Synthesis, characterization and cytotoxicity of new 2-isonicotinoyl-N-phenylhydrazine-1-carbothioamide and its metal complexes

Article abstract of DOI:10.1002/aoc.4998

The reaction of the newly synthesized ligand, 2-isonicotinoyl-N-phenylhydrazine-1-carbothioamide (H₃L), with acetate salt of Co (II), Cu (II),Ni (II) and Zn (II) led to isolation of four solid complexes. The ligand and complexes structure elucidation were based on elemental analyses, spectral analyses (IR, UV–Visible, ¹H and¹³C-NMR, MS and ESR), TGA, molar conductivity and magnetic moments measurements. The results indicated that the ligand exists in the thioketo form, while on coordination to the metal ions; it behaves as mono-negative bidentate chelate and exists in enol form. The optical band gap measurements of the ligand and its metal complexes are in the range 3.83–4.48?eV indicating their semi-conducting character. The cytotoxicity examination of H₃L and its Zn (II) complex showed that the ligand have very strong cytotoxicity against both HCT-116 and HEPG-2 cell lines while, Zn (II) complex has moderate activity.

Full text of DOI:10.1002/aoc.4998

Received: 15 July 2018
DOI: 10.1002/aoc.4998
Revised: 16 November 2018
Accepted: 23 April 2019
F U L L P A P E R
Synthesis, characterization and cytotoxicity of new
‐isonicotinoyl‐N‐phenylhydrazine‐1‐carbothioamide and
2
its metal complexes
1
1
1
2
Nasser M. Hosny
| Nader Y. Hassan | Heba M. Mahmoud | Mohamed H. Abdel‐Rhman
1
Chemistry Department, Faculty of
Science, Port Said University, 23
December Street, POB 42522 Port Said,
Egypt
The reaction of the newly synthesized ligand, 2‐isonicotinoyl‐N‐
phenylhydrazine‐1‐carbothioamide (H L), with acetate salt of Co (II), Cu (II),
3
Ni (II) and Zn (II) led to isolation of four solid complexes. The ligand and
2
Chemistry Department, Faculty of
complexes structure elucidation were based on elemental analyses, spectral
Science, Mansoura University, Mansoura,
Egypt
1
13
analyses (IR, UV–Visible, H and C‐NMR, MS and ESR), TGA, molar conduc-
tivity and magnetic moments measurements. The results indicated that the
ligand exists in the thioketo form, while on coordination to the metal ions; it
behaves as mono‐negative bidentate chelate and exists in enol form. The
optical band gap measurements of the ligand and its metal complexes are in
the range 3.83–4.48 eV indicating their semi‐conducting character. The
Correspondence
Nasser M. Hosny, Chemistry Department,
Faculty of Science, Port Said University,
2
4
3 December Street, Port Said, Egypt, POB
2522.
Email: nasserh56@yahoo.com
Mohamed H. Abdel‐Rhman, Chemistry
Department, Faculty of Science, Mansoura
University, Mansoura, Egypt.
cytotoxicity examination of H L and its Zn (II) complex showed that the ligand
3
have very strong cytotoxicity against both HCT‐116 and HEPG‐2 cell lines
while, Zn (II) complex has moderate activity.
Email: mhassan2371@yahoo.com
KEYWORDS
anticancer activity, isonicotinic hydrazide, optical properties, spectral study, thiosemicarbazides
1
| INTRODUCTION
Gram positive and negative bacteria in addition exhibited
good cytotoxicity activities.
[
5]
Isonicotinic hydrazide (isoniazid, INH) is one of the most
important hydrazides due to its wide biological activity as
antitubercular, antimicrobial, anticonvulsant, analgesic,
anti‐inflammatory, anti‐platelet and anti‐tumor activi-
On the other hand, thiosemicarbazides have high bio-
logical and antitumor activities. Coordination with metal
ions increases the activity of the thiosemicarbazides.
[6]
To obtain efficient chemotherapeutic agents, much more
efforts have been directed to modify the structure and to
the interpretation of the structure activity relationships
(SAR). For example, in the pyridylthiosemicarbazide
derivatives, the replacement of the thiocarbonyl sulfur
atom by oxygen leads to decrease the activity whereas,
selenium retains the activity. Also, the position of
the attached substituents to the pyridyl ring is very
[
1,2]
ties.
Isoniazid (INH) has very high in vivo inhibitory
activity towards M. tuberculosis H37Rv. Various INH
derivatives were synthesized and their activities against
[3]
various strains of M. tuberculosis were studied. The cop-
per complexes of INH derivatives have been synthesized
and the activities of these complexes have been evaluated
as antitumor agents. The antitumor activity of the
complexes was attributed to the inhibition of ribonucleo-
[7]
effective factor in determining the antitumor activity.
[1]
tide reductase enzyme.
