Experimental and theoretical analysis of molecular structure, vibrational spectra and biological properties of the new Co(II), Ni(II) and Cu(II) Schiff base metal complexes

Article abstract of DOI:10.1016/j.molstruc.2021.130097

A new novel Cobalt, Nickel and Copper metal complexes were synthesized from Schiff base ligand of 2,2′-((1E,1′E)-((4-nitro-1,2-phenylene) bis(azanylylidene)) bis(methanylylidene)) diphenol. The structures of all the synthesised compounds have been analyse

Full text of DOI:10.1016/j.molstruc.2021.130097

Journal of Molecular Structure 1233 (2021) 130097
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstr
Experimental and theoretical analysis of molecular structure,
vibrational spectra and biological properties of the new Co(II), Ni(II)
and Cu(II) Schiff base metal complexes
a
a
b,∗
c
d
e
R.V. Sakthivel , P. Sankudevan , P. Vennila , G. Venkatesh , S. Kaya , G. Serdaro g˘ lu
a
Department of Chemistry, Arignar Anna Government Arts College, Namakkal–637 002, India
b
Department of Chemistry, Thiruvalluvar Government arts college, Rasipuram–637 401, India
c
Department of Chemistry, VSA Group of Institutions, Salem- 636010, India
d
Department of Chemistry, Cumhuriyet University, Sivas-58140, Turkey
e
Sivas Cumhuriyet University, Faculty of Education, Math. and Sci. Edu. 58140, Sivas, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
A new novel Cobalt, Nickel and Copper metal complexes were synthesized from Schiff base ligand of
Received 21 November 2020
Revised 5 February 2021
Accepted 5 February 2021
Available online 15 February 2021
ꢀ ꢀ
2
,2 -((1E,1 E)-((4-nitro-1,2-phenylene) bis(azanylylidene)) bis(methanylylidene)) diphenol. The structures
of all the synthesised compounds have been analysed using Fourier-Transform Infrared (FT-IR), Nuclear
Magnetic Resonance (NMR) spectroscopy, Ultraviolet-Visible (UV-Vis) spectrum, elemental analysis and
Powder X-ray diffraction (PXRD). The experimental spectral frequencies of ligand and metal complexes
are correlated with theoretically computed vibrational frequencies. The molecular structure of the ligand
and its metal complexes has been optimized using B3LYP-6-311G(d,p)/LANL2DZ basis set and their pa-
rameters have been discussed. Natural bond orbital and Frontier Molecular Orbital analysis have assessed
the presence of a metal-ligand bond in complexes. Further, biological activity studies such as antioxidant,
anti-inflammatory, antidiabetic have also been analyzed using various methods. In addition, molecular
docking studies have also been performed on all complexes using the α-amylase enzyme structure to
calculate the possible binding energy of inhibitors.
Keywords:
Schiff base
Ultraviolet-visible
Geometrical parameters
Antioxidant activity
Molecular docking
©
2021 Published by Elsevier B.V.
1
. Introduction
sors for tracking cellular operations in organisms [8]. A Saadeh re-
searcher claimed that several Cu(II) N, O, S-donor chelators have
acted as an excellent anticancer agent due to its strong bind-
ing capacity among DNA base pairs [9]. Schiff base based on the
metal complexes was examined against Gram positive and nega-
tive pathogenic microorganisms [10,11]. The transition metal ions
such as Co(II), Ni(II) and Cu(II) complexes continue to exist as co-
factors in several oxidative enzymes as tyrosinase hydrogenase and
lactase [12].
Schiff bases and their metal complexes are extremely utilized
in catalytic and the medicinal field due to their greater stability
and chelating properties [1]. Similarly, more attention has been fo-
cused on the production of transition metal complexes with Schiff
bases due to occurrences of N and O donor atoms [2-4]. Transition
metal complexes based on the nitro and halogen groups have rich
antimicrobial properties. In the past, several researchers suggested
that the biological behaviour, e.g., antibacterial, antifungal and an-
titumor activities, is demonstrated by salicylaldehyde derivatives
along with halogen aromatic rings [5,6]. The transition metal com-
plexes provide constant and colored metal complexes with attrac-
tive physic-chemical properties, as well as advantageous biological
character. Transitional metal complexes binding analysis have re-
cently become the most significant sector in the growth of DNA
probes and chemotherapy [7]. In addition, it is also used as sen-
Simple compounds that are associated and interact with DNA
usually increase their biological potential. 3d-transition metal com-
plexes are a group of compounds containing metal centre and het-
eroatoms such as N, O and S, which have been capable of inter-
acting with nucleic acid through the formation of H-bonds [13-
15]. Usually, biologically active compounds improve their cleav-
age activity and thus provide a qualified anti-proliferative agent
for various tumor types. Transition metals and ligand integrating
this heterocyclic group may undergo a variety of unexpected re-
actions leading to novel structures and products, several of which
are of directly relevant to biological processes [15]. A great deal
of importance in the transition metal complexes of 4-Nitro-o-
∗
Corresponding author.
E-mail address: vennilaindhu84@gmail.com (P. Vennila).
https://doi.org/10.1016/j.molstruc.2021.130097
0
022-2860/© 2021 Published by Elsevier B.V.

