Research Article
Open Access
Co (II), Ni (II) and Cu (II) Complexes with Schiff Base
Ligand: Syntheses, Characterization, Antimicrobial
Studies and Molecular Docking Studies
Arumugam AP1, Guhanathan S2 and Elango G1*
1 Department of Chemistry, Govt Arts College, Tiruvannamalai, Tamil Nadu, India
2 PG & Research Department of Chemistry, Muthurangam Government Arts College, Vellore-632002, Tamil Nadu, India
*Corresponding author: Elango G, Department of Chemistry, Govt Arts College, Tiruvannamalai, Tamil Nadu, India; E-mail:
@;
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Received: September 04, 2017; Accepted: September 28, 2017; Published: October 03, 2017
Citation: Elango G, Arumugam AP, Guhanathan S (2017) Co (II), Ni (II) and Cu (II) Complexes with Schiff Base Ligand: Syntheses,Characterization, Antimicrobial Studies and Molecular Docking Studies. SOJ Mater Sci Eng 5(2): 1-12.
This paper is an analysis about the Schiff base ligands and its
Co (II), Ni (II) and Cu (II) complexes. In the past few decades there
has been an increased interest in this area. Synthesis of Schiff base
can be done in many ways, but the most common method is the
nucleophilic attack of primary amines on the carbon of aldehydes or
ketones. The end result of this reaction is a compound in which C=O
is replaced by a C=N. This study reported the synthesis of the new
ligands, (E)-4-((5-benzoyl-2-((E)-(2-hydroxybenzylidine) amino)
phenyl) amino) pentan-2-one. These Schiff base type ligands were
respectively obtained by means of the reaction of Salicylaldehyde, 3,
4-diaminobenzophenone and acetyl acetone at molar ratio 1:1:1. The
respective Co (II), Ni (II) and Cu (II) complexes were synthesized by
the reaction of Ligand with metal nitrate hexa hydrate, at molar ratio
1:1. The chemical identification of ligands and respective complexes
was established through spectroscopic data (FT-IR, UV-Vis, 1H NMR
and 13C NMR). Macro cyclic complexes are non-electrolytic nature
as their molar conductivities (ΛM) in DMSO of 10-3 M solution from
the EPR study the complexes proposed to be octahedral geometry.
The complexes have been tested against gram positive and gram
negative bacteria using agar well diffusion method. It was found
that compounds show different activity of inhibition on growth of
the bacteria and finally the biological importance of the synthesized
ligands are assessed by performing docking studies using Auto Dock
VinaPyRx software.
Keywords: Schiff base; EPR study; Antimicrobial Activity;
Docking study;
Introduction
Transition metals are metallic elements that have an
incomplete d or f shells in the neutral or cationic states. These
incomplete valance shell orbitals allow it to accept electrons
from Lewis bases to form coordination complexes very easily
compared to other group of elements. Ligands therefore must be
a Lewis base. They must contain at least one pair of non-bonding
electrons that can be donated to a metal ion. The Schiff base is
named after Hugo Schiff and is a compound with a functional
group that contains a C-N double bond with the nitrogen
connected to an aryl or alkyl group. Schiff bases in a broad sense
have the general formula R1R2C=NR3, where R is an organic side
chain. Schiff base is synonymous with azomethine and may also
be referred to as imines.
Recently, Schiff bases are used as intermediates for the
synthesis of amino acids or as ligands for preparation of metal
complexes having a series of different structures [1]. Schiff
base compounds and their metal complexes are very important
as catalysts in various biological systems, polymers, dyes
and medicinal and pharmaceutical fields [2,3] they comprise
miscellaneous therapeutically potent applications in the field of
medicinal chemistry [4].Their use in birth control, food packages
and as an O2 de-tector is also outlined [3]. They have been
shown to exhibit a broad range of biological activities, including
antifungal, antibacterial, an-timalarial, anti-inflammatory,
antiviral, and antipyretic properties [5,6].
