New cobalt(II) Schiff base complex: Synthesis, characterization, DFT calculation and antimicrobial activity

Article abstract of DOI:10.1016/j.inoche.2020.108350

A new cobalt(II) Schiff-base complex [Co(L)₂] was prepared by using equivalent molar of Schiff-base ligand [HL=(E)-N'-(2-hydroxy-3-methoxybenzylidene)isonicotinohydrazide] and CoCl₂·6H₂O. The structure of the complex was c

Full text of DOI:10.1016/j.inoche.2020.108350

Journal Pre-proofs
Short communication
New cobalt(II) Schiff base complex: synthesis, characterization, DFT calcula-
tion and antimicrobial activity
Jian-Hong Jiang, Yan-Hua Lei, Xu Li, Yiyuan Pi, He Zhu, Qiang-Guo Li,
Chuan-Hua Li
PII:
S1387-7003(20)30940-0
DOI:
https://doi.org/10.1016/j.inoche.2020.108350
INOCHE 108350
Reference:
To appear in:
Inorganic Chemistry Communications
Received Date:
Revised Date:
Accepted Date:
26 August 2020
15 November 2020
18 November 2020
Please cite this article as: J-H. Jiang, Y-H. Lei, X. Li, Y. Pi, H. Zhu, Q-G. Li, C-H. Li, New cobalt(II) Schiff base
complex: synthesis, characterization, DFT calculation and antimicrobial activity, Inorganic Chemistry
Communications (2020), doi: https://doi.org/10.1016/j.inoche.2020.108350
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover
page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version
will undergo additional copyediting, typesetting and review before it is published in its final form, but we are
providing this version to give early visibility of the article. Please note that, during the production process, errors
may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
©
2020 Elsevier B.V. All rights reserved.

New cobalt(II) Schiff base complex: synthesis, characterization, DFT
calculation and antimicrobial activity
Jian-Hong Jiang, Yan-Hua Lei, Xu Li, Yiyuan Pi, He Zhu, Qiang-Guo Li, Chuan-Hua Li*
Hunan Provincial Key Laboratory of Xiangnan Rare-Precious Metals Compounds and Applications,
College of Chemical Biology and Environmental Engineering, Xiangnan University, Chenzhou
4
23043, Hunan Province, P.R. China.
*Corresponding author. Tel./Fax: +86-735-2653353
E-mail address: lichuanhua0526@126.com (C.-H. Li)
Abstract
A new cobalt(II) Schiff-base complex [Co(L) ] was prepared by using equivalent molar of
2
Schiff-base ligand [HL=(E)-N'-(2-hydroxy-3-methoxybenzylidene)isonicotinohydrazide] and
CoCl •6H O. The structure of the complex was characterized by single-crystal X-ray diffraction, IR,
2
2
ESI-MS, elemental analysis and DFT method. X-ray crystal structure analysis showed that the
complex crystallized in space group Pbca, with two symmetry-independent molecules. The
experimental vibrational bands(IR) have been discussed and assigned based on DFT calculations.
The antibacterial activity of Schiff base and its complex against S. pombe were assessed by
o
bio-microcalorimetry at 32 C. Some thermokinetic parameters (k, Pmax, tG and Qtotal) were derived
from the metabolic power–time curves, and their quantitative relationship with the concentration
were analyzed. The half inhibition concentration (IC ) of Schiff base and its complex were
5
0
-2
-1
-3
-1
calculated to be 1.18×10 mol L and 1.07×10 mol L , respectively. The inhibition effect of the
complex showed much stronger than that of Schiff base.
Keywords: Isoniazid; Schiff base; Cobalt(II) complex; DFT calculations; Bio-microcalorimetry;
Thermokinetic parameters
1

1
. Introduction
Schiff base is a class of organic compound containing an azomethine (-HC=N-) or imine
>C=N-) group, which is usually formed by condensation of active carbonyl group (aldehyde or
(
ketone) with a primary amine under azeotropic distillation [1]. Over the years, the coordination
chemistry of Schiff bases has received much attention of researchers due to their flexible
coordination modes and multiple metal coordination behaviors. Complexes constructed by Schiff
bases possess important medicinal properties such as antimicrobial, antibacterial, antifungal and
anticancer activity [2-6]. Isoniazid (also, Nicotinic Acid Hydrazide, INH or H) was known as early
as 1912 [7]. The appearance of Isoniazid has been regarded as a very important milestone in the
history of the conquest of tuberculosis. Isoniazid, along with rifampicin (RIF), ethambutanol (EMB),
pyrazinamide (PZA) and streptomycin, has been identified by World Health Organization(WHO) as
the first-line antitubercular drug [8]. The function of isoniazid is to inhibit the production of Mycolic
Acid, which is an essential cell wall component in tuberculosis [9].
In recent years, there has been also considerable interest in the chemistry of isoniazid Schiff
bases and their complexes. Isoniazid, possessing an amino group, can react with various carbonyl
compounds (aldehydes and ketones) to form Schiff bases (hydrazones), containing the characteristic
H-C=N-NH- group. There is a possibility of tautomerism between the carbonyl group and the amino
group in isoniazid Schiff base moiety in some cases [10]. Compared with the -C=N group, the
presence of OH or NH groups in an appropriate position have greater chance to increase
intramolecular as well as intermolecular interactions [11]. This indicates that isoniazid Schiff base
may display much stronger bioactivity owing to improved interactions with the binding sites. Some
transition-metal complexes of isoniazid Schiff bases have been investigated such as Cu(II), Zn(II)
and
Mn(II)
[12-14].
Cobalt(II)
complexes
of
(
E)-N'-(2-hydroxy-3-methoxybenzylidene)isonicotinohydrazide [Co(HL) ](NO ) •3H O has been
2
3 2
2
described in previous literature [15]. In this study, in continuation of our research on the on synthesis
of Schiff base and their complexes [16-19], we have described the synthesis and characterization of
new cobalt(II) complex of Schiff base derived from 3-methoxysalicylaldehyde with isoniazid
(Scheme 1). The determinations of the X-ray structure of the complex and DFT calculations on it
have been undertaken. The antibacterial activity of Schiff base and its cobalt(II) complex against S.
pombe was investigated.
2