R.V. Sakthivel, P. Sankudevan, P. Vennila et al.
Journal of Molecular Structure 1233 (2021) 130097
phenylenediamine as well as its derivatives has been thoroughly
discussed in recent years owing to its unique biological properties
and improved DNA binding capabilities. Density Functional The-
ory (DFT) based on a theoretical calculation of molecular structural
properties, HOMO and LUMO are strongly interpreted with the de-
sign of the drug molecules. In addition, molecular docking studies
have made a significant contribution to the interactions of tran-
sition metal complexes between reactive protein target sites that
are responsible for antioxidant and biological activity. There is a
demand for synthesis of innovative compounds with antimicrobial,
DNA-binding and other activity.
the Gaussian 09W program [20]. The optimized structure is visual-
ized by Gauss view 5.0.8 version. In the Conceptual Density Func-
tional Theory [20], the relationship with total electronic energy
(E), the number of electrons (N), ionization energy (I) and elec-
tron affinity (A) of quantum chemical descriptors like electroneg-
ativity (χ), chemical potential (μ), hardness (η) and softness (σ)
at a constant external potential are described with the help of the
following formulas.
ꢀ
ꢁ
∂
∂
E
I + A
μ = −χ =
= −{
}
(1)
(2)
(3)
N
2
v(r)
Observation of the above-mentioned literature revealed that the
Schiff base transition metal complexes were frequently used for
pharmaceutical applications. In the present study, an interesting
report from the research literature, it is planned to synthesize
a few new 3d-transition metal complexes of bis(salicylaldehyde)
with Nitro-O-phenylenediamine of Schiff base ligand. Further,
molecular characterization, biological activity (such as total an-
tioxidant, anti-inflammatory, anti-diabetic) molecular docking and
physicochemical parameters of metal complexes are also discussed
with the theoretical calculation.
ꢀ
ꢁ
2
1 ∂ E
I − A
η =
σ =
= {
}
2
2 ∂N
2
v(r)
1
η
It is required to measure the ionization energy and electron
affinity values for determining the experimental values of hard-
ness and chemical potential. On the other hand, Koopmans Theo-
rem [21], which is a bridge between Conceptual Density Functional
Theory and Molecular Orbital Theory can be used for the approx-
imate prediction of ionization energy and electron affinity values
of molecules. According to this theorem, the negative values of en-
ergies of HOMO and LUMO orbitals of any molecule correspond to
its ionization energy and electron affinity, respectively. In this way,
the aforementioned quantum chemical parameters are calculated
using frontier orbital energies. To describe the electrophilic power
of chemical species, in 1999, Parr, Szentpaly and Liu [22] modelled
electrophilicity index (ω) based on electronegativity (or chemical
potential) and hardness of chemical species via the following for-
mula. Then Chattaraj defined the nucleophilicity (ε) is the multi-
plicative inverse of electrophilicity index.
2. Experimental
2
.1. Materials and methods
All chemicals were purchased from Sigma Aldrich (spectro-
scopic grade) and used without further purification. The elements
C, N and H) were analyzed by Vario EL III CHN type of equip-
ment. The FT-IR spectra of synthesized ligand and its metal com-
(
−
1
1
plexes were recorded in the region 4000–400 cm
in evacuation
resolution on a
−
mode using a KBr pellet technique with 1.0 cm
PERKIN ELMER FT-IR spectrophotometer (SAIF, IIT, Chennai, India).
The chemical shifts of 13C and 1H-NMR have been recorded on a
Bruker-DRX-400 MHz spectrophotometer using DMSO-d6 with in-
ternal reference as TMS (Sastra university, Thanjavur, Tamil Nadu).
The UV-Vis spectra were recorded using a shimadzu 1800 PC spec-
trophotometer in the range of 200-800 nm using a DMSO solvent
2
μ2
χ
ω = 2
=
(4)
(5)
η
2η
1
ε =
(
Central Research Laboratory, Erode-Tamil Nadu).
ω
Polarizability (α) is another reactivity descriptor and it is calcu-
2.1.1. Synthesis of ligand
lated depending on diagonal components of polarizability tensor.
The Schiff base ligand is prepared with a condensation reaction
of 0.1 mol of 4-Nitro-o-phenylenediamine and 0.2 mol of salicy-
laldehyde blended with 50 ml ethanol and the mixture solution is
stirred well with reflux for 2 hours after the mixture slowly turned
into yellow precipitate. The precipitate is filtered and washed with
distilled water several times. The precipitate is recrystallized using
methanol followed by drying at 50°C overnight [16,17].
α¯ = 1/3[αxx + αyy + αzz]
(6)
Addition, the second order-perturbative energies of Co(II), Ni(II)
and Cu(II) complexes obtained from the natural bond orbital analy-
sis (NBO) [23,24] have been used in elucidating of the intramolec-
ular interactions.
2
.1.2. Synthesis of metal complexes
Three hydrated metal salts (CoCl .6H O, NiCl .2H O and
2
2
.2. Biological study
2
2
2
2
CuCl .2H O) have been used to synthesize Schiff base metal (II)
2
2
.2.1. Total antioxidant activity
complexes. Schiff base ligand 0.74 g (3 mol) is separately added
with each metal chlorides of 0.18 g of CoCl .6H O, 0.10 g of
The total antioxidant properties of the title metal complexes
2
2
were calculated by the method of prito et al. [25].
NiCl .2H O and 0.26 g of CuCl .2H O in 20 ml of ethanol solution.
2
2
2
2
After the mixture was well stirred at room temperature colored
metal complexes are obtained and the color precipitate is filtrated
followed by washing with ethanol, then dried.
2
.2.2. Antidiabetic activity
The antidiabetic activity was performed using the appha amy-
lase method [26]. The procedures are given in supplementary ma-
terial.
2
.1.3. Computation study
Vibrational frequency and geometrical optimization calcula-
tions of ligand and their complexes were performed by B3LYP-6-
11G(d,p)/LANL2DZ [18,19] functional. The optimized structure of
2.2.3. Anti-inflammatory activity (BSA denaturation technique)
The in vitro anti-inflammatory behaviour of metal complexes
was investigated via bovine serum albumin (protein denaturation
technique) [27]. The procedures are given in supplementary mate-
rial.
3
ligand and metal complexes have established to the ground state
using the absence of imaginary frequency in the force constant
method and were predicted without symmetry constraint utilizing
2

