New Schiff bases of 2-(quinolin-8-yloxy)acetohydrazide and their Cu(ii), and Zn(ii) metal complexes: Their in vitro antimicrobial potentials and in silico physicochemical and pharmacokinetics properties

Article abstract of DOI:10.1515/chem-2020-0085

The purpose of this work was to prepare Schiff base ligands containing quinoline moiety and using them for preparing Cu(ii) and Zn(ii) complexes. Four bidentate Schiff base ligands (SL1-SL4) with quinoline hydrazine scaffold and a series of mononuclear Cu(ii) and Zn(ii) complexes were successfully prepared and characterized. The in vitro antibacterial and antifungal potential experimentation revealed that the ligands exhibited moderate antibacterial activity against the Gram-positive bacterial types and were inactive against the Gram-negative bacteria and the fungus strains. The metal complexes showed some enhancement in the activity against the Gram-positive bacterial strains and were inactive against the Gram-negative bacteria and the fungus strains similar to the parent ligands. The complex [Cu(SL1)2] was the most toxic compound against both Gram-positive S. aureus and E. faecalis bacteria. The in silico physicochemical investigation revealed that the ligand SL4 showed highest in silico absorption (82.61percent) and the two complexes [Cu(SL4)2] and [Zn(SL4)2] showed highest in silico absorption with 56.23percent for both compounds. The in silico pharmacokinetics predictions showed that the ligands have high gastrointestinal (GI) absorption and the complexes showed low GI absorption. The ligands showed a good bioavailability score of 0.55 where the complexes showed moderate to poor bioavailability.

Full text of DOI:10.1515/chem-2020-0085

Open Chemistry 2020; 18: 591–607
Research Article
Hanan A. Althobiti, Sami A. Zabin*
New Schiff bases of 2-(quinolin-8-yloxy)acetohydrazide
and their Cu(II), and Zn(II) metal complexes: their in vitro
antimicrobial potentials and in silico physicochemical
and pharmacokinetics properties
https://doi.org/10.1515/chem-2020-0085
received December 27, 2019; accepted April 18, 2020
1 Introduction
The chemical compounds containing azomethine group
called Schiff bases are an excellent class of ligands and
are widely used in coordination chemistry. These
chemicals have the ability to react with metal ions
producing versatile coordination metal complexes,
which have wide applications in different fields [1,2]. It
is well established in the literature that the presence of
the main functional azomethine group (–CH]N–) in the
structure of the Schiff bases is a characteristic feature of
these compounds and responsible for their various
Abstract: The purpose of this work was to prepare Schiff
base ligands containing quinoline moiety and using
them for preparing Cu(II) and Zn(II) complexes. Four
bidentate Schiff base ligands (SL1–SL4) with quinoline
hydrazine scaffold and a series of mononuclear Cu(II)
and Zn(II) complexes were successfully prepared and
characterized. The in vitro antibacterial and antifungal
potential experimentation revealed that the ligands
exhibited moderate antibacterial activity against the
Gram-positive bacterial types and were inactive against
biological potentials and medicinal actions [3,4].
the Gram-negative bacteria and the fungus strains. The
The Schiff bases containing heterocyclic systems
metal complexes showed some enhancement in the
have been a fertile area of research for a long period,
and there is a vast literature work on Schiff base
complexes comprising heterocyclic structures [5]. The
complexes derived from quinoline and quinoline deri-
activity against the Gram-positive bacterial strains and
were inactive against the Gram-negative bacteria and the
fungus strains similar to the parent ligands. The complex
[Cu(SL1)2] was the most toxic compound against both
vatives currently attracted the interest among the Schiff
Gram-positive S. aureus and E. faecalis bacteria. The
base ligands containing heterocyclic ring. The Schiff
in silico physicochemical investigation revealed that the
bases containing quinoline nucleus have more favored
ligand SL4 showed highest in silico absorption (82.61%)
attention mainly due to their potential applications in
and the two complexes [Cu(SL4)2] and [Zn(SL4)2] showed
the medicinal field [6–10].
highest in silico absorption with 56.23% for both
In view of the facts and the important features of
compounds. The in silico pharmacokinetics predictions
showed that the ligands have high gastrointestinal (GI)
absorption and the complexes showed low GI absorption.
The ligands showed a good bioavailability score of
0.55 where the complexes showed moderate to poor
bioavailability.
Schiff bases containing quinoline moiety as reported in
the literature, we encouraged and focused our investiga-
tion to design new ligand compounds with such struc-
tures. The suggested Schiff base ligands were derived
from 2-(quinolin-8-yloxy)acetohydrazide as a primary
amine condensed with different aromatic aldehydes such
Key words: Schiff bases, quinoline hydrazine, metal
complexes, antimicrobial, in silico predictions
as salicylaldehyde, o-vaniline, 2-hydroxy-1-naphthaldehyde,
and 3-pyridinecarbaldehyde. The synthesized ligands
were used further to synthesize metal complexes with
copper and zinc metal ions. All synthesized compounds
were investigated in vitro for their antibacterial and
antifungal potentials. Moreover, the prepared com-
pounds were subjected to in silico physicochemical and
pharmacokinetics investigation to predict the absorption,
distribution, metabolism, and elimination (ADME) drug-
likeness properties.

* Corresponding author: Sami A. Zabin, Chemistry Department,
Faculty of Science, Albaha University, Al-Baha, Saudi Arabia,
e-mail: samizabin@gmail.com, szabin@bu.edu.sa,
tel: +966 554676466
Hanan A. Althobiti: Chemistry Department, Faculty of Science,
Albaha University, Al-Baha, Saudi Arabia
Open Access. © 2020 Hanan A. Althobiti and Sami A. Zabin, published by De Gruyter.
Attribution 4.0 Public License.
This work is licensed under the Creative Commons