O
HC
NH2 + HO
H
O
N
CH OH, rt
3
N
N
N
H
no catalyst
O
HO
N
O
O
H
N
N
O
N
CoCl2 6H O
2
O
O
o
CH OH, 60 C
3
Co
O
O
O
N
N
N
H
Scheme 1 Synthesis of cobalt(II) complex.
2
. Experimental
2
.1. Chemicals and physical measurements
-Methoxysalicylaldehyde and isoniazid with analytical grade were purchased from Thermo
Fisher Scientific. Other chemicals were purchased from the Sinopharm Chemical Reagent Co., Ltd.
3
(Shanghai,
China)
and
used
without
further
purification.
(E)-N'-(2-hydroxy-3-methoxybenzylidene)isonicotinohydrazide was prepared according to the
published literature [14]. Schizosaccharomyces pombe (S. pombe) (ACCC 20047) was bought from
Beijing Century Aoke Biological Technology Co., Ltd. YES medium (per liter) consisted of yeast
(
5.000 g), glucose (30.000 g), L-leu (0.225 g), L-lys (0.225 g), L-his (0.225 g), adenine (0.225 g),
and uracil (0.225 g).
Carbon, hydrogen, and nitrogen analyses were determined using an elemental analyzer
(
Perkin-Elmer 2400 II). FT-IR spectra was measured with KBr discs on an Avatar 360 (Nicolet,
-
1
Madison, USA) spectrophotometer in the wavenumber range of 4000–400 cm with an average of
-
1
3
3
2 scans and 4 cm of spectral resolution. A microcalorimetric study was carried out on a
116-2/3239 TAM Air calorimeter (Thermometric AB, Sweden) [20]. Molecular weight of the
complex was determined using a thermo TSQ Quantum Ultra Access triple-quadrupole mass
spectrometer (Thermo Fisher Scientific, Waltham, MA). X-ray photoelectron spectroscopy (XPS)
was measured on a Thermo Scientific Nexsa using monochromatized Al Kα radiation (1486.6 eV).
2
.2. Synthesis of Schiff base
A mixture of isonicotinohydrazide (2 mmol, 0.274 g), 3-methoxysalicylaldehyde (2 mmol,
.304 g) and methanol (25 mL) was allowed to stir for 2h without catalyst at room temperature.
0
3

The reaction mixture was concentrated on a rotary evaporator to the desired volume. The light
yellow precipitate formed was collected by filtration under suction, washed repeatedly with
o
methanol, and recrystallized twice with methanol. The pure product was dried at 60 C in a vacuum
oven, and then kept in a dessicator over anhydrous CaCl . Yield: 84%. The solid product was
2
identified as C H O N . Spectroscopic data of Schiff base were given as follows: IR (KBr): 3024
1
4
13
3
3
-
1
-1
-1
-1
-1
cm (ν
), 2840cm (ν ), 1690 cm (ν ), 1603, 1567 cm (ν ), 1464 cm (δas C-H), 1289
C-H C=N C=C
C=C-H
-1
-1
-1
1
cm , 1247 cm (ν ), 741 cm . H NMR(500MHz, DMSO-d6): δ 3.82 (s, 3H, CH O), 6.86-7.22
Ph-O
3
(3H, Ar), 7.84-7.85 (d, 2H, Ar), 8.70 (s, 1H, CH=N), 8.79-8.80 (d, 2H, Ar), 10.69(s, 1H, NH), 12.26
(
s, 1H, OH). Elemental analysis for C H O N , Calc. (Found): C 61.99 (61.97), H 4.83 (4.80), N
1
4
13
3
3
1
5.49 (15.51) %.
2
.3. Synthesis of the complex
A methanolic solution (5 mL) of CoCl •6H O (0.5 mmol, 0.119 g) was added dropwise to a
2
2
o
methanolic solution (20 mL) of Schiff base (0.5 mmol, 0.136 g) at 60 C. Immediately after
addition, the color of the solution changed from light green to dark-brown. The reaction mixture
was allowed to stir for 3 h. The precipitate was collected by filtration, washed with methanol
followed by ethyl ether, and air dried. The black-block single crystal appeared after about ten days
of slow evaporation of mother liquor. Solubility: DMSO, DMF; Yield: 0.093 g, 62.0%. The solid
product was identified as [Co(C H O N ) ]. Spectroscopic data of the complex were given as
1
4
12
-1
3
3 2
-1
-1
-1
-1
follows: 3026 cm (ν
), 2834 cm (ν ), 1602 cm (ν ), 1548, 1506 cm (ν ), 1433 cm (δ
C=C-H
C-H
C=N
C=C
as
-1
-1
-1
C-H), 1241 cm , 1212 cm (ν ), 737 cm . Elemental analysis for [Co(C H O N ) ], Calc.
Ph-O
14 12
3
3 2
(Found): C 56.1 (56.0), H 4.0 (4.2), N 14.0 (13.8) %. ESI-MS (m/z): 599.9.
2
.4. Computational details
The geometry optimization and frequency calculations of the dimer motif were performed in gas
phase using the Gaussian 09 software package [21]. The starting geometry for the calculation was
taken from the experimentally determined crystal structure. Geometrical optimization of Schiff base
and its complex were carried out with the DFT B3LYP method [22,23]. We used the effective core
potentials (ECPs) of Hav and Wadt with a double -valence basis set LANL2DZ for the cobalt atoms
[24], and the 6-31 G(d, p) basis sets for H, C, O, N atoms. Vibrational analyses were performed to
ensure all stationary points to be local minima in the potential energy surfaces and no correction
coefficient was used. The vibration bands were assigned by using Gauss View program.
4

