Synthesis and cytotoxic evaluation of some substituted pyrazole zirconium (IV) complexes and their biological assay

Article abstract of DOI:10.1002/aoc.4503

Pyrazole and their derivatives are found to have intense biological efficiency. In the present work some substituted pyrazole derivatives were synthesized and used as ligands (4-[2-vinylthiophene]-3-methyl pyrozolin-5(4H) - one (L₁), 4-[4-chloro benzylidine]-3-methyl pyrozolin-5(4H) - one (L₂) and 4-[4-dimethylnitro benzylidine]-3-methylpyrozolin-5(4H) - one (L₃)) to prepare the zirconium (IV) complexes. The synthesized ligands and their complexes were obtained as colored powdered materials and were characterized using magnetic measurements, melting point, molar conductance, infrared, electronic, ¹HNMR, mass spectra and thermogravimetric analyses. All of the tested compounds showed good microbial activity against pathogenic microorganisms. The tested compounds exhibited considerable antitumor activity and cytotoxic specificity towards human colon carcinoma cell line (HCT-116).

Full text of DOI:10.1002/aoc.4503

Received: 3 April 2018
DOI: 10.1002/aoc.4503
Revised: 15 May 2018
Accepted: 12 June 2018
F U L L P A P E R
Synthesis and cytotoxic evaluation of some substituted
pyrazole zirconium (IV) complexes and their biological
assay
Walaa H. El‐Shwiniy
| Wesam S. Shehab | Soha F. Mohamed | Hend G. Ibrahium
Department of Chemistry, Faculty of
Science, Zagazig University, Zagazig
44519, Egypt
Pyrazole and their derivatives are found to have intense biological efficiency.
In the present work some substituted pyrazole derivatives were synthesized
and used as ligands (4‐[2‐vinylthiophene]‐3‐methyl pyrozolin‐5(4H) ‐ one
(L1), 4‐[4‐chloro benzylidine]‐3‐methyl pyrozolin‐5(4H) ‐ one (L2) and
Correspondence
Walaa H. El‐Shwiniy, Department of
Chemistry, Faculty of Science, Zagazig
University, Zagazig, 44519, Egypt.
Email: walaa1986@zu.edu.eg;
wh595949@gmail.com
4‐[4‐dimethylnitro benzylidine]‐3‐methylpyrozolin‐5(4H) ‐ one (L3)) to prepare
the zirconium (IV) complexes. The synthesized ligands and their complexes
were obtained as colored powdered materials and were characterized using
magnetic measurements, melting point, molar conductance, infrared,
electronic, 1HNMR, mass spectra and thermogravimetric analyses. All of
the tested compounds showed good microbial activity against pathogenic
microorganisms. The tested compounds exhibited considerable antitumor
activity and cytotoxic specificity towards human colon carcinoma cell line
(HCT‐116).
KEYWORDS
antitumor, complexes, pyrazole derivatives, spectral study, zirconium (IV)
1 | INTRODUCTION
The stability of the zirconium acyl complexes has been
found to depend upon the nature of the co‐ligands and
Pyrazolone played a particular role due to both their
broad spectrum of bioactivity and their wide ranging
utility as synthetic tools in the design of various bioac-
tive molecules. In recent years, substituted pyrazole
derivatives have drawn considerable attention owing to
their broad spectrum biological properties. Compounds
with pyrazole functional units exhibit antimicrobial,[1]
herbicidal,[2] antitumor,[3–5] insecticidal,[6–8] fungicidal[9]
and antiviral activities.[10,11]Lamberth[12] has summa-
rized the significance of pyrazole derivatives in crop
protection chemistry, including herbicidally‐, fungicid-
ally‐ and insecticidally‐active pyrazole classes. Moreover,
some substituted pyrazole derivatives (L1, L2, L3) had
been synthesized, and the compound belongs to a
very important class with pharmacological activity
(Scheme 1).
decreases as the N‐donor capacity of the co‐ligand
increases.[13] It is possible, therefore, that the use of stron-
ger electron‐donor ligands in place of C5H5 might facilitate
displacement of an acyl ligand. Due to its wide range of bio-
logical activity, pyrazoles have received a considerable
interest in the field of drug discovery and therefore
pyrazole ring constitutes a relevant synthetic target in
pharmaceutical industry. In fact, such a heterocyclic moi-
ety represents the core structure of a number of drugs.
Therefore, in the present study, we investigated the
coordination behavior of L1, L2, L3 for Zr (IV) and the data
are correlated with their thermal properties. In this vein,
we have been developed novel pyrazole derivatives (L1,
L2, L3) and Zr (IV) in order to hopefully produce new com-
pounds with antitumor activity. The as‐prepared new com-
pounds were designed, synthesized and characterized.
Appl Organometal Chem. 2018;e4503.
wileyonlinelibrary.com/journal/aoc
© 2018 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.4503

