Theoretical and experimental investigations of new bis (amino triazole) schiff base ligand: Preparation of its UO2(II), Er (III), and La (III) complexes, studying of their antibacterial, anticancer, and molecular docking

Article abstract of DOI:10.1002/aoc.6292

UO₂(II), Er (III), and La (III) complexes were prepared from new bis (amino triazole) Schiff base ligand. The ligand was synthesized by condensation of 1,3-bis(4-amino-5-phenyl-1,2,4-triazol-3-ylsulfanyl)propane with benzaldehyde. The structure

Full text of DOI:10.1002/aoc.6292

Received: 21 October 2020
DOI: 10.1002/aoc.6292
Revised: 18 April 2021
Accepted: 25 April 2021
F U L L P A P E R
Theoretical and experimental investigations of new bis
(amino triazole) schiff base ligand: Preparation of its
UO2(II), Er (III), and La (III) complexes, studying of their
antibacterial, anticancer, and molecular docking
Reem G. Deghadi
| Ashraf A. Abbas
| Gehad G. Mohamed
Chemistry Department, Faculty of
Science, Cairo University, Giza, 12613,
Egypt
UO2(II), Er (III), and La (III) complexes were prepared from new bis (amino
triazole) Schiff base ligand. The ligand was synthesized by condensation of
1,3-bis(4-amino-5-phenyl-1,2,4-triazol-3-ylsulfanyl)propane with benzalde-
hyde. The structure of the prepared compounds was confirmed by some spec-
troscopic tools such as 1H-NMR, UV-Vis, and IR, as well as molar
conductance, mass spectrometry, elemental analysis, thermogravimetric analy-
sis (TG), differential thermogravimetric (DTG), and differential thermal analy-
sis (DTA) studies. The data revealed coordination of the complexes with
tetradentate Schiff base. All complexes were octahedral. Computational studies
for the prepared ligand by using DFT/B3LYP method were reported. The theo-
retical results described its bond lengths, angles, and dipole moment, and
other parameters were calculated. The theoretical studies were supported the
experimental data of the ligand and confirmed its successful preparation. Also,
their antibacterial activities against four types of bacteria species (Pseudomonas
aeruginosa, Escherichia coli, Bacillus subtilis, and Staphylococcus aureus) were
investigated. The prepared complexes were biologically active compounds. The
synthesized compounds were estimated for their anticancer activities against
two cell lines (MCF-7 and HepG2). The lowest IC50 values were 17.6 and
23 μM for uranyl complex against MCF-7 and ligand against HepG2 cell lines,
respectively, which make them very important materials as anticancer drugs
in the future researches. Finally, molecular docking studies were checked up
for all prepared compounds with different protein receptors (3HB5 and 2GYT)
to confirm their anticancer activities data.
Correspondence
Reem G. Deghadi, Chemistry Department,
Faculty of Science, Cairo University, Giza
12613, Egypt.
Email: reemgd90@yahoo.com
K E Y W O R D S
Er (III) complex, La (III) complex, MOE studies, triazole Schiff base, uranyl (II) complex
1 | INTRODUCTION
complexes derived from Schiff base ligands have applica-
ble biological activities, so they considered as one of the
There has been various effort toward the improvement of
novel chemical compounds which able to reverse or
arrest the development of cancer.[1] The transition metal
most exhaustively studied topic in coordination chemis-
try. This may be due to their enhanced activities com-
pared to non-Schiff base complexes.[2,3]
Appl Organomet Chem. 2021;e6292.
wileyonlinelibrary.com/journal/aoc
© 2021 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.6292

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DEGHADI ET AL.
Most prepared Schiff bases are easily accessible using
the two axial coordination sites occupied by oxo groups
can interact with different ligands in the equatorial
plane to give four, five, or six coordination sites.[19] The
uranyl-salophen complex was previously prepared,
which had pentagonal bipyramidal geometry structure.
The two oxygen atoms of the UO2(II) were in the apical
positions, while the U atom was coordinated with the
four donor atoms of the salophen ligand.[20] This com-
plex could be used as catalysts, sensors, or molecular
recognition.[21]
simple synthetic procedures and with careful selection of
a carbonyl compound and an amine precursor. The Schiff
base ligands could potentially stabilize metals in different
oxidation states and induce stability in heterogeneous
and homogeneous catalysts.[4] Schiff base metal com-
plexes have various applications in different research
areas, such as catalysis, molecular magnetism, and medi-
cal sciences.[5,6] A large number of various Schiff base
complexes have been used in several fields, such as mate-
rials science like optical switching, solar shell, third-order
non-linear optics, Langmuir films, electrochemical sens-
ing, and photo-initiated polymerization.[7,8] Furthermore,
they have important biological applications as antifungal,
antibacterial, antiviral, anti-protozoal, anti-HIV, and
anti-cancer agents.[9–12]
The 1,2,4-triazole nucleus is the main structural unit of
many medicines currently in market.[13] Letrozole, flucon-
azole, ribavirin, anastrozole, and itraconazole are a few to
name which are currently in use as medicines.
1,2,4-Triazole and its heterocyclic derivatives have great
attention due to their synthetic and effective biological
importance. The 1,2,4-triazole moieties had been incorpo-
rated into a different therapeutically interesting drug can-
didates, such as anti-migraine (rizatriptan), antiviral
(ribavarin), antianxiety (alprazolam), and antifungal (flu-
conazole) compounds.[14] 1,2,4-Triazoles and their deriva-
tives have magnificent applications as antiviral, antifungal,
antibacterial, antiasthamatic, pesticidal, hypnotic, breast
cancer preventive, anticancer, antiinflammatory, anticon-
vulsant, CNS depressant, and antihypertensive.[15] Fur-
thermore, they may be used as mimics, isosteres, plant
growth regulating, anticoagulant properties, and psycho-
tropic, vasodilatory, 5-lipoxygenase, and cyclooxygenase
inhibition.[15] It has been reported that triazoles are less
susceptible to metabolic degradation and have wider spec-
trum of activities and higher target specificity as compared
to imidazoles.[16] Moreover, the incorporation of
azomethine Schiff base linkage into 1,2,4-triazole scaffold
resulted in the formation of several therapeutically active
compounds, which may significantly potentiate the anti-
microbial activities.[17]
Lanthanides coordination compounds are the sub-
ject of intense research efforts owing to their unique
structures and their potential applications in advanced
materials such as Ln doped semiconductors, magnetic,
catalytic, fluorescent, and nonlinear optical materials.
The coordination chemistry of lanthanide (III) ions is
very importance, due to incorporation of these com-
pounds in basic and applied research in various scien-
tific areas such as chemistry, material science, and life
science. Nowadays, erbium atom enters in preparation
of different and important metal complexes. Duo to its
optical fluorescent properties, erbium-doped crystals can
be used as optical amplification media and photo-
graphic filter.[22] On the basis of the above facts, it was
conducted in this research article to synthesize and
characterize uranyl (II), erbium (III), and lanthanum
(III) complexes with a new tetradentate triazole Schiff
base. The ligand and its complexes were prepared, and
their structure was established by using different spec-
troscopic tools. Also, we interested in comparing the
theoretical data by DFT/B3LYP method with the experi-
mental results for confirming the structure of the
ligand. Their antibacterial activities against four differ-
ent species were screened, and their anticancer activi-
ties were investigated against two cell lines MCF-7 and
HepG2. The mode of binding between different protein
receptors and the reported compounds was studied
using molecular docking.
2 | EXPERIMENTAL
So transition metal complexes of 1,2,4-triazole Schiff
base have great importance due to their excellent coordi-
nation potential and wonderful pharmacological proper-
ties in antibacterial, antitumor, and antifungal activities.
Letrozole, vorozole, and anastrozole are commercially
1,2,4-triazole drugs that can be used in treatment of
breast cancer. Also, fluconazole that used as antifungal
drugs and trazodone is known for its antidepressant
properties.[18]
2.1 | Materials and reagents
All chemicals used were very pure and of the
analytical reagent grade (AR). The chemicals used
included 4-amino-5-phenyl-1,2,4-triazole-3-(2H)-thione,
1,3-dibromopropane,
benzaldehyde,
UO2(NO3)2,
ErCl3—6H2O and LaCl3—7H2O were supplied from
Sigma-Aldrich. Organic solvents that used were ethyl
alcohol (95%), N,N-dimethylformamide (DMF), KOH,
and glacial acetic acid. Deionized water was usually used
in all preparations.
During the development of actinide chemistry over
the last six decades, it is obvious that uranyl ion with