2
.5. Microcalorimetric measurement
The microcalorimetric experiments were determined on a TAM air isothermal microcalorimeter
o
at 32 C using the ampoule method. The principle and structure of the instrument were described in
previous literature [20]. All 20-mL glass ampoules were cleaned and sterilized in high-pressure
o
steam (0.1 MPa) at 120 C before use. 5 mL YES culture medium containing S. pombe at the cell
6
density of 1 × 10 colony-forming units (CFU)/mL was inoculated in a sterilized 20-mL glass
ampoule, and then Schiff base and its complex at increasing concentrations were injected into each
ampoule. All ampoules were sealed with special caps, shaken-up gently and placed in measuring
channels. The metabolic power-time curves of S. pombe growth in the presence of two tested drugs
were recorded in situ by a computer in a real-time manner.
2
.6. X-ray single-crystal diffraction analysis
A single crystal of dimensions 0.13 × 0.12 × 0.1 mm for the complex was selected. Crystal
3
data were collected with a SuperNova, Dual, Cu at zero, AtlasS2 diffractometer using
monochromated Cu Ka radiation (λ = 1.54184) at 100.01(10) K. The crystal data were dealt with
the program CrysAlisPro, Agilent Technologies Version 1.171.36.28 during data collection. The
crystal displayed good diffraction quality and no variation in intensity during the course of data
collection. A total of 29990 integrated reflections were collected, reducing to a data set of 10683
[
R(int)=0.0994], and completeness of data to theta = 66.97° of 99.93%.
Using the program Olex2 [25], the structure was solved with the ShelXS structure solution
program by direct methods and refined using full-matrix least-squares against F2 using SHELXL
26]. All non-hydrogen atoms were assigned anisotropic displacement parameters and refined
[
without positional constraints. Hydrogen atoms were refined in geometrically idealized position
with isotropic thermal parameters. The detailed crystallographic data and structure refinement
parameters of the complex are summarized in Table 1. CCDC reference numbers: 2007789.
Graphics were drawn with DIAMOND (Version 3.2) [27].
3
3
. Results and discussion
.1. The crystal structure of the complex
X-ray crystallographic analysis reveals that the complex crystallizes in the orthorhombic space
group of Pbca symmetry. Its crystal structure consists of two symmetry-independent molecules (Fig.
a). Two molecules are not only nearly identical in their distances and angles but also in their
1
configuration. As shown in Fig. 1a, Co(II) ion is attached to the ligand in a ratio of 1:2. It is
5

six-coordinated to two azomethine nitrogen atoms, two carbonyl oxygen atoms and two phenolic
oxygen atoms from two ligands. As depicted in Fig. 1b, Co(II) ion exhibits a slightly distorted
octahedral configuration with two phenolic oxygen (O2 and O5), amide oxygen atom (O3 and O4)
from two monoanion ligands consisting of the equatorial plane and two azomethine nitrogen atoms
(N3 and N4) occupying the axial site. Selected bond lengths and angles are listed in Table 2. The
Co–N bonds involved two azomethine nitrogen atoms were 1.866(6) Å and 1.865(6) Å, respectively.
The Co–O bonds varied from 1.865(5) to 1.919(5) Å. The bond distances Co–N and Co–O in the
complex are consistent with those reported in literatures [15,28]. Crystal packing of the complex is
achieved by intramolecular and intermolecular hydrogen bonds. The hydrogen bond geometry is
given in Table 1s. Hydrogen-bonds are formed between the oxygen atoms of methoxy or hydoroxy
group and the hydrogen atoms of carbon atoms in the pyridine rings (Fig. 1s). Here, it should be
noted that the oxidation sate of the cobalt has been verified to be +2 according to the XPS spectrum
of the complex (Fig. 2s). This is because that there are seven 3d electrons in outermost shell of
cobalt(II) and six electrons of cobalt(III). The cobalt(II) can provide more intense shake-up satellite
in the high spin state, while cobalt(III) is diamagnetic and has no satellite peak [29].
3
3
.2. Theoretical studies
.2.1 Geometry optimization
The optimized molecular structures of Schiff base and its complex are shown in Fig. 2 and some
selected structure parameters are shown in Table 2s. It should be pointed out that the phenol
hydroxyl in Schiff base forms negative ion in the complex. Due to the instability of low spin state,
the 3d electrons of Co2+ in the complex are in the weak electron field and high spin state. The
calculated bond parameters are consistent with the experimental values, whereas the calculated bond
length of cobalt ion with ligand and the torsion angle of pyridine ring deviates from experimental
values. These deviations may be caused by the strong intermolecular force. The pyridine ring in the
complex crystal is almost coplanar with the other groups due to the intermolecular π-π stack. In the
gas phase, the intramolecular repulsive force leads to the pyridine ring departure from the conjugate
plane, with the torsion angle about 26o.
The most important orbitals in a molecule are the frontier molecular orbitals. The frontier
molecular orbitals for the closed shell molecule include the highest occupied molecular orbital
(HOMO) and the lowest unoccupied molecular orbital (LUMO). While for the open shell molecules,
the HOMO may be singly occupied molecular orbitals (SOMO). The HOMO of Schiff base mainly
comes from the lone electron pair of oxygen atom, as shown in Fig. 3. The LUMO mainly locate at
the π* anti-bond orbital of C-N bond in the pyridine ring. The formed energy gap between HOMO
6

