Three mixed ligand mononuclear Zn(II) complexes of 4-acyl pyrazolones: Synthesis, characterization, crystal study and anti-malarial activity

Article abstract of DOI:10.1016/j.poly.2020.114528

Three novel mixed ligand Zn(II) complexes {complex 1 = [Zn(L1)₂(bpy)], complex 2 = [Zn(L2)₂(bpy)], complex 3 = [Zn(L2)₂(phen)], where bpy = 2,2′-bipyridine and phen = 1,10-phenanthroline} of 4-(4-chlorobenzoyl)-2-(3-chlorophenyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one (HL1) and 4-(4-chlorobenzoyl)-5-methyl-2-(p-tolyl)-2,4-dihydro-3H-pyrazol-3-one (HL2) were synthesized and characterized by ¹H and ¹³C NMR, FTIR, TG-DTA, UV–Vis, elemental analysis, molar conductance and single crystal X-ray structure determination. Based on analytical and spectroscopic techniques, all the three Zn(II) complexes were found to have a distorted octahedral geometry. The ligands and the complexes were screened for antimalarial activity against plasmodium falciparum. The zinc(II) complexes showed greater antimalarial activity than their parent ligands.

Full text of DOI:10.1016/j.poly.2020.114528

Polyhedron 183 (2020) 114528
Contents lists available at ScienceDirect
Polyhedron
journal homepage: www.elsevier.com/locate/poly
Three mixed ligand mononuclear Zn(II) complexes of 4-acyl
pyrazolones: Synthesis, characterization, crystal study and anti-malarial
activity
b
Irfan Shaikh a, R.N. Jadeja a, , Rajesh Patel
⇑
a Department of Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara 390 002, India
b Department of Bioscience, Veer Narmad South Gujarat University, Surat 395007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Three novel mixed ligand Zn(II) complexes {complex 1 = [Zn(L1)2(bpy)], complex 2 = [Zn(L2)2(bpy)],
complex
3 = [Zn(L2)2(phen)], where bpy = = 1,10-phenanthroline}
2,20-bipyridine and phen
Received 20 February 2020
Accepted 18 March 2020
Available online 23 March 2020
of 4-(4-chlorobenzoyl)-2-(3-chlorophenyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one (HL1) and 4-(4-
chlorobenzoyl)-5-methyl-2-(p-tolyl)-2,4-dihydro-3H-pyrazol-3-one (HL2) were synthesized and
characterized by 1H and 13C NMR, FTIR, TG-DTA, UV–Vis, elemental analysis, molar conductance and sin-
gle crystal X-ray structure determination. Based on analytical and spectroscopic techniques, all the three
Zn(II) complexes were found to have a distorted octahedral geometry. The ligands and the complexes
were screened for antimalarial activity against plasmodium falciparum. The zinc(II) complexes showed
greater antimalarial activity than their parent ligands.
Keywords:
Acyl pyrazolone
Antimalarial
Mixed ligand complex
Single crystal
Zinc(II) complexes
Ó 2020 Elsevier Ltd. All rights reserved.
1. Introduction
to explore better treatment for Plasmodium falciparum. Pyrazolone
derivatives complexed with the zinc(II) metal have been investi-
The two nitrogen atoms of an amidic ketone containing pyra-
zolone react with acid chlorides to give substitution on the 4th
position of the pyrazolone, giving the commonly named 4-acyl
pyrazolone. 4-Acyl pyrazolones have proven to be very useful in
coordination chemistry as an –OO bidentate ligand [1–8]. There
are reports in the literature on metal complexes of 4-acyl pyra-
zolones for d-block metals which display good antimalarial, anti-
cancer, antibacterial, antifungal and catalytic activities.[2,6,8–11]
The lack of zinc can be a problem in biological systems and is
responsible for various disease states [6,12]. Zinc has been used
to reduce gastro toxicity, in which any extra drug binds to zinc
and is released from the human body [13,14]. Malaria is an infec-
tious disease caused by a parasite called Plasmodium and it is a
serious problem for human health, especially in the so-called
‘‘Third World” [15]. The diseases are mainly caused by the main
five parasite species: Plasmodium falciparum, Plasmodium vivax,
Plasmodium malariae, Plasmodium ovale and Plasmodium knowlesi
[16]. Amongst them, Plasmodium falciparum is the most deadly.
Malaria is an entirely preventable and treatable mosquito-borne
illness. However, drug resistance to currently available drugs
increases multiple fold in the real world [17]. This prompted us
gated [18]. The current study explores 4-acyl pyrazolones and their
zinc(II) complexes, which show promising antimalarial activity [4].
The studies performed using in vitro assays on P. falciparum strains
with various concentrations of the metal complexes and ligands
showed that the complexes were able to inhibit the parasite
growth in a more effective manner than the parent compounds.
With the same dose, the metal complexes showed greater activity
than the ligands against malaria [4,19–22].
2. Experimental
2.1. Materials and methods
The pyrazolones were obtained from Sidhdhanath Industries,
Sachin (Surat), India as free gift samples. All necessary reagents
and solvents were obtained from commercial sources. Zinc acetate,
2,20-bipyridine and 1,10-phenanthroline were purchased from
Spectrochem PVT. LTD., Mumbai. P-chloro benzoyl chloride was
purchased from SRL Chemical, Mumbai.
Infrared (IR) spectra were recorded on a Bruker Alpha Fourier
transform IR (FT-IR) spectrometer as KBr pellets. 1H NMR spectra
of the ligands were recorded with an AV 400 MHz Bruker FT-
NMR instrument. Single crystal data were collected on a Bruker
⇑
Corresponding author.
E-mail address: rjadeja-chem@msubaroda.ac.in (R.N. Jadeja).
https://doi.org/10.1016/j.poly.2020.114528
0277-5387/Ó 2020 Elsevier Ltd. All rights reserved.

2
I. Shaikh et al. / Polyhedron 183 (2020) 114528
CCD area-detector diffractometer. The electronic spectra were
recorded on a Perkin Elmer Lambda 35 UV–Vis spectrometer.
