Molecular structure, molecular docking, thermal, spectroscopic and biological activity studies of bis-Schiff base ligand and its metal complexes

Article abstract of DOI:10.1002/aoc.3952

Coordination compounds of Fe(III), Zn(II), Ni(II), Co(II), Cu(II), Cd(II) and Mn(II) ions were synthesized from the ligand [4,4′-((((ethane-1,2-diylbis(oxy))bis(2,1-phenylene))bis(methanylylidene))bis(azanylylidene))diphenol]ethane (H₂L) derive

Full text of DOI:10.1002/aoc.3952

Received: 1 May 2017
DOI: 10.1002/aoc.3952
Revised: 7 June 2017
Accepted: 16 June 2017
F U L L P A P E R
Molecular structure, molecular docking, thermal,
spectroscopic and biological activity studies of bis‐Schiff
base ligand and its metal complexes
Ehab M. Zayed1
| Ahmed M.M. Hindy2 | Gehad G. Mohamed2
1 Green Chemistry Department, Research
Centre, 33 El Bohouth st. (former El Tahrir
st.), Dokki, Giza, 12622, Egypt
2 Chemistry Department, Faculty of
Science, Cairo University, Giza, 12613,
Egypt
Coordination compounds of Fe(III), Zn(II), Ni(II), Co(II), Cu(II), Cd(II) and
Mn(II) ions were synthesized from the ligand [4,4′‐((((ethane‐1,2‐diylbis(oxy))
bis(2,1‐phenylene))bis(methanylylidene))bis(azanylylidene))diphenol]ethane
(H2L) derived from the condensation of bisaldehyde and 4‐aminophenol.
1
Microanalysis, magnetic susceptibility, infrared, H NMR and mass spectros-
Correspondence
copies, molar conductance, X ray powder diffraction and thermal analysis were
used to confirm the structure of the synthesized chelates. According to the data
obtained, the composition of the 1:1 metal ion–bis‐Schiff base ligand was found
to be [M(H2L)(H2O)2]Cln (M = Zn(II), Ni(II), Co(II), Cu(II), Cd(II) and Mn(II),
n = 2; Fe(III), n = 3). Magnetic susceptibility measurements and reflectance
spectra suggested an octahedral geometry for the complexes. Central metals
ions and bis‐Schiff base coordinated together via O2 and N2 donor sites which
as evident from infrared spectra. The Gaussian09 program was applied to opti-
mize the structural formula for the investigated Schiff base ligand. The energy
gaps and other important theoretical parameters were calculated applying the
DFT/B3LYP method. Molecular docking using AutoDock tools was utilized to
explain the experimental behaviour of the Schiff base ligand towards proteins
of Bacillus subtilis (5 h67), Escherichia coli (3 t88), Proteus vulgaris (5i39) and
Staphylococcus aureus (3ty7) microorganisms through theoretical calculations.
The docked protein receptors were investigated and the energies of hydrogen
bonding were calculated. These complexes were then subjected to in vitro anti-
bacterial studies against several organisms, both Gram negative (P. vulgaris and
E. coli) and Gram positive (S. pyogones and B. subtilis). The ligand and metal
complexes exhibited good microbial activity against the Gram‐positive and
Gram‐negative bacteria.
Gehad G. Mohamed, Chemistry
Department, Faculty of Science, Cairo
University, Giza 12613, Egypt.
Email: ggenidy68@hotmail.com
Funding information
Green Chemistry Department, Grant/
Award Number: 11090305
KEYWORDS
bioinorganic chemistry, bis‐Schiff base ligand, in vitro biological activity, IR spectroscopy, metal
complexes, thermal analysis
Appl Organometal Chem. 2017;e3952.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
1 of 16
https://doi.org/10.1002/aoc.3952

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ZAYED ET AL.
features is that small modifications in the structure have
the ability to significantly alter the key properties of the
corresponding complexes.[36] In a continuation of our
interest in bis‐Schiff base ligands and the properties of their
complexes,[16,36–42] in this paper, the structures of a newly
synthesized bis‐Schiff base ligand, namely [4,4′‐((((ethane‐
1,2‐diylbis(oxy))bis(2,1‐phenylene))bis(methanylylidene))
bis(azanylylidene))diphenol]ethane (H2L), and its di‐ and
trivalent metal ions are reported. The prepared ligand has
several central donor atoms which can coordinate to
mononuclear metal ions. Such complexes may display very
good spectral data which deepen the structural characteri-
zation of the isolated complexes. The structures of these
complexes were fully characterized via elemental analysis,
spectral studies, X‐ray diffraction (XRD) and thermal
analysis. Their antimicrobial activity was a focus of the
study. The geometric structure of the Schiff base ligand
was optimized using the DFT/B3LYP method. The binding
of Bacillus subtilis (5 h67), Escherichia coli (3 t88), Proteus
vulgaris (5i39) and Staphylococcus aureus (3ty7) receptors
with the Schiff base ligand was investigated using a molec-
ular docking study.
1 | INTRODUCTION
New Schiff base ligands display distinctive characteristics
and effectiveness, and their preparation is an important
step in the development of metal complexes. Therefore,
various studies have been conducted on the properties of
electron acceptor and donor ligands, function groups of
ligands and coordination sphere of ligands in
complexes.[1–13] Some groups attracted interest years ago
and are still studied, especially the azomethine group, fre-
quently exhibiting unusual structural properties in com-
plexes made with a diverse number of transition
metals.[12,13] Studies of ligand complexes found that their
properties have a wide variety of biological applica-
tions.[14] Schiff base complexes are more attractive than
many others among various complexes.[15,16] This is due
to their synthesis process being simple, and their having
excellent characteristics and various applications such as
in bioactivity, catalysis and in optical sensors.[16–19] Nota-
ble biological activities of Schiff base metal complexes
include antiviral, anti‐tubercular, antioxidant, anti‐
inflammatory, antifungal, analgesic and antibacterial
effects, as investigated in previous studies.[20–25] Also,
ligands containing N¼C‐C¼N units display a strong che-
lating ability through electron delocalization, which is
combined with extended conjugation. This may affect
the nature of a complex. Also, mono‐ or polynuclear com-
plexes were prepared with multi‐centred Schiff base
ligands, some of which are biologically active.[22,23] Com-
plexes of the first row of transition metals particularly
have wide applications in different areas.[26] These useful
features mean that Schiff bases play an important role in
chemistry and are considered as target substances for
many synthetic scientists.
Some Schiff base complexes are also used as model
molecules for biological oxygen carrier systems[25] as well
as having applications in analytical fields.[27] Schiff base
ligands with sulfur and nitrogen donor atoms in their
structures act as good chelating agents for transition and
non‐transition metal ions.[28] Coordination of such com-
pounds with metal ions such as copper, nickel and iron
often enhances their activities,[29] as has been reported
for pathogenic fungi,[30] because of the presence of both
hard nitrogen or oxygen and soft sulfur donor atoms in
the backbones of these ligands. They readily coordinate
with a wide range of transition metal ions yielding stable
and intensely coloured metal complexes some of which
have been shown to exhibit interesting physical and
chemical properties[31–35] and potentially useful biological
activities.
2 | EXPERIMENTAL
2.1 | Materials and reagents
All chemicals used in this study were of analytical reagent
grade and of the highest purity available. They included
salicylaldehyde (Sigma‐Aldrich), 1,2‐dibromoethane
(Merck), 4‐aminophenol (Sigma‐Aldrich), CuCl2⋅2H2O
(Sigma), CoCl2⋅6H2O, CdCl2⋅2H2O and NiCl2⋅6H2O
(BDH), MnCl2⋅2H2O (Sigma), FeCl3⋅6H2O (Prolabo) and
ZnCl2⋅2H2O (Ubichem). Organic solvents used included
absolute ethyl alcohol and dimethylformamide (DMF).
These solvents were spectroscopically pure from BDH.
Double‐distilled water was used in all preparations.
2.2 | Instrumentation
The molar conductance of solid chelates in DMF was
measured using a Jenway 4010 conductivity meter. Solid
reflectance spectra were measured with a Shimadzu
3101pc spectrophotometer. 1H NMR spectra were
recorded using a 300 MHz Varian‐Oxford Mercury. The
solvent used was deuterated dimethylsulfoxide (DMSO‐
d6) and the spectra extended from 0 to 15 ppm. Powder
XRD analyses were carried out using a Philips Analytical
BV X‐ray diffractometer, type PW 1840. Radiation was
provided by a copper target (Cu anode, 2000 W) high‐
intensity X‐ray tube operated at 40 kV and 25 mA. Diver-
gence and receiving slits were 1 and 0.2, respectively.
Molar magnetic susceptibility was measured using
Some communications reporting investigations of
complexes containing Fe ions with Schiff base ligands are
of particular interest.[31] One of their most important

