Crystal structure, spectroscopic studies, DFT calculations, cyclic voltammetry and biological activity of a copper (II) Schiff base complex

Article abstract of DOI:10.1016/j.molstruc.2019.127313

Herein we describe the chemical synthesis of a novel tetradentate Schiff base ligand (H₂L), bridged with a pyridine, and its corresponding mononuclear copper complex (Cu(II)L). H₂L, derived from the condensation of 2,3-diaminopyridin

Full text of DOI:10.1016/j.molstruc.2019.127313

Journal Pre-proof
Crystal structure, Spectroscopic Studies, DFT Calculations, Cyclic Voltammetry
and Biological Activity of a Copper (II) Schiff Base Complex
Wafa BENABID, Kamel OUARI, Sabrina BENDIA, Riadh BOURZAMI, Mustapha
AIT-ALI
PII:
S0022-2860(19)31422-X
DOI:
https://doi.org/10.1016/j.molstruc.2019.127313
MOLSTR 127313
Reference:
To appear in:
Journal of Molecular Structure
Received Date:
Accepted Date:
15 May 2019
28 October 2019
Please cite this article as: Wafa BENABID, Kamel OUARI, Sabrina BENDIA, Riadh BOURZAMI,
Mustapha AIT-ALI, Crystal structure, Spectroscopic Studies, DFT Calculations, Cyclic Voltammetry
and Biological Activity of a Copper (II) Schiff Base Complex, Journal of Molecular Structure (2019),
https://doi.org/10.1016/j.molstruc.2019.127313
This is a PDF file of an article that has undergone enhancements after acceptance, such as the
addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive
version of record. This version will undergo additional copyediting, typesetting and review before it
is published in its final form, but we are providing this version to give early visibility of the article.
Please note that, during the production process, errors may be discovered which could affect the
content, and all legal disclaimers that apply to the journal pertain.
© 2019 Published by Elsevier.

Journal Pre-proof
Crystal structure, Spectroscopic Studies, DFT Calculations, Cyclic Voltammetry
and Biological Activity of a Copper (II) Schiff Base Complex
Wafa BENABIDa, Kamel OUARI*a, Sabrina BENDIAa, Riadh BOURZAMIb and Mustapha
AIT-ALIc
a
Laboratoire d’Electrochimie, d’Ingénierie Moléculaire et de Catalyse Rédox (LEIMCR), Faculté de
Technologie, Université Ferhat Abbas Sétif 1, 19000, Sétif, Algérie.
b Emergent Materials Unit, Université Ferhat Abbas Sétif 1, 19000, Sétif, Algérie.
c
laboratoire de Chimie de Coordination et Catalyse, Département de Chimie, Faculté des Sciences, Université
Cadi Ayyad Semlalia, BP 2390, 40001, Marrakech, Maroc.
* kamel_ouari@univ-setif.dz, Tel: +213772487875
ABSTRACT
Herein we describe the chemical synthesis of a novel tetradentate Schiff base ligand
(H2L), bridged with a pyridine, and its corresponding mononuclear copper complex
(Cu(II)L). H2L, derived from the condensation of 2,3-diaminopyridine and 5-
bromosalicylaldehyde, and Cu(II)L were structurally confirmed by routine spectral
techniques, UV-Vis, FT-IR, 1H-NMR, MS and elemental analysis. Single crystal X-ray
diffraction analysis of Cu(II)L complex showed a monoclinic system with P21/C space group
and Z = 4 molecules per unit cell. The characterization data of the complex revealed strong
coordination via azomethine nitrogen (N) and bromo-phenolate oxygen (O). Moreover, the
experimental parameters were found in line with the theoretical parameters. The conductivity
measurement showed a non-electrolytic nature of the complex and the electrochemical
behavior exhibits two quasi reversible redox processes. In-vitro antimicrobial studies on the
synthesized compounds revealed a significant activity of the complex on some bacteria strains
than the free ligand. DFT calculations were fully optimized using B3LYP and confirmed
practical electrochemical and antibacterial results.
Keywords: Schiff base, Copper complex, single crystal, DFT calculations, Cyclic
Voltammetry, Antibacterial activity.
1. Introduction
Schiff-base ligands and their coordination compounds have attracted the researchers’
attention and taken an important area in chemistry as compounds having azomethine linkage
1

Journal Pre-proof
(C═N) [1-3]. This interest is still growing due to their attractive properties, simple synthesis,
stability, low toxicity, good biocompatibility [4,5] and diverse fields of applications in
industry, medicine, analytic and catalysis [6-8].
The copper(II) complexes constitute an important class in chemistry not only for their
proper interesting coordination chemistry, such as flexible redox properties, geometry and
oxidation state [9,10] but also for their extensive application in various areas such as catalyst
in oxidation, reduction and epoxidation reactions [11,12]. They are also used in many type of
polymerization and as anticorrosion agents in industry [13,14]. Furthermore, the copper(II)-
based compounds exhibit broad spectrum of pharmacological activities and have been largely
explored in medicine for the treatment of various diseases [15-18], which are closely related
to their metal complexation ability [19]. As an example, upon coordination, the lipophilicity,
which controls the rate of entry into the cell, is modified thereby reducing some of the side
effects and the complexes may exhibit new set of bioactive properties which are not displayed
by the free ligand [20,21].
In addition, there are numerous researches reporting that Schiff base complexes
containing one or more halo-atoms in their aromatic ring have been widely investigated
because of their antimicrobial properties [22-26]. However, much less information is
available regarding the Schiff bases derived from diamino-pyridines with other carbonyl
compounds, this kind of compounds has not yet been studied systematically. There are only a
few publications concerning the reactivity of 2,3-diamino-pyridine with various carbonyl
compounds such as aromatic aldehydes. Thus, it is a challenge for researchers to study the
reactivity of heterocyclic complexes with a pyridine ring in their structures to provide useful
insight into the chemistry and biochemistry of bio-active molecules [27,28]. As an extension
of these studies, we were interested in checking the behavior of a copper complex when a
brome substituent on the aromatic ring moieties and a pyridine bridge were introduced,
In the current study, we highlight the synthesis and characterization of tetra-dentate
Schiff base ligand derived from 5-bromosalicylaldehyde and 2.3-diaminopyridine and the
corresponding copper (II) complex. The structural geometry of the complex has been
determined by X-ray crystallography and the electrochemical properties have been
investigated by cyclic voltammetry. In addition, and for a better understanding of the
structural activity correlation, DFT calculations were performed and the antibacterial activity
of prepared ligand and copper (II) complex, were studied towards some pathogenic strains of
Gram positive and Gram negative bacteria.
2

