Spectroscopic evaluation of chalcone derivatives and their zinc metal complexes: A combined experimental and computational approach studying the interactions of the complexes with the serum albumin

Article abstract of DOI:10.1016/j.molstruc.2021.130052

Three chalcone derivatives (L₁, L₂, L₃) were synthesized using Claisen-Schmidt condensation reaction. Their molecular structures and spectroscopic properties (IR, UV-vis, ¹HNMR), were calculated at B3LYP level. Electrostatic interactions and HOMO-LUMO properties were calculated using TD-DFT method. Molecular docking was used to compare the HSA (human serum albumin) interactions with the ligands and their Zn complexes (C₁, C₂, C₃) which were synthesized by interaction between the ligands and the Zn (II) ion in a 2:1 M ratio. Elemental analysis, FT-IR, and UV–Vis spectroscopy studies investigated the structure of the synthesized complexes. UV–Vis, molecular docking and molecular dynamics were used to study the interactions of the Zn complexes with the BSA (bovine serum albumin). The biological activity of the Zn-Chalcone complexes was generally higher than the chalcones when evaluated spectroscopically and theoretically.

Full text of DOI:10.1016/j.molstruc.2021.130052

Journal of Molecular Structure 1232 (2021) 130052
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstr
Spectroscopic evaluation of chalcone derivatives and their zinc metal
complexes: A combined experimental and computational approach
studying the interactions of the complexes with the serum albumin
Manos C. Vlasiou∗, Amina Al Hatahta
Department of Life and Health Sciences, University of Nicosia, Nicosia 2417, Cyprus
a r t i c l e i n f o
a b s t r a c t
Article history:
Three chalcone derivatives (L1, L2, L3) were synthesized using Claisen-Schmidt condensation reaction.
Their molecular structures and spectroscopic properties (IR, UV-vis, 1HNMR), were calculated at B3LYP
level. Electrostatic interactions and HOMO-LUMO properties were calculated using TD-DFT method.
Molecular docking was used to compare the HSA (human serum albumin) interactions with the ligands
and their Zn complexes (C1, C2, C3) which were synthesized by interaction between the ligands and the
Zn (II) ion in a 2:1 M ratio. Elemental analysis, FT-IR, and UV–Vis spectroscopy studies investigated the
structure of the synthesized complexes. UV–Vis, molecular docking and molecular dynamics were used to
study the interactions of the Zn complexes with the BSA (bovine serum albumin). The biological activity
of the Zn-Chalcone complexes was generally higher than the chalcones when evaluated spectroscopically
and theoretically.
Received 2 December 2020
Revised 22 January 2021
Accepted 28 January 2021
Available online 4 February 2021
Keywords:
Chalcone
Zinc
Spectroscopy
Docking
Molecular dynamics
Complexes
DFT
© 2021 Elsevier B.V. All rights reserved.
HSA
1. Introduction
volves cross aldol condensation of appropriate aldehydes and ke-
tones by base catalysed or acid catalysed reactions followed by de-
Chalcones, are belonging to the flavonoid family, having
a
hydration [10].
medicinal importance because of the CO-CH=CH- (ketoethylenic
group). There are intermediates of flavonoids and they exhibit
anti-inflammatory, antifungal, antimicrobial, antioxidant and anti-
tumor activity [1,2]. This biological activity is because of the α, β-
unsaturated keto function. Chalcone contains two aromatic rings
linked by a three carbon α, β-unsaturated carbonic system and
they are selected because of their low toxicity and possible chem-
ical modification [3,4]. In nature, chalcone (1,3-diphenyl-2-propen-
1-one) is one of the open chain flavonoids containing 15-carbon ar-
ranged in a C6C3-C6 configuration [5]. The bioactivity of chalcones
have been studied and several biological activities have been found
such as, antioxidant, cytotoxic, antiviral, tyrosinase inhibitory, anti-
malarial, antibacterial, and anti-inflammatory [6]. Additionally, the
synthesis of Pd (II) and Pt (II) complexes and Co (II), Cu (II), Mn
(III) of a chalcone compound has been proposed elsewhere [7,8]
and this is because chalcones are effective metal ion chelators and
they can easily create metal-coordinated compounds [9]. Chalcones
are synthesized by Claisen–Schmidt condensation. This reaction in-
It is known that Zinc-containing compounds play a key role in
carbonic anhydrases, peptidases, proteases, and deaminases [11].