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Hanan A. Althobiti and Sami A. Zabin
The targeted compounds were prepared success- The magnetic susceptibilities of complexes were mea-
fully, and their antimicrobial potential was compara- sured by the Gouy method at room temperature using
tively weak.
the Sherwood scientific magnetic susceptibility balance
(UK) and using distilled water as the calibrant. The
measurements were carried out at the Central Labora-
tory, Faculty of Science, Cairo University, Egypt. Molar
conductance of the metal complexes was measured
using the Fisher Scientific AP85 Portable Waterproof PH/
conductivity meter (Italy). The molar conductance
measurements were performed using 0.001 M solu-
tions of the complexes in DMSO at room tempera-
ture. Thermal analysis measurements were performed
on Shimadzu thermo-analyzer TG-50H (Japan) in a
nitrogen atmosphere and rate flow 20.0 mL/min at a
heating rate of 10°C/min in the temperature range
25–1,000°C.
2 Materials and methods
2.1 Materials
All starting chemicals and solvents used in this study
were of reagent grade, obtained from Sigma-Aldrich,
Luba, and BDH Chemical Companies. The primary
aromatic amine compound 2-(quinolin-8-yloxy)aceto-
hydrazide was synthesized from 8-hydroxy quinoline in
our laboratory following the literature reported method
[11,12].
2.3 Preparation of 2-(quinolin-8-yloxy)
2.2 Instrumentation and physical
measurements
actohydrazide precursor
The main primary amine compound 2-(quinolin-8-yloxy)
acetohydrazide (Figure 1) was prepared in two steps
following reported method by the reaction of 8-hydroxy-
quinoline (0.02 mol) with ethyl chloroacetate (0.02 mol) in
dry acetone to get ethyl ester of o-alkylated 8-hydroxy-
quinoline and then reacted with hydrazine hydrate
(0.04 mol). The yield was 81.3% and the melting point
measured 138°C similar to the reported one [11–13].
For characterization of the prepared ligands and their
metal complexes, we used different physical and
spectroscopic analysis techniques. The melting points
were measured utilizing the electro-thermal IA9100
digital melting point apparatus. The micro-elemental
analysis was determined using the Thermo Fisher
Scientific CHN/S/O analyzer instrument (Leco Model
VTF-900 CHN-S-O 932 version 1.3x USA). Metal percen-
tage in the complexes was determined using Inductively
Coupled Plasma Optical Emission Spectrometry (ICP-
OES). For this purpose, the instrument used was Thermo
Fisher Scientific ICP-7000 plus Series ICP-OS spectro-
photometer (USA). Mass spectroscopy was obtained from
the Thermo Fisher Scientific-LCQ fleet ion trap mass
spectrometer (USA) using the electrospray ionization
(ESI) method.
NH
NH
2
O
O
N
Figure 1: Structure of 2-(quinolin-8-yloxy)acetohydrazide.
UV-visible absorption spectra measurements were
performed on Thermo Fisher Scientific Evolution 300 2.4 General method for synthesis of the
UV-visible double beam spectrophotometer (USA) using
Schiff base ligands (SL1–SL4)
0.001 M dimethyl sulfoxide (DMSO) solution. FT-IR
spectra were obtained in the range 400–4,000 cm−1 on
Thermo Fisher Scientific Nicolet iS50 FT-IR spectro- The organic Schiff base ligands (SL1–SL4) were synthe-
sized according to the standard methods [14]. The primary
photometer (USA) using attenuated total reflection (ATR)
method for direct measurement of the IR spectrum for amine 2-(quinolin-8-yloxy)acetohydrazide (0.01 mol) was
the powder solid samples. 1H and 13C NMR spectra of the dissolved in ethanol and mixed with the stoichiometric
ligands and the metal complexes were recorded via quantity (0.01 mol) of the aldehydic compound dissolved
Bruker 400 MHz spectrometer (Germany) using DMSO as the in ethanol with continuous stirring using a hot-stage
solvent at the Faculty of Science, Suhag University, Egypt. magnetic stirrer and refluxing the mixture for a proper

New Schiff bases of 2-(quinolin-8-yloxy)acetohydrazide

593
time of 1–2 h. Completion of reactions was checked with was refluxed with continuous stirring using a hot-stage
thin layer chromatography (TLC), and the obtained magnetic stirrer for nearly 2 hours. The off-white solid
products after cooling to room temperature were filtered, precipitate was filtered, washed with ethanol, dried, and
dried, and finally purified by recrystallization. Physical finally recrystallized in hot ethanol. The yield obtained
characteristics, elemental analysis, and percentage of was 89%, and the measured melting point was 117°C.
yield for each prepared Schiff base are detailed in the
following sections.
Elemental analysis for C19H17N3O4: cal. (found), %C
65.01 (64.95), %H 4.84 (4.71), %N 11.97 (12.22), and %O
18.23 (17.86).
2.4.1 Synthesis of N′-[(E)-(2-hydroxyphenyl)
methylidene]-2-[(quinolin-8-yl)oxy]
acetohydrazide (SL1)
2.4.3 Synthesis of N′-[(E)-(2-hydroxynaphthalen-1-yl)
methylidene]-2-[(quinolin-8-yl)oxy]
acetohydrazide (SL3)
For the preparation of SL1 (Figure 2), a mixture of
2-(quinolin-8-yloxy)acetohydrazide 0.01 mol was reacted SL3 (Figure 4) was synthesized by condensation reaction
with 0.01 mol salicylaldehyde in ethanol with stirring using 0.01 mol of 2-(quinolin-8-yloxy)acetohydrazide
using a hot-stage magnetic stirrer and refluxed for and mixed with 0.01 mol 2-hydroxy-1-naphthaldehyde
nearly 2 hours. The whitish-yellow solid precipitate in 30 mL ethanol in a round-bottomed flask. The mixture
was filtered, washed with ethanol, dried, and finally was refluxed with continuous stirring using a hot-stage
recrystallized in hot ethanol. The yield obtained was magnetic stirrer for nearly two and a half hours. The
82%, and the measured melting point was 132°C. yellow solid precipitate was filtered, washed with
Elemental analysis for C18H15N3O3: cal. (found), %C ethanol, dried, and finally recrystallized in hot ethanol.
67.34 (67.02), %H 4.67 (4.77), %N 13.08 (13.36), and The yield obtained was 94%, and the measured melting
%O 14.95 (14.63).
point was 180°C.
NH
NH
O
N
O
O
N
N
O
N
HO
HO
Figure 4: Structure of SL3 ligand.
Figure 2: Structure of SL1 ligand.
2.4.2 Synthesis of N′-[(E)-(2-hydroxy-3-
methoxyphenyl) methylidene]-2-[(quinolin-8-yl)
oxy]acetohydrazide (SL2)
Elemental analysis for C22H17N3O3: cal. (found), %C 71.22
(71.63), %H 4.58 (4.54), %N 11.32 (11.59), and %O
12.94 (12.64).
For the preparation of SL2 (Figure 3), 0.01 mol of
2-(quinolin-8-yloxy)acetohydrazide was mixed with
0.01 mol o-vaniline (2-hydroxy-3-methoxybenzaldehyde)
in 30 mL ethanol in a round-bottomed flask. The mixture
2.4.4 Synthesis of N′-[(E)-(pyridin-3-yl)methylidene]-
2-[(quinolin-8-yl)oxy]acetohydrazide (SL4)
SL4 (Figure 5) was synthesized by condensation reaction
using 0.01 mol of 2-(quinolin-8-yloxy)acetohydrazide as
a primary amine and mixed with 0.01 mol pyridine-3-
carboxaldehyde as an aldehydic compound in 30 mL
ethanol in a round-bottomed flask. The reaction mixture
was refluxed with continuous stirring using a hot-stage
magnetic stirrer for nearly 2 hours. The yellowish-white
(beige) solid precipitate was filtered, washed with
ethanol, dried, and finally recrystallized in hot ethanol.
NH
O
N
O
N
HO
OCH
3
Figure 3: Structure of SL2 ligand.