R.V. Sakthivel, P. Sankudevan, P. Vennila et al.
Journal of Molecular Structure 1233 (2021) 130097
Table 1
Physical data and elemental analysis of the ligand and metal complexes.
Compound
Molecular formula
Colour
M.Pt (°C)
Elemental analysis (%)
Found (Cal.) (Metal %)
Molar conductance
C
H
N
Ligand
C20H15N3O4
Yellow
361
489
488
493
66.48
49.21
49.13
48.85
4.19
2.78
2.81
2.65
11.83
8.69
8.59
8.51
-
-
Cobalt complex
Nickel complex
Copper complex
C20H13CoN3O4
C20H13NiN3O4
C20H13CuN3O4
Brown
12.16
12.00
12.88
11.14
12.21
14.48
Light green
Green
Scheme 1. Synthetic route of Schiff base ligand and its metal complexes.
2
.2.4. Molecular docking
3.1. Electronic spectra
The molecular docking studies are performed using HEX 8.0
software. The three-dimensional structure of the title compounds
was built by using Chem Bio 3D ultra 13.0 software and is mini-
mized by MM2 with a maximum number of 5000 iterations and
a minimum RMS gradient of 0.10. Crystal protein structure (PDB
ID: 1HNY.pdb) were obtained by Protein Data Bank (www.rcsb.org)
and docked molecules imaged by discovery studio 4.1 [28].
The observed electronic spectra of the ligand and its metal
complexes were recorded in DMSO solutions at 200-800 nm ranges
[29]. Electronic spectra of the metal complexes are closely inter-
preted with ligand and shown in Fig. 1. The absorption bands of
the Schiff base ligand vary with their metal complexes which re-
vealed that ligand coordination with the metal ions. The Schiff
base ligand, displayed two strong absorption bands at 284 and 478
nm were attributed to n→π∗ and π→π∗ electronic transitions re-
spectively. Consequently, the electronic spectra of Co(II) complex
3. Results and discussion
appeared in medium intensity bands at 336, 389, 496 nm were
attributed to π→π , L→M (LMCT), 4A2F
∗
→
4T1p transitions, indi-
The percentage of elemental analysis of ligand and metal com-
cating that less-spin distorted tetrahedral geometry. Similarly, the
magnetic moment value of the Co(II) complex was determined to
be 3.88 B.M. and is also responsible for the predicted distorted
tetrahedral geometry [15,30]. Further, electronic absorption spectra
plexes is well associated with the suggested structure [29,30]. The
title metal complexes and neutral Schiff base ligand were ther-
mally stable (room temperature) and soluble in DMF and DMSO,
though partly soluble in alcohol. The percentage of CHN data,
physical data and molar conductance for synthesized compounds
are tabulated in Table 1. The proposed structure of Cobalt, Nickel
and Copper metal complexes are illustrated in Scheme 1.
of Ni(II) complex are observed three absorption bands at 332, 384
and 492 nm due to π→π , L→M (LMCT), 1A1g
∗
→
1A2g transitions,
respectively [29,30]. Likewise, Ni(II) complex exhibits a magnetic
3

R.V. Sakthivel, P. Sankudevan, P. Vennila et al.
Journal of Molecular Structure 1233 (2021) 130097
Table 2
Calculated energies, dipole moments (μ), maximum absorption wavelengths (λmax), excitation energies (eV), oscillator strengths (f), assign-
ment of electronic transitions (HOMO(H)→LUMO(L)) and major contribution (%) for the metal complexes and ligand in DMSO solvents.
Ligand &
Parameters
Etotal (a.u)
-
complexes
Dipole moment
6.552
λ
max
f
Transition energy
Electronic transition
Major % contribution
Ligand
286.48
476.52
310.59
452.18
313.48
458.66
324.66
498.84
0.3024
0.1436
0.1984
0.0129
0.2817
0.0146
0.4434
0.0109
2.6475
2.9938
1.8193
2.0314
2.1936
2.2886
2.8556
3.0143
H→L
94.60%
95.26%
94.38%
95.62%
93.35%
94.24%
95.26%
96.39%
1
-
236.23
H-1→L
H→L
Cobalt
5.293
2.714
5.131
complex
Nickel
2300.42
H-1→L
H→L
-
complex
Copper
complex
2325.22
-
H-1→L
H→L
2351.39
H-1→L
Fig. 2. Calculated UV-Vis absorption bands of metal complexes and Schiff base lig-
and.
Fig. 1. Electronic spectra of metal complexes and Schiff base ligand.
moment value of zero B.M., which indicates a square planar geom-
etry [31]. Additionally, the absorption bands of Cu(II) complex ex-
∗
isted at 318, 444, 528 nm were assigned to π→π , L→M (LMCT),
2
2
B g→ A g transitions and magnetic moment value was found to
1
1
be 1.86 B.M., which suggests that the Cu(II) complex had a square
planar geometry [15,30,32]. In addition, the calculated dipole mo-
ment (μ), wavelength maxima (λmax), electronic transition, atomic
orbital major contribution, oscillator strength (f) and absorption
energy (E) are shown in Table 2. The calculated strong absorption
bands were found to be 476.52 nm for Schiff base ligand, 452.18
nm for Co(II) complex, 458.66 nm for Ni(II) complex and 498.84
nm for Cu(II) complex and are shown in Fig. 2. The results sug-
gesting that electrons occurred from EHOMO to ELUMO transition
(
95.26, 95.62, 94.24 and 96.39 % orbital contribution).
3
.2. Powder X-ray diffraction (XRD) study
Powder X-ray diffraction peaks of title compounds were ob-
Fig. 3. Powder X-ray diffraction of ligand and metal complexes.
served in the range of 2θ=10-90° using XPERT-3 diffractometer at
5°C [33]. While single crystal X-ray crystallography is the most
2
Co2 , Ni
+
2+
2+
and Cu complexes and ligand comprise an average
reliable source of information on the structure of the complex, the
difficulty of obtaining appropriate crystals in the correct symmetri-
cal form has made this approach unsuitable for such a study. Dur-
ing the powder X-ray diffraction study (Fig. 3) showed, only Cu (II)
complexes displayed sharp peaks, although no peaks were seen for
the rest of the complexes suggesting their amorphous existence. A
comparison of ligand diffractograms and complexes revealed the
crystalline nature of the complex. The average grain size of the
complexes was calculated using the Debye Scherer equation. The
crystalline size of 24.1 nm, 42.3 nm and 28.4 nm and 59.6 nm, re-
spectively.
3.3. Vibrational spectra
Vibrational study on the basis of both experimental and the-
oretical approaches provides a detailed understanding of the na-
ture of functional groups, the evaluation of structural changes and
4