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EL‐SHWINIY ET AL.
SCHEME 1 Structure of the
synthesized compounds
2 | EXPERIMENTAL
2.2 | Synthesis
A series of 4‐arylidene‐3‐methyl‐5‐pyrazolone derivatives
have been synthesized by condensing 3‐methyl‐5‐
pyrazolone with substituted aromatic aldehydes as
illustrated in Scheme 1. Structures of the synthesized
compounds (2–4) as follow:
2.1 | Materials and methods
2.1.1 | Chemicals
All chemicals used for the preparation of the complexes
were of analytical reagent grade, commercially available
from different sources and used without further purifica-
tion. CHN analysis was executed on a Perkin Elmer CHN
2400. The percentages of the metal ions were determined
gravimetrically by transforming the solid products into metal
ion. The percentages of the metal ions were also estimated
using an atomic absorption spectrometer. The spectrometer
model was PYE‐UNICAM SP 1900 and fitted with the
corresponding lamp. IR spectra were recorded on FT‐IR 460
2.2.1 | Synthesis of 3‐methyl‐5‐pyrazolone
(Scheme 1)[14]
In this work take ethyl acetoacetate in a beaker and stirred
magnetically and add to a solution of hydrazine hydrate in
absolute alcohol.[14] The reaction mixture was kept at 60°C
and the crystalline was separated after stirring for 1 hr at
60°C. The crystallization complete when the reaction mix-
ture cooled in ice bath. Then crystalline solid was washed
with cold alcohol and dried. The 3‐ methyl‐5‐pyrazolone
so obtained was kept for next step of the synthetic
scheme.[15] Yellow solid, Yield 81%, m.p.: 207–210°C.
IR (KBr, v, cm−1): 2566.47 cm−1 (CH3 group), 3283.05 cm−1
(N‐H Stretch), 1609.91 cm−1 (CH=CHstretch),
1735.77 cm−1, 1676.28 cm−1 (ketone group), 1342–
1266 cm−1 (C‐N stretch), 3000–2840 cm−1 (C‐H stretch).
1HNMR (DMSO‐d6, 300 MHz): δ = 0.265 (s, 1H, NH,
Pyrazolonenucleus), δ, ppm: 1.652 (s, 2H, CH2), δ, ppm:
0.8263 (s, 3H, CH3). Anal. Calcd for C4H6N2O (98.1): C,
48.97; H, 6.16; N, 28.56; Found C, 48.96; H, 6.15; N, 28.56%.
PLUS (KBr discs) in the range from 4000–400 cm−1. H
1
and 13C NMR spectra were recorded on a Bruker
300 MHz NMR Spectrometer using tetramethylsilane
(TMS) as the internal standard, chemical shifts are
expressed in δ (ppm) and DMSO‐d6 was used as the sol-
vent. TGA‐DTG measurements were carried out with
heating rate of 20οC min−1 under N2 atmosphere from
ο
room temperature to 1000 C using TGA‐50H Shimadzu.
The mass of sample was accurately weighted out in an
aluminum crucible. Absorbance measurements were
conducted on a double beam spectrophotometer (T80
UV/Vis) with wavelength range 190 nm ~ 1100 nm,
spectral bandwidth of 2 nm. Magnetic measurements were
carried out on a Sherwood scientific magnetic balance
using Gouy balance using Hg [Co (SCN)4] as calibrate.
All melting points are uncorrected and were determined
on a Gallen Kamp electric melting point apparatus. Molar
conductivities of the solutions of the ligand and metal
2.2.2 | Synthesis of 3‐methyl‐5‐pyrazolone
derivatives[16–18]
Take synthesized pyrazolone in freshly prepared
20% sodium hydroxide (alcoholic solution) was poured
into it and stirred magnetically for 30 min. Substituted
aromatic aldehyde was added to the reaction mixture
and kept under constant stirring for 8 hrs. Reaction
complexes in DMSO with concentrations of 1 × 10−3
were measured on CONSORT K410. The completion of
the reactions was confirmed using thin layer chromatogra-
phy (TLC) on silica gel coated aluminum sheets.
M

EL‐SHWINIY ET AL.
3 of 16
mixture was transferred to crushed ice and
neutralizedwith dil. HCl to precipitate the product in
Scheme 1. Synthesis of 3‐methyl‐5‐pyrazolone (intermedi-
ate) via Knorrpyrazolone reaction and further reaction
with substituted arylaldehydes to obtain 3‐methyl‐5‐
pyrazolone derivatives.[19]
(s, 6H, ‐N (CH3)2), 6.51 (S, 1H, =CH‐Ar), 7.51–7.60 (m,
4H, Ar‐H), 8.97 (s, 1H, ‐NH). Anal. Calcd for
C13H15N3O (229.14): C, 68.08; H, 6.54; N 18.32; Found
C, 68.07; H, 6.13; N, 18.10.
2.2.6 | [ZrO(L1)Cl]Cl•H2O
Grey; Yield: 77%; m.p.: 120οC; M.Wt: 580.22; Elemental
analysis for ZrC18H18N4O4S2Cl2: found, C, 38.16; H,
3.02; N, 9.37; Zr, 16.00; Cl, 12.83. Calcd, C, 38.41; H, 3.10;
N, 9.69; Zr, 16.22; Cl, 12.62; Λm = 99.50 S cm2 mol−1; IR
(KBr, v, cm−1): 3390 m,br (NH), 1600 m (C=O), 1457vw
cm−1 (C=N) and 1054 m cm−1(C=S), 544w and 492w
(M–N). HNMR (DMSO‐d6, 300 MHz): δ = 2.49 (s, 3H,
CH3), 3.42 (s, 2H, H2O), 6.75 (S, 1H, =CH‐Ar), 8.11 (d,
3H, Ar‐H).
2.2.3 | 4‐[2‐vinylthiophene]‐3‐methyl
pyrozolin‐5(4H) ‐ one (L1)
Black, m.p.: 260°C, Yield 79% IR (KBr, v, cm−1): 3413
(NH), 1595 (C=O), 1406 cm−1 (C=N) and 1011 cm−1
1
(C=S). HNMR (DMSO‐d6, 300 MHz): δ = 1.98 (s, 3H,
1
CH3), 6.75 (S, 1H, =CH‐Ar), 8.11 (d, 3H, Ar‐H), 11.15
(s, 1H, ‐NH). Anal. Calcd for C9H8N2OS (192): C, 56.25;
H, 4.16; N 14.58; S, 16.66; Found C, 56.00; H, 4.75; N,
14.55; S, 16.56%.
2.2.7 | [ZrO(L2)Cl]Cl•H2O
2.2.4 | 4‐[4‐chloro benzylidine]‐3‐methyl
pyrozolin‐5(4H) ‐ one (L2)
Orange; Yield: 81%; m.p.: 296οC; M.Wt: 637.22; Elemental
analysis for ZrC22H20N4O4Cl4: found, C, 42.33; H, 3.12;
N, 9.00; Zr, 14.21; Cl, 22.43. Calcd, C, 42.63; H, 3.31; N,
9.04; Zr, 14.73; Cl, 22.93; Λm = 89.00 S cm2 mol−1; IR
(KBr, v, cm−1): 3400 m,br (NH), 1599 m (C=O),
1421 m cm−1 (C=N) and 638w and 539w (M–N). 1HNMR
(DMSO‐d6, 300 MHz): δ = 2.07 (s, 3H, CH3), 7.33 (S, 1H,
=CH‐Ar), 7.37–7.94 (d, 3H, Ar‐H), 3.46 (s, 2H, H2O).
Yellow, m.p.: 240°C, Yield 84% IR (KBr, v, cm−1): 3413
(NH), 1590 (C=O) and 1406 cm−1 (C=N). 1H NMR
(DMSO‐d6, 300 MHz): δ = 1.88 (s, 3H, CH3), 6.51 (S, 1H,
=CH‐Ar), 7.39 (m, 4H, Ar‐H), 8.64 (s, 1H, ‐NH). Anal.
Calcd for C11H9N2OCl (220.5): C, 59.86; H, 4.08; N 12.69;
Cl, 16.09; Found C, 59.42; H, 4.03; N, 12.26; Cl, 16.00%.
2.2.5 | 4‐[4‐dimethylnitro benzylidine]‐3‐
methylpyrozolin‐5(4H)‐ one (L3)
Orange, m.p.: 180°C, Yield 65% IR (KBr, v, cm−1): 3418
(NH), 1613 (C=O) and 1406 cm−1 (C=N). 1H NMR
(DMSO‐d6, 300 MHz): δ = 1.91 (s, 3H, CH3), 3.71
2.2.8 | [ZrO(L3)Cl]Cl•H2O
Brown; Yield: 69%; m.p.: 110οC; M.Wt: 654.50; Elemental
analysis for ZrC26H32N6O4Cl2: found, C, 48.99; H, 4.41; N,
9.00; Zr, 14.15; Cl, 11.05. Calcd, C, 49.01; H, 4.88; N,
13.19; Zr, 14.33; Cl, 11.15; Λm = 91.51 S cm2 mol−1; IR
TABLE 1 Some selected Infrared frequenciesa (cm−1) and tentative assignmentsb for L1, L2, L3 and their complexes.
L1
[ZrO(L1)2Cl]Cl•H2O
L2
[ZrO(L2)2Cl]Cl•H2O
L3
[ZrO(L3)2Cl]Cl•H2O
Assignmentsb
‐
3397v,br
3390m,br
3090
2917
1600m
1457s
1430s
830 m
544
‐
3402m,br
3400m,br
3070
‐
3399m,br
3399m,br
3065
ν(O‐H); H2O
ν(N‐H); ‐NH
ν(C‐H); aromatic
ν(C‐H); aliphatic
ν(C=O)
3413
3413m,br
3413m,br
m,br
3093w
3070m
3060w
2917m
2925m
2925
2917m
2915
1595ms
1590m,sh
1599m
1421m
1450m
833w
638
1613vs
1615m
1433vw
1410vw
862 m
593
1406m
1406s
1406m
ν(C=N),
1406m
1491m
1400m
ν(C=C)
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
ν(Zr = O)
ν(M‐N)
492
539
543
‐
680 s
as = strong, w = weak, v = very, m = medium, br = broad, sh = shoulder,
bν = stretching, δb = bendin, δr = rocking.