Journal Pre-proof
2. Experimental
2.1. Materials and measurements
All solvents and chemicals reagents were purchased from Aldrich and Merck and used
as received, without further purification. UV-Vis spectra (in DMF, 200-800 nm) were
recorded on a Shimadzu UV-1800 spectrophotometer. FTIR spectra (KBr pellets, 4000-400
cm-1) were obtained on a Shimadzu FTIR Affinity-1 spectrophotometer.1H-NMR spectrum
(in CDCl3/TMS) was measured with a Bruker 300 Advance spectrometer and the mass
spectrum was obtained with a Bruker Daltonics Flex Analysis spectrometer. Microanalyses
were carried out using an Elementar-Vario EL III CHNOS analyzer. The molar conductance
in DMF, 10-3 M) was determined at room temperature using a MeterLab CDM-210
conductivitymeter and the melting point was measured on a Kofler Bank 7779 apparatus.
In the electrochemical study, dimethylformamide (DMF) was employed as solvent,
lithium perchlorate (LiClO4) used as the supporting electrolyte; using a three-electrode cell in
which a glassy carbon (GC) was the working electrode, a saturated calomel electrode (SCE)
was the reference electrode and a platinum wire (PT) was used as an auxiliary electrode. The
measurements are carried out in nitrogen atmosphere at room temperature.
The voltammograms were scanned in the potential range +1600 to -2200 mV, at a
sweep rate of 100 mVs-1. Ferrocene/Ferrocenium (Fc/Fc+) is used as an internal standard with
the half wave potential E1/2 = 472 mV/ECS. All solutions were deoxygenated by passing a
stream of pre-purified N2 into the solution for at least 10 min prior to recording the
voltammograms.
2.2. Synthesis of the ligand H2L
Schema 1 shows the synthetic route of the Schiff base ligand H2L by mixing 0.5 mmol
of 2,3-diaminopyridine (0.0545 g) with 1 mmol 5-bromosalicylaldehyde (0.201 g) in 20 mL
methanol with continuous stirring and reflux for 3 h at 75 °C. The yellow precipitate was
washed with methanol and diethyl ether and then dried in vacuum over a night. Yield: 80 %;
mp ˃ 250 °C. Anal. calc. for C19H13N3O2Br2: C: 48 %, H:2.7 %, N: 8.8 %, found: C: 47.7 %,
H: 2.9 %, N: 8.8 %, IR (KBr pellets, ῡ cm-1): 1622 (C=N), 1572 (C=C), 1274 (C-O), UV-Vis:
1
DMF, λ nm, [ε M-1 cm-1 ]: 275 [75280], 346 [17440], H-NMR: (CDCl3, δ ppm): 6.5-8.5 (m,
ArH), 13.38 (s, OH), 12.80 (s, OH), 9.47 (s, CH=N), 8.57 (s, CH=N), MS (MALDI-TOF,
ditranol) [MH]+= 473.938.
3

Journal Pre-proof
2.3. Synthesis of the Cu(II)L complex
Cu(II)L complex Schiff base was prepared according to the literature method [29].
1 mmol of Cu(OAc)2 (0.0907 g) dissolved in methanol, was added drop-wise to a methanolic
solution of Schiff base ligand H2L (0.475 g) (Scheme 1). The obtained mixture was stirred at
75 °C for 2 h under nitrogen atmosphere. The obtained brown precipitate was filtered, washed
with methanol and diethyl ether. Single crystals suitable for X-ray diffraction were obtained
in pyridine/MeOH solvent. Yield: 78 %; mp˃ 250 °C. Anal.calc. for C19H11N3O2CuBr2:
C: 42.5 %, H: 2.06 %, N: 7.9 %; found: C: 42.5 %, H: 2.1 %, N: 7.8 %; MS (MALDI-TOF,
+
ditranol): [MH ] = 534.825; IR (KBr pellets, ῡ cm-1): 1606 (C=N), 1560 (C=C), 1312 (C-O),
524 (Cu-O), 483 (Cu-N); UV-Vis: DMF, λ nm, [ε M-1 cm-1 ]: 271 [42560], 326 [45300], 441
[43660].
N
H
HC
N
N
CH
C
O
Reflux N2
MeOH
N
Br
OH HO
Br
2
Br
OH
H2N
NH2
Cu(OAc)2
Reflux N2
MeOH
N
HC
N
N
CH
Cu
Br
O
O
Br
Scheme.1. Synthesis of the ligand H2L and the copper complex Cu(II)L.
2.4. X-ray crystallography
Single crystals of Cu(II)L complex were grown by slow layer diffusion of pyridine into
a MeOH solution at room temperature. A brown plate single crystal of dimensions (0.20 ×
0.15 × 0.10) mm3 suitable for X-ray analysis, was used for data collection at 173(2) K on a
Nonius Kappa-CCD diffractometer equipped with an Oxford Cryosystem liquid N2 device,
using graphite-monochromated Mo/Ka (k = 0.71073 Å) radiation. A semi-empirical
4