ZAYED ET AL.
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powdered samples with the Faraday method. Diamag-
netic corrections were made by Pascal's constant and
Hg[Co(SCN)4] was used as a calibrant. Infrared (IR) spec-
tra were recorded with a PerkinElmer FT‐IR type 1650
spectrophotometer in the range 400–4000 cm−1. The spec-
tra were recorded as KBr pellets. Elemental microanalyses
of the separated solid chelates for C, H, N and Cl were
performed at the Microanalytical Center, Cairo
University, using a CHNS‐932 (LECO) Vario elemental
analyser. The analyses were repeated twice to check the
accuracy of the data. Mass spectra were recorded using
the EI technique at 70 eV using an MS‐5988 GS‐MS
Hewlett‐Packard instrument at the Microanalytical Cen-
ter, Cairo University. Thermal analyses (TG, DTG and
DTA) were carried out in dynamic nitrogen atmosphere
(20 ml min−1) with a heating rate of 10 °C min−1 using
a Shimadzu TG‐60 H simultaneous DTA‐TG apparatus.
mixture was refluxed for 3 h in a water bath whereupon
the complexes precipitated. These were then filtered off
and washed thoroughly with ethanol and diethyl ether
for further purification then dried in vacuum.
[4,4′‐((((Ethane‐1,2‐diylbis(oxy))bis(2,1‐phenylene))
bis(methanylylidene))bis(azanylylidene))diphenol]ethane
diaquo manganese(II) chloride (3a, C28H28Cl2MnN2O6).
Dark blue solid; yield 86%; m.p. 270 °C. Found (calcu-
lated) (%): C = 54.69 (54.72), H = 4.54 (4.56), N = 4.49
(4.56), Cl = 11.47 (11.56), Mn = 8.88 (8.96); μeff
(BM) = 3.69; Λm (Ω−1 mol−1 cm2) = 150. IR (cm−1):
1678 (HC¼N)azomethine, 1057 (C‐O‐C)ether, 3410 (OH),
933 and 862 (H2O), 602 (M‐O), 498 (M‐N).
4,4′‐((((Ethane‐1,2‐diylbis(oxy))bis(2,1‐phenylene))
bis(methanylylidene))bis(azanylylidene))diphenol]ethane
diaquo iron(III) chloride (3b, C28H28Cl3FeN2O6). Dark
green solid; yield 87%; m.p. 284 °C. Found (calculated)
(%): C = 51.63 (51.65), H = 4.28 (4.30), N = 4.24 (4.30),
Cl = 16.29 (16.37), Fe = 8.52 (8.61); μeff (BM) = 5.20; Λm
(Ω−1 mol−1 cm2) = 240. IR (cm−1): 1681 (HC¼N)
azomethine, 1057 (C‐O‐C)ether, 3414 (OH), 915 and 842
(H2O), 606 (M‐O), 493 (M‐N).
[4,4′‐((((Ethane‐1,2‐diylbis(oxy))bis(2,1‐phenylene))
bis(methanylylidene))bis(azanylylidene))diphenol]ethane
diaquo cobalt(II) chloride (3c, C28H28Cl2CoN2O6). Dark
blue; yield 73%; m.p. 250 °C. Found (calculated) (%):
C = 54.31 (54.37), H = 4.49 (4.53), N = 4.48 (4.53),
Cl = 11.41 (11.49), Co = 9.47 (9.55); μeff (BM) = 3.78;
Λm (Ω−1 mol−1 cm2) = 130.8. IR (cm−1): 1678 (HC¼N)
azomethine, 1053 (C‐O‐C)ether, 3409 (OH), 934 and 850
(H2O), 609 (M‐O), 498 (M‐N).
[4,4′‐((((Ethane‐1,2‐diylbis(oxy))bis(2,1‐phenylene))
bis(methanylylidene))bis(azanylylidene))diphenol]ethane
diaquo nickel(II) chloride (3d, C28H28Cl2NiN2O6). Pale
brown; yield 93%; m.p. >300 °C. Found (calculated) (%):
C = 54.25 (54.37), H = 4.49 (4.53), N = 4.27 (4.53),
Cl = 11.39 (11.49), Ni = 9.44 (9.55); μeff (BM) = 3.36; Λm
(Ω−1 mol−1 cm2) = 147. IR (cm−1): 1658 (HCHC¼N)
azomethine, 1061 (C‐O‐C)ether, 3414 (OH), 929 and 832
(H2O), 540 (M‐O), 432 (M‐N).
[4,4′‐((((Ethane‐1,2‐diylbis(oxy))bis(2,1‐phenylene))
bis(methanylylidene))bis(azanylylidene))diphenol]ethane
diaquo copper(II) chloride (3e, C28H28Cl2CuN2O6).
Brown solid; yield 85%; m.p. >300 °C. Found (calculated)
(%): C = 53.91 (53.98), H = 4.47 (4.50), N = 4.44 (4.50),
Cl = 11.32 (11.41), Cu = 10.17 (10.20); μeff (BM) = 1.82;
Λm (Ω−1 mol−1 cm2) = 110.4. IR (cm−1): 1659 (HC¼N)
azomethine, 1060 (C‐O‐C)ether, 3448 (OH), 931 and 863
(H2O), 597 (M‐O), 474 (M‐N).
2.3 | Synthesis of Bisaldehyde ligand
Salicylaldehyde (20 mmol) was dissolved in hot ethanolic
KOH solution (prepared by dissolving 1.12 g (20 mmol) of
KOH in 20 ml of absolute ethanol). Then the solvent was
removed in vacuo. The remaining material was dissolved
in DMF (15 ml) and 1,2‐dibromoethane (10 mmol) was
added. The reaction mixture was refluxed for 5 min dur-
ing which KCl was separated. The solvent was then
removed in vacuo and the remaining material was washed
with water and purified by crystallization.[37–42]
2.4 | Synthesis of Bis‐Schiff Base ligand
(H2L)
The bis‐Schiff base was prepared by refluxing a mixture of
equimolar amounts of bisaldehyde (4 g, 0.02 mmol) and 4‐
aminophenol (3.24 g, 0.04 mmol) in ethanolic medium in
a water bath for 6 h. The resulting yellow precipitate was
filtered and purified by crystallization from ethanol then
dried in vacuum to give the desired bis‐Schiff base ligand.
The yellow bis‐Schiff base ligand was produced in 89%
yield.
H2L (C28H24N2O4). Yellow solid; yield 89%; m.p. 96 °C.
Found (calculated) (%): C = 74.29 (74.33), H = 5.17 (5.31),
N = 5.88 (6.19). IR (cm−1): 1601 (HC¼N)azomethine, 1026
1
(C‐O‐C)ether. H NMR (δ, ppm): 8.76 (s, 2H, OH), 4.53
(m, 4H, OCH2), 6.72–7.91 (m, 16, ArH), 8.26 (s, 2H,
CH¼N).
2.5 | Synthesis of metal complexes
[4,4′‐((((Ethane‐1,2‐diylbis(oxy))bis(2,1‐phenylene))
bis(methanylylidene))bis(azanylylidene))diphenol]ethane
diaquo zinc(II) chloride (3f, C28H28Cl2ZnN2O6). White
solid; yield 72%; m.p. 300 °C. Found (calculated) (%):
To a solution of the Schiff base ligand (0.3 g, 0.664 mmol)
in ethanol (30 cm3) was added a solution of metal(II)/(III)
chloride (0.664 mmol) in ethanol (15 cm3). The resulting

