Transition metal complexes derived from N′-(4-fluorobenzylidene)-2-(quinolin-2-yloxy) acetohydrazide: Synthesis, structural characterization, and biocidal evaluation

Article abstract of DOI:10.1002/aoc.5898

Mononuclear Mn²⁺ and Cu²⁺, - VO²⁺, Co²⁺, Ni²⁺, - and Zn²⁺ complexes of a synthetic novel hydrazone containing a quinoline moiety were prepared. The composition and structure of the prepared

Full text of DOI:10.1002/aoc.5898

Received: 8 March 2020
DOI: 10.1002/aoc.5898
Revised: 25 May 2020
Accepted: 26 May 2020
F U L L P A P E R
Transition metal complexes derived from
N0-(4-fluorobenzylidene)-2-(quinolin-2-yloxy)
acetohydrazide: Synthesis, structural characterization, and
biocidal evaluation
Fathy A. El-saied1
Adel M.E. Shakdofa1
| Mohamad M.E. Shakdofa2,3
| Ahmed N. Al-Hakimi4,5
|
1Department of Chemistry, Faculty of
Science, Menoufia University, Shebin
El-Kom, Egypt
2Department of Chemistry, College of
Science and Arts, Khulais, University of
Jeddah, Saudi Arabia
3Inorganic Chemistry Department,
National Research Centre, P.O. 12622,
El-Bohouth St., Dokki, Cairo, Egypt
4Department of Chemistry, College of
Science, Qassim University, Saudi Arabia
Mononuclear Mn2+ and Cu2+, - VO2+, Co2+, Ni2+, - and Zn2+ complexes of a
synthetic novel hydrazone containing a quinoline moiety were prepared. The
composition and structure of the prepared compounds were elucidated by
spectral and analytical techniques. The results reveal that all complexes were
formed in 1:1 mole ratio except Mn2+ and Cu2+ complexes (3) and (7), which
were formed in 1 M:2 L mole ratio. It was also found that the ligand binds the
metal ions via NO donor sites as a monobasic bidentate chelator in all com-
plexes through the enolic carbonyl oxygen and azomethine nitrogen atoms.
The electronic absorption spectra and magnetic moment data demonstrated
square pyramidal and octahedral geometries for the VO2+ and Ni2+ complexes,
respectively, while the other complexes adopted tetrahedral geometry. The
thermal decomposition of the complexes was discussed in relation to structure.
The thermal analysis data demonstrated that all complexes were decomposed
in one, two, three or four stages starting with the dehydration process, removal
of coordination water molecules or elimination of anions and ended with the
formation of the metal oxide. The bactericidal activities of the prepared
compounds demonstrated that hydrazone (1) exerted a highly inhibitory effect
against B. subtilis while VO2+, Co2+, and Cu2+ complexes (2), (4), and (7)
showed an inhibitory effect against E. coli more than the tetracycline.
Additionally, the inhibitory effect of the prepared compound against A. niger
showed that the Cu2+ complex (6) is the most active while the Ni2+, Cu2+, and
Zn2+ complexes (5–8) exhibited an extremely inhibitory effect against
C. albicans.
5Department of Chemistry, Faculty of
Science, Ibb University, Ibb, Yemen
Correspondence
Prof. Mohamad M. E. Shakdofa, Inorganic
Chemistry Department, National
Research Centre, P.O. 12622, El-Bohouth
St., Dokki. Cairo, Egypt.
Email: mshakdofa@gmail.com
K E Y W O R D S
acetohydrazide, biocidal activities, complexes, hydrazone, quinoline
Appl Organomet Chem. 2020;e5898.
wileyonlinelibrary.com/journal/aoc
© 2020 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.5898

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EL-SAIED ET AL.
1 | INTRODUCTION
was synthesized according to a published method.[43] The
purity of the prepared compounds was confirmed by
thin-layer chromatography.
