Synthesis, Spectroscopy, and Anticancer Activity of Two New Nanoscale Au(III) N4 Schiff Base Complexes

Article abstract of DOI:10.1134/S1070363219080255

Mononuclear Au(III) Schiff base complexes are synthesized by the reaction of 4-aminoantipyrine with hydrazine. The chemical structures of new Schiff bases and their Au(III) complexes are elucidated from their conductance, XRD, and spectroscopic (IR, UV-Vi

Full text of DOI:10.1134/S1070363219080255

ISSN 1070-3632, Russian Journal of General Chemistry, 2019, Vol. 89, No. 8, pp. 1702–1706. © Pleiades Publishing, Ltd., 2019.
Synthesis, Spectroscopy, and Anticancer Activity
of Two New Nanoscale Au(III) N4 Schiff Base Complexes
A. M. Naglaha,b, M. A. Al-Omara, A. Kalmouchb, A. A. Gobouric, S. H. Abdel-Hafezc,d,
S. M. El-Megharbelc,e, and M. S. Refatc,f*
a Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry,
College of Pharmacy, King Saud University, Riyadh, 11451 Saudi Arabi
b Peptide Chemistry Department, Chemical Industries Research Division, National Research Centre,
Dokki, Cairo, 12622 Egypt
c Chemistry Department, Faculty of Science, Taif University, P.O. Box 888, Al-Hawiah, Taif, 21974 Saudi Arabia
d Chemistry Department, Faculty of Science, Assiut University, Assiut, 71516 Egypt
e Chemistry Department, Faculty of Science, Zagazig University, Zagazig, 44519 Egypt
f
Department of Chemistry, Faculty of Science, Port Said, Port Said University, Egypt
*e-mail: msrefat@yahoo.com
Received May 16, 2019; revised July 27, 2019; accepted August 3, 2019
Abstract―Mononuclear Au(III) Schiff base complexes are synthesized by the reaction of 4-aminoantipyrine
with hydrazine. The chemical structures of new Schiff bases and their Au(III) complexes are elucidated from their
conductance, XRD, and spectroscopic (IR, UV-Vis, 1H, and 13C NMR) data. Au(III) Ion is coordinated with the
synthesized Schiff bases via four nitrogen atoms of the antipyrine and azomethine groups. Au(III) Complexes are
electrolytes with three uncoordinated Cl– ions, and have a square planar geometry. Their morphology is character-
ized by SEM and TEM methods. Cytotoxic effect of the complexes is tested against human breast cancer (MCF-7)
and hepatocellular carcinoma (HepG-2) cell lines.
Keywords: Schiff base, aminoantipyrine, gold, complexes, TEM, nanoparticles, spectroscopy
DOI: 10.1134/S1070363219080255
INTRODUCTION
on a UV2 Unicam UV/Vis Spectrophotometer. NMR
spectra were measured on a Varian Mercury VX-300
NMR Spectrometer using DMSO-d6 as a solvent. Mag-
netic moments were measured on a Magnetic balance,
Sherwood Scientific, Cambridge, England, at 25°C. X-ray
diffraction was measured on an X’Pert PRO PAN ana-
lytical X-ray powder diffractometer, target copper with
secondary monochromate. SEM images were produced
on a Quanta FEG 250 equipment. TEM images were
produced on a JEOL 100s microscope.
4-Aminoantipyrine derivatives are used for treatment
of oxidative damages as well as prophylactic of cancer
[1]. Metal complexes of 4-aminoantipyrine are used in
catalysis [2] and demonstrate biological activities as an-
timicrobial, anti-inflammatory, antiviral, and antitumor
agents [3, 4].
Herein synthesis of two new tetradentate Schiff bases
and their Au(III) complexes is presented. Their molar
conductance, magnetic, SEM, TEM, UV-Vis, FTIR, 1H,
and 13C NMR, and XRD characteristics are determined.
Anticancer activity of the products is assessed.
Synthesis of 4-aminoantipyrine hydrazine Schiff
base (L1). A mixture of 4-aminoantipyrine (2.03 g,
0.02 mol) with hydrazine (0.32 g, 0.01 mol) was refluxed
in methanol (20 mL) for 2 h. The precipitate was filtered
off, recrystallized from methanol, and dried over anhy-
drous CaCl2 under vacuum to accumulate the product as
a yellow-orange solid, yield 72%, mp 180°C (Scheme 1).
EXPERIMENTAL
Chemicals used were purchased from Sigma-Aldrich,
and were of high analytical grade. Elemental analysis
was carried out on a Perkin Elmer CHN 2400 analyzer.
Electrolytic character was determined on a Jenway 4010
conductivity meter. IR spectra were recorded on a Bruker
FTIR Spectrophotometer. UV-Vis spectra were recorded
Synthesis of 4-aminoantipyrine–benzaldehyde–hy-
drazine Schiff base (L2). 4-Aminoantipyrine (2 mmol)
dissolved in methanol and benzaldehyde (2 mmol) were
1702

