attributed to the coordination of the Schiff base to the metal ion.

D.M. Abd El-Aziz et al. / Journal of Molecular Structure 1048 (2013) 487–499
497
Table 4
Bond distances of metal complexes obtained from the PM3 calculations.
Bond lengths and
angle
Cu
complex
Bond lengths and
angle
Fe
complex
Bond lengths and
angle
Co
complex
Bond lengths and
angle
Ni
complex
Bond lengths and
angle
Zn
complex
Cu18AN10
Cu18AN17
Cu18AN28
Cu18AN35
Cu18AO36
Cu18AO39
1.877 Fe18AN10
1.874
1.858
2.000
1.985
2.263
2.249
86.3
93.3
88.2
102.0
169.9
94.3
91.2
171.6
85.8
174.4
83.7
80.9
90.8
98.3
85.8
Co18AN10
Co18AN17
Co18AO27
Co18ACl19
N10ACo18AN17
N10ACo18ACl19
N10ACo18AO27
N17ACo18ACl19
N17ACo18AO27
Cl19ACo18AO27
1.874
1.901
2.064
2.234
88.8
175.8
99.1
88.6
Ni49AN10
Ni49AN17
Ni49AN27
Ni49AN34
Ni49AO47
Ni49AO40
1.906
1.876
1.890
1.876
1.860
1.861
90.3
177.2
92.5
90.3
92.2
92.0
94.2
168.6
82.9
Zn18AN10
Zn18AN17
Zn18AN28
Zn18AN35
Zn18AO41
Zn18AO48
1.949
1.911
1.982
2.001
1.901
1.856
76.7
176.6
102.1
86.4
100.9
100.1
85.4
91.2
172.8
76.0
1854
Fe18AN17
1.855 Fe18AO31
1.895 Fe18AO21
1.876 Fe18ACl19
1.889 Fe18ACl20
N10ACu18AN17
N10ACu18AN28
N10ACu18AN35
N10ACu18AO36
N10ACu18AO39
N17ACu18AN28
N17ACu18AN35
N17ACu18AO36
N17ACu18AO39
N28ACu18AN35
N28ACu18AO36
N28ACu18AO39
N35ACu18AO36
N35ACu18AO39
O36ACu18AO39
79.9
N10AFe18AN17
N10A Fe18ACl19
N10A Fe18ACl20
N10AFe18AO21
N10AFe18AO31
N17AFe18ACl19
N17AFe18ACl20
N17AFe18AO21
N17AFe18AO31
Cl19AFe18ACl20
Cl19AFe18AO21
Cl19AFe18AO31
Cl20AFe18AO21
Cl20AFe18AO31
Cl21AFe18AO31
N10ANi49AN17
N10ANi49AN27
N10ANi49AN34
N10ANi49AO40
N10ANi49AO47
N17ANi49AN27
N17ANi49AN34
N17ANi49AO40
N17ANi49AO47
N27ANi49-N34
N27ANi49AO40
N27ANi49AO47
N34ANi49AO40
N34ANi49AO47
O40ANi49AO47
N10AZn18AN17
N10AZn18AN28
N10AZn18AN35
N10AZn18AO41
N10AZn18AO48
N17AZn18AN28
N17AZn18AN35
N17AZn18AO41
N17AZn18AO48
N28AZn18AN35
N28AZn18AO41
N28AZn18AO48
N35AZn18AO41
N35AZn18AO48
O41AZn18AO48
174.5
99.1
97.4
86.7
104.9
90.5
175.7
90.3
78.3
77.9
95.9
93.2
174.2
86.2
118.5
85.1
88.9
87.1
86.5
97.2
174.5
85.6
95.2
82.0
169.8
88.4
95.5
band, observed at 460 nm (21,739 cmꢁ1), is due to ligand metal
charge transfer (LMCT) [10]. The electronic spectrum of the Fe(III)
complex displays absorption bands at 660 nm (15,152 cmꢁ1),
575 nm (17,391 cmꢁ1) and 490 nm (20,408 cmꢁ1). These bands
are attributed to 6A1g ? 4T1g (G), 6A1g ? 4T2g (G) and 6A1g ? 4Eg
(G), respectively. The number, position and assignment of the d-d
transition bands are consistent with a six-coordinated octahedral
2.02 corresponds to low spin iron (III). On the other hand, the weak
signal with g-value at 3.73 is known to be characteristic of dis-
torted high spin iron (III) [41,42]. These two signals confirm the
probability of the equilibrium between high and low spin states.