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ZAYED ET AL.
C = 53.76 (53.85), H = 4.47 (4.49), N = 4.42 (4.49),
Cl = 11.27 (11.38), Zn = 10.38 (10.42); μeff (BM) = diamag-
netic; Λm (Ω−1 mol−1 cm2) = 160. IR (cm−1): 1671
(HC¼N)azomethine, 1053 (C‐O‐C)ether, 3414 (H2O), 950
and 847 (H2O), 505 (M‐O), 480 (M‐N). 1H NMR (δ,
ppm): 8.72 (s, 2H, OH), 4.85 (m, 4H, OCH2), 6.98–7.91
(m, 16, ArH), 8.14 (s, 2H, CH¼N).
step of 0.2 Å, and quaternion and torsion steps of 5 were
utilized.
2.8 | Biological activity
The diffusion agar technique was used. Spore suspension
(0.5 ml, 10−6–10−7 spores ml−1) of each of the investigated
organisms was added to a sterile agar medium just before
solidification, then poured into sterile Petri dishes (9 cm
in diameter) and left to solidify. Using a sterile cork borer
(6 mm in diameter), three holes (wells) were made in each
dish, and then 0.1 ml of the test compound dissolved in
DMF (100 mg ml−1) was poured into the holes. The dishes
were incubated at 37 °C for 48 h where clear or inhibition
zones were detected around each hole. DMF (0.1 ml) was
used as a control under the same conditions. By
subtracting the diameter of the inhibition zone obtained
with DMF from that obtained from each metal complex
or the free bis‐Schiff base, antibacterial activities were cal-
culated as a mean of three replicates.[26] MIC50 was deter-
mined and was defined as the lowest drug concentration
that inhibits growth by 50%.
[4,4′‐((((Ethane‐1,2‐diylbis(oxy))bis(2,1‐phenylene))
bis(methanylylidene))bis(azanylylidene))diphenol]ethane
diaquo cadmium(II) chloride (3 g, C28H28Cl2CdN2O6).
Dark green solid; yield 91%; m.p. 215 °C. Found (calcu-
lated) (%): C = 49.93 (50.07), H = 4.14 (4.17), N = 4.11
(4.17), Cl = 10.48 (10.58), Cd = 16.67 (16.69); μeff
(BM) = diamagnetic; Λm (Ω−1 mol−1 cm2) = 120.2. IR
(cm−1): 1674 (HC¼N)azomethine, 1060 (C‐O‐C)ether, 3437
(OH), 916 and 852 (H2O), 501 (M‐O), 436 (M‐N).
2.6 | Molecular modelling methodology
The optimized structural geometry of the Schiff base
ligand was determined using the DFT/B3LYP method
with different base sets using Gaussian09 software.[43]
Gauss‐View molecular visualization program was used
to display Gaussian files.[44] In agreement with the
numerical pattern appearing in the view of the com-
pounds in gas phase, DFT/B3LYP quantum chemical
parameters were calculated from HOMO–LUMO ener-
gies. Also, significant bond lengths, oscillator strengths,
excitation energies and effective charges for coordinating
groups in optimized structures were deduced.
3 | RESULTS AND DISCUSSION
3.1 | Characterization of ligand
The bis‐Schiff base ligand was prepared according to
Figure 1 and its structure was characterized based on ele-
1
mental analysis and IR, mass and H NMR spectra. The
mass spectrum of the ligand (H2L) showed a peak at
452.5 amu corresponding to the macrocyclic moiety
[C28H26N2O4] (Scheme 1). Other peaks like 65, 109, 213
and 359 amu were suggested according to diverse frag-
ments. From this study, it was found that the intensity
of the peaks gave information on the stability of fragmen-
tation. But the IR spectrum of the bis‐Schiff base ligand
did not display any band according to free groups such
as diamine or keto. This suggested full condensation of
the keto group with the amino group. A new band
resulting from ν(CH¼N) of the azomethine group
appeared at 1601 cm−1 which confirmed the formation
of the bis‐Schiff base ligand. For previously investigated
bis‐Schiff base ligands, the azomethine group band was
2.7 | Molecular docking
AutoDock tools 4.2, docking computations applying
Gasteiger partial charges added to ligand (designed drug)
atoms, were used. On the ligand–protein pattern, the cal-
culations were executed. Non‐polar hydrogen atoms were
conjoined, and rotatable bonds were clarified. After the
addition of fundamental hydrogen atoms, Kollman united
atom type charges and salvation parameters the
AutoDock tools were applied.[45,46] Determining van der
Waals and electrostatic terms was performed by
AutoDock parameter set‐ and distance‐dependent dielec-
tric functions, respectively. Simulative docking was exe-
cuted by Solis & Wets local search method and
Lamarckian genetic algorithm.[47] Incidentally, initial
position, orientation and torsions of the ligand molecule
were set. All rotatable torsions were omitted during
docking. Ten different runs were used to derive each
docking experiment, which was set to block after an ulti-
mate of 250 000 energy estimations. The size was
established to 150. Throughout the study, a translational
found at 1597 cm−1[40–42] and 1601 cm−1 [37]
band of C‐O‐C appeared at 1026 cm−1 for the bis‐Schiff
base, but this band was found at 1049 cm−1 [40,42]
1020 cm−1[41] and 1028 cm−1 [37]
.
Stretching
,
.
3.2 | Molecular modelling
Molecular modelling theoretical tool implemented with
the Gaussian09 program was employed for the Schiff base