Journal Pre-proof
absorption correction was applied using the MUL scan ABS routine in PLATON [30].
Transmission factors: Tmin/Tmax = 0.38499/0.53425. Atomic scattering factors and anomalous
dispersion constants were taken from the International Tables for Crystallography; Volume C
[31].The structure was solved by direct methods using the SHELXS-97 and SHELXL-97
programs and refined on F2 by the full-matrix least-squares methods. All of the non-hydrogen
atoms were refined anisotropically and the hydrogen atoms were included in geometric
positions but not refined.
2.5. Quantum calculation using Density Functional Theory (DFT) calculation
The full geometry optimization were carried out using the Gaussian 9 program, based
on density functional theory (DFT) [32], using Beck’s three parameter hybrid exchange
functional [33], with Lee-Yang-Parr correlation functional (B3LYP) and 6-31G (d, p) basis
set [34,35].
2.6. Antibacterial activity
The Schiff base ligand and the copper complex were tested in vitro for their
antibacterial activity against Pseudomonas aeruginosa, Klebseilla pneumoniae, Escherichia
coli and Proteus mirabilis as Gram negative bacteria and Staphylococcus aureus, Methicillin
resistant S.aureus (MRSA), Streptococcus pyogones and Micrococcus luteus as Gram positive
bacteria in Muller Hinton Agar medium (MHA) using disc diffusion method [20]. The stock
solution was prepared by dissolving the compounds in DMSO to prepare two concentrations
10 and 5 mg/mL. The sterilized filter paper discs (6 mm diameter) of Watman N°1 was
soaked in different test solutions and placed in the surface of sterile petri plates (9 mm
diameter) previously seeded with the microorganisms. The petri plates were incubated for 24
h at 37 °C and the inhibitions zone were measured around each disc. Three standards
antimicrobial agents were used in this study: Gentamicin, Amoxicillin and Ciprofloxacin;
DMSO was taken as negative control which shows no inhibitory effect on bacterial growth.
3. Results and discussion
3.1. Elemental analysis and conductivity studies
Elemental analysis results of the ligand H2L and the copper complex Cu(II)L are in
good agreement with the calculated values. The molar conductance values for H2L and
Cu(II)L in 10-3 M DMF at room temperature are 10.38 and 5.26 Ω-1cm2mol-1 respectively.
5

Journal Pre-proof
These very low conductance values indicate the non-electrolytic nature of the compounds
[36,37].
3.2. IR Spectroscopic Properties
The FT-IR spectrum (Table 1) of the ligand shows an absorption band at 3437 cm-1,
corresponding to inter and intra-molecular hydrogen bonds, which is attributed to the
stretching vibrations of the hydroxyl band (O-H) [38].
The characteristic vibration of azomethine group (C═N) in the ligand appears at 1622
cm-1. This absorption shifts to a lower wave number, 1606 cm-1, in the case of the complex,
indicating the coordination of the nitrogen atom of azomethine group to the metal [39,40].
Another broad band appearing at 1560 cm-1, is assigned to (C═C) stretching absorption.
In addition the coordination of the ligand is further supported by the band around 1274
cm-1, which shifts to a higher wave number of (C─O) in the complex (1312 cm-1). This
behavior is due to the coordination of the oxygen atom of the ligand to the copper, as reported
in the literature [41]. The absorptions at 524 and 483 cm-1 are due respectively to the Cu─O
and Cu─N vibration bands in the complex Cu(II)L [42].
3.3. Electronic spectra
The electronic spectra of the ligand and the copper (II) complex, were recorded, in
DMF at room temperature, between 800-200 nm (Table 1). The electronic spectrum of H2L
shows two absorptions. The first at 275 nm is attributed to π→π* transitions while the second
one, very large, observed at 346 nm is ascribed to n→π* transitions. Electronic spectrum of
Cu(II)L complex exhibits three absorptions, the bands at the higher energy region 271 and
326 nm are assigned to the π→π* and n→π* transitions of the ligand as already reported [43].
The band appearing at 441 nm, less intense than the first, is associated to the ligand-metal
charge-transfer (LMCT) transitions due to the transitions  (imine)→metal [29].
Table.1. FT-IR and UV–Vis spectral data of the Schiff base ligand H2L and the copper
complex Cu(II)L.
Infrared (cm−1)
UV–Vis (in DMF)
Compounds
ῡ (O─H) ῡ (C═N) ῡ (C═C) ῡ (C─O)
ῡ (Cu─O)
ῡ (Cu─N)
λmax (nm)
H2L
3437
3446
1622
1606
1572
1560
1274
1312
/
/
275; 346
Cu(II)L
524
483
271 ; 326 ; 441
6

Journal Pre-proof
3.4.1H-NMR
The proton NMR results (Figure 1) for the Schiff base ligand show two de-shielded
signals for the protons of the hydroxyl groups at 12.80 and 13.38 ppm. The two singlets
appearing at 8.57 ppm and 9.46 ppm, are attributed to the azomethine protons [44]. Aromatic
protons appear as multiplets in the range of 6.5-8.5 ppm and are in good agreement with the
integral areas [45].
Figure.1. 1H-NMR spectrum of the ligand H2L.
3.5. Mass spectra
The mass spectra of the Schiff base ligand and the copper complex were obtained using
MALDI-TOF spectrometer in DMSO as solvent. The Mass spectra show that the molecular
peaks observed at [MH] + = 473.938 and 534.825, are consistent with the molecular weight of
ligand and complex respectively (Figure 2).
The molecular peak cluster, in the mass spectrum of the dibrominated complex, shows
the expected relative abundance of the bromine isotopes [46].
7

Journal Pre-proof
+
+
536.840
[M H ] + 2
475. 939 [M H ] + 2
1600
1200
1000
800
600
400
200
0
.+
Cu (II) L
H L
2
475,939 [M] +2
1400
1200
1000
800
+
538.852 [MH] + 4
+
477.939 [M H ] + 4
+
+
[M H ] 473. 938
[M H ] 534.825
537.854
600
400
200
0
539.868
540.871
535.837
476.939
478.950
474.946
533.800
541.874
558.832 560.836
479.940
530
535
540
545
470
475
480
485
Figure.2. The masse spectra of the H2L ligand and the Copper complex Cu(II)L.
3.6. Single crystal X-ray diffraction
The single crystal X-ray diffraction reveals that the complex Cu(II)L has molecular
formula C19H11Br2CuN3O2. Table 2 shows crystal data, data collection and structure
refinement parameters.
Table.2. Crystal data, data collection and structure refinement parameters.
Compound
Cu(II)L
Molecular formula
Molecular weight
Temperature (K)
C19H11Br2CuN3O2
536.67
173(2)
Mo-Kα(0.71073)
Monoclinic
P21/c
12.0712(7)
8.0472(5)
18.8974(9)
90.00
Radiation
Crystal system
Space group
a/Å
b/ Å
c/ Å
alpha°
Beta°
gamma°
V/Å3
111.134(3)
90.00
1712.21 (17)
4
Z
Dcalc (mg m-3)
Crystal size (mm3)
Crystal description
Crystal colour
Absorption coefficient
F(000)
2.082
0.20 x 0.15 x 0.10
plate
brown
5.964
1044
Reflections
Range/indices (h, k, l)
Tetalimit
9255/2607
−150, 15; −10, 9; −24, 24
1.81, –27.49
No. of observed data, 2607
8