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EL‐SHWINIY ET AL.
(KBr, v, cm−1): 3399 m,br (NH), 1615 m (C=O) and
1433vw cm−1 (C=N) and 593w and 543w (M–N). 1HNMR
(DMSO‐d6, 300 MHz): δ = 1.84 (s, 3H, CH3), 2.11–2.54
(s, 6H, ‐N (CH3)2), 7.64 (S, 1H, =CH‐Ar), 7.45–7.64
(m, 4H, Ar‐H), 3.40 (s, 2H, H2O).
counter ions for the isolated complexes and this was
agreed with IR‐data and molar conductance.
3.1 | Infra‐red Spectra analysis
The infra‐red spectra for the three free ligands (L1, L2, L3)
and their metal complexes were showed in Figure S1 and
listed in Table 1. From these spectra the site and kind of
2.3 | Biological activity and in vitro
cytotoxicity assays
The procedures of antibacterial activity assay were
evaluated according to the literature.[20] The synthesized
compounds were tested against colon carcinoma cell line
(HCT‐116).[21] Antitumor viability assay was performed
by the described method by Saintigny and Monnat Jr.[22]
3 | RESULTS AND DISCUSSION
The complexes of L1, L2, L3 with Zr(IV) were prepared
and studied. Depending on elemental analysis, the molar
ratio of the prepared complexes was determined. Conduc-
tance measurements, magnetic susceptibilities and spec-
tral measurements were different parameters used to
obtain the geometry and formulas of prepared complexes.
From magnetic measurments, the prepared complexes
have diamagnetic properties. For Zr(IV) complexes and
its corresponding ligands, the conductivity measurements
were done in DMSO at 1.0 × 10P−3PM and were found
from 5.03 to 99.50 S cm2 mol‐1[23] and it indicated that
they were electrolytes.[24–26] Chloride ion was found as
SCHEME
complexes
2
The proposed structures of the synthesized
FIGURE 1 Electronic absorption for L1, [ZrO (L1)2Cl]Cl•H2O,
L2, [ZrO (L2)2Cl]Cl•H2O, L3 and [ZrO (L3)2Cl]Cl•H2O