Moreover, iproniazid, N′‐
Beside the biological activity of the thiosemicarbazide
derivatives, they have wide applications in catalysis,
non‐linear optics, chemical analysis and various indus-
isopropylisonicotinohydrazide, is used as antituberculosis
[4]
and antidepressant drug. Hydrazones derived from INH
and pyridinecarboxaldehydes showed activity against
[
8]
trial aspects.
Appl Organometal Chem. 2019;e4998.
wileyonlinelibrary.com/journal/aoc
© 2019 John Wiley & Sons, Ltd.
1 of 11
https://doi.org/10.1002/aoc.4998

2
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HOSNY ET AL.
The wide applications of isoniazid and thiosemi-
carbazide derivatives prompted us to synthesize and
2.3 | Deconvolution analysis of IR spectra
study the cytotoxicity of N‐ethyl‐2‐isonicotinoylhydra-
IR spectra deconvolution analyses were carried out using
[9]
[14]
zine‐1‐carbothioamide,
N‐(2‐isonicotinoyl hydrazine
Peak Fit program.
The spectra were corrected for the
[10]
carbonothioyl)benzamide, 2‐isonicotinoyl‐N‐phenylhy-
dark current noises and background. The Gaussian peaks
exhibited the best‐fitted data and the full width at half
maximum, the intensity and position were adjusted auto-
matically on the basis of the minimization of the devia-
[
11]
drazine‐1‐carboxamide
and N‐benzoyl‐2‐isonicotinoyl-
[
12]
hydrazine‐1‐carboxamide
ligands and some of their
metal complexes.
[15,16]
Thus, on continuation to the efforts of looking for new
derivatives of isonicotinic thiosemicarbazides with
promising anti‐cancer activity, this work presents the
synthesize and characterization of a new ligand, 2‐
isonicotinoyl‐N‐phenylhydrazine‐1‐carbothioamide and
its metal complexes. To shed some light on the possible
applications, the cytotoxicity and the optical band gap
were tested. The ligand has very strong cytotoxicity
against both HCT‐116 and HEPG‐2 cell lines. Further-
more, the present compounds, are semi‐conductors.
tions between experimental and simulated spectrum.
2.4 | Synthesis of the ligand
Phenylisothiocyanate (0.01 mol) was added to
isonicotinic hydrazide (0.01 mol) in 20 mL absolute etha-
nol dropwise and the reaction mixture was refluxed for
1
hr. White crystals were isolated after cooling to room
temperature; filtered off, washed with ethanol and dried
in air. Yield: 85%, m.p.: 184 °C.
2
2
| EXPERIMENTAL
.1 | Reagents
2
.5 | Synthesis of the metal complexes
To 30 ml hot ethanolic solution of the ligand (0.01 mol),
equivalent amounts(0.01 mol) of Co (II), Cu (II), Ni (II)
or Zn (II) acetates in 25 ml absolute ethanol were added
dropwise with constant stirring. The reaction mixtures
were refluxed for 2 hr, where colored precipitates were
isolated on reflux. The precipitates were filtered off,
washed successfully with ethanol, ether and dried at
room temperature. Elemental analysis data and colors
for the complexes are given in Table 1.
Phenylisothiocyanate (98.0%) and isonicotinic hydrazide
(99.0%) were purchased from Sigma‐Aldrich. Co (II), Cu
(II), Ni (II) and Zn (II) acetate salts were purchased from
Merck. Colorectal (HCT‐116) and Hepatocellular (HePG‐
) carcinoma were obtained from ATCC. The reagents,
Fetal Bovine serum purchased from GIBCO, UK. RPMI‐
640 medium, MTT and 5‐fluorouracil were obtained
from Sigma.
2
1
2.2 | Measurements
2.6 | Cytotoxicity assay
The carbon and hydrogen contents were determined by
Perkin‐Elmer model 2400 CHN analyzer. The metals con-
tent were determined volumetrically using suitable indi-
The cell lines, HePG‐2 and HCT‐116, were used to deter-
mine the inhibitory effects of the compounds on cell
growth using the MTT assay. This colorimetric assay is
based on the conversion of the yellow tetrazolium
bromide (MTT) to a purple formazan derivative by mito-
chondrial succinate dehydrogenase in viable cells. Cell
lines were cultured in RPMI‐1640 medium with 10% fetal
bovine serum. Antibiotics added were 100 units/ml Pen-
icillin and 100 μg/ml Streptomycin at 37 °C in a 5% CO2
incubator. The cell lines were seeded in a 96‐well plate at
[13]
cators.