and LUMO indicates the molecular chemical stability. Molecules which have a large HOMO-LUMO
energy gap maybe called hard and which have a small energy gap maybe called soft [30]. The
calculated band gap for Schiff base is 4.05 eV, which means good stability and a high chemical
hardness for Schiff base. But the calculated band gap for the complex is only 2.64 eV.
3
.2.2 Vibrational assignments
The experimental and theoretical IR spectra of the complex in 400-4000 cm region are shown
-1
in Fig. 4. The vibrational wavenumbers were calculated according to the optimized geometries in gas
phase by using B3LYP method with the basis set. It is noted that none of the frequency calculations
is found to exhibit any imaginary frequency, which is consistent with an energy minimum for the
-1
optimized geometry that proves the reliability of the obtained results. The peaks at 1602 cm is a
coupled vibration coming from azomethine group (C=N) and carbonyl group (C=O), were calculated
-1
-1
-1
at 1665 cm for the complex. The peak of at 1548 cm , 1506 cm for C=C ring stretch of aromatic
-1
-1
groups, the calculated peak is located at 1593 cm , 1575 cm . The asymmetric stretching vibration
-1
-1
of C-H bond appears at 1433 cm , while the corresponding theoretical value is 1492 cm . The
-1
-1
absorption at 1241 cm , 1212 cm for the phenolic oxygen group (Ph-O), the calculated value is
-1
-1
recorded in 1284 cm , 1243 cm .
3
3
.3. Microcalorimetry
.3.1 The normal metabolic power–time curve of S. pombe
The metabolic power–time curve of S. pombe growth at 32 °C in the absence of tested drug is
shown in Fig. 5a. As S. pombe was inoculated in YES culture medium under isochoric conditions
and limited nutrients and oxygen, the metabolic process could be divided into four phases, namely, a
lag phase (AB), a log(exponential) phase (BC), a stationary phase (CD) and a decline phase (DE).
During the log phase, the power–time curves could obey the following equation [31]:
P = P exp[k(t–t )]
t
0
0
or
ln P = ln P +kt–kt
0
t
0
The above equations are called biothermokinetic equation of growth metabolic of S. pombe, where
P and P stand for the heat–output power at initial time t = 0 and any time t, respectively. k is the
0
t
growth rate constant for S. pombe at specified condition. The growth rate constant k of the
exponential phase was calculated by fitting lnP and t to a linear equation.
t
3
.3.2 Metabolic power–time curves of S. pombe affected by Schiff base and its complex
7

When the suspensions of S. pombe were introduced into the ampoules with different
concentrations of tested drugs, there existed corresponding changes in the power–time curves. As
presented in Fig. 5b and 5c, compared with the blank control group, the height, peak time and shape
of each experimental group were significantly changed. From the metabolic power–time curves of S.
pombe growth, four quantitative thermokinetic parameters (k, P, t and Q) were obtained and are
G
illustrated in Table 3. In comparison with the control, k, P and Q decreased and t increased with the
G
increase of drug concentration. The inhibition ratio (I) of the growth metabolism of S. pombe by the
tested drugs could be descried as the following equation:
(
k  k )
0
c
I 
100%
k
0
Where k is the rate constant of the control and k is the rate constant under an inhibitor with a
0
c
concentration of c. When the inhibition ratio (I) is 50%, the corresponding concentration of inhibitor
is called as the half inhibition concentration IC . To explore the inhibitory effect of the tested drugs
5
0
on S. pombe, the values of I and IC were calculated. As are shown in Table 3, the half inhibition
5
0
-2
-1
-3
-1
concentration (IC50) of Schiff base and its complex are 1.18×10 mol L and 1.07×10 mol L ,
respectively, which indicates the complex has a stronger inhibition effect than that of Schiff base on
S. pombe growth. It is possible that the biological activity of the complex is not only related to the
structure of the ligand, but also depends on the property of the central metal ion [32].
3
.3.3 Quantitative relationship between thermokinetic parameters and concentrations of Schiff
base and its complex.
3
.3.3.1 Relationship between I and C
Plotting the inhibition ratio (I) against the concentration (c) of Schiff base and its complex, Fig.
s was obtained. According to Fig. 3s, when the concentration of the tested drugs increased, I values
3
increased gradually, which reveals that both Schiff base and its complex have inhibition effect on S.
pombe growth. Using the Logistic curve fitting from data of I and c, the I-c equations could be
described in Eqs. (1) and (2) (see Table 4):
3
.3.3.2 Relationship between k and c
Drawing the inhibition ratio (k) of S. pombe growth against concentration (c), the corresponding
curves are shown in Fig.4s. Fig. 4s illustrated that as the concentrations of the tested drugs increased,
the growth rate constant (k) of S. pombe decreased. The quantitative relationship between k and c by
nonlinear fitting were given in Eqs. (3) and (4) (see Table 4):
8

3
.3.3.3 Relationship between Pmax and c
The Pmax-c curves were drawn relied on the maximum heat-output power (Pmax) and the
different concentration (c) of the tested drugs. As presented in Fig. 5s, as the concentration of the
tested drugs increased, the Pmax of S. pombe decreased. The Pmax-c equations were shown in Eqs. (5)
and (6) of Table 4 by using the nonlinear fitting method, in which the correlation coefficients R of
Schiff base and its complex were 0.9843 and 0.9935, respectively.
3
.3.3.4 Relationship between t and c
G
As the biothermokinetic equation was very similar to the indefinite integral relation of rate
equation of the first order reaction, the mathematical expression of generation time (t ) of S. pombe
G
was defined by simulating the relationship between the half-life of the first order reaction and the
rate constant of the reaction. The generation time (t ) of the growth metabolism S. pombe treated by
G
drugs was defined as follows:
tG= ln2/k
where t was generation time and k was growth rate constant of S. pombe. The t of S. pombe
G
G
were calculated at different concentration of the tested drugs, as summarized in Table 3. The t -c
G
curves were drawn from t and c. As could be seen from Fig. 6s, the generation time (t ) of S. pombe
G
G
increased with the increasing concentration of the tested drugs. The t -c equations were produced by
G
using the nonlinear fitting method (see Eqs. (7) and (8) in Table 4)
3
.3.3.5 Relationship between Qtotal and c
Plotting the total heat-output (Qtotal) against the concentration (c), the curves were illustrated in
Fig. 7s. As shown in Fig. 7s, with the increase of the concentrations of the tested drugs, the Qtotal of
S. pombe decreased. Using the logistic curve fitting from data of the the total heat-output (Qtotal) of S.
pombe growth against concentration (c), the Qtotal-c equations were produced (as shown in Eqs. (9)
and (10) of Table 4). The correlation coefficients R of Schiff base and its complex were 0.9671 and
0
.9890, respectively.
4
. Conclusions
In conclusion, a new cobalt(II) Schiff-base complex has been synthesized and characterized.
X-ray crystallographic analysis revealed that a cobalt(II) was coordinated by two Schiff-base ligands
via azomethine, carbonyl oxygen atoms and phenolic oxygen atoms. DFT calculations have been
done for Schiff base and its complex. Their calculated band gaps are 4.05 eV and 2.64 eV,
9