R.V. Sakthivel, P. Sankudevan, P. Vennila et al.
Journal of Molecular Structure 1233 (2021) 130097
Table 3
Assignments of fundamental vibrations of metal complexes.
Metal complexes/
Functional group
Copper complex
Nickel complex
Cobalt complex
S. no.
Exp.
Scaled
Exp.
Scaled
Exp.
Scaled
1
2
3
4
5
6
νCH
νNC
βNC
νON
νC=C
νOC
3154
1644
865
3088
1629
908
3211
1613
815
3094
1668
912
3076
1626
806
3115
1659
854
1341
1441
1031
1356
1482
1044
1412
1496
996
1436
1463
1021
1337
1458
964
1362
1469
985
compound of chemical shifts isotropic carbons is obtainable in the
range of 100-160 ppm. The 13C and 1H NMR spectra of Schiff base
ligand are shown in Fig.S2 and S3. The 13C and 1H NMR spectra
of ligand is calculated by B3LYP function/6-311++G (2d,p) basis
set, which quite agreed with experimental NMR spectra shown in
Table 4. In this analysis, 13C chemical shift aromatic carbon (C5)
is detected at 158.2 ppm due to increased electronegativity of the
NO2 group assigned to the aromatic ring. The observed 13C chem-
ical shifts of aromatic ring carbons arrived at C29 (138.5), C18
(
136.9), C1 (135.8), C6 (128.4), C32 (127.6), C28 (123.4), C19 (122.5),
C33 (118.8), C33 (119.3), C27 (119.6), C17 (118.2), C4 (121.6), C21
123.4), C3 (126.8) and C20 (119.2) ppm were in quite agreement
(
with the theoretically calculated chemical shifts. The aliphatic car-
bon C15 and C16 chemical shift are obtained at 55.4 and 61.5 ppm.
The results (Table 4) are clearly shown that the electronegative
assets polarizing of O and N have influenced the distribution of
the electron adjacent carbon atoms, which have decreased electron
density as well as chemical shifts are appeared in higher down
filed values. Similarly, H39 and H40 proton chemical shifts are ar-
rived at 8.6 and 8.4 ppm, respectively. Additionally, H41 and H42
proton chemical shifts found to be 3.4 and 2.9 ppm and also coin-
cide with calculated values.
Fig. 4. Experimental FT-IR spectra of metal complexes and Schiff base ligand.
the prediction of their spectral characteristics. The experimental
and theoretically calculated vibration spectra of title compounds
are shown in Fig. 4 and S1. The observed (O-H stretching fre-
quencies) vibrational spectra of ligand showed large bands at 3512,
3.5. Geometrical parameters
−
3
3
429 cm 1, which are correlated well with calculated bands of
440 and 3438. In the present study, experimentally observed C-
The applicable geometrical parameters of metal complexes and
neutral ligand are numbered according to the convention shown
in Fig. 5. The physic-chemical parameter of bond length, bond
angle and dihedral angles of title compounds are presented in
(supplementary material) Tables S2-S5. The theoretically calculated
H vibrational bands of ligand have appeared in the ranges 3158-
2
846 cm 1 whereas the calculated vibration bands were assigned
−
−
1
to 3145-2878 cm (refer supplementary material in Table S1).
The observed C-N stretching frequencies of ligand are assigned
at 1672, 1654 cm 1, which also agreed with calculated bands of
−
˚
(ligand) bond lengths of N-O ≈1.29 (1.28 A), C=N ≈ 1.29 (1.28
1
655 and 1642 cm 1. The coordination of metal through the N
−
A), C-N ≈1.39 (1.42 A), C-O ≈1.37 (1.34 A), O-H ≈0.99 (0.97 A)
˚
˚
˚
˚
˚
and O atoms of aromatic ring cause significant changes in the
bands arrived for ligand after the complexation, which was evident
from IR bands of both ligand and metal complexes [32-35]. The
metal complexes sharp absorption frequencies appeared at 1644
slightly deviate (RMSD ≈ 0.95 A) from the literature data [17,33
and 34]. The important bond length (C-N and C-C) of metal com-
plexes M-O and M-N (Metal(M)) have slightly deviated than ligand
(refer Table S2-S5 supplementary material) due to some amount
of charge transferred metal ion to ligand (ligand coordinated to
metal ion). This result also accords with the prediction of IR
and NMR spectra. In Co(II) complex, the bond length of Co41-
O38, O37-Co41, N11-Co41, N10-Co41 are 1.90 (2.11°), 1.91 (2.06°),
1.93 (1.98°), 1.91 (1.96°), respectively. The bond angles of O38-
Co41-N10, O37-Co41-O38, N11-Co41-N10, N11-Co41-O37 are 104.9
(110.5°), 85.4 (90.6°), 110.5 (108.9°), 94.6 (91.4°) respectively. Sim-
ilarly in Ni(II) complex, the bond length of Ni41-N10, N11-Ni41,
Ni41-Co37, Ni41-Co38 are 1.87 (1.85°), 1.88 (1.86°), 1.83 (1.84°), 1.84
(
Cu(II)), 1613 (Ni(II)) and 1626 (Co(II)) cm 1, which are also cor-
−
related with calculated bands. Similarly, C-N bending vibrational
−1
frequencies are assigned at 865 (Cu(II)), 815 (Ni(II)) and 806 cm
Co(II)), which correlated well with calculated bands (Table 3).
The observed medium C-C stretching vibrational band appeared at
(
1
441 (Cu(II)), 1496 (Ni(II)) and 1458 (Co(II)) cm 1. Further, the ex-
−
perimental N-O stretching vibrational frequencies arrived at 1341
Cu(II)), 1412 (Ni(II)) and 1337 (Co(II)) cm 1. It is noted that the
−
(
band moved towards the lesser frequency after its complexation.
(
1.83°), respectively. The bond angle of N10-Ni41-N11, N10-Ni41-
N11, O38-Ni41-O37, N11-Ni41-O37 are 108.3 (114.8°), 111.8 (110.9°),
6.9 (90.4°), 98.4 (92.6°), respectively. Further, in Cu(II) complex,
3
.4. NMR spectra
8
The NMR spectroscopy are powerful tools for the direct detec-
O38-Cu41, N10-Cu41, N11-Cu41, O37-Cu41 are 1.94 (1.91°), 1.99
(1.92°), 2.03 (1.93°), 1.99 (1.94°), respectively. The bond angle of
O38-Cu41-N10, N11-Cu41-N10, N11-Cu41-O37, O37-Cu41-O38 are
108.3 (11.8°), 109.2 (115.4°), 94.8 (90.5°), 88.45 (91.4°), respectively.
The calculated bond angles of the metal complexes and the neu-
tion of chemical species and forms of molecular interactions in
complex materials. The NMR spectral analysis provided a compre-
hensive account that was considered to be suitable for the assign-
ment of protons ( H) and carbon (13C). Commonly, the aromatic
1
5