Journal Pre-proof
No. of variables
244
Goodness of fit on F 2
R1, wR2 [I>2σ(I)]a
R1, wR2 (all data)a
1.013
0.0519, 0.0968
0.0934, 0.1096
The asymmetric unit of Cu(II)L with atom numbering is shown in Figure 3.
(b)
(a)
Figure.3. Asymmetric unit of Cu(II)L, (a) opposite view, (b) side view.
The Figure 3(a) shows that the metal is coordinated to two oxygen atoms of two 5-
bromo-salicylaldehyde groups (O1 and O2) and two nitrogen atoms of 2,3-diaminopyridine
(N1 and N2) of Schiff base ligand, the distances between the coordinated nitrogen and oxygen
atoms and the metal Cu-O1, Cu-N2, Cu-O2 and Cu-N3 are 1.898(3), 1.941(3), 1.883(3) and
1.940(3) Å respectively. The chelating angles O2-Cu1-O1, O1-Cu1-N2, O2-Cu1-N3 and N2-
Cu1-N3 have values 88.33(13), 93.89(14), 93.52(14) and 84.26(15) ° respectively. The bond
distances and angles are in good agreement with those reported in similar Schiff bases
complexes [47,48]. In addition, the Figure 3(b) shows that the atoms N2, N3, O1 and O2 are
coplanar and define a basal plane, proving quadridentate symmetrical Schiff base ligand.
The Table 3 summarizes cited bonds lengths and angles values in comparison with
theoretical calculated values, and proving a good arrangement, which confirm the structure
conformation.
Table. 3. Selected experimental and theoretical bond lengths (Å) and angles values (°)
for Cu(II)L complex.
Bond lenghts (Å)
Bond angles (°)
Experimental calculated
Experimental calculated
Cu1-O2
Cu1-O1
Cu1-N2
Cu1-N3
1.883(3)
1.898(3)
1.941(3)
1.940(4)
1.887(6)
1.891(1)
1.961(3)
1.937(3)
O2-Cu1-O1
O2-Cu1-N2
O1-Cu1-N2
O1-Cu1-N3
N2-Cu1-N3
O2-Cu1-N3
88.33(13)
177.71(15)
93.89(14)
178.13(14)
84.26(15)
93.52(14)
89.658(2)
177.176(3)
93.165(2)
177.474(1)
84.309(2)
92.868(3)
9

Journal Pre-proof
The packing of the Cu(II)L molecules is shown in Figure 4, it is observed that, four
molecules (Z = 4) crystalize in a monoclinic unit cell with P21/c space group, the unit cell is
non centrosymmetric, characterized by an inversion point at the center O, 2-fold screw axis
with direction [0, 1, 0] at 0, y, ¼ with screw component [0, ½, 0] and glide plane
perpendicular to the plan [0 1 0] with glide component [0, 0, ½].
Figure.4. Packing in unit cell.
The 3D network is stabilized by intermolecular hydrogen bonds of the type C-H∙∙∙Br,
with the corresponding lengths, donor acceptor 3.303(3) Å, donor hydrogen 0.951(2) Å and
hydrogen acceptor 3.127(2) Å, and with corresponding angle donor hydrogen acceptor about
92.17(5) °, this hydrogen bond builds helical chiral chains (Figure 5), however, in one formal
unit cell, each molecule belongs to separate chiral helical chain, giving complicate wire rack
3D network.
10

Journal Pre-proof
(1)
(2)
a
O
b
c
O
a
Figure.5. Helical chiral chain constructed by C-H∙∙∙Br, (1) Oab plan (2) Oca plan.
3.7. Quantum calculations results
A comparison of molecular electrostatic potential and frontier orbital molecular
calculations, was effectuated between the ligand H2L and the complex Cu(II)L.
3.7.1. Molecular Electrostatic Potential (MEP)
The total electron density surface mapped with electrostatic potential is very
comparable for both molecules H2L and Cu(II)L as shown in Figures 6 (a) and (b), which
indicates the presence of high negative charge around oxygen atoms. The corresponding
mapped electrostatic potential is indicated by red color, the most negative values are about
-5,786.10-2 V and -6.333.10-2 V for H2L and Cu(II)L respectively. The blue region indicates
the mapped electrostatic potential generated by the partially positive charge. This last is
centered around hydrogen and carbon atoms, the most positive values is about +5,786.10-2 V
and +6.333.10-2 V for H2L and Cu(II)L respectively. The yellow regions indicate the slightly
rich electron and the green regions indicate neutral. The difference of charge density between
the both molecules is attribute two different values of the dipolar moment: 3.707 and 4.767
Debeye for H2L and Cu(II)L respectively.
11