respectively, which means Schiff base has good stability and a high chemical hardness. They have
also been screened for their antibacterial (S. pombe) by bio-microcalorimetry. The antibacterial test
referred that the complex recorded significant inhibition efficiency against S. pombe than Schiff
base. According to the metabolic power–time curves, some thermokinetic parameters were obtained,
and their quantitative relationship with the concentration were discussed. As a basic research, the
purpose of this study is to afford some valuable reference data for further study of Schiff bases and
their complexes.
Acknowledgements
The authors thank The National Natural Science Foundation of China (No. 21273190), The
Hunan Provincial Natural Science Foundation of China (No. 2017JJ2240), The Project of Scientific
Research of Hunan Provincial Education Department (No. 18B499, 20A463), The Hunan University
Students' Innovation and Entrepreneurship Training Program Project (No. S202010545008) and
Science and Technology Plan Project of Chenzhou city (No. ZDYF2020154) for financial support.
Appendix A. Supplementary data
CCDC 2007789 contains the supplementary crystallographic data for the complex. These data
can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44)
1
223-336-033; or e-mail: deposit@ccdc.cam.ac.uk.
References
[
[
[
1] X. Liu, J.R. Hamon, Recent developments in penta-, hexa- and heptadentate Schiff base ligands
and their metal complexes, Coord. Chem. Rev. 389 (2019) 94-118.
2] V.B. Badwaik, R.D. Deshmukh, A.S. Aswar, Transition metal complexes of a Schiff base:
synthesis, characterization, and antibacterial studies, J. Coord. Chem. 62 (2009) 2037-2047.
3] D. Sinha, A.K. Tiwari, S. Singh, G. Shukla, P. Mishra, H. Chandra, A.K. Mishra, Synthesis,
characterization and biological activity of Schiff base analogues of indole-3-carboxaldehyde,
Eur. J. Med. Chem. 43 (2008) 160-165.
[
4] S. Adsule, V. Barve, D. Chen, F. Ahmed, Q.P. Dou, S. Padhye, F.H. Sarkar, Novel Schiff base
copper complexes of quinoline-2 carboxaldehyde as proteasome inhibitors in human prostate
cancer cells, J. Med. Chem. 49 (2006) 7242-7246.
1
0

[
5] S. Ren, R. Wang, K. Komatsu, P. Bonaz-Krause, Y. Zyrianov, C.E. McKenna, C. Csipke, Z.A.
Tokes, E.J. Lien, Synthesis, biological evaluation, and quantitative structure-activity
relationship analysis of new Schiff bases of hydroxysemicarbazide as potential antitumor
Agents, J. Med. Chem. 45 (2002) 410-419.
[
6] A.K. Ghosh. M. Mitra, A. Fathima, H. Yadav, A.R. Choudhury, B.U. Nair, R. Ghosh,
Antibacterial and catecholase activities of Co(III) and Ni(II) Schiff base complexes, Polyhedron
1
07 (2016) 1-8
[
7] C.R. Krishna Murti, Isonicotinic acid hydrazide, in: J.W. Corcoran, F.E. Hahn, J.F. Snell, K.L.
Arora (Eds.), Mechanism of action of antimicrobial and antitumor agents, Springer-Verlag
Berlin Heidelberg, 1975, pp. 623-652.
[
[
[
8] S. Somasundaram, A. Ram, L. Sankaranarayanan, isoniazid and rifampicin as therapeutic
regimen in the current era: a review, Journal of Tuberculosis Research, 2 (2014) 40-51.
9] B.F. Lei, C.J. Wei, Action mechanism of antitubercular isoniazid, The Journal of Biological
Chemistry, 275 (2000) 2520-2526.
10] E.N. Mainsah, P.T. Ndifon, E.N. Nfor, J.N. Njapba, Synthesis, characterization and antibacterial
properties of some transition metal complexes of (1H-pyrrol-2-yl)isonicotinoyl hydrazine, Bull.
Chem. Soc. Ethio. 27 (2013) 395-404.
[
[
[
[
11] O. Berkesi, T. Kortvelyesi, C. Hetenyi, T. Nemeth, I. Palinko, Hydrogen bonding interaction of
benzylidene type Schiff bases studied by vibrational spectroscopic and computational methods,
Phys. Chem. Chem. Phys. 5 (2003) 2009-2014.
12] L. Habala, S. Varenyi, A. Bilkova, P. Herich, J. Valentova, J. Kozisek, F. Devinsky,
Antimicrobial activity and urease inhibition of Schiff bases derived from isoniazid and
fluorinated benzaldehydes and of their copper(II) complexes, Molecules 21 (2016) 1742.
13] E.N. Mainsah, S.J.E. Ntum, M. Samje, F. Chongwa, P.T. Ndifon, J.N Yong, Synthesis and
anti-onchocercal activity of isonicotinoyl hydrazones and their copper(II) and zinc(II)
complexes, Anti-Infective Agents. 14 (2016) 47-52.
14]
J.
Xu,
Synthesis,
crystal
structure,
and
antibacterial
activity
of
N′-(2-hydroxy-3-methoxybenzylidene)isonicotinohydrazide and its dinuclear manganese(II)
complex with N′-(2-hydroxy-3-methoxybenzylidene)isonicotinohydrazide, Synth. React. Inorg.
M. 43 (2013) 1329-1333.
[
15] M. Tabatabae, A. Taghinezhadkoshknou, M. Dusek, K. Fejfarova, Synthesis and
characterization of a cobalt(II) complex with (E)-N'-(2-hydroxy-3-methoxybenzylidene)
isonicotinohydrazide and (E)-N'-(2-hydroxy-3-methoxybenzylidene)isonicotinohydrazidanium
nitrate as a by-product, Synth. React. Inorg. M. 45 (2015) 1506-1512.
1
1