ZAYED ET AL.
5 of 16
FIGURE 1 Synthesis of bis‐Schiff base ligand (H2L)
SCHEME 1 Mass fragmentation
pattern of bis‐Schiff base ligand
ligand to find the essential quantum parameters and opti-
mized geometries. The border orbital energy gap between
EHOMO and ELUMO is an essential parameter used to rec-
ognize the electronic structure of Schiff base ligand.[48]
Images of MOs of free Schiff base ligand (Figure 2).
showed that the HOMO and LUMO were mainly centred
on donor atoms, azomethine nitrogens and etheric oxy-
gens, which are considered the location for donors and
acceptors (Figure 2). Electronegativity (χ), chemical
potential (μ), global hardness (η), global softness (S),
global electrophilicity index (ω) and absolute softness
(S) were evaluated according to various equations and
the data obtained are listed in Table 1.[49,50] One impor-
tant quantum parameter is ω which reflects the relative
toxicity and reactivity of different selective sites. Electro-
philicity may define the biological activity of proposed
drugs, and also indicates the stabilization energy while
acquiring extra negative charge from the environment
by drug systems. Parameters η and S are indicators for
the molecular stability and reactivity. Also, their concepts
belong to each other. The softness indicators are the oppo-
site character for global hardness.[51,52]
The quantum parameters were calculated (supporting
information, Tables S2 and S3) and the comparative inves-
tigation introduces the following points concerning the
free Schiff base ligand. Flexible reactivity towards the
metal atoms was deduced from the soft character of the
Schiff base ligand. Positive χ and negative μ values indi-
cated that the compound able to capture electrons from
its environment and its energy decreases accordingly.
3.3 | Characterization of metal complexes
From the elemental analysis, it was found that the com-
plexes have composition [M(H2L)(H2O)2]Cl2 (M = Mn(II),
Co(II), Ni(II), Cu(II), Zn(II) and Cd(II)) and [Fe(H2L)

6 of 16
ZAYED ET AL.
TABLE 1 Calculated quantum chemical parameters of the Schiff
base ligand
Parameter
EHOMO (a.u.)
ELUMO (a.u.)
μ (D)
−0.1878
−0.6034
5.867
TE (a.u.)
ΔE (a.u.)
χ (a.u.)
−1483.583
−0.4156
0.3956
η (a.u.)
σ (a.u.)−1
−0.2078
−4.812
Pi (a.u.)
−0.3956
−2.406
S (a.u.)−1
ω(a.u.)
−0.3763
1.9036
ΔNmax
found that the molar conductance value of the Fe(III)
chelate was 240 Ω−1 mol−1 cm2, which suggested the
ionic nature of that complex and indicated that chloride
anion was non‐bonded to the Fe(III) ion. The Fe(III)
chelate is an electrolyte on the basis of this result. It
was found that the molar conductance of metal ion
complexes has values 110.4, 160, 130.8, 147, 120.2 and
150 Ω−1 mol−1 cm2 for Cu(II), Zn(II), Co(II), Ni(II),
Cd(II) and Mn(II), respectively. From these values, it
is evident that the complexes are ionic in nature and
hence have electrolytic nature.[27]
3.5 | IR spectra and mode of bonding
From the IR spectra, it was observed that the ν(CH¼N)
stretching vibration of the azomethine nitrogen for the
bis‐Schiff base was at 1601 cm−1. But this band is
changed to higher wavenumbers in the spectra of the
chelates (1659–1681 cm−1). This was evidence of the par-
ticipation of the azomethine nitrogen group in coordina-
tion.[39–42] Stretching band of C‐O‐C appeared at 1026 cm
−1 for the bis‐Schiff base, but this band for the complexes
FIGURE 2 HOMO and LUMO patterns of bis‐Schiff base ligand
(H2O)2]Cl3. Complexes were prepared and dried under
vacuum and then subjected to elemental analyses. The
elemental analyses results (C, H, N, Cl) with molecular
formulae and some diverse physical properties such as
melting points, colour and percent yield are detailed in
Section 1. It was found that the results obtained were
compatible with the calculated results of suggested formu-
lae. Sharpness of melting points indicated the purity of
the complexes. IR and 1H NMR spectra were used to con-
firm the structure of the complexes.
appeared at 1053–1061 cm−1 [39–42]
The changes indi-
.
cated the participation of oxygen atoms in coordination
to the metal ions.[39–42,52] The bands at 915–950 and
832–863 cm−1 were assigned to stretching vibrations of
coordinated water molecules. Some new bands were
present in the spectra of the complexes at 505–609 cm
−1
attributed to ν(M‐O) stretching vibrations. Other
bands appeared at 432–493 cm−1 which were attributed
to ν(M‐N) mode.[31] The OH band was observed at
3430 cm−1 but this band for the complexes was shifted
to 3409–3448 cm−1 which may be higher or lower than
that for the ligand. This shift can be attributed to
3.4 | Molar conductivity measurements
The measurements of conductivity for the complexes are
detailed in Section 1. Of the results recorded, it was