Simultaneous TG/DTA were carried out on an SII EXSTAR6000
TG/DTA 6300 instrument. The experiments were performed in N2
at a heating rate of 10 °C minꢀ1 in the temperature range 30–
550 °C using an aluminium pan. The purity of the ligands and their
complexes was evaluated by thin-layer chromatography. Gravi-
metric and volumetric analyses were performed for the determina-
tion of zinc after decomposition of the complexes in nitric acid.
A local strain of P. falciparum from Gujarat State, India was cul-
tured continuously according to the candle-jar method of Trager
and Jensen (1976), in vitro in human red blood cells, with 5%
haematocrit in RPMI (Roswell Park Memorial Institute) 1640 med-
ium (Himedia Laboratories, India) supplemented with 25 mM
HEPES (Himedia Laboratories, India), 0.23% sodium bicarbonate
(Himedia Laboratories, India) and 10% heat-inactivated human
O+serum.
Scheme 1. Synthesis route for ligands HL1 and HL2.
p-chloro benzoyl), 138.13 (CAN, pyz-phenyl), 147.54 (C@N, pyra-
zolone), 160.62 (C@O, CAO, pyz), 191.38 (C@O, 4-chloro benzoyl).
The synthesis of the ligands is summarized in Scheme 1.
2.2. Synthesis of the ligands
2.2.1. Synthesis of 4-(4-chlorobenzoyl)-2-(3-chlorophenyl)-5-methyl-
2,4-dihydro-3H-pyrazol-3-one [HL1]
2.3. Synthesis of the Zn(II) complexes
The ligand synthesis was reported previously by us [3]. 2-(3-
Chlorophenyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one (31.20 g,
0.1500 mol) was dissolved in 1,4-dioxane (120 ml) in a three
necked 500 ml round bottom flask, with an addition funnel and
reflux condenser attached. The reaction mixture was heated at
80 °C for 15 min. Calcium hydroxide (22.23 g, 0.3000 mol) was
added, and after 10 min p-chloro benzoyl chloride (19.23 ml,
0.1500 mol) was added dropwise to the reaction mixture. The reac-
tion mixture converted into a thick paste during this addition. After
the complete addition, the reaction mixture was placed for reflux
for 3 h. The reaction mixture was poured into a 300 ml solution
of ice-cold hydrochloric acid (2 mol Lꢀ1) under stirring. The colored
precipitates that formed were filtered, washed with hot water and
dried in a bulb oven. After drying, a pale yellow solid was obtained
and recrystallized in rectified spirit [4]. Yield: 78%. Anal. Calcd for
2.3.1. Synthesis of complex 1
In the synthesis procedure for complex 1, zinc acetate (1 mmol)
was dissolved in a small amount of methanol and mixed with a
methanolic solution of the ligand HL1 (2 mmol). After half an hour,
a methanolic solution of 2,20-bipyridine (1 mmol) was added drop-
wise. Subsequently, a small amount of sodium acetate was added
and the reaction mixture placed on a stirrer. The reaction mixture
was heated and reflux for 4 h [4]. The obtained light-yellow crys-
talline precipitates were filtered and washed with hot MeOH and
hot water. A small amount of product was recrystallized from a
DMF and ethanol mixture at room temperature. Yield: 64%, Anal.
Calcd for C44H34Cl4N6O4Zn (%): C, 57.57; H, 3.73; N, 9.16; Found
(%): C, 56.58; H, 3.74; N, 9.22. Metal estimation, gravimetrically
and volumetrically, Zn = 7.12%. M.w.: 917.97. M.P.: >210 °C. Km
(S cm2 molꢀ1): 9.9. FTIR (KBr plates)
t
(cmꢀ1): 1621 (m) (C@O,
C
17H12Cl2N2O2 (%): C, 58.81; H, 3.48; N, 8.07; Found (%): C, 58.57;
H, 3.71; N, 8.15. M.w.: 347.20. M.P.: 105 °C. Km (S cm2 molꢀ1):
8.8. FTIR (KBr plates)
(cmꢀ1): 1625 (s) (C@O, amide of pyra-
4-chloro benzoyl), 955 (s) (NAN of pyrazolone), 14,701 (m)
(ACACA aromatic), 493 (s) (OAM), 411 (s) (N-M). 1H NMR (CDCl3)
d ppm: 2.2 (s, 3H, pyrazolone CACH3), 7.0–7.34 (m, 2H, 3-chloro-
phenyl), 7.64–7.67 (m, 2H, 4-chloro benzoyl), 7.77–7.79 (m, 1H,
4-chloro benzoyl), 8.01–8.08 (m, 1H, 3-chlorophenyl), 9.07–9.08
(d, 1H, J = 4 Hz, bpy), 8.22–8.24 (d, 1H, J = 8 Hz, bpy), 8.10–8.12
(t, 1H, J = 8 Hz, bpy). 13C NMR (CDCl3) d ppm: 16.56 (ACH3-pyra-
zolone), 104.79 (C-pyz), 117.59, 119.51, 121.03, 124.06, 126.40,
128.27, 129.23, 129.53, 133.90, 136.21, 139.36, 139.91, 140.20,
148.99, 149.22 (CAN, pyz-phenyl), 149.63 (C@N, pyz), 166.93
(CAOA, pyz), 190.04 (C@O, p-chloro benzoyl).
t
zolone), 1590 (m) (C@O, 4-chloro benzoyl), 966 (s) (NAN of pyra-
zolone), 1486 (m) (aromatic ACAC). 1H NMR (CDCl3) d ppm: 2.14
(s, 3H, pyrazolone CACH3), 7.28–7.30 (m, 1H, m-chloro Ph), 7.39–
7.43 (m, 1H, m-chlorophenyl), 7.51–7.63 (m, 4H, p-chloro benzoyl),
7.83–7.85 (m, 1H, m-chloro Ph), 7.963–7.968 (m, 1H, m-chloro Ph).
13C NMR (CDCl3) d ppm: 16.01 (ACH3-pyrazolone), 103.69 (C-pyra-
zolone ring), 118.35 (C-phenyl), 120.59 (C-phenyl), 126.66, 128.88,
129.47, 130.20, 134.93, 135.47 (CACl, m-chloro phenyl), 138.19
(CACl, p-chloro benzoyl), 138.46 (CAN, pyz with phenyl), 147.98
(C@N, pyrazolone ring), 162.02 (CAO, pyz), 190.13 (C@O, 4-chloro
benzoyl).