R.V. Sakthivel, P. Sankudevan, P. Vennila et al.
Journal of Molecular Structure 1233 (2021) 130097
Table 4
1H & 13 C NMR spectral data of Schiff base ligand.
Atoms
Experimental chemical
B3LYP/6-311+G(2d,p) GIAO
Atoms
Experimental chemical
B3LYP/6-311+G(2d,p) GIAO
shift (σ) ppm
shift (σ) ppm
C5
158.2
138.5
136.9
135.8
136.4
128.4
127.6
123.4
122.5
118.8
119.3
119.6
118.2
121.6
123.4
123.9
126.8
119.2
154.43
139.9
138.1
137.1
135.5
132.5
128.3
118.9
118.5
114.0
113.5
119.0
118.9
115.8
103.9
103.9
120.8
115.4
C15
C16
H39
H40
H8
55.4
61.5
8.5
8.3
7.2
7.4
7.5
7.6
6.9
6.6
6.4
6.2
5.8
6.4
5.9
3.4
2.9
-
64.9
76.9
8.6
8.4
6.9
6.7
6.1
6.0
5.9
5.8
5.6
5.6
5.4
4.8
4.7
3.6
3.5
-
C29
C18
C1
C2
C6
H9
C32
C28
C19
C23
C33
C27
C17
C4
H31
H22
H26
H36
H34
H25
H7
H24
H35
H42
H41
-
C21
C30
C3
C20
Fig. 5. Optimized molecular structure (a) Schiff base ligand (b) Cobalt complex (c) Nickel complex and (d) Copper complex.
tral ligand are close to the values of literature and the sligltly
3.6. Frontier molecular orbitals
˚
deviated is approximately 0.98 A (RMSD). Additionally, the dihe-
dral angles of the metal complexes and the neutral ligand indicate
that the fragment does not have the same plane as the rest of the
complex.
Some electronic structure principle called as Maximum Hard-
ness Principle [36], Hard and Soft Acids Bases Principle [37], Min-
imum Electrophilicity Principle [38], Minimum Polarizability Prin-
6

