New heterocyclic Schiff base-metal complex: Synthesis, characterization, density functional theory study, and antimicrobial evaluation

Article abstract of DOI:10.1002/aoc.6322

A new series of heterocyclic Schiff base complexes derived from the condensation of nicotinohydrazide with different heterocyclic aldehyde, followed by metalation with Co (II) and Cu (II) metal ions. The chemical structures of the synthesized compounds have been characterized by elemental analysis, Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, ultraviolet–visible spectroscopy, and magnetic susceptibility. The spectral and magnetic data confirmed their chemical structures, furthermore, the geometry of Cu (II) and Co (II) complexes were square-planar or distorted tetrahedral. X-ray diffraction measurements supported the crystalline structures of the metal complexes rather than the amorphous form of the parent Schiff bases. Thermogravimetric analysis revealed the upgrading of the thermal stability of metal complexes compared to their Schiff base ligands. Antimicrobial efficacies of the Schiff base ligands and their corresponded metal complexes were screened against Staphylococcus aureus and Bacillus subtilis as Gram-positive bacteria, Escherichia coli, and Proteus vulgaris as Gram-negative bacteria, and fungi Aspergillus flavus, Candida albicans. The antimicrobial inhibitory data revealed higher antimicrobial activities of metal complexes compared to their Schiff base ligands. Density functional theory module by Gaussian 09 W software proved the chemical reactivity of the prepared Schiff base ligands based on the total energy, energy gap, E_HOMO, and E_LUMO energies.

Full text of DOI:10.1002/aoc.6322

Received: 10 February 2021
DOI: 10.1002/aoc.6322
Revised: 7 May 2021
Accepted: 17 May 2021
F U L L P A P E R
New heterocyclic Schiff base-metal complex: Synthesis,
characterization, density functional theory study, and
antimicrobial evaluation
1
2
2
Heba E. Hashem
| Eslam A. Mohamed
| Ahmed A. Farag
|
2
1
Nabel A. Negm
| Eman A. M. Azmy
1
Chemistry Department, Faculty of
Women, Ain Shams University,
Heliopolis, Egypt
A new series of heterocyclic Schiff base complexes derived from the condensa-
tion of nicotinohydrazide with different heterocyclic aldehyde, followed by
metalation with Co (II) and Cu (II) metal ions. The chemical structures of the
synthesized compounds have been characterized by elemental analysis,
Fourier transform infrared spectroscopy, proton nuclear magnetic resonance,
ultraviolet–visible spectroscopy, and magnetic susceptibility. The spectral and
magnetic data confirmed their chemical structures, furthermore, the geometry
of Cu (II) and Co (II) complexes were square-planar or distorted tetrahedral.
X-ray diffraction measurements supported the crystalline structures of the
metal complexes rather than the amorphous form of the parent Schiff bases.
Thermogravimetric analysis revealed the upgrading of the thermal stability of
metal complexes compared to their Schiff base ligands. Antimicrobial efficacies
of the Schiff base ligands and their corresponded metal complexes were
screened against Staphylococcus aureus and Bacillus subtilis as Gram-positive
bacteria, Escherichia coli, and Proteus vulgaris as Gram-negative bacteria, and
fungi Aspergillus flavus, Candida albicans. The antimicrobial inhibitory data
revealed higher antimicrobial activities of metal complexes compared to their
Schiff base ligands. Density functional theory module by Gaussian 09 W soft-
ware proved the chemical reactivity of the prepared Schiff base ligands based
on the total energy, energy gap, EHOMO, and ELUMO energies.
2
Chemistry Department, Egyptian
Petroleum Research Institute, Nasr City,
Egypt
Correspondence
Heba E. Hashem, Chemistry Department,
Faculty of Women, Ain Shams University,
Heliopolis, Cairo, Egypt.
Email: heba.hashem@women.asu.edu.eg
K E Y W O R D S
biological studies, DFT calculations, nicotinic acid, Schiff base, transition metal
(
II) complexes
1
| INTRODUCTION
without side effects is a biomedical problem. Nicotinic acid
derivatives are naturally occurring compounds. Low
amount of nicotinic acid present in all living cells, liver,
yeast, and corn. Many nicotinic acid derivatives have great
importance in organic synthesis for their anti-bacterial
In the past decades, the problem of multi-drug resistant
microorganisms has reached an alarming level around the
world. Therefore, the synthesis of new compounds that
are used for the effective treatment of microbial infections
[
1–3]
and anti-mycotic activities.
On the other hand, Schiff
Appl Organomet Chem. 2021;e6322.
wileyonlinelibrary.com/journal/aoc
© 2021 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.6322

