Novel Schiff base ligand and its metal complexes with some transition elements. Synthesis, spectroscopic, thermal analysis, antimicrobial and in vitro anticancer activity

Article abstract of DOI:10.1002/aoc.3420

A novel Schiff base ligand (H₂L) was prepared through condensation of 2,6-diaminopyridine and o-benzoylbenzoic acid in a 1:2 ratio. This Schiff base ligand was characterized using elemental and spectroscopic analyses. A new series of Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) metal complexes of H₂L were prepared and characterized using elemental analysis, spectroscopy (¹H NMR, mass, UV-visible, Fourier transform infrared, electron spin resonance), magnetic susceptibility, molar conductivity, X-ray powder diffraction and thermal analysis. The complexes are found to have trigonal bipyramidal geometry except Cr(III), Mn(II) and Fe(III) complexes which have octahedral geometry based on magnetic moment and solid reflectance measurements. The infrared spectral studies reveal that H₂L behaves as a neutral bidentate ligand and coordinates to the metal ions via the two azomethine nitrogens. ¹H NMR spectra confirm the non-involvement of the carboxylic COOH proton in complex formation. The presence of water molecules in all reported complexes is supported by thermogravimetric studies. Kinetic and thermodynamic parameters were determined using Coats-Redfern and Horowitz-Metzger equations. The synthesized ligand and its complexes were screened for antimicrobial activities against two Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), two Gram-negative bacteria (Escherichia coli and Neisseria gonorrhoeae) and one fungus (Candida albicans). Anticancer activities of the ligand and its metal complexes against human breast cancer cell line (MCF7) were investigated.

Full text of DOI:10.1002/aoc.3420

Full paper
Received: 2 November 2015
Revised: 16 November 2015
Accepted: 18 November 2015
Published online in Wiley Online Library: 5 January 2016
(wileyonlinelibrary.com) DOI 10.1002/aoc.3420
Novel Schiff base ligand and its metal
complexes with some transition elements.
Synthesis, spectroscopic, thermal analysis,
antimicrobial and in vitro anticancer activity
Walaa H. Mahmoud*, Reem G. Deghadi and Gehad G. Mohamed
A novel Schiff base ligand (H
:2 ratio. This Schiff base ligand was characterized using elemental and spectroscopic analyses. A new series of Cr(III), Mn(II),
Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) metal complexes of H L were prepared and characterized using elemental analysis,
2
L) was prepared through condensation of 2,6-diaminopyridine and o-benzoylbenzoic acid in a
1
2
1
spectroscopy ( H NMR, mass, UV–visible, Fourier transform infrared, electron spin resonance), magnetic susceptibility, molar
conductivity, X-ray powder diffraction and thermal analysis. The complexes are found to have trigonal bipyramidal geometry
except Cr(III), Mn(II) and Fe(III) complexes which have octahedral geometry based on magnetic moment and solid reflectance
measurements. The infrared spectral studies reveal that H L behaves as a neutral bidentate ligand and coordinates to the
2
1
metal ions via the two azomethine nitrogens. H NMR spectra confirm the non-involvement of the carboxylic COOH proton
in complex formation. The presence of water molecules in all reported complexes is supported by thermogravimetric studies.
Kinetic and thermodynamic parameters were determined using Coats–Redfern and Horowitz–Metzger equations. The synthe-
sized ligand and its complexes were screened for antimicrobial activities against two Gram-positive bacteria (Bacillus subtilis
and Staphylococcus aureus), two Gram-negative bacteria (Escherichia coli and Neisseria gonorrhoeae) and one fungus (Candida
albicans). Anticancer activities of the ligand and its metal complexes against human breast cancer cell line (MCF7) were
investigated. Copyright © 2016 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web site.
Keywords: Schiff base ligand; spectroscopic analyses; thermal analysis; kinetic; antimicrobial activities; breast cancer
diaminopyridine with other compounds such as 1,4-bis(2-
Introduction
[
9]
carboxyaldehydephenoxy)butane, 1,7-bis(2-formylphenyl)-1,4,7-
[
10]
[11]
For decades, coordination chemistry of Schiff base ligands has been
the subject of great interest. Schiff bases are capable of forming
coordinate bonds with many metal ions via azomethine and
phenolic groups, so they have been used for the synthesis of metal
complexes due to their easy formation and strong metal binding
trioxaheptane,
1,3-bis(2-carboxyaldehydephenoxy)propane
[
12]
and 1,2-bis(2-carboxyaldehydephenoxy)ethane.
In the work presented here, a new Schiff base ligand was
synthesized by condensation of 2,6-diaminopyridine with o-
benzoylbenzoic acid. Its coordination behaviour with various
transition metal ions was studied. The anticancer and antimicrobial
activities are also discussed.
[1]
ability.
A broad variety of Schiff base ligands and their complexes can be
utilized for metal biosite modelling, models of reaction centres of
metalloenzymes, nonlinear optical materials, catalysts for many or-
ganic reactions, effective catalysts in asymmetric synthesis and lu-
[2,3]
Experimental
minescence materials.
Furthermore these compounds exhibit
biological activity as anticancer, antifungal, antibacterial, antiviral
and antiparasitic agents in addition to other biological perfor-
mances. These compounds have also played a great role in the de-
Materials and reagents
All chemicals used were of analytical reagent grade (AR), and of
highest purity available. They included 2,6-diaminopyridine (Acros),
o-benzoylbenzoic acid (Sigma), CrCl
[
4–6]
velopment of chemistry.
3
ꢀ6H
2
O (Sigma), MnCl
2
ꢀ2H
2
O
O
The structure of 2,6-diaminopyridine has a symmetrical feature,
possessing three nitrogen lone pairs. Pyridine is one of the most
common heterocyclic compounds found in various therapeutic
2 2
(Sigma), NiCl ꢀ6H O (BDH), FeCl
3
ꢀ6H O (Prolabo), CoCl
2
2
ꢀ6H
2
[7]
agents. Pyridine-based Schiff base systems are important in
*
Correspondence to: Walaa H. Mahmoud, Chemistry Department, Faculty of
Science, Cairo University, Giza 12613, Egypt. E-mail: dr.walaa@yahoo.com
metal chelation, host–guest systems, extraction, enzyme mimics,
[
8]
antibiotics and natural products such as marine alkaloids.
Some Schiff bases can be derived from condensation of 2,6-
Chemistry Department, Faculty of Science, Cairo University, Giza 12613, Egypt
Appl. Organometal. Chem. 2016, 30, 221–230
Copyright © 2016 John Wiley & Sons, Ltd.

W. H. Mahmoud et al.
(
Aldrich), CuCl
2
ꢀ2H
2
O (Merck), CdCl
2
(Aldrich) and ZnCl
2
(Strem
Electronic spectra were recorded at room temperature as
Chemicals). Dimethylsulfoxide (DMSO), RPMI-1640 medium, so-
dium bicarbonate, isotonic trypan blue, foetal bovine serum (FBS),
penicillin, streptomycin, trypsin, acetic acid, sulforhodamine-B
solutions in ethanol with a Shimadzu 3101pc spectrophotometer.