2.3.2. Synthesis of complex 2
Complex 2 was synthesized by dissolving zinc acetate (1 mmol)
in methanol followed by the addition of a methanolic solution of
the ligand HL2 (2 mmol). After half an hour, 2,20-bipyridine
(1 mmol) was added to the reaction mixture, followed by refluxing
for 4 h. After this, the reaction mixture gave a light yellowish crys-
talline product. The product was filtered with a Whatman filter
paper, washed with 10 ml methanol and then with hot water. A
small amount of the product was recrystallized from DMF at room
temperature [4]. Yield: 85.2%. Anal. Calcd for C46H36Cl2N6O4Zn (%):
C, 63.28; H, 4.16; N, 9.63; Found (%): C, 63.21, H, 4.23, N, 9.68.
Metal estimation, gravimetrically and volumetrically, Zn = 7.49%.
M.w.: 873.11. M.P.: >210 °C. Km (S cm2 molꢀ1): 10.5. FTIR (KBr,
cmꢀ1): 1629 (C@O, 4-chloro benzoyl group), 1597 (C@N, cyclic),
943 (s) (NAN), 1435 (s) (ArACACAC). 1H NMR (CDCl3, 400 MHz)
d ppm: 1.6 (s, 3H, CH3ACAr), 2.2 (s, 3H, PyzACCACCH3), 6.99–
2.2.2. Synthesis of 4-(4-chlorobenzoyl)-5-methyl-2-(p-tolyl)-2,4-
dihydro-3H-pyrazol-3-one (HL2)
This ligand was reported in our recent publication [4]. Yield:
76%, Anal. Calcd for C18H15ClN2O2 (%): C, 66.16; H, 4.63; N, 8.57;
Found (%): C, 66.11; H, 4.71, N, 8.77. M.w.: 326.78. M.P.: 108 °C.
Km (S cm2 molꢀ1): 10.1. IR (KBr, cmꢀ1): 1551 (C@N, cyclic), 1590
(C@O, 4-chloro benzoyl group) 1625 (m) (C@O, Pyrazolone ring);
1H NMR (CDCl3, 400 MHz) d ppm: 2.1 (s, 3H, Pyrazolone C-CH3),
2.38–2.39 (m, 1H, ACH-cyclic), 2.4 (s, 3H, CH3-Ar), 7.28–7.30 (d,
2H, aromatic, J = 8 Hz), 7.50–7.52 (m, 2H, aromatic), 7.60–7.62
(d, 2H, p-chloro benzoyl-, J = 8 Hz), 7.72–7.74 (d, 2H, p-chloro ben-
zoyl-, J = 8 Hz); 13C NMR (CDCl3, 400 MHz) d ppm: 15.90 (ACH3,
pyrazolone), 21.10 (ACH3 tolyl), 103.37 (C-pyrazolone), 120.94,
128.79, 129.32, 129.72, 131.48, 134.59, 136.34, 136.87 (C-Cl,

I. Shaikh et al. / Polyhedron 183 (2020) 114528
3
7.02 (d, 2H, aromatic-H, J = 8 Hz), 7.57–8.2 (m, 6H, ar-H), 9.00–9.02
(d, 1H, J = 8 Hz, bpy).
mined by JSB staining (Sing, 1956) was used to assess the
percent parasitaemia (rings) and uniformly maintained with 50%
RBCs (O+) [29]. A stock solution of 5 mg/ml of each of the test sam-
ples was prepared in DMSO and subsequent dilutions were pre-
pared with the culture medium. The diluted samples of 20 ml
volume were added to the test wells containing the parasitized cell
preparation to obtain final concentrations (at five-fold dilutions),
ranging from 0.4 to 100 mg/ml. The culture plates were incubated
at 37 °C in a candle jar. After 36–40 h incubation, thin blood smears
from each well were prepared and stained with JSB stain. The
slides were microscopically observed to record the maturation of
the ring-stage parasites into trophozoites and schizonts in the
presence of different concentrations of the test agents. The test
concentration which inhibited the complete maturation into sch-
izonts was recorded as the minimum inhibitory concentration
(MIC). Chloroquine was used as the reference drug (Fig. 2).
2.3.3. Synthesis of complex 3
The procedure for the preparation of complex 3 is similar to that
for complex 2, except that 2,20-bipyridine was replaced with 1,10-
phenanthroline. Complex 3 was recrystallized from a DMF and
ethanol mixture at room temperature [4]. Yield: 86.7%. Anal. Calcd
for C48H40Cl2N6O4Zn (%): C, 63.98; H, 4.47; N, 9.33; Found (%): C,
64.01, H, 4.55; N, 9.65. M.w.: 901.17. M.P.: >200 °C. Km (S cm2-
molꢀ1): 9.7. Metal estimation, gravimetrically and volumetrically,
Zn = 7.26%. FTIR (KBr, cmꢀ1): 1562 (C@N, cyclic), 1622 (C@O, 4-
chloro benzoyl group), 943 (s) (NAN), 1436 (s) (ArACACAC). 1H
NMR (CDCl3, 400 MHz) d ppm: 1.6 (s, 3H, CH3-tolyl), 2.2 (s, 3H,
Pyz-C-CH3), 6.99–7.02 (d, 2H, aromatic-H, J = 8 Hz), 7.24–7.31
(m, 2H, ar-H), 7.60–7.62 (d, 2H, aromatic-H, J = 8 Hz), 7.72–7.74
(d, 2H, 4-chloro benzoyl-, J = 8 Hz), 9.30–9.31 (m, 1H, aromatic),
8.49–8.51 (m, 1H, phen). The synthesis route for complexes 1–3
is summarized in Scheme 2.
3. Results and discussion
3.1. Crystal structures of the ligands and complexes
2.4. X-ray structure determination
The crystallographic data of the two ligands (HL1 and HL2) and
the three complexes 1–3 are given in Table 1. The structures with
atom numbering schemes are represented in Fig. 1. Selected bond
length and bond angles of the ligands (HL1 and HL2) and com-
plexes 1–3 are given in Tables 2 and 3.