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HASHEM ET AL.
base compounds attract considerable research due to their
pharmacological activity and the tendency toward the for-
mation of complexes with almost all the transition
Panalytical-X-ray diffractometer (XRD)-X'Pert Powder
with Cu-Kα radiation with wavelength (1.541 Å). The
monochromator was adjusted at a voltage (40 kV) and an
intensity of 40 mA. Electron spin resonance spectra were
also recorded on JES-FE2XG ESR spectrophotometer at
room temperature at a microwave frequency 9.1 GHZ
and field set 3000 G. Thermogravimetric analysis (TGA)
was conducted by SDT Q600 V20.5 Build 15 under a flow
[4,5]
metals.
These metal complexes of Schiff bases possess
high inspect in medicinal chemistry, such as antiviral,
anticancer, antibacterial, antifungal, antioxidant anticon-
[6,7]
vulsant, and anti-inflammatory activities.
It was
reported that Schiff base compounds formed from amine
of carbohydrazide with heterocyclic aldehyde are more
stable and have high abilities to coordinate with the transi-
ꢀ
ꢁ1
of dry nitrogen with 10 C min of heating rates.
[8]
tion metal ions. The chelating ligands containing O and
N donor atoms show broad biological activity and have a
2.2 | Synthesis of nicotinic acid
hydrazide
[1,9]
special interest in bonding to metal ions.
These com-
pounds have unique properties such as photochromic
properties, the ability to reversibly bind oxygen, and com-
The synthesis procedure was performed according to the
reported in the literature. where a mixture of nicotinic
[10,11]
[9]
plexing activity toward toxic metals.
gated that the Co (II), Cu (II), and Zn (II)metal complexes
have potential biological application such as
antibacterial, antifungal, anti-inflammatory, total antioxi-
It was investi-
acid (0.03 mol) and phosphorous pentachloride
(0.05 mol) in anhydrous carbon tetrachloride (20 ml) was
a
ꢀ
refluxed at 100 C for 2 hr, then the solvent was distilled
[12]
dant, antidiabetic, and DNA binding studies.
Based on
off to obtained acid chloride as a solid product. The
ꢀ
this view, the presented work aims to use nicotinic acid
hydrazide for the synthesis of new Schiff base with differ-
ent heterocycle aldehydes, followed by complexion with
Co (II) and Cu (II) as transition metal ions using a new
simple procedure. The chemical structure of the produced
complexes was elucidated with different techniques and
studying their biological activities.
hydrazine hydrate (0.1 mol) was added dropwise at 0 C
to the produced solid of acid chloride (0.03 mol) and the
resultant mixture was stirred for 5 hr at room tempera-
ture. The produced solid was washed with aqueous
sodium bicarbonate (10%), dried in a vacuum, and rec-
rystallized using ethanol.
2
.3 | Synthesis of Schiff bases
2
2
| EXPERIMENTAL
A mixture of nicotinohydrazide (0.01 mol) and aromatic
heterocyclic aldehyde naming 1H-pyrrole-
-carbaldehyde, 1H-indole-3-carbaldehyde, or
.1 | Materials and techniques
2
All chemicals were analytical grade and were purchased
from Sigma–Aldrich. They were used as received from
the sources without further purification. All melting
points are uncorrected and measured on a Gallen Kamp
electric melting point apparatus. The elemental analysis
was conducted using a Varia Elementary device. The IR
spectra recorded using potassium bromide disks on an
Fourier transform infrared spectroscopy (FTIR) Thermo
Electron Nicolet 7600 (USA) IR-spectrophotometer at the
Central Laboratory of Faculty of Science, Ain Shams
1,3-diphenyl-1H-pyrazole-4-carbaldehyde (0.01 mol) in
absolute ethyl alcohol (20 ml) with few drops of glacial
acetic acid was heated under reflux for 1 hr. The solid
product formed while cooling to room temperature was
filtered off and recrystallized from ethanol to give the
Schiff bases (L1–L3), respectively (Scheme 1).
0
2.3.1 | N -([1H-pyrrol-2-yl]methylene)
nicotinohydrazide (L1)
1
University. H-NMR spectra run at 300 MHz on a
ꢀ
GEMINI 300 BB NMR spectrometer using tetramethyl
silane as an internal standard in deuterated dimethyl
sulfoxide (DMSO-d6) at Faculty of Pharmacy, Ain Shams
University. Electronic spectral changes in electron distri-
bution between ligand–metal in complexes were recorded
in the wavelength range of 200–700 using UV–Visible at
the Egyptian Petroleum Research Institute. TLC was per-
formed on Merck Kissel gel 60 F254 aluminum backed
plates. Powder X-ray diffraction was recorded by Malvern
(Yield 88%); brown crystals; m.p. 204–206 C; UV–Visible
ꢁ
1
(DMSO, nm): 320, 340; IR (KBr) (υ, cm ): 3226, 3137
(NH), 3051, (CHarom), 1638 (CO), 1605 (C=N), 1559
1
(C=C); HNMR (DMSO-d6) δ: 6.15–6.93 (m, 3H, CH-pyr-
role), 7.53–8.28 (m, 3H, CH-nicotine), 8.75 (s, 1H,
CH=NNH), 9.05 (s, 1H, Nicotine [N=CH-CCO]), 11.58
(br.s, 1H, CONHN, exchangeable), 11.71 (br.s, 1H, NH-
pyrrole); Anal. Calcd. For C11H10N4O (%): C, 61.67; H,
4.71; N, 26.15; Found (%): C, 61.91; H, 4.84; N, 27.21.