1
6
H NMR spectra, as solutions in DMSO-d , were recorded with a
300 MHz Varian-Oxford Mercury at room temperature using
tetramethylsilane as an internal standard. Electron spin resonance
spectra were recorded with a JES-FE2XG ESR spectrophotometer
at the Microanalytical Center, Tanta University. Mass spectra
were recorded using the electron ionization technique at 70 eV
with an MS-5988 GS-MS Hewlett-Packard instrument at the
Microanalytical Center, National Center for Research, Egypt.
UV–visible spectra were obtained with a Shimadzu UVmini-1240
spectrophotometer.
(
SRB) and trichloroacetic acid were supplied by Sigma Chemical
Co., St Louis, MO, USA. Organic solvents used were ethyl alcohol
90%) and dimethylformamide (DMF). Deionized water was usually
(
used in all preparations.
Solutions
Stock solutions of metal complexes at a concentration of
1
DMF for measuring the conductivity for all metal complexes. Solu-
tions of the Schiff base ligand and its metal complexes
(
ꢁ3
× 10 M were prepared by dissolving a certain weight in
Molar magnetic susceptibility was measured on powdered
samples using the Faraday method. Diamagnetic corrections were
made using Pascal’s constant and Hg[Co(SCN) ] was used as a
4
ꢁ
4
ꢁ5
ꢁ3
1 × 10 M), except for Cu(II) and Fe(III) (5 × 10 M), were pre-
calibrant. Molar conductivities of 10 M solutions of the solid
pared by dilution of the previously prepared solutions to measure
UV–visible spectra.
complexes in ethanol were measured using a Jenway 4010 conduc-
tivity meter.
Thermogravimetric (TG) and differential thermogravimetric
(
DTG) analyses of the solid complexes were carried out from room
Anticancer activity experiments
temperature to 1000°C using a Shimadzu TG-50H thermal analyser.
Powder X-ray diffraction (XRD) analyses were carried out using a
Philips Analytical 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. Divergence and the receiv-
ing slits were 1 and 0.2, respectively.
Antimicrobial measurements were carried out at the Microana-
lytical Center, Cairo University, Egypt. Anticancer activity experi-
ments were performed at the National Cancer Institute, Cancer
Biology Department, Pharmacology Department, Cairo University.
The optical density (OD) of each well was measured spectrophoto-
metrically at 564 nm with an ELIZA microplate reader (Meter tech. R
960, USA).
ꢁ
3
A fresh stock solution (1 × 10
M) of Schiff base ligand
ꢁ
1
(
0.0012 g L ) was prepared in the appropriate volume of
ethanol (90%). DMSO was used in cryopreservation of cells.
RPMI-1640 medium was used. The medium was used for cultur-
ing and maintenance of the human tumour cell line. The me-
dium was supplied in a powder form. It was prepared as
follows: 10.4 g of medium was weighed, mixed with 2 g of so-
dium bicarbonate, completed to 1 L with distilled water and
shaken carefully until complete dissolution. The medium was
then sterilized by filtration in
a
Millipore bacterial filter
0.22 mL). The prepared medium was kept in a refrigerator
4°C) and checked at regular intervals for contamination. Before
(
(
use, the medium was warmed at 37°C in a water bath and sup-
plemented with penicillin–streptomycin and FBS. Sodium bicar-
bonate was used for the preparation of RPMI-1640 medium.
Isotonic trypan blue solution (0.05%) was prepared in normal sa-
line and was used for viability counting. FBS (10%, heat
Synthesis of Schiff base ligand
2
The symmetric Schiff base ligand (H L) was synthesized by conden-
ꢁ
1
sation of 2,6-diaminopyridine with o-benzoylbenzoic acid (1). A so-
lution of o-benzoylbenzoic acid (55 mmol, 12.4 g) dissolved in DMF
was added dropwise to 2,6-diaminopyridine (27.5 mmol, 3 g) dis-
solved in ethanol. The resulting mixture was stirred under reflux
for about 4–5 h at 100–150°C, during which a yellowish green solid
compound was separated. It was filtered, washed, recrystallized
from diethyl ether and dried in vacuum.
inactivated at 56°C for 30 min), 100 units mL penicillin and
ꢁ
1
2
mg mL streptomycin were used for the supplementation
of RPMI-1640 medium prior to use. Trypsin (0.025% w/v) was
used for the harvesting of cells. Acetic acid (1% v/v) was used
for dissolving unbound SRB dye. SRB (0.4%) dissolved in 1%
acetic acid was used as a protein dye. A stock solution of trichlo-
roacetic acid (50%) was prepared and stored. An amount of 50 μL
of the stock was added to 200 μL of RPMI-1640 medium per well
to yield a final concentration of 10% used for protein precipita-
tion. Isopropanol (100%) and ethanol (70%) were used. Tris base
(
(
10 mM; pH = 10.5) was used for SRB dye solubilization. Tris base
121.1 g) was dissolved in 1000 mL of distilled water and the pH
was adjusted using hydrochloric acid (2 M).
Instrumentation
Microanalyses of carbon, hydrogen and nitrogen were carried out
at the Microanalytical Center, Cairo University, Egypt, using a
CHNS-932 (LECO) Vario elemental analyser. Analyses of the metals
were conducted by dissolving the solid complexes in concentrated
HNO , neutralizing the diluted aqueous solutions with ammonia
3
and titrating the metal solutions with EDTA.
Fourier transform infrared (FT-IR) spectra were recorded with a
ꢁ
1
PerkinElmer 1650 spectrometer (400–4000 cm ) in KBr pellets.
2
Scheme 1. Synthesis of symmetric Schiff base ligand (H L).
wileyonlinelibrary.com/journal/aoc
Copyright © 2016 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2016, 30, 221–230

Synthesis and characterization of novel Schiff base metal complexes
Yield 90%; m.p. 130°C; yellowish green solid. Anal. Calcd for
ꢁ
1
6.01; Co, 8.01. FT-IR (cm ): hydroxyl ν(OH) 3415, azomethine
ꢁ
C
33
H
23
N
3
O
4
(%): C, 75.43; H, 4.38; N, 8.0. Found (%): C, 75.40; H,
ν(C=N) 1604, asymmetric carboxylic ν(COO )asym 1487, symmetric
carboxylic ν(COO )sym 1389, ν(H
nated water 932 and 843, ν(M-O) stretching bands of coordinated
water 561, metal–nitrogen bond ν(M-N) 473. λmax (nm): 213 and
245 π–π*, 335 n–π*, 13 050, 15 886 and 17 594 cm ; fourth band
ꢁ
1
ꢁ
4.46; N, 7.74. FT-IR (cm ): hydroxyl ν(OH) 3455, azomethine
2
O) stretching bands of coordi-
ꢁ
ν(C=N) 1596, asymmetric carboxylic ν(COO )asym 1540, symmetric
carboxylic ν(COO )sym 1380. H NMR (300 MHz, DMSO-d , δ,
ppm): 7.17–8.00 (m, 21H, Ar H), 5.68 (s, 2H, OH carboxylate).