EL‐SHWINIY ET AL.
5 of 16
donation that may be involved in chelation could be
identified.[27,28] At 3413 and 1406 cm−1 two bands attrib-
uted to the stretching vibration of ν(N‐H) amino and for
ν(C=N) hydrazono groups. i.e. respectively for L1, L2,
L3.[29,30] From shifting to higher and lower frequency
values for ν(C=N), the coordination between the ligand
molecule and Zr(IV) through the nitrogen atom of
hydrazono group was confirmed. The following higher
frequencies (1457, 1421 and 1433) values of ν(C=N) may
indicate an increase of C=N bond strength as a result of
coordination.
330 nm are assigned to n‐π* (‐C=O,‐NH and –C=N) tran-
sition, in case of unsaturated hydrocarbons obtained by
cyanide and ketone group,[26] occur slightly shifted to
lower values (hypsochromic shift) and wavelength
(bathochromic shift), when ligands and metal cheated
new bands appear in reflection spectra of complexes refer
to the metal complexes were formed these new bands
shown in the range from 375 to 487 nm which may be
assigned to the ligand to metal charge‐transfer.[35,36]
3.3 | Nuclear magnetic resonance
Upon coordination to Zr(IV) the electron density on
the nitrogen atom was decreased this lead to a decrease
in the electron repulsion between the nitrogen lone pair
and the double bond electrons and as a result C=N bond
(1HNMR)
The 1H NMR spectra of L1 and their metal complex
(Figure S2 (A, B)) confirm the suggested structures. The
proton of –NH signal for ligand observed at δ:
11.15 ppm (s, 1H, –NH, exchange with D2O) showed no
observed it in complex. This enhances the hypothesis that
–NH is the coordinating group. The new signal are
observed in δ: 3.42 ppm due to presence of H2O molecule
in complex. On the other hand, the values of protons of
‐CH aliphatic (methyl) observed in δ: 1.978 ppm (s, 3H,
–CH3), that of aromatic ring are in δ: 8.11 ppm (d, 3H,
Aromatic–H) and the proton of (=CH‐Ar) group observed
in δ: 6.75 ppm (S, 1H, =CH‐Ar) increased and the inten-
sity of signals is increased, as shown in Table 2.[37] From
1HNMR and FT‐IR results, it was proposed that the L1
coordinated to the central metal ion as bidentate ligand
through the two nitrogen atom of pyrazolone group.[35]
became a strong band with a higher frequency.[29–31]
A
lower frequency value (3390, 3400 and 3399 cm−1) for
the shifting of ν(N‐H) indicated a decrease of the N‐H
bond strength upon coordination.[29] These changes of
the IR spectra suggest that L1, L2, L3 are coordinated to
the Zr(IV) via two nitrogen atoms of amino (N‐H) and
hydrazono (C=N) groups. The ν(O‐H) vibration of the
water molecules in the prepared complexes were found
at 3397–3402 cm‐1[27–33] also, the ν(C=O) was found at
1599–1615 cm−1
.
A group of new bands with different intensities was
found which characteristics for ν(M‐N). The ν(M‐N)
bands observed at 544, 492 cm−1 for Zr(IV)‐L1, 638,
539 cm−1 for Zr (IV)‐L2 and 593 and 543 cm−1 for
Zr(IV)‐L3, which are absent in the spectra of L1, L2 and
L3.[27–34] From the above mentioned result the coordina-
tion of L1, L2, and L3 was done through two C=N and
N‐H groups (Scheme 2).
1
The HNMR spectra of L2 and their metal complex
(Figure S2 (C, D)) confirm the suggested structures. The
proton of –NH signal for ligand observed at δ:
8.64 ppm (s, 1H, –NH, exchange with D2O) showed no
observed it in complex. This enhances the hypothesis
that –NH is the coordinating group. The new signalare
observed in δ: 3.46 ppm due to presence of H2O molecule
in complexes. On the other hand, the values of protons
of ‐CH aliphatic (methyl) observed in δ: 1.88 ppm
(s, 3H, –CH3), that of aromatic ring are in δ: 7.39 ppm
(m, 4H, Aromatic–H) and the proton of (=CH‐Ar) group
observed in δ: 6.51 ppm (S, 1H, =CH‐Ar) increased and
the intensity of signals is increased, as shown in
3.2 | UV–Vis. spectra
From the UV–Visible data of the ligands (L1, L2, and L3)
and their Zr(IV) chelates in the wavelength interval from
200 to 800 nm were recorded (Table S1 and Figure 1). The
spectra of the three ligands was absorbed by three absorp-
tion bands at 245, 283 and 282 nm. Which attributed to
π‐π*(phenyl ring) transition also, the three bands at
1
TABLE 2 Selected HNMR data of L1, L2, L3 and their diamagnetic complexes
Compounds δ H; H2O δH; ‐CH aliphatic (methyl) δH; ‐CH aromatic δH; =CH aromatic δH;‐N (CH3)2 δH; ‐NH hydrazid
L1
‐
1.978
2.49
1.88
2.074
1.91
1.84
8.105
6.75
‐‐
11.159
‐‐
L1/Zr(IV)
L2
3.418
‐
8.155
6.641
6.513
7.33
‐‐
7.37–7.39
7.307
‐‐
8.64
‐‐
L2/Zr(IV)
L3
3.469
‐
‐‐
7.51–7.603
7.453
6.505
7.640
3.718
2.11–2.54
8.97
‐‐
L3/Zr(IV)
3.400

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EL‐SHWINIY ET AL.
FIGURE 2 Mass spectra diagrams for
(A) L1, (B) [ZrO (L1)2Cl]Cl•H2O, (C) L2,
(D) [ZrO (L2)2Cl]Cl•H2O, (E) L3 and (F)
[ZrO (L3)2Cl]Cl•H2O

EL‐SHWINIY ET AL.
7 of 16
1
Table 2. From HNMR and FT‐IR results, it was pro-
posed that the L2 coordinated to the central metal ion
as bidentate ligand through the two nitrogen atom of
pyrazolone group.[28]
values, Tmax/οC, together with the corresponding weight
loss for each step of decomposition of the compounds
together with theoretical percentage mass losses are given
in Table 3 (Figure 3).
1
The HNMR spectra of L3 and their metal complex
The thermal decomposition for the ligand (L1) started
at 44°C and finished at 601°C with two stages. The first
stage of degradation takes place at maximum tempera-
ture of 133, 276 and 532°C is accompanied by a total
weight loss of 83.134%, close to the calculated value
83.33%. Corresponding to loss of 4C2H2 + CO + N2 mol-
ecule and activation energy of 105.29 KJ mol−1 (endother-
mic). The second step of decomposition occurs at
maximum 544°C and the actual weight loss from these
step is 16.866%, close to the calculated value 16.66% corre-
sponding to value of S.
(Figure S2 (E, F)) confirm the suggested structures. The
proton of –NH signal for ligand observed at δ: 8.97 ppm
(s, 1H, –NH, exchange with D2O) showed no observed it
in complex. This enhances the hypothesis that –NH is
the coordinating group. The new signal are observed in
δ: 3.40 ppm due to presence of H2O molecule in complex.
On the other hand, the values of protons of ‐CH aliphatic
(methyl) observed in δ: 1.91 ppm (s, 3H, –CH3), that of
aromatic ring are in δ: 7.51–7.60 ppm (m, 4H, Aro-
matic–H),the proton of (=CH‐Ar) group observed in δ:
6.51 ppm (S, 1H, =CH‐Ar) and protons of (N (CH3)2)
group observed in δ: 3.71 ppm (s, 6H, ‐N (CH3)2)
increased and the intensity of signals is increased, as
The thermal degradation of [ZrO(L1)2Cl]Cl•H2O com-
plex occurs in two degradation stages, the first stage
of decomposition occurs at maximum 94οC and is
accompained by a weight loss of 3.10% corresponding
1
shown in Table 2. From HNMR and FT‐IR results, it
was proposed that the L3 coordinated to the central metal
ion as bidentate ligand through the two nitrogen atom of
pyrazolone.[30]
to loss of H2O with an activation energy 47.06 KJ mol−1
.
The second step of decomposition occurs at
different temperatures and is accompanied by
a
weight loss of 81.17%; corresponding to thevalue of
8C2H2 + 2CO + 2 N2 + Cl2 + S2O theoretically, the
weight loss in this step 81.69%. The experimental value
of 15.72% corresponding to Zr agrees with the calculated
value 15.22%.
The thermal degradation for the ligand (L2) started
at 43°C and finished at 642°C with one stage. This
stage is accompanied by total weight loss of 90.185%,
close to the calculated value 89.115%. Corresponding
to loss of 4C2H2 + HCl + CO + N2 molecule and
3.4 | Thermal studies
The most commonly used thermal analysis techniques
are thermogravimetry (TG) for the characterization of
both organic and inorganic materials. TG measurements
give fundamental information about the thermal proper-
ties of the chelates. Representative thermogravimetric
curves are shown in Figure 2. The maximum temperature
TABLE 3 Thermogravimetric data of L1, L2, L3 and their metal complexes
% Estimated (calculated)
Mass loss Total mass loss Lost species
Assignment
Compounds
Decomposition DTG
(°C)
max
L1
First step
Residue
133,276,532,544 83.134 (83.33) 83.134 (83.33)
16.866 (16.66)
4C2H2 + CO + N2
S
192, C9H8ON2S
[ZrO(L1)2Cl]Cl•H2O
580.22, ZrC18H18N4O4S2Cl2 Second step
Residue
First step
94
3.10 (3.08)
81.17 (81.69)
15.72 (15.22)
84.27 (84.77)
H2O
281,422,744,809
8C2H2 + 2CO + 2 N2 + Cl2 + S2O
Zr
L2
First step
Residue
237,642
90.185 (89.115) 90.185 (89.115)
9.815 (10.88)
4C2H2 + HCl + CO + N2
2C
220.5, C11H9N2OCl
[ZrO(L2)2Cl]Cl•H2O
637.22, ZrC22H20O4N4Cl4 Second step
Residue
First step
78
2.82 (2.78)
80.97 (80.30)
16.198 (16.66)
83.79 (83.08)
H2O
9C2H2 + 2 N2 + 3CO + 2Cl2
Zr + C
286,557,660
L3
First step
323,568,901
100 (99.82)
100 (99.82)
6C2H2 + CO + NH3 + N2
229.14, C13H15ON3
[ZrO(L3)2Cl]Cl•H2O
654.5, ZrC26H32O4N6Cl2
First step
Second step
Residue
80
2.75 (2.60)
86.06 (85.76)
H2O
192,299,563,551,873 83.31 (83.16)
13.93 (13.33)
11C2H2 + 2C2H4 + Cl2 + 3N2O
Zr