One of the most extensively studied objectives in
medicinal chemistry is the development of powerful and
effective medicinal drugs. The derivatives of quinoline
and hydrazone constitute significant categories of
compounds that have found multiple applications in
therapeutic chemistry because of their wide range of
pharmacokinetic properties,[1–3] especially their promi-
nence in drug discovery programs.[4,5] The derivatives of
quinoline and hydrazone and their complexes have been
2.2 | Physical measurements
The elemental analysis (C, H, N) of hydrazone (1) and its
metal complexes was carried out in the Micro-Analytical
Laboratory, Cairo University, Egypt. The metal and
chloride ion content was analyzed using standard
analytical methods.[44,45] Infrared spectra of the
hydrazone and its metal complexes were measured in
the 400–4,000 cm−1 range with the KBr disc technique
on a Perkin–Elmer 1430 infrared spectrophotometer,
Beaconsfield. Beaconsfield, England. The electronic
absorption spectra in the 200–1,100 nm region were
recorded using 1-cm quartz cells using dimethyl sulfoxide
(DMSO) as a solvent. on a Shmadzu 2600 spectrophotom-
eter, Kyoto, Japan. A Jeol JMS-AX-500 mass spectrome-
ter, AKISHIMA, TOKYO, Japan, was used to record the
mass spectrum. A Jeol EX-270 MHz FT-NMR spectrome-
ter was used to measure the NMR spectra in deuterated
DMSO (DMSO-d6) as a solvent. A Perkin–Elmer 7 Series
thermal analyzer was used to carry out the thermal
analysis (TG) from room temperature to 1,000ꢀC at a
heating rate of 10ꢀC/min. A Gouy Matthey balance was
used to measure the magnetic susceptibilities at 25ꢀC
and the magnetic susceptibilities were calculated by a
published equation.[46] Diamagnetic corrections were
estimated from Pascal's constant.[47] A Tacussel-type
CD6NG conductivity bridge was used to record the
molar conductivity of 10−3 M solutions (dimethyl
formamide, DMF). The resistance was measured in ohms
and the molar conductivities were calculated using the
published equation.[48]
reported to demonstrate
a widespread spectrum of
biological properties,[6–8] such as antimicrobial,[9–11] anti-
bacterial,[12–14] antifungal,[15,16] antiviral,[17] antiplatelet[18]
antimalarial,[19] antitubercular, antimycobacterial,[20,21]
anticancer,[21–24] antianalgesic, anticonvulsant,[25] and
antileishmanial,[26,27] The hydrazones and their metal
complexes also have anti-uropathogenic,[28] anti-
arthritic,[29] antiproliferative,[30] and antioxidant[31–33]
properties and act as inhibitors for COX-2,[22] potent
antiangiogenic agents in atherosclerosis,[31] and potent
immunomodulatory agents.[34] They play a role in the
treatment of Alzheimer's disease[35,36] and inhibit the
corrosion of mild steel in acidic media.[37] They are also
used in the detection of some ions[38,39] and as colorimet-
ric chemosensors for expeditious detection of CN− in
aqueous media,[40] as well acting as a catalyst in several
reactions.[41,42] Because of the broad applications of quin-
oline and acetohydrazide derivatives, this study aimed to
synthesize mononuclear Mn2+ and Cu2+, and binuclear
VO2+, Co2+, Ni2+, Cu2+, and Zn2+ complexes with a new
chelator,
N0-(4-fluorobenzylidene)-2-(quinolin-2-yloxy)
acetohydrazide. The coordination behavior of the
hydrazone (1). The structure of the prepared compounds
was investigated by spectral and analytical techniques
such as infrared, nuclear magnetic resonance (NMR),
and mass and electronic absorption spectra as well as ele-
mental and thermal analyses in addition to the magnetic
and molar conductance measurements for complexes.
The work was extended to investigate the in vitro bacteri-
cidal and fungicidal activities of the prepared compounds
toward bacterial strains E. coli and B. subtilis as well as
fungal strain A. niger and yeast C. albicans by the agar
well diffusion method.
2.3 | Synthesis of ligand HL
N0-(4-fluorobenzylidene)-2-(quinolin-8-yloxy) acetohydra-
zide (HL) was synthesized by refluxing equimolar quanti-
ties of 4-fluorobenzaldehyde (124 mg, 1.0 mmol in 20 ml
of ethanol) with 2-(quinolin-8-yloxy) acetohydrazide
(217 mg, 1.0 mmol in 20 ml of ethanol) for 4 hr (Scheme
1). The solid product was filtered off, washed with cold
ethanol, crystallized from ethanol, and finally dried
under vacuum over P4O10. Yield 79%, m.p. 204ꢀC; buff
color. Anal. calcd for C18H14N3O2F (Formula Weight
323.32 g/mol): C 66.87, H 4.36, N 12.78; found: C 67.23,
H 4.32, N 13.00. IR (KBr, cm−1): 3,195 ν(NH), 1,682
ν(C=O), 1,604 ν(C=N), 1,598 ν(C=Nring), 1,289 ν(C–O),
1,093 ν(O–C–O), 1,015 ν(N–N), 818 ν(quinoline). 1H
2 | EXPERIMENTAL
2.1 | Materials
All the reagents used in the synthesis of the titled ligand
and its complexes were synthetic grade and used without
further purification. 2-(quinolin-8-yloxy) acetohydrazide

EL-SAIED ET AL.