NMR (300 MHz, DMSO-d , δ, ppm): 161.6 (C1 and C6; pyridine ring),
14.3 (C2 and C4; pyridine ring), 136.5 (C3; pyridine ring), 174.1 (C5;
ꢁ
1
6
13
ꢁ1
C
ꢁ
1
6
at 21 378 cm (charge transfer band).
1
C=N azomethine), 167.5 (C14; COOH), 136.4 (C6; Ar), 129 (C7, C11;
Ar), 128.6 (C8, C10; Ar), 130.8 (C9, Ar), 137.7 (C12; benzoic), 131.6
2
NiH L
Yield 80%; yellowish green solid, m.p. 90°C. Anal. Calcd for Ni
) (%): C, 55.85; H, 4.09; N, 5.92; Ni, 8.32. Found (%):
(C13; benzoic), 128.3 (C15; benzoic), 130.6 (C16; benzoic), 133.8
33 2 3 7
(C H29Cl N O
(C17; benzoic), 125.8 (C18; benzoic). λmax (nm): 217 and 246 π–π*,
ꢁ
1
C, 56.02; H, 3.77; N, 6.23; Ni, 8.74. FT-IR (cm ): hydroxyl ν(OH)
333 n–π*.
ꢁ
3319, azomethine ν(C=N) 1604, asymmetric carboxylic ν(COO )asym
ꢁ
1487, symmetric carboxylic ν(COO )sym 1393, ν(H
2
O) stretching
Synthesis of metal complexes
Complexes of H L with Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II)
bands of coordinated water 993 and 884, ν(M-O) stretching bands
of coordinated water 570, metal–nitrogen bond ν(M-N) 471. λmax
(nm): 213 and 245 π–π*, 335 n–π*, 13 670 cm ( B
2
ꢁ
1
3
3
and Cd(II) metal ions were prepared by reaction of 1:1 molar
mixture of hot ethanolic solution (60°C) of the appropriate metal
1
→ E), 17
ꢁ
1
3
3
ꢁ1
3
3
ꢁ1
245 cm ( B
1
→ A
2
), 21 444 cm ( B
1
→ E), 27 379 cm (ligand
chloride (0.76 mmol) and H L (0.4 g, 0.76 mmol). The resulting mix-
to metal charge transfer).
2
ture was stirred under reflux for 1 h whereupon the complexes
precipitated. They were collected by filtration and purified by wash-
ing several times with diethyl ether.
2
CuH L
Yield 81%; black solid, m.p. >300°C. Anal. Calcd for Cu
) (%): C, 55.50; H, 4.07; N, 5.89; Cu, 8.90. Found (%):
2
CrH L
33 2 3 7
(C H29Cl N O
ꢁ
1
C, 55.10; H, 3.97; N, 5.81; Cu, 8.74. FT-IR (cm ): hydroxyl ν(OH)
Yield 88%; green solid, m.p. 118°C. Anal. Calcd for Cr(C33
3 3 8
H31Cl N O )
ꢁ
3318, azomethine ν(C=N) 1578, asymmetric carboxylic ν(COO )asym
(
5
%): C, 52.42; H, 4.10; N, 5.56; Cr, 6.88. Found (%): C, 52.10; H, 4.50; N,
ꢁ
ꢁ
1
1466, symmetric carboxylic ν(COO )
bands of coordinated water 932 and 886, ν(M-O) stretching bands
of coordinated water 534, metal–nitrogen bond ν(M-N) 458. λ
sym 2
1400, ν(H O) stretching
.70; Cr, 6.53. FT-IR (cm ): hydroxyl ν(OH) 3319, azomethine ν(C=N)
ꢁ
absent, asymmetric carboxylic ν(COO )asym 1487, symmetric car-
boxylic ν(COO )sym 1410, ν(H
ꢁ
max
2
O) stretching bands of coordinated
ꢁ
1
(nm): 231 π–π*, 318 n–π*, 12 466, 15 750 and 19 945 cm ; another
water 932 and 896, ν(M-O) stretching bands of coordinated water
19, metal–nitrogen bond ν(M-N) 479. λmax (nm): 213 and 245
ꢁ
1
band at 30 452 cm (ligand to metal charge transfer band).
5
ꢁ
1
π–π*, 335 n–π*, 17 249, 20 014, 21 457 and 22 059 cm assignable
to A (F) → T (F), A (F) → T (F), A (F) → T (F) and A
4
4
4
4
4
4
4
2
ZnH L
2
g
4
2g
2g
2g
2g
1g
2g
(F) → T (P) transitions.
1g
Yield 79%; yellowish green solid, m.p. 129°C. Anal. Calcd for Zn
(C33H29Cl N O ) (%): C, 55.39; H, 4.06; N, 5.87; Zn, 9.09. Found (%):
2 3 7
C, 55.50; H, 3.80; N, 5.57; Zn, 8.91. FT-IR (cm ): hydroxyl ν(OH)
2
MnH L
ꢁ
1
Yield 87%; yellowish green solid, m.p. 90°C. Anal. Calcd for Mn
) (%): C, 54.77; H, 4.29; N, 5.81; Mn, 7.61. Found (%):
ꢁ
3416, azomethine ν(C=N) 1604, asymmetric carboxylic ν(COO )
asym
(
C
33
H
31Cl
2
N
3
O
8
ꢁ
1482, symmetric carboxylic ν(COO )sym 1390, ν(H
2
O) stretching
ꢁ
1
C, 54.33; H, 4.60; N, 5.58; Mn, 8.01. FT-IR (cm ): hydroxyl ν(OH)
3
1
bands of coordinated water 933 and 842, ν(M-O) stretching bands
of coordinated water 533, metal–nitrogen bond ν(M-N) 470. H
NMR (300 MHz, DMSO-d
ꢁ
450, azomethine ν(C=N) 1615, asymmetric carboxylic ν(COO )asym
542, symmetric carboxylic ν(COO )sym 1383, ν(H
1
ꢁ
2
O) stretching
6
13
, δ, ppm): 7.27–8.00 (m, 21H, Ar H), 5.74
bands of coordinated water 931 and 837, ν(M-O) stretching bands
of coordinated water 559, metal–nitrogen bond ν(M-N) 479. λmax
6
(s, 2H, OH carboxylate). C NMR (300 MHz, DMSO-d , δ, ppm):
161.5 (C1 and C6; pyridine ring), 114.3 (C2 and C4; pyridine ring),
(
8
nm): 217 and 243 π–π*, 335 n–π*, 15 560, 21 478 and 27
136.6 (C3; pyridine ring), 174.2 (C5; C=N azomethine), 167.4 (C14;
ꢁ
1
4
6
4
6
4
76 cm assignable to T1g → A1g, T2g(G) → A1g and T1g
COOH), 136.3 (C6; Ar), 129.1 (C7, C11; Ar), 128.5 (C8, C10; Ar), 130.7
C9; Ar), 137.8 (C12; benzoic), 131.5 (C13; benzoic), 128.2 (C15;
6
(D) → A transitions.