8 of 16
EL‐SHWINIY ET AL.
FIGURE 3 TGA and DTG diagrams for (a) L1, (b) [ZrO(L1)2Cl]Cl•H2O, (c) L2, (d) [ZrO(L2)2Cl]Cl•H2O, (e) L3 and (f) [ZrO(L3)2Cl]Cl•H2O
activation energy of 14.07 KJ mol−1 (endothermic). The
Residue value decomposition occurs at maximum 642°C
and the actual weight loss from these step is 9.815%, close
to the calculated value 10.88% corresponding to 2C.
The thermal degradation of [ZrO(L2)2Cl]Cl•H2O
complex takes place in two degradation stages, the first
stage of decomposition occurs at maximum 78οC and is
accompained by a weight loss of 2.82% corresponding to
The second step of decomposition happens at different
temperatures is 192, 299, 551, 563, 873οC and is accompa-
nied by a weight loss of 83.31%; corresponding to the
value of 11C2H2 + 2C2H4 + 3N2O + Cl2 theoretically,
the weight loss in this step 83.16%. The experimental
value of 13.93% corresponding to Zr agrees with the cal-
culated value 13.33%.
loss of H2O with an activation energy 25.91 KJ mol−1
.
3.5 | Kinetic data
The second step of decomposition occurs at different
temperatures is 286, 557, 660οC and is accompanied by
a weight loss of 80.97%; corresponding to the value of
9C2H2 + 3CO + 2 N2 + Cl2 theoretically, the weight
loss in this step 80.30%. The experimental value of
16.198% corresponding to Zr + 2C agrees with the cal-
culated value 16.66%.
The thermal decomposition for the ligand (L3) started
at 47°C and finished at 901°C with one stage. This stage is
accompanied by a total weight loss of 100%, close to the
calculated value 99.82% corresponding to loss of
6C2H2 + NH3 + CO + N2 molecule and an activation
energy of 75.13 KJ mol−1 (endothermic).
Activation energies, E*, entropies, ΔS*, enthalpies, ΔH*,
and Gibbs free energies, ΔG* below to kinetic thermo-
dynamic parameters. The Coats‐Redfern (CR) and
Horowitz‐Metzger (HM) relationships used to estimate
graphically by employing for the decomposition.[37,38]
Their parameters were detected using the above men-
tioned methods by graphical means and they are listed
in Table 4. The activation energies of decomposition
were found to be in the range 35.33–137.93 kJ mol−1
.
The maximum values of the activation energies refer
to the thermal stability of the complexes, while the neg-
ative values of entropy of activation indicate that all
complexes with decomposition reactions proceeded with
a lower rate than the normal ones (Figure 4). From the
kinetic data obtained DTG curves, all the chelates had
negative entropy, which refer that activated complexes
have more ordered systems than reactants.
The thermal degradation of [ZrO (L3)2Cl]Cl•H2O
complex occurs in two degradation stages, the first stage
of decomposition occurs at maximum 80οC and is
accompained by a weight loss of 2.75% corresponding to
loss of H2O with an activation energy 46.32KJ mol−1
.