[
[
[
16] C.H. Li, J.H. Jiang, X. Li, L.M. Tao, S.X. Xiao, H.W. Gu, H. Zhang, C. Jiang, J.Q. Xie,
M.N. Peng, L.L. Pan, X.M. Xia, Q.G. Li, Synthesis, crystal structure and biological
properties of a bismuth(III) Schiff-base complex, RSC Adv. 5 (2015) 94267-94275
.
17] C.H. Li, J.H. Jiang, P. Yang, X. Li, S.X. Xiao, X. Tao, J.Q. Xie, Q.G Li, Preparation,
structure and thermochemical properties of a copper(II) Schiff-base complex, J. Therm. Anal.
Calorim. 119 (2015) 1285-1292.
18] J.Q. Xie, C.H. Li, J.X. Dong, W. Qu, L. Pan, M.L. Peng, M.A. Xie, X. Tao, C.M. Yu, Y. Zhu,
P.H. Zhang, C.G. Tang, Q.G. Li, The standard molar enthalpy of formation of a new copper(II)
Schiff-base complex and its interaction with bovine serum albumin, Thermochim. Acta 589
(2014) 7-15.
[19] C.H. Li, X.Z. Song, J.H. Jiang, H.W. Gu, L.M. Tao, P. Yang, X. Li, S.X. Xiao, F.H. Yao,
W.Q. Liu, J.Q. Xie, M.N. Peng, L. Pan, X.B. Wu, C. Jiang, S. Wang, M.F. Xu, Q.G. Li,
Synthesis, crystal structure and thermodynamic properties of a new praseodymium Schiff-base
complex, Thermochim. Acta 581 (2014) 118-122.
[
20] X. Li, J.H. Jiang, Q.Q. Chen, S.X. Xiao, C.H. Li, H.W. Gu, H. Zhang, J.L. Hu, F.H. Yao, Q.G.
Li, Synthesis of nordihydroguaiaretic acid derivatives and their bioactivities on S. pombe and
K562 cell lines, Eur. J. Med. Chem. 62 (2013) 605-613.
[
21] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G.
Scalmani, V. Barone, B. Mennucci, G.A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H.P.
Hratchian, A.F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K.
Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T.
Vreven, J.A. Montgomery, Jr., J.E. Peralta, F. Ogliaro, M. Bearpark, J.J. Heyd, E. Brothers,
K.N. Kudin, V.N. Staroverov, T. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A.
Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J.M. Millam, M. Klene, J.E.
Knox, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev,
A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, R.L. Martin, K. Morokuma, V.G.
Zakrzewski, G. A. Voth, P. Salvador, J.J. Dannenberg, S. Dapprich, A.D. Daniels, O. Farkas,
J.B. Foresman, J.V. Ortiz, J. Cioslowski, D.J. Fox, Gaussian 09, Revision B. 01, Gaussian Inc.,
Wallingford CT, 2010.
[
[
[
22] C. Lee, W. Yang, R.G. Parr, Development of the Colle-Salvetti correlation-energy formula into
a functional of the electron density, Phys. Rev. B 37 (1988) 785-789.
23] A.D.J. Becke, Density-functional thermochemistry. III. The role of exact exchange, J. Chem.
Phys. 98 (1993) 5648-5652.
24] M. Couty, M.B. Hall, Basis sets for transition metals: optimized outer p functions. J. Comput.
1
2

Chem. 17 (1996) 1359-1370.
[
25] O.V. Dolomanov, L.J. Bourhis, R.J. Gildea, J.A.K. Howard, H. Puschmann, OLEX2: a
complete structure solution, refinement and analysis program, J. Appl. Crystallogr. 42 (2009)
3
39-341.
[
[
26] G.M. Sheldrick, A short history of SHELX, Acta. Crystallogr. A 64 (2008) 112-122.
27] K. Brandenburg, Diamond (Version 3.2), Crystal and Molecular Structure Visualization,
Germany, 2009, http://www.crystalimpact.com/diamon.
[
28] E. Gungor, S. Celen, D. Azazb, H. Kara, Two tridentate Schiff base ligands and their
mononuclear cobalt (III) complexes: synthesis, characterization, antibacterial and antifungal
activities, Spectrochim. Acta Part A. 94 (2012) 216-221.
[
29] J.A. Sans, J.F. Sanchez-Royo, J. Pellicer-Porres, A. Segura, E. Guillotel, G. Martinez-Criado, J.
Susini, A. Munoz-Paez, V. Lopez-Flores, Optical, X-ray absorption and photoelectron
spectroscopy investigation of the Co site configuration in Zn Co O films prepared by pulsed
1
−x
x
laser deposition, Superlattices and Microstructures. 42 (2007) 226-230.
[30] E.F. Silva-Júnior, D.L. Silva, P.F.S. Santos-Júnior, I.J.S. Nascimento, S.W.D. Silva, T.L.
Balliano, T.M. Aquino, J.X. Araújo-Júnior, Crystal structure and DFT calculations of
4
,5-dichloropyridazin-3-(2H)-one, J. Chem. Pharm. Res. 8 (2016) 279-286.
[
31] C.L. Xie, H.K. Tang, Z.H. Song, S.S. Qu, Y.T. Liao, H.S. Liu, Microcalorimetric study of
bacterial growth, Thermochim. Acta 123 (1988) 33-41.
[
32] X. Li, C.H. Li, J.H. Jiang, H.W. Gu, D.L. Wei, L.J. Ye, J.L. Hu, S.X. Xiao, D.C. Guo, X. Li, H.
Zhang, Q.G. Li, Synthesis and microcalorimetric determination of the bioactivities of a new
Schiff base and its bismuth(III) complex derived from o-vanillin and 2,6-pyridinediamine, J.
Therm. Anal. Calorim. 127 (2017) 1767-1776.
1
3