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Hanan A. Althobiti and Sami A. Zabin
The yield obtained was 78%, and the measured melting Al-Baha City, KSA. The method followed was agar disk-
point was 105°C. diffusion assessment method according to the Clinical
Elemental analysis for C17H14N4O2: cal. (found), %C and Laboratory Standards Institute (CLSI) [15]. Muller
66.72 (66.33), %H 4.58 (4.85), %N 18.30 (18.71), and %O Hinton Agar was used as a growth medium for bacterial
10.46 (10.12).
strains, while Sabouraud dextrose agar nutrient was
used as a microbiological growth medium for fungal
strains. Stock solutions of the examined compounds
were prepared by dissolving 0.02 g of each compound in
5.0 mL DMSO solvent and used for experimental tests.
DMSO solvent was used as the negative control. The
common antibacterial amoxicillin and the antifungal
fluconazole drugs were used as references for compar-
ison. The zones of complete inhibition (in millimeters)
after the incubation period were measured around
every compound, which indicates the lethality of the
tested compound on the microbial microorganisms in
question.
NH
O
N
O
N
N
Figure 5: Structure of SL4 ligand.
2.5 General procedure for preparation of
metal complexes
The targeted Cu(II) and Zn(II) metal complexes were
prepared by the general reported procedure [14]. A
solution of metal salt dissolved in ethanol was mixed
gradually with the ethanolic solutions of the Schiff bases
(SL1–SL4) obtained as mentioned before in 1:2 (metal to
ligand) molar ratio. The reaction mixture was refluxed
with continuous stirring using a hot-stage magnetic
stirrer for 4–6 h at nearly 90°C. The precipitated
compounds obtained were separated by filtration,
washed with hot ethanol, and finally with diethyl ether.
The compounds were dried in open air; the yield, color,
mass spectra, and elemental analysis are given later. The
melting points for all metal complexes were above 300°C.
The elemental analysis and physical characteristics of the
prepared complexes are presented in Table 1.
2.7 In silico predictions
The prepared ligands and their metal complexes were
subjected to in silico physicochemical investigation, and
the number of rotatable bonds, lipophilicity, and
topological polar surface area (TPSA) were calculated
to understand the drug transport properties. In silico %
age absorption was calculated using the reported
formula [(%ABS = 109 − (0.345 × TPSA)] [16,17]. In
addition, the in silico pharmacokinetic predictions were
carried out to predict the absorption, distribution,
metabolism, and elimination (ADME) for the targeted
ligands, and their corresponding metal complexes were
determined by Swiss ADME web interface (http//www.
sib.swiss) [18]. The Lipinski, Ghose, Veber, Egan, and
Muegge rules were applied to predict whether the
targeted compounds are likely to be bioactive [19].
2.6 Antimicrobial activity assessment –
in vitro experimentation
Ethical approval: The conducted research is not related
to either human or animal use.
The microbial susceptibility of the free organic ligands
and their Cu(II) and Zn(II) metal complexes was assessed
for their antimicrobial capacity against different patho-
genic Gram-negative and Gram-positive bacterial strains
and fungal strains. The two Gram-negative bacterial
strains used in the experimentation were P. aeruginosa
(ATCC 27853) and E. coli (ATCC25922), and the two
Gram-positive bacterial strains used in the experimenta-
tion were S. aureus (ATCC 25923) and E. faecalis (ATCC
29212). For antifungal experimentation potentials, we used
the common pathogenic yeast C. albicans (ATCC10231).
The assessment experiments were performed in vitro at the
Department of Clinical Microbiology, Blood Bank Centre,
3 Results and discussion
3.1 Synthesis and characterization
The main purpose of this research work was to
synthesize and characterize new Schiff base ligands
incorporating quinoline moiety and to use them for
preparing metal complexes with the transition metal
ions Cu2+ and Zn2+. To achieve this goal, the key primary

New Schiff bases of 2-(quinolin-8-yloxy)acetohydrazide

595
amine compound 2-(quinolin-8-yloxy)acetohydrazide
containing quinoline moiety was selected and synthesized
in the laboratory following the reported procedure [11–13].
The structure of the key compound was confirmed before
proceeding for the next step. Furthermore, the synthesized
primary amine 2-(quinolin-8-yloxy)acetohydrazide was
coupled with different aromatic aldehydes such as
salicylaldehyde, o-vaniline, 2-hydroxy-1-naphthaldehyde,
and pyridine-3-carboxaldehyde in (1:1) stoichiometric
ratio to produce four different quinoline-hydrazone Schiff
base ligands (SL1–SL4).
3.1.1 Characterization of the Schiff base ligands
The isolated Schiff bases were purified by recrystallization
using hot ethanol and were in good yields (78–94%). They
were mostly yellow colored and were soluble in hot ethanol,
N,N-dimethylformamide (DMF), and dimethyl sulfoxide
(DMSO). The isolated Schiff base ligands were characterized,
and the proposed structures were confirmed before pro-
ceeding for the preparation of the targeted Cu(II) and Zn(II)
metal complexes step. The elemental analysis results for C, H,
N, and O found were in good agreement with the theoretically
calculated percentage values for the proposed molecular
formulae, in favor of the expected structures of the Schiff base
ligands. The obtained mass spectra (m/z) for each of the
prepared ligand compounds (SL1–SL4) were also in agreement
with the molecular formulae of the prepared Schiff bases.
The IR spectrum of the organic Schiff base com-
pounds exhibited characteristic peaks (Table 2), which
were helpful in proving the proposed structures of the
ligands. The sharp bands appeared at 1,500, 1,502, 1,504
and 1,505 in the spectrum of the ligands SL1–SL4,
respectively, designed to the characteristic azomethine
group (–CH]N–), which indicates the formation of the
Schiff base ligands [20]. The presence of the aromatic
(–OH) group in the spectrum of the ligands exhibited
peaks at 3,500, 3,513, 3,570, and 3,606 cm−1, respectively
[21]. The intense bands observed in the range 1,225–1,255
in the IR spectrum of the ligands (SL1–SL3) are due to the
phenolic C–O linkage [22]. The sharp transmission bands
at 1,660, 1,665, 1,685, and 1,671 cm−1 in the spectra of
SL1, SL2 SL3, and SL4, respectively, are due to the
presence of the stretching carbonyl C]O group [9,12,23].
Weak transmission bands observed in the range
2,985–2,988 cm−1 may be assigned to the –N–H amide
group [9,23]. The transmission bands observed at 1,115,
1,114, 1,110, and 1,112 cm−1 in the spectra of SL1, SL2 SL3,
and SL4, respectively, can be assigned to the –N–N–
linkage [24].