SYNTHESIS, SPECTROSCOPY, AND ANTICANCER ACTIVITY
1703
Scheme 1. Synthesis of Schiff base chelate chelate (L1).
Me
Me
Me
Me
N
N
N
N
NH2
NH2
O
N
NH2NH2
Me
N
Me
NH2
Me
N
N
N
N
NH2
O
Me
mixed and refluxed gently for 2 h. The precipitate was
filtered off and re-crystallized from methanol as a pale
yellow powder, which was washed with a mixture al-
cohol–ether and dried over CaCl2 under vacuum. Thus
formed intermediate (2 mmol) and hydrazine (1 mmol)
were refluxed in methanol for 2 h upon constant stirring.
Upon completion of the process, the reaction mixture was
treated with crushed ice. A brownish yellow precipitate
was filtered off and re-crystallized from methanol to give
the product (L2). Yield 66%, mp 195°C. IR spectrum, ν,
cm–1: 3430 and 3330 (NH2), 1645 and 1560 (C=N), 1275
(C–N) (Scheme 2).
AuCl3 (0.02 mol) in 50 mL of CH3OH was refluxed for
2 h. The orange (L1) or brown (L2) solution formed was
evaporated to half of its original volume. A precipitate
was filtered off, washed with methanol and dried in a
vacuum desiccator over anhydrous CaCl2 to give the
corresponding product.
[Au(L1)]Cl3 (1). Yield 58%, Tdecomp > 250°C. IR
spectrum, ν, cm–1: 1635 br (C=N), 3420 and 3130 (NH2),
ca 500 (Au-N). 1H NMR spectrum, δ, ppm: 2.13 s (6H,
2CH3), 2.77 s (6H, 2NCH3), 3.42 s (4H, 2NH2), 7.28 m
(4H, phenyl), 7.51 m (6H, phenyl). 13C NMR spectrum, δ,
ppm: 9.8, 40.1, 120.0, 121.8, 125.1, 128.8, 135.5, 161.4.
Found, %: C 37.21; H 3.60; N 15.53; Au 27.49. Calcu-
lated, %: C 37.44; H 3.71; N 15.88; Au 27.91.
Synthesis ofAu(III) Schiff bases (L1, L2) complexes
1, 2. The mixture of an appropriate ligand (0.02 mol) with
Scheme 2. . Synthesis of Schiff base chelate (L2).
Me
Me
H
C
O
Me
Me
N
N
N
N
N C
NH2
H
O
O
Me
Me
Me
N
Me
N
N
N
N
N
C
H
O
C
H
N
Me
NH2NH2
Me
N
N
N
N
N
C
H
C
H
N
O
N
Me
Me
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 8 2019

1704
NAGLAH et al.
Me
Me
Me
N
Me
N
N
N
N
C
H
NH2
N
N
Au
·Cl3
·Cl3
Au
N
N
N
C
H
NH2
Me
N
N
Me
N
N
Me
Me
1
2
Fig. 1. Speculated structures of complexes 1 and 2.
[Au(L2)]Cl3 (2). Yield 61%, Tdecomp > 250°C. IR
spectrum, ν, cm–1: 1623 and 1511 (C=N), ca 495 (Au-N).
1H NMR spectrum, δ, ppm: 2.11 s [6H, 2CH3(C3)], 3.18–
3.42 s (6H, 2NCH3), 7.39–8.73 m (20H, phenyl), 9.62
s (2H, N=CH). 13C NMR spectrum, δ, ppm: 9.7, 38.5,
116.3, 124.6, 128.6, 130.1, 134.5, 137.5, 152.1, 154.4,
159.6, 161.4. Found, %: C 48.94; H 3.81; N 12.64; Au
22.12. Calculated, %: C 49.02; H 3.89; N 12.70;Au 22.33.
RESULTS AND DISCUSSION
The synthesized compounds had low solubility in
cationic and anionic solvents, and high solubility in DMF
and DMSO. Molar conductance of the complexes 1 and
2 was measured to be 67 and 70 μs/cm, respectively.
Electrolytic measurements of the complexes indicated
that Cl– anions were uncoordinated and existed outside
the coordination sphere [7]. The test of the complexes
on Cl– carried out with AgNO3 was positive, which also
confirmed the anions existence in the outer coordination
sphere. According to the elemental analysis, the molar
ratio Au(III) : ligand was 1 : 1. The coordination mode
is presented in Fig. 1.
Anti-cancer activity. Human breast cancer (MCF-7)
and hepatocellular cancer (HepG-2) cells were gained
from the American culture collection. The cells were
grown in RPMI-1640 medium and supplemented with
10% and 50 μg/mL fetal calf serum and gentamycin.
The 50% inhibitory concentration (IC50) was estimated
from graphic plots [5,6]. The standard drugs cisplatin and
doxorubicin were used in the tests.
Electronic and magnetic measurements. Au(III)
Schiff bases complexes (1 and 2) had diamagnetic na-
ture, and low spin d8, characteristic for square planar
(a)
(b)
Fig. 2. SEM images of (a) [Au(L1)]∙Cl3 and (b) [Au(L2)]∙Cl3 complexes.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 8 2019