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824 ν(quinoline), 534 ν(V–O), 498 ν(V N), 954 ν(V=O),
UV–Vis (1 cm quartz cell, DMF): 267, 300, 335, 390,
495, 549, 1,096 nm.
2.4.2 | Complex (3)
Yield 60%, m.p. >300ꢀC, violet. ΛM = 13.4 ohm−1cm2mol−1
,
μeff = 5.73 BM. Anal. calcd for [Mn(L)(CH3COO)
(H2O)].2H2O, C20H22N3O7Mn (FW 490.35 g/mol): C
48.35, H 4.49, N 8.57, Mn 11.20; found: C 48.59, H 4.52, N
8.23, Mn 10.99. IR (KBr, cm−1): 1,602 ν(C=N), 1,572
ν(C=Nring), 1,375 ν(C–O), 1,103 ν(O–C–O), 1,030 ν(N–N),
824 ν(quinoline), 533 ν(Mn–O), 516 ν(Mn N), 1,554,
1,377 (Δ = 177) νsCH3COO, νasCH3COO, UV. vis. (1 cm
quartz cell, DMF) 277, 305, 331, 393, 507, 600 nm.
SCHEME 1 Preparation of hydrazone ligand (1)
NMR data (270 MHz, δ ppm DMSO-d6): 13.07 (1H, s,
OH), 9.82 (1H, s, NH), 8.84 (1H, s, N–CH), 7.06–8.32
(10H, m, aromatic protons), 3.38 (2H, s, O–CH2). 13C
NMR data (60 MHz, DMSO-d6): 122.34 (1C), 148.65
(2C–N), 136.58 (4C=N), 128.02 (5C), 132.67 (6C), 153.83
(7C–O), 116.02 (8C), 127.89 (9C), 118.24 (10C), 111.82
(12C), 166.94,166.43 (13C=O, 13C–OH,), 138.99 (17C=N),
129.32 (18C), 132.59 (19&23C), 116.21 (20&22C), 164.44
(21C–F). MS m/z: 323, 304, 229, 202, 186, 158, 145, 129.
UV–Vis (1 cm quartz cell, DMF): 271, 295, 305, 329 nm.
2.4.3 | Complex (4)
Yield 60%, m.p. >300ꢀC, violet. ΛM = 3.3 ohm−1cm2mol−1
,
μeff = 3.83 BM. Anal. calcd for [Co(L)2], C36H26N6O6F2Co
(FW 703.57 g/mol): C 61.11, H 3.89, N 11.95, Co 8.01;
found: C 61.46, H 3.72, N 11.70, Co 8.09. IR (KBr, cm−1):
1,577 ν(C=N), 1,543 ν(C=Nring), 1,380 ν(C–O), 1,108
ν(O–C–O), 1,032 ν(N–N), 825 ν(quinoline), 505 ν(Co–O),
446 ν(Co N), UV–Vis (1 cm quartz cell, DMF): 271, 323,
340, 408, 620, 1,082 nm.
2.4 | Synthesis of metal complexes
Complexes (2), (4–6), and (8) were synthesized by
refluxing a hot ethanolic solution of the hydrazone
(1) (646 mg 2 mmol, 30 ml of ethanol) with a
suitable amount of
a hot ethanolic solution of
VOSO4ꢁ2H2O, Co(CH3COO)2ꢁ6H2O, Ni(CH3COO)2ꢁ6H2O,
Cu(CH3COO)2ꢁ2H2O, or Zn(CH3COO)2ꢁ2H2O (1 mmol,
in 30 ml of ethanol) for 4 hr. The colored products were
filtered off, washed with ethanol then by diethyl ether,
and dried in a vacuum desiccator over P4O10. The metal
complexes (3) and (7) were synthesized by refluxing a hot
ethanoic solution of the ligand (323.3 mg 1 mmol, 30 ml
of ethanol) with a suitable amount of a hot ethanoic
solution of Mn(CH3COO)2ꢁ4H2O or CuCl2.2H2O (1 mmol
in 30 ml of ethanol) for 4 hr. The colored products were
filtered off, washed with ethanol then by diethyl ether,
and dried in a vacuum desiccator over P4O10.