The single crystal X-ray crystallographic data for the ligands
(HL1 and HL2) and the complexes (1, 2 and 3) are summarized in
Table 1. The single crystal crystallographic data were collected on
a
Bruker CCD area-detector diffractometer with graphite
monochromated MoK radiation (k = 0.71073 Å). The Mercury
a
software package was used for the ORTEP views of the ligands
and the complexes and these are given in Fig. 1. All structures were
solved by direct methods, using SHELXS97 [23]. All non-hydrogen
atoms of the molecules were located in the expected positions in
the obtained structures. For the refinement, full-matrix least-
squares refinement was carried out using SHELXL97 [24]. All
hydrogen atoms were included as idealized atoms riding on their
respective carbon atoms with CAH bond lengths appropriate to
the carbon atom hybridization [25,26].
3.1.1. Crystal structure of the ligand HL1
In the ligand, the C8AO1 (1.243 Å) and C11AO2 bonds (1.222 Å)
have lengths that are near to typical CAO double bond lengths
[11,30]. The bond length of C7AC8 is 1.427 Å, near to a typical
CAC single bond length, and the bond length of C8AC9 is 1.390 Å
near to a typical CAC double bond length. Furthermore the
C7AN1 bond (1.310 Å) is longer than a CAN double bond and since
an H atom is attached to the N atom, this reveals that the ligand is
present in the NH amino diketone form [11,30]. Selected bond
lengths and bond angles for the ligand are given in Table 2.
There is intermolecular hydrogen bonding between the ANH
group of one molecule and the carbonyl (C@O) group of the pyra-
zolone ring of a second molecule of the ligand. The parameters
(DAHꢁ ꢁ ꢁA) are as follows: N2AH2 (0.860 Å), H2ꢁ ꢁ ꢁO1 (1.790 Å),
N2AO1 (2.631 Å) and N2AH2AO1 (165.51°). The stability of the
NH amino diketone form may be due to the presence of the inter-
molecular hydrogen bonding. Furthermore, in the crystal packing
system, the molecule arrangement design appears as zigzag lines
from the ‘b’ axis (Fig. 3).
2.5. P. falciparum in vitro growth inhibition assay
The in vitro antimalarial assay was performed as described by
Rieckmann et al., (1978) with minor modifications [27]. The P. fal-
ciparum cultures were synchronized by treatment with 5% D-sor-
bitol (Himedia Laboratories, India) to obtained ring stage
parasitized cells (Lambros and Vanderberg, 1979) [28]. For the
assay, an initial ring stage parasitaemia of 0.8 to 1.5% at 3% haema-
tocrit in a total volume of 200 ml of medium RPMI-1640 deter-
3.1.2. Crystal structure of the ligand HL2
In the ligand HL2, the crystal data show two molecules of HL2 in
the same plane. Selected bond length and bond angles are pre-
sented in Table 2. There is intramolecular hydrogen bonding
between the AOH group of one molecule and the carbonyl (C@O)
group of the same ligand. The parameters (DAHꢁ ꢁ ꢁA) are as fol-
lows: O1AH1 (0.820 Å), H1ꢁ ꢁ ꢁO2 (1.811 Å), O1AO2 (2.501 Å) and
O1AH1. . .O2 (140.84°) (Fig. 4).
3.1.3. Crystal structure of [Zn(L1)2(bpy)] (complex 1)
The single crystal X-ray analysis for complex 1 gives the general
structural formula ML2L0 (where L = L1 and L0 = 2,20-bipyridine).
The zinc(II) ion is hexacoordinated by four oxygen atoms (O1,
O2, O3 and O4) of two acyl pyrazolone ligands (L1) and two nitro-
gen atoms (N5 and N6) of the 2,20-bipyridine ligand. The structure
of complex 1 is illustrated in Fig. 1. Selected bond lengths and bond
angles are listed in Table 3. The coordination geometry is styled as
octahedral. Two oxygen atoms [O(2)and O(3)] from two HL1
Scheme 2. Synthesis route for mixed ligand complexes 1–3.

4
I. Shaikh et al. / Polyhedron 183 (2020) 114528
Table 1
Crystal data and structure refinement for HL1, HL2, and complexes 1–3.
Identification code
HL1
HL2
Complex 1
Complex 2
Complex 3
Empirical formula
Formula weight
Temperature/K
Crystal system
Space group
a/Å
C
17H11Cl2N2O2
C18H15Cl1N2O2
326.77
293
Triclinic
P-1
7.9800(6)
11.6196(6)
18.0179(9)
84.835(4)
78.544(5)
72.202(6)
1558.28(17)
2
C44H30Cl4N6O4Zn
913.91
293
Triclinic
P-1
9.0491(4)
12.6789(6)
18.7081(6)
82.155(3)
79.592(3)
81.754(4)
2075.78(15)
2
C49Cl2N7O5Zn
902.83
293
Monoclinic
P21/n
12.5956(6)
26.5655(10)
14.6544(7)
90
110.822(5)
90
4583.2(4)
4
1.308
0.705
C51H42Cl2N7O5Zn
969.18
293
Triclinic
P-1
13.4212(8)
13.7150(8)
14.0396(7)
88.005(4)
80.209(4)
66.901(5)
2341.0(2)
2
346.18
293
Monoclinic
P21/c
15.1886(17)
9.6726(7)
11.8403(12)
90
112.599(13)
90
b/Å
c/Å
a
/°
b/°
/°
c
Volume/Å3
Z
1605.9(3)
4
1.432
q