SYNTHESIS, SPECTROSCOPY, AND ANTICANCER ACTIVITY
1705
The concentration dependent inhibitory activity of the synthesized complexes against MCF-7 and HepG-2 cell lines
Inhibitory, %
Sample
concentration,
HepG-2 cell
Doxorubicin
MCF-7 cell
Doxorubicin
μg/mL
Cisplatin
96.92
95.69
93.25
87.61
77.02
68.13
59.38
52.11
39.25
31.83
3.67
Au-L1
68.22
50.75
27.69
13.08
5.72
0.53
0
Au-L2
74.11
57.22
39.06
24.87
13.16
5.94
1.29
0
Cisplatin
96.28
95.02
92.17
85.32
76.21
65.38
53.29
47.15
38.26
29.12
5.71
Au-L1
88.11
75.35
61.59
30.48
11.83
2.77
0
Au-L2
500
98.28
97.30
95.78
93.87
86.95
81.87
79.19
74.41
70.50
61.61
0.36
98.49
97.64
96.79
94.93
93.07
84.54
80.11
75.02
68.31
59.83
0.35
65.48
42.16
20.59
6.14
0.52
0
250
125
62.5
31.25
15.60
7.80
3.90
2.0
0
0
0
0
0
0
0
0
1.0
0
0
0
0
IC50
23.5
24.7
6.0
18.4
geometry [8]. The electronic spectra of free Schiff base
ligands exhibited bands at 290 and 350 nm attributed to
π–π* and n–π* transitions in benzene rings, NH2 and the
azomethine groups. Electronic spectra of the complexes
demonstrated three absorption bands at 380, 350 and
285 nm due to A1g→1Α2g, A1g→1Β1g, A1g→1Εg and
charge transfer transitions, respectively. The bands were
in agreement with low-spin square planar configuration
[9].
2θ = 38, 44, 65, and 78 were assigned to the planes (111),
(200), (220), and (311) of face centered cubic crystal lat-
tice structure of AuNPs [13].
SEM images (Fig. 2) of the complexes [Au(L1)]·Cl3
(1) and [Au(L2)]·Cl3 (2) demonstrated that complex (1)
had a semispherical with aggregation character, and com-
plex (2) exhibited irregularly shaped particles.
1
1
1
TEM photograph of [Au(L1)]·Cl3 (1) indicated spheri-
cal NPs of Au(III) and the diameter was in the range of
10 nm, which was identical with the XRD values.
Crystalline structure and morphological stud-
ies. Crystallinity of the synthesized complexes was
calculated from the major diffraction patterns using the
Deby-Scherrer equation [10]. The calculated grain sizes
were determined to be 10 nm for [Au(L1)]·Cl3 complex
(1). The X-ray diffraction of [Au(L2)] ·Cl3 complex re-
ferred to its amorphous feature. The crystallite sizes (D)
were calculated using the Scherrer formula [11] from the
full-width half-maximum (FWHM) (β). The strain (ε =
1.60×10–4) was calculated using the equation
Anticancer assessments. The cytotoxic assessment
of Au(III) complexes was carried out on human breast
(MCF-7) and hepatocellular cancer (HepG-2) cell lines in
presence of the standard drugs cisplatin and doxorubicin
(see the table).According to the accumulated dataAu(III)-
L1 complex (1) was more efficient against HepG-2 and
MCF-7 cell lines than Au(III)-L2 complex (2).
CONFLICT OF INTEREST
β = λ/Dcos θ – εtan θ.
No conflict of interest was declared by the authors.
Since the dislocation density and strain are the mani-
festation of dislocation network in the complexes, the
decrease in the strain and dislocation density indicate
the formation of high quality complexes. The disloca-
tion density (δ = 0.007×1012 lin/m2) was calculated by
equation δ = 1/D2 [12]. The diffraction patterns present at
ACKNOWLEDGMENTS
The authors are grateful to the Deanship of Scientific
Research, king Saud University for funding through Vice
Deanship of Scientific Research Chairs.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 8 2019

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7. Refat, M.S., J. Mol. Struct., 2007, vol. 842, p. 24. doi
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