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Hanan A. Althobiti and Sami A. Zabin
Table 2: Important characteristic IR bands (cm−1) of the ligands and metal complexes
Compounds
νC]N
νOH
νC–O (phenolic)
νC]O (carbonyl)
NN—H
νM–N
νM–O
ν–N–N–
SL1
SL2
SL3
SL4
[Cu(SL1)2]
[Zn(SL1)2]
[Cu(SL2)2]
[Zn(SL2)2]
[Cu(SL3)2]
[Zn(SL3)2]
[Cu(SL4)2]
[Zn(SL4)2]
1,500
1,502
1,504
1,505
1,534
1,550
1,541
1,543
1,553
1,557
1,545
1,540
3,500
3,513
3,570
3,606
—
—
—
—
—
1,225
1,255
1,242
—
1,252
1,261
1,212
1,223
1,211
1,218
—
1,660
1,655
1,685
1,671
1,653
1,659
1,684
1,653
1,662
1,684
1,670
1,663
3,050
3,045
2,995
2,988
3,012
3,062
2,988w
3,015
3,021w
3,050
3,010
3,024w
—
—
—
—
480
484
479
456
451
462
451
488
—
—
—
—
586
571
583
577
532
569
568
542
1,115
1,114
1,110
1,112
1,112
1,114
1,110
1,115
1,114
1,113
1,112
1,127
—
—
—
—
w = weak band.
The observed UV-visible absorption spectra for the synthesis of the designed metal complexes in this
free organic Schiff base ligands (SL1–SL4) show two main research project. These metals are familiar, important
bands. The first observed at lower wavelength bands at metals and form interesting coordination compounds.
295, 284, 262, and 301 nm in the spectrum of the ligands
The targeted coordination metal complexes were
SL1, SL2, SL3, and SL4, respectively, that can be assigned prepared successfully by reacting to the metal salts of
to π → π* transitions within the benzene and quinoline the selected metals with the prepared Schiff base ligands
rings [25,26]. The second bands were observed at 324, (SL1–SL4) in (1:2) stoichiometric ratio according to the
326, 322, 317 nm in the spectrum of the ligands SL1, SL2, described template method. The separated metal com-
SL3, and SL4, respectively, which may involve π → π* and plexes were stable solids at room temperature and
n → π* transitions of the (–C]N–) group [26].
nonhygroscopic. They were solids insoluble in common
1
In the H NMR Spectra of all the Schiff base ligands organic solvents but soluble in DMF and DMSO. They
(SL1–SL4), the imine protons were observed at 8.58–8.98 ppm were purified by recrystallization from hot DMF and
as a singlet. Moreover, the peaks at 11.05–12.23 ppm, which DMSO solvents. All prepared metal complexes had high
are singlets, can be attributed to aromatic –OH protons in the melting points (above 300°C).
ligand SL1, SL2, and SL3 [27]. This shift in the position of the
The elemental analysis measurements suggested 1:2
singlet may be due to the possibility effect of the formation metal to ligand stoichiometric ratio forming tetra-
of intramolecular hydrogen bonding interaction. The coordinate monomeric Cu(II) and Zn(II) metal complexes.
singlets appeared in the range of 12.18–12.52 ppm in the The measured percentages of the carbon, hydrogen,
1H NMR spectrum of all Schiff base ligands are due to the nitrogen, oxygen, and metal ion are in agreement with
–NH– linkage [28]. The peaks due to the aromatic the calculated ones according to the suggested structure
hydrogens appeared in the range of 7.00–8.98 ppm [29].
of the complexes as shown in Figure 6(a–d). The Schiff
In 13C NMR spectra of the ligands SL1, SL2, SL3, and base quinoline acetohydrazone ligands containing NO
SL4, the peaks appeared at 148.75, 148.48, 147.62, and coordination sites behave as monobasic bidentate
145.69 ppm, respectively, are assigned to the carbon ligands. The general formula for the prepared complexes
atom of the azomethine group [27]. The singlet peaks suggested to be [M(SL1–4)2] for all metal complexes
observed in the range of 164.81–169.57 ppm is due to the
According to the above-proposed structures, the
carbon atom of the C]O group [30]. Moreover, the prepared Cu(II) and Zn(II) complexes are suggested to be
peaks observed in the region 109.00–154.49 ppm are mononuclear complexes. The ligands SL1–SL3 bind to
because of the carbon atoms of the aromatic ring [9].
metal ions through the nitrogen atom of the azomethine
(–CH]N–) group and the oxygen atom of the phenolic
(–OH) group forming square planar geometry. Moreover,
3.1.2 Synthesis and characterization of metal complexes the bidentate Schiff base ligands SL1, SL2, and SL3 forms
six-membered chelate rings at the Cu(II) and Zn(II)
Copper(II) and Zinc(II) from the first transition elements acceptor centers. The ligand SL4 binds to metal ions
series of the d-block elements were chosen for the through the N atom of –C]N– group and the O atom of