The magnetic susceptibilities were measured
using a Sherwood Scientific magnetic balance. Molar
conductivities were determined on an YSI model 32 con-
ductivity bridge. The FT‐IR spectra were recorded, as KBr
discs, on a Thermo‐Nicolet IS10 spectrometer. Electronic
spectra measurements were carried out on Unicam UV/
Vis., spectrometer UV2 using1 cm Silica cells. The NMR
1
13
4
H and C spectra of the ligand and its Zn (II) complex
a density of 1.0x10 cells/well at 37 °C for 48 hr under 5%
were recorded on Bruker Ascend 400 MHz. ESR spectra
of the Cu (II) complex were measured at room tempera-
ture using Brucker E 500 ESR spectrometer (9.808 GHz,
CO . After incubation, different concentration of the
2
compounds under investigation were added to the cells
and incubated for 24 hr. After 24 h treatment, 20 μl of
MTT solution at 5 mg/ml added and incubated for 4 hr.
Dimethyl sulfoxide (DMSO), 100 μL, is added into each
well to dissolve the purple formazan formed. The colori-
metric assay recorded at absorbance of 570 nm using a
1
2
00 kHz field modulation) from 480 to 6480 Gauss in a
mm quartz capillary. The thermal analysis (TG) were
carried out using Shimadzu model 50 at heating rate
0 °C/min and the nitrogen flow rate 20 ml/min.
1

HOSNY ET AL.
3 of 11
TABLE 1 Elemental analyses of the ligand and its metal complexes
Elemental analyses % Found (Calcd.)
Compound (Formula)
L (C13 OS)
Cu(H L)Ac]H O (C15
Co(H L)Ac]H O (C15
L)Ac]3H O (C15
L)Ac]H O (C15
Color
M.Wt. Yield %
m.p. (°C)
C
H
M
H
3
H
12
N
4
White
272.33 95.07
411.92 70.08
407.31 66.18
443.10 68.70
413.76 73.10
184
>300
>300
>300
>300
57.44 (57.34)
43.81 (43.74)
44.10 (44.23)
40.82 (40.66)
43.42 (43.54)
4.32 (4.44)
4.01 (3.92)
4.11 (3.96)
4.37 (4.55)
4.00 (3.90)
‐
[
[
[
[
2
2
H
16
16
20
16
N
4
O
4
SCu)
SCo)
SNi)
SZn)
Dark green
dark green
dark green
yellow
15.80 (15.43)
14.55 (14.47)
13.34 (13.25)
15.88 (15.80)
2
2
H
N
4
O
4
Ni(H
2
2
H
N
4
O
6
Zn(H
2
2
H
N
4
O
4
plate reader (EXL 800, TM, USA Absorbance Microplate
Reader). The relative cell viability in percentage was cal-
culated as (A570 of treated samples/A570 of untreated
sample) × 100. Doxorubicin was used as a standard anti-
[17,18]
cancer drug for comparison.
3
| RESULTS AND DISCUSSION
The elemental analyses data of the isolated compounds
are shown in Table 1. The results indicate 1:1 (M:L) stoi-
chiometric ratio for the isolated complexes. The melting
points of the isolated complexes are >300 °C. They are
insoluble in polar or nonpolar solvents but soluble in
coordinating solvents as DMF and DMSO. The molar
conductance of all complexes lies in the range 2.0–
−
1
2
−1
5
.0 Ω cm mol indicating their non‐electrolytic nature.
3
FIGURE 1 Infrared spectra of H L
3.1 | Infrared spectra
The infrared spectra of the ligand, as KBr disc, showed
−
1
two strong bands at 3266, 3116 cm with a shoulder at
FIGURE 2 Structure of the ligand
−
1
4
1
2
3
218 cm due to ν(N H), ν(N H) and ν(N H) vibrations,
Moreover, another two sharp bands
were observed at 1673 and 1638 cm due to ν(C=O)
[9–11]
respectively.
On the other hand, the spectral data of H L metal
3
complexes (Table 2) indicate that, all the complexes
−
1
[9–11]
−1
and ν(C=N)Py vibrations,
displayed also, four bands in the range 1550–1450 cm
due to amide II, amide III, thioamide I and thioamide
, respectively. The spectrum
showed a band in 3428–3390 cm range attributed to ν
−
1
[21]
(OH)solvent
.
Moreover, the spectra of the metal
complexes displayed strong bands in the range 3272–
[10,11,19]
−1
−1
4
[10,11]
II.
Furthermore, the band at 844 cm
assigned to ν(C=S), while those at 773 and 746 cm were
was
3259 cm due to ν(N H) vibration.
Comparison
−
1
with the ligand spectral data revealed that the position
of the azomethine of the pyridyl ring remains at the same
position indicating that it did not take part in coordina-
[19]
attributed to ρ (NH) vibration.