l
calcg/cm3
1.393
0.256
1.462
0.900
1.375
0.694
/mmꢀ1
0.414
F(0 0 0)
708.0
680.0
932.0
1788.0
1002.0
Crystal size/mm3
Radiation(/Å)
0.3 ꢂ 0.2 ꢂ 0.2
0.3 ꢂ 0.2 ꢂ 0.2
0.3 ꢂ 0.2 ꢂ 0.2
0.3 ꢂ 0.2 ꢂ 0.2
0.3 ꢂ 0.2 ꢂ 0.2
MoK
a
(k = 0.71073)
MoK
a
(k = 0.71073)
MoK
a
(k = 0.71073)
MoK
a
(k = 0.71073)
MoKa (k = 0.71073)
The 2
H
range for
6.882 to 57.73
5.996 to 58.014
6.506 to 58.424
6.144 to 58.722
6.19 to 58.224
data collection/°
Index ranges
ꢀ17 ꢃ h ꢃ 20,
ꢀ10 ꢃ h ꢃ 10,
ꢀ12 ꢃ h ꢃ 11,
ꢀ17 ꢃ k ꢃ 17,
ꢀ25 ꢃ l ꢃ 25
45,888
10,074 [Rint = 0.0450,
Rsigma = 0.0441]
7546/0/420
ꢀ16 ꢃ h ꢃ 16,
ꢀ36 ꢃ k ꢃ 36,
ꢀ19 ꢃ l ꢃ 18
51,601
11,254 [Rint = 0.0873,
Rsigma = 0.0834]
10074/0/534
ꢀ18 ꢃ h ꢃ 17,
ꢀ18 ꢃ k ꢃ 18,
ꢀ19 ꢃ l ꢃ 19
51,456
11,368 [Rint = 0.1462,
Rsigma = 0.1772]
11254/0/577
ꢀ5 ꢃ k ꢃ 13, ꢀ16 ꢃ l ꢃ 8 ꢀ15 ꢃ k ꢃ 15,
ꢀ24 ꢃ l ꢃ 24
Reflections collected
Independent
reflections
5321
3299 [Rint = 0.0211,
Rsigma = 0.0350]
33,561
7546 [Rint = 0.0433,
Rsigma = 0.0477]
Data/
restraints/parameters 3299/0/209
11368/0/601
Goodness-of-fit on F2 1.045
1.319
1.030
1.039
1.007
Final R indexes
[I>=2 (I)]
Final R indexes [all
R1 = 0.0546,
R1 = 0.0729, wR2 = 0.2059
R1 = 0.0469, wR2 = 0.0932 R1 = 0.0814, wR2 = 0.2186
R1 = 0.0718, wR2 = 0.1206
r
wR2 = 0.1319
R1 = 0.0880,
wR2 = 0.1470
0.42/ꢀ0.48
R1 = 0.1227, wR2 = 0.2383 R1 = 0.0867, wR2 = 0.1098 R1 = 0.1519, wR2 = 0.2646 R1 = 0.2135, wR2 = 0.1701
1.29/ꢀ0.76 0.47/ꢀ0.55 0.58/ꢀ0.48 0.39/ꢀ0.34
data]
Largest diff.
peak/hole/e Åꢀ3
O(4) angles are 167.91(7), 174.87(7) and 175.91(6)°, respectively,
which are deviated from the theoretical value of 180° for the
proper geometric structure. The O(2)AZn(1)AO(1), O(3)AZn(1)A
O(1), O(1)AZn(1)AN(5), O(1)AZn(1)AN(6), O(2)AZn(1)AO(4), O
(3)AZn(1)AO(4), O(4)AZn(1)AN(5) and O(4)AZn(1)AN(6) angles
are 86.65(6), 90.15(7), 89.10(7), 93.57(7), 91.67(6), 86.13(7),
100.59(8) and 90.25(7)° respectively, which are deviated from
the 90° angle between the axial line and equatorial plane. There-
fore, the local coordination geometry around the zinc ion in the
complex is distorted octahedral (Fig. 5) [4,6,31].
3.1.4. Crystal structure of [Zn(L2)2(bpy)] (complex 2)
Complex 2 contains the 2,20-bipyridine ligand together with
two acyl pyrazolone (HL2) ligands. Selected bond lengths and bond
angles of complex 2 are presented in Table 2. The single crystal X-
ray analysis for complex 2 shows the general structural formula M
(L2)2L0 (where L0 is 2,20-bipyridine). The zinc(II) ion is hexacoordi-
nated by four oxygen atoms (O1, O2, O3 and O4) of the two acyl
pyrazolone ligands (L2) and two nitrogen atoms (N5 and N6) of
the 2,20-bipyridine ligand. The structure of complex 2 is illustrated
in Fig. 1. Two oxygen atoms [O(1)and O(3)] from the two HL2
ligands and two nitrogen atoms [N(5) and N(6)] from the 2,20-
bipyridine ligand create the equatorial plane. The deviations of
the coordination atoms O(1), O(3), N(5) and N(6) from the mean
plane are 0.128, 0.131, 0.157 and 0.154 Å, respectively. The Zn(II)
metal ion strays from the equatorial plane by 0.015 Å. The coordi-
nation plane around the Zn(1) ion is composed of the O(1), O(3), N
(5) and N(6) atoms and the regular bond distances for Zn(1)AO(1),
Zn(1)AO(3), Zn(1)AN(5) and Zn(1)AN(6) are 2.071(3), 2.064(3),
2.126(4) and 2.111(4) Å, respectively. Two oxygen atoms [O(2)
and O(4)] of the HL2 ligands are in axial positions with the distance
Fig. 1A. ORTEP diagrams of the ligands with 40% probability ellipsoids (a) HL1 and
(b) HL2.
ligands and two nitrogen atoms [N(5) and N(6)] from the 2,20-
bipyridine ligand comprise the equatorial planes. The deviations
of the coordination atoms O(2), O(3), N(5) and N(6) from the mean
plane are 0.0073, 0.069, 0.077 and 0.081 Å, respectively. The Zn(II)
metal ion strays from the equatorial plane by 0.008 Å. The coordi-
nation plane around the Zn(1) ion is composed of the O(2), O(3), N
(5) and N(6) atoms and the regular bond distances for Zn(1)AO(2),
Zn(1)AO(3), Zn(1)AN(5) and Zn(1)AN(6) are 2.069(15), 2.061(17),
2.150(2) and 2.140(2) Å, respectively. Two oxygen atoms [O(1) and
O(4)] of the HL1 ligands are in axial positions, with the distance
from the equatorial plane being 2.109 and 2.129 Å, respectively
[3,4]. The O(2)AZn(1)AN(5), O(3)AZn(1)AN(6) and O(1)AZn(1)A

I. Shaikh et al. / Polyhedron 183 (2020) 114528
5
Fig. 1B. ORTEP diagrams with 40% probability ellipsoids (a) complex 1, (b) complex 2 and (c) complex 3. Hydrogen atoms and solvent molecules have been omitted for clarity.