A variety of Schiff’s base and its complexes have been
studied extensively. Several mo¬del systems, including those
with bidentate, tridentate, tetradentate, multidentate Schiff base
ligands, and their coordination chemistry of cobalt (II), Nickel (II)
and copper (II) attracts much attention because of its biological
relevance and its own interesting coordination chemistry such
as geometry, flexible redox property. In this paper to discuss the
synthesis, spectroscopic and antimicrobial studies of Schiff’s
base and its cobalt (II), nickel (II) and copper (II) complexes. The
structures of the compounds are characterized by using IR, UV,
NMR, ESI mass and EPR spectroscopic techniques.
Experimental
All the chemicals used were of analytic grade, and were
purchased from Sigma-Aldrich. Metal salt were purchased from
E. Merck and were used as received. All solvents used were of
standard/spectroscopic grade.
Synthesis of Ligand (L)
Ligand (L) was synthesized by refluxing a hot ethanolic
Ligand (L) was synthesized by refluxing a hot ethanolic solution of Acetyl acetone, Salicylaldehyde. They were mixed
slowly with constant stirring. To the above mixture was added
an ethanolic solution of 3, 4-diaminobenzophenone. Their molar
ratio is 1:1:1 temperature was maintained at 70° C for 2.30 h in the
presence of Concentrated HCl. On cooling the content overnight
at 0°C an off white crystalline compound was separated out. This
was filtered, washed several times with ethanol and dried in a
vacuum desiccator over anhydrous calcium chloride. Yield 62%,
m.pt. 238°C.
Synthesis of complex
Hot ethanolic solution of ligand and hot ethanolic solution
of a given metal salt (cobalt nitrate, nickel nitrate and copper
nitrate hexa hydrate) in 1:1 molar ratio were mixed together with
constant stirring. The reaction mixture was refluxed at 70° C for
2.30 h. The volume of the reaction mixture was reduced to 20-
25%. The precipitate that formed was filtered off and washed
with ethanol and dried under vacuum over anhydrous CaCl2.
These are insoluble in water, chloroform, carbon tetrachloride,
acetonitrile and partially soluble in ether, alcohol but freely
soluble in DMF and DMSO.
Physical methods
The infrared spectrum was recorded using KBr pellets in
the range 4400-400 cm1. UV-Visible spectra of the ligand and
the complexes were recorded on Perkin Elmer Lambda 3B UVVisible
Spectrophotometer in the range 200-900 nm. The molar conductance of the ligand and the complexes were measured
using 10-3M solution of DMSO at 25°C using an Elico cm-180
Conductivity meter and Elico type CC-03 Conductivity cell of cell
constant 1.05 cm-1.The 1H&13C NMR spectra of the ligand and
complex was recorded in Joel 500 MHz NMR spectrometer using
(CD3)2SO. The mass spectra of the complexes were recorded by
JEOL GC mate Mass Spectrophotometer. Magnetic susceptibility
was measured at room temperature on a Gouy balance using
CuSO4.5H2O as a callibrant. The EPR spectra of the complex were
recorded as crystalline sample and in the solution of DMF at room
temperature on JEX-X3 Series of a system using the DPPH as the
g-marker. Antimicrobial activity was tested by using agar well
diffusion method and molecular docking studies were record
using Auto Dock VinaPyRx software.
Result and discussion
Ligand
The purity of the ligand (L) 98.62% has been checked by
HPLC. The ESI-mass spectrum (Figure 2) of the ligand (L) shows
a parental ion peak (M+) m/z = 398. The spectrum exhibit a
peak at m/z = 356 is due to C23H20N2O2 caution. A peak with high
intensity is present at m/z = 315 (85%) is due to base peak. This
peak is corresponding to cationic species with three aromatic
rings. The other peaks at 271, 237, 220, 179, 157, 119, 96, 82 and
59 are corresponding to other fragments.
Figure 1:Proposed structure of Ligand)
Figure 2:ESI Mass spectrum of Ligand (L)
The FTIR spectrum of the ligand (Figure 3) shows at 1607 cm-1
corresponding to the ν(C=N) stretching vibration and 3291cm-1
phenolic hydroxyl group. IR spectra of the ligand showed band
at 1287 cm-1 which is ascribed to the stretching vibration of the
phenolic aromatic oxygen [7]. The bands at 2671 cm-1 and 3070 cm-1 are corresponding to C-H stretching of aromatic ring [8].