1g
(
benzoic), 130.4 (C16; benzoic), 133.7 (C17; benzoic), 125.7 (C18;
2
FeH L
benzoic). λmax (nm): 217and 245 π–π*, 332 n–π*.
Yield 85%; black solid, m.p. 121°C. Anal. Calcd for Fe(C33
3 3 8
H31Cl N O )
(
5
1
%): C, 52.14; H, 4.08; N, 5.53; Fe, 7.37. Found (%): C, 51.80; H, 3.98; N,
ꢁ
1
2
CdH L
.84; Fe, 7.69. FT-IR (cm ): hydroxyl ν(OH) 3348, azomethine ν(C=N)
ꢁ
604, asymmetric carboxylic ν(COO )asym 1486, symmetric carbox-
Yield 85%; yellowish green solid, m.p. 140°C. Anal. Calcd for Cd
(C H Cl N O ) (%): C, 51.97; H, 3.81; N, 5.51; Cd, 14.70. Found
ꢁ
ylic ν(COO )sym 1403, ν(H
9
2
O) stretching bands of coordinated water
33
29
2 3 7
ꢁ
1
32 and 875, ν(M-O) stretching bands of coordinated water 583,
(%): C, 52.21; H, 4.13; N, 5.55; Cd, 14.57. FT-IR (cm ): hydroxyl
metal–nitrogen bond ν(M-N) 488. λmax (nm): 227 π–π*, 317 n–π*,
ν(OH) 3439, azomethine ν(C=N) 1604, asymmetric carboxylic
6
ꢁ1
6
5
ꢁ
ꢁ
sym
2
1 357 ( A1g → T2g) (G), 17 135 and 12 970 cm ( A1g → T1g),
ν(COO )
asym
1545, symmetric carboxylic ν(COO )
2
1384, ν(H O)
ꢁ
1
24 805 cm (ligand to metal charge transfer).
stretching bands of coordinated water 931 and 844, ν(M-O)
stretching bands of coordinated water 561, metal–nitrogen bond
2
CoH L
1
6
ν(M-N) 489. H NMR (300 MHz, DMSO-d , δ, ppm): 7.17–8.00 (m,
Yield 89%; blue solid, m.p. 120°C. Anal. Calcd for Co(C33
H
29Cl
2
N
3
O
7
)
21H, Ar H), 5.70 (s, 2H, OH carboxylate). λmax (nm): 240 π–π*,
334 n–π*.
(%): C, 55.85; H, 4.09; N, 5.92; Co, 8.32. Found (%): C, 55.84; H, 4.26; N,
Appl. Organometal. Chem. 2016, 30, 221–230
Copyright © 2016 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

W. H. Mahmoud et al.
Spectrophotometric studies
Results and discussion
ꢁ
4
The absorption spectra were recorded for 1 × 10 M solutions of
the Schiff base ligand and its metal complexes in DMF, except for
Characterization of Schiff base ligand
The symmetric Schiff base ligand was prepared by stirring an ap-
propriate amount of o-benzoylbenzoic acid with the corresponding
Cu(II) and Fe(III) complexes that had
a
concentration of
ꢁ
5
5
× 10 M. The spectra were scanned within the wavelength range
2,6-diaminopyridine in ethanol. The new Schiff base ligand formed
from 200 to 700 nm.
was characterized with respect to its composition using elemental
and spectral analyses.
Pharmacology
Antimicrobial activity
Elemental Analysis
A filter paper disc (5 mm) was transferred into each of 250 mL flasks
The synthesized Schiff base ligand, namely 2,2′-((1Z,1′Z)-(pyridine-
2,6-diylbis(azanylylidene))-bis(phenylmethanylylidene))dibenzoic
acid, is a yellowish green solid and stable at room temperature. It is
soluble in ethanol, DMF and DMSO. The results obtained are in
good agreement with those calculated for the suggested formula.
The structure of the symmetric Schiff base ligand under study is
shown in Fig. 1.
ꢁ
1
containing 20 mL ofworking volume oftest solution (100 mg mL ).
All flasks were autoclaved for 20 min at 121°C. LB agar media
surfaces were inoculated with four investigated bacteria
(Gram-positive bacteria: Bacillus subtilis and Staphylococcus aureus;
Gram-negative bacteria: Neisseria gonorrhoeae and Escherichia coli)
and one strain of fungi (Candida albicans) using the diffusion agar
[13–15]
technique.
They were then transferred to saturated discs with
Mass Spectrum
a test solution in the centre of Petri dishes (agar plates). All the com-
pounds were placed at four equidistant places at a distance of 2 cm
from the centre of the inoculated Petri dishes. DMSO served as con-
trol. Finally, all these Petri dishes were incubated at 25°C for 48 h
where clear or inhibition zones were detected around each disc.
Control flask of the experiment was designed to perform the exper-
iment under the same condition described previously for each
microorganism but with DMF solution only and by subtracting
the diameter of the inhibition zone resulting from DMF from that
obtained in each case, so antibacterial activity could be
The mass spectrum of the Schiff base ligand was recorded and the
obtained molecular ion (m/z) peaks confirm its proposed formula
and geometry. The ligand shows a peak at m/z = 526 amu corre-
+
sponding to the [C33H N O
23 3 4
] ion. It also showed a series of peaks
at m/z = 499, 404, 372, 316, 233, 196, 105 and 56 corresponding to
various fragments. The intensity of these peaks gives an idea of the
stabilities of fragments.
FT-IR Spectrum
[16,17]
calculated.
Amikacin and ketokonazole were used as reference
The FT-IR spectrum of 2,6-diaminopyridine shows a pair of medium
compounds for antibacterial and antifungal activities, respectively.
All experiments were performed as triplicate and data plotted were
the mean values.
ꢁ
1
intensity bands present at 3200–3400 cm which correspond to
ν(NH ) stretching vibration. These bands are absent in the spectrum
of the Schiff base ligand. Also, no strong absorption band is
2
ꢁ
1
Anticancer activity
observed at 1735 cm indicating the absence of ν(C=O) group of
o-benzoylbenzoic acid. This indicates that the condensation of car-
bonyl groups of o-benzoylbenzoic acid and amino groups of 2,6-
Potential cytotoxicity of the compounds was tested using
[
16,18]
the method of Skehan and Storeng.
Cells were plated in a
[
19,20]
diaminopyridine has taken place.
A new band for the
96-multiwell plate (104 cells per well) for 24 h before treatment with
azomethine ν(C=N) stretching vibration was recorded due to this
the compounds to allow attachment of cells to the wall of the plate.
Various concentrations of the compounds under investigation
ꢁ
1 [21,22]
condensation reaction at 1596 cm
.
ꢁ
1
(
0, 5, 12.5, 25, 50 and 100 μg mL ) were added and cell monolayer
1
H NMR Spectrum
triplicate wells were prepared for each individual dose. The mono-
layer cells were incubated with the compounds for 48 h at 37°C and
1
In the H NMR spectrum of H
2
L, the aromatic ring protons are ob-
[
23]
served as a multiplet, in the range 7.17–8.00 ppm.