Legends to Figures
Fig. 1 (a) Molecular structure of the complex. (b) Coordination polyhedron of Co(II) ion in the
complex.
Fig. 2 Theoretical structure of (a) Schiff base and (b) the complex.
Fig. 3 The frontier orbit of Schiff base and the complex. (a) HOMO of Schiff base. (b) LUMO of
Schiff base. (c) SOMO of the complex. (d) LUMO of the complex.
Fig. 4 Experimental and theoretical IR spectra of the complex.
Fig. 5 Metabolic power-time curves of S. pombe cells affected by the tested drugs at 32.00 °C. (a)
for control. (b) Schiff base. (c) the complex.
1
4

(a)
(b)
Fig. 1 (a) Molecular structure of the complex. (b) Coordination polyhedron of Co(II) ion in the
complex.
(a)
(b)
Fig. 2 Theoretical structure of (a) Schiff base and (b) the complex.
1
5

Fig.
3
The
frontier
orbit of
Schiff
base
and the
comple
x. (a)
HOMO
of
(a)
(c)
Schiff
base.
(b)
LUMO
of
Schiff
base.
(c)
SOMO
of the
comple
x. (d)
LUMO
of the
comple
x.
(b)
(d)
1
6

180
160
140
120
100
-3
-1
1
1
1
1
80
60
40
20
C(Schiff base) /10 mol L
C.
.
D
(a)
1
1
3
5
7
0.00
3.13
6.27
10.45
2
4
6
8
1.57
(b)
4.70
7.84
14.37
2
3
4
100
5
6
8
6
4
0
0
0
80
60
40
20
7
8
A
B
.E
.
.
20
0
-
200
0
200
400
600
800 1000 1200 1400 1600 1800
-
200
0
200
400
600
800 1000 1200 1400 1600 1800
t/min
t/min
-
4
-1
C(the complex) /10 mol L
1
3
5
7
0.00
5.20
8.17
11.14
2
4
6
3.72
6.69
9.66
12.63
(c)
180
160
140
120
100
8
1
2
3
4
80
60
40
20
5
6
7
8
0
200
400
600
800
1000
t/min
Fig. 4 Experimental and theoretical IR spectra of the complex.
Fig. 5 Metabolic power-time curves of S. pombe cells affected by the tested drugs at 32.00 °C. (a)
for control. (b) Schiff base. (c) the complex.
1
7

Legends to Tables
Table 1 Crystallographic data for the complex.
Table 2 Selected bond lengths (Å) and bond angles (°) for the complex.
Table 3 Thermokinetic parameters of the growth of S. pombe affected by different concentrations of
o
Schiff base and its complex at 32 C.
Table 4 Quantitative relationship between thermokinetic parameters and concentrations of Schiff
base and its complex.
Table 1
Crystallographic data for the complex.
Crystal data
1
8