R.V. Sakthivel, P. Sankudevan, P. Vennila et al.
Journal of Molecular Structure 1233 (2021) 130097
Table 5
Quantum Chemical Parameters of Cobalt, Nickel and Copper complexes at B3LYP/6-
11G(d,p)/LANL2DZ.
3
Parameters
Schiff base ligand
Cobalt complex
Nickel complex
Copper complex
HOMO (-I)
LUMO (-A)
-5.97
-2.27
3.70
-9.63
-8.71
0.92
-9.64
-8.43
1.21
-9.75
-8.49
1.27
ꢀ
E (L-H)
μ=-(I+A)/2
η=(I-A)/2
-4.12
1.85
-9.17
0.46
-9.04
0.61
-9.12
0.63
∗
ω=μ μ/2η
4.59
90.88
19.82
494.25
3.94
67.33
14.90
395.59
6.12
65.66
14.40
508.15
3.33
ꢀ
Nmax=-μ/η
2.23
α (au)
299.99
9.41
DM (debye)
DE (a.u)
-1236.18
-2300.36
-2325.17
-2351.33
ciple [39] and Minimum Magnetizability Principle [40] in the lit-
erature provide useful information about stability or reactivity of
molecules. Chemical hardness is defined as the resistance to charge
transfer of chemical species. HSAB theory suggests that "hard acids
tend to coordinate hard bases and soft acids tend to coordinate
soft bases." According to Maximum Hardness Theorem, chemical
hardness is a prerequisite for consistency and hard molecules are
more stable compared to soft ones. In the hard and soft classifi-
MEP plots obtained from the total SCF (self-consistent-field) den-
sity clearly represent the electron-rich and electron-poor region
based on the electrostatic potential. As expected, the surround-
ing of the oxygen and nitrogen atoms are the red color demon-
strating the electron-rich field having the highest negative elec-
trostatic potential value. And the hydrogen atoms of the hydroxy
group are the blue color implying the electron-poor regions hav-
ing the highest positive electrostatic potential value. The presence
of the metal atom in the molecule influences the distribution of
the electron density: all-metal complexes mainly show the green-
blue color all over their surfaces. Here, the electrostatic potential
value has been determined as Cu(II) (± 0.778e) > Ni(II) (± 0.353e)
> Co(II) (± 0.214e) that support the tendency of the antioxidant ac-
tivity of these complexes.
cation of Pearson, Co2 , Ni , Cu
+
2+
2+
ions appear among borderline
acids. Experimental hardness values of these ions obey the order:
Cu2 > Ni > Co
2+
[40,41]. In our calculations, we obtained the
+
2+
same order. It is apparent from the data given in the related table
that the ligand considered in this study is harder than the afore-
mentioned ions. If so, one can say that the ligand interacts more
powerful with Cu2 ion. Already, hardness value of Copper com-
plex is higher than that of others and this complex is more stable
compared to Nickel and Cobalt complexes (refer Table 5).
+
3.7. Natural bond orbitals
Minimum Electrophilicity Principle and Minimum Polarizability
Principle have been suggested by inspiring from Maximum Hard-
ness Principle. Minimum Electrophilicity Principle states that in an
exothermic reaction, sum of the electrophilicity values of prod-
ucts should be smaller than that of reactants. It can be understood
from this information, electrophilicity can be also used in reactiv-
ity analysis of molecules. Stable molecules should have lower elec-
trophilicity values compared to reactive molecules. If so, Minimum
Electrophilicity also confirms the stability of Copper complex. Ac-
cording to the Minimum Polarizability Principle, in a stable state,
polarizability is minimized. It is important to note that the relation
between polarizability and softness has been proven by Ghanty
and Ghosh. Minimum Polarizability Principle and the polarizabil-
ity data given in the related table imply that Nickel complex will
be more stable compared to others. This result is not compatible
with experimental observations and the results of Maximum Hard-
ness and Minimum Electrophilicity Principles. It is well known that
there is a remarkable correlation between dipole moment and po-
larizability. Some researchers noted that dipole moment is a mea-
sure of polarizability. The molecules having high dipole moment
values are more polarizable [42]. One can say that dipole moment
values also support the stability of Copper complex.
The NBO analysis was performed for predicting the existence of
the donor-acceptor interaction on the molecule [44], and the re-
sults were presented in supplementary material Table S6. Due to
the existence of the unsaturated rings, the resonance interactions
are mainly contributed to the stabilization of the ligand and its
metal complexes in addition to the cieplak interactions predicted
for the metal complexes [23, 24]. For the ligand, the lone pair elec-
tron of the oxygen atoms of the hydroxyl group has a main role in
contributing to the stabilization energy; the stabilization energy of
∗
∗
the interactions LP(2) O37→ π C29-C32 and LP(2)O38 → π C18-
C20 are calculated as 32.68 and 32.79 kcal/mol, respectively. If the
MEP plot of the Ligand molecule is recalled, the surrounding of the
oxygen atoms is in red color. On the other hand, the presence of
the Co, Ni, and Cu metals in the center of the molecule provides
the complexes more electrophilicity. For the Copper complex, the
∗
∗
interactions πC20-C23(2) → π C18-O38 and πC3-C4(2)→ π C2-
N10 have greatly supported the stabilization with the energies
∗
of 25.23 and 22.67 kcal/mol. Addition, πC17-C19(2)→ π N10-C15,
∗
∗
πC21-C23(2) → π C17-C19, and LP(2) O38 → π C18-C20, 48.01,
32.67, and 30.83 kcal/mol. For the Nickel complex, the stabilization
∗
energy of the interactions πC17-C19(2) → π N10-C15, πC21-C23
∗
∗
(2) → π C17-C19, and LP (2) O38 → π C18-C20 are found to be in
48.01, 32.67 and 30.83 kcal/mol, respectively. For the Cobalt com-
plexes complex, the resonance interactions have quite provided the
Fig. 6 presents the frontier molecular orbital densities and MEP
plots of the Ligand and three metal complexes [43]. For the lig-
and molecule, the EHOMO density as an indicator of the nucle-
ophilic attack site is expanded over on the whole surface, except
for the oxygen atom of the nitro group. Also, the ELUMO density
depicting the electrophilic attack site is mainly distributed over the
whole surface and partly on the benzylic group that connects the
two (E)-2-((methylimino) methyl) phenol rings. The EHOMO and
ELUMO amplitudes show over the L-M complex in a different dis-
tribution from each other. For instance, the EHOMO density of the
cobalt complex distributes over the surrounding of the center of
the Co-chelating while the EHOMO of the nickel complex has po-
sitioned on the whole surface except for the -NO2 group. Also,
∗
stabilization, E(2) of the interactions for πC1-N11 (2) → π C16-
∗
∗
C27, π C2-N10(2)→ π C15-C17, πC3-C4(2)→ π C1-N11, πC20-
∗
∗
C23(2)→ π C18-O38, πC32-C33(2)→ π C29-O37 are calculated as
29.08, 29.63, 30.39, 28.48, and 28.28 kcal/mol.
3
.8. Natural population analysis (NPA) and Metal–Ligand charge
interaction analysis
The transfer of charges acting a vital role in applying quantum
chemical calculations to molecular system due to atomic charges
affecting the dipole moment, polarization, molecular nature (acid-
7