Journal Pre-proof
(b)
(a)
-5.86.10-2
-6.333.10-2
5.786.10-2V
6.333.10-2V
Figure.6. The total electron density mapped with electrostatic potential of (a) H2L
(b) Cu(II)L.
3.7.2. Orbital frontiers (FMOS)
Figure 7 shows the calculated electron acceptor distribution in lowest unoccupied
molecular orbital and the calculated electron donor distribution in highest occupied molecular
orbital. Figure 7 (a) shows the HOMO and LUMO orbitals for H2L. The SOMO and SUMO
orbitals, for Cu(II)L, are presented in Figure 7 (b) α-spin and (c) β-spin. The Table 4
summarizes the HOMO/SOMO and LUMO/SUMO energies and some related
physicochemical parameters characteristic of both molecules H2L and Cu(II)L.
(a)
(c)
(b)
SUMO (α-spin)
LUMO
HOMO
SUMO (β-spin)
(a)
(c)
(b)
(b)
SOMO (α-spin)
SOMO (β-spin)
Figure.7. Frontiers Molecular Orbitals plot (a) of H2L (b) of Cu(II)L α-spin and (c) β-spin.
12

Journal Pre-proof
Table.4. Band energies, chemical reactivity calculated parameters.
H2L
Cu(II)L
Electronic band energies (eV)
EHOMO/SOMO
ELUMO/SUMO
-5.86
-2.44
3.42
-5.64
-2.33
3.31
Energy gap (∆)
Electrochimical parameters
Dipolar moment (Debye)
Ionization potentiel (I)
Electron affinity (A)
Global hardness (η)
3.707
5.86
2.44
1.71
0.58
4.04
4.77
4.14
4.767
5.64
2.33
1.65
0.61
3.98
4.80
4.14
Global softness (σ)
Electronegativity (χ)
Global electrophilicity (ω)
Chemical potentiel (μ)
I=-EHOMO, A=-ELUMO, χ =-[1/2(ELUMO+ EHOMO)], η=1/2(ELUMO- EHOMO), ω= χ2/2η. σ=1/ η, μ=-1/2(A+I).
The frontier orbital calculations help to predict the chemical reactivity and kinetic
stability of the molecule. For example, molecules with a small frontier orbital gap are more
polarizable and are generally associated with a high chemical reactivity. In this work, we
studied and compared biological activity of synthesized compounds.
3.8. Electrochemical study
Electrochemical properties of the H2L and the Cu(II)L (Figure 8) were studied by cyclic
voltammetry in the potential range +1600 to -2200 mV/SCE in DMF solvent containing 10-1
M LiClO4 as supporting electrolyte, using 100 mVs-1 under nitrogen atmosphere. The
international standard Fc/Fc+ was used as reference.
The cyclic voltammogram of the copper (II) complex exhibits two quasi-reversible
1
2
processes at
=310 and
E1/2
= -899 mV/SCE. The first process is assigned to the oxidation
E1/2
of CuII/CuIII redox couple (Epa= 560 and Epc= 240 mV) [49,50] and the second is attributed to
the reduction of CuII/CuI redox system (Epa= -833 and Epc= -965 mV) [43,50].
On the other hand, two oxidation peaks observed at Epa1 = + 1160 and Epa2 = + 1400
mV/SCE, are attributed to the oxidation of the ligand [51], the reduction peak, reported at Epc
= -1740 mV/SCE, is assigned to the reduction of the azomethine group [42], the latter
accelerates the transfer of electrons on the metal [52].
Moreover, the DFT calculation can explain the electrochemical behavior, since a
correlation can be established between CV waves and frontier orbitals energies, the HOMO
and LUMO energies of the ligand H2L can be calculated using the oxidation and reduction
13

Journal Pre-proof
waves respectively following the empirical relations EHOMO = -[Eoxydation-E1/2(ferrocene)+4.8] eV
and ELUMO = -[Ereduction-E1/2(ferrocene)+4.8] eV. The corresponding gap value is found ∆ = 4.1
eV, which is close from the theoretical value.
For the complex Cu(II)L, the anodic peak observed at 560 mV removes an electron
from the β-SOMO. Otherwise, the cathodic peak at -965 mV correspond to addition of an
electron in β-SUMO, indicating that the first reduction and the first oxidation take place on
the Cu(II) centers, finally, the peak observed at -1740 mV corresponds to the reduction of an
electron from the conjugated π system of the ligand.
100
(b)
(c)
(a)
50
0
-50
-2,0
-1,5
-1,0
-0,5
0,0
0,5
1,0
1,5
E (V/SCE)
Figure.8. Cyclic voltammograms of H2L (a), Cu(II)L (b), and Fc/Fc+ (c) in 0.1 M
LiClO4/DMF at scan rate 100 mVs-1.
An increase of the anodic current Ipa with the increase of the scanning speed, in the
range -600 to -1400 mV/SCE (Figure 9), is observed and the square root of scan rate present a
linear relationship with this current (Ipa = f (v1/2)) (inset of Figure 9). These facts mean that
these electrochemical processes are mainly diffusion controlled [53].
The large peak-to-peak separation (Ep), approximately equal to 132 mV, expressing an
electrochemical oxidation of Cu(I), would be due to a quasi-reversible behavior of the couple
Cu(II)L + e–→ Cu(I)L. The results of cyclic voltammetry measurement are grouped in Table
5.
14

Journal Pre-proof
2
0
3,2
3,0
2,8
2,6
2,4
Y=-1.7096+0.1386X
R2=0.999
-2
-4
-6
-8
5
6
7
8
9
10
V1/2(mV/s)1/2
-1,4
-1,2
-1,0
-0,8
-0,6
E(V/SCE)
Figure.9. Cyclic voltammograms of Cu(II)L in 0.1 M LiClO4/DMF at various scan rate of 25,
50, 75 and 100 mVs-1. The inset shows the anodic peak current.
Table.5. Cyclic voltammetric parameters of the copper complex Cu(II)L at different scan
rates
V(mVs-1)
-Epa(mV/SCE)
806
-Epc(mV/SCE) -E1/2(mV/SCE) Ep(mV)
Ipa(A)
2.4
Ipc(A)
3.5
Ipa/ Ipc
0.68
0.70
0.71
0.75
25
922
934
944
965
864
873
882
899
116
122
123
132
50
812
2.6
3.7
75
821
2.8
3.9
100
833
3.1
4.1
3.9. Antibacterial activity
The antibacterial activity of the ligand and the copper complex, against various strains
of Gram negative bacteria (Pseudomonas aeruginosa, Klebseilla pneumoniae, Escherichia
coli and Proteus mirabilis) and of Gram positive bacteria (Staphylococcus aureus, Methicillin
resistant S. aureus (MRSA), Streptococcus pyogones and Micrococcus luteus) , was tested by
the disc diffusion method in Muller Hinton Agar medium (MHA).
Gentamicin, Amoxicillin and Ciprofloxacin were used as positive control and the
DMSO solvent as negative control. The results are listed in Table 6 and they are represented
graphically in Figure 10. It is observed that the Cu(II)L complex shows more inhibitory
activity compared to the corresponding ligand. The antibacterial effect of these compounds
on Gram (+) is higher than Gram (-) bacteria. This result can be explained by the difference in
the complexity of structure of the cell walls of Gram (-) and Gam (+) bacteria which play a
15