Fig. 2. Intermolecular H-bond in HL1 viewed down the ‘b’ axis.
from the equatorial plane being 2.144 and 2.080 Å respectively
[3,4]. The O(1)AZn(1)AN(5), O(3)AZn(1)AN(6) and O(2)AZn (1)A
O(4) angles are 168.02(14), 164.78(15) and 170.44(13)°, respec-
tively, which are deviated from the theoretical value of 180° for
the proper geometric structure. The O(2)AZn(1)AO(1), O(3)AZn
(1)AO (1), O(2)AZn(1)AN(5), O(2)AZn(1)AN(6), O(1)AZn(1)AO
(4), O(3)AZn(1)AO(4), O(4)AZn(1)AN(5) and O(4)AZn(1)AN(6)
angles are 83.89(13), 98.68(13), 89.83(14), 99.07(14), 88.20(14),
85.69(14), 98.89(15) and 86.83(14)°, respectively, which are devi-
ated from the 90° angle between the axial line and the equatorial
plane. Therefore, the geometry around the zinc ion in the complex
is distorted octahedral (Fig. 5) [4,6,31].
two oxygen atoms, O(2) and O(3), of each 4-acyl pyrazolone (L2)
ligand are in the equatorial plane together with two nitrogen
atoms of the 1,10-phenanthroline ligand. The deviations of the
coordination atoms O(2), O(3), N(5) and N(6) from the mean plane
are 0.108, 0.111, 0.130 and 0.131 Å, respectively. The Zn(II) metal
ion strays from the equatorial plane by 0.018 Å. The coordination
plane around the Zn(II) ion is composed of the O(2), O(4), N(5)
and N(6) atoms and the regular bond distances for Zn(1)AO(2),
Zn(1)AO(4), Zn(1)AN(5) and Zn(1)AN(6) are 2.042(3), 2.034(3),
2.144(4) and 2.154(3) Å, respectively [4,32,33]. Two oxygen atoms,
O(1) and O(3), of the acyl pyrazolone (L2) ligands are in axial posi-
tions. The O(2)AZn(1)AN(6), O(4)AZn(1)AN(5) and O(1)AZn(1)AO
(3) angles are 166.95(13), 164.65(12) and 163.50(10)°, respec-
tively. These angles are deviated from the theoretical value of
180° for the proper geometric structure. The O(4)AZn(1)AO(2), O
(4)AZn(1)AN(6), N(5)AZn(1)AN(6), O(2)AZn(1)AN(5), O(1)AZn
(1)AO(4), O(3)AZn(1)AO(4), O(1)AZn(1)AN(5) and O(3)AZn(1)A
3.1.5. Crystal structure of [Zn(L2)2(phen)] (complex 3)
The mixed ligand complex 3 has 1,10-phenanthroline as a sec-
ondary ligand in its structure. Selected bond lengths and bond
angles are illustrated in Table 3. In the geometry of complex 3,

6
I. Shaikh et al. / Polyhedron 183 (2020) 114528
Table 2
Table 3
Selected bond angles and bond lengths for the ligands HL1 and HL2.
Selected bond angles and bond lengths for complexes 1–3.
HL1
Complex 1
Atoms
Length/Å
Atoms
Angle/°
Atoms
Length/Å
Atoms
Angle/°
Cl1AC5
Cl2AC15
O1AC7
N2AN1
N2AC9
N1AC7
N1AC1
O2AC11
C7AC8
C9AC8
C9AC10
C8AC11
C1AC6
1.747(3)
1.740(3)
1.243(3)
1.366(3)
1.314(3)
1.394(3)
1.414(3)
1.222(3)
1.427(4)
1.391(3)
1.481(4)
1.460(4)
1.386(3)
C9AN2AN1
N2AN1AC7
N2AN1AC1
C7AN1AC1
O1AC7AN1
O1AC7AC8
N1AC7AC8
N2AC9AC8
N2AC9AC10
C8AC9AC10
C7AC8AC11
C9AC8AC7
C9AC8AC11
110.20(18)
108.42(19)
120.21(18)
130.7(2)
121.4(2)
133.1(2)
105.4(2)
109.2(2)
119.7(2)
131.1(2)
129.6(2)
106.8(2)
123.5(2)
Zn1AO4
Zn1AO3
Zn1AO1
Zn1AO2
Zn1AN6
Zn1AN5
Cl2AC15
Cl1AC3
Cl4AC32
O4AC28
O3AC24
O1AC11
O2AC7
2.1225(16)
2.0610(17)
2.1187(16)
2.0693(15)
2.140(2)
2.150(2)
1.740(3)
1.740(3)
1.743(3)
1.263(3)
1.273(3)
1.266(3)
1.270(3)
O4AZn1AN6
O4AZn1AN5
O3AZn1AO4
O3AZn1AO1
O3AZn1AO2
O3AZn1AN6
O3AZn1AN5
O1AZn1AO4
O1AZn1AN6
O1AZn1AN5
O2AZn1AO4
O2AZn1AO1
O2AZn1AN6
90.25(7)
93.26(7)
86.13(7)
90.15(7)
90.74(6)
174.87(7)
100.59(8)
175.91(6)
93.57(7)
89.10(7)
91.67(6)
86.65(6)
93.00(7)
HL2
Complex 2
Atoms
Atoms
Length/Å
Atoms
Angle/°
Length/Å
Atoms
Angle/°
O1AC8
1.310(3)
1.261(3)
1.427(4)
1.403(4)
1.431(4)
1.504(4)
1.396(3)
1.312(3)
1.423(3)
1.336(3)
1.736(3)
C10AN2AN1
N2AN1AC1
C8AN1AN2
106.1(2)
120.0(2)
110.4(2)
129.5(2)
119.0(2)
119.5(2)
121.5(3)
118.7(2)
119.1(2)
120.5(2)
127.9(2)
Zn1AO2
Zn1AO3
Zn1AO1
Zn1AO4
Zn1AN5
Zn1AN6
Cl2AC16
Cl1AC34
O2AC12
O3AC26
2.138(3)
2.064(3)
2.071(3)
2.103(3)
2.126(4)
2.111(4)
1.734(5)
1.732(6)
1.265(5)
1.267(6)
O3AZn1AO2
O3AZn1AO1
O3AZn1AO4
O3AZn1AN5
O3AZn1AN6
O1AZn1AO2
O1AZn1AO4
O1AZn1AN5
O1AZn1AN6
O4AZn1AO2
O4AZn1AN5
90.21(14)
98.68(13)
85.69(14)
91.52(15)
164.78(15)
83.89(13)
88.20(14)
168.02(14)
94.31(14)
170.44(13)