EL‐SHWINIY ET AL.
9 of 16
TABLE 4 Thermal behavior and kinetic parameters determined using the Coats–Redfern (CR) and Horowitz–Metzger (HM) operated for
L1, L2, L3 and their complexes
Parameter
Decomposition Ts
Range (K)
E*
(K) Method (KJ/mol) A (s−1
ΔS*
ΔH*
ΔG*
Compounds
)
(KJ/mol. K) (KJ/mol) (KJ/mol) Ra
SDb
L1
672–873
805 CR
HM
939 CR
HM
105.296 368.535 × 103
137.726 107.982 × 103
249.270
268.430
−446.853
−436.647
−469.744
−457.413
98.597
131.033
241.463
260.623
458.319 0.885 0.433
482.533 0.933 0.177
682.865 0.938 0.283
690.133 0.923 0.170
(C9H8N2OS)
876–1029
7.022 × 106
1.531 × 106
[ZrO (L1)2Cl]Cl•H2O 473–603
(ZrC18H10N4O4S2Cl2)
625–807
554 CR
HM
695 CR
HM
47.065
59.294
95.414
99.884
21.787 × 103
44.212 × 103
6.276 × 105
3.904 × 106
−426.446
−432.329
−452.502
−467.701
42.459
54.688
89.635
94.105
278.710 0.912 0.266
294.198 0.906 0.139
404.124 0.968 0.185
419.157 0.958 0.117
L2 316–689
(C11H9N2OCl)
510 CR
HM
915 CR
HM
14.076
24.303
94.210
117.980
8.267 × 103
8.633 × 103
13.481 × 103
45.024 × 104
−476.509
−419.466
−418.283
−447.453
9.835
20.06
86.600
110.372
252.853 0.972 0.126
233.990 0.956 0.117
469.331 0.944 0.308
519.792 0.984 0.072
709–997
[ZrO (L2)2Cl]Cl•H2O 292–429
(ZrC22H20N4O4Cl4)
720–898
351 CR
HM
830 CR
HM
25.910
30.666
4.968 × 103
5.354 × 103
−417.949
−418.573
−446.344
−445.504
22.991
27.747
101.854
121.047
169.691 0.948 0.243
174.666 0.935 0.145
472.319 0.980 0.165
490.814 0.982 0.077
108.755 357.423 × 103
127.947
323.088
L3
533–721
779–981
596 CR
HM
841 CR
HM
75.131
74.134
144.306
157.916 × 103
385.385 × 103
25.408 × 103
−442.306
−449.724
−424.253
−436.850
70.225
69.178
137.310
137.639
333.840 0.802 0.574
337.211 0.795 0.286
494.110 0.921 0.329
505.030 0.925 0.152
(C13H15N3O)
144.632 115.609 × 103
[ZrO (L3)2Cl]Cl•H2O 317–521
ZrC26H32 N6O4Cl2
537–687
465 CR
HM
572 CR
HM
46.320
54.193
87.957
87.266
73.252 × 103
180.209 × 103
7.145 × 103
−437.983
−445.467
−416.911
−422.850
42.453
50.326
83.201
82.510
246.116 0.982 0.115
257.469 0.990 0.0432
321.674 0.802 0.496
324.380 0.790 0.243
14.597 × 103
a= correlation coefficients of the Arrhenius plots and
b= standard deviation
ion peak [a] was appeared at m/z = 580 (20.2%) lossed
C10H8S2 to give [b] at m/z = 388 (16.43%). The molecular
ion peak [a] losses C9H9O2S2 to give [C] at m/z = 367
(6.3%) and it losses [C10H12S2] to give [d] at m/z = 384 (10%).
The mass spectrum of the L2 displayed molecular
structure is given as an example in (Scheme S2),
(Figure 2). The molecular ion peak [a] appeared at
m/z = 220 (96.1%), it lose C6H4Cl to give [b] at
m/z = 109 (28%), Then a molecular ion peak [b] lossed
CH3Oto give [c] at m/z = 78 (6.5%) and molecular ion
peak [c] loss CH to give fragment [d] at m/z = 65
(24.3%) alsothe molecular ion peak [a] loses [O] to give
[e] at m/z = 204 (4.5%) then [e] loss CH3 to give [f] at
m/z = 189 (1.6%) and it loss C7H5Cl to give fragment
[g] at m/z = 96 (2.4%) then a molecular ion peak [g] loss
CH3 to give [h] at m/z = 81 (35.9%).
3.6 | Mass spectra
Mass spectrometry was found benefit as a complementary
method. Mass spectrum of the L1 is in a good agreement
with the suggested structure (Scheme 3), (Figure 2). The
L1 showed molecular ion peak (M+.) with m/z = 192
(71.00%) and M+1 at m/z = 193 (7.1%). The molecular
ion peak [a] losses C4H3S to give fragment [b] at m/
z = 109 (99.9%), molecular ion peak [b] lossesCH3O to
give fragment [c] at m/z = 78 (83.3%) and this [c] losses
CH to give fragment [d] at m/z = 65 (7.2%). Also it loses
[O] to give fragment [E] at m/z = 176 (9.1%). The
molecular ion peak [a] losses CH3O to give fragment [F]
at m/z = 161 (6%).
The mass spectra of Zr(IV) complex displayed molecu-
lar peak at m/z = 580 (20.2%), suggesting that the molecular
weight of the assigned product matching with elemental
and thermogravimetric analyses (Scheme 4), (Figure 2).
Fragmentation pattern of the complex [ZrO(L1)2Cl]
Cl•H2O is given as an example in Scheme S1. The molecular
Fragmentation pattern of the complex [ZrO(L2)2Cl]
Cl•H2O is given as an example in (Scheme S3),
(Figure 2). The molecular ion peak [a] appeared at
m/z = 637 (21.5%) it loss C12H8Cl2 to give fragment [b]

10 of 16
EL‐SHWINIY ET AL.
FIGURE 4 The diagrams of kinetic parameters of L1, [ZrO (L1)2Cl]Cl•H2O, L2, [ZrO (L2)2Cl]Cl•H2O, L3 and [ZrO (L3)2Cl]Cl•H2O using
Coats‐Redfern (CR) and Horowitz‐Metzger (HM) equations
at m/z = 414 (31.2%), then molecular ion peak [b] loss
C2H6O2 to give [c] at m/z = 352 (14%) then [c] losses
C2H2 to give [d] at m/z = 326 (18%).
The mass spectrum of the L3 displayed molecular struc-
ture is given as an example in (Scheme S4), (Figure 2). The
molecular ion peak [a] appeared at m/z = 229 (78.3%), it