DEGHADI ET AL.
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2.2 | Solutions
optical density (OD) of each well was measured spectro-
photometrically at 564 nm with an ELIZA microplate
reader (Meter tech. R960, USA). The powder X-ray dif-
fraction (PXRD) was recorded by Bruker D8 Discover
(Bruker AXS Inc., 35 KV, 30 mA) X-ray diffractometer
in Egypt Nanotechnology Center (EGNC), with a step
size of 0.02 and speed scan 0.016 using Cu Kα radiation
(λ = 1.5406 Å) for 2 h with 2θ ranging between
5 and 70.
Stock solutions of the Schiff base ligand and its metal
complexes of 1 Â 10À3 M were prepared by dissolving an
accurately weighed amount in DMF. Then, the conduc-
tivity measured for 1 Â 10À3 M solution of the metal
complexes. Dilute solutions of the Schiff base ligand and
its metal complexes (1 Â 10À4 M) were prepared by accu-
rate dilution from the previous prepared stock solutions
for measuring their UV-Vis spectra.
2.4 | Synthesis of bis (amino triazole)
Schiff base ligand (L)
2.3 | Instrumentation
Microanalyses of carbon, hydrogen, and nitrogen were
carried out at the Microanalytical Center, Cairo Univer-
sity, Egypt, using a CHNS-932 (LECO) Vario elemental
analyzer. Analyses of the metals were conducted by dis-
solving the solid complexes in concentrated HNO3 and
dissolving the residue in deionized water. The metal
content was carried out using inductively coupled
plasma atomic absorption spectrometry (ICP-AES),
Egyptian Petroleum Research Institute. Fourier trans-
form infrared (FT-IR) spectra were recorded with a
PerkinElmer 1650 spectrometer (400–4,000 cmÀ1) as
4-amino-5-phenyl-1,2,4-triazole-3(2H)-thione (1) was
reacted with 1,3-dibromopropane (2) in ethanol-water
(1:1) mixture containing KOH to give the corresponding
1,3-bis(4-amino-5-phenyl-1,2,4-triazol-3-ylsulfanyl)propane
(3). Condensation of the latter compound with benzalde-
hyde in glacial acetic acid afforded the corresponding
Schiff base 1,3-bis(4-benzylideneamino-5-phenyl-1,2,4-
triazol-3-ylsulfanyl)propane (L) (4) in 65% yield as shown
in Scheme 1.
To a solution of 1 (50 mmol) in ethanol-water mixture
(50 ml, 50%) containing KOH (50 mmol) was added
1,3-dibromopropane (2) (25 mmol). The reaction mixture
was heated under reflux for 1 h. The solvent was then
removed in vacuo, and the remaining solid was collected
and crystallized from DMF to give colorless crystals of
compounds (3) as previously prepared.[23]
1
KBr pellets. H-NMR spectra, as solutions in DMSO-d6,
were recorded with a 300 MHz Varian-Oxford Mercury
at room temperature using TMS as an internal stan-
dard. Mass spectra were recorded using the electron
ionization technique at 70 eV with an MS-5988 GS-MS
Hewlett-Packard instrument at the Microanalytical Cen-
ter, National Center for Research, Egypt. UV-Visible
spectra were obtained with a Shimadzu UVmini-1240
To a solution of each of 3 (20 mmol) in glacial
acetic acid (15 ml) was added benzaldehyde (40 mmol).
The reaction mixture was heated under reflux for 2 h.
The solvent was then removed in vacuo, and the
remaining solid was collected and crystallized from eth-
anol as colorless crystals (compound 4) (65%),
mp. 168ꢀC; %). FT-IR (ν, cmÀ1): azomethine (CH═N)
spectrophotometer. Molar conductivities of 1 Â 10À3
M
solutions of the solid complexes were measured using a
Jenway 4010 conductivity meter. Thermogravimetric
(TG), differential thermal analysis (DTA), and differen-
tial thermogravimetric (DTG) analyses of the solid com-
pounds were carried out from room temperature to
1,000ꢀC using a Shimadzu TG-50H thermal analyzer.
Antibacterial measurements were carried out at the
Microanalytical Center, Cairo University, Egypt. Anti-
cancer activity experiments were performed at the
National Cancer Institute, Cancer Biology Department,
Pharmacology Department, Cairo University. The
1
1,603sh, triazole (C═N) 1571sh, (C—S) 767sh. H-NMR
(DMSO) δ 2.35 (quintet, 2H, J = 6.6 Hz, SCH2CH2),
3.44 (t, 4H, J = 6.6 Hz, SCH2), 7.42–7.91 (m, 20H,
ArH's), 8.50 (s, 2H, CH═N) ppm. Anal. for C33H28N8S2
(600.76 g/mol) Calc.: C, 65.98; H, 4.70; N, 18.65.
Found: C, 65.97; H, 4.82; N, 18.58%. UV-Vis (λmax, nm):
251 (π–π* of phenyl groups) and 342 (n–π* of CH═N
azomethine group).
SCHEME 1 Synthesis of Schiff base
ligand 4