3.8. Molecular modeling
geometry [36]. The spectra show also
a band at 420 nm
Geometric and electronic structure of the Schiff base and its me-
tal complexes are calculated by the optimization of their bond
lengths, bond angles and dihedral angles. The optimized molecular
structure of the Schiff base with minimum energy obtained from
the calculations is shown in Fig. 7. The photoinduced charge redis-
tribution over the whole molecular skeleton of the Schiff base is
well represented by plot of the Frontier molecular orbitals (HOMO
and LUMO) as illustrated in Fig. 8. EHOMO is a quantum chemical
descriptor which is often associated with the electron donating
ability of the molecule. High value of EHOMO indicates a tendency
of the molecule to donate electrons to appropriate acceptor mole-
cule of low empty molecular orbital energy. However, ELUMO indi-
cates the ability of the molecule to accept electrons. It is well
known that the lower value of ELUMO, the more probable for the
molecule to accept electrons [43]. The HOMO electronic density
distribution for the Schiff base can be represented as localization
of charge density on the bridging nitrogen atom, sulfur and nitrogen
atoms of benzothiazole moiety. In the case of LUMO level, the
charge is mostly localized that can facilitate the back donation from
the metal ion to azomethine group. Quantum chemical parameters
(23,810 cmꢁ1) which may be attributed to ligand-metal charge
transfer. The magnetic moment of 4.17 BM for the Fe(III) complex
suggests the presence of a mixture of high spin as well as low spin
states [37]. The electronic absorption spectrum of the green Co(II)
complex exhibits band at 680 nm (14,706 cmꢁ1). This band can be
assigned to the transitions 4A2 (F) ? 4T1 (P) and a band at 620 nm
(16,129 cmꢁ1
) due to spin coupling. The band at 465 nm
(21,505 cmꢁ1) can be assigned to charge transfer transition. These
transitions as well as the measured value of magnetic moment
(leff = 4.69 BM) suggest a tetrahedral structure around Co(II) com-
plex [24,26,38]. The electronic absorption spectrum of the brown
Ni(II) complex shows absorption bands at 590 nm (16949 cmꢁ1
)
)
3
and 365 nm (27397 cmꢁ1) assignable to A2g (F) ? 3T1g (F) (m2
3
and A2g (F) ? 3T1g (P) (
m
3) transitions, respectively [33,39]. It is
noted that the low energy A2g (F) ? 3T2g (P) (
m1) transition is not
3
observed in the spectra. This is believed to be in the near infrared
and it is out of the range of the used instrument. The high energy
band at 265 nm (37,736 cmꢁ1) may be assigned to charge transfer
band. The magnetic moment value (2.75 BM) is consistent with
octahedral geometry around Ni(II). The electronic transition spec-
trum of the brown Zn(II) complex exhibits shoulder band at
460 nm (21,739 cmꢁ1). This band can be attributed to the LMCT
transition and it is consistent with octahedral geometry [40]. The
Zn(II) complex is found to be diamagnetic as expected for d10
configuration.