EL‐SHWINIY ET AL.
11 of 16
m/z = 78 (5.5%) and ion [d] loss CH to give [e] at
m/z = 65 (12.5%) also the molecular ion peak [a] loss
C9H11N to give [F] at m/z = 96 (25%) then [f] loss [O] to
give [g] at m/z = 80 (1.4%) and molecular ion peak [g] loss
CH3 to give [h] at m/z = 65 (12.5%).
Fragmentation pattern of the complex [ZrO(L3)2Cl]
Cl•H2O is given as an example in (Scheme S1), (Figure 2).
The molecular ion peak [a] appeared at m/z = 654 (20%)
it loss C16H20N2 to give fragment [b] at m/z = 414 (10.2%),
then molecular ion peak [b] loss C2H4O to give [c] at
m/z = 370 (5.2%) and molecular ion peak [c] loss C2H4O
to give [d] at m/z = 326 (57.8%). Then a molecular ion peak
[a] losses C19H25N2O to give [E] at m/z = 357 (9%).
3.7 | Antimicrobial efficiency
In this experiment, the antimicrobial potency of the
free ligands (L1, L2, L3) and their complexes, this stud-
ies were carried out on, E. Coli ATCC11229, Coliform
ATCC8729, S. aureus ATCC6538, and Salmonella typhi
ATCC14028 and antifungal screening was studied
against two species, Aspergillus niger and Pencillum
expansum, and detected by measuring size of the inhi-
bitions zone (Table 5) according to the results of the
antimicrobial study of the three ligands and their metal
complexes have inhibitory action against all types of
organism (Figure 5).
SCHEME 3 Fragmentation pattern of L1
lose N (CH3)2 to give [b] at m/z = 185 (99%), Then a molec-
ular ion peak [b] lossed C6H4 to give [c] at m/z = 109 (7%),
molecular ion peak [c] loss CH3O to give fragment [d] at
The Zr(IV) – (L1)2 complex showed a significant dif-
ference against E. Coli ATCC11229 than its free ligand.
SCHEME 4 Fragmentation pattern of
[Zr (L1)2ɑ]ɑ•H2O

12 of 16
EL‐SHWINIY ET AL.
TABLE 5 The inhibitation diameter zone values (mm) for L1, L2, L3 and their complexes
Microbial species
Bacteria
fungi
Salmonella typhi A.niger
Compounds
E. coli
Coliform
S. aureus
P.expansum
L1
9.3+1 0.67 9.3+1 0.88
29+3 2.2
9.3+1 0.91
21+3 2.4
9.3+1 1.1
15+2 1.1
12.6+1 1.5
20.6+3 2.6
00
NA
NA
18+2 1.6
L1/Zr (IV)
L2
28+3 2.7
15+1 1.2
22+2 25
14+1 1.3
22+2 2.1
00
15.3+2 1.3
7.4+1 0.8
14+2 1.3
9.3+1 0.56
12+1 1.1
00
NA
NA
21+2 2.5
26+3 2.2
15+1 1.1
30.3+3 2.6
00
11.3+1 0.85 15.3+1 0.78
L2/Zr (IV)
L3
NA
NA
NA
NA
00
NA
L3/Zr (IV)
ZrOCl2.8H2O
Control (DMF)
Standard Nystain
20+3 1.9
00
00
00
00
00
00
00
00
00
00
00
00
00
19 1.1
00
00
00
00
00
11 1.2
00
00
00
00
Fluconazole
Amoxycillin/Clavulanic
Cetaxime
00
00
00
17 1.2
00
14 0.96
00
Statistical significance PNS – P not significant, P > 0.05; P+1 – P significant, P < 0.05; P+2 – P highly significant, P < 0.01; P+3 – P very highly significant,
P > 0.001; Student's t‐test (Paired).
complex of Zr (IV) – (L1)2 showed a significant difference
that showed the highly results followed by complex Zr(IV)
– (L3)2, then complex Zr(IV) – (L2)2,. So that the results
ensured that, the three ligands recoding lower results than
its complexes. The effect of different ligands and other
complexes on the two testes fungal strains, A. niger
recorded that Zr(IV) – (L3)2 showed a significant differ-
ence the highly results while the result of free its ligand
showed result less than its complex. Others showed no
any activity against tested fungi. The activity of different
ligands and other complexes on P. expansum showed the
highest broad spectrum of activity on L1 followed by L2.
Antimicrbial potency of standared antibiotics (AMC,
CTX, NS, FU). The AMC mixture and NS recorded a less
FIGURE 5 Statistical representation for biological activity of L1,
L2, L3 and their metal complexes
inhibitory activity than the synthesis ligands and its com-
plexes on the tested microorganisms.
Finally, bacterial strains showed a varied response to
While the Zr(IV) – (L2)2 and Zr(IV) – (L3)2 chelates
recorded the same result (22 mm) with the same strain
and the free ligand achieved the lower result than their
complexes. For Coliform ATCC8729 showed that highly
significant for the complex of Zr(IV) – (L1)2 than its
ligand. The complexes of other ligands Zr(IV) – (L2)2
and Zr(IV) – (L3)2 represented high results compared to
other ligands respectively. Gram‐positive bacteria S.
aureus ATCC6538 recorded the best result with the
complex of Zr(IV) – (L3)2 recording (30) followed by L1
that recording (29) although its complex recording nega-
tive result for this strain while the complexes for Zr(IV),
for L2 obtained result higher its ligand. Salmonella typhi
ATCC14028, that represent gram‐negative bacteria, The
the three free ligands and its complexes antimicrobial
activity but the results ensured that the highly activity
of the complexes better than its free ligands. The two fun-
gal strains more resistance than bacterial strains on the
synthesis ligands and its complexes.[39,40]
3.8 | Determination of MIC for the most
sensitive organisms
The antimicrobial potency of the synthetic ligands and
their complexes were determined against the most sensi-
tive bacteria and fungi (Table (6A‐6B‐6C‐6D) and
Figure 6). The lowest MIC for E. coli against the ligands
and their complexes recorded that L3 and its complex at