2.4.4 | Complex (5)
Yield 72%, m.p. >300ꢀC, green. ΛM = 7.5 ohm−1cm2mol−1
μeff 2.73 BM. Anal. calcd for [Ni(L)2(H2O)2],
,
=
C36H30N6O6F2Ni (FW 739.3 6g/mol): C 59.46, H 3.96, N
11.73, Ni 7.94; found: C 58.98, H 4.09, N 11.46, Ni
7.66. IR (KBr, cm−1): 1,578 ν(C=N), 1,556 ν(C=Nring),
1,382 ν(C–O), 1,110 ν(O–C–O), 1,032 ν(N–N),
821 ν(quinoline), 502 ν(Ni–O), 456 ν(Ni N), UV–Vis
(1 cm quartz cell, DMF): 272, 315, 338, 347, 394, 500,
620, 1,020 nm.
2.4.5 | Complex (6)
2.4.1 | Complex 2
Yield 58%, m.p. >300ꢀC, green. ΛM = 5.7 ohm−1cm2mol−1
μeff 2.01 BM. Anal. calcd for [Cu(L)2].5H2O,
,
Yield 49%, m.p. >300ꢀC, green. ΛM (molar conductivity) =
9.5 ohm−1cm2mol−1, μeff = 1.76 BM (Bohr Magneton).
Anal. calcd for [VO(L)2 (H2O)].3H2O, C36H32N6O8F2V
(Formula weight [FW] 783.64 g/mol): C 55.18, H
4.85, N 10.72, V 6.50; found: C 55.48, H 4.81, N
11.05, V 6.21. IR (KBr, cm−1): 1,601 ν(C=N), 1,574
ν(C=Nring), 1,373 ν(C–O), 1,104 ν(O–C–O), 1,044 ν(N–N),
=
C36H36N6O9F2Cu (FW 798.26g/mol): C 54.17, H 4.55, N
10.53, Cu 7.96; found: C 54.20, H 4.86, N 10.21, Cu 7.56.
IR (KBr, cm−1): 1,597 ν(C=N), 1,573 ν(C=Nring), 1,378
ν(C–O), 1,110 ν(O–C–O), 1,032 ν(N–N), 828 ν(quinoline),
522 ν(Cu–O), 476 ν(Cu N). UV–Vis (1 cm quartz cell,
DMF) 275, 322, 338, 413,578, 1,090 nm.

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2.4.6 | Complex (7)
USA) was used for the bacteria while nystatin (Sigma)
was used for the fungal as well as yeast strains. A nega-
tive control (DMSO, 2% v/v) was also included to com-
pare the activity. The appearance of zones of inhibition
was regarded as positive for the presence of antimicrobial
action in the test substance. Subsequently, each value
was the average of three independent replicates and the
activity index for the complexes was calculated by follow-
Yield 65%, m.p. >300ꢀC, green. ΛM = 17.5 ohm−1cm2mol−1
,
μeff
= 2.17 BM. Anal. calcd for [Cu(L)(H2O)Cl],
C18H15N3O3FCuCl (FW 439.33 g/mol): C 49.21, H 3.44, N
9.56, Cu 14.46, Cl 8.07; found: C 49.52, H 3.89, N 9.80, Cu
13.99, Cl 7.78. IR (KBr, cm−1): 1,597 ν(C=N), 1,576
ν(C=Nring), 1,377 ν(C–O), 1,111 ν(O–C–O), 1,033 ν(N–N),
822 ν(quinoline), 563 ν(Cu–O), 520 ν(Cu N), UV–Vis
(1 cm quartz cell, DMF): 271, 321, 338, 416,
590, 1,086 nm.
ing formula[51]
:
diameter of inhibition zone for test compound
diameter of inhibition zone for standard
activity index =
× 100
2.4.7 | Complex (8)
Yield 50%, m.p. >300ꢀC, white. ΛM = 9.3 ohm−1cm2mol−1
μeff dia. Anal. calcd for [Zn(L)2(H2O)2].H2O,
,
3 | RESULTS AND DISCUSSION
=
C36H32N6O7F2Zn (FW 764.06 g/mol): C 56.62, H 4.00, N
11.00, Zn 8.56; found: C 56.59, H 4.22, N 10.67, Zn 8.16.