ZAYED ET AL.
7 of 16
hydrogen bond formation. So, from the result of IR spec-
tra, it was found that the bis‐Schiff base ligand coordi-
nated to the metal ions via the two azomethine N and
two ether O atoms and acting in a neutral tetradentate
3.7 | Mass spectral studies
The mass spectrum of the [Fe(H2L)(H2O)2]Cl3 complex
(Figure 3) showed a molecular ion peak at 650 g mol−1
which was in good agreement with the calculated value
(650.5 g mol−1). This result further supports the elemental
and thermal analyses data.
manner.[41,42]
Condensation
salicylaldehyde and triethylenetetramine,[40] propane‐
1,3‐diamine,[41] ethylenediamine[42]
and 2‐
reaction
of
bis‐
aminothiophenol[37] resulted in the formation of bis‐
Schiff bases bound to metal ions in neutral O2N4
hexadentate, neutral O2N2 tetradentate, neutral O2N2
tetradentate and binegative O2N2S2 hexadentate man-
ners, respectively. All of them had the same coordination
sites and the only difference was found in the amine
regarding if it had a donor centre or not.
3.8 | Thermal analysis
From the results of thermal decomposition of the bis‐
Schiff base (Table 2). the TG curve of the ligand showed
two successive steps of decomposition. In the first stage,
the estimated mass loss was 65.41% (calcd 65.64%) at
30–480 °C. This can be accounted for by the decomposi-
tion of C18H20N2O2 molecule. The final stage, from 480
to 800 °C, with estimated mass loss of 34.47% (calcd
34.33%), can be accounted for by loss of C10H4O2 molecule
with full decomposition.
3.6 | 1H NMR spectra
1
The H NMR spectra showed sharp bands at 4.53 and
4.85 ppm which may be assigned to the OCH2 protons of
the free bis‐Schiff base and Zn(II) complex, respectively.
The OH signal appeared at 8.76 and 8.72 ppm in the free
bis‐Schiff base ligand and Zn(II) complex spectra, respec-
tively. In spite of the OH group not being included in che-
late formation, this change can be a result of hydrogen
bond formation. Multiple bands assigned to the aromatic
protons were found at 6.72–7.91 and 6.98–7.96 ppm for
the free bis‐Schiff base ligand and Zn(II) complex, respec-
tively. The azomethine (HC¼N) signal was found at
8.26 ppm in the spectrum of bis‐Schiff base ligand. But this
signal appeared at 8.14 ppm for the Zn(II) chelate.[37,40–42]
The shift can be attributed to the involvement of
azomethine N atom in chelation.
The thermograms of [Cu(H2L)(H2O)2]Cl2 (3e) and
[Zn(H2L)(H2O)2]Cl2 (3f) chelates showed four stages of
decomposition within the range 30–800 °C (Table 2).
The first stage of decomposition at 30–150 °C corresponds
to the loss of 2H2O and HCl molecules with estimated
mass loss of 11.71% (calcd 11.65%) and 12.49% (calcd
11.62%) for Cu(II) and Zn(II) complexes, respectively.
The second stage corresponds to the loss of HCl and O2
and HCl and CH4 molecules with mass loss of 10.42%
(calcd 11.00%) and 8.15% (calcd 8.41%) within the ranges
150–250 and 150–280 °C for Cu(II) and Zn(II) complexes,
respectively. The third stage of decomposition occurred at
250–450 and 280–450 °C corresponding to loss of C2H4NO
and C2H2N2O2 molecules with mass loss of 9.56% (calcd
FIGURE 3 Mass spectrum of [Fe(H2L)(H2O)2]Cl3 complex

8 of 16
ZAYED ET AL.
TABLE 2 Thermoanalytical results (TG, DTG and DTA) of ligand and its metal complexes
TG range DTGmax
Mass loss Total mass loss Calcd
(found) (%)
Metallic
residue
Complex
(°C)
(°C)
DTA (°C)
na
Assignment
H2L
30–480
480–800
330 382(+), 570(−)
550
1
1
65.41 (65.64) 99.88 (99.97)
34.47 (34.33)
– Loss of C18H20N2O2
– Loss of C10H4O2
—
[cu(H2L)(H2O)2]
Cl2 (3e)
30–150
150–250
250–450
450–800
77 110(+), 240(−)
190 340(−), 590(+)
332
672
1
1
1
1
11.65 (11.71) 87.23 (87.15)
11.00 (10.42)
9.32 (9.56)
– Loss of 2H2O and HCl CuO
– Loss of HCl and O2
– Loss of C2H4NO
55.26 (55.46)
– Loss of C26H18N
[Zn(H2L)(H2O)2]
Cl2 (3f)
30–150
150–280
280–450
450–800
76
64(+), 250(+)
1
1
1
1
11.62 (12.49) 87.02 (87.65)
8.41 (8.15)
13.78 (14.55)
– Loss of 2H2O and HCl ZnO
– Loss of HCl and CH4
– Loss of C2H2N2O2
200 410(−), 640(−)
320
575
53.21 (52.46)
– Loss of C25H16O
[co(H2L)(H2O)2]
Cl2 (3c)
30–150
75
70(+), 256(−)
1
2
11.73 (11.56) 87.86 (87.56)
12.70 (12.85)
– Loss of 2H2O and HCl CoO
– Loss of HCl and
C2H4N
150–470 240, 375 438(−), 542(+)
470–800
570
1
63.43 (63.15)
– Loss of C26H18NO3
[Fe(H2L)(H2O)2]
Cl3 (3b)
50–200
200–500
82
330
69(−), 339(+)
457(−)
1
1
9.84 (8.45) 89.86 (87.26)
17.99 (17.33)
– Loss of 2H2O and CO ½Fe2O3
– Loss of 2HCl and
CH4NO
500–800
610
1
62.03 (61.48)
– Loss of HCl and
C26H17NO1.5.
[Ni(H2L)(H2O)2]
Cl2 (3d)
30–150
150–480
480–800
65 111(+), 160(−)
190 557(+)
500
1
1
1
11.73 (11.57) 87.86 (87.58)
10.76 (9.56)
65.37 (66.45)
– Loss of 2H2O and HCl NiO
– Loss of HCl and CH2O
– Loss of C27H20N2O2
[cd(H2L)(H2O)2]
Cl2 (3 g)
30–280
280–400
80 51 (+), 137(+)
310 283(−), 540(−)
1
1
10.80 (10.55) 80.92 (80.58)
53.88(53.42)
– Loss of 2H2O and HCl CdO
– Loss of HCl and
C22H15NO2
400–600
440
1
16.24 (16.61)
– Loss of C6H7NO
[Mn(H2L)(H2O)2]
Cl2 (3a)
50–200
200–480
80 110(+), 320(−),
270 366(−), 562(−),
1
2
11.81 (11.73) 88.44 (89.31)
12.46 (12.36)
– Loss of 2H2O and HCl MnO
– Loss of HCl and
C2H2N
703(−)
480–600
600–800
510
640
1
1
30.78 (30.65)
33.39 (34.57)
– Loss of C11H11NO2
– Loss of C15H9O
aNumber of decomposition steps.
9.32%) and 14.55% (calcd 13.78%) for Cu(II) and Zn(II)
complexes, respectively. The last stage at 450–800 °C
showed the loss of C26H18N and C25H16O molecules with
an estimated mass loss of 55.46% (calcd 55.26%) and
52.46% (calcd. 53.21%) leaving CuO and ZnO as residue
of Cu(II) and Zn(II) complexes, respectively.
The TG curves of [Co(H2L)(H2O)2]Cl2 (3c) and
[Mn(H2L)(H2O)2]Cl2 (3a) chelates showed four stages of
decomposition in the ranges 30–800 and 50–800 °C
(Table 2).for Co(II) and Mn(II) complexes, respectively.
The first step corresponded to the loss of 2H2O and HCl
molecules at 30–150 and 50–200 °C with mass loss of
11.56% (calcd 11.73%) and 11.73% (calcd 11.81%) for
Co(II) and Mn(II) complexes, respectively. The second
stage of decomposition at 150–470 and 200–480 °C
corresponded to loss of HCl and C2H4N and HCl and
C2H2N molecules with mass loss of 12.85% (calcd
12.70%) and 12.36% (calcd 12.46%) for Co(II) and Mn(II)
complexes, respectively. The third step occurred at
470–800 and 480–600 °C, corresponding to the removal
of C26H18NO3 and C11H11NO2 molecules with mass loss
of 63.15% (calcd 63.43%) and 30.65% (calcd 30.78%) for
Co(II) and Mn(II) complexes, respectively. The last stage
at 600–800 °C corresponded to the loss of C15H9O mole-
cules with mass loss of 34.57% (calcd 33.39%) for Mn(II)
complex. CoO and MnO were the residues for decomposi-
tion of Co(II) and Mn(II) complexes, respectively.
The [Fe(H2L)(H2O)2]Cl3 (3b) and [Ni(H2L)(H2O)2]Cl2
(3d) complexes exhibited three stages of decomposition.
The first stage corresponds to the loss of 2H2O and CO
and 2H2O and HCl molecules within the ranges 50–200
and 30–50 °C with mass loss of 8.45% (calcd 9.84%) and
11.57% (calcd 11.73%) for Fe(III) and Ni(II) complexes,
respectively. The second stage (200–500 and 150–480 °C)
corresponds to the loss of 2HCl and CH4NO and HCl
and CH2O molecules with mass loss of 17.33% (calcd