HASHEM ET AL.
3 of 14
SCHEME 1 Synthesis of Schiff
base ligands
0
2
.3.2 | N -([1H-indol-3-yl]methylene)
temperature. The resulting mixture was then refluxed at
70 C for 1 hr on a water bath. A colored product
ꢀ
nicotinohydrazide (L2)
appeared on standing and cooling the above solution.
The complexes were filtered, washed with ether, and
ꢀ
ꢁ
(
(
Yield 89%); yellow crystals; m.p. 210–212 C; UV–Visible
1
DMSO, nm): 325,345; IR (KBr) (υ, cm ): 3178 (NH),
047, (CHarom), 1657 (CO), 1600 (C=N), 1575 (C=C);
dried under reduced pressure over anhydrous CaCl in a
2
3
desiccator. All formed metal complexes are colored solids
1
ꢀ
HNMR (DMSO-d6) δ: 7.13–8.76 (m, 7H, Ar-H + [nico-
tine ring]), 7.87 (s, 1H, indole-H), 8.63 (s,1H, CH=NNH),
crystals, with high melting points >300 C.
9
.09 (s, 1H, Nicotine [N=CH-CCO]), 11.56 (br.s, 1H,
2.4.1 | [Co(L1) (NO ) ]
2
3 2
CONHN, exchangeable), 11.64 (br.s, 1H, NH-indole);
Anal. Calcd. For C H N O (%): C, 68.17; H, 4.58; N,
Yield (88%); reddish brown solid, Anal. Calcd. for
C H CoN O (%): C, 43.22; H, 3.30; Co, 9.64; N, 22.91.
15
12 4
2
1.20; Found (%): C, C, 68.35; H, 4.19; N, 21.51.
22
20
10 8
Found (%): C, 43.32; H, 3.52; Co, 9.93; N, 23.12.; IR (KBr)
0
ꢁ1
ꢁ
2
.3.3 | N -([1,3-diphenyl-1H-pyrazol-4-yl]
(υ, cm ): 1614 (C=O), 1537 (C=N), 1357, 1014 (NO3 ),
570 (Co-O), 490 (Co-N), UV–Visible (DMSO, nm): 250
methylene)nicotinohydrazide (L3)
(π-π*), 380 (n-π*).
ꢀ
ꢁ
(
(
Yield 96%); white crystals; m.p. 220–222 C; UV–Visible
1
DMSO, nm): 330, 350; IR (KBr) (υ, cm ): 3216 (NH),
058, (CHarom), 1671 (CO), 1613 (C=N), 1598 (C=C);
2.4.2 | [Co(L2) (NO ) ]
2 3 2
3
1
HNMR (DMSO-d6) δ: 7.37–8.27 (m, 13H, Ar-H + [nico-
tine ring]), 8.57 ((s,1H, CH=NNH), 8.76 (s, 1H, CH-
Pyrazole), 9.07 (s, 1H, Nicotine [N=CH-CCO]), 11.90 (br.
s, 1H, NH, exchangeable); Anal. Calcd. For C H N O
Yield (95%); reddish brown solid, Anal. Calcd. for
C H CoN O (%): C, 50.64; H, 3.40; Co, 8.28; N, 19.69.;
30
24
10 8
Found (%): C, 50.43; H, 3.67; Co, 8.78; N, 19.79; IR (KBr)
ꢁ
1
ꢁ
(υ, cm ): 1590 (C=O), 1540 (C=N), 1332, 1025 (NO3 ),
540 (Co-O), 481 (Co-N), UV–Visible (DMSO, nm): 240
(π-π*), 385 (n-π*).
22
17 5
(
%): C, 71.92; H, 4.66; N, 19.06; Found (%): C, 71.63; H,
4
.81; N, 19.23.
2.4 | Synthesis of metal complexes
2
.4.3 | [Co(L3) (NO ) ]
2 3 2
The metal complexes have been prepared by addition of
the ethanolic solution of Copper (II) acetate or cobalt
Yield (89%); reddish brown solid, Anal. Calcd. for
C H CoN O (%):C, 57.58; H, 3.73; Co, 6.42; N,
(II) nitrate (0.01 mol) dropwise to the stirring ethanolic
44
34
12 8
solution of the Schiff bases (L1–L3) (0.02 mol) at room
18.31Found (%):C, 57.93; H, 3.84; Co, 7.12; N, 18.62.; IR