R.V. Sakthivel, P. Sankudevan, P. Vennila et al.
Journal of Molecular Structure 1233 (2021) 130097
Fig. 6. a) HOMO, b) LUMO (isoval: 0.02) and c) MEP (iso value: 0.0004) plots of the Schiff base ligand and metal complexes using the B3LYP/6-311G(d,p)/LANL2DZ basis set.
ity and basicity) and such other properties of the molecular system
45]. Furthermore, the electron interaction between ligand to metal
uation of the metal-ligand constant stability at 35 and 45°C in
ethanol-water (75:25%) medium and at constant ionic strength at
[
could be predicted by NPA. Natural atomic charges (NAC) were de-
termined earlier in experimental section. The presence of both N
and O as ligand coordinated atoms allows enriching the Schiff base
electron donation tendency. The NAC and valence electron configu-
rations of the ligand and complexes with half the symmetry details
are shown in Table 6 [45 and 46]. The calculated NAC of Co, Ni and
Cu ions are observed as 0.3124, 0.4428 and 0.7673, respectively and
are considerably below than formal charge (+2). The results show
that, since negative electron density is being transferred from the
ligand, the atomic charge of metal ions could be reduced. From the
observation, the significant amount of charge transferred occurred
from metal to ligand have been identified.
μ=0.1 M (NaNO ). While temperatures rise, the value of metal lig-
3
and stability constant decreases, indicating that low temperature
is favourable for complex formation [47]. Mean stability constant
values were observed to decrease with growing ion intensity in
all cases and to demonstrate a diminishing trend with rising tem-
peratures. The thermodynamic parameters (ꢀH, ꢀG and ꢀS) have
been estimated and are given in supplementary material Table S8.
In addition, log(K) values decrease with an increase in complex-
ing temperature. The negative values of ꢀG indicated spontaneous
reactions between metals and ligand and negative values of ꢀH
demonstrated the exothermic existence of the interaction between
metal and ligand. Further, the positive ꢀS values suggest that the
entropy effects is considered to also be predominant over enthalpy
effect. In the structures of analysis, Schiff base ligand acts as a
donor species and metal ion acts as an acceptor. Co(II), Ni(II) and
3
.9. Thermodynamic parameters
7
8
9
Metal-ligand stability constants were calculated using Half In-
Cu(II) with unoccupied d orbitals (d , d , d system) have a ca-
pacity to accept π-donation from Schiff base ligand, while Co(II)
complexes also with lowest electron at d orbital have a higher
constant formation than other metal complexes. The results have
tegral & Graphical procedure and the values are shown in supple-
mentary material Table S7. The Co(II), Ni(II) and Cu(II) complexes
of the representation Schiff base ligand were chosen for the eval-
8

R.V. Sakthivel, P. Sankudevan, P. Vennila et al.
Journal of Molecular Structure 1233 (2021) 130097
Fig. 7. Molecular docking interaction of cobalt complex with α-amylase (1HNY.pdb).
Table 6
Natural Atomic charges and electron configurations from the natural population analysis (NPA) of title compounds.
Compounds
Ligand
Atoms
Natural charge
Natural electron configuration
N11
N12
O37
O38
N11
N12
O37
O38
Co41
N11
N12
O37
O38
Ni41
N11
N12
O37
O38
Cu41
-0.5452
-0.5509
-0.6979
-0.6998
-0.6321
-0.6244
-0.6865
-0.6984
0.3124
[core]2S(1.40)2p(2.97)3p(0.01)
[core]2S(1.09)2p(3.41)3p(0.03)
[core]2S(1.71)2p(4.95)3p(0.01)
[core]2S(1.77)2p(4.86)3p(0.01)
[core]2S(1.29)2p(4.10)3p(0.01)
[core]2S(1.25)2p(3.81)3S(0.01)
[core]2S(1.63)2p(4.82)3p(0.01)
[core]2S(1.63)2p(4.85)3p(0.01)
[core]4S(0.37)3d(7.19)4p(0.78)5p(0.01)
[core]2S(1.26)2p(4.17)3p(0.01)
[core]2S(1.21)2p(3.69)3S(0.01)
[core]2S(1.66)2p(4.85)3p(0.01)
[core]2S(1.65)2p(4.85)3p(0.01)
[core]4S(0.40)3d(8.04)4p(0.73)
[core]2S(1.29)2p(4.17)3p(0.02)
[core]2S(1.07)2p(3.41)3S(0.01)3p(0.03)
[core]2S(1.66)2p(4.86)3p(0.01)
[core]2S(1.66)2p(4.91)3p(0.01)
[core]4S(0.38)3d(9.02)4p(0.58)5p(0.01)
Cobalt
complex
Nickel
-0.7136
-0.7128
-0.5506
-0.5473
0.4428
complex
Copper
-0.4608
-0.4691
-0.6068
-0.6163
0.7673
complex
shown that formulation constant for Cu(II) is greater than the Ni(II)
complex, which could be attributable towards its positive energy
distribution and ligand deformation geometry. The stability of the
metal complexes follows a trend: Co(II) > Ni(II) > Cu (II).
trations (50-500 mM) [48 and 49] and antioxidant activities ob-
servation values illustrated in Fig.S4 (refer Table S9 supplementary
material). The percentage of inhibition of complexes are compared
with control and are given the following order Ascorbic acid >
Cu(II) > Ni(II) > Co(II). The results of Schiff base ligand, Nickel
and Cobalt complexes showed almost nearer performance to the
standard at concentrations of 50-500 mM and Nickel and Copper
complexes have higher antioxidant than Cobalt complexes complex
but lower than Ascorbic acid. The results suggested that Nickel and
Copper complexes have very good antioxidant activity. The oxidiz-
3
3
.10. Biological study
.10.1. In vitro antioxidant activity (Phosphomolybdenum method)
Antioxidant activity of the Schiff base ligand and metal com-
plexes concerning Ascorbic acid and compared in various concen-
9