CCDC No.
2007789
Z
16
1.466
5.420
0.13 × 0.12 × 0.1
29990
10683
99.93 %
5.214 -147.526
-23 ≤ h ≤ 23, -20 ≤ k ≤ 11,
3
Empirical formula
Formula weight
Temperature (K)
Wavelength (Å)
Crystal system
Space group
a (Å)
C
28
H
24CoN
6
O
6
Dcalc (g/cm )
Absorption coefficient (mm )
Crystal size (mm)
-1
599.46
100.01(10)
1.54184
orthorhombic
Pbca
19.1448(18)
16.7388(12)
Reflections collected
Independent reflections (Rint)
Completeness to theta =66.97° (%)
2Θ range for data collection/°
h, k, l range
b (Å)
-31 ≤ l ≤ 41
c (Å)
α (°)
β (°)
γ (°)
33.892(4)
90
90
90
Data/restraints/parameters
Goodness-of-fit on F
Final R indices [I > 2σ(I)]
R indices (all data)
10683/54/743
1.036
2
R
R
1
= 0.0912, wR
= 0.1630, wR
2
2
= 0.2380
= 0.2930
1
3
V (Å )
10861.1(18)
Table 2
Selected bond lengths (Å) and bond angles (°) for the complex.
Bond distances (Å)
Co(1)–O(2)
Co(1)–O(3)
Co(1)–O(4)
Co(1)–O(5)
1.865(5)
1.903(5)
1.919(5)
1.886(4)
Co(1)–N(3)
Co(1)–N(4)
C(14)–O(4)
C(8)–O(3)
1.866(6)
1.865(6)
1.298(8)
1.278(8)
Table
Bond angles (°)
O(2)–Co(1)–O(3)
O(2)–Co(1)–O(4)
O(2)–Co(1)–O(5)
O(2)–Co(1)–N(3)
O(2)–Co(1)–N(4)
O(3)–Co(1)–O(4)
O(5)–Co(1)–O(3)
O(5)–Co(1)–O(4)
3
90.4(2)
179.7(2)
90.4(2)
87.3(2)
96.2(3)
89.9(2)
179.0(2)
89.3(2)
N(3)–Co(1)–O(3)
N(3)–Co(1)–O(4)
N(3)–Co(1)–O(5)
N(4)–Co(1)–O(3)
N(4)–Co(1)–O(4)
N(4)–Co(1)–O(5)
N(4)–Co(1)–N(3)
83.4(2)
92.9(2)
95.9(2)
91.9(2)
83.6(2)
88.7(2)
174.2(2)
Thermokinetic parameters of the growth of S. pombe affected by different concentrations of Schiff
o
base and its complex at 32 C.
Ca/
mol L
0
ICd50/
P emax/
W
Q
g
total/
J
kb/s-1
R
Ic/%
t /s
G
f
Drugs
-1
mol L-1
5.54×10-5h ± 7.57×10-8
0.9956
0.9907
0.9919
0.9940
0.9919
0.9932
0.9912
0.9916
0.9922
0.9839
0.9901
0.9832
0.9955
0.9908
0.9916
0
1.65×10
-3
1.25×104
1.30×104
1.32×104
1.35×104
1.41×104
1.53×104
1.98×104
6.12×104
1.32×104
1.39×104
1.44×104
1.54×104
1.83×104
2.20×104
2.91×104
59.07
.57×10-3
5.34×10 ± 9.85×10
-5
-8
-8
-8
-8
-8
-8
-8
3.68
5.55
7.04
10.99
18.33
36.88
79.56
0
1.43×10-3
1.26×10-3
1.13×10-3
1.02×10-3
9.28×10-4
7.78×10-4
2.84×10-4
1.69×10-3
1.36×10-3
1.16×10-3
8.72×10-4
5.25×10-4
4.79×10-4
3.48×10-4
38.41
31.31
27.33
25.50
23.45
18.06
1.52
1
3
4
6
7
.13×10-3
.70×10-3
.27×10-3
.84×10-3
5.23×10 ± 9.31×10
-5
-5
5.15×10 ± 7.96×10
Schiff base
1.18×10-2
-5
4.93×10 ± 8.76×10
-5
4.53×10 ± 7.07×10
.045×10-2
.437×10-2
0
3.50×10 ± 5.88×10
-5
1
1
-5
1.13×10 ± 1.74×10
-5
-8
-8
5.26×10 ± 7.31×10
15.10
7.22
.72×10-4
.20×10-4
4.97×10 ± 9.69×10
-5
5.39
8.55
14.30
27.88
40.01
54.74
3
-5
-8
-8
-8
-8
-8
5
4.81×10 ± 7.55×10
6.35
-5
1.07×10-3
the complex
6.69×10-4
4.51×10 ± 1.00×10
6.14
.17×10-4
.66×10-4
3.79×10 ± 5.09×10
-5
3.41
8
9
-5
3.15×10 ± 5.82×10
3.10
.114×10-3
2.38×10 ± 4.38×10
-5
1.98
1
1
9

1
.263×10-3
The concentration
1.55×10 ±3.27×10
-5
-8
0.9902
70.53
2.93×10-4
4.47×104
1.22
a
b
c
d
e
f
The growth rate constant of S. pombe
The inhibition ratio
The half inhibition concentration
The maximum heat-output power
The generation time
g
h
The total heat-output
Mean ± S.D.; n = 3
Table 4 Quantitative relationship between thermokinetic parameters and concentrations of Schiff
base and its complex.
B
z  A 
c
m
1
 ( )
D
Serial
number
z
I
A
B
D
m
R
2
–
7363.23
–27360.95
142.93
2.55
0.9982
(1)a
2
05.33
1510.54
5.54
59957.06
.09
041.00
905.50
31275.67
1404.74
–204.50
1515.96
10.75
1.58
142.92
1.58
2.92
2.55
2.92
0.9985
0.9982
0.9985
(2)b
(3) a
(4) b
k
–
–
59958.68
1.59
–2039.67
–8904.10
31333.95
1419.81
2.11×10-6
0.90
2.93
6.10
5.06
0.48
0.52
0.9843
0.9935
0.9992
0.9971
0.9671
0.9890
(5) a
Pmax
0
0.64
38.72
6.12
8.37×10
95682.13
(6) b
(7) a
2
8
–
–
tG
b
(8)
(9)
6
a
Qtotal
b
(10)
Note: z refers to thermokinetic parameters (I, k, Pmax, t
G
and Qtotal).
c refers to the concentration.
R is correlation coefficient.
a
-1
-2
-1
For Schiff base, 0.00 mol L ≤ cSchiff base ≤ 1.44×10 mol L .
b
-1
-3
-1
For the complex, 0.00 mol L ≤ cthe complex ≤ 1.26×10 mol L .
2
0

Graphical Abstract
-
4
-1
C(the complex) /10 mol L
1
3
5
7
0.00
5.20
8.17
11.14
2
4
6
3.72
6.69
9.66
12.63
180
160
140
120
100
8
1
2
3
4
80
60
40
20
5
6
7
8
ESOMO = -4.60eV
E = 2.64eV
0
200
400
600
800
1000
t/min
ELUMO = -1.96eV
H
N
N
N
O
O
O
Co
O
O
O
N
N
N
H
2
1

Highlights





A new cobalt(II) complex was synthesized and characterized.
Theoretical studies using DFT calculations.
The bioactivity of cobalt(II) complex was assessed by bio-microcalorimetry.
The complex displayed much stronger antibacterial activity than Schiff base.
Some thermokinetic parameters (k, Pmax, t and Qtotal) were derived.
G
2
2

Credit Author Statement
Jian-Hong Jiang: Methodology, Validation. Yan-Hua Lei: Formal analysis, Validation. Xu Li:
Visualization. Yiyuan Pi: Writing-Original Draft. He Zhu: Investigation. Qiang-Guo Li:
Resources, Funding acquisition, Project administration, Writing-review & editing. Chuan-Hua Li:
Conceptualization, Methodology, Writing-review & editing, Data curation.
2
3

Declaration of interests
☒
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.
☐
The authors declare the following financial interests/personal relationships which may be considered as
potential competing interests:
2
4