.68 ppm is attributed to proton of the carboxylic acid group.
A peak at
in 5% CO atmosphere. After 48 h, cells were fixed, washed and
2
[24]
5
stained with SRB. Excess stain was washed with acetic acid and at-
tached stain was recovered with Tris–EDTA buffer. The OD of each
well was measured spectrophotometrically at 564 nm with an ELIZA
microplate reader and the mean background absorbance was auto-
matically subtracted, and mean values of each drug concentration
were calculated. The relation between surviving fraction and drug
concentration was plotted to get the survival curve of breast
tumour cell line for each compound.
This small shift can be attributed to the intramolecular hydrogen
bonding with the solvent.
Compositions and structures of metal complexes
Elemental analyses
Metal complexes were prepared by the reaction of metal ions with
Schiff base ligand at a metal-to-ligand ratio of 1:1. The Schiff base
ligand and its metal complexes are stable at room temperature.
The percentage of cell survival was calculated as follows:
OD ðtreated cellsÞ
Survival fraction ¼
OD ðcontrol cellsÞ
The IC50 values (the concentrations of the Schiff base ligand or
its complexes required to produce 50% inhibition of cell growth)
were calculated. The experiment was repeated three times for
MCF7 cell line.
2
Figure 1. Structure of macrocyclic Schiff base ligand (H L).
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Appl. Organometal. Chem. 2016, 30, 221–230

Synthesis and characterization of novel Schiff base metal complexes
The ligand and its metal complexes are commonly soluble in DMF
and DMSO. The analytical data are compatible with the proposed
stoichiometry of the complexes.
Mass spectral studies
[
25]
Mass spectroscopy has been increasingly used as a powerful struc-
tural characterization technique in coordination chemistry. The
spectra of the Mn(II) and Ni(II) complexes show molecular ion peaks
at m/z = 701.22 and 705.71 amu, respectively, which are equivalent
to their molecular weights of 705 and 709 amu, respectively. The
molecular ion peaks are in good agreement with the suggested
molecular formulae indicated from elemental and TG analyses.
Molar conductance measurements
The molar conductance values of the complexes were measured at
room temperature. These values show that Cu(II), Zn(II) and Cd(II)
complexes have no conductance and they are considered as non-
electrolytes. Cr(III), Mn(II), Co(II) and Ni(II) complexes have molar
UV–visible absorption studies
ꢁ
1
ꢁ1
2
conductivity values of 77, 75, 60 and 61 Ω mol cm , respec-
tively. These data suggest that these complexes are ionic in nature
and they are 1:1 electrolytes. The Fe(III) complex has a molar con-
The electronic spectra of the Schiff base ligand and its complexes
were recorded in DMF solvent within the wavelength range
ꢁ
1
ꢁ1
2
200–700 nm. In the UV–visible spectrum of the Schiff base ligand,
ductivity value of 111 Ω mol cm , which suggests that this
[
26]
two absorption bands are observed at 217 and 246 nm which
may be assigned to π–π* transitions of the aromatic rings.
complex is ionic in nature and it is a 1:2 electrolyte.
[38,39]
Also,
the absorption band at 333 nm may be assigned to n–π* transition
of the azomethine or carboxylate groups. Due to the coordination
of azomethine nitrogen to the metal ions, this band is seen in the
absorption spectra of all complexes at 317–335 nm. Also, the band
due to π–π* transition is observed at 213–245 nm in the spectra of
FT-IR spectral studies and mode of bonding
The FT-IR spectral data for the Schiff base ligand and its complexes
are listed in Table S1 of the supporting information. The FT-IR spec-
tra of the complexes were compared with that of the free ligand in
order to determine the involvement of coordination sites in chela-
tion. The FT-IR spectra of the metal complexes exhibit a broad band
[
40]
all metal complexes.
Electronic spectra and magnetic moment measurements
ꢁ
1
around 3318–3450 cm which is assigned to ν(OH) of coordinated
water molecules associated with the complex, while it appears in
The Cr(III) chelate which is six-coordinated with octahedral symme-
try shows four spin-allowed bands at 17 249, 20 014, 21 457 and 22
ꢁ
1
the ligand spectrum at 3455 cm . This band may be assigned to
[
27,28]
ꢁ1
4
4
4
the presence of hydrogen bonded O H.
The FT-IR spectrum of the ligand shows a characteristic absorp-
059 cm . These bands may be assigned to A2g(F) → T2g(F), A2g
4
4
4
4
4
(F) → T2g(F), A2g(F) → T1g(F) and A2g(F) → T1g(P) transitions in-
dicating the octahedral geometry of the complex. The magnetic
moment value of 3.82 BM indicates the presence of Cr(III) complex
ꢁ
1
tion band at 1596 cm corresponding to ν(C=N) of azomethine
group. For all the metal complexes, the ν(C=N) band of the
ꢁ
1
[26]
azomethine is shifted to 1578–1615 cm , while it is absent in case
in an octahedral structure.
of the Cr(III) complex, suggesting coordination of azomethine nitro-
The diffuse reflectance spectrum of the Mn(II) complex shows
three bands at 15 560, 21 478 and 27 876 cm assignable to
[29]
ꢁ1
gen to metal ions.
The νasym(COO ) and νsym(COO ) stretching vibrations are
observed at 1540 and 1380 cm in the FT-IR spectrum of H
ꢁ
ꢁ
4
6
4
6
4
6
1g
T → A , T2g(G) → A1g and T1g(D) → A1g transitions,
1g
[25]
ꢁ
1
[30]
2
L.
respectively. The magnetic moment value of 5.44 BM indicates
the presence of Mn(II) complex in an octahedral structure.
The diffuse reflectance spectrum of the Fe(III) chelate exhibits a
These bands are present in the range 1466–1545 and
ꢁ
1
[31]
1
383–1410 cm in the spectra of the metal complexes.
This
ꢁ
1
6
shift can be attributed to intramolecular hydrogen bonding. The co-
ordinating water in the complexes is characterized by the appear-
band at 21 357 cm , which may be assigned to the A1g → T2g
[
41]
(G) transition of octahedral geometry of the complex.
The
ꢁ
1 [32]
6
5
ance of two bands at 931–993 and 837–896 cm
.
A1g → T1g transition appears to be split into two bands at 17
ꢁ
1
The coordination of the azomethine nitrogen is supported by the
135 and 12 970 cm . The observed magnetic moment of the Fe
(III) complex is 5.38 BM. Thus, the complex formed has octahedral
geometry involving d sp hybridization in Fe(III) ion. The spec-
trum also shows a band at 24 805 cm which may attributed to
ligand to metal charge transfer.
ꢁ
1
appearance of a new metal–ligand weak band at 458–489 cm
[33,34]
2
3
[42]
due to ν(M-N).
Additional support for the formation of the complexes is pro-
vided by presence of weak-intensity bands at 519–583 cm which
ꢁ
1
ꢁ
1
are attributed to the formation of M-O of coordinated water in the
complexes.