The electronic spectrum of the Schiff base ligand (Figure
4) shows mainly two absorption bands at 252 and 345 nm.
The first band arise from π-π* transition with the azomethine
chromospheres [7].The second band at 350 nm is due to the n-π*
transition which is overlapping with the intermolecular CT from
the phenyl ring to the azomethine group. On the complexationthe absorption bands undergo a bathochromic shift compared to
the free ligand as a result of coordination via the nitrogen atoms
of the azomethine group.
In the 1H NMR spectrum of ligand (Figure 5) exhibit signals
at 2.50 ppm due to CH2-CN,3.39 ppm due to –CO-CH2, 2.11 ppm
due to CH3-C,[8]8.10 ppm due to Ar-CH=N [9]A sharp multiplet
signals7.03 – 7.81 ppm due to Ar-H. A singlet corresponding
to one proton observed at 12.80 ppm is due to Ar-OH. As well
as in the 13C NMR spectrum of ligand (Figure 6) indicated new
resonance are 19.05(C-CH3), 56 (C-CH2-CO), 113-138(C=C),
158.45(C=N), 195.95(Ph-CO-Ph) [14].

Figure 3:IR spectrum of Ligand (L))
Figure 4:Electronic spectrum of Ligand (L)
Figure 5:1H NMR spectrum of ligand (L)
Figure 6:13C NMR spectrum of ligand (L))
Metal Complexes
On the basis of molar conductance measurements (Table 1) of
the complexes in DMSO corresponds to be non-electrolytic nature
of the complexes. Thus the complexes may be formulated as [M (L)(NO3)-2].xH2O where M=Co(II), Ni(II) and Cu(II) and L is (E)-4-
((5-benzoyl-2-((E)-(2-hydroxybenzylidine)amino)phenyl)imino)
pentan-2-one.
Table 1: Molar conductance and Electronic Spectroscopic Data of the Schiff Base Ligand and its metal complex
Compound |
Molar conductance
Ω-1cm2mol-1 |
Colour |
M.P(oC) |
Yield (%) |
Λmax (nm) |
Ligand(L) |
- |
Off white |
237 |
68 |
252,345 |
[Co(L)(NO3)2
].xH2O |
16.23 |
Brown |
> 300 |
48 |
268,345,437,514,776 |
[Ni(L)(NO3)2
].xH2O |
9.80 |
Brown black |
> 300 |
45 |
258,335,437,550,776 |
[Cu(L)(NO3)2
].xH2O |
10.54 |
Dark brown |
294 |
50 |
285,367,431,660,730 |
Infra-red spectral bands due to anion
A comparative study of the FTIR spectra of ligand and its
metal complexes discloses that some peaks are common and
therefore, only important peaks, which have either shifted or
have newly appeared, are discussed. (Table 2) shows that ν(C-O)
and ν(C=N) modes appear at 1287-1327cm-1 and 1607-1618cm-1
respectively. The shifting of (C-O) to higher frequency as compared
to the ligand (1287cm-1) is owing to the conversion of hydrogen
bonded structure into a covalent metal bonded structure. Metalligand
bond is further confirmed by the appearance of a medium
intensity band in the range 474-478 and 522-536cm-1 in the
spectra of the complexes allotted to stretching frequencies of (MN)
bond and (M-O) bond formation respectively [10]IR spectra
of the nitrate complexes (Figure 7(a-c)), display three medium
intensity bands due to (N-O) stretching in the region ~1382–1384 cm-1, suggesting that both the nitrate groups are coordinated to
the central metal ion [11].