IR (KBr, cm−1): 1,606 ν(C=N), 1,578 ν(C=Nring), 1,382
ν(C–O), 1,109 ν(O–C–O), 1,036 ν(N–N), 825 ν(quinoline),
The reaction of 4-fluorobenzaldehyde with 2-(quinolin-
8-yloxy) acetohydrazide in molar ratio (1:1) gave the
ligand N0-(4-fluorobenzylidene)-2-(quinolin-8-yloxy) acet-
ohydrazide (HL) as shown in Scheme 1 . The chelation of
ligand with VO2+, Mn2+, Co2+, Ni2+, Cu2+, and Zn2+
metal salts in molar ratios 1 L:1 M or 2 L:1 M gave stable,
colored, and solid complexes (2–8), which are soluble in
both DMF and DMSO. Physical, elemental, thermal,
spectral, and biological measurements are given in the
Section 2 and Supporting Information Table S1. The ana-
lytical data agree with the presumed structure shown in
Figures 1 and 2, and show that all complexes except
Mn2+ and Cu2+ complexes (3) and (7) were formed in
1 M:2 L molar ratio, while complexes (3) and (7) were
formed in 1 M: 1 L molar ratio. The molar conductivity
values for the complexes are in the range 3.1–17.5
ohm−1cm2mol−1, that is within the expected range for
nonelectrolytes complexes (1–35 ohm−1cm2mol−1).[52]
1
531 ν(Zn–O), 500 ν(Zn N). H NMR (270 MHz, δ ppm
DMSO-d6): 8.89 (1H, s, N=C-H), 6.83–8.70 (10H, m, aro-
matic protons), 3.18 (2H, s, O–CH2). UV–Vis (1 cm quartz
cell, DMF) 271, 324, 340, 395 nm.
2.5 | Biocidal activities
The assessment of the antimicrobial activities of all com-
pounds (1–8) were tested against different strains of
gram-positive and gram-negative bacteria as well as fun-
gal and yeast strains by the agar well diffusion
method.[49,50] The tested strains were Escherichia coli,
Bacillus subtilis, Aspergillus niger and Candida albicans.
The bacteria and filamentous fungi were cultured on
Mueller–Hinton agar medium and Czapek Dox's agar
(CDA) medium, respectively, at pH 7.4. The agar plates
were incubated at 37ꢀC for 24 hr (bacteria) and at 28ꢀC
for 4 days (fungi). The yeast C. albicans was grown in
yeast peptone dextrose (YPD) agar at 30ꢀC to test the
activity of the tested compound. Tetracycline (Sigma,
3.1 | NMR spectrum of hydrazone 1
1
The H NMR for N0-(4-fluorobenzylidene)-2-(quinolin-
8-yloxy) acetohydrazide was measured in DMSO-d6
(Figure 3). It displayed two signals at δ = 13.07 and
9.82 ppm. The first signal could be assigned to the
hydroxyl proton of the enol form while the second signal
could be assigned to imine proton of the keto form. These
two singlets that looked at high values of δ may be due
FIGURE 1 Structures of VO2+, Co2+, Ni2+, Cu2+, and Zn2+
complexes 2, 4–6, and 8
FIGURE 2 Structures of Mn2+ and Cu2+ complexes 3 and 7

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FIGURE 3 The 1H NMR spectrum of hydrazone 1
the attachment of the proton to electro-negative atoms
(O or N). This was confirmed by the disappearance of
these signals in the spectrum with D2O (Supporting
Information Figure S2). This finding demonstrates that
hydrazone 1 is present in keto-enol tautomerization
(Supporting Information Figure S3). The proton of the
azomethine group H–17C=N was seen as a singlet at
δ = 8.84 ppm while the aromatic protons can be observed
in the 7.06–8.32 ppm range. The signal characteristic for
the methylene (O–CH2) group appeared as a singlet at
3.38 ppm. The 1H NMR for the Zn2+ complex
(Supporting Information Figure S4) shows that the
proton of the amide group CO–NH is missed referring to
the bonding of the acetohydrazide 1 with the Zn2+ ion in
its enolic form. The 13C NMR spectrum of hydrazone
1 (Figure 4) has two consecutive singlets at 166.94 and
166.43 ppm, which could be ascribed to the carbon atoms
of the ketonic and enolic carbonyl groups (13C=O and
13C–OH). The signal for the carbon attached to the fluo-
rine atom (21C–F) was observed at 164.44 ppm. Signals
FIGURE 4 The 13C NMR
spectrum of hydrazone (1)

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for the carbon atoms attached to the etheric oxygen atom
(7C–O–C12) were seen at 153.83 and 111.82 ppm, respec-
tively.[28] The chemical shift for the azomethine carbon
atom (17C=N) was seen at 138.99 ppm. The other
quinolin-8-yloxy carbon atoms (1C, 2C, 4C, 5C, 6C, 7C, 8C,
9C, and 10C)-were observed at 122.34, 148.65, 136.58,
128.02, 132.67, 116.02, 127.89, and 118.24 ppm, respec-
tively, consistent with Alodeani et al.[28] The aromatic
carbons of the phenyl moiety were seen at 129.32, 132.59,
and 116.21 ppm.