4
of 14
HASHEM ET AL.
ꢁ
1
(
(
KBr) (υ, cm ): 1596 (C=O), 1550 (C=N), 1346, 1012
2.6 | Density functional theory studies
ꢁ
NO3 ), 525 (Co-O), 472 (Co-N), UV–Visible (DMSO,
nm): 230 (π-π*), 360 (n-π*).
Chemical reactivity and other properties of the prepared
compounds were identified by density functional theory
(
DFT) using Becke three-parameter hybrid exchange and
2
.4.4 | [Cu(L1) (OCOCH ) ]
Lee–Yang–Parr correlation functional (B3LYP/3-21G) for
2
3 2
ligand and B3LYP/LANL2DZ for metal complexes using
[
14,15]
Yield (93%); brownish green solid, Anal. Calcd. for
C H CuN O (%): C, 51.19; H, 4.30; Cu, 10.42; N, 18.37;
Found (%): C, 51.37; H, 4.62; Cu, 10.98; N, 18.64; IR
GAUSSIAN09 program
. The Gaussian files obtained
through this method were visualized using Gauss-View
05 molecular visualization program.
26
26
8 6
ꢁ
1
(
(
KBr) (υ, cm ): 1600 (C=O), 1519 (C=N), 1442, 1210
ꢁ
OAc), 531 (Cu-O), 463 (Cu-N), UV–Visible (DMSO,
nm): 290 (π-π*),370 (n-π*).
3 | RESULTS AND DISCUSSION
3.1 | Chemistry
2
.4.5 | [Cu(L2) (OCOCH ) ]
2 3 2
The condensation reaction of nicotinocarbohydrazide
Yield (85%); green solid, Anal. Calcd. for
C34H30CuN8O6 (%): C, 57.50; H, 4.26; Cu, 8.95; N,
with different heterocyclic aldehyde naming 1H-pyrrole-
2-carbaldehyde,
1H-indole-3-carbaldehyde,
or
1
5.78; Found (%): C, 57.87; H, 4.41; Cu, 9.13; N, 15.65; IR
1,3-diphenyl-1H-pyrazole-4-carbaldehyde affording Schiff
base compounds (L1–L3) (cf. Scheme 1). The suggested
structures of the synthesized compounds are elucidated
from Their spectral data. The IR spectrum showed
ꢁ
1
(
(
KBr) (υ, cm ): 1605 (C=O), 1580 (C=N), 1456, 1225
ꢁ
OAc), 520 (Cu-O), 492 (Cu-N), UV–Visible (DMSO,
nm): 260 (π-π*), 385 (n-π*).
2
.4.6 | [Cu(L3) (OCOCH ) ]
2 3 2
Yield (91%); green solid, Anal. Calcd. for C H CuN O
10 6
48
40
(
6
1
%): C, 62.91; H, 4.40; Cu, 6.93; N, 15.28; Found (%): C,
ꢁ
1
3.21; H, 4.65; Cu, 7.32; N, 15.41; IR (KBr) (υ, cm ):
ꢁ
610 (C=O), 1520 (C=N), 1481, 1231 ( OAc), 518 (Cu-
O), 475 (Cu-N), UV–Visible (DMSO, nm): 290 (π-π*),
70 (n-π*).
3
2.5 | Antimicrobial studies
Invitro antimicrobial activities of the synthesized ligands
Schiff Bases) and related metal complex were screened
(
against Gram-positive bacteria (Staphylococcus aureus
RCMB010010), (Bacillus subtilis RCMB 015 [1]),
Gram-negative bacteria (Escherichia coli RCMB 010052),
(
Proteus vulgaris RCMB 004 [1]) and fungi (Aspergillus
flavus RCMB 002002), (Candida albicans RCMB 005003
[
13]
[1]) by disc diffusion method in DMSO as a solvent.
Gentamycin and Ketoconazole were used as standard
antibacterial and antifungal, respectively. The resulting
inhibition zone for each compound was measured in mm
for the growth of bacterial or fungal around the discs
were measured and summarized in Table 3. The mean
value obtained for three individual replicates was used to
calculate the average value of inhibition zone of each
sample.
SCHEME 2 Synthesis of the Schiff base metal complexes