ZAYED ET AL.
9 of 16
17.99%) and 9.56% (calcd 10.76%) for Fe(III) and Ni(II)
complexes, respectively. The final stage at 500–800 and
480–800 °C corresponds to the loss of HCl and
C26H17NO1.5 and C27H20N2O2 molecules with mass loss
of 61.48% (calcd 62.03%) and 66.45% (calcd 65.37%) leav-
ing ½Fe2O3 and NiO as residues of decomposition.
The TG curve of the [Cd(H2L)(H2O)2]Cl2 (3 g) chelate
showed three steps of decomposition from 30 to 600 °C
(Table 2). The first step of decomposition corresponds to
the loss of 2H2O and HCl molecules at 30–280 °C with
mass loss of 10.55% (calcd 10.80%). The second decompo-
sition stage at 280–400 °C corresponded to loss of HCl and
C22H15NO2 molecule with mass loss of 53.42% (calcd
53.88%). The final step occurred from 400 to 600 °C and
corresponded to the removal of C6H7NO molecule with
mass loss of 16.61% (calcd 16.24%) leaving CdO as a
residue.
to the decomposition of complexes, namely activation
energy(E*), enthalpy (ΔH*), entropy (ΔS*) and Gibbs free
energy (ΔG*). These parameters are presented in Table 3.
From the data, it was found that E* for decomposition has
the range 24.89–310.5 kJ mol−1. The high value of E* indi-
cated the thermal stability of the chelates. It was found
that ΔS* had negative values for all complexes which
showed that the decomposition reactions of the com-
plexes proceed at less of a rate than the normal process
or the decomposition reaction that occurs spontaneously.
3.9 | Reflectance spectra and magnetic
susceptibility
In the spectral reflectance spectrum of the Cu(II) com-
plex, two peaks appeared at 17 331 and 21 691 cm−1
.
The split which occurred under the effect of the tetragonal
distortion was due to the states of 2Eg and 2T2g of the octa-
hedral Cu(II) ion (d9) and the distortion can likely cause
Differential thermal analysis data are given in Table 2.
The decomposition of the complexes showed exothermic
or endothermic peaks within the temperature of
decomposition.
2
2
the three transitions B1g
!
2B2g, B1g
!
2Eg and
2B1g ! A1g to remain in the spectrum unresolved.[41]
This assignment was compatible with the general obser-
vation that Cu(II) d–d transitions are usually close in
2
The Coats–Redfern relationship[47] can be used to
evaluate the thermodynamic activation parameters due
TABLE 3 Thermodynamic data for bis‐ Schiff base ligand and its metal complexes
Compound
Decomp. Temp. (°C) E* (kJ mol−1
)
A (s−1
1.08 × 104
5.6 × 108
)
ΔS* (J K−1 mol−1
)
ΔH* (kJ mol−1
)
ΔG* (kJ mol−1
)
H2L
30–480
76.64
78.55
−30.77
−84.71
73.07
58.63
214.13
54.63
480–800
[cu(H2L)(H2O)2]Cl2
[Zn(H2L)(H2O)2]Cl2
[co(H2L)(H2O)2]Cl2
30–150
150–250
250–450
450–800
44.43
69.81
89.35
215.2
2.47 × 106
5.03 × 107
3.68 × 1012
7.33 × 107
−116.0
−108.0
−56.06
−63.96
42.83
73.61
28.69
195.0
41.51
78.97
100.36
198.0
30–150
150–280
280–450
450–800
79.89
135.7
220.7
235.4
4.71 × 108
7.68 × 1014
4.89 × 105
3.66 × 106
−35.69
−109.8
−184.9
−201.3
73.12
194.5
262.3
268.2
87.32
156.0
201.3
220.1
30–150
150–280
280–470
470–800
98.76
116.5
217.3
310.5
2.23 × 106
7.04 × 108
6.86 × 1012
6.58 × 109
−59.21
−45.34
−50.52
−126.9
55.73
129.4
216.6
341.9
85.66
166.8
205.9
305.1
[Fe(H2L)(H2O)2]Cl3
[Ni(H2L)(H2O)2]Cl2
[cd(H2L)(H2O)2]Cl2
[Mn(H2L)(H2O)2]Cl2
50–200
200–500
500–800
25.64
50.38
72.36
2.51 × 105
4.19 × 107
6.05 × 1010
−38.47
−60.81
−99.87
44.92
77.10
115.6
66.00
113.5
197.8
30–150
150–480
480–800
32.56
57.25
64.69
1.25 × 106
1.07 × 107
2.57 × 106
−20.39
−52.34
−90.62
31.53
65.11
112.3
39.63
94.05
195.9
30–280
280–400
400–600
98.76
116.5
217.3
2.23 × 106
7.04 × 108
6.86 × 1012
−59.21
−45.34
−50.52
55.73
129.4
216.6
85.66
166.8
205.9
50–200
200–480
480–600
600–800
24.89
35.20
72.05
101.3
3.81 × 106
5.09 × 108
6.25 × 109
4.52 × 108
−37.12
−66.73
−103.2
−120.5
36.56
74.13
107.6
132.5
48.92
109.0
167.8
198.2