hydrazone (1) has
a
very broad band in the
3,450–2,565 cm−1 region with weak bands at 3405 and
3200 which could be assigned to the hydroxyl and imine
groups of the enolic and ketonic forms participating in
intramolecular and intermolecular hydrogen bonding
(C=O … H–N and C–O–H … N).[53] The very intense
bands at 1683, 1604, 1,289, 1,093, and 1,015 cm−1 were
assigned to the carbonyl ν(C=O)[28] and azomethine
ν(C=N) groups,[54,55] and to the enolic ν(C–OH), ether
ν(O–C–O),[56] and ν(N–N)[53] linkages, respectively. The
coordination mode of the ligand was found by comparing
the IR spectral data of complexes with that of the free
hydrazone (1). This comparison shows that acet-
ohydrazide 1 acts as a monobasic bidentate chelator in all
the complexes. It binds to metal ions via azomethine
nitrogen and enolic carbonyl oxygen atoms. This mode of
bonding was confirmed by the following indications:
(i) the disappearance of the bands for the carbonyl and
imine groups (NH), showing that the ligand chelated in
its enolic form, (ii) the appearance of new peaks at
1577–1606 and 1,375–1,383 cm−1 assigned to the conju-
gated system ν(C=N–N=C)[57] and the enolic carbonyl
group ν(C–O),[58] respectively, (iii) the presence of new
peaks in the 502–582 and 446–521 cm−1 regions for vari-
ous complexes may be imputed to the ν(M–O) and
ν(M N) consecutively. The new band at 954 cm−1 in the
spectrum for the VO2+ complex (2) was ascribed to
ν(V=O).[57] In the acetato complex (3), the two bands at
1554 and 1,377 cm−1 were assigned to νas(CO2−) and
νs(CO2−), respectively, demonstrating the contribution of
the acetate group to the chelation. The difference in
magnitude (Δ) between νas(CO2−) and νs(CO2−) was
177 cm−1, indicating that the acetate moiety was chelated
in a monodentate fashion.[59,60]
3.2 | Mass spectrum of acetohydrazide (1)
The mass spectrum of hydrazone (1) (Figure 5) had a
fragmentation pattern that agrees with the suggested
formula, with a molecular ion peak (m/z) equal to
323, which loses a fluoride ion to give fragment
A. Moreover, six other fragments could be observed. The
signal at m/z 229 corresponds to fragment B (loss of
the fluoro benzene moiety), m/z 202 is attributed to
fragment C (loss of N–CH2), m/z 186 corresponds to
fragment
D (loss of the amino group), leaving
2-(quinolin-8-yloxy)acetaldehyde and the base peak for
8-methoxyquinoline, fragment E, with m/z 158. There
are also two fragments at m/z 145 and 129, which can be
assigned fragments quinolin-8-ol (F) and quinoline (G),
respectively (Figure 5).
3.3 | Infrared spectra
The IR spectral data of hydrazone (1) and its complexes
(2-8) are shown in Section 2. The infrared spectrum for
FIGURE 5 The mass spectrum and fragmentation pattern of hydrazone 1

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3.4 | Electronic absorption spectra and
magnetic moment measurements
1,086–1,090 nm, which correspond to the transitions
2B2! E(ν1) and B2! A,2B1(ν2), respectively, which is
compatible with tetrahedral geometry around the Cu2+
ions (Figures 1 and 2).[63,70] These complexes have μeff
values of 2.01 and 2.17 BM range related to spin-only
value. The diamagnetic Zn2+ complex (8) has a d10 sys-
tem, so it does not exhibit d–d transitions.