Figure 7:IR spectral bands of anions (a) [Co (L) (NO3)2].xH2O; (b) [Ni (L) (NO3)2] .xH2O; (c) [Cu (L)(NO3)2].xH2O
Table 2: Infrared Spectroscopic Data of the Schiff Base Ligand and its metal complex
Compound |
ν (C=N) |
ν (C-O) |
ν (M-N) |
ν (M-O) |
Ionic nitrate |
Ligand(L) |
1607 |
1287 |
- |
- |
- |
[Co(L)(NO3)2
].xH2O |
1616 |
1327 |
476 |
536 |
1382 |
[Ni(L)(NO3)2
].xH2O |
1618 |
1323 |
478 |
534 |
1382 |
[Cu(L)(NO3)2
].xH2O |
1610 |
1317 |
474 |
522 |
1384 |
Cobalt (II) complex
The magnetic moment measurement of the cobalt (II)
complex at room temperature lies in the range 4.98 –5.01 B.M.
The electronic spectrum of Co (II) complex show three bands
(Figure 8). These bands may be assigned to 4T1g→ 4sup>T2g (F) (ν1),
4T1g→4A2g (F) (ν2) and 4T1g→4T1g (P)(ν3) transitions, respectively
[12,13]. In the 1H NMR spectrum of cobalt (II) complex (Figure
9) exhibit A sharp multiplet signals 7.09 – 7.76 ppm due to Ar-H.
A singlet corresponding to one proton observed at 12.00-13.00
ppm is due to Ar-OH. [8, 9] As well as the13C NMR spectrum
(Figure10) agree with the expected absorptions indicated new
resonance are 47.86 (C-CH2-CO), 113-138(C=C), 159.00 (C=N),
195.64(Ph-CO-Ph) [14].
Figure 8:Electronic spectrum of Co (II) complex
Figure 9:1H NMR spectrum of Cobalt (II) Complex
Figure 10:13CNMR spectrum of Cobalt (II) Complex
Nickel (II) complex
The magnetic moment of the Ni(II) complex at room
temperature lie in the range 2.96-2.98 B.M.[15]These values show
the presence of octahedral configuration. These complex display
three electronic spectral bands (Figure 11) at 776, 570 and
437nm assignable to 3A2g→3T2g (F) (ν1), 3A2g→3T1g (F) (ν2) and
3A2g→3T1g (P) (ν3) transitions, respectively. These bands indicate
that the complex have also confirm an octahedral geometry and
might possess D4h symmetry [12].The 1H NMR and 13C NMR
spectrum shown in the (figure12, 13). These signals also confirm
the hydrogen and the Carbon environment of the complex.
Figure 11:Electronic spectrum of Ni (II) complex
Table 3: Diameter of zone inhibition (mm) for the Schiff base ligand and its complexes
Microorganism |
Escherichia coli |
Staphylococcus |
Enterococci |
Pseudomonas |
25 |
50 |
100 |
25 |
50 |
100 |
25 |
50 |
100 |
25 |
50 |
100 |
Ligand(L) |
- |
5mm |
9mm |
8mm |
10mm |
11mm |
4mm |
7mm |
13mm |
- |
- |
- |
[Co(L)(NO3)2
].xH2O |
- |
8mm |
10mm |
- |
- |
- |
5mm |
7mm |
9 mm |
- |
4mm |
9mm |
[Ni(L)(NO3)2
].xH2O |
- |
5mm |
8mm |
6mm |
8mm |
10mm |
7mm |
9mm |
12mm |
- |
- |
7mm |
[Cu(L)(NO3)2
].xH2O |
- |
- |
- |
- |
- |
- |
- |
- |
5 mm |
- |
- |
4mm |
Ligand/Complex |
Binding Affinity (kcal/mol) |
Ligand |
-7.9 |
Copper (II) complex |
-9.0 |
Nickel (II) complex |
-9.5 |
Figure 12:1H NMR spectrum of Cobalt (II) Complex
Figure 13:1H NMR spectrum of Cobalt (II) Complex
Copper (II) complex
The magnetic moment measurement of the copper(II)
complex at room temperature lie in the range 1.83 –1.85 B.M.