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DEGHADI ET AL.
2.5 | Synthesis of metal complexes
(M—O) 578w, (M—N) 506w, (M—S) 417w. UV-Vis (λmax,
nm): 251 (π–π* of phenyl groups) and 338 (n–π* of C═N
azomethine group). 1H-NMR (DMSO) δ 2.50 (quintet,
2H, SCH2CH2), 3.25 (t, 4H, SCH2), 7.46–7.94 (m, 20H,
ArH's) and 8.86 (s, 2H, CH═N) ppm.
UO2(II), Er (III), or La (III) complexes were prepared by
a reaction of 1:1 molar mixture of hot ethanolic solution
(60ꢀC) of UO2(NO3)2 (0.263 g, 6.67 Â 10À4 mol),
ErCl3—6H2O (0.255, 6.67 Â 10À4 mol) or LaCl3—7H2O
(0.248 g, 6.67 Â 10À4 mol) and DMF solution of Schiff
base ligand (L) (0.4 g, 6.67 Â 10À4 mol). The resulting
compounds were stirred under refluxing for 1 h, where-
upon the complexes precipitated. They were collected by
filtration and purified by washing several times with
diethyl ether. The solid complexes then dried in desicca-
tor over anhydrous calcium chloride.
2.6 | Spectrophotometric studies
The absorption spectra were recorded for 1 Â 10À4
M
solutions of the free Schiff base ligand (L) and its metal
complexes. The spectra were scanned within the wave-
length range from 200 to 700 nm.
2.5.1 | [UO2(l)].2NO3
2.7 | Antibacterial activity
Yield 75%; m.p. 156ꢀC; yellow precipitate. Anal. Calc. for
C33H28UN10O8S2 (%): C, 39.94; H, 2.82; N, 14.09; U,
23.94. Found (%): C, 39.01; H, 2.19; N, 14.82; U, 23.12. Λm
(ΩÀ1 molÀ1 cm2) = 134; FT-IR (ν, cmÀ1): azomethine
(CH═N) 1646sh, triazole (C═N) 1,571 s, asy (O═U═O)
921, sym (O═U═O) 826, (C—S) 772 m, (M—N) 499 s,
(M—S) 454w. UV-Vis (λmax, nm): 250 (π–π* of phenyl
The in vitro antibacterial activity tests were performed
through the disc diffusion method.[24] The bacterial
organisms that have been used were Pseudomonas
aeruginosa, Escherichia coli, Bacillus subtilis, and Staph-
ylococcus aureus. Stock solution (0.001 mol) was pre-
pared by dissolving the compounds in DMSO. The
nutrient agar medium for antibacterial was (0.5% pep-
tone, 0.1% beef extract, 0.2% yeast extract, 0.5% NaCl,
and 1.5% agar-agar) was prepared, cooled to 47ꢀC and
then seeded with tested microorganisms. After solidifi-
cation 5 mm diameter holes were punched by a sterile
corkborer. The investigated compounds, that is, Schiff
base ligand (L) and its metal complexes, were intro-
duced in Petri-dishes (only 0.1 m) after dissolving in
DMSO at 1.0 Â 10À3 M. These culture plates were then
incubated at 37ꢀC for 20 h for bacteria. By measuring
the diameter of inhibition zone (in mm), the activity
could be determined. The plates were kept for incuba-
tion at 37ꢀC for 24 h, and then, the plates were exam-
ined for the formation of zone of inhibition. The
diameter of the inhibition zone was measured in milli-
meters. Antimicrobial activities were performed in trip-
licate and the average was taken as the final
reading.[25]
1
groups) and 331 (n–π* of C═N azomethine group). H-
NMR (DMSO) δ 2.49 (quintet, 2H, SCH2CH2), 3.32 (t,
4H, SCH2), 7.48–7.90 (m, 20H, ArH's) and 8.87 (s, 2H,
CH═N) ppm.
2.5.2 | [Er(L)(H2O)cl]Cl2.3H2O
Yield 80%; m.p. 237ꢀC; pink precipitate. Anal. Calc. for
C33H36Cl3ErN8O4S2 (%): C, 41.87; H, 3.81; N, 11.84; Er,
17.66. Found (%): C, 41.22; H, 3.75; N, 11.62; Er, 17.01.
Λ
m (ΩÀ1 molÀ1 cm2) = 130; FT-IR (ν, cmÀ1): azomethine
(CH═N) 1,634 m, triazole (C═N) 1,572 s, H2O stretching
of coordinated water 924w and 880w, (C—S) 758 s,
(M—O) 577 s, (M—N) 501 s, (M—S) 454w. UV–Vis
(λmax, nm): 250 (π–π* of phenyl groups) and 334 (n–π* of
C═N azomethine group). 1H-NMR (DMSO) δ 2.50
(quintet, 2H, SCH2CH2), 3.34 (t, 4H, SCH2), 7.48–7.90
(m, 20H, ArH's) and 8.86 (s, 2H, CH═N) ppm.
2.8 | Anticancer activity
2.5.3 | [La(L)(H2O)cl]Cl2.4H2O
Potential cytotoxicity of all prepared compounds was
tested using the method of Skehan and Storeng.[26] Cells
were plated in 96-multiwell plate (104 cells/well) for 24 h
before treatment with the compounds to allow attach-
ment of cell to the wall of the plate. Different concentra-
tions of the compounds under investigation (5, 12.5,
25, 50, and 100 μM) were added to the cell monolayer,
and triplicate wells were prepared for each individual
Yield 75%; m.p. 180ꢀC; ivory precipitate. Anal. Calc. for
C33H38Cl3LaN8O5S2 (%): C, 42.33; H, 4.06; N, 11.97; La,
14.86. Found (%): C, 41.98; H, 3.75; N, 11.29; La, 14.01.
Λ
m (ΩÀ1 molÀ1 cm2) = 119; FT-IR (ν, cmÀ1): azomethine
(CH═N) 1,656sh, triazole (C═N) 1,572w, H2O stretching
of coordinated water 924w and 880w, (C—S) 761 s,

DEGHADI ET AL.
5 of 17
dose. The monolayer cells were incubated with the com-
pounds for 48 h at 37ꢀC and in 5% CO2 atmosphere. After
48 h, the cells were fixed; then, they were washed and
finally stained with SRB stain. To remove excess stain,
they were washed with acetic acid, and attached stain
was recovered with tris-EDTA buffer. The optical density
(O.D.) of each well was measured spectrophotometrically
at 564 nm with an ELIZA microplate reader, and the
mean background absorbance was automatically sub-
tracted, and mean values of each drug concentration
were calculated. The relation between drug
concentration and surviving fraction is plotted to get the
survival curve of breast tumor cell line for each
compound.
using density functional theory (DFT). The molecular
geometry for the prepared ligand was fully optimized by
using density functional theory (DFT) which based on
the B3LYP method along with the LANL2DZ basis set.
The structure of the ligand (L) was first optimized by
using Chemcraft version 1.6 package[30] and GaussView
version 5.0.9.[31]
3 | RESULTS AND DISCUSSION
3.1 | Experimental characterization of
the ligand (L) and its metal complexes
The structure of the ligand, UO2(II), Er (III), and La (III)
complexes were confirmed by using different spectro-
scopic and physicochemical techniques. These analyses
are elemental analysis (C, H, N, and M), molar conduc-
tance, IR, 1H-NMR, UV-Vis, mass spectrometry, XRD,
and thermal analyses.
2.8.1 | Calculation
The % of cell survival was calculated according to the fol-
lowing relation:
Survival fraction = O.D. (treated cells) /O.D. (control
cells). The IC50 values (the concentrations of the Schiff
base ligand (L) or complexes required to produce 50%
inhibition of cell growth). This experiment was repeated
three times.
3.1.1 | Elemental analysis
The results of elemental analysis together with some
physical properties such as color and melting point were
reported previously in experimental part. The data of the
new prepared Schiff base ligand (L) (compound 4) was
Anal. calc.: C, 65.98; H, 4.70; N, 18.65. Found: C,
65.97; H, 4.82; N, 18.58%. That proved the proposed
molecular formulas C33H28N8S2 of the ligand. Also, the
analytical data of the metal complexes indicated that
the complexes have 1:1 (metal: ligand) stoichiometry
ratio. The prepared compounds were colorless, yellow,
pink, and ivory colored crystals for ligand, uranyl (II),
erbium (II), and lanthanum (III) complexes, respectively.
They are non-hygroscopic, stable at room temperature,
and soluble in DMF and DMSO solvents.
2.9 | Molecular docking
Molecular docking studies were elaborated using MOE
2008 software, and it is a rigid molecular docking soft-
ware. These studies are very important for predicting the
possible binding modes of the most active compounds
against the receptors of breast cancer mutant oxidoreduc-
tase (PDB ID: 3HB5) and crystal structure of the liver
cancer (PDB ID: 2GYT).[27] Docking is an interactive
molecular graphics program which can be used to calcu-
late and display feasible docking modes of a receptor,
ligand, and complex molecules. It necessitates the ligand,
the receptor as input in PDB format. The water mole-
cules, co-crystallized ligands, and other unsupported ele-
ments (e.g., Na, K, and Hg) were removed, but the amino
acid chain was kept.[28] The structure of ligand in PDB
file format was created by Gaussian09 software. The crys-
tal structures of the three receptors were downloaded
from the protein data bank (http://www.rcsb.org./pdb).
3.1.2 | Molar conductivity measurements
The UO2(II), Er (III), and La (III) complexes were dis-
solved in DMF solvent. Their molar conductivities of the
1 Â 10À3 mol LÀ1 solutions at room temperature were
measured. The conductivity measurements are tested the
degree of ionization of the prepared complexes.[32]
The higher value of conductivity than 50 ΩÀ1 molÀ1 cm2
corresponds to the presence of counter ions outside the
coordination sphere and vice versa. The results showed
values of 134, 130, and 119 ΩÀ1 molÀ1 cm2 for
[UO2(L)]—2NO3, [Er(L)(H2O)Cl]Cl2—3H2O, and [La(L)
(H2O)Cl]Cl2—4H2O complexes, respectively. It is
2.10 | Computational methodology
Molecular modeling theoretical calculations and DFT
studies for the prepared triazole Schiff base ligand
(L) were carried out on the Gaussian03 package,[29] by