10 of 16
ZAYED ET AL.
energy.[34–36,38–41] This complex had a magnetic moment
of 1.82 BM, which was located within the range usually
observed for octahedral Cu(II) chelates.[37,39–42,53–56]
The magnetic moment of the Co(II) complex is 5.78
BM which confirmed octahedral geometry.[39–42,57–59]
The spectrum of the Co(II) complex showed three peaks
at 15 772, 17 391 and 21 978 cm−1 which were assigned
4
4
4
4
to T1g(F) ! T2g(F) (ν1), T1g(F) ! A2g(F) (ν2) and
4T1g(F) ! T1g(P) (ν3) transitions, respectively, which sug-
4
gested that there was an octahedral geometry around the
Co(II) ion. The diffuse reflectance spectrum of the Fe(III)
FIGURE 4 Structure of metal complexes of bis‐Schiff base ligand
chelate exhibited bands at 18 822, 19 722 and 23 809 cm−1
,
complexes were crystalline. In addition, all the metal
complexes previously reported by Khalil et al.[42] were
found to be amorphous in nature, except the Cr(III),
Ni(II), Cu(II) and Zn(II) chelates that had crystalline
phase.
6
which can be attributed to the A1g ! T2g(G) and
6A1g ! T1g transitions in octahedral geometry of the che-
5
late.[60–63] The magnetic moment of the Fe(III) complex is
of 5.20 BM, indicating octahedral geometry and involving
d2sp3 in Fe(III) ion.[54,59]
The value of magnetic moment for the Ni(II) complex
is 3.36 BM, which indicates high‐spin octahedral geome-
try.[39–42] Its diffuse reflectance spectrum showed three
3.12 | Molecular docking
bands at 14 792 (ν1), 15 267 (ν2) and 21 786 cm−1 (ν3),
AutoDock tools were used to clarify the biological fea-
tures of drugs and support the experimental results.
Molecular docking was carried out for Schiff base ligand
(guest) with various protein receptors (host): B. subtilis
(5 h67), E. coli (3 t88), P. vulgaris (5i39) and S. aureus
(3ty7) (Figures 6–9). The energies for the docking proce-
dure were calculated. According to computation, HB
plots (Figures 6–9) clarify a strong interaction with all
receptors with comparable results. This refers to variable
capability of multi‐central groups for hydrogen‐bonding
interaction inside docking complexes. Inter‐hydrogen
bonding appeared clearly with all proteins. Two‐dimen-
sional plots (Figures 6–9) verify the mode of interaction
inside the docking molecules. It was clear that amino
acids of proteins reacted with the Schiff base ligand by
hydrogen bonds as follows:
3
which may be assigned to A2g(F)
!
3T2g(F),
3A2g(F) ! T1g(F) and A2g(F) ! T1g(P) transitions,
respectively.[39–42,59–63] In the spectrum of the Mn(II)
complex, three bands were found at 15 661, 17 361 and
3
3
3
27 505 cm−1 which can be attributed to T1g ! A1g,
4
6
4T2g(G) ! A1g and T1g(D) ! A1g transitions, respec-
tively.[54,58,59] The complex had magnetic moment value
of 5.69 BM, which confirmed octahedral geometry around
the Mn(II) centre.
6
4
6
3.10 | Structural interpretation
According to the elemental analysis, 1:1 metal complexes
were formed and they were electrolytes as evidenced from
the measurements of molar conductance. Also, IR spec-
tral results showed that the bis‐Schiff base ligand acted
as a neutral tetradentate ligand with NNOO donor sites,
1
while H NMR results support the non‐involvement of
OH protons in chelate formation. The thermal behaviour
of the complexes was also studied where metal oxides
were found to be the residues of decomposition. There-
fore, the structure of the complexes is as shown in
Figure 4.
3.11 | Powder XRD
The XRD patterns of Co(II) and Cu(II) chelates
showed that they have amorphous structures as the
patterns lack sharp peaks while the Mn(II) complex
had a crystalline structure (Figure 5). In a previous
study[40] it was reported that all the complexes had
amorphous structure while Cr(III) and Fe(III)
FIGURE 5 XRD patterns of [Mn(H2L)(H2O)2]Cl2 complex

ZAYED ET AL.
11 of 16
FIGURE 6 Three‐dimensional plot of
interaction of Schiff base ligand with 3 t88
E. coli receptor
FIGURE 7 Three‐dimensional plot of
interaction of Schiff base ligand with 3ty7
S. aureus receptor

12 of 16
ZAYED ET AL.
FIGURE 8 Three‐dimensional plot of
interaction of Schiff base ligand with 5 h67
B. subtilis receptor
FIGURE 9 Three‐dimensional plot of
interaction of Schiff base ligand with 5i39
P. vulgaris receptor