98.89(15)
O2AC12
C9AC10
C9AC8
C9AC12
C10AC11
N2AN1
N2AC10
N1AC1
C8AN1AC1
C17AC16ACl1
C15AC16ACl1
C15AC16AC17
C14AC13AC12
C14AC13AC18
C2AC1AN1
N1AC8
Cl1AC16
O1AC8AC9
Complex 3
Atoms
Length/Å
Atoms
Angle/°
Zn1AO3
Zn1AO2
Zn1AO1
Zn1AO4
Zn1AN6
Zn1AN5
Cl1AC16
Cl2AC34
O3AC30
O2AC8
2.160(3)
2.042(3)
2.160(3)
2.034(3)
2.154(3)
2.144(4)
1.744(4)
1.734(4)
1.260(4)
1.262(5)
1.268(5)
1.272(4)
O3AZn1AO1
O2AZn1AO3
O2AZn1AO1
O2AZn1AN6
O2AZn1AN5
O4AZn1AO3
O4AZn1AO2
O4AZn1AO1
O4AZn1AN6
O4AZn1AN5
N6AZn1AO3
N6AZn1AO1
163.50(10)
81.95(11)
86.47(11)
166.95(13)
91.90(13)
87.02(11)
101.76(12)
83.87(11)
90.37(13)
164.65(12)
94.03(11)
99.74(11)
N(6) angles are 101.76(12), 90.37(13), 76.73(14), 91.90(13), 83.87
(11), 87.02(11), 90.08(12) and 94.03(11)°, respectively, which are
deviated from the 90° angle between the axial line and equatorial
plane. Therefore the geometry around the zinc ion in the complex
is distorted octahedral (Fig. 5) [3,4,6].
3.2. 1H and 13C NMR spectra
O1AC12
O4AC26
The synthesized ligands HL1 and HL2 have been characterized
by their 1H and 13C NMR spectra in CDCl3. The spectra are in good
agreement with the proposed structures of the ligands. In the 1H
NMR spectrum of HL1, a singlet appears at d 2.13 ppm for the
methyl protons of the 3-methyl pyrazolone. The ligand shows mul-
tiplets in the region d 7.3–7.9 ppm, corresponding to the aromatic
protons. In the 1H NMR spectrum of HL2, there are two singlets at d
2.13 and 2.39 ppm, corresponding to methyl protons of CH3-pyra-
zolone and tolyl pyrazolone, respectively. The peaks for the aro-
matic protons of the acyl pyrazolone are observed in the range d
7.3–7.7 ppm (Fig. 6).
In the 1H NMR spectrum of complex 2, there are two singlets at
d 1.6 and 2.2 ppm for the methyl and tolyl groups of the HL2 ligand.
Multiplet signals in the aromatic region are observed which corre-
spond to the aromatic protons of the HL2 and 2,20-bipyridine
ligands [4,6].
In the 1H NMR spectrum of complex 3, the methyl group of
pyrazolone gives a signal at d 1.66 ppm and a singlet for the tolyl
protons is observed at d 2.28 ppm. The aromatic protons of the acyl
pyrazolone and 1,10-phenanthroline ligands are observed in the
range d 7–9 ppm [4,6].
In the 13C NMR spectra of the ligands, there are fifteen signals
observed for HL1 and fourteen signals observed for HL2. The car-
bon atoms of the methyl group of the pyrazolone ring appeared
at d 16.01 and 15.90 ppm for HL1 and HL2, respectively. The
methyl group of tolyl group of HL2 appears at d 21.10 ppm. The sig-
nals of the carbonyl carbon atom of the p-chloro benzoyl group are
observed at d 190 and 191 ppm for HL1 and HL2, respectively. In
the range d 103–148 ppm, signals are found for the aromatic rings
of the pyrazolone and p-chloro benzoyl groups for both ligands
(Fig. 7).
In the 13C NMR spectrum of complex 1, twenty NMR signals
have been observed, which are in complete agreement with the
total number of carbon atoms in this Zn(II) complex. In complex
1, the carbonyl carbon atom of p-chloro benzoyl and one carbon
atom (CAOA) of the pyrazolone ring are observed at d 190 and
166 ppm, respectively [4,6]. The 1H and 13C NMR spectra of the
ligands and the complexes are presented in the supporting infor-
mation (S1–S8) (Fig. 8).
In the 1H NMR spectrum of complex 1, the proton signal of the
methyl group of pyrazolone is observed at d 1.6 ppm. The aromatic
protons of the acyl pyrazolone ligand are observed between d 7 and
8 ppm. A triplet and two doublets for the aromatic protons of the
2,20-bipyridine ligand are observed in the range d 8–9.1 ppm [4,6].
3.3. IR spectroscopy
The FT-IR spectrum of the ligand HL1 shows bands at 3426,
1625 and 1590 cmꢀ1, which can be assigned to
tNAH,
tCO
(amide)
and tCO
respectively. The HL1 ligand band at 1173 cmꢀ1
(ketone),

I. Shaikh et al. / Polyhedron 183 (2020) 114528
7
Fig. 3. Zigzag view of the crystal packing of the HL1 molecule viewed down the ’b’ axis. Thin black lines indicate short contacts in the crystal packing.