Journal Pre-proof
role in the impermeability of the cell, or by the difference in ribosomes in microbial cell [54].
Furthermore, it is shown that the activity increases with increasing concentration of the test
solution of the different compounds.
The reason for the increase in the antibacterial activity of Cu(II)L complex , can be
demonstrated on the basis of Overtone’s concept and Tweedy’s chelation theory. Within the
Overtone’s concept of the cell permeability, the lipid membrane that surrounds the cell wall
favors the passage of only the lipid soluble materials; this means that one of the most
important factor to control this activity, is the liposolubility [55,39]. On chelation, the
coordination reduces the polarity of the metal ion, principally because of the partial sharing of
its cation with the donor groups. Moreover, the chelation increases the delocalization of
-electrons over the whole chelate ring; this consequently increases the lipophilic character of
the chelates, favoring the permeation through lipid layers of the bacterial membrane [16, 28].
This process, in turn, may block the enzymatic activity of the cell which stopped the
respiration process of the microorganisms [56].
M.P. Kumar and al. [25] have observed that the tetradentate copper complexes tested
against the bacteria E. coli, P. putida, K. pneumoniae, B. subtilisand S. aureus exhibit a
significant antimicrobial activity. Similarly, S.O. Bahaffi and al. [23] have studied and
reported that copper complexes show a good inhibitory action against bacteria strains: S.
aureus, S. epidermidis, E. coli, and P. aeruginosai. However, the results obtained for our
complex are similar to those described.
Table.6. Antibacterial activity of Schiff base ligand and the copper (II) complex.
Diameter of inhibition zone (mm)
Gram negative
Gram positive
Conc.
Compound
H2L
mg.mL-1
Klebseilla
pneumoniae
Pseudomenas
aeroginosa
E.
Proteus
mirabilis
Staphylococcus
aureus
Streptococcus
pyogones
Micrococcus
luteus
MRSA
coli
10
5
15
11
16
13
20
11
9
11
10
14
12
22
/
/
13
13
20
18
16
16
15
17
15
/
17
18
17
20
17
20
15
20
18
26
10
5
16
12
25
11
11
/
Cu(II)L
Gentamicin
Amoxicillin
/
/
15
/
19
/
24
13
16

Journal Pre-proof
Ciprofloxacin
DMSO
40
/
34
/
38
/
/
/
35
/
22
/
40
/
35
/
Figure.10. Zone of inhibitions (in mm) of reported compounds (10 mg/mL) and antibiotics
against Gram (+) and Gram (-) bacteria strains.
3.10. Structure activity relationship
According to the chelation theory [57], the enhancement of antibacterial activity of the
complex Cu(II)L compared to the ligand H2L can be explained by many major factors a
nature of the coordinated groups, chelate effect, total charge of the complex and nuclearity of
the central metal ion [58]. On the other side, the biological activity is correlated to the ground
state properties, the higher reactivity of the complex Cu(II)L compared to the ligand can be
explained by energy gap which having 3.42 eV and 3.31 eV for H2L and Cu(II)L
respectively, the decrease of gap energy for the complex increases the reactivity, this decrease
is accompanied by the increase of the amount of electronic charge transfer from the ligand to
the central metal ion, and this last electronic factor influence considerably the biological
activity [59]. This theoretical prediction is observed toward Gram (+) and Gram (-) bacteria.
17

Journal Pre-proof
It is well known that electron-transfer is involved in various Cu-catalyzed oxidative
transformations in chemistry and biology and It is essential that the redox potential for the
central Cu+2/Cu+1 couple lies around -1―0 V, i.e. in a similar range as the potentials of the
+
.
O2/O2. ― /O22 ― NO /NO/NO
biologically important redox couples
,
― . Hoshino et al. [60]
state that recycling redox reactions between Cu2+ and Cu1+ are possible at the surface of E.
coli cells, generating H2O2 and causing damage to the cytoplasmic membrane. So, we thought
that electrochemical behavior of the electroactive metal is important to study to assess the
redox characteristics of the complex, but it is not easy to make a direct correlation between
the biological activity and the electrochemical parameters of the complex.
According to the recycling redox reactions between Cu2+ and Cu1+, copper has the
potential to disrupt cell function and destroy the bacterial cell wall; the cytoplasm is then
degraded and disappears, leading finally to cell death, so the copper reduce ability of
microorganisms to develop resistance against copper complex [60]. Furthermore, the complex
may exhibit new set of bioactive properties which are not displayed by the free ligand. It is
hoped that, in future, copper complex could replace some antibiotic medicines used to combat
pathogenic bacteria.
4. Conclusion
A tetradentate copper complex (Cu(II)L) was prepared in good yield and well
characterized by different spectroscopic techniques. The four coordinated complex, through
both N and O donor sets, is revealed by the single crystal X-ray diffraction. DFT calculations
were applied successfully to predict the structural geometry and a good agreement is shown
1
between the theoretical and experimental results. Two quasi reversible processes,
=310
E1/2
2
and
= -899 mV/SCE, are observed and a correlation is established between CV waves and
E1/2
frontier orbitals energies. The antimicrobial studies show that the complex has better
inhibitory activity against the tested bacteria compared to the uncomplexed Schiff base and
the inhibitory effect is correlated with the energy gap. These results are similar to those
obtained from M.P. Kumar and al. [25] for Coppe (II) complexes containing heterocyclic
bases. Furthermore, the novel complex exhibits good antibacterial effect upon the studies
bacteria in comparison with the standard drugs gentamicin and amoxicillin. Taking a count of
these results, the Copper(II) complex could replace some antibiotic medicines used to combat
18