New Schiff bases of 2-(quinolin-8-yloxy)acetohydrazide

597
N
N
NH
NH
O
N
O
OCH
N
3
O
O
O
O
M
M
O
O
O
O
N
N
O
H CO
O
3
NH
NH
N
N
(a)
(b)
N
H
N
N
N
NH
O
N
O
N
O
N
O
O
M
M
O
O
N
O
O
O
NH
N
N
H
N
N
(c)
(d)
Figure 6: Structure of the synthesized complexes with (a) SL1, (b) SL2, (c) SL3, and (d) SL4 where M = Cu(II) or Ni(II).
the carbonyl group forming square planar geometry. The the azomethine group was indicated through the shift
bidentate SL4 ligand forms a five-membered ring at the (blue shift) of the νC]N band in the IR spectrum of the
metal acceptor center.
complexes when compared with the free organic
To prove the proposed structures for the prepared ligands. This also was supported by the appearance of
metal complexes, we performed different analytical the new weak band in the spectrum of the metal
techniques. Mass spectrometry analysis was carried out complexes at the range of 437–488 cm−1 attributed to
to help in quantifying and structure elucidation of the the formation of M–N bonds [1]. The formation of M–N
obtained complexes and confirm the molecular weights. bond leads to the weakening of the C]N band due to
The measured (m/z) peaks indicated that the observed the donation of electrons from the nitrogen atom to the
molecular peaks for all prepared metal complexes vacant d-orbitals in the metal atoms, which causes the
are equivalent to the theoretically calculated formula shift of the azomethine band in the metal com-
weights according to the proposed structures. plexes [16].
These observations support and prove the suggested
structures for the prepared metal complexes shown in shown in the IR spectrum of the free Schiff bases
Figure 6(a–d). (SL1–SL3) due to the phenolic (νOH) group were
The bands (3,500, 3,513, 3,570, and 3,606 cm−1)
The comparison between the IR spectral data of the disappeared in the IR spectrum of the corresponding
free organic ligands (SL1–SL4) and that of the corre- Cu(II) and Zn(II) complexes. This is a sign of the binding
sponding Cu(II) and Zn(II) metal complexes demonstrate of the oxygen atom of the phenolic group to the metal
that the ligands were binding to the metal ions. The atoms [22,31]. Moreover, the intense bands observed
coordination of the ligands through the nitrogen atom of in the IR spectrum of the ligands (SL1–SL3) due to the

598
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Hanan A. Althobiti and Sami A. Zabin
phenolic C–O linkage were shifted and appeared in accountable for the 2B1g → 2A1g transitions that are
the range of 1,211–1,265 cm−1 is another proof for the consistent with square-planar geometry around the Cu(II)
involvement of the OH group in bonding with the metal centers [36,37]. Moreover, the magnetic moment values
ions [22]. In addition, a weak band was observed in the (Table 3) were between 1.906 and 2.261 BM which lies
IR spectrum of these complexes at the range of within the permissible values reported for one unpaired
542–595 cm−1 which is assigned to the νM–O mode, electron, and it is an evident that supports the square-
evidence for the formation of M–O bonds [32,33].
planar geometry of Cu(II) complexes [37]. This geometry is
It was also observed that the band 1,671 cm−1 due to achieved through the coordination of two bidentate
the νC]O of the carbonyl group in the IR spectrum of ligands (SL1–SL4) to the metal center in trans-geometry
SL4 ligand was shifted slightly in the spectrum of the with respect to each other as shown in Figure 6(a–d).
corresponding metal complexes, which indicate the
binding of the oxygen atom to the metal ions [33].
The most important bands observed in the IR 3.1.4 Zn(II) complexes
spectrum of the metal complexes are shown in Table 2.
The UV-visible and magnetic moment susceptibility The transmission bands observed in the range 269–277 nm
(μeff) data are helpful tools to deduce the nature of the in the UV-visible spectrum of Zn(II) complexes can be
ligand field around the metal ion and the geometry of assigned to the π → π* transitions. The weak bands in the
the obtained metal complexes. The observed UV-visible range of 305–318 nm were assigned to n → π* transitions.
transmission bands for the prepared Cu(II) and Zn(II) Moreover, the bands observed in the range 423–438 nm may
complexes are shown in Table 3. The UV-visible spectra be attributed to the ligand-to-metal charge transfer transi-
indicate that there is a relative shift to lower wave- tions [27,38]. The lowest energy bands at the range
lengths (bathochromic shift) of the transmission bands 610–685 nm were due to the d → d transition of Zn2+.
due to π–π* and n–π* transitions that observed in the These observations are consistent with square-planar
spectrum of the free prepared Schiff base ligand. This geometry. The observed magnetic moment (Table 3) for all
observation may be because of the coordination of the Zn(II) complexes were diamagnetic, which is in support of
ligands to the metal core, which causes a change in the square-planar geometry [27,38].
the distribution of electrons between the ligands and the
metal ions [25,26,34,35].
The discussion for each metal complexes is dis- bidentate (SL1–SL4) ligands to the metal center in
cussed in the following sections.
The four-coordinated mononuclear complexes of Zn
(II) are achieved through the coordination of the
trans-geometry with respect to each other as shown in
Figure 6(a–d). The coordination is through two N atoms
and two oxygen atoms from two same Schiff base
ligands in a square-planar geometry.
3.1.3 Cu(II) metal complexes
The 1H NMR analysis was further performed to
The observed UV-visible spectra of the synthesized achieve concrete evidence of the binding of the Cu2+ and
mononuclear copper(II) complexes showed transmission Zn2+ to the ligands. Upon complexation, the peaks due
bands in the range λmax = 648–675 nm, which may be to the proton of the imine group in the Schiff base
ligands were showed field up shift slightly by Δδ
=
0.40–0.80 ppm. The singlet peaks due to the phenolic
Table 3: UV-visible transmission bands and μeff values for the
metal complexes
1
proton in the H NMR spectra of SL1, SL2, and SL3 were
disappeared indicating the deprotonation of this group.
These observations proved that the N atom of the
azomethine (>CH=N–) group and the O atom of the
phenolic (–OH) group participate in coordination and
formation of the metal complexes [27]. The peaks
observed for the –NH– proton did not show any shift
and remained at the same position in the spectra of the
metal complexes, which were an indication of no-
participation of this group in bonding to the metal ions.
Thermal analysis studies of some prepared metal
complexes were investigated at the heating rate of 10
Compound Transmission bands
Magnetic moment
μeff (B.M.)
(λmax in nm)
[Cu(SL1)2]
[Zn(SL1)2]
[Cu(SL2)2]
[Zn(SL2)2]
[Cu(SL3)2]
[Zn(SL3)2]
[Cu(SL4)2]
[Zn(SL4)2]
305, 385, 661
277, 418, 685
313, 390, 675
305, 415, 610
321, 377, 650
273, 428, 622
345, 374, 648
269, 433, 612
1.961
Diamagnetic
2.261
Diamagnetic
1.924
Diamagnetic
1.906
Diamagnetic

New Schiff bases of 2-(quinolin-8-yloxy)acetohydrazide

599
Figure 7: TGA–DTA curves of [Zn(SL1)2].
(°C/min) under the nitrogen atmosphere from room studied metal complexes were decomposed in three succes-
temperature to 800°C. These thermogravimetric studies sive stages. The TGA curves of anhydrous complexes do not
are helpful tools and good supports in the characteriza- display any mass losses up to 260°C, which indicate the
tion of the prepared metal complexes.
thermal stability of the metal complexes and confirm the
The results of representative TG/DTA plots of the absence of water molecules in the complex structures. In
analyzed metal complexes are shown in Figure 7 and 8. The Figure 7, the first step for the complex [Zn(SL1)2] (molecular
results show good harmony with the proposed chemical weight = 706.3) started decomposition between 256 and 331°C
structures suggested from the analytical data as discussed and weight loss observed was 28.416% which is corre-
earlier. It is obvious from the decomposition pattern that the sponding to two molecules of the salicylaldehyde part from
Figure 8: TGA–DTA curves of [Zn(SL3)2].