Thus, the above obser-
vations clarify the existence of the ligand in the keto‐
form, where NH's, carbonyl and thiocarbonyl vibrations
exist (Figure 1). On comparison with the isonicotinic
hydrazide spectrum, it was found that the ν(C=O) vibra-
tion was shifted to a higher position in addition to the
appearance of ν(N H) vibrations as a shoulder may be
attributed to the involvement in intramolecular hydrogen
bond (Figure 2). The appearance of a new band at
2
tion to the metal ions. On contrary, the ν(N H) vibration
−
1
band was observed at lower wavenumber (3142 cm ) in
case of Co (II) and Zn (II) complexes which is taken as an
evidence for its involvement in coordination to the metal
ions. While, in the case of Cu (II) and Ni (II) complexes, it
was observed at 3210 which indicates that, this group is
2
[
9]
−1
free. The region 1750–1400 cm has overlapped bands,
to overcome this overlapping deconvolution analysis was
employed to resolve these bands (Table 3). The data
−
1
1
965 cm is an additional evidence for intramolecular
[20]
hydrogen bond.

4
of 11
HOSNY ET AL.
TABLE 2 Infrared spectral data of the ligand and its metal
complexes
TABLE 3 Deconvolution analyses data of complexes infrared
spectra in 1710–1400 cm range
−
1
Complexes
Co (II) complex
Ni (II) complex
(R = 0.9999)
2
2
(
R = 0.9996)
H
3
L
Cu (II) Co (II) Ni (II) Zn (II)
Peak Center FWHM % Area Center FWHM % Area
ν (OH)solvent
‐
3428
3259
3210
1612
1635
1544
1521
1456
1224
1224
1168
1066
836
3390
3270
3141
1629
1636
1562
1524
1457
1224
1224
1166
1062
838
3398
3272
3209
1614
1650
1575
1516
1460
1224
1224
1164
1064
836
3419
3265
3142
1605
1628
1560
1522
1455
1224
1224
1164
1066
838
4
1
2
3
4
5
6
7
8
9
1
1
1483
1490
1502
1524
1562
1591
1605
1629
1636
8.14
13.49
22.19
37.39
46.53
16.10
24.82
12.41
53.15
1.02
2.78
1284
1308
1346
1422
1460
1485
1516
1574
1613
1650
1697
24.51
43.50
66.61
98.77
26.01
43.90
59.91
85.93
39.02
50.23
49.13
0.78
4.49
ν(N H)
3266
3218
‐
2
ν(N H)
1
6.10
10.18
21.90
1.22
ν(C=N )
16.85
31.47
2.60
ν(C=N)Py
Amide II
1638
1550
1515
4.01
Thioamide I
13.81
0.65
10.17
27.73
4.95
Thioamide II 1448
Thioamide III 1255
15.49
Amide III
ν(N‐N)
ν(C‐O)
1228
1149
1066
844
0
1
9.13
5.38
Zn (II) complex
Cu (II) complex
(R = 0.9995)
ν(C=S)
ρ (NH)
ν(M‐O)
ν(M‐N)
2
2
(
R = 0.9999)
773, 746
‐
754
754
752
752
Peak Center FWHM % Area Center FWHM % Area
574
566
572
568
1
2
3
4
5
6
7
8
1487
1500
1522
1557
1601
1627
1702
13.88
23.10
36.73
53.06
41.14
90.27
52.64
1.59
4.77
1456
1490
1521
1570
1600
1612
1635
1709
13.94
29.43
55.88
56.71
20.81
31.21
35.38
28.73
0.91
5.44
‐
495
489
491
485
−
1
14.73
32.22
10.19
32.94
3.53
31.24
40.07
1.75
showed two new bands in 1709–1697 cm and 1591–
−
1
1
557 cm assigned to νas (OAc) and ν (OAc) vibrations,
s
respectively of coordinated acetate ion in a bidentate fash-
ion (the difference between ν and ν is ~ 150 cm ). In
addition, the spectra of the metal complexes displayed
−
1 [19]
as
s
11.16
7.25
−
1
new bands in the region 1613–1629 cm attributed to
the vibrations of the newly formed azomethine group ν
2.14
1
[9–11]
(
C=N ).
Furthermore, two new bands observed in
−
1
the regions 574–566 and 495–485 cm may be due to
ν(M‐O) and ν(M‐N) vibrations, respectively.
could be deduced that the ligand coordinates to the metal
ions in a mononegative bidentate fashion through the
deprotonated enolic carbonyl oxygen and the amine nitro-
respectively. The appearance of these signals confirms
the existence of the ligand in keto‐thion form. Multiplet
signals observed in the region 7.44–7.17 ppm due to the
phenyl group protons (Table 4). The pyridyl ring showed
[19]
Thus, it
two doublet signals at 8.78 and 7.86 ppm due to the pro-
1
[23]
gen as supported by the following: The obscure of ν(N H)
and ν(C=O)Py bands with appearance of new ν(C=N )
tons at (2 and 6) and (3 and 5) positions,
respectively.
1
1
H‐NMR spectrum of [Zn(H L)OAc]H O shows two
2
2
band (Figure 3). The shift to lower wavenumber of
ν(N H) band was taken as an evidence for the involvement
of these groups in coordination to metal ions. The position
of the band due to ν(C=S) vibration, approximately did
not suffer from any change which indicates the inertness
of sulfur atom towards coordination to the metal ions.
singlet signals at 9.59 and 9.42 ppm assigned to the pro-
2
4
2
tons of N H and N H group, respectively. On comparison
1
with the ligand spectrum, it is clear that N H signal has
disappeared which is taken as an evidence for the
enolization of the ligand with liberation of the hydrogen
[
24]
ion after chelation.