Interestingly, the coordination chemistry of zinc in proteins and
peptides involves N, O, and S donors of the side chains of histi-
dine, glutamate/aspartate, and/or cysteine with any permutation
of these ligands and with the number of protein ligands rang-
ing from three to six [12]. On the other hand, Zn plays a vi-
tal role in a variety of biological processes but, excessive expo-
sure of Zn2+ to human beings can cause toxicity, inducing a se-
ries of overt poisoning symptoms and neurodegenerative disorders
[13].
HSA is responsible to maintaining stable osmotic pressure and
to carrying endogenous or exogenous compounds. Additionally,
most lipophilic drugs are substrates of HSA and are transferred to
target tissues via the bloodstream. The chemical structure of HSA
includes three homologous α-helical domains (I, II and III), each
of which possesses two subdomains (A and B) [14]. Various bind-
ing and denaturation studies have shown to be a rapid and effec-
tive tool for the characterization of albumin binding sites and their
enantioselectivity, and for the study of the changes in the binding
properties of the protein caused by interaction between different
ligands [15-18].
∗
Corresponding author.
E-mail address: vlasiou.m@unic.ac.cy (M.C. Vlasiou).
https://doi.org/10.1016/j.molstruc.2021.130052
0022-2860/© 2021 Elsevier B.V. All rights reserved.

M.C. Vlasiou and A.A. Hatahta
Journal of Molecular Structure 1232 (2021) 130052
The last years more and more scientists are using computa-
tional chemistry and theoretical tools to evaluate their molecular
structures [19-21]. Moreover, some researchers are using computa-
tional tools to evaluate the biological activity of the molecules of
interest [22-26]. This is because of the quick results that the com-
putational tool is giving to the researcher, and the added scientific
value to the findings. All that, at minimum cost and resources. As
the technological improvements are running fast, more and more
theoretical tools are going to save time to the researcher and give
a different perspective, using the predictive character of the com-
puterized models.
40% aqueous NaOH solution (15 mL) was gradually added. 4-
dimethylamino benzaldehyde (0.003 mol) was added and the re-
action took place for 20 h at 25°C. Any precipitate formed was re-
moved by filtration and the filtrate was acidified with dilute HCl
and then extracted with chloroform. Orange solid, M. P: 54-55 °
C; 1H NMR (300 MHz, DMSO-d6): δ 2.34 (s, -CH3), 3.06 (s, -CH3),
5.35 (s, -OH), 7.02 (m, -CH aromatic), 7.34 (m, -CH aromatic), 8.33
(d, -H) ppm.
2.3.3. Synthesis of (E)-1-(2-hydroxy-5methoxyphenyl)-
3-(2-nitrophenyl) prop-2-en-1-one
In a round bottom flask (100 ml), to an ethanolic solution
(20 ml) of 1-(4-hydroxy-3methoxyphenyl) ethanone 0.003 mol)
a 40% aqueous NaOH solution (20 mL) was gradually added. 2-
nitrobenzaldehyde (0.003 mol) was added and the reaction took
place for 24 h at 25°C. Any precipitate formed was removed by fil-
tration and the filtrate was acidified with dilute HCl. Yellow-green
solid, M. P: 57-59 ° C; 1H NMR (300 MHz, DMSO-d6): δ 3.84 (s, -
CH3), 5.33 (s, -OH), 7.10 (m, -CH aromatic), 7.27 (m, -CH aromatic),
7.79 (m, -CH aromatic), 7.89 (m, -CH aromatic), 8.21 (m, -CH aro-
matic), 8.60 (d, -H).