600

Hanan A. Althobiti and Sami A. Zabin
the ligand (i.e., C14H12) (calculated weight percentage of the metal complexes, the heat flow in the 90–600°C
30.02%) may be due to breaking the azomethine linkage temperature range was shown as endothermic peaks.
during heating. The second step of decomposition was
between 421.02 and 569.41°C with an observed weight loss of
54.243%, which can correspond to the ligand and aromatic
3.2 Molar conductance of the prepared
ring (C6H4) (calculated weight percentage 54.44%). The third
step on further heating above 600°C, metal complexes
decompose to stable zinc oxide. In Figure 8, the first step
for the decomposition of [Zn(SL3)2] (molecular weight =
806.15) started decomposition between 230 and 310°C and
weight loss observed was 52.37% which is corresponding to
two molecules of the amine part (i.e., C22H18O4N6) from the
organic ligand (calculated weight percentage 53.35%). In the
second step, the observed weight loss was 44.83% which
corresponds to the organic ligand (C22H17N3O3) (calculated
weight percentage = 46.02%). Final step above 630°C decom-
pose the complex to the stable zinc oxide. In the DTA curve
metal complexes
To examine the electrolytic or nonelectrolyte nature of the
prepared metal complexes, we measured the molar con-
ductance (Λm) of freshly prepared 1.0 × 10−3 M solutions of
the synthesized metal coordination compounds in DMSO at
room temperature (24°C). The measured values are presented
in Table 4. The molar conductance values obtained were in
the range (2.16–35.4 Ω−1 cm2 mol−1) which are considered very
low. It is evident from these results that the prepared
Cu(II) and Zn(II) complexes are nonionic in nature (non-
electrolytes). Moreover, it is confirmed that the ligands are
involved in the coordination sphere [38,39].
Table 4: The measured molar conductivity for the metal complexes
Molar conductance (Ω−1 cm2 mol−1
)
3.3 In vitro anti-microbial potentials
Metal complex
[Cu(SL1)2]
[Zn(SL1)2]
[Cu(SL2)2]
[Zn(SL2)2]
[Cu(SL3)2]
[Zn(SL3)2]
[Cu(SL4)2]
[Zn(SL4)2]
7.22
7.26
6.32
27.9
2.16
35.4
12.6
11.8
The free prepared organic ligands (SL1–SL4) and their
corresponding Cu(II), and Zn(II) metal complexes were
assayed in vitro for their potential antibacterial and
antifungal activities utilizing the agar disc-diffusion
method. The zones of complete inhibition (in milli-
meters) were measured, and the observations are
presented in Table 5 as arithmetic mean values.
Table 5: Antimicrobial observations for the ligands and their Cu(II) and Zn(II) complexes
Compound
Zone of inhibition (mm)
Gram-positive bacteria
Gram-negative bacteria
Fungus
S. aureus
E. faecalis
E. coli
P. aeruginosa
C. albicans
SL1
SL2
SL3
SL4
19
22
24
20
31
18
24
25
25
29
26
9
21
23
08
20
32
18
0
28
15
30
11
7
0
0
0
12
0
0
0
6
13
0
0
0
0
0
0
0
0
0
0
0
0
0
—
37
0
0
0
0
0
0
3
0
0
0
0
0
17
42
[Cu(SL1)2]
[Zn(SL1)2]
[Cu(SL2)2]
[Zn(SL2)2]
[Cu(SL3)2]
[Zn(SL3)2]
[Cu(SL4)2]
[Zn(SL4)2]
Amoxicillin
Fluconazole
0
38
35
0
23
35
40
36

New Schiff bases of 2-(quinolin-8-yloxy)acetohydrazide

601
The ligands (SL1–SL4) exhibited moderate antibacterial liposolubity and influences the cell membrane permeability
activity against the Gram-positive bacterial types with zones of the metal complexes into the microbial cell [1,40]. This
of inhibitions in the range of 8–25 mm. They showed no facilitation in the lipophilicity and penetration of the metal
activity against the Gram-negative bacterial types and the complexes inside the microbial cell give rise to adverse
fungal strain too. SL3 ligand compound showed the highest effects in the cell environment and enzymes of the cell and
activity when compared with other ligands with a zone of further affects the proliferation of the microorganism [20,41].
inhibition of 24 mm against S. aureus. Compared to the Moreover, the possibility of the formation of hydrogen
amoxicillin and fluconazole as standards, the activity of the bonds through the >CH=N– group with cell components
ligands was much lower.
can cause and interfere with normal cell processes [31].
The higher activity of the Cu(II) complexes compared
The corresponding metal complexes, in general,
showed some enhancement antibacterial activity against to the Zn(II) complexes may be interpreted on the
both Gram-positive S. aureus and E. faecalis bacterial strains stability of these complexes [42].
with zones of inhibitions in the range of 18–32 mm. While
Figures 9 and 10 show some photographs of the
similar to the parent ligands, the complexes showed no antibacterial and antifungal tests.
activity against the Gram-negative bacterial stains and the
fungal strain. Few metal complexes showed weak activity
against the Gram-negative bacteria E. coli with zones of 3.4 In silico prediction
inhibition less than 15 mm. On comparing between the
metal complexes, it was observed that [Cu(SL1)2] was the New drug discovery and development demand considerable
most toxic compound against the Gram-positive bacteria. facilities, materials, and time. For this reason, theoretical
[Cu(SL1)2] exhibited activity with zones of inhibition of 31 investigations have a major role in reducing these factors
and 32 mm against S. aureus and E. faecalis, respectively. and predicting the possibility of prospective drug applica-
On comparing the activities of the metal complexes with the tions. It is not sufficient for a chemical to show in vitro
standard drugs, the metal complexes exhibited less excellent biological activities, but in addition, it is required
antibacterial and antifungal activity.
to satisfy the pharmacokinetic parameters ADME. These
Based on the Tweedy’s chelation theory and Overtone’s parameters can be validated by the in silico investigations
permeability principles, the antibacterial enhancement through computing the physicochemical criteria.
activity of the metal complexes can be interpreted [40].
According to the chelation theory, the coordination of
organic ligands with metals reduces the polarity of the 3.4.1 Physicochemical properties
metal due to overlap of the orbitals of the ligand with the
metal orbitals and the generation of delocalized π-electrons The pharmacological or therapeutic effect is related to
over the entire coordination sphere. This enhances the the influence of various physicochemical properties of
Figure 9: Photographs of some antibacterial tests against S. aureus bacterial strains. (a) Shows some of the active compounds 8 = SL3,
10 = [Zn(SL3)2] and 11 = [Cu(SL3)2]; (b) shows the activity of compound 14 = [Cu(SL1)2].