HASHEM ET AL.
5 of 14
FIGURE 1 Fourier transform infrared spectroscopy (FTIR) spectra of ligands and their Co and Cu complexes
FIGURE 2 UV–visible spectra
of ligands and their Co and Cu
ꢁ
3
complexes in 10 M DMF solution
absorptions characteristic for NH, CN, and C O groups.
The H-NMR spectrum exhibited multiplet signals in the
range δ7–9 ppm for aromatic protons as well as broad
singlet signal in the downfield region attributable to NH
proton. Further evidence was gained from their elemen-
tal analysis was in good agreement with the calculated
values (cf. experimental). The prepared Schiff bases (L1–
L3) are used as a reactive chelating agent to form new
1

6
of 14
HASHEM ET AL.
metal complexes with Co (II) and Cu (II) (Scheme 2).
The chemical structure of the obtained complexes was
elucidated with different techniques including elemental
analysis, FTIR, UV–Vis, XRD, TGA, and magnetic
susceptibility.
on the complexes, indicating the involvement of the car-
bonyl group in the bonding to metal. The absorption
band correlated to the imine group, υ(C=N) appeared at
ꢁ
1
1600–1613 cm for the free ligand (L1–L3) and shifted
ꢁ
1
lower to 1519, and 1580 cm for the Co and Cu metal
complexes. This agreed with the involvement of the nitro-
gen atom of the υ(C=N) in the bonding with the metal
ꢁ
3
.2 | Structure analysis
(II) ions. The stretching vibrations of nitrate (NO ), and
3
ꢁ
acetate (CH COO ) ions for Co and Cu complexes were
3
ꢁ
1
3
.2.1 | Fourier transform infrared
observed at 1332–1357 and 1441–1482 cm , respectively.
This indicates that nitrate and acetate ions were involved
in the inner sphere coordination of the metal complex.
FT-IR spectra showed an absorption band for υ N–H
stretching at 3178–3226 cm region for the ligands (L1–
L3). The stretching υ (NH) of the ligand is not shifted in
the spectra of the metal complexes indicate the non-
participation of the nitrogen atom of υ (NH) in the chela-
spectroscopy spectral studies
The FTIR spectra of the ligand and its copper and cobalt
complexes are represented in Figure 1. The IR spectra of
the metal complexes were compared with those of the
free ligand to determine the involvement of coordination
sites in the complexes. Characteristic peaks in the spectra
of the ligand and complexes were considered and com-
pared. The absorption band in the spectra of the ligands
L1–L3 at 1638–1671 cmꢁ has been assigned to
ꢁ
1
[
17]
tion.
Hence, it is concluded that Schiff base ligands
(L1–L3) act as a neutral bidentate ligand. Furthermore,
IR spectra of the metal complex showed two new
stretching bands in the lower wavelength region ranging
1
[16]
υ(C=O).
This band was shifted to a lower wavelength
5
18–570 and 463–492 which correlated to the M (II)-O
ꢁ
1
[18–20]
and M (II)-N cm , respectively.
3.2.2 | Electronic spectral and magnetic
susceptibility studies
The electronic absorption spectra of all ligands and
related copper and cobalt complexes were recorded in
ꢁ
3
10
M DMF solution at room temperature over the
wavelength range of 200 to 800 nm (Figure 2). Ligands
L1–L3) exhibit two intense absorption bands at short
(
wavelengths, the first absorption bands at (320–330) due
to π ! π* transition of the aromatic ring and the second
shoulder absorption bands appear at (340–350 nm) which
[
21]
are assigned to n ! π* transition.
Copper and Cobalt
complexes exhibited two bands at a shifted wavelength
within (230–290) and (360–385) attributable to (π ! π*
transition) and (n ! π* transition), respectively, con-
firming coordination of the oxygen and nitrogen atoms of
FIGURE 3 Powder X-ray diffraction analysis of the prepared
Schiff bases (L1) and their Cu (II) and Co (II) complexes;
4
,6,8 = Co (II) complexes of L1-L3, respectively; 5,7,9 = Cu
[
4]
(
II) complexes of L1-L3, respectively
ligands (L1–L3) to the metal centers. Cu (II) and Co
FIGURE 4 Thermogravimetric
analysis of: (a) L1 (representative for
L1-L3); (b) metal complexes 4–9