6 of 17
DEGHADI ET AL.
considered as 1:2 electrolytes where two chloride ions are
present outside the coordination sphere in Er (III) and La
(III) complexes. And two nitrate groups were presented
outside the coordination sphere in UO2(II) complex.[33]
(La—S). The ν (La—OH2) bands were appeared at
924 and 880 cmÀ1 that indicated the participation of
water molecule in the coordination.[42]
The four IR spectra of the prepared compounds were
shown in Figure 1. The results of IR showed that the
ligand behaved as a neutral tetradentate ligand that coor-
dinated to metal ions via four sites of donation (N, N, S,
and S).
3.1.3 | IR spectra
The structure of triazole Schiff base is confirmed by the
appearance of new strong azomethine ν (CH═N) band at
1,603 cmÀ1 in its spectrum.[34] Also, the spectrum of the
ligand showed band at 1,571 cmÀ1 corresponded to
ν(C═N) of triazole moiety and 767 cmÀ1 of C—S
bond.[35,36]
3.1.4 | 1H-NMR spectra
The 1H-NMR spectra of the Schiff base ligand (L),
[UO2(L)]—2NO3, [Er(L)(H2O)Cl]Cl2—3H2O, and [La(L)
(H2O)Cl]Cl2—4H2O complexes were studied. The spec-
trum of the ligand showed signals at 2.35 (quintet, 2H,
J = 6.6 Hz, SCH2CH2), 3.44 (t, 4H, J = 6.6 Hz, SCH2),
7.42–7.91 (m, 20H, ArH's), and 8.50 (s, 2H, CH═N)
ppm.[43–45]
In IR spectrum of uranyl (II) complex, it reported that
azomethine ν (CH═N) band appeared at 1,646 cmÀ1. This
band shifted by about 43 cmÀ1, indicating the participa-
tion of this group in coordination. The triazole group still
appeared at the same value as at the free ligand. Further-
more, there are shifting in the band of ν(C—S) which
appeared in the complex at 772 cmÀ1 confirming the sec-
ond participation of the ligand with the metal ion. The
spectrum of uranyl complex showed two bands at
The spectrum of [UO2(L)]—2NO3 complex showed
signals at 2.49 (quintet, 2H, SCH2CH2), 3.32 (t, 4H,
SCH2), 7.48–7.90 (m, 20H, ArH's), and 8.87 (s, 2H,
CH═N) ppm. While, spectrum of [Er(L)(H2O)Cl]
Cl2—3H2O complex indicated signals at 2.50 (quintet,
2H, SCH2CH2), 3.34 (t, 4H, SCH2), 7.48–7.90 (m, 20H,
ArH's), and 8.86 (s, 2H, CH═N) ppm. Also, spectrum of
[La(L)(H2O)Cl]Cl2—4H2O complex indicated signals at
2.50 (quintet, 2H, SCH2CH2), 3.25 (t, 4H, SCH2), 7.46–
7.94 (m, 20H, ArH's), and 8.86 (s, 2H, CH═N) ppm. The
signal corresponding to azomethine group was shifted
from the free ligand by about 0.36, or 0.37 ppm, suggests
the coordination through azomethime nitrogen of the
ligand to erbium, lanthanum, or uranyl atoms. Also,
there are shifting in signals of SCH2CH2 to higher values
by about 0.14 in uranyl complex or 0.15 ppm in erbium
and lanthanum complexes, and signals of SCH2 to lower
values by about À0.12, À0.10, and À0.19 ppm for
UO2(II), Er (III), and La (III) complexes, respectively. All
spectra of the prepared compounds were reported in
921 and 826 cmÀ1 assigned to
νasy(O═U═O) and
νsy(O═U═O), respectively.[37] These results exhibited that
the UO2 moiety is virtually linear.[38] New band observed
in the complex at 499 cmÀ1 which related to ν(U—N),
while the band appeared at 454 cmÀ1 was corresponded
to ν(U—S).[18,34] The spectrum also exhibited band at
1,385 cmÀ1 corresponded to an uncoordinated nitrate
group.[36] The IR spectrum of UO2(II) complex exhibited
two non-ligand bands at 1,448 and 1,256 cmÀ1 which
support the monodentate nature of NO3 group.[39,40]
The same observation in IR spectrum of Er (III) com-
plex, which the azomethine group was shifted by about
31 cmÀ1, and C—S band was appeared at 758 cmÀ1
.
These results confirmed the involvement of these four
heteroatoms in coordination. The triazole band also
appeared at the same position as in the free ligand. New
bands were observed at 577 and 501 cmÀ1 related to
(Er—O) and (Er—N) vibrations.[41] The band appeared
at 454 cmÀ1 was corresponded to ν (Er—S). The ν
(Er—OH2) bands were appeared at 924 and 880 cmÀ1
that indicated the participation of water molecule in the
coordination.[42]
1
Figure 2. The H-NMR results indicated the successful
preparation of the Schiff base and its metal complexes.
3.1.5 | Mass spectra
Furthermore, in IR spectrum of La (III) complex, the
azomethine group was shifted by about 53 cmÀ1, and
C—S band was appeared at 761 cmÀ1. These data con-
firmed the involvement of these sites also in coordina-
tion. The triazole band appeared at the same position as
in the free ligand. New bands were observed at 576 and
506 cmÀ1 related to (La—O) and (La—N) vibrations.[41]
The band appeared at 417 cmÀ1 was corresponded to ν
The mass spectra of the ligand and its complexes were
recorded and investigated at 70 eV of electron energy. It
is recognized that the molecular ion peaks of the four
prepared compounds are in good agreement with their
suggested empirical formula as shown from elemental
analyses. The ion peaks were 994.30, 945.40, 939.0, and
600.20 m/z which were compatible with their molecular
weight of 994, 945.76, 935.5, and 600 g/mol for UO2(II),

DEGHADI ET AL.
7 of 17
FIGURE 2 1H-NMR spectra of (a) Schiff base ligand,
(b) [UO2(L)]—2NO3, (c) [Er(L)(H2O)Cl]Cl2—3H2O, and (d) La(L)
(H2O)Cl]Cl2—4H2O
Er (III), and La (III) complexes and Schiff base ligand
(L), respectively. Then, the spectra were recorded in
Figure S1.
3.1.6 | UV-visible spectra
FIGURE 1 The IR spectra of (a) Schiff base ligand, (b) [Er(L)
(H2O)Cl]Cl2—3H2O, (c) [UO2(L)]—2NO3, and (d) [La(L)(H2O)Cl]
Cl2—4H2O
The synthesis of UO2(II)/Er (III)/La (III)-Schiff base com-
plexes was also confirmed by using UV/Vis spectra.

8 of 17
DEGHADI ET AL.
Electronic spectra of the prepared Schiff base ligand
(L) and its metal complexes were recorded in DMF solu-
tion, at wavelength range 200–700 nm with concentra-
tion 1 Â 10À4 M. The spectrum of the ligand showed two
absorption bands at 342 and 251 nm. The first band cor-
responded to nÀπ* transition of (CH═N) azomethine
group in the free ligand.[46] At which the second band
related to π–π* transition of phenyl groups.[47] The
342 value was shifted to 334 nm in Er (III) complex,
while shifted in UO2(II) complex to 331 nm and to
338 nm in La (III)-complex. This shifting confirmed the
participation of the azomethine group in combination
and coordination. The second band at 251 nm in the
ligand appeared at the same region in the three
complexes.
3.1.7 | X-ray diffraction
X-ray diffraction (XRD) was performed to obtain further
evidence about the structure of the metal complexes.[48]
Also, it performed the average grain size, crystallinity,
and other structural parameter. The diffractograms
obtained for the Schiff base and its metal complexes were
given in Figure 3. The XRD patterns of the compounds
under investigation showed good intense peaks indicat-
ing high crystallinity of the prepared compounds. Except
[La(L)(H2O)Cl]Cl2—4H2O complex which had semi-
crystalline behavior.
It can be clearly seen that the pattern of the Schiff
base changed from its metal complexes, which may be
approved to the formation of a well-defined distorted
crystalline metal complexes structure.
3.1.8 | Thermal analysis of Schiff base
ligand, UO2(II), Er (III), and La (III) complexes
FIGURE 3 XRD patterns of (a) Schiff base ligand,
(b) [UO2(L)]—2NO3, (c) [Er(L)(H2O)Cl]Cl2—3H2O, and (d) La(L)
(H2O)Cl]Cl2—4H2O
The thermal stability of the synthesized ligand
(L) and its metal complexes was investigated by
using thermogravimetric analysis (TG), differential
thermogravimetric analysis (DTG), and differential ther-
mal analysis (DTA) within the temperature range of 25–
900ꢀC. The results comprising temperature ranges, stages
of decomposition, decomposition product lost, and the
calculated mass loss percentages were listed in Table 1.
And all TGA/DTG/DTA spectra were represented in
Figure S2.
The thermal decomposition of the Schiff base ligand
involved one decomposition step. It was started at 170ꢀC
and finished at 530ꢀC, which involved the removal of
C33H28N8S2 molecule (found 99.40% and calc. = 100%).
The maximum temperature peak was at 262ꢀC. No
residues were found after decomposition of the ligand.
From DTA curve, it showed endothermic peaks with
t
max = 162ꢀC and 289ꢀC, in which the lower temperature
is closed to the melting point of the ligand. The overall
weight loss amounted to 99.40% (calc. = 100%).
[UO2(L)]—2NO3 complex showed two decomposition
stages. The first stage is two steps. This stage was in the
temperature range of 25–320ꢀC, which congruent to
the loss of 2HNO3 and C28H25N7S molecules
(found = 62.02% and calc. = 62.07%). The maximum
temperature peaks were at 207ꢀC and 294ꢀC. This stage
was accompanied by two endothermic peaks with
tmax = 138 and 286ꢀC on DTA curve. The second stage is