The Cu(II) complex shows broad bands at 12 466, 15 750 and 19
945 cm . These bands are generally completely consistent with a
[22]
ꢁ1
[
43–45]
five-coordinate geometry for Cu(II) complexes.
The spectrum
ꢁ
1
1
also shows a band at 30 452 cm which may be assigned to ligand
to Cu charge transfer band. The magnetic moment value of 1.78 BM
is indicative of a trigonal bipyramidal structure.
The diffuse reflectance spectrum of the Co(II) complex shows
that the complex has five-coordinated geometry,
bands are observed at 13 050, 15 886 and 17 594 cm . The fourth
band at 21 378 cm is attributed to the charge transfer band. The
value of the magnetic moment of the complex is 5.0 BM, which is
low compared with those observed for tetrahedral or octahedral
complexes, and which supports five-coordinate geometry.
The reflectance spectrum of the Ni(II) complex shows three
bands at 13 670, 17 245 and 21 444 cm . The positions of these
spectral bands are completely consistent with those predicted for
a five-coordinate Ni(II) complex. Those bands can be assigned,
H NMR spectral studies
[
43,44,46,47]
Proof of the type of bonding type of H L with the metal ions was
2
1
also confirmed by recording their H NMR spectra in DMSO-d
6
[
33–35]
[47]
and in the deutrated solvent.
In the spectrum of H L a singlet
where three
2
ꢁ
1
peak appears at 5.68 ppm (s, 2H, COOH carboxylic). This peak is
found in the spectra of Zn(II) and Cd(II) complexes at 5.74 and
ꢁ
1
5
.70 ppm, respectively, indicating that the carboxylic groups play
[
36]
no important part in coordination. This small shift can be attrib-
uted to the intramolecular hydrogen bonding with the solvent.
[
47]
1
The H NMR spectrum of the ligand reveals signals at
ꢁ
1
7.17–8.00 ppm (m, 21H, Ar-H), while for Zn(II) and Cd(II) complexes
the signals are at 7.27–8.00 and 7.17–8.01 ppm (m, 21H, Ar-H), re-
[
37]
[48]
spectively, which can assigned to the aromatic protons.
Appl. Organometal. Chem. 2016, 30, 221–230
Copyright © 2016 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

W. H. Mahmoud et al.
[
48]
3
3
3
3
3
3
respectively, to B
1
→ E, B
1
→ A
2
and B
1
→ E transitions as-
corresponds to the loss of C
a peak at 325°C. The final two steps occur within the range
355–1000°C with estimated mass loss of 50.95% (calculated mass
loss = 50.86%) which corresponds to the loss of C18
2
H
7
O
2
fragment. The DTG curve gives
ꢁ
1
suming the effective symmetry to be C4v. The band at 27 379 cm
[
47]
may be assigned to ligand to metal charge transfer band. The
low magnetic moment value (3.21 BM) may support the five-
coordinate geometry.
The Zn(II) and Cd(II) complexes are diamagnetic. According to
their empirical formulae, the Zn(II) and Cd(II) complexes are sug-
9 3
H N fragment.
The TG curve for the [Cr(H L)(H O) Cl O complex shows
2
2
2
2
]Clꢀ2H
2
three weight loss events. The first step of decomposition occurs
within the range 30–140°C, with a maximum at 124°C and corre-
sponds to the loss of two water molecules of hydration with esti-
mated mass loss of 5.59% (calculated mass loss = 4.77%). The
second step of decomposition occurs in the range 140–410°C with
[
26]
gested to have trigonal bipyramidal geometry.
Powder XRD studies
Powder diffraction is a technique that uses X-ray, neutron or elec-
tron diffraction on powder or microcrystalline samples for structural
characterization of materials. It throws light only on the fact that
each solid represents a definite compound of a definite structure
which is not contaminated with starting materials. The identifica-
tion of the complexes was performed using a known standard
maximum temperature at 281°C and corresponds to the loss of two
3
coordinated water molecules, /
Cl
gas and C10H10 molecule with
2
2
estimated mass loss of 35.76% (calculated mass loss = 36.07%).
The final three steps occur within the range 410–1000°C with three
maxima at 481, 752 and 894°C which correspond to loss of
C
23
H
N
O
fragment with estimated mass loss of 49.97% (calcu-
13
3
3
[26]
method. The results suggest that the synthesized Fe(III), Co(II),
Ni(II), Cu(II), Zn(II) and Cd(II) complexes are amorphous. In contrast,
lated mass loss = 50.17%) leaving behind ½Cr as the product
O
2 3
of decomposition. The overall weight loss amounts to 91.32%
(calculated mass loss = 91.01%).
2
the XRD spectra of H L and its Cr(III) and Mn(II) complexes indicate a
[49,50]
crystalline character.
The average crystallite size (ξ) can be calculated from the XRD
The [Mn(H
2
L)(H
2
O)
3
Cl]ClꢀH
2
O complex loses water upon heating
in the first step of decomposition within the range 30–120°C with
maximum at 90°C with estimated mass loss of 2.81% (calculated
mass loss = 2.49%). The second step can be attributed to the loss
[
51,52]
pattern according to the Debye–Scherrer equation:
2
of 3H O and 2CN gas within the range 120–310°C with maximum
at 242°C with estimated mass loss of 14.90% (calculated mass
loss = 14.66%). The last two steps are attributed to loss of
Kλ
cosθ
=2
ξ ¼ β
(1)
1
C
20
H
23
N
3
O
3
within the range 310–1000°C with two maxima at
The equation uses the reference peak width at angle θ, where λ is
the wavelength of the X-rays (1.542475 Å), K is a constant taken as
443 and 792°C with estimated mass loss of 54.34% (calculated mass
loss = 54.77%), leaving MnO contaminated with carbon as residue
of decomposition. The overall weight loss amounts to 72.05%
[
51]
0.95 for organic compounds and β1/2 is the width at half maxi-
mum of the reference diffraction peak measured in radians. The dis-
location density, δ, is the number of dislocation lines per unit area of
the crystal. The value of δ is related to the average particle diameter
(calculated 71.92%).
The [Fe(H L)(H O)
2
2
3 2 2
Cl]Cl ꢀH O complex is thermally decomposed
in six steps within the range 30–1000°C. The first decomposition
step with an estimated mass loss of 3.59% (calculated 2.37%) occurs
within the range 30–140°C with maximum at 63°C. This step may be
attributed to the liberation of the hydrated water molecule. The
second and third decomposition steps are observed within the
range 140–440°C with two maxima at 250 and 432°C. The estimated
mass loss of 16.98% (calculated 17.31%) is reasonably accounted
for by the removal of 3H O, ½Cl and C H molecules in two steps.
[53,54]
(ξ) by the relation
1
δ ¼
(2)
2
ξ
The value of ξ is calculated and found to be 0.146 nm and the
ꢁ
2
value of δ is 46.91 nm for both H L and the Mn(II) complex, while
2
2
2
3 6
ꢁ
2
the value of ξ is 0.1455 nm and value of δ is 47.24 nm for the Cr
III) complex.