Herein, we propose the synthesis of some chalcone ana-
logues, and their complexation with Zn (II) metal ions. In total,
6 molecules were prepared and evaluated spectroscopically, both
in situ and theoretically. More specifically, we used TD-DFT studies
[26-31], to evaluate our chalcone derivatives in terms of structure
and activity, molecular docking [32-35], to evaluate their interac-
tion with human serum albumin (HSA) and spectroscopy to eval-
uate their binding interactions with bovine serum albumin (BSA).
The biological activity of the chalcone derivatives, was compared
with the biological activity of their counter Zn complexes.
2.4. Synthesis of Zinc (II) Complexes
2. Experimental
Zn (II) complexes with ligands L1-L3
2.1. Materials
An ethanolic solution (30 ml) of Zn (II) chloride (0.01 mol) was
added to a refluxing solution of appropriate chalcone analogue L1-
L3 (0.02 mol) in ethanol (30 ml). The reaction mixture was refluxed
for 6 h. The coloured complexes were obtained, filtered off, washed
with ethanol and dried under vacuum. Elemental Analysis: L1: C,
54.84; H, 3.45; Cl, 10.12; N, 4.00; O, 18.26; Zn, 9.33. L2: C, 62.04;
H, 5.21; Cl, 10.17; N, 4.02; O, 9.18; Zn, 9.38. L3: C, 52.45; H, 3.30;
Cl, 9.68; N, 3.82; O, 21.83; Zn, 8.92. Molar Conductance (M hos.cm2
mol−1): C1: 12.03, C2: 12.09, C3: 11.99.
2-nitrobenzaldehyde,
2-(methylamino)
benzaldehyde,
2-
hydroxy-5-methylphenyl ethanone, 1-(2-hydroxy-5-methylphenyl)
ethanone, 4-hydroxy-3-methoxyphenyl ethanone, were purchased
from Merck. Solvents were used without any further purifica-
tion. Other reagents were of analytical grade. BSA (bovine serum
albumin) (purity ≥ 98%) was purchased from Merck.
2.2. Instruments
2.5. Theoretical Studies
All the chalcone analogues and their zinc complexes were char-
acterized by 1HNMR, recorded on Bruker 300 MHz spectrometer
using DMSO-d6 as solvent and TMS as an internal standard. The
chemical shifts were expressed in δ ppm. The absorption spectrum
of all the reaction mixtures was then taken in a range of 200-400
nm in a JASCO (Tokyo, Japan) UV-visible spectrophotometer using
a 1cm path length quartz cuvette.
2.5.1. Optimization and vibration frequency calculations were made
at B3LYP level with ORCA version 4.0.1 program
B3LYP is a hybrid density functional theory method. Among
the ever-increasing number of DFT methods, the hybrid functional
B3LYP, as a good compromise between computational cost, cover-
age, and accuracy of results [36]. It has become a standard method
used to study organic chemistry in the gas phase. UV-vis spec-
trums at the same level calculated by time-dependent density
functional theory (TD-DFT) method. ORCA input files were created
by AVOGADRO version 1.2.0 software. HOMO energy (EHOMO) and
LUMO energy (ELUMO) were taken from the output file. Chalcone
analogues and their zinc complexes were docked against human
serum albumin. Molecular docking studies were carried out by us-
ing iGEMDOCK 2.1 software [11]. The HSA coded crystal structure
was selected from the Protein Data Bank (www.rcsb.org). The pop-
ulation size was = 200, generations = 70, number of solutions = 3.
2.3. Synthesis of chalcones analogues
2.3.1. Synthesis of (E)-1-(2-hydroxy-5-methylphenyl)-3-
(2-nitrophenyl) prop-2-en-1-one
In a round bottom flask (100 ml), to a methanolic solution
(20 ml) of 2-hydroxy-5-methylphenyl ethanone (0.003 mol)
a
40% aqueous NaOH solution (15 mL) was gradually added. 2-
nitrobenzaldehyde (0.003 mol) was added and the reaction took
place for 20 h at 25°C. Any precipitate formed was removed by
filtration and the filtrate was acidified with dilute HCl and then
extracted with chloroform. The concentrate of the chloroform was
chromatographed over silica gel to obtain the desired product.