DEGHADI ET AL.
9 of 17
TABLE 1 Thermoanalytical results (TG, DTG, and DTA) of Schiff base (L) and its metal complexes
TG range
(ꢀC)
DTGmax
(ꢀC)
DTAmax
(ꢀC)
Mass loss total mass loss
Estim (Calc.) %
Compound
n
1
2
Assignment
Residues
Schiff base (L)
[UO2(L)]—2NO3
170–530
25–320
262
162, 289
138, 286
99.4 (100)
Loss of C33H28N8S2
—
207, 294
62.02, (62.07)
Loss of 2HNO3 and
C28H25N7S
UO2
320–645
40–160
431
406
84
1
2
10.57 (10.97), 72.59 (73.04)
18.66 (18.35)
Loss of C5H3NS
[Er(L)(H2O)Cl]
Cl2—3H2O
77, 116
Loss of 2H2O, Cl2, HCl
and C2H6
½ Er2O3
160–900
30–190
217, 267
79, 159
162
2
2
61.09 (61.43), 79.75 (79.78)
15.22 (15.23)
Loss of C31H25N8S2O0.5
[La(L)(H2O)Cl]
Cl2—4H2O
81, 158
Loss of 3H2O, HCl and
C4H4
½ La2O3
+ 5C
190–525
228, 277
266, 417
2
61.14 (61.04), 76.36 (76.27)
Loss of Cl2,
C24H28N8S2O0.5
Note: n = number of decomposition steps.
one step. It was in the temperature range of 320–645ꢀC
represented the loss of C5H3NS molecule which accom-
panied by endothermic peak at tmax = 406 on DTA curve
(found = 10.57% and calc. = 10.97%). The maximum
temperature peak was at 431ꢀC. Finally, the UO2 oxide
remained as residues with overall weight loss amounted
to 72.59% (calc. = 73.04%).
[Er(L)(H2O)Cl]Cl2—3H2O complex showed also two
decomposition stages. The first stage is two steps in the
temperature range of 40–160ꢀC. Which congruent to
the loss of two water molecules, Cl2 gas, HCl, and C2H6
molecules (found = 18.66% and calc. = 18.35%). The
maximum temperature peaks were at 77ꢀC and 116ꢀC.
The second stage was also two steps. It was in the tem-
perature range of 160–900ꢀC represented the loss of
C31H25N8S2O0.5 molecule (found = 61.09% and calc. =
61.43%), with maximum temperature peaks at 217ꢀC and
267ꢀC. The spectrum of DTA curve accompanied by two
endothermic peaks at tmax = 84ꢀC and 162ꢀC. Finally,
the erbium oxide remained as residues with overall
weight loss amounted to 79.75% (calc. = 79.78%).
3.1.9 | Antimicrobial activities
In vitro antibacterial activities of the Schiff base ligand,
uranyl, erbium, and lanthanum complexes are given in
Table 2. The solvent DMF is used as negative control,
while Ampicillin is used as positive standard for
antibacterial. Finally, the experiment is repeated three
times under similar conditions.
The antibacterial activity of the prepared compounds
investigated that the complexes showed higher activity
than the ligand that had 0.0 mm/mg values. The order of
their activity was represented as [UO2(L)]—2NO3 > [La
(L)(H2O)Cl]Cl2—4H2O < [Er(L)(H2O)Cl]Cl2—
3H2O > Ligand (L) against different four bacterial
species.
The data showed that the activity values against Bacil-
lus subtilis was 12, 12, and 11 mm/mg; Staphylococcus
aureus was 15, 13, and 12 mm/mg; Escherichia coli was
13, 12, and 11 mm/mg; and Pseudomonas aeruginosa
was 15, 13, and 13 mm/mg, for uranyl, lanthanum, and
erbium complexes, respectively.
[La(L)(H2O)Cl]Cl2—4H2O complex showed also two
decomposition stages. The first stage is two steps in the
temperature range of 30–190ꢀC, which congruent to
the loss of three water molecules, HCl and C4H4 mole-
cules (found = 15.22% and calc. = 15.23%). The maxi-
mum temperature peaks were at 79ꢀC and 159ꢀC. The
second stage was also two steps. It was in the tempera-
ture range of 190–525ꢀC represented the loss of Cl2 gas
and C24H28N8S2O0.5 molecules (found = 61.14% and calc.
= 61.04%), with maximum temperature peaks at 228ꢀC
and 277ꢀC. The spectrum of DTA curve accompanied by
four endothermic peaks at tmax = 81ꢀC, 158ꢀC, 266ꢀC,
and 417ꢀC. Finally, the lanthanum oxide contaminated
with carbon remained as residues with overall weight
loss amounted to 76.36% (calc. = 76.27%).
The difference in the effectiveness of the various com-
pounds that prepared against any organisms depends up
on the difference in the ribosome of the microbial cells or
on their impermeability of the microbial cells.[49] The
metal complexes showed higher antimicrobial activity
than the free Schiff base ligand. This increase may be as
reason of the effect of metal ion on normal cell process.
This phenomenon can be explained on the basis of Over-
tone's concept.[50] and chelation theory.[51]
3.1.10 | Anticancer activities
The effect of ligand, uranyl, erbium, and lanthanum com-
plexes on the growth of tumor cells was investigated

10 of 17
DEGHADI ET AL.
TABLE 2 Antibacterial activity of Schiff base (L) and its metal complexes
Inhibition zone diameter (mm/mg sample)
(Gram positive)
(Gram negative)
Sample
Bacillus subtilis
Staphylococcus aureus
Escherichia coli
Pseudomonas aeruginosa
Control: DMSO
Schiff base (L)
0
NA
12
0
NA
15
0
NA
13
0
NA
15
[UO2(L)]—2NO3
[Er(L)(H2O)Cl]Cl2—3H2O
[La(L)(H2O)Cl]Cl2—4H2O
Ampicilin
11
12
11
13
12
13
12
13
26
21
25
26
Abbreviation: NA, no activity.
TABLE 3 Anticancer activities of Schiff base (L) and its metal complexes against MCF-7 and HepG2 cell lines
Schiff base
(L)
[UO2(L)]—
2NO3
[Er(L)(H2O)Cl]—
Cl2—3H2O
[La(L)(H2O)Cl]—
Cl2—4H2O
Compounds Conc. (μM)
Surviving fraction (MCF-7)
0.000
5.000
1.000
0.870
0.565
0.478
0.464
23
1.000
0.696
0.565
0.536
0.502
ꢁ50
1.000
0.623
0.580
0.565
0.377
35
1.000
0.896
0.709
0.560
0.410
36
12.500
25.000
50.000
IC50
Surviving fraction (HepG2)
0.000
5.000
1.000
0.916
0.870
0.551
0.501
ꢁ50
1.000
0.681
0.522
0.464
0.319
17.6
1.000
0.681
0.536
0.435
0.333
18
1.000
0.846
0.769
0.538
0.423
33
12.500
25.000
50.000
IC50
FIGURE 4 Anticancer activities of Schiff base ligand (L) and its metal complexes against (a) MCF-7 and (b) HepG2 cell lines
against two-cell line, as shown in Table 3. The synthe-
sized compounds were recorded for their cytotoxic
(Figure 4) effects against MCF-7 and HepG2 cell lines.
Cultures were exposed to the prepared compounds at
four different concentrations of (5, 12.5, 25, and 50 μM),
and then, their IC50 values were calculated. First, against
breast cancer cell line, the results appeared to be very
good for the prepared compounds, at which the ligand
showed the highest IC50 value with 23 μM, while uranyl,
erbium, and lanthanum complexes had ꢁ50, 35, and
36 μM, respectively. Second, against hepatic cancer cell
line, the prepared compounds showed results as