Fig. 4. (a) Intramolecular H-bond in the HL2 ligand, viewed down the ‘a’ axis. (b) Parallel arrangement of molecules in the crystal packing of the ligand HL2.
may be attributed to
at 3441, 1625 and 1590 cmꢀ1 which can be assigned to
and CO respectively [4,11].
t
C-N. Similarly, the ligand HL2 exhibits bands
In the FTIR spectrum of complex 2, absorptions are observed at
t
NAH, CO
t
1626 and 1564 cmꢀ1 due to
tCO(ketone) and tC@N, respectively.
t
New bands were observed at 476 and 415 cmꢀ1 due to v(ZnAO)
and v(ZnAN), respectively [4,8,11].
(amide)
(ketone),
Complex 1 shows an absorption at 1625–1621 cmꢀ1, assigned
CO. In comparison with the ligand’s spectrum, this band is
to
t
Complex 3 exhibited bands at 1622 and 1562 cmꢀ1 due to
shifted to a lower wavelength, which may be due to the interaction
t
CO(ketone) and
476 and 424 cmꢀ1 due to
parison between the FT-IR spectra of the ligands and the com-
t
C@N, respectively. New bands were observed at
with the metal ion. Complex 1 shows bands at 471 and 439 cmꢀ1
t
MAO and MAN, respectively. A com-
t
due to tMAO and tMAN, respectively [3,4,6,12].

8
I. Shaikh et al. / Polyhedron 183 (2020) 114528
Fig. 5. Distorted octahedral geometry of all the zinc(II) complexes (a) complex 1, (b) complex 2 and (c) complex 3. Structures are in wireframe with a polyhedral style.
Fig. 6. Crystal packing viewed down the ‘a’ axis of complex 1. The bipyridyl rings are arranged parallel to each other.
plexes revealed that complexes 1 and 3 contain 2,20-bipyridine and
1,10-phenanthroline, respectively, with the corresponding acyl
pyrzolone ligands [4,8,11]. The FTIR spectra are presented in the
supporting information (S9–S13).
for a d10 configuration. A broad band in the region 320–400 nm
may be attributed to a ligand to metal charge transfer [3,4].
3.5. Thermogravimetric analysis.
3.4. Electronic spectral studies
3.5.1. TGA of [Zn(L1)2(bpy)] (complex 1)
The TGA graph of complex 1 showed the complex was air stable
and it had high thermal stability (Fig. 10). The thermal study was
carried out using the thermogravimetric technique with a heating
rate of 10 °C minꢀ1. Slowly degradation started up to 250 °C, which
The electronic spectra of the ligands HL1 and HL2 and their zinc
complexes 1, 2 and 3 were recorded in DMSO (Fig. 9). In the spectra
of the Zn(II) complexes, no d-d bands were observed, as expected

I. Shaikh et al. / Polyhedron 183 (2020) 114528
9
Fig. 7. Crystal packing viewed down the ‘c’ axis of complex 2. The bipyridyl rings are arranged parallel to each other in complex 2.
Fig. 8. Crystal packing system viewed down the ‘c’ axis of complex 3.
was due to loss of the lattice solvent molecule. A second degrada-
tion stage started after 250 °C due to pyrolysis of the primary (HL1)
and secondary (bpy) ligands [4].
3.5.2. TGA of [Zn(L2)2(bpy)] (complex 2)
The TGA results revealed that the zinc complex 2 was air stable
and it had high thermal stability (Fig. 10). Degradation observed

10
I. Shaikh et al. / Polyhedron 183 (2020) 114528
3.5.3. TGA of [Zn(L2)2(phen)] (complex 3)
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
HL1
Complex 3 was found to be air stable and to have high thermal
stability from its TGA plot (Fig. 10). Degradation observed after
250 °C was due to pyrolysis of the ligand HL2 and the secondary
ligand (phen) [4].
HL2
complex
complex
complex
1
2
3
3.5.4. Antimalarial activity of the compounds
All five derivatives under study (the two ligands and three com-
plexes) exhibited considerable inhibitory effects against P. falci-
parum in the in-vitro assay (Fig. 11). The lowest minimal
inhibitory concentration of 0.11
1, followed by 0.14, 0.95, 2.97 and 4.50
l
M/L was obtained for complex
M/L respectively for com-
l
plex 2, complex 3, HL2 and HL1.
4. Conclusion
280 300 320 340 360 380 400 420 440 460 480 500
Wavelength (nm)
Two acyl pyrazolones (HL1 and HL2) have been synthesized. A
single crystal X-ray diffraction study revealed that the ligands
HL1 and HL2 have inter-molecular and intra-molecular H-bonds,
respectively. Three Zn((II) complexes (1–3) of these two ligands
have been synthesized and characterized by various analytical
and spectroscopic techniques. X-ray diffraction has confirmed their
structures. The low molar conductance in DMSO indicated the non-
electrolyte property of these complexes. Complexes 1–3 possess a
distorted octahedral coordination geometry, with four coordina-
tion sites being occupied by two 4-acyl pyrazolone ligands and
two coordination sites being occupied by the bidentate ligand
(bpy or phen) (Fig. 1). The ligands and complexes have been
screened for antimalarial activity. Complex 1 is reported to have
the best activity from an in vitro P. falciparum growth inhibition
assay. The present study reveals the possibility of complex 1 being
a candidate for an antimalarial drug.
Fig. 9. UV–Vis spectra of the ligands and complexes 1–3.
CRediT authorship contribution statement
Irfan Shaikh: Methodology, Software, Data curation, Writing -
original draft, Investigation. R.N. Jadeja: Conceptualization, Super-
vision, Writing - review & editing. Rajesh Patel: Software, Valida-
tion, Visualization.
Fig. 10. TGA graphs of complexes 1–3.
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
after 240 °C was due to pyrolysis of the acyl pyrazolone (HL2) and
secondary (bpy) ligands [4].
Fig. 11. Antimalarial activity of the synthesized compounds. P. falciparum was used in the in vitro assay.

I. Shaikh et al. / Polyhedron 183 (2020) 114528
11
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CCDC 1985004–1985008 contain the supplementary crystallo-
graphic data for complex 1, complex 2, complex 3, HL1 and HL2
respectively. This data can be obtained free of charge at www.
ccdc.cam.ac.uk/conts/retrievel.html or from the Cambridge Crys-
tallographic Data Center, 12 Union Road, Cambridge CB2 1EZ,
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