Furthermore, a new singlet signal
was observed at 1.88 ppm attributed to the methyl protons
[
10,11]
of the acetate group.
Moreover, the phenyl and pyri-
3
.2 | Nuclear magnetic resonance spectra
dyl protons appeared at more or less the same positions.
13
C‐NMR spectrum of H L, in DMSO‐d (Figure 4),
3
6
1
H‐NMR spectral data of the ligand, in DMSO‐d , exhibits
shows number of signals represent the number of chemi-
cally non‐equivalent carbon atoms of the organic moiety.
The signal due to the carbonyl carbon appears at
6
4
three singlet signals corresponding to the protons of N H,
N H and N H at 10.48, 9.86 and 9.79 ppm,
2
1
[22]

HOSNY ET AL.
5 of 11
FIGURE 3 Suggested structures of the
metal complexes
*
TABLE 4 NMR data of ligand and its Zn (II) complex
thiocarbonyl, carbonyl groups and (n → π ) of pyridyl
ring, respectively.
[
9]
1
13
H‐NMR
C‐NMR
The spectrum of Co (II) complex, in DMSO, showed
Protons
H
3
L
Zn (II) complex
Carbons
H
3
L
−1
4
4
only one band at 17065 cm attributed to A → T (P)
2
1
4
N H
10.84
9.86
9.79
8.78
7.86
7.44
7.34
7.17
‐
9.59
9.42
‐
2,6‐Py
3‐Py
150.15
121.67
120.63
139.61
125.15
128.06
139.61
139.11
164.49
181.11
transition, which suggests tetrahedral geometry around
[
25]
−1
2
the Co (II) ion.
and assigned to the ligand to metal charge transfer
LMCT). Moreover, the spectral data in Nujol mull
showed the d‐d transition and the LMCT bands at
Another band observed at 23700 cm
N H
1
N H
5‐Py
(
2
3
2
3
4
,6‐Py
,5‐Py
,6‐Ph
,5‐Ph
‐Ph
8.66
7.81
7.58
7.34
7.15
1.88
4‐Py
−
1
2,6‐Ph
3,5‐Ph
4‐Ph
1‐Ph
C=O
C=S
1
6610 and 22025 cm , respectively, confirming the tetra-
hedral structure of the solid complex and indicated that
[
9,25]
DMF did not alter the geometrical structure.
magnetic moment of Co (II) complex was found to be
.59 B.M. (Table 5). Utilizing the magnetic moment
value and d‐d transition, the 10Dq can be calculated
using the following equation, where λ = −170 cm
and μspin‐only = 3.87 B.M. The obtained 10Dq was found
The
4
(
3 OAc
CH )
−
1
−
1
[22]
to be 3579 cm and confirms the tetrahedral geometry
1
64.49 ppm,
observed at ≈ 181 ppm.
‐ and 5‐positions were observed at 121.67 ppm, while
while the thiocarbonyl carbon were
[
25]
[22]
of the Co (II) complex.
The pyridyl ring carbons at
3
ꢀ
ꢁ
4
λ
those at 2‐ and 6‐position were at 150.15 ppm. The phenyl
group carbons displayed signals in the range 125.15–
μeff ¼ μspin − only 1 −
10Dq
[22]
1
39.11 ppm.
The data confirm the existence of the
Moreover, the spectrum of Cu (II) complex recorded in
DMSO, exhibited a broad band which the deconvolution
analysis resolved it two overlapped bands at 16130 and
ligand in the keto‐form.
−
1
3.3 | Electronic spectra and magnetic
13335 cm (Figure 5A). In addition, the Nujol mull spec-
−
1
moments
trum showed a broad band at 16805 cm with a shoulder
−
1
2
2
2
2
at 14870 cm attributed to B1g → E and B → A
1g
1g
1g
25,26]
[
The electronic spectrum of the ligand, in DMSO, showed
two bands at 34965 and 33335 cm attributed to (π → π )
transition of pyridyl and phenyl rings, respectively.
transitions, respectively, of square planar geometry.
−
1
*
Several bands were observed also in the range 21000–
[
9]
−1
22600 cm due to LMCT. The magnetic moment value
−
1
Moreover, two bands at 25910 and 25000 cm with a
of the complex is 1.68 B.M., which is lower than the
normal value (1.73–2.0 B.M.) of Cu (II) complexes due
−
1
*
shoulder at 27625 cm due to n → π transitions of
1
3
FIGURE 4
3
C‐NMR spectra of H L

6
of 11
HOSNY ET AL.