R.V. Sakthivel, P. Sankudevan, P. Vennila et al.
Journal of Molecular Structure 1233 (2021) 130097
Fig. 8. Molecular docking interaction of Nickel complex with α-amylase (1HNY.pdb).
ing ability of metal complexes is correlated with the presence of
compounds to exercise action by splitting the free radical chain
by contributing hydrogen atoms. The results provide a link to the
use of the title complexes in the treatment of pathological diseases
caused by oxidative stress.
drug and also an excellent percentage of inhibition (see Table S11
supplementary material), which is almost equal to the standard di-
clofenac sodium drug [50].
3
.10.2. Antidiabetic activity
3.10.4. Molecular docking study with a-amylase
The α-amylase enzymes are involved in the digestion of car-
Molecular docking studies are an important tool for computer-
aided drug design and have further attempted to determine the
structural mode of the active sites of the receptors through their
various cellular functional interactions [51]. The docking studies
are very useful for predicting the ability of the Schiff base of stud-
ied metal complexes to bind to α-amylase enzyme (1HNY.pdb)
and to explain an interesting new therapeutic target for antidi-
abetic activity. In the present study, Schiff base metal complexes
are shown to have a good bonding interaction with the active site
and the results are given in Table 7 and Figs. 7-9. The binding
energies of Cobalt complex as -291.83, Nickel complex as -287.43
and Copper complex as -296.54KJ/mol were identified, whereas
the Copper complexes showed strong hydrogen bonding to amino
acid residues of 1HNY [51]. In addition, two forms of hydro-
gen bonding interaction are observed in the case of the Cop-
per complex, azomethine group (C-N with phenyl ring-NH) in-
bohydrates which are broken down into glucose units. The in-
hibition activity of α-amylase has been investigated for the re-
duction of postprandial blood glucose levels, a therapeutic tar-
get for diabetic conditions. The title complexes antidiabetic ac-
tivities were analyzed with a-amylase enzyme inhibition (various
concentrations 50, 100, 200, 250, 500 mM) (refer Table S10 sup-
plementary material) and the results are represented in Fig.S5.
The results showed that the Copper complex could have bet-
ter performance than Nickel and Cobalt complexes and the vari-
ation antidiabetic activities are due to the nature of the metal
ions [26].
3
.10.3. Anti-inflammatory activity
The human body defends itself against pathogens, allergens,
burns, poisonous substances and other nociceptive stimuli, and sev-
eral of them are chronic pathogens. The Schiff base metal complex
has a rich anti-inflammatory ability and is widely used to prevent
inflammation. The anti-inflammatory activity of the title complexes
were analyzed at different concentrations of 50 μg/mL, 100 μg/mL,
˚
teracted with THR163 bond distance 3.09 A as well as phenolic
group (– N = O imidazole NH) interacted with TRP59 it bond
˚
distance 2.72 A. Similarly, Cobalt complex hydrogen bonding in-
teractions were found N=O and guanidine NH of ARG252 (bond
˚
2
00μg/mL, 250 μg/mL and 500 μg/mL using the Bovine Serum Al-
distance 1.98 A) as well as Nickel complex hydrogen bonding in-
bumin (BSA) denaturation technique, while diclofenac sodium was
used as a reference drug. The percentages of inhibition are shown
in Fig.S6. The Cobalt, Nickel and Copper complexes showed effec-
tive anti-inflammatory activity compared to the diclofenac sodium
teractions were identified carbonyl oxygen of GLY249 (bond dis-
˚
tance 2.69A) [28 and 52]. The results suggest that the azome-
thine group (C-N)/phenolic group –O unit is essential to protein
interactions.
10

R.V. Sakthivel, P. Sankudevan, P. Vennila et al.
Journal of Molecular Structure 1233 (2021) 130097
Table 7
Molecular docking interaction of metal complexes with α-amylase (1HNY.pdb).
S.
Metal
Binding energy
KJ/mol
No. of hydrogen
bonding
no
complexes
Interacted amino acid residue
1
Copper
-296.54
2
THR163 [π-donor hydrogen bonding (3.09 A˚ , phenyl ring—-NH of
complex
THR163)], TRP59 [conventional hydrogen bonding (2.72 A˚ ,
N=O—-imidazole NH of TRP59]
2
3
Cobalt
-291.83
-286.64
1
1
ARG252 [conventional hydrogen bonding (1.98 A˚ , N=O——guavinidine
complex
Nickel
NH of ARG252)]
GLY249 [carbon hydrogen bonding (2.69 A˚ , imine HC—–O=C of
complex
GLY249)]
Fig. 9. Molecular docking interaction of Copper complex with α-amylase (1HNY.pdb).
4. Conclusion
ligand. The value of the energy difference between the HOMO and
the LUMO suggests the title compounds stable. The electrostatic
potential value has been determined as Cu(II) (± 0.778e) > Ni(II)
(± 0.353e) > Co(II) (± 0.214e) complexes that support the tendency
of the antioxidant activity of these complexes. The stability values
of the metal complexes follow a trend: Co(II) > Ni(II) > Cu (II). In-
cluding antioxidant, antidiabetic and anti-inflammatory function of
copper complex, biological activities are found to have improved
action than cobalt and nickel complexes. The molecular docking
studies further illustrated the intense energy interaction of metal
complexes with the enzyme α-amylase.
The present study describes the competent synthetic path-
ꢀ
ꢀ
way for the synthesis of 2,2 -((1E,1 E)-((4-nitro-1,2-phenylene)
bis(azanylylidene)) bis(methanylylidene)) diphenol and Cobalt,
Nickel and Copper complexes were synthesized and characterized
using conductance measurements, elemental analysis, FT-IR spectra
and UV-Visible spectra. The Cobalt, Nickel and Copper complexes
were proven to induce the corresponding complexes by ligand co-
ordinated to metal ions via O and N atoms. Magnetic and elec-
tronic spectral analysis shows tetrahedral geometry for the Co(II)
complex, while the Ni(II) and Cu(II) complexes have square plane
geometry. The powder X-ray diffraction study revealed that only Cu
Declaration of Competing Interest
(
II) complexes had sharp peaks, although no peaks were seen for
the rest of the complexes implying their amorphous nature. The re-
sults of the geometrical parameters suggested a good conjugation
effect that would aid transfer excited electron from metal ions to
The authors declare that they have no known competing finan-
cial interestsor personal relationships that could have appeared to
influence the work reported in this paper.
11

R.V. Sakthivel, P. Sankudevan, P. Vennila et al.
Journal of Molecular Structure 1233 (2021) 130097
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