2
2
2
The electronic absorption spectra (EAS) data for com-
pounds (1–8) in DMF are given in the Section 2, since
the data of magnetic moment for (2–7). In the spectrum
for the ligand, there are four peaks at 271, 295, 305, and
329 nm, which can be assigned to the π!π* and n!π*
transitions, respectively, in the aromatic moiety,
carbonyl, and azomethine groups.[61,62] In the EAS of
metal complexes the shift in the position of n–π* transi-
tions could be due to the chelation of carbonyl and
azomethine groups to the metal ion. The EAS for the
VO2+ complex has three peaks at 1080, 549, and
495 nm that can be assigned to the transitions
3.5 | Thermal analysis of complexes
The thermal analyses of the complexes (2–8) gave extra
insight into the suggested formulae and the thermal sta-
bility of the complexes under investigation. The thermal
data (Supporting Information Table S1) demonstrate that
the complexes decompose in one, two, three or four
phases and there is agreement in the weight loss
between the calculated and proposed formulae that
could be explained as follows. The first step is the dehy-
dration process for complexes (2), (3), (6), and (8),
which occurs in temperature range 50–105ꢀC, with mass
losses equal to 6.83%, 7.91%, 10.79%, and 2.30% (calcd
6.90%, 7.35%, 11.28%, and 2.36%), corresponding to
exclusion of three, two, five, and one hydrated water
molecule, respectively. The second step is the elimina-
tion of the coordination water molecules of complexes
(2), (3), (5), (7), and (8) which occurs in the temperature
range 90–140ꢀC, with weight losses equal to 2.45%,
3.60%, 5.01%, 3.87%, and 4.81% (calcd 2.30%, 3.67%,
4.87%, 4.10%, and 4.72%), corresponding to exclusion of
one or two coordinated water molecules. The third phase
is the removal of an acetate or chloride anion from com-
plexes (3) and (7), which occurs in the temperature
range from 150 to 245ꢀC, with weight losses equal to
12.20% and 8.11% (calcd 12.12% and 8.07%),
corresponding to the exclusion of one acetate and chlo-
ride ions. The last stage is the complete decomposition
of all complexes through the departure of the organic
part, which occurs in the temperature range 140–525ꢀC,
leaving the metal oxide, which can be confirmed from
the weight loss percentage (Supporting Information
Table S1).
3
2
2B2(dxy)! E1(dxz,dyz)(ν1), 2B2(dxy)! B1(dx2-y2)(ν2), and
2
2B2(dxy)! A1(dz2) (ν3), respectively. This spectrum illus-
trates that the VO2+ complex has square pyramidal
geometry (Figure 1).[63,64] The VO2+ complex has a mag-
netic moment (μeff) of 1.76 BM, which is compatible with
a spin-only value. The EAS for the Mn2+ complex has
weak peaks at 600 and 507 nm that can be attributed to
6A1g! T1g(4G)(υ1) and 6A1g! T2g(υ2) transitions, respec-
tively, which are well suited to tetrahedral geometry
around the Mn2+ ion (Figure 2). The third and fourth
4
4
6
4
4
6
4
bands for A1g! Eg(G), A1g(G)(v3), and A1g! T2g(D)
(v4) do not appear here because of the broaden of the
bands.[63,65] The Mn2+ complex had μeff equal to 5.73 BM,
consistent with five unpaired electrons system and close
to high spin Mn2+ ion (d5).[66] In a sphere of tetrahedral
4
4
symmetry of Co2+, the F ground state is split into A2,
4T2, and 4T1(F), and three spin-allowed transitions,
4
4
4
4A2! T2(v1), 4A2! T1(F)(v2), and 4A2! T1(P)(v3), are
anticipated. The EAS for the Co2+ complex (4) has two
peaks at 600 and 1,082 nm, assigned to transitions
4
4
4A2! T1(F)(v2) and 4A2! T1(P)(v3), respectively, indicat-
ing a tetrahedral Co2+ complex (Figure 1).[63,67] The third
4
4
band for A2! T2(v1) does not appear here because it is
buried beneath the high intensive CT peak.[63,68] The μeff
value of the Co2+ complex is 3.83 BM, corresponding to
three unpaired electrons and close to that of a high-spin
Co2+ ion (d7).[67] The EAS for the Ni2+ complex has three
peaks at 1020, 620, and 500 nm, corresponding to
3
3
3
3
the A2g(F) ! T2g(F)(ν1), A2g(F)! T1g(F)(v2), and
3A2g(F)! T1g(P)(ν3) transitions, respectively, and com-
3.6 | Bactericidal and fungicidal activities
3
patible with an octahedral geometry (Figure 1).[63,64,67]
The ν2/ν1 ratio is 1.65, which is close to the normal range
for an octahedral Ni2+ complex (1.5–1.75), demonstrating
that the Ni2+ complex has octahedral geometry.[67] The
μeff value for the Ni2+ complex is 2.73 BM, which is in
the range for d8 electronic configuration of Ni2+ com-
plexes in an octahedral field.[69] The EAS of the Cu2+
complexes (6 and 7) have two peaks at 578–590 and
The in vitro bactericidal and fungicidal activities of
hydrazone (1) and its complexes (2–8) were assessed by
the agar well diffusion method against bacterial species
E. coli and B. subtilis, and fungal species A. niger and
C. albicans. The inhibition zone (IZ, mm) and activity
index (AI, %) values of all compounds are listed in
Table 1. The microbicidal data show that the hydrazone

8 of 11
EL-SAIED ET AL.