DEGHADI ET AL.
11 of 17
[UO2(L)]—2NO3 (17.6 μM) > [Er(L)(H2O)Cl]Cl2—3H2O
ring. Then, the lipophilic character of the central metal
atom improved which increase the liposolubility and
hydrophobic character of the complex. This cause the
permeation through the lipid layers of the cell membrane
of different organisms very easy.[52]
(18 μM) > [La(L)(H2O)Cl]Cl2—4H2O
(33 μM) > Schiff
base ligand (ꢁ50 μM). Their results indicated that the
prepared compounds had good activities against different
cell lines. From all the previous data, the ligand and its
complexes showed anti-tumor activity that may be help
in the future in-vivo researches and can be used after
testing on different organisms as effective drugs for treat-
ment of breast and hepatic carcinoma.The effective
results of the metal complexes against different bacterial
species and various anticancer cell lines may be due to
the effect of the metal ion on the normal cell process
according to Tweedy's chelation theory. Upon chelation,
the polarity of the metal ions was decreased due to partial
sharing of its positive charge with the possible π-electron
delocalization and donor group in the whole complex
3.2 | Theoretical characterization of the
Schiff base ligand (L)
To confirm the successful preparation of the ligand, it
was computed theoretically by DFT method. The opti-
mized structure, some quantum parameters, MEP, and
IR spectrum were reported. All data were compatible
with the experimental one which confirming the
preparation.
3.2.1 | Geometrical optimization of the
ligand
The stable configuration of the triazole ligand was shown
in Figure 5. The spheres had color as blue, yellow, and
gray corresponding to N, S, and C atoms, respectively.[20]
Also, its bond length and angles were calculated and
listed in Table S4. The dipole moment of the ligand was
calculated from Gaussian 09, and its value is 8.6228
Debye. Furthermore, the total energy of the ligand
appeared to be À2495.276 a.u.
3.2.2 | Molecular electrostatic potential
The electrostatic potential maps were calculated from
DFT method for identification of the electronic charge
distribution around molecular surface and then
predicting the sites of reactions. The map of the ligand
FIGURE 5 The optimized structure of triazole Schiff base
ligand (L)
FIGURE 6 Molecular electrostatic potential
map of Schiff base ligand (L), the electron
density isosurface is 0.004 a.u.

12 of 17
DEGHADI ET AL.
was represented by using the same basis set of optimiza-
tion.[53] This 3D plot of molecular electrostatic potential
(MEP) was showed in the Figure 6.
calculated infrared spectra in the range of 4,000 to
400 cmÀ1. The theoretical results had been calculated
by using B3LYP/DFT. The vibrational frequencies
computed by quantum chemical methods such as
DFT reported some systematic errors. For overcoming
The map had different colors that corresponding to
electron rich or poor area. The red color represents the
electron-rich region (electrophilic attack), while blue
color represents the electron-poor region (nucleophilic
attack). The green color points to neutral electrostatic
potential region.[54] The ligand showed uniform distribu-
tion of charge density. The nitrogen and sulfur atoms
were surrounded by a greater negative charge surface,
making these sites potentially more favorable for electro-
philic attack (red to orange). The aromatic rings appeared
as green color.
TABLE 4 The different Mullikan charges of Schiff base ligand
Atoms Mullikan charges Atoms Mullikan charges
C1
0.632795
0.19538
C30
C31
C33
C25
C39
C40
C41
C42
C44
C46
C50
C51
C52
C53
C55
C57
S61
0.040488
0.023364
0.014136
0.025642
À0.05104
0.011845
0.0535
C2
N3
À0.37799
À0.3788
À0.61736
À0.36785
À0.37637
À0.61731
0.638785
0.214411
À0.31527
À0.3206
0.390687
0.388241
À0.05096
0.005402
0.043974
0.016381
0.014631
0.014513
À0.04547
0.017759
N4
N5
3.2.3 | Mulliken charge analyses
N6
The Mulliken electronegativity (Figure 7 and Table 4)
also indicated the increase of electronegativity of sulfur
and nitrogen atoms than the carbon atoms as represented
from the results. These data indicated the favorable sites
of donation (electrophilic attack) and the high probability
of electron transfer from these atoms to the uranyl,
erbium, and lanthanum ions in the proposed com-
plexes[55], where the nitrogen and sulfur atoms had more
negative charges than the other atoms. The C1, C2, C9,
and C10 atoms had higher positive atomic charges than
the other carbon atoms. This was due to the attachment
of sulfur and nitrogen atoms (electronegative atoms) to
carbon atoms.
N7
N8
0.001446
0.005753
0.004388
À0.04915
0.058541
0.009994
0.01043
C9
C10
N11
N12
C13
C14
C17
C18
C19
C20
C22
C24
C28
C29
0.001834
0.009877
À0.41558
À0.3959
À0.09825
0.103765
À0.09303
S62
C63
C66
C69
3.2.4 | Vibrational properties
Figure
8 showed theoretical IR spectrum of the
ligand. Then, compare between the experimental and
FIGURE 7 Mullikan charges of Schiff base ligand

DEGHADI ET AL.
13 of 17
FIGURE 8 Theoretical IR spectrum of the
ligand
TABLE 5 Energy values obtained in docking calculations of ligand (L), [UO2(L)]—2NO3, [Er(L)(H2O)Cl]Cl2—3H2O, and [La(L)(H2O)
Cl]Cl2—4H2O with 3HB5 and 2GYT receptors
Ligand
Receptor moiety
Compound
Receptor site
Interaction Distance (Aꢀ) E (kcal/mol)
Ligand (L)
3HB5
N7
N, GLY, 92, (X)
NZ, LYS,195, (X)
NE, ARG, 37, (X)
NZ, LYS, 195, (X)
OXT, LYS, 76, (A)
O, LYS, 76, (A)
H—acceptor 3.35
H—acceptor 3.42
À0.9
À1.9
À0.7
À6.8
À1.7
À0.4
À0.3
À1.2
À0.9
À0.7
À2.9
À1.3
À0.6
À0.8
À3.9
À28.0
À2.2
À7.4
À4.1
À1.3
À4.6
À3.9
À5.0
À3.8
À4.1
À0.3
À2.5
N11
6-ring
5-ring
S61
π—cation
π—cation
H—donor
H—donor
H—donor
π—cation
π—H
3.87
4.69
3.94
3.80
3.80
3.82
4.30
4.20
2GYT
S62
S62
OXT, LYS, 76, (A)
NZ, LYS, 4, (A)
CG, GLN, 13, (A),
CB, MET, 75, (A),
N, GLY, 92, (X)
NE, ARG, 37, (X)
6-ring
5-ring
6-ring
N7
π—H
[UO2(L)].2NO3 complex
3HB5
H—acceptor 3.16
6-ring
6-ring
6-ring
6-ring
O73
O74
O73
S61
π—cation
3.85
3.60
4.20
4.46
NH2, ARG, 37, (X) π—cation
CB, ALA, 91, (X)
NZ, LYS, 195, (X)
NZ, LYS, 4, (A)
NZ, LYS, 4, (A)
NZ, LYS, 4, (A)
O, GLY, 92, (X)
O, GLY, 9, (X)
O, GLY, 92, (X)
N, SER, 11, (X)
π—H
π—cation
2GYT
3HB5
H—acceptor 2.63
H—acceptor 2.85
ionic
2.63
3.37
4.03
2.73
[Er(L)(H2O) Cl]Cl2.3H2O
complex
H—donor
H—donor
H—donor
S62
O74
N6
H—acceptor 3.04
2.92
Er72
N7
NH2, ARG, 37, (X) ionic
2GYT
3HB5
2GYT
NZ, LYS, 4, (A)
NZ, LYS, 40, (X)
SD, MET, 1, (A),
O, LYS, 76, (A),
H—acceptor 3.29
H—acceptor 3.34
[La(L) (H2O)Cl] Cl2.4H2O
complex
N3
N4
H—donor
H—donor
3.95
3.47
Cl72