ZAYED ET AL.
13 of 16
For B. subtilis (5 h67): A/ASN`33/OD1; A/LYS`37/
HZ1; A/ASN`39/1HD2 and A/ILE`65/O with binding
energy of −7.6 kcal mol−1
For E. coli (3 t88): 3 t88‐A‐GLN`189‐1HE2 and 3 t88‐
A‐GLN`88‐H with binding energy of −6.5 kcal mol−1
For P. vulgaris (5i39): A/GLY`90/H and A/GLY`409/H
with binding energy of −9.6 kcal mol−1
organisms were used: Gram‐positive bacteria (S. pyogones
ATTC 12600 and B. subtilis ATTC 6051) and Gram‐
negative bacteria (P. vulgaris ATTC 13315 and E. coli
ATTC 11775). The antibacterial activity can be calculated
by measuring the inhibition zone and MIC50 (Table 4 and
Figure 10). Comparing the results for the bis‐Schiff base, it
was found that the sensitivity of the bis‐Schiff base was
higher for Gram‐positive than Gram‐negative bacteria
and the order of activity was as follows: S. pyogones > B.
subtilis > P. vulgaris > E. coli. It was observed that the bio-
logical activity of the complexes is in the order as follow s:
Co(II) > Cu(II) > Mn(II) > Fe(III) = Ni(II) > Cd(II) =
Zn(II). For the Gram‐negative bacteria it was found that
the Co(II) complex was the most effective antibacterial
agent, giving the highest inhibition zones (30 and
.
.
.
For S. aureus (3ty7): ASN`17/O; ASN`40/1HD2 and
ASP`45/OD2 with binding energy of −5.1 kcal mol−1
.
3.13 | Biological activity
Schiff bases are an important class of compounds as they
have a wide range of applications in various fields, includ-
ing in the medical and pharmaceutical industries. They
also show a variety of biological applications, having anti-
bacterial[38,39,57] and anti‐tumour activities. Microbes
encounter many metal ions in their environmental sur-
roundings and interact with them, which can be helpful
or harmful depending on the nature of the metal ion,
whether chemical/physical nature as well as the oxidation
state. Important metal ions are those that are present
mostly in the forms of uniform cations or oxyanions or
in the forms of uniform salts, oxides or amorphous precip-
itates as in crystalline and insoluble form. Their impor-
tance to microbes lies in the ability to bind the central
metal ions to the outer surface of a cell and then transport
into the cell for a variety of cell functions. All kinds of
microbes, whether prokaryotes or eukaryotes, use metal
ions to control the functional structure of cells. The agar
method can be used to test the antibacterial activity of
the bis‐Schiff base and also its metal complexes, and this
method was also used with streptomycin as a reference
antibiotic for antibacterial activities. Two types of
32 mm), respectively, and the lowest MIC50 (>50 mg ml−1
for both tested bacteria.
)
From the data listed in Table 4, it was found that the
Cu(II) complex had moderate inhibitory activity (28 and
29 mm) for E. coli and P. vulgaris, respectively. On the
other hand, it registered high MIC50 (>100 mg ml−1) for
both microorganisms.[64–66] But the Mn(II) complex has
poorer inhibitory activity, where the diameters of the
inhibition zone are 24 and 22 mm for E. coli and P.
vulgaris, respectively. The parent bis‐Schiff base (H2L)
and Fe(III) and Ni(II) complexes have slight inhibitory
activity, where the inhibition zone diameters are 15 to
26 mm for the two Gram‐negative bacteria and these com-
pounds registered high MIC50 (>100 mg ml−1). From the
data given in Table 4, it was obvious that the antibacterial
activity against both Gram‐negative and Gram‐positive
bacteria has been completely lost for Cd(II) and Zn(II)
complexes. The Co(II) complex shows the most potent
antibacterial activity for Gram‐positive bacteria (B. subtilis
and S. pyogones), and registered the highest diameter of
TABLE 4 Biological activity of bis‐Schiff base ligand and its metal complexes
Inhibition zone (mm mg−1 sample)/MIC50 (mg ml−1
)
Gram negative
Gram positive
Sample
Escherichia coli
Proteus Vulgaris
Bacillus subtilis
Staphylococcus pyogones
H2L
25
26
32
37
[Mn(H2L)(H2O)2]Cl2
[Fe(H2L)(H2O)2]Cl3
[co(H2L)(H2O)2]Cl2
[Ni(H2L)(H2O)2]Cl2
[cu(H2L)(H2O)2]Cl2
[Zn(H2L)(H2O)2]Cl2
[cd(H2L)(H2O)2]Cl2
Standard
24 > 100
20 > 100
30 > 50
14 > 100
28 > 100
9 > 100
9 > 100
40 > 100
22 > 100
19 > 100
32 > 50
23 > 100
18 > 100
45 > 25
21 > 100
16 > 100
38 > 50
12 > 100
25 > 100
8 > 100
8 > 100
40 > 100
15 > 100
29 > 100
10 > 100
10 > 100
40 > 100
13 > 100
27 > 100
11 > 100
11 > 100
40 > 100

14 of 16
ZAYED ET AL.
FIGURE 10 Biological activity of bis‐Schiff base ligand and its metal complexes
inhibition zones (45 and 37 mm), and the lowest MIC50
(>25 and >50 mg ml−1). Most of the complexes reported
herein had higher biological activity than those previously
reported[18] and lower than those reported by the
authors.[41] This can be attributed to the absence of ether
O and the presence of furan O in the compounds of the
previous study.[18] Meanwhile, the presence of a cavity
in the coordination sphere of the ligand previously
reported[41] gave it higher activity than the ligand in the
present study. The parent bis‐Schiff base has inhibitory
activity (32 and 37 mm) for both B. subtilis and S.
pyogones, respectively, which are good, and registered also
high MIC50 (>100 mg ml−1) when compared with previ-
ous data.[18,41]
study revealed an octahedral geometry around the
M(II)/M(III) complexes as indicated from diffuse reflec-
tance and magnetic moment measurements.[64–66] IR
spectra revealed that the bis‐Schiff base ligand acts as a
tetradentate ligand and its manner of coordination is
through the nitrogen atoms of the azomethine (CH¼N)
and etheric O groups. The thermal behaviour as well as
powder XRD were studied in order to give an idea about
thermal decomposition and crystallinity of the complexes,
respectively. The results for antimicrobial activity indicate
that the metal chelates show greater inhibitory effects
than the parent bis‐Schiff base ligand. It is also proposed
that concentration plays a vital role in increasing the
degree of inhibition: as the concentration increases, the
activity increases.
The inhibitory activity of the Cu(II) complex is moder-
ate and inhibition zone diameters of 27 and 25 mm were
registered for B. subtilis and S. pyogones, respectively,
and high MIC50 value >100 mg ml−1. The antibacterial
activity the Mn(II) complex was found to follow that of
the Cu(II) complex and the diameter of inhibition zone
is 23 and 21 mm for B. subtilis and S. pyogones, respec-
ACKNOWLEDGEMENTS
Authors acknowledge chemicals, analyses and measure-
ment supports given by Green Chemistry Department
and for financial support (project no. 11090305), National
Research Centre, Dokki, Giza, Egypt and Chemistry
Department, Faculty of Science, Cairo University, Giza,
Egypt.
tively, and registered high MIC50 value >100 mg ml−1
.
But the inhibitory activities of the Fe(III) and Ni(II) com-
plexes were weak with the diameters of inhibition zones
ranging from 12 to 18 mm for Gram‐positive bacteria
and the MIC50 values were >100 mg ml−1 for both
bacteria.
REFERENCES
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2016, 45, 13135.
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How to cite this article: Zayed EM, Hindy
AMM, Mohamed GG. Molecular structure,
molecular docking, thermal, spectroscopic and
biological activity studies of bis‐Schiff base ligand
and its metal complexes. Appl Organometal Chem.
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