602

Hanan A. Althobiti and Sami A. Zabin
Figure 10: Representative photographs for antibacterial and antifungal tests for each strain used: (a) E. faecalis, (b) E. coli,
(c) P. aeruginosa, (d) C. albicans.
the chemical on the biomolecules that it interacts with. presented in Table 6. The results of in silico absorption
Different physicochemical parameters of a drug candi- percentage calculations indicated that the percentage of
date play a crucial role in their pharmacokinetic absorption was in the range of 76.90–82.61% among
behavior [43]. In view of this, their calculation and ligands, where the ligand SL4 was the highest with an
measurement help in prioritizing compounds for absorption percentage of 82.61%. The in silico absorption
screening as an efficient drug candidate and enable percentage (42.84–56.23) among complexes observations
preliminary decisions in drug discovery [44]. The showed that the complexes [Cu(SL4)2] and [Zn(SL4)2]
prepared ligands and their metal complexes were showed the highest absorption percentage with the
subjected to in silico physicochemical studies such as value of 56.23% for both complexes. On comparing the
number of rotatable bonds, hydrogen bond acceptor, ligands and their corresponding metal complexes, it is
hydrogen bond donor, molecular reactivity, water- clear that the ligands showed a much higher absorption
solubility, lipophilicity, and topological polar surface percentage. Moreover, the obtained TPSA values for the
ligands were below 140 Å2 (the accepted limit of polar
surface area), indicating that ligands had considerable
area (TPSA), which were calculated for understanding
the drug transport properties. All results obtained are

New Schiff bases of 2-(quinolin-8-yloxy)acetohydrazide

603
Table 6: Physicochemical properties of the ligands and their complexes
Compound no.
Fraction
Csp3 a
No. of rotatable
bonds
HBAb
HBDc
MilogPd
Molar
refractivity
ESOL
log Se
TPSAf
In silico %
absorption
SL1
SL2
SL3
SL4
[Cu(SL1)2]
[Zn(SL1)2]
[Cu(SL2)2]
[Zn(SL2)2]
[Cu(SL3)2]
[Zn(SL3)2]
[Cu(SL4)2]
[Zn(SL4)2]
0.06
0.11
6
7
6
5
6
5
2
2
2
1
2
2
2
2
2
2
2
2
1.96
2.7
2.61
1.74
0
0
0
0
0
91.05
97.54
108.55
86.82
179.3
−3.68
−3.74
−4.81
−3.16
−7.53
−7.54
−7.7
−7.71
−9.76
−9.78
−6.35
−6.36
83.81
93.04
83.81
80.08
76.90
80.08
82.61
49.20
49.20
42.84
42.84
49.20
49.20
56.23
56.23
0.05
0.06
0.06
0.06
0.11
6
5
76.47
16
16
18
18
16
16
12
12
10
10
12
12
10
10
10
10
173.28
173.28
191.74
191.74
173.28
173.28
152.94
152.94
179.3
192.29
192.29
214.31
214.31
173.64
173.64
0.11
0.05
0.05
0.06
0.06
0
36.16
−45.4
a The ratio of sp3 hybridized carbons over the total carbon count of the molecule. b Number of hydrogen bond acceptor. c Number of
f
hydrogen bond donor. d Lipophilicity. e Water solubility. Topological polar surface area (0A2). ESOL = estimated solubility.
permeability into the cellular plasma membrane [45]. had excellent absorption possibility from the intestine
While the TPSA values for the examined metal com- after oral administration, while the complexes showed
plexes were very high (>140 Å2) marking low perme-
low GI absorption and hence had low absorption
ability into the cellular plasma membrane. The log S
(that is the coefficient of solubility determined by the
estimated solubility (ESOL) method computed on Swiss
ADME) for many known drugs available in the market
showed values more than −4.00 [45]. In our investiga-
tion, the obtained values of log S (Table 6) for the
ligands SL1, SL2, and SL4 were little more than −4.00,
indicating that these compounds are considered mod-
erate soluble. While SL2 was having a value of (−4.81)
which is less and hence this compound considered
insoluble. In the case of the metal complexes, the log S
values are much less than (−4.00), and hence, the metal
complexes are considered highly insoluble.
possibility from the intestine. It was very interesting
that all the ligands and complexes were unable to
penetrate through the blood–brain barrier (BBB) except
the ligand SL4. Besides this drug-likeness is the other
parameter, which gives the probability of the molecules
for the drug candidate. In the light of the drug-likeness
definition, the chemical has a logarithm of the partition
(log P) (i.e., octanol/water partition coefficient used to
predict the solubility of a probable oral drug) between
−0.4 and 5.6 values [46]. The skin permeability
coefficient (Kp) is a criterion that considers the octanol/
water partition coefficient to be a direct effect on the
transdermal movement of chemical molecules and used
to quantitatively describe the potential of dermal
absorption for the synthesized compounds. In our study,
log Kp values for all examined ligands and complexes
were in the range of −7.50 to −5.04, which are below
−0.4 indicating low lipophilicity and cannot penetrate
through the lipid bilayers of the cells and suggesting
that the synthesized compounds have bad drug-likeness.
In addition, to discriminate between the drug-like and
non-drug-like chemical substances, the Lipinski (rule-
of-five) that describes the relationship between pharmaco-
kinetic and physicochemical parameters, Ghose, Veber,
Egan, and Muegge rules were applied to predict whether
the target compounds are likely to be bioactive and assess
qualitatively the chance of these compounds to become
oral drug candidates [19]. The number of violations to
these rules is listed in Table 8. All the ligands fulfilled
Lipinski rule and other rules and showed zero violation
3.4.2 In silico pharmacokinetic/ADME and drug-
likeness properties
Pharmacokinetics is used to investigate the time course
of chemical absorption, distribution, metabolism, and
excretion (ADME) and determines the fate of the
chemical administered to the living organisms. In this
paper, we have performed in silico pharmacokinetic
predictions for the prepared four Schiff base ligands
(SL1–SL4) and the prepared corresponding Cu(II) and
Zn(II) metal complexes and the obtained results are
presented in Table 7. The gastrointestinal (GI) absorp-
tion score measures the extent of absorption of a
chemical from the intestine, the results pointed out
that all the ligands have high GI absorption and hence