14 of 17
DEGHADI ET AL.
these systematic errors, it used a scaling factor as
0.9648 for LanL2DZ (which can be formed from
harmonicity).[56]
The experimental bands of the ligand were observed
at 1,603, 1,571, and 767 cmÀ1 that corresponded to
azomethine, triazole moiety, and C—S vibrations, respec-
tively, and theoretically, these bands are computed at
1625.17, 1,551.32, and 793.73 cmÀ1, respectively.[57] The
results confirmed the successful preparation of the tri-
azole ligand.
3.2.5 | Molecular modeling of Schiff base
ligand (L), [UO2(L)]—2NO3, [Er(L)(H2O)cl]
Cl2—3H2O and [La(L)(H2O)cl]Cl2—4H2O
complexes with different receptors:
Docking study
The ligand, uranyl (II), erbium (III), and lanthanum (III)
complexes were subjected to molecular docking with
3HB5 and 2GYT receptors using Auto Dock Tools. This is
theoretical tool that used to confirm the results observed
FIGURE 9 Three-dimensional plots of the
interaction between Schiff base with receptors
of (a) 3HB5, (b) 2GYT, [UO2(L)]—2NO3 with
receptors of (c) 3HB5, (d) 2GYT, [Er(L)(H2O)Cl]
Cl2—3H2O with receptors of (e) 3HB5 and (f)
2GYT, and [La(L)(H2O)Cl]Cl2—4H2O with
receptors of (g) 3HB5 and (h) 2GYT

DEGHADI ET AL.
15 of 17
from experimental anticancer activities. They were ana-
lyzed for their docking conformations in terms of binding
energy, hydrogen bonding, and hydrophobic interactions
with different protein receptors.[57,58] The crystal struc-
ture of these receptors was obtained from the protein
data bank. Finally, the results of different types of bond-
ing and minimum energy values were listed in Table 5.
The 3D plots of the interaction of the prepared com-
pounds with different receptors were also represented in
Figure 9.
First, the compounds were investigated against
crystal structure of breast cancer mutant oxidoreduc-
tase (PDB ID: 3HB5). The ligand showed four interac-
tions with amino acids LYS, ARG, and GLY. These
interactions were H—acceptors and pi—cation bonds,
in which the ligand showed the lowest binding energy
À6.8 kcal/mol, while uranyl, erbium, and lanthanum
complexes showed some different interaction besides
H—acceptors and pi—cation as H—donor, pi—H, and
ionic bonds. The binding energies were appeared at
À3.9, À4.1, and À5.0 for [UO2(L)]—2NO3 (ꢁ50 μM),
[La(L)(H2O)Cl]Cl2—4H2O (36 μM), and [Er(L)(H2O)Cl]
Cl2—3H2O (35 μM) complexes, respectively. The data
confirmed the results reported previously about MCF-7
cell line of anticancer activity as L > Er-L > La-
L > UO2-L.
FIGURE 10 Structure of [UO2(L)] 2NO3, [Er(L)(H2O)Cl]
Cl2 3H2O, and [La(L)(H2O)Cl]Cl2 4H2O complexes
Second, the compounds were investigated against
crystal structure of hepatic cancer (PDB ID: 2GYT). The
ligand reported six interactions with various amino acids
as LYS, GLN, and MET. These interactions were H—
donor, pi—cation, and pi—H bonds, with binding energy
value À1.7 kcal/mol. H-acceptor interaction was
appeared in Er—L, H—donor interaction for La—L, and
H—acceptor and ionic bonds for UO2—L. The values of
their binding energies were À28.0, À3.8, and À2.5 kcal/
mol for [UO2(L)]—2NO3 (17.6 μM), [Er(L)(H2O)Cl]
Cl2—3H2O (18 μM), and [La(L)(H2O)Cl]Cl2—4H2O
(33 μM), respectively. Furthermore, these data confirmed
the results reported previously about HepG2 cell line of
anticancer activity as UO2—L > Er—L > La—L > L.
Finally, these theoretical data from molecular dock-
ing well confirmed the experimental results that
appeared about anticancer activity of the ligand and its
complexes.
4 | CONCLUSION
The present investigation described the synthesis, exper-
imental, and theoretical characterization of bis (amino
triazole) Schiff base ligand by using DFT method. Its
uranyl (II), erbium (III), and lanthanum (III) complexes
were also prepared. The compounds were investigated
against four bacteria species. Also, their anticancer
activities against two cell lines (MCF-7 and HepG2)
were screened. From elemental analysis data, it was
shown that the ligand was prepared in 1:2 ratio of
1,3-bis(4-amino-5-phenyl-1,2,4-triazol-3-ylsulfanyl)propane
with benzaldehyde, while the complexes were prepared
in 1:1 molar ratio with metal ions. IR spectral data
reported that ligand behaved as a neutral tetradentate
N,N,S,S-ligand. Conductivity measurements indicated
that the UO2(II), Er (III), and La (III) complexes are 1:2
electrolytes. All complexes had octahedral geometry.
Their bacterial activity against two Gram-positive
bacteria (Bacillus subtilis and Staphylococcus aureus) and
two Gram-negative bacteria (Escherichia coli and
Pseudomonas aeruginosa) showed that ligand had no
activity against four types of bacteria but UO2(II) had
the higher bacterial activity. The anticancer activity indi-
cated that ligand had the lowest IC50 value (23 μM) for
MCF-7 cell line, while the [UO2(L)]—2NO3 complex had
3.2.6 | Structural interpretation
The structures of uranyl (II), erbium (III), and lantha-
num (III) complexes were elucidated by elemental analy-
1
sis, IR, H-NMR, MS, molar conductance, UV/Vis, and
thermal analyses. Then, their structures were represented
in Figure 10.