TABLE 5 Electronic spectral and magnetic moment data of ligands and its complexes
−1
Compound
Band position (cm
)
Assignment
μ
eff (BM)
*
*
*
*
H
3
L
34965, 33335, 27625, 25910, 25000
(π → π )Py, (π → π )Ph, (n → π )Py, (n → π )C=S
(
,
‐
*
n → π )C=O,
*
*
*
1
*
Cu (II)
complex
33115 (34015), 31450, 28410 (28410), 27475,
25125 (25640), 23925, 22625 (20000) (21645),
(π → π )Ph, (π → π )C=S, (π → π )C=N , (n → π )Py
,
1.77
4.59
2.95
‐
*
*
1
2
2
(n → π )C=S,(n → π )C=N , LMCT, B1g → E1g
1g → A1g
,
2
2
1
6130 (16805), 13335 (14870)
B
*
*
*
1
*
Co (II)
complex
32680 (33115), 31445, 28250 (28570), 27475,
25380, 24275 (24390), 23700 (22026), 17065
(π → π )Ph, (π → π )C=S, (π → π )C=N ,(n → π )Py
,
*
*
1
4
4
(n → π )C=S,(n → π )C=N , LMCT, A
2
→ T
1
(P)
(16610)
*
*
*
1
*
Ni (II)
Complex
33115, (31450), 28735, 27780 (27030), 25640,
24630, 22935 (22940), 20835 (20920), 18655
(π → π )Ph, (π → π )C=S, (π → π )C=N ,(n → π )Py
,
*
*
1
(n → π )C=S,(n → π )C=N
LMCT, A2g(F) → T1g(P), A2g(F) → T1g(F)
,
3
3
3
3
(17730), 16610 (14795)
*
*
*
1
*
Zn (II)
complex
34015 (34015), 31450, 28090, 27475 (27030),
25910, 23255 (22625)
(π → π )Py, (π → π )C=S, (π → π )C=N ,(n → π )Py
,
*
*
1
(n → π )C=S,(n → π )C=N , LMCT
Values between brackets for Nujol mul
to the presence of some Cu‐Cu interactions between the
neighboring molecules.
The spectrum of Ni (II) complex, in DMSO, displayed
−
1
two bands at 22935 and 20835 cm attributed to the
ligand to metal charge transfer transition (LMCT). In
−
1
addition, a broad band at 16610 cm
assigned to
3
3
T → T (P) transition of tetrahedral geometry around
1
1
[
9,25]
Ni (II) ion,
respectively (Figure 5B). Moreover, the
Nujol mull spectrum displayed the LMCT transitions at
−
1
2
0920 and 19160 cm , while transitions were observed
−
1
at 17730 and 14795 cm , respectively, were assigned to
3
3
3
1
T1
→ T1(P) and T1 → E transitions, respectively.
Furthermore, the magnetic moment values of the
complex confirmed the tetrahedral geometry where it
was found to be 3.4 B.M., which is in the range of tetrahe-
dral structure (3.4–4.3 BM).
Finally, the electronic spectral data of Zn (II) complex
displayed intra‐ligand transitions, shown in Table 5. The
spectrum displayed three bands at 34015, 31450 and
−
1
*
*
2
8090 cm attributed to (π → π ) , (π → π )
and
Ph
C=S
*
(π → π )
, respectively, in addition to LMCT band at
C=N*
−
1
*
2
1740 cm . The obscure of bands due to π → π and
*
n → π transitions of carbonyl group was taken as an
additional evidence for enolization of both groups.
3.4 | Electron spin resonance
For Cu (II) complexes, in which the Cu (II) ion has
9
electronic configuration 3d , ESR spectroscopy can distin-
guish the ground states based on the principal values of
2
the g‐tensor. Thus, when B1g is the ground state the
2
FIGURE 5 Electronic spectra of [Cu(H
2
L) Ac]H
2
O(A) and
g > g > 2.0023, while in case of A ground state the
g > g > 2.0023.
⊥ ||
|
|
⊥
1g
[
27]
[
Ni(H
2
L)Ac]3H
2
O (B)

HOSNY ET AL.
7 of 11
[
29]
octahedral or square planar geometry.
The exchange
interaction between Cu (II) centers in solid state may be
expressed by the axial symmetry parameter, G, where
G = (g ‐ 2)/(g ‐ 2). If G > 4, the exchange interaction
|
|
⊥
is negligible, whereas when G < 4, a an exchange interac-
tion is indicated. The calculated G value was 2.54 suggest-
ing the presence of copper‐copper exchange interactions
[30]
in the solid state between neighboring molecules.
This
G value is close to the value reported for previously
[31]
synthesized Schiff base complex (MC)(CuCl) .2H O.
2
2
The orbital reduction factor, K, was used as a measure
of covalency, where for ionic environment K = 1, and for
covalent K < 1. The orbital reduction factor is calculated
using the following simplified expressions where K and
∥
K⊥ are the parallel and perpendicular components of
orbital reduction factor, respectively, λ is the spin‐orbit
°
−
1
[31–33]
coupling constant(−828 cm ).