604

Hanan A. Althobiti and Sami A. Zabin
Table 7: Pharmacokinetic/ADME (absorption, distribution, metabolism, and excretion) properties of the ligands and complex compounds
Compound no.
Pharmacokinetic/ADME properties
i
GI
Absa
BBB
Permeantb
P-gp
CYP1A2
Inhibitord
CYP2C19
Inhibitore
CYP2C9
Inhibitorf
CYP2D6
Inhibitorg
CYP3A4
Inhibitorh
log Kp
Substratec
SL1
SL2
SL3
SL4
[Cu(SL1)2]
[Zn(SL1)2]
[Cu(SL2)2]
[Zn(SL2)2]
[Cu(SL3)2]
[Zn(SL3)2]
[Cu(SL4)2]
[Zn(SL4)2]
High
High
High
High
Low
Low
Low
Low
Low
Low
Low
Low
No
No
No
Yes
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
No
No
No
No
No
No
No
Yes
Yes
No
No
No
No
No
No
No
No
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
No
No
No
No
No
No
No
No
No
−6.29
−6.49
−5.7
−6.7
−6.2
−6.21
−6.61
−6.62
−5.04
−5.05
−7.49
−7.5
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
No
No
a Gastro intestinal absorption. b Blood–brain barrier permeant. c P-glycoprotein substrate. d CYP1A2: cytochrome P450 family1 subfamily A
member 2(PDBHI4). e CYP2C19: cytochrome P450 family2 subfamily C member 19(PDB4GQS). f CYP2C9: cytochrome P450 family2 subfamily
C member 9 (PDB1OG2). g CYP2D6: cytochrome P450 family 2 subfamily D member 6 (PDB5TFT). h CYP3A4: cytochrome P450 family 3
i
subfamily A member 4 (PDB4K9T). Skin permeation in cm/s.
against all the rules, while all the complexes showed two significant pharmacokinetic interactions that lead to
violations against the Lipinski rule and different violations toxic effect through inhibition of these isoenzymes. The
against the other rules. All the ligands in the screening CYP450 inhibition prediction results (Table 7) indicated
processes showed good bioavailability with a score of 0.55, that all synthesized ligands have probable inhibition to
which is an indication that all organic ligands reach the the CYP1A2, CYP2C9 and CYP2D6 isoforms. The ligand
circulation system, whereas the complexes showed mod- SL3 showed inhibition possibility for all CYP450 iso-
erate to poor bioavailability with scores in the range forms. The majority of metal complexes showed inhibi-
0.11–0.17 and hence cannot reach the circulation system tion possibility to the CYP3A4 isoform and no inhibition
easily.
to the other CYP450 isoforms. The complexes with SL4
The prediction of the interaction of the tested ligand [Cu(SL4)2] and [Zn(SL4)2] showed no inhibition to
compounds with cytochromes CYP450 major isoforms all isoforms. Moreover, the probability of the compounds
(CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4) was to be the substrate of P-glycoprotein (P-gp) was
performed in order to check which compound will cause suggesting that ligands and the majority of complexes
Table 8: Drug likeness predictions of the target compounds
Compounds no. Lipinski violations Ghose violation Veber violation Egan violation Muegge violation Bioavailability score
SL1
SL2
SL3
SL4
[Cu(SL1)2]
[Zn(SL1)2]
[Cu(SL2)2]
[Zn(SL2)2]
[Cu(SL3)2]
[Zn(SL3)2]
[Cu(SL4)2]
[Zn(SL4)2]
0
0
0
0
2
2
2
2
2
2
2
2
0
0
0
0
3
3
3
3
4
4
3
3
0
0
0
0
2
2
2
2
2
2
2
2
0
0
0
0
1
1
1
1
0
0
0
0
4
4
5
5
5
5
2
2
0.55
0.55
0.55
0.55
0.11
0.11
0.11
0.11
0.11
0.11
0.17
0.17
2
2
1
1

New Schiff bases of 2-(quinolin-8-yloxy)acetohydrazide

605
have a probability to be nonsubstrate of P-gp. The
complexes obtained from SL3 and SL4 showed
In silico physicochemical investigation revealed
that among the ligands, the ligand SL4 showed highest
a
probability to be the substrate of P-gp. These results in silico absorption with 82.61% and [Cu(SL4)2] and
suggesting the more favor of non-drug-likeness of the [Zn(SL4)2] complexes showed highest in silico absorption
tested compounds.
percentage of 56.23% among the complexes. The in silico
pharmacokinetics predictions showed that the ligands
have high GI absorption and the complexes showed low
GI absorption. The ligands showed a good bioavailability
score of 0.55 where the complexes showed moderate to
poor bioavailability.
4 Conclusion
We have successfully prepared four new Schiff base
Finally, we recommend further investigations on the
ligands (SL1–SL4) with a quinoline hydrazine scaffold. Schiff base ligands containing quinoline moiety and
The prepared Schiff base ligands were characterized, preparation of metal complexes using other metal ions
and their structures were proved before proceeding for and examining their biological activities. Moreover,
the next step. A series of Cu(II) and Zn(II) complexes were other investigations are going on for their applications
synthesized using these ligands. The chemical and as catalysts, corrosion inhibitors, using these Schiff base
spectroscopic analyses results revealed that the ligands ligands as chemosensors for the detection of heavy
behaved as bidentate ligands and coordinated to the metal ions in different sources.
Cu(II) and Zn(II) metal ions through the N atom of the
azomethine group and the O atom of the phenolic group Acknowledgment: The authors are very grateful to the
or the ketonic O atom in case of SL4 ligand and forming Head of the Chemistry Department and the Dean,
square-planar geometry. All the complexes were mono- Faculty of Science at Albaha University for laboratory
nuclear and the general formula for complexes obtained facilities and encouragements.
from the ligands was of the type [M(SL1—4)2].
For proving the proposed structures of synthesized Conflict of interest: The authors declare that no conflict
ligands and their corresponding metal complexes, we of interest exists.
performed elemental analysis and various spectroscopic
measurements, which showed similarities with the
theoretically expected results indicating the formation
of the compounds and proving their structures.
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