2.6. Effect of the ligand and the complex on the absorption spectrum
of BSA
The compound then crystallized from chloroform-petroleum ether
The effect of the ligands and their corresponding complexes,
on the absorption spectrum of BSA, was studied using UV–visible
spectrophotometry. Briefly, BSA (5 μM) were incubated in the ab-
sence and presence of 2-9 μM of L1, L2, L3, C1, C2 and C3 for 30
min at RT.
o
(50:50). Olive green solid, M.P: 55-57
C; 1H NMR (300 MHz,
DMSO-d6): δ 2.36 (s,-CH3), 5.37 (s, -OH), 7.04 (m, -CH aromatic),
7.36 (m, -CH aromatic), 7.44 (m, -CH aromatic), 7.65 (m, -H), 7.89
(m, -CH), 8.23 (m, -CH), 8.64 (m. -H) ppm.
2.3.2. Synthesis of (E)-3-(4-dimethylamino) phenyl)-1-(2-hydroxy-5-
methylphenyl) prop-2-en-1-one
2.7. Conductance studies on the Zn-complexes interaction with BSA
In a round bottom flask (100 ml), to a methanolic solution
All stock solutions were prepared freshly by weighing and using
freshly prepared solvents. Conductivity measurements were made
(20 ml) of 2-hydroxy-5-methylphenyl ethanone (0.003 mol)
a
2

M.C. Vlasiou and A.A. Hatahta
Journal of Molecular Structure 1232 (2021) 130052
Fig. 1. Synthetic routes of the three chalcone derivatives.
using EC/TEMP meter AD 130 model at room temperature. A stan-
dard addition method has been used for measuring the conduc-
tance of the ligand-protein complexes. BSA (5 μM) was left to react
with different concentrations of the C1, C2, C3 molecules. A certain
amount of solution was injected into the conductivity cell and the
conductivity of the solution was measured. 10 additions have been
made throughout.
lowed by the second stage which is a nucleophilic addition re-
action. Here, the enolate or carbanion ion formed at stage one
acts as a nucleophile that attacks the carbonyl group of benzalde-
hyde. An alkoxide ion is formed which has an excess of electron
charge in the O atom. Next, is the formation of an aldol. Aldol
is a compound formed from aldehydes and ketones where aldol
takes protons from solvent molecules, H2O. Alkoxide ions take hy-
drogen protons from H2O molecules to form β-hydroxyketone (al-
dol). Then the hydroxide ion from H2O binds to the sodium ion
and returns to form a NaOH base catalyst. Finally, the dehydration
reaction of the aldol compound takes place in Claisen-Schmidt re-
action. Dehydration reaction is a reaction of the release of water
molecules. Carbonyl β-hydroxy like aldol is easily dehydrated, be-
cause the double bonds in the compound conjugate with the car-
bonyl group. The disappearance of the chemical shift at 2.5 ppm
attributed to -CH3 hydrogens of acetophenone, it is a good evi-
dence of the resulted chalcone derivatives. Moreover, the increase
of the melting points from 47°C to 57°C is another indicator of the
successful synthesis.
3. Results and discussion
Synthesis of Chalcone Derivatives and their Zinc Complexes
Chalcone derivatives were synthesized based on Claisen-
Schmidt condensation reaction. Acetophenones analogues reacted
in (1:1) ratio with benzaldehydes analogues in methanolic solu-
tions resulting the chalcone derivatives (L1, L2 and L3). The syn-
thetic routes and conditions are depicted in Fig. 1. Reactions took
place at room temperature resulting colourful precipitates after 20
h mixing. Any precipitate formed was removed by filtration before
acidification. The formation of carbanion or enolate ions is consid-
ered to be the first stage of the condensation reaction. Aromatic
ketones having α hydrogen if treated with alkaline solutions (in
this case NaOH), the hydroxide ion from the base will attack hy-
drogen α from the ketone so that a carbanion is formed which
can be stabilized by resonance and release the H2O molecule. Fol-
Zn (II) complexes (C1, C2 and C3) resulted after mixing ethano-
lic chalcone derivative solution (L1, L2 and L3) with ZnCl2 at (1:2)
ratio, using reflux for 6 h. Coloured complexes obtained after filtra-
tion. The three complexes are soluble to DMSO and DMF. Elemen-
tal analyser indicated that the complexes have 1:2 metal to ligands
stoichiometry of the types [ZnL2(Cl)2], whereas L are the chalcone
3

M.C. Vlasiou and A.A. Hatahta
Journal of Molecular Structure 1232 (2021) 130052
Fig. 2. Optimized structures of the synthesized chalcones.