HASHEM ET AL.
7 of 14
ꢀ
(II) complexes show an absorption band at 650 nm and
180 C, assignable to the loss of water of crystallization.
Then, gradual increase in the weight loss of the com-
plexes reached to the semi-decay. The metal complexes
showed higher thermal stability than the parent ligands.
6
40 nm, respectively, which were attributed to
2
2
B1g ! A transition. That was compatible with the
1g
[
22]
square-planner or distorted octahedral structures.
The magnetic moments of the complexes were measured
for the coordination mechanism. As expected, the pre-
pared Schiff bases based-on azomethine group is a strong
ligand with multi-dentate that they squeezed to d-orbital
electrons of the metal ions. The magnetic moment of Cu
3.2.5 | Electron spin resonance
Electron spin resonance is one of the most powerful tech-
niques for studying the electronic structure of many spe-
cies including organic free radical, biradical, and most
transition metals. The ESR spectra of copper
(II) complexes provide information of important in study-
ing the metal ion environment. The X-band ESR spec-
trum of three cupper complexes [Cu(L1)2(OCOCH3)2],
[Cu(L2)2(OCOCH3)2], and [Cu(L3)2(OCOCH3)2] were
recorded in the polycrystalline form at room temperature
at a microwave frequency 9.1 GHZ and field set 3000 G.
The spectrum has been studied and depicted in Figure 5.
All these cupper complexes are similar and display a
resolved axial dx2-y2 ground state spectrum consistent
with tetragonally elongated octahedral or square planar
(II) complexes was found in the range of 1.7–1.8 B. M
which corresponds to a single unpaired electron in the
final d-orbital contribution, which confirms the square-
planar geometry of the Cu (II) complexes. While the Co
(II) complexes reported herein are high spin at room
temperature with the magnetic moment in the range of
4
.1–4.3 B. M, which indicates that the complexes of Co
(II) have a six-coordinate with a square planner or octa-
[23]
hedral geometrical structure.
3.2.3 | X-ray diffractometer spectroscopy
[
24]
During powder X-ray diffraction analysis (Figure 3), the
synthesized Schiff base ligands L1-L3 showed two types
configuration around copper (II).
In addition to the
hyperfine structure of copper (II) complexes in the gll
region. The (g) values and the nuclear hyper line cou-
pling constant (A) have been calculated from the center
of the each of the hyperfine lines and the spacing
between the two consecutive lines, respectively, of the
ꢀ
ꢀ
of peaks, two peaks at 2theta = 3 , and 17 ; while a broad
peak was appeared for the three Schiff bases L1–L3 in the
entire range of 2 theta. That indicates the Schiff bases are
amorphous in nature with a minor crystallinity (Figure 3
SC, representative profile for the prepared Schiff bases
L1-L3). On the other hand, the metal complexes showed
high crystallinity compared to the diffractogram of the
parent ligands due to the appearance of several peaks.
Cobalt complexes of L1-L3 showed characteristic XRD
[
24]
spectrum.
The values of gll and g⊥ were calculated by
using the formula
7
1:4484ꢂυðinGHzÞ
g ¼
Bðin mTÞ
ꢀ
peaks at: 2θ = 7, 9, 11, 12, 15, 17, 20, and 22 . While cop-
per complexes of L1-L3 represented several XRD peaks
ꢀ
[24,25]
at: 2θ = 12.5, 15, 16, 18, 24, 26, and 28 .
where g is proportionality factor, υ is frequency of the X-
band (in GHz) and B is magnetic field (in mT). The
3.2.4 | Thermogravimetric analysis
ꢀ
TGA study was carried out up to 800 C for the prepared
compounds (Figure 4). The TGA thermograms of the pre-
pared ligands (L1–L3) and their metal complexes (4–9)
showed gradual weight loss, indicating decomposition by
fragmentation with increase in temperature. For all the
ligands, there was a gradual increase in the weight loss in
ꢀ
the temperature range of 80–275 C reached about 85%.
Then a sudden decrease in the weight loss reached to
complete decay of the compounds was observed in the
ꢀ
temperature range of 275–400 C. That indicate the pre-
pared ligands have moderate thermal stability up to
ꢀ
2
70 C. For all the complexes, similar stages were
FIGURE 5 ESR spectrum of Cu (II) complexes of Schiff base
observed, including a small weight loss in the range of
ligands