2 2
FIGURE 6 ESR spectrum of [Cu(H L) Ac]H O
ꢂ
ꢃ
g∥ − 2:0023
2
K ¼
× d–d transition
× d–d transition
The ESR spectrum of Cu (II) complex (Figure 6)
∥
8
× λ∘
showed g‐tensor values g = 2.15 and g = 2.06. The
||
⊥
ðg − 2:0023Þ
2
⊥
K ¼
observed values of g is less than 2.3 suggesting a signifi-
⊥
||
2
2
∥
× λ∘
[28]
ꢂ
ꢃ
cant covalent character of metal–ligand bonds.
Also,
2
⊥
K þ 2K
The g‐values were g > g > 2.0023 which indicates that
||
⊥
2
K ¼
the Cu (II) has a d
x2−y2
ground state characteristic for the
3
3
FIGURE 7 Mass spectra of H L
SCHEME 1 Fragmentation pattern of
the ligand

8
of 11
HOSNY ET AL.
The obtained data showed that K = 0.51, implies
Both the pathways undergo further fragmentation steps
to give a base peak at m/z = 78 (100.0%) corresponding
to the pyridyl ring (Scheme 1).
[34]
total covalent character.
For pure σ‐bonding,-
K∥ ≈ K⊥ ≈ 0.77while if K <K , reveal the in‐plane π‐
∥
⊥
bonding, whereas out‐of‐plane π‐bonding showed K >K .
∥
⊥
The calculated values of K and K were 0.60 and 0.77,
respectively. These values lie in the same range
∥
⊥
3.6 | Thermal analyses
(
0.48–0.72) as that of a series of large covalent Schiff base
Thermal gravimetric analyses (TGA) were carried for the
isolated solid complexes to have some idea on their ther-
mal stabilities and to help in supporting the suggested
structures. The decomposition stages of the synthesized
metal complexes were listed in Table 6.
[31]
complexes reported by Shauib et al.
indicates that the covalency in‐plane is greater than of
the out‐of‐plane π‐bonding.
This comparison
[35,36]
Finally, the magnetic moment for the Cu (II) complex,
μ , can be calculated utilizing the ESR spectral data,
g‐values, by the following expression.
cated that it is close to the obtained value from magnetic
susceptibility measurements (1.70 B.M.) and found to
be1.81 B.M., respectively.
eff
[37]
The TG diagram of [Cu(H L)Ac]H O showed a decom-
2 2
The data indi-
position step (36–125 °C) corresponds to loss of H O
2
molecule (Calcd. 4.37; Found 4.10%). The second stage
(
165 to 250 °C) due to loss of the C H O (Calcd. 14.33;
2 3 2
Found 14.51%). The next steps were due to decomposition
of the ligand leaving a residue of CuO (Calcd. 19.33;
Found 21.23%).
qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
1
2
∥
2
⊥
μeff ¼ 2 g þ 2g
TG curve of [Co(H L)Ac]H O shows four stages of
2
2
decomposition, the first starts from 18 to 100 °C and cor-
responds to the loss of water molecule outside the coordi-
nation sphere (Calcd. 4.42; Found 4.81%). The second
step (100–500 °C) was attributed to the loss of C H O
3.5 | Mass spectra
2
3 2
The mass spectrum of the H L ligand shows the molecu-
and C H NS fragments (Calcd. 47.93; Found 47.49%).
3
7 6
lar ion peak at m/z = 272 (27.5%), which matches with
the suggested formula (Figure 7). The ligand has two pos-
sible fragmentation pathways where in the first it loses
The other two steps occur in the range 500–1000 °C,
due to complete decomposition of the ligand leading to
a residue of Co O (Calcd. 19.18; Found 20.37%).
2
3
H O giving a peak at m/z = 254 (1.12%) and in the second
2
The TGA of [Ni(H L)Ac]3H O decomposes in three
2 2
it loses (PhNH ) leading to a peak at m/z = 179 (1.16%).