Table 1
˚
Selected bond lengths (A) and bond angles (°) of the synthe-
sized chalcones.
L1
Atoms
Angle
Atoms
Length
C5-C1-O1
C2-C1-C5
119.2789
118.1423
118.5631
122.4757
107.4257
109.1858
123.7386
119.113
H4-C8
C8-C9
H13-O2
C10-O2
O4-N
1.08865
1.40054
0.972961
1.36579
1.23645
1.47324
C1-C7-H1
C14-C15-N
H10-C16-H12
C10-O2-H13
O3-N-O4
N-C15
C15-N-O4
L2
C2-C1-C6
120.0083
120.0048
120.0014
119.9951
109.4628
108.0009
119.9963
109.4457
H15-C17
C17-N
1.11298
1.47004
1.3949
C1-C2-H1
C5-C4-O2
C12-C11
C7-O1
C12-C13-N
H10-C16-H12
C4-O2-H13
C17-N-C18
N-C17-H15
1.20804
0.97205
H13-O2
L3
C2-C1-C6
119.9986
120.0016
120.033
H13-C16
C16-O3
C13-C14
O5-N
1.11302
1.40206
1.39477
1.31001
1.24809
0.971976
C2-C1-O3
C3-C2-H1
C14-C15-N
C4-O2-H10
C1-O3-C16
H12-C16-H13
O3-C16-H11
C15-N-O4
119.9599
107.9991
110.8014
109.5253
109.4976
120.004
C15-N
H10-O2
derivatives resulted after the condensation of the correct acetophe-
none analogue with the correct benzaldehyde analogue. In addi-
tion, low molar conductance values indicate that the complexes are
not electrolytes.
Fig. 3. Calculated UV-vis spectra of L1, L2 and L3 molecules.
main theoretically calculated bond lengths and bond angles of the
molecules.
Theoretical Studies on Chalcone Derivatives
Molecular Geometry
Spectroscopy
The ground state optimization structures of the synthesized
chalcone molecules were obtained in the aqueous phase at B3LYP
def2-TZVP Grid5 level and are given in Fig. 2.
The spectroscopic UV-vis spectrum of the three ligand
molecules, and their electronic transitions can be computerized
and analyzed by time-depended density functional theory or TD-
DFT. Additional information in the molecular structure prediction
can be taken by electronic spectroscopy. In Fig. 3 we can see the
The geometrical parameters have been procured from opti-
mized molecular structure and summarized in Table 1, giving the
4

M.C. Vlasiou and A.A. Hatahta
Journal of Molecular Structure 1232 (2021) 130052
Fig. 4. Calculated 1HNMR spectra of L1, L2 and L3 molecules.
Table 2
calculated UV-vis spectrum of the molecules taken in the aqueous
phase using B3LYP def2-TZVP Grid5 level algorithm.
1HNMR chemical shifts of chalcone molecules calculated at aqueous phase.
As seen in Fig. 3, for L1 and L3 are observed similar spectrums
giving two bands for π→π∗ and n→ π∗ transitions respectively.
Most absorption spectroscopy of organic compounds is based on
transitions of n or π electrons to the π∗ excited state [37]. This
is because the absorption peaks for these transitions fall in an ex-
perimentally convenient region of the spectrum (200 - 700 nm).
These transitions need an unsaturated group in the molecule to
provide the π electrons. For L2 molecule only one transition is ob-
served the π→π∗. The similarity of the bands shapes and close
wavelengths show that the structures of the studied molecules are
quite similar as they are belonging to the same family of the chal-
cones. 1HNMR spectrum calculated data also suggest the similarity
of the structures.