The last three steps with estimated mass loss of 45.24% (calculated
46.08%) occur within the range 440–1000°C with three maxima at
(
5
94, 912 and 984°C and correspond to loss of Cl2 gas and
Thermal analysis studies (TG and DTG)
C H N O fragment leaving ½Fe O contaminated with carbon
15
15
3
2.5
2 3
The thermal properties of ligand and its complexes were character-
ized on the basis of TG and DTG methods within a temperature
range from room temperature to 1000°C. These methods are used
to get information about the thermal stability of these new com-
plexes, to decide whether the water molecules (if present) are in-
side or outside the inner coordination sphere of the central metal
ion and to suggest a general scheme for thermal decomposition
of these chelates. The temperature intervals and the percentage
of loss of masses are listed in Table S2 of the supporting
information.
as residue. The overall weight loss amounts to 65.81% (calculated
65.76%).
The DTG curve of [Co(H L)(H O) Cl]ClꢀH O shows a peak at 137°C
2
2
2
2
in the range 50–160°C which is due to weight loss of 3.77% (calcu-
lated weight loss = 2.54%) corresponding to the elimination of hy-
drated water molecule. The second and third steps of the thermal
decomposition, which occur in the range 160–525°C with two max-
ima at 233 and 439°C, are assigned to the loss of Cl gas, 2H O and
2
2
C H O fragment (found 26.68%; calculated 27.50%). The fourth
5
12
and fifth steps of the thermal decomposition, which occur in the
range 525–940°C, are assigned to the loss of C28 (found
The Schiff base ligand with molecular formula [C33
23 3 4
H N O ] is
H N O
11 3 2
thermally decomposed in five successive decomposition steps.
The first and second steps with estimated mass loss of 36.54%
58.08%; calculated 59.38%). At the end of the thermogram, the
metal oxide CoO is the residue, with total weight loss amounting
to 88.53% (calculated = 89.42%).
(calculated mass loss = 37.14%) within the temperature range
3
0–290°C may be attributed to the loss of C13 molecule. The
H
7
O
2
The [Ni(H
2
L)(H
2
O)
2
Cl]ClꢀH
2
O complex gives a decomposition pat-
DTG curve gives maximum peak temperatures at 66 and 256°C.
The third step occurs within the range 290–355°C with an esti-
mated mass loss of 12.11% (calculated mass loss = 12.00%) which
tern starting at 30°C and finishing at 785°C with three stages. The
first stage is one step within the range 30–105°C with maximum
at 85°C, representing the loss of H O (hydrated) and ½Cl with a
2 2
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Synthesis and characterization of novel Schiff base metal complexes
mass loss of 6.21% (calculated 7.55%). The second stage is also one
ꢂ
ꢃ
ꢀ
ꢁ
ꢂ
ꢁ lnð1 ꢁ αÞ
ꢁE
AR
ln
¼
þ ln
2
ꢂ
step representing the loss of ½Cl
3.21% (calculated 13.75%) within the range 105–235°C with max-
imum at 140°C. The final stage is four steps representing the loss of
with a mass loss of 69.28% (calculated 68.12%) within
2 2
, 2H O and CN with a mass loss of
T
RT
φE
1
If a plot of the left-hand side against 1/T is drawn, E* (the energy
of activation in kJ mol ) is calculated from the slope and A in (s
from the intercept. The entropy of activation ΔS* (in J K mol ) is
calculated using the equation
ꢁ
1
ꢁ1
ꢁ1
32 23 2 3
C H N O
)
ꢁ
1
the range 235–785°C. At the end of the thermogram, the metal ox-
ide NiO is the residue, which is in good agreement with the calcu-
lated metal content obtained and the results of elemental analyses.
The complex [Cu(H L)(H O)Cl ]ꢀ2H O is thermally decomposed
ꢀ
ꢁ
2
2
2
2
Ah
ꢂ
ΔS þ R ln
in five successive decomposition steps. The first estimated mass
loss of 4.26% (calculated mass loss = 5.05%) within the range
KBTs
2
5–190°C may be attributed to the loss of two hydrated water
molecules. The DTG curve gives an exothermic peak at 79°C
the maximum peak temperature). The second step occurs within
where K is the Boltzmann constant, h is the Planck constant and
Ts is the DTG peak temperature.
B
(
the range 190–380°C with an estimated mass loss of 40.12% (calcu-
Horowitz–Metzger equation
lated mass loss = 39.38%) which corresponds to the loss of H O, Cl2
2
The Horowitz–Metzger equation is illustrative of the approximation
methods. Those authors derived the relation
and C H N fragment. The DTG curve gives an exothermic peak at
1
3 8 2
2
67°C. The final three steps occur within the temperature range
o
380-950 C with the estimated mass loss 44.68% (calculated mass
"
#
1
ꢁn
ꢂ
ð1 ꢁ αÞ
E θ
loss = 44.43%) which corresponds to the loss of C H NO frag-
20
15
3
log 1 ꢁ
¼
for n≠ 1
2
ment. The DTG curve gives three exothermic peaks at 426, 492
and 742°C, leaving metal oxide CuO as residue. Total estimated
mass loss is 89.06% (calculated mass loss = 88.86%).
1 ꢁ n
2:303RTs
When n = 1, the left-hand side would be log[ꢁlog(1 ꢁ α)]. For a
first-order kinetic process the Horowitz–Metzger equation may be
written in the form
The [Zn(H
steps. The first and second steps in the range 30–330°C with two
maxima at 81 and 238°C represent losses of 3H O and CN molecule
2 2 2 2
L)(H O)Cl ]ꢀ2H O chelate exhibits four decomposition
2
ꢂ
ꢀ
ꢁꢃ
with estimated mass loss of 10.79% (calculated 11.19%).The third
step at 330–510°C with maximum at 433°C corresponds to loss of
ꢂ
wα
wγ
E θ
log log
¼
ꢁ log2:303
2
2:303RTs
Cl
.93%). The fourth step within the range 510–910°C with maximum
at 674°C corresponds to elimination of C30 with a mass loss
3.98% (calculated 64.20%), leaving ZnO and 2C as residues. The
overall weight loss amounts to 85.56% (calculated 85.32%).
The [Cd(H L)(H O)Cl O complex decomposes within the
2
molecule with estimated mass loss of 10.79% (calculated
9
where θ =Tꢁ T
s
, w
γ
= w
α
ꢁ w, w
α
is mass loss at the completion of
23 2 3
H N O
α γ
the reaction and w is mass loss up to time t. A plot of log[log(w /w )]
6
versus θ is found to be linear, from the slope of which E* is calculated.