8
of 14
HASHEM ET AL.
various Spin-Hamiltonian parameters for the copper
and Neiman suggested that when g-value for copper
(II) complexes is greater than 2 indicating to present of
Cu-O and Cu-N bonds in the molecules. The giso value
has been calculated by using
(II) complexes were calculated and recorded in Table 1.
According to calculation data, all the g-tensor value
follows the rule: gll > g⊥ > g where g was (A free elec-
tron in vacuum has a g value = 2.00232). This trend
observed in these complexes suggests that the unpaired
electron lies predominantly in the dx2-y2 and implying
ðgllþ2g ⊥ Þ
giso
¼
3
2
B1g orbital of the copper (II) ion and that the spectral
[25]
features are characteristic of axial symmetry.
Kivelson
The giso in the range of 2.100 and 2.154 which was less
than 2.3 indicating covalent character of the metal–ligand
bond of solid polycrystalline cupper complexes and
TABLE 1 Powder ESR parameters for copper (II) complexes at
[26]
suggested the presence of elongated tetragonal axes.
room temperature
The G factor is indicative of exchange interaction
between the copper (II) centers in polycrystalline solids
and can be calculated using formula
Compound
g k
g┴
g
iso
G
[
[
[
Cu(L1)2(OCOCH3)2]
Cu(L2)2(OCOCH3)2]
Cu(L3)2(OCOCH3)2]
2.249
2.0341
2.2261
2.019
2.0681
2.0360
2.1540
2.1245
2.1001
1.113
3.751
3.600
ðgllꢁ2:00232Þ
G ¼
ðg ⊥ ꢁ2:00232Þ
FIGURE 6 Optimized geometrical structure of ligands (L1–L3) and M-complex

HASHEM ET AL.
9 of 14
the G value of all copper (II) complexes is less than
orange > red. In the presented maps for the prepared
ligands (Figure 7), the most negative electrostatic poten-
tial area is localized in the region of the O and N atoms.
It is clear that C = O and C=N, groups are the most
favored region for an electrophilic attack. Additionally,
the frontier molecular orbitals (FMOs) energy gap of the
ligand and its metal complex affords valuable electronic
properties regarding the dynamic stability and chemical
reactivity. In the Schiff base ligand, the highest occupied
molecular orbital (HOMO) and the lowest unoccupied
molecular orbital (LUMO) are mainly placed overall
molecular system which supports the π-π* electron trans-
fer on the ligand molecule. While, in the L-M complex,
HOMO and LUMO orbitals are mainly placed on the
donor site of the ligand and surrounding the metal center
(Figure 8). The frontier molecular orbital energy gap of
the ligands was higher than the metal complex. These
results are strongly in agreement with the complexation
of transition metal to the ligand Schiff base.
4
(Table 1) indicating the presence of very weak exchange
[27]
coupling in the polycrystalline solids.
This suggests
that the distorted octahedral geometry for Cu
[
28]
(II) complex of Schiff base ligand L and acetate ion.
3.3 | Computational analysis
For further approaches to the examined properties of the
prepared Schiff base compounds and metal complexes,
theoretical studies using DFT calculations at the
B3LYP/3-21G and B3LYP/LANL2DZ level of theory were
executed in the gas phase. Figure 6 shows the optimized
geometrical structure of the synthesized Schiff base com-
pounds and their metal complexes. The molecular elec-
trostatic potential MEP delivers an important idea
regarding the nucleophilic and electrophilic reactivity of
the ligands. The negative and positive electrostatic poten-
tial areas in MEP map was represented in the form of
color-coding. Red color indicates the electrophilic attack
Additional parameter such as global softness (S),
chemical hardness (η), which indicate the molecular
reactivity and stability of the molecules. Electronegativity
(X), chemical potential (μ), and electrophilicity value (ω)
which reflect the biological activity of the molecules are
(maximum negative region) and the blue color indicates
the nucleophilic (maximum positive region). The poten-
tial reduces in the order of blue > green > yellow >
FIGURE 7 (a) Computed molecular
electrostatic potential MEP
(
b) electrostatic potential plot for the
prepared Schiff bas L1–L3