EL‐SHWINIY ET AL.
13 of 16
concentration 0.02 mg/100 ml followed by L2 at conc.
0.05 mg/100 ml then the complex Zr(IV) for L1 at conc.
0.07 mg/100 ml. Finally, L1 and the complex of Zr(IV)
for L2 recorded MIC at the conc. 0.1 mg/ 100 ml. The low-
est MIC for Coliform against the ligands and their com-
plexes recorded that L2 and their complexes at
concentration 0.02 mg/100 ml then followed by the com-
plex of Zr(IV) for L1 at conc. 0.05 mg/100 ml while the
complex of Zr(IV) for L3 at conc. 0.07 mg/100 ml recorded
the best MIC. Finally, L1 recorded MIC at the conc.
0.1 mg/100 ml. The MIC for Salmonella typhi showed
that, the best results of ligands and their complexes L3
and their complex also the complexe of Zr(IV) for L2 at
conc. 0.02 mg/100 ml. On the other hand, the ligands L1
and L2 recorded the MIC at conc. 0.07 mg/ 100 ml while
the complex of Zr(IV) for L1 showed the MIC at
0.1 mg/100 ml. The determination of MIC for S. aureus
recorded the lowest conc. 0.02 mg/ 100 ml for the complex
Zr(IV) for L2 while the Ligand (L3) and their complexes
showed the MIC at conc. 0.07 mg/100 ml. Other ligands
as L1 and L2 recorded MIC at 0.1 mg/100 ml while the
complex of Zr(IV) for L1 shows no activity for S. aureus.
Data in Table (6E‐6F) and Figure 7 showed that
the lowest MIC for the two tested strains at conc.
0.02 mg/100 ml at the L2 then Zr(IV) for L3 at conc.
0.02 mg/100 ml. The ligand L1, its complex, L3 and
the complex of Zr(IV) for L2 showed no activity
against the tested strains. These results ensured that
the activity of synthetic ligands and their complexes
TABLE 6C Of One‐way ANOVA: S. aureus versus MIC
Compounds
Grouping Information Using the Fisher LSD Method
Compounds
N
Mean
Grouping
Zr (IV)‐ L2
3
3
3
3
3
3
0.02
0.07
0.07
0.10
0.10
0.00
A
B
B
C
C
D
L3
Zr (IV)‐ L3
L1
L2
Zr (IV)‐ L1
Means that do not share a letter are significantly different
Fisher 95% Simultaneous Confidence Intervals
TABLE 6D of One‐way ANOVA: Salm. typhi versus MIC
Compounds
TABLE 6A Of One‐way ANOVA: E. coli versus MIC Compounds
Grouping Information Using the Fisher LSD Method
Grouping Information Using the Fisher LSD Method
Compounds
N
Mean
Grouping
Compounds
N
Mean
Grouping
L1
3
3
3
3
3
3
0.02
0.02
0.02
0.02
0.07
0.10
A
A
A
A
B
L3
3
3
3
3
3
3
0.02
0.02
0.05
0.07
0.10
0.10
A
A
B
B
C
C
Zr (IV)‐ L2
L3
Zr (IV)‐ L3
L2
Zr (IV)‐ L3
L2
Zr (IV)‐ L1
L1
Zr (IV)‐ L1
C
Zr (IV)‐ L2
Means that do not share a letter are significantly different
Fisher 95% Simultaneous Confidence Intervals
Means that do not share a letter are significantly different
Fisher 95% Simultaneous Confidence Intervals
TABLE 6B Of One‐way ANOVA: Coliform versus MIC
Compounds
Grouping Information Using the Fisher LSD Method
Compounds
N
Mean
Grouping
Zr (IV)‐ L1
3
3
3
3
3
3
0.02
0.02
0.05
0.05
0.07
0.10
A
A
B
B
C
D
Zr (IV)‐ L2
L3
Zr (IV)‐ L3
L2
L1
Means that do not share a letter are significantly different
Fisher 95% Simultaneous Confidence Intervals
FIGURE 6 MIC for the most sensitive bacteria of L1, L2, L3 and
their complexes

14 of 16
EL‐SHWINIY ET AL.
on the pathogenic bacteria and fungi and showed the
most sensitive pathogens dedicated the minimum inhibi-
tory concentration (MIC).
3.9 | Cytotoxic activity
The in vitro growth inhibitory activity of the prepared
compounds was tested using crystal violet colorimetric
viability assay (Doxorubicin standard drugs). Generated
data were carried to plot a dose–response curve, which
the concentration of prepared compounds required to kill
50% of cell population (IC50) had measured and the
results showed that all the tested compounds have inhib-
itory activity in a tumor cell lines in a concentration
dependent manner. Cytotoxic activity was referring to
the mean IC50 of three independent experiments. The
results are shown in Table 7 and Figure 8 showing that
TABLE 6E Of One‐way ANOVA: A.niger versus MIC
Compounds
Grouping Information Using the Fisher LSD Method
Compounds
N
Mean
Grouping
L2
3
3
3
3
3
3
8.00
10.00
0.00
0.00
0.00
0.00
B
C
D
D
D
D
Zr (IV)‐ L3
L3
Zr (IV)‐ L2
Zr (IV)‐ L1
L1
TABLE 7 The in vitro inhibitory activity of free three ligands and
their metal complexes against tumor cell line expressed as IC50
values (μg/ml) standard deviation from six replicates
Means that do not share a letter are significantly different
Fisher 95% Simultaneous Confidence Intervals
Tumor cell lines
Tested compounds
HCT‐116
S.D. ( )
TABLE 6F Of One‐way ANOVA: P.expansum versus MIC
Compounds
L1
148.0
53.2
110.0
46.9
60.8
28.3
0.46
3.9
0.6
0.7
1.1
0.2
0.2
0.4
0.1
0.1
[ZrO (L1)2Cl]Cl•H2O
L2
Grouping Information Using the Fisher LSD Method
Compounds
N
Mean
Grouping
[ZrO (L2)2Cl]Cl•H2O
L3
L1
3
3
3
3
3
3
8.0
7.0
0.0
0.0
0.0
0.0
A
A
B
B
B
B
L2
[ZrO (L3)2Cl]Cl•H2O
Doxorubicin standard
5‐Flurouracil standard
Zr (IV)‐ L1
Zr (IV)‐ L2
L3
Zr (IV)‐ L3
Means that do not share a letter are significantly different
Fisher 95% Simultaneous Confidence Intervals
FIGURE 8 The dose response curve showing the in vitro
inhibitory activity of free three ligands and its metal complexes
against human colon carcinoma (HCT‐116) cell line
FIGURE 7 MIC for the most sensitive fungi of L1, L2, L3 and
their complexes

EL‐SHWINIY ET AL.
15 of 16
[2] G. Meaza, F. Bettarini, L. P. Porta, P. Piccardi, E. Signorini, D.
free three ligand (L1, L2 and L3), the parent compound
showed inhibitory activities with IC50 values of 148.0,
110.0 and 60.8 μg/ml against colon cell line, respectively.
The tested compounds showed high inhibitory activities
against a human colon carcinoma (HCT‐116) cell line.
[ZrO(L3)2Cl]Cl•H2O was the most active against HCT‐
116 followed by [ZrO(L2)2Cl]Cl•H2O and [ZrO(L1)2Cl]
Cl•H2O with IC50 values 28.3, 46.9 and 53.2 μg/ml,
respectively.
Portoso, L. Fornara, Pest Manag. Sci. 2004, 60, 1178.
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The preparation and characterization of three novel com-
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This research holds no conflict of interest and is not
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How to cite this article: El‐Shwiniy WH, Shehab
WS, Mohamed SF, Ibrahium HG. Synthesis and
cytotoxic evaluation of some substituted pyrazole
zirconium (IV) complexes and their biological
assay. Appl Organometal Chem. 2018;e4503.
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