The pre-exponential factor, A, is calculated from the equation
2
2
2
]ꢀ2H
2
range 75–1000°C with four steps as follows. The first step is within
the range 75–205°C with maximum at 93°C, representing the loss
ꢂ
E
A
¼
RT2s
ꢂ
φ expðꢁE =RTsÞ
2
H
2
O with a found mass loss of 4.03% (calculated 4.72%). The sec-
ond step represents the loss of H O, Cl and C with a mass loss
of 19.62% (calculated 19.03%) within the range 205–295°C. The
other two steps represent elimination of C29 with a mass
2
2
4 8
H
The entropy of activation, ΔS*, enthalpy of activation, ΔH* and
Gibbs free energy, ΔG*, are calculated using the following equa-
tions:
15 3 3
H N O
loss of 60.84% (calculated 59.45%) within the range 295–1000°C.
At the end of the thermogram, the metal oxide CdO is the residue.
Total estimated mass loss is 84.49% (calculated 83.20%).
ꢂ
ꢂ
ΔH ¼ E ꢁ RT
ꢂ
ꢂ
ꢂ
ΔG ¼ ΔH ꢁ TΔS
Kinetics
The activation energies of decomposition are found to be in the
range 12.50–130.8 kJ mol . The greater positive values of E* indi-
The kinetic thermodynamic parameters such as energy of activa-
tion (E*), enthalpy (ΔH*), entropy (ΔS*) and free energy change
ꢁ1
cate that these processes involve translational, vibrational, rota-
tional states and changes in mechanical potential energy for the
complexes. The high values of the activation energies show the
thermal stability of the complexes. The entropy of activation is
found to have negative values for all metal complexes which indi-
cate that decomposition reactions proceed with a lower rate than
normal ones. Also, according to the kinetic data obtained, all of
the complexes have negative entropy, which indicates that acti-
(
Gibbs free energy) of decomposition (ΔG*) are evaluated graphi-
[45] [55]
cally by employing the Coats–Redfern and Horowitz–Metzger
equations. The data are summarized in Table S3 of the supporting
information.
Coats–Redfern equation
The Coats–Redfern equation, which is a typical integral method,
can be represented as:
[56–58]
vated complexes have more ordered systems than reactants.
ꢀ
ꢂꢁ
α
∫0
dα
ð1 ꢁ αÞ
A T2
ꢁE
¼
∫
exp
dt
Structural interpretation
n
T1
α
RT
On the basis of the various physicochemical and spectral data pre-
sented and discussed above, the structures of the Cr(III), Mn(II), Fe
(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes are shown in Fig. 2.
1
For convenience of integration, the lower limit T is usually taken
as zero. This equation on integration gives
Appl. Organometal. Chem. 2016, 30, 221–230
Copyright © 2016 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

W. H. Mahmoud et al.
2
Figure 3. (a) Biological activity of Schiff base ligand (H L) and its metal
complexes and (b) variation of biological activity with atomic weight of
metal ion.
(
(
for E. coli); Zn(II) > Cd(II) > Cu(II) > Cr(III) = Ni(II) > Fe(III) = Co
[
16]
2
II) > H L > Mn(II) > amikacin (for N. gonorrhoeae).
It is obvious that the biological activities of the metal complexes
are more than that of the parent Schiff base ligand which means
that the complexes can have better action than the parent ligand.
The biological activities of the Schiff base ligand and its complexes
are higher than that of amikacin standard.
Figure 2. Structures of metal complexes.
By comparing the results of antifungal activity of the Schiff base
ligand and its complexes with the standard, it is obvious that they
have no activity against C. albicans strain, except Co(II), Ni(II) and
Cd(II) complexes which have high activity. The variation in the activ-
ity of the metal complexes against different organisms depends on
the impermeability of the microorganism cells or on differences in
Antimicrobial activity
The principal aim of any antimicrobial compound is to inhibit the
causal microbes without any side effects on patients.
[
59]
The Schiff base ligand and its metal complexes were tested
against four different bacteria species: S. aureus, B. subtilis, E. coli
and N. gonorrhoeae. Also, they were screened against C. albicans
[
63]
ribosome of microbial cells.
The size of the inhibition zone depends upon the culture me-
dium, incubation conditions, rate of diffusion and concentration
of antibacterial agent. The activities of all the tested complexes
may be explained on the basis of chelation theory where chelation
reduces the polarity of the metal atom mainly because of partial
sharing of its positive charge with the donor groups and possible
p-electron delocalization within the whole chelate ring. Also, chela-
tion increases the lipophilic nature of the central atom which subse-
quently favours its permeation through the lipid layer of cell
[60]
fungal strain.
complexes were compared with those of the standards amikacin
The biological activities of the ligand and its
[
26]
as antibacterial agent and ketokonazole as antifungal agent.
The experimental data are presented in Table S4 of the
supporting information and compared with standards as shown
in Fig. 3. These data show that the metal complexes are more
potent in inhibiting the growth of microorganisms than the Schiff
base ligand, except the Fe(III) complex which has no activity against
B. subtilis and E. coli and the Cd(II) complex which also has no
activity against S. aureus. It is determined that the synthesized Mn
[
64]
membranes.
The importance of this study lies in the fact that these complexes
could be applied in the treatment of some common diseases
caused by E. coli, e.g. septicaemia, gastroenteritis, urinary tract in-
(II) complex may have the same antibacterial activity as that of
[
61,62]
the parent Schiff base ligand but higher against S. aureus.
The bacterial growth inhibitory capacity of the ligand and its
[65]
fections and hospital-acquired infections.
complexes follows the order Zn(II) = Cd(II) > Cu(II) > Cr(III) > Co
(
(
(
(
II) = Ni(II) > H
II) Mn(II)
II) > H L > amikacin > Cd(II) (for S. aureus); Zn(II) > Co(II) > Cd
II) > Cu(II) > Cr(III) = Ni(II) > Mn(II) > H L > amikacin > Fe(III)
2
L = Mn(II) > amikacin > Fe(III) (for B. subtilis); Co
Anticancer activity
>
=
Cu(II) Zn(II) Cr(III) Fe(III) Ni
>
>
=
>
2
The in vitro cytotoxicity of H
cell line MCF-7 was studied. The results of the IC50 values of the
2
L and its metal complexes on human
2
wileyonlinelibrary.com/journal/aoc
Copyright © 2016 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2016, 30, 221–230

Synthesis and characterization of novel Schiff base metal complexes
(
(
M = Cu(II), Zn(II) and Cd(II)) and [M(H
III)). XRD spectra show that the Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and
2
L)(H
2
O)
2
Cl
2
]Clꢀ2H
2
O (M = Cr
Cd(II) complexes are amorphous. On the other hand, the ligand
and its Cr(III) and Mn(II) complexes have a crystalline character.
The ligand and metal complexes are found to possess appreciable
antibacterial activity, except the Fe(III) complex which has no
activity against B. subtilis and E. coli and the Cd(II) complex which
also has no activity against S. aureus. The Co(II), Ni(II) and Cd(II)
complexes have high antifungal activity. In addition, the cytotoxic-
ity of the Cu(II) complex indicates a higher anticancer activity than
ꢁ
1
the others with IC50 of 19.7 μg mL , which might become a good
anticancer agent in clinical trials or biological agents.
2
Figure 4. IC50 values of Schiff base ligand (H L) and its metal complexes.
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