steps, the first in 38–125 °C range, corresponding to loss
2
TABLE 6 Thermal gravimetry analysis data of metal complexes
complex
Temp. range °C
Wt. loss %
Fragment loss (Fragment %)
O (4.37)
[
Cu(H
2
L)Ac]H
2
O
36–165
4.10
14.51
22.02
15.02
23.19
21.23
H
2
165–250
250–300
300–360
360–1000
C
C
2
H
3
O
2
(14.33)
6
H
6
N (22.36)
CHNS (14.35)
N (22.14)
CuO (19.33)
6 5
C H
residue
[Co(H
2
L)Ac]H
2
O
18–100
00–500
00–625
25–1000
4.81
47.49
7.74
21.01
19.18
H
2
O (4.42)
+ C
H (7.12)
N (22.3)
(20.37)
1
5
6
C
2
H
3
O
2
7 6
H NS(47.93)
N
2
5 5
C H
Co
residue
2
O
3
[
Ni(H
2
L)Ac]3H
2
O
38–115
55–505
05–1000
3.98
45.51
33.21
17.31
H
2
O (4.07)
2H O + C
N + CHN
NiO (17.25)
1
5
2
2 3 2 7 6
H O + C H N (44.96)
C
5
H
5
2
OS (34.28)
residue
[
Zn(H
2
L)Ac]H
2
O
40–210
10–485
85–850
50–1000
4.09
48.14
19.06
9.71
2
H O (4.35)
2
4
8
C
C
2
H
3
O
2
+ C
7 6
H
NS(47.19)
5
H
5
N (18.87)
NH (9.97)
residue
19.00
ZnO (19.96)

HOSNY ET AL.
9 of 11
TABLE 7 Cytotoxic activity of some compounds against human
tumor cells
In vitro Cytotoxicity IC50 (μg/ml)*
Compounds
HCT116
HePG2
DOX**
5.23 ± 0.3
7.68 ± 0.8
53.00 ± 3.1
4.50 ± 0.2
8.44 ± 0.9
38.30 ± 2.4
3
H L
Zn (II) complex
*
IC50 (μg/ml): 1–10 (very strong), 11–20 (strong), 21–50 (moderate), 51–100
weak) and above 100 (non‐cytotoxic).
*DOX: Doxorubicin.
(
*
4.35; Found 4.09%) was observed at 40–110 °C. The
second decomposition step occurs from 210 to 485 °C,
due to the loss of C H O and C H NS fragments (Calcd.
2
3
2
7
6
47.19; Found 48.14%). The last steps were observed in the
ranges 485–850 and 850–1000 °C due to the decomposi-
tion of the organic chelator leaving a residue matches
with ZnO (Calcd. 19.96; Found 19.00%).
3.7 | Optical band gap
Molecular materials have recent applications in molecu-
[38–40]
lar electronics because of their semi‐conductivities.
To have some idea about the conductivity of the isolated
complexes, the optical band gaps (E ) have been deter-
g
mined from UV–visible spectra. The relation: αhν = A
m
(
hν ‐ E ) , (m = 2 for direct transition and 1/2 for indirect
g
[
41,42]
transition; A = energy constant)
graphical representation of (αhν) versus hν gives the
was applied. The
2
band gap of the ligand and its metal complexes
(
Figure 8). The band gap (E ) value for H L was 3.88
g 3
and for its complexes were Cu (II) = 3.83; Co (II) = 3.82;
Ni (II) = 4.48 and Zn (II) = 3.83 eV. It is clear that, these
compounds are semi‐conductors and are suitable to be
[
43,44]
used in solar cells applications.
3.8 | Cytotoxic effect
The in vitro cytotoxicity activities of the ligand (H L) and
3
Zn (II) complex were studied as representative examples
of isolated compounds. Their activities were compared
with the standard doxorubicin (Tables 7, 8). The mini-
3
FIGURE 8 Energy gap plots of (A) H L,(B) Zn (II)and(C) Ni (II)
complexes
of water molecules outside the coordination sphere
Calcd. 11.98; Found 12.2%). The second stage from 155
to 505 °C due to the loss of C H O in addition to
mum inhibitory concentration of H Lwas found to be
3
(
8.20 and 8.0 μg/ml against HCT‐116 and HEPG‐2 cell
lines, respectively. On the other hand, the minimum
inhibitory concentration of Zn (II) complex was found
to be 38.30 and 32.1 μg/ml against HCT‐116 and HEPG‐
2 cell lines, respectively (Figure 9). The colorimetric cyto-
2
3 2
C H N fragments (Calcd. 36.38; Found 36.51%). Finally,
7
6
the third stage starts at 505 °C leading to a residue of
NiO (Calcd. 17.25; Found 17.31%).
[
Zn(H L)Ac]H O displayed three thermal decomposi-
toxic tests exhibited that the ligand H L has very strong
2
2
3
tion steps, the first corresponds to loss of H O (Calcd.
cytotoxicity against the two investigated cell lines. While,
2

10 of 11
HOSNY ET AL.
TABLE 8 Relative viability of cells (%)
DOX
H
3
L
Zn (II) complex
HCT116
Conc. (μg/ml)
HCT116
HePG2
HCT116
HePG2
HePG2
1
5
2
1
6
3
1
00
0
7.1
13.9
18.7
31.4
47.9
60.5
73.8
6.3
11.2
14.1
28.3
45.8
57.6
71.2
8.2
16.5
25.3
31.4
54.7
71.5
89.1
8.0
15.6
23.7
36.8
56.2
73.9
93.1
38.3
51.2
64.1
75.4
92.6
100
32.1
43.2
57.4
68.6
90.7
100
5
2.5
.25
.125
.56
100
100
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