[16,17] Three spin allowed transition may be expected in the
visible region and the Eg and T2g levels of 2D free ion will split
into B1g, A1g, B2g and Eg levels respectively. Electronic spectrum
(Figure14) of six coordinated copper complex display band at
730,660 and 431nm corresponding to the following transitions
2B1g →2B2g; 2B1g →2Eg and 2B1g →2A1g. The EPR spectrum of
Cu (II) complex (Figure15) is recorded at room temperature in
DMF solution, lie in the range 2.0204-2.01142. The trend g|| >g┴
>2.0023 observed for the complex indicates that the unpaired
electron is localized in the dx dx2-y2 orbital of the Cu (II) ion and
is characteristic for the axial symmetry. The shape of the ESR
line indicates that the present complex has distorted octahedral
complex
Figure 14:Electronic spectrum of Cu (II) complex
Figure 15:EPR spectrum of Cu (II) complex
Antimicrobial activity
Antimicrobial activity was estimated as described by [18]
Surface of the Mueller Hinton Agar (MHA) plates were inoculated
by spreading a volume of the microbial inoculums (0.5 McFarland
standards) over the entire agar surface. Then, a hole with a
diameter of 6 to 8mm was punched aseptically with a sterile
cork borer and a volume (20–100 mL) of the extract solution at
desired concentration is introduced into the wells. Then, agar
plates were incubated at 37°C for 24hours. The antimicrobial
agent diffuses in the agar medium and inhibits the growth of the
microbial strain tested the zone of inhibition was measured with
a measuring scale. The antimicrobial activity of the ligand and
its Co(II),Ni(II) and Cu(II) metal complexes were assayed against
(i) Gram-positive bacteria: Staphylococcus aureus, Enterococci
and (ii) Gram-negative bacteria: Escherichia coli, Pseudomonas
aeruginosa. The result of antimicrobial activity is summarized
in (Table 3). From the data it is clear that the metal complex is
effective against bacteria.
Molecular docking study
The biological importance of the synthesized ligands are
assessed by performing docking studies using Auto Dock
VinaPyRx software [19]. The retrieved pdb file (4s1y) is given as
input in Auto Dock Vina and assigned as macromolecule that adds
charges and hydrogen bonds to the atoms thus preparing the
protein. Ligand preparation including the generation of various
tautomers, assigning bond orders, ring conformations and stereo
chemistries of the ligand were carried out. All the conformations
generated were further used for docking study. A receptor grid
was generated around the protein active site by selecting the
active residues (His 288, Met 298, Met 329, and Met 548) and
Run auto grid option. The docking calculations were performed
using Run Vina and the Binding affinity was used to determine
the best docked structure from the output. The predicted binding
affinity is in kcal/mol. The pdb structure 4s1y [20] of human
serum albumin is used for docking studies which plays a key role
in increasing the growth and productivity of cells and increases
overall cell health. The best docked complex selected has a binding
score of -9.5 for Cu (II) complex which predicts a good inhibition.
The pdb structure 4sy1 of human serum albumin is used for
the docking studies with 2 different compounds containing the
Copper and Nickel complexes. The one with best binding affinity
is considered for analysis. The following table shows the binding
affinity of ligand with 4sy1.
Docking score using Auto dock Vina with the macro molecule
4s1y.
The docked ligand interacts with the protein by forming
three H bonds with the residues Ser192 and Glu292 with bond
distances 3.33Å and 3.53Å respectively (Figure 16).
Similarly Copper (II) complex also forms 3 H-bonds with the
protein in residues Glu292, Gln196, Lys 199 with bond distances
3.43 Å, 3.09Å and 3.21 Å respectively (Figure 17). Nickel (II)
complex forms 2 H-bonds with Lys195Å and Ala191Å residue
with bond distance 3.20Å and 3.35Å (Figure 18).

Figure 16:Ligand docked with 4s1y showing formation of hydrogen bond and distances
Figure 17:Copper (II) complex docked with 4s1y showing formation of hydrogen bond and distances
Figure 18:Nickel (II) complex docked with 4s1y showing formation of hydrogen bond and distances
Conclusions
Some new di-imino Schiff base ligands and their complexes
with Co (II), Ni (II) and Cu (II) were synthesized and characterized.
All the complexes were octahedral in nature. The binding affinity
values were determined from docking studies using Auto Dock
VinaPyRx software. The antimicrobial activity of the ligand and
its metal complexes were assayed against Gram-positive and
Gram-negative bacteria. The result of antimicrobial activity is
shown that the metal complexes are effective against bacteria
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