Journal Pre-proof
pathogenic bacteria and could be also useful, in future work, to study the antifungal,
anticancer, antioxidant and DNA cleavage activities.
Supplementary data
CCDC 730120 contains the supplementary crystallographic data for Cu(II)L. These data
can be obtained free of charge via http:// www.ccdc.cam.ac.uk/conts/retrieving.html, or from
the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax:
+44 1223 336 033; or e-mail: deposit@ccdc.cam.ac.uk.
Acknowledgements
The authors gratefully acknowledge the financial support from The Algerian Ministry of
Higher Education and Scientific Research. They also acknowledge the help of Dr J. Weiss
from the CLAC laboratory at the Institut de Chimie, Université de Strasbourg, France and Pr
D. Benachour from LMPMP laboratory at the faculty of technology, Université Sétif-1.
References
[1] P. Mahapatra, A. Bauzá, A. Frontera, M.G. Drew, A. Ghosh, Inorg. Chim. Acta. 477
(2018) 89-101.
[2] W. Al Zoubi, Y.G. Ko, J. Organomet. Chem. 822 (2016) 173-188.
[3] S.Y. Ebrahimipour, I. Sheikhshoaie, J. Castro, W. Haase, M. Mohamadi, S. Foro, M.
Sheikhshoaie, S.E. Mahani, Inorg. Chim. Acta. 430 (2015) 245–252.
[4] M. Shabbir, Z. Akhter, H. Ismail, B. Mirza, J. Mol. Struct. 1146 (2017) 57-61
[5] L. Jia, J. Xu , X. Zhao, S. Shen, T. Zhou, Z. Xu, T. Zhu , R. Chen, T. Ma, J. Xie, K. Dong,
J. Huang, J. Inorg. Biochem.159 (2016) 107–119.
[6] H.M. Aly, M.E. Moustafa, M.Y. Nassar, E.A. Abdelrahman, J. Mol. Struct. 1086 (2015)
223-231.
[7] F. Zhao, W. Wang, W. Lu, L. Xu, S. Yang, X.M. Cai, M. Zhou, M. Lei, M. Ma, H.J. Xu,
F. Cao, Eur. J. Med. Chem.146 (2018) 451-459.
[8] X. Liu, C. Manzur, N. Novoa, S. Celedón, D. Carrillo, J.R. Hamon, Coord. Chem. Rev.
357 (2018) 144–172.
[9] A.D. Khalaji, M. Ghorbani, N. Feizi, A. Akbari, V. Eigner, M. Dusek, Polyhedron.
121(2017) 9-12.
[10] H. Barfeie, G. Grivani, V. Eigner, M. Dusek, A.D. Khalaj, Polyhedron. 146 (2018) 19-
25.
[11] N. Beyazit, D. Çakmak, C, Demetgül, Tetrahedron. vol 73, Issue 19 (2017) 2774-2779
[12] Z. Abbasi, M. Behzad, A. Ghaffari, H.A. Rudbari, G. Bruno, Inorg. Chim. Acta. 414
(2014) 78-84
19

Journal Pre-proof
[13] A. Routaray, N. Nath , S. Mantri, T. Maharana, A.K. Sutar, Chinese. J .Catal. 36
(2015) 764–770
[14] M. Mishra, K. Tiwari, P. Mourya, M.M. Singh, V.P. Singh, Polyhedron. 89 (2015)
29–38.
[15] K. Dhahagani, M.P. Kesavan, G.V. Kumar, L. Ravi, G. Rajagopal, J. Rajesh, Mater. Sci.
Eng., C 90 (2018) 119–130.
[16] V.P. Radha, S.J. Kirubavathy, S. Chitra, J. Mol. Struct. 1165 (2018) 246-258.
[17] U. Kendur, G.H. Chimmalagi, S.M. Patil, K.B. Gudasi, C.S. Frampton, C.V,
Mangannavar, I.S. Muchchandi, J. Mol. Struct. 1153 (2018) 299-310.
[18] K. Venkateswarlu, M.P. Kumar, A. Rambabu, N. Vamsikrishna, S. Daravath, K. Rangan,
Shivaraj, J. Mol. Struct. 1160 (2018) 198-207.
[19] S. Sangeeta, K. Ahmad, N. Noorussabah, S. Bharti, M.K. Mishra, S.R. Sharma, M.
Choudhary, J. Mol. Struct. 1156 (2018) 1-11.
[20] B. Iftikhar, K. Javed, M. Khan, Z. Akhter, B. Mirza, V. Mckee, J. Mol. Struct.1155
(2018) 337-348.
[21] V.A. Joseph, J.H. Pandya, R.N. Jadeja, J. Mol. Struct. 1081 (2015) 443–448.
[22] K.F. Ansari, C. Lal, Eur. J. Med. Chem. 44 (2009) 2294–2299.
[23] S.O. Bahaffi, A.A. Abdel Aziz, M.M. El-Naggar, J. Mol. Struct. 120 (2012) 188-196.
[24]P. Noblia, M. Vieites, B.S. Parajo n-Costa, E.J. Baran, H. Cerecetto, P. Draper,
M.Gonzalez, O.E. Piro, E.E. Castellano, A. Azqueta, A.L. Cerain, A. Monge-Vega, D.
Gambino, J. Inorg. Biochem. 99 (2005) 443–451.
[25] M.P. Kumar, S. Tejaswi, A. Rambabu, V.K.A. Kalalbandi, Shivaraj, Polyhedron. 102
(2015) 111-120.
[26] A.N. Kursunlu, E. Guler, F. Sevgi, B. Ozkalp, J. Mol. Struct. 1048 (2013) 476–481.
[27] P. Tyagi, S. Chandra, B-S. Saraswat, D. Yadav, Spectrochim. Acta, Part A. 145 (2015)
155-164.
[28] L.H. AbdelRahman, N.M. Ismail, M. Ismael, A.M. AbuDief, E.A. Ahmed, J. Mol. Struct.
1134 (2017) 851-862.
[29] S. Dekar, K. Ouari, S. Bendia, D. Hannachi, J. Weiss, J. Organomet. Chem. 866 (2018)
165-176.
[30] A.L. Spek, J. Appl. Cryst. 36 (2003) 7–13.
[31] International tables for crystallography, vol C. Kluwer Academic Publishers, Dordrecht
(2004).
[32] W. Kohn, L.J. Sham, Phys.Rev .140 (1965) 1133-1138.
[33] A-D. Becke, J. Chem. Phys .98 (1993) 648-5652.
[34] C. Lee, W. Yang, R.G. Parr, Phys. Rev. 37 (1998) 785-789.
[35] B. Miehlich, A. Savin, A. Stoll, H. Preuss, Chem. Phys. Lett. 157 (1989) 200-206.
[36] F. Niu, K.X. Yan, L. Pang, D. Qu, X. Zhao, Z. You, Inorg. Chim. Acta. 435 (2015) 299–
304.
20