16 of 17
DEGHADI ET AL.
[15] K. M. Khan, S. Siddiqui, M. Saleem, M. Taha, S. M. Saad, S.
Perveen, M. I. Choudhary, Bioorg. Med. Chem. 2014, 22, 6509.
[16] K. El Akri, K. Bougrin, J. Balzarini, A. Faraj, R. Benhida, Bio-
org. Med. Chem. Lett. 2007, 17(23), 6656.
[17] A. F. Alghamdi, N. Rezki, J. Taibah Univer. Sci. 2017, 11
(5), 759.
the lowest IC50 value (17.6 μM) for HepG2 cell line. The
study of molecular docking between the three prepared
compounds with receptors of 3HB5 and 2GYT was inves-
tigated for confirming the experimental anticancer activ-
ity results.
[18] P. Tyagi, M. Tyagi, S. Agrawal, S. Chandra, H. Ojha, M.
Pathak, Spectrochim. Acta A 2017, 171, 246.
AUTHOR CONTRIBUTIONS
Reem Deghadi: Formal analysis; methodology;
resources. Ashraf Abbas: Data curation; formal analysis;
methodology; resources. Gehad Mohamed: Data
curation; project administration; supervision.
[19] J. L. Sonnenberg, P. J. Hay, R. L. Martin, B. E. Bursten, Inorg.
Chem. 2005, 44, 2255.
[20] X. L. Li, J. Luo, Y. W. Lin, L. F. Liao, C. M. Nie, J. Radioanal.
Nucl. Chem. 2016, 307, 407.
[21] X. Shen, L. Liao, L. Chen, Y. He, C. Xu, X. Xiao, Y. Lin, C.
Nie, Spectrochim. Acta A 2014, 123, 110.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are avail-
able on request from the corresponding author. The data
are not publicly available due to privacy or ethical
restrictions.
[22] A. L. El-Ansary, N. S. Abdel-Kader, Inter. J. Inorg. Chem. 2012.
13 pages
[23] A. H. M. Elwahy, A. A. Abbas, Y. A. Ibrahim, J. Chem. Res.
1996, 4, 182.
[24] A. Albert, Selective Toxicity: Physico-Chemical Basis of Therapy,
6th ed., Wiley, New York 1979.
[25] S. Chandra, D. Jain, A. K. Sharma, P. Sharma, Molecules 2009,
14(1), 174.
[26] P. Skehan, R. Storeng, D. Scudiero, A. Monks, J. McMahon, D.
Vistica, J. T. Warren, H. Bokesch, S. Kenney, M. R. Boyd,
J. National Cancer Instit. 1990, 82(13), 1107.
[27] C. J. Dhanaraj, I. U. Hassan, J. Johnson, J. Joseph, R. S.
Joseyphus, J. Photochem. Photobiol. B 2016, 162, 115.
[28] C. Balakrishnan, L. Subha, M. A. Neelakantan, S. S.
Mariappan, Spectrochim. Acta A 2015, 150, 671.
[29] M. J. Frisch, Gaussian 03, Revision C.01, Gaussian Inc, Wal-
lingford CT 2004.
[30] G. G. Mohamed, Z. H. Abd El-Wahab, Spectrochim. Acta A
2005, 61, 1059.
[31] R. Dennington, T. Keith, J. Millam, editorsGaussView, Version
5.0.8, R.KS, Semichem Inc., Shawnee Mission, Dennington
2009.
ORCID
Reem G. Deghadi https://orcid.org/0000-0002-4988-
8907
Ashraf A. Abbas https://orcid.org/0000-0001-7061-9907
Gehad G. Mohamed https://orcid.org/0000-0002-1525-
5271
REFERENCES
[1] H. Q. Chang, L. Jia, J. Xu, T. F. Zhu, Z. Q. Xu, R. H. Chen,
T. L. Ma, Y. Wang, W. N. Wu, J. Mol. Struct. 2015, 1106, 366.
[2] K. J. Davis, C. Richardson, J. L. Beck, B. M. Knowles, A.
Guedin, J. L. Mergny, A. C. Willis, S. F. Ralph, Dalton Trans.
2015, 44, 3136.
[3] S. Khani, M. Montazerozohori, R. Naghiha, J. Phys. Org. Chem.
2018, 31(12), e3873.
[32] W. H. Mahmoud, R. G. Deghadi, G. G. Mohamed, Arabian
J. Chem. 2020, 13, 5390.
[4] H. Makio, N. Kashiwa, T. Fujita, Adv. Syn. Catalysis. 2002,
344(5), 477.
[33] G. G. Mohamed, E. M. Zayed, A. M. M. Hindy, Spectrochim.
Acta A 2015, 145, 76.
[34] A. S. Munde, A. N. Jagdale, S. M. Jadhav, T. K. Chondhekar,
J. Serb. Chem. Soc. 2010, 75(3), 349.
[35] A. Antony, F. Fasna, P. A. Ajil, J. T. Varkey, Res. Rev. J. Chem.
2016, 5(2), 37.
[36] M. Shakir, M. Azam, M. F. Ullah, S. M. Hadi, J. Photochem.
Photobiol. B 2011, 104, 449.
[37] M. Gabera, H. A. El-Ghamry, S. K. Fathalla, M. A. Mansour,
Mater. Sci. Eng. C 2018, 83, 78.
[38] R. C. Maurya, B. Shukla, J. Chourasia, S. Roy, P. Bohre, S.
Sahu, M. H. Martin, Arabian J Chem 2015, 8(5), 655.
[39] L. J. Bellamy, The IR spectra of complex molecules, Ethuen,
London 1985.
[5] T. D. Pasatoiu, J. P. Sutter, A. M. Madalan, F. Z. Fellah, C.
Duhayon, M. Andruh, Inorg. Chem. 2011, 50(13), 5890.
[6] S. A. Mousavi, M. Montazerozohori, R. Naghiha, A.
Masoudias, S. Mojahedi, T. Doert, Appl. Organomet. Chem.
2020, 34(4), e5550.
[7] L. Mishra, S. K. Dubey, Spectrochim. Acta. Part A 2007,
68, 364.
[8] P. M. Ronad, M. N. Noolvi, S. Sapkal, S. Dharbhamulla, V. S.
Maddi, Eur. J. Med. Chem. 2010, 45, 85.
[9] G. Ceyhan, M. Tümer, M. Kose, V. McKee, S. Akar, JOL 2012,
132, 2917.
[10] W. A. Abbas, A. S. Al-Hamdani, I. P. Widiantara, R. G.
Hamoodah, Y. G. Ko, J. Phys. Org. Chem. 2017, 30(12), e3707.
[11] L. Touafri, A. Hellal, S. Chafaa, A. Khelifa, A. Kadri, J. Mol.
Struct. 2017, 1149, 750.
[12] M. Montazerozohori, S. M. Jahromi, A. Naghiha, J. Indust.
Eng. Chem. 2014, 22, 248.
[13] U. Yunus, M. H. Bhatti, N. Rahman, N. Mussarat, S. Asghar,
B. Masood, J. Chem. 2013, 8.
[40] H. A. ElGhamry, R. G. El-Sharkawy, M. Gaber, J. Iran. Chem.
Soc. 2014, 11, 379.
[41] A. Rauf, A. Shah, K. S. Munawar, A. A. Khan, R. Abbasi,
M. A. Yameen, A. M. Khan, A. R. Khan, I. Z. Qureshi, H. B.
Kraatz, Z. Rehman, J. Mol. Struct. 2017, 1145, 132.
[42] R. G. Deghadi, W. H. Mahmoud, G. G. Mohamed, Appl.
Organomet. Chem. 2020, 34(10), e5883.
[14] N. G. Kandile, M. I. Mohamed, H. M. Ismaeel, J. Enzyme
Inhib. Med. Chem. 2017, 32(1), 119.

DEGHADI ET AL.
17 of 17
[43] S. Muche, I. Levacheva, O. Samsonova, A. Biernasiuk, A.
Malm, R. Lonsdale, L. Popiołek, U. Bakowsky, M. Holynska,
J. Mol. Struct. 2017, 1127, 231.
[44] D. Xu, Q. Sun, Z. Quan, W. Sun, X. Wang, Tetrahedron: Asym-
metry 2017, 28, 954.
[45] M. A. Arafath, F. Adam, M. R. Razali, L. E. A. Hassan,
M. B. K. Ahamed, A. M. S. A. Majd, J. Mol. Struct. 2017,
1130, 791.
[46] M. Barwiolek, J. Sawicka, M. Babinska, A. Wojtczak, A.
Surdykowski, R. Szczesny, E. Szlyk, Polyhedron 2017, 135, 153.
[47] A. A. Abdel Aziz, S. H. Seda, Appl. Organomet. 2017, 31(12),
e3879.
[54] W. H. Mahmoud, R. G. Deghadi, G. G. Mohamed, Appl.
Organomet. Chem. 2017, 32(4), 4289.
[55] W. H. Mahmoud, N. F. Mahmoud, G. G. Mohamed, Appl.
Organomet. Chem. 2017, 31(12), e3858.
[56] H. Vural, M. Orbay, J. Mol. Struct. 2017, 1146, 669.
[57] W. H. Mahmoud, R. G. Deghadi, G. G. Mohamed, Indian
J. Chem. 2019, 58A, 1319.
[58] W. H. Mahmoud, R. G. Deghadi, M. M. I. El Desssouky, Appl.
Organomet. Chem. 2019, 33, e4556.
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
[48] M. A. Neelakantan, S. S. Marriappan, J. Dharmaraja, T.
Jeyakumar, K. Muthukumaran, Spectrochim. Acta A 2008,
71, 628.
[49] J. D. Chellaian, J. Johnson, Spectrochim. Acta
127, 396.
A 2014,
[50] S. A. Sadeek, W. H. El-Shwiniy, W. A. Zordok, A. M. El-
Didamony, J. Argent. Chem. Soc. 2009, 97, 128.
[51] B. G. Tweedy, Phytopathology 1964, 25, 910.
[52] R. Fekri, M. Salehi, A. Asadi, M. Kubicki, J. Inorg. Chim. Acta.
2019, 484, 245.
How to cite this article: R. G. Deghadi, A.
A. Abbas, G. G. Mohamed, Appl Organomet Chem
2021, e6292. https://doi.org/10.1002/aoc.6292
[53] W. H. Mahmoud, G. G. Mohamed, O. Y. El-Sayed, Appl.
Organomet. Chem. 2017, 32(2), e4051.