TABLE 1 Antimicrobial activities of the ligand (1) and its complexes (2-8) against A. niger, C. albicans, E. coli and B. subtilis
A. niger
C. albicans
E. coli
B. subtilis
Compound.
IZ (mm)
AI (%)
IZ (mm)
AI (%)
IZ (mm)
AI (%)
IZ (mm)
AI (%)
DMSO
0
37
–
0
32
–
0
–
0
–
Nystatin
100
–
100
–
–
100
122
66
Tetracycline
35
35
40
28
36
15
30
40
20
100
100
114
80
41
50
27
30
22
18
33
32
18
Acetohydrazide (1)
VO2+ complex (2)
Mn2+ complex (3)
Co2+ complex (4)
Ni2+ complex (5)
Cu2+ complex (6)
Cu2+ complex (7)
Zn2+ complex (8)
15
24
25
25
26
42
35
28
41
68
68
68
70
114
95
76
14
15
31
25
50
41
43
33
47
47
97
73
78
103
43
54
156
128
134
103
44
86
80
114
57
78
44
(1) exerts medium activity against E. coli, A. niger, and
C. albicans with IZ = 14– 19 mm with AI = 41– 47%, and
exert excellent activity against B. subtilis with IZ = 50 mm
with AI = 122%. This activity may be related to the
existence of the heteroaromatic (quinoline) moiety and
the azomethine linkage. A comparative biostudy of
hydrazone (1) and its complexes showed that all com-
plexes demonstrate good biocidal effect compared with
the free acetohydrazide against A. niger, C. albicans, and
E. coli. The most bio-effective complex against A. niger is
the Cu2+ complex (6), with IZ = 42 mm and AI = 114%,
complexes (5–8) are effective against C. albicans with IZ
ranged from 33 to 50 mm and AI ranged from 103 to
156%, and the VO2+ and Co2+ complexes are effective
against E. coli with IZ = 40 and 36 mm, with AI =114%
and 103%, respectively. The other complexes showed
FIGURE 6 The order of the inhibition zones of the ligand (1) and its complexes (2-8) against A. niger, C. albicans, E. coli, and B. subtilis

EL-SAIED ET AL.
9 of 11
medium to good activity against the four species with
IZ in the 24–35 mm range, AI = 68– 95%, IZ in the
15–31 mm range, AI = 47– 97%, IZin the 15–30 mm
range, AI = 43– 86%, and IZ in the 18–33 mm range,
AI = 44- 80%. The order of compound activities is shown
in Figure 6. The enhancement of microbicide activity of
some complexes could be illustrated basing on the Over-
tone's concept and Tweedy's chelation theory.[71]
According to Overtone's concept of cell permeability, the
cell lipid membrane allows only the lipid-soluble sub-
stance to pass through it, which makes the lipo-solubility
a major factor controlling the microbicide effect. On che-
lation, the metal ion polarity would be lowered because
of the overlapping of its orbital with ligand orbitals and
partial sharing of the positive charge of the metal ion
with donor groups. Moreover, it enhances the π-electron
delocalization over the entire chelating ring and rein-
forces the lipophilicity of the complexes, which in turn
boosts their permeation into lipid membranes and blocks
the metal binding sites in the microorganism enzymes.
There are many reasons for the increased activity of the
complexes, such as their high solubility, the size of the
metal ion, hydrogen bond formation between the
azomethine group and the active cente of the cell compo-
nents which lead to the intervene with the normal cell
operations, discourage of ATP production and DNA
synthesis.[71–73]
E. coli. These biostudy data encourage us to prepare more
hydrazonehelators and their complexes to obtain new
bioactive compounds for treatment of systemic infections
with fewer side effects.
ORCID
Fathy A. El-saied https://orcid.org/0000-0002-4793-
4527
Mohamad M.E. Shakdofa https://orcid.org/0000-0003-
0399-1658
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How to cite this article: El-saied FA,
Shakdofa MME, Al-Hakimi AN, Shakdofa AME.
Transition metal complexes derived from N0-(4-
fluorobenzylidene)-2-(quinolin-2-yloxy)
acetohydrazide: Synthesis, structural
characterization, and biocidal evaluation. Appl
Organomet Chem. 2020;e5898. https://doi.org/10.
1002/aoc.5898
SUPPORTING INFORMATION
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