(EHOMO, ELUMO and the energy gap,
DE = ELUMO–EHOMO) are found to
be ꢁ9.6211, ꢁ4.645779 and 4.975321 e.v, respectively. Molecular
modeling studies using PM3 calculations are performed to gain a
better understanding of geometrical structures of the investigated
complexes (Fig. 9). The Cu, Ni and Zn-complexes acquire N4O2
geometry but Fe-complex exhibits N2O2Cl2 geometry. The bond dis-
tances of the Ni-complex are in the range of 1.86–1.90 Å and the
bond angles are nearly 90°. However, N10ANi49AN17 bond angle
equals to 177.2° indicating octahedral geometry. On the other hand,
the coordination environment around the Cu and Zn-complexes are
slightly distorted octahedral geometry as indicated by the bond
lengths and angles (Table 4). The Fe-complex exhibits distorted
octahedral structure due to the presence of the axial chloride ions
with bond lengths of 2.24–2.26 Å (Table 4). The energy minimiza-
tion results of square planar and tetrahedral structures of Co-com-
3.7. EPR
The EPR spectrum of Cu(II) complex at room temperature
(300 K) (Fig. 6) exhibits a symmetrical singlet line characteristic
of isotropic pattern with only one value gisotropic = 2.049. The g-va-
lue and the pattern of EPR spectrum suggest octahedral geometry
around Cu(II). The EPR spectrum of Fe(III) complex exhibits a broad
signal of axial symmetry with hyperfine structure. The g-value at

498
D.M. Abd El-Aziz et al. / Journal of Molecular Structure 1048 (2013) 487–499
L
HELA
HELA
[CuL2(H2O)2]Cl2
1.1
1
1.5
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
0.5
0
0
1
2.5
5
10
0
5
12.5
25
50
Conc ug/well
Conc ug/well
MCF7
MCF7
[NiL2(OAc)2]2H2O
1.5
1
[CuL2(H2O)2]Cl2
1.5
1
0.5
0
0.5
0
0
1
2.5
5
10
0
1
2.5
5
10
Conc ug/well
Conc ug/well
HELA
HELA
[ZnL2(OAc)2]
[NiL2(OAc)2]2H2O
1.5
1
1.5
1
0.5
0
0.5
0
0
1
2.5
5
10
0
1
2.5
5
10
Conc ug/well
Conc ug/well
HEP2
HCT116
[ZnL2(OAc)2]
[ZnL2(OAc)2]
1.5
1
1.5
1
0.5
0
0.5
0
0
1
2.5
5
10
0
1
2.5
5
10
Conc ug/well
Conc ug/well
MCF7
MCF7
[ZnL2(OAc)2]
[ZnL2(OAc)2]
1.5
1
1.5
1
0.5
0
0.5
0
0
1
2.5
5
10
0
1
2.5
5
10
Conc ug/well
Conc ug/well
Fig. 10. Survival curves of some tumor cell lines.
plex without restriction indicate that the strain energy of the square
planar structure is more than that of the tetrahedral structure. The
bond lengths of the Co-complex; Co18AO27, Co18AC119,
Co18AN10 and Co18AN17 are 2.06, 2.23, 1.87 and 1.90 Å, respec-
tively. However, the bond angles; N17ACo18AO27,
N10ACo18AO27, N10ACo18AO27, N10ACo18AN17 and

D.M. Abd El-Aziz et al. / Journal of Molecular Structure 1048 (2013) 487–499
499
Table 5
IC50 M) dose of the compound which survival to 50%.
Acknowledgements
(l
Compounds
Cell lines
HELA
The authors are grateful to Prof. M.K. Awad (Theoretical Applied
Chemistry Unit, Faculty of Science, Department of Chemistry, Tanta
University) for technical assistance and valuable advice in the com-
putational study.
MCF7
HEPG2
HCT116
HEP2
IC50 (lM)
L
0.320
0.015
0.027
0.030
–
–
–
–
–
–
–
–
–
–
[CuL2 (H2O)2]Cl2
[NiL2(OAc)2] 2H2O
[ZnL2 (OAc)2]
0.017
ꢁve
0.015
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5.24 ꢄ 10ꢁ3
6.94 ꢄ 10ꢁ3
0.017
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