Journal Pre-proof
[37] Y.T. Liu, J. Sheng, D.W. Yin, H. Xin, X.M. Yang, Q.Y. Qiao, Z.J. Yang, J. Organomet.
Chem. 856 (2018) 27-33.
[38] O. El Sherif, N.S. AbdelKader, Spectrochim. Acta, Part A. 117(2014) 519-526.
[39] A. Rambabu, M.P. Kumar, S. Tejaswi, N. Vamsikrishna, Shivaraj, J. Photochem.
Photobiol, B. 165 (2016) 147–156.
[40] M. Merzougui, K. Ouari, J. Weiss, J. Mol. Struct. 1120 (2016) 239-244.
[41] S.A. Patil, S.N. Unki, A.D. Kulkarni, V.H. Naik, P.S. Badami, Spectrochim. Acta, Part
A. 79 (2011) 1128– 1136.
[42] M. Sarıgül, S.E. Kariper, P. Deveci, H. Atabey, D. Karakaş, M. Kurtoglu, J. Mol. Struct.
1149(2017) 520-529.
[43] M.H. Habibi, R. Mokhtari, M. Mikhak, M. Amirnasr, A. Amiri, Spectrochim. Acta, Part
A. 79 (2011) 1524-1527.
[44] S. Dekar, S. Bendia, K. Ouari, IUCrData (2017). 2, x170077
[45] K. Ouari, S. Bendia, J. Weiss, C. Bailly, Spectrochim. Acta, Part A. 135 (2015) 624-631.
[46] I.V. Korendovych, E.R. Akimova, Acta. Cryst. C. 60 (2004) 82-84.
[47] N. Benferrah, M. Hammadi, C. Philouze, F. Berthiol, F. Thomas, Inorg Chem Comm 72
(2016) 17-22.
[48] L. Chiang, K. Herasymchuk, F. Thomas, T. Storr, Inorg Chem 54 (2015) 5970-5980.
[49] A. Palanimurugan, A. Kulandaisamy, J. Organomet. Chem. 861 (2018) 263-274.
[50] Z. Abbasi, M. Salehi, M. Kubicki, A. Khaleghian, J. Coord. Chem.vol 70, Issue 12
(2017) 2074-2093.
[51] J. Losada, I. Peso, L. Beyer, Inorg. Chim. Acta. 321 (2001) 107-115.
[52] S. Abolfazl, H. Yazdi, A. Mirzaahmadi, P.S. Aghdam, A.A. Khandar, G. Mahmoudi,
W.S. Kassel, W.G. Dougherty, Inorg Chim Acta 414 (2014) 115–120.
[53] J.M. Fernfindez, M.R. Patifiomaya, R.A. Toscano, L. Velasco, M. Oterolopez, M.
Aguilarmartinez, Polyhedron. 16 (1997) 4371-4378
[54] S. Sobha, R. Mahalakshmi, N. Raman, Spectrochim. Acta, Part A. 92 (2012) 175-183.
[55] A.N. Srivastva, N.P. Singh, C.K. Shriwastaw, Arab. J .Chem.9 (2016) 48-61.
[56] A.B. Gündüzalp, I. Özsen, H. Alyar, S. Alyar, N. Özbek, J. Mol. Struct. 1120 (2016)
259-266.
[57] P. K. Panchal, H. M. Parekh, P. B. Pansuriya, M. N. Patel, J. Enzyme Inhib. Med. Chem.
21 (2006) 203-209.
[58] C. D. Samara, G. Psomas, C. P. Raptopoulou, D. P. Kessissoglou, J. Inorg. Biochem. 83
(2001) 7-16.
[59] H.F. ElShafiy, M. Saif, M.M. Mashaly, S. Abdel Halim, M.F. Eid, A.I. Nabeel, R.
Fouad, J. Mol. Struct. 1147(2017) 452-461.
[60] N. Hoshino, T. Kimura, A. Yamaji, T. Ando, Free Radic Biol Med. 27(1999) 1245–1250.
21

Journal Pre-proof
SUMO (α-spin)
LUMO
(a)
SUMO (β-spin)
(b)
(c)
(b)
HOMO
SOMO (α-spin)
SOMO (β-spin)
Figure.7. Frontiers Molecular Orbitals plot (a) H2L (b) Cu(II)L α-spin and (c) Cu(II)L β-spin.

Journal Pre-proof
Highlights
 A Schiff base ligand (H2L) and the corresponding copper complex Cu(II)L are
synthetized with good yields.
 Structural features are confirmed by different spectroscopic techniques.
 Structure of copper complex Cu(II)L was revealed by single crystal X-ray diffraction;
the geometry was calculated and confirmed by DFT.
 Cyclic voltammetry study of the Cu(II)L complex indicated two quasi reversible
processes.
 The antimicrobial activity of the copper complex Cu(II)L shows a better activity than
the ligand (H2L).