10 of 14
HASHEM ET AL.
value of the metal complexes agrees with biological
results which showed that the metal complex has a
higher antimicrobial effect than ligand Schiff base. The
lower energy gap for ligands may be related to low
kinetic stability, which performs electronic charge trans-
fer interaction and high chemical reactivity, increasing
[
32,33]
the contribution to metal ions.
3.4 | Antimicrobial activity
Antibacterial activities of the synthesized ligands (Schiff
Bases) and related metal complexes were screened against
Gram-positive bacteria (S. aureus RCMB010010),
(
B. subtilis RCMB 015 (1)), gram-negative bacteria (E. coli
RCMB 010052), (P. vulgaris RCMB 004 (1)) and fungi
A. flavus RCMB 002002), (C. albicans RCMB 005003 (1))
(
by disc diffusion method in DMSO as a solvent. The
antibacterial activity of a common standard antibiotic
Gentamycin and antifungal Ketoconazole were also
recorded. The results of study are given in Table 3 and
Figure 9. The ligands 1, 2, and 3 have little activity against
all the bacterial pathogens, compared to their metal com-
plexes. The observed activity of ligand may be arise from
the interference in the normal cell process of an organism
caused by the formation of a hydrogen bond through the
azomethine group with the active center of cell
[
34]
constituents. Further, the uncoordinated heteroatom of
aromatic heterocyclic aldehyde naming 1H-pyrrole-
2
1
-carbaldehyde,
,3-diphenyl-1H-pyrazole-4-carbaldehyde moiety also
1H-indole-3-carbaldehyde,
or
contributes to microbial growth inhibition. Moreover, the
metal complexes showed better antibacterial activity than
those of the ligands, which can be explained based on
overtone's concept and chelation theory. On chelation, the
polarity of the metal ion will be reduced to a greater extent
due to the overlap of the ligand orbital and partial sharing
of the positive charge of the metal ion with donor
[
35]
groups.
Chelation Also enhanced activity of the com-
plexes may be attributed to chelation of Schiff base with
metal ions that provide stability and more susceptibility
against the bacterial pathogens. It has been suggested that
possessing azomethine group (C=N), as well as nitrogen
and oxygen donor systems inhibit enzyme activity through
their deactivation by metal coordination. That also facili-
tates its efficient permeation through the organism's lipid
layer and destroys their activity. The chelation process
rises the lipophilicity of metal complexes by increasing the
delocalization of π electrons over the full chelate ring. The
improved lipophilicity helps the metal complexes to pene-
trate the lipid membranes and block the metal-binding
sites of enzymes of microorganisms. The metal complexes
also affect the protein synthesis and further growth of
FIGURE 8 The frontier molecular orbital frontier molecular
orbital (FMO) structure of Ligand 1–3 and related metal complexes
by DFT/B3LYP method
calculated utilizing reported equations in the litera-
[29–31]
ture.
The results of these parameters are summa-
rized in Table 2 and showed that all prepared Schiff bases
have good chemical reactivity and soft. The higher ω

HASHEM ET AL.
11 of 14

12 of 14
HASHEM ET AL.
TABLE 3 Antimicrobial studies for the synthesized Schiff base and their metal complexes measured as inhibition zone diameter (mm)
by well diffusion agar assay
Inhibition zone diameter (mm)
Sample
Gram positive bacteria
Gram negative bacteria
Fungi
S. aureus
RCMB010010
B. subtilis
RCMB 015
14
E. coli RCMB
010052
P. vulgaris
RCMB 004
13
A. flavus RCMB
002002
C. albicans RCMB
005003
L1
13
12
9
11
10
9
12
11
10
16
14
15
18
15
14
—
20
15
13
12
17
15
16
19
18
17
—
24
L2
13
10
17
19
17
22
20
19
26
—
12
12
14
15
14
19
18
17
25
—
L3
4
15
17
18
20
19
18
24
—
13
14
13
17
16
14
30
—
6
8
5
7
9
Gentamycin
Ketoconazole
FIGURE 9 Biological activity of
organometallic Schiff base ligands (L1–L3) and
their metal complexes
microorganisms by inhibiting the respiration process of
hydrazide. Their chemical structures were confirmed
using several spectroscopic tools including IR, UV, XRD,
and ESR spectra. It was revealed that all Schiff base ligand
act as bident agent in all metal complex through the
azomethine nitrogen and carbonyl group of nicotine moi-
ety. Based on the magnetic measurements and ESR
results, it was elucidated that all Cu (II) complexes
appeared as a square-planar or distorted octahedral geom-
etry. XRD spectroscopy showed that all parent Schiff bases
are amorphous structures, and the crystallinity of the
metal complexes was raised after complexation. Further
elucidation for the metalation of the synthesized Schiff
base was performed through DFT theory and calculation
of some chemical parameters. In vitro antibacterial
[34]
the cell.
The weak antibacterial activity for Cu-ligand
and Co-ligand against gram-negative bacteria was ascribed
to the presence of an outer membrane, which poses hydro-
philic polysaccharides chains as a barrier to these com-
plexes. Cobalt is not generally considered to be a very toxic
[36,37]
element.
4
| CONCLUSIONS
New Schiff base ligands and their Co (II) and Cu (II) metal
complexes were successfully synthesized with bident N
and O donor Schiff base ligand derived from nicotinic acid

HASHEM ET AL.
13 of 14
activities were studied and demonstrate that the
Complexes formation increased their antimicrobial activi-
ties toward gram-positive and gram-negative bacteria.
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analysis; funding acquisition; investigation; methodology;
project administration; software; supervision; visualiza-
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CONFLICT OF INTEREST
The authors declare that they have no known competing
financial interests or personal relationships that could
have appeared to influence the work reported in this
paper.
[
[
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are avail-
able from the corresponding author upon reasonable
request.
4
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