L1
L2
L3
Group
Shift (ppm)
Group
Shift (ppm)
Group
Shift (ppm)
OH
CH
CH
CH
CH
CH
CH
CH
CH3
H
5.35
7.02
8.21
7.43
8
OH
CH
CH
CH
CH
CH
CH
CH
CH3
CH3
CH3
H
5.35
7.02
6.71
7.43
7.2
OH
CH
CH
CH
CH
CH
CH
CH
CH3
H
5.35
7.1
7.33
8.21
7.27
8
7.34
7.89
7.79
2.34
8.02
7.66
7.34
7.15
6.74
3.06
3.06
2.34
8.33
7.42
7.89
7.89
3.83
8.62
7.66
H
H
H
For structural characterization 1HNMR spectra of chalcone
molecules were calculated and peaks were attributed to the cor-
rect chemical groups. Chemical shifts were given according to
the TMS reference and calculated from δ=ꢀTMS-ꢀrelation, whereas
ꢀTMS corresponds to the shielding of proton to the TMS and ꢀ,
the shielding of proton in the sample. The 1HNMR spectrum cal-
culated at B3LYP DEF2-TZVPP DEF2 level in aqueous phase and are
given in Fig. 4.
hybridization (sp3) the found in a low ppm chemical shift. The
aromatic region of the spectra of the three chalcone derivatives
are quite similar. As can be seen from Table 2. the -OH group is
present at three molecules as well, at the same chemical shift 5.35
ppm. The hydrogens of the phenol group of the chalcones can be
found at 8.02 and 7.66 ppm for L1, 8.33 and 7.42 ppm for L2, and
8.62 and 7.66 ppm for L3.
Chemical shifts of 1HNMR, are given in Table 2.
As can be seen in Fig. 4, the spectra are similar for molecules
L1, L3 same as the UV-vis spectra. The only difference is the shift of
the first chemical shift from 3.83 to 2.34 ppm due to the presence
of the extra methyl group on L3. The presence of the 3.06 ppm
chemical shift that it is characteristic for the L2 and corresponds
to the -CH3 group of the molecule, dominates the anomeric region.
Because they are attached to carbon atoms with low s-character
An additional way to verify the structures of the chalcone
derivatives, is the vibrational spectrum. It has been calculated by
BP86 DEF2-SVP FREQ algorithm. The high intensity peaks with the
harmonic vibration frequencies are given in Fig. 5.
The characteristic high frequency peak at 3500 cm−1, of s(O-H)
is common for the three analogues, while the peak at 1200 cm−1
for L1, indicating the s(N-H) vibration. The methoxy group of L3,
5

M.C. Vlasiou and A.A. Hatahta
Journal of Molecular Structure 1232 (2021) 130052
Table 3
Calculated energy values of the molecules.
Molecule
L1
L2
L3
Potential Energy (Kcal/mol)
-2.015
-1.871
-2.175
Kinetic Energy (Kcal/mol)
Magnitute (a.u)
1.003
2.202
157.90
-1.013
-1.013
37.09
-1.013
-1.817
-4.057
2.24
9.317
3.991
215.90
-9.385
-9.385
33.74
-9.386
0.58
1.089
2.326
237.07
-1.085
-1.085
33.11
-1.085
-4.259
-4.646
0.38
Zero Point Energy (Kcal/mol)
Total Thermal Energy (Kcal/mol)
Total Enthalpy (Kcal/mol)
Final Entropy (Kcal/mol)
Gibbs Free Energy (Kcal/mol)
ELumo (eV)
EHomo (eV)
-1.757
2.34
ꢀE (eV)
bital (EHOMO) and lowest unoccupied molecular orbital (ELUMO)
energies plays a very important role in stability and reactivity of
molecules. The EHOMO energies of molecules show the molecule’s
ability to give electrons. On the other hand, ELUMO characterizes
the ability of the compound to accept electrons [38]. Thus, the one
is nucleophile and the other electrophile. Molecules with small en-
ergy gaps are considering to have a higher chemical reactivity and
softer structures, while molecules having larger energy gaps are
considering to be more stable and chemically harder. The com-
puted values of the three chalcone derivatives can be found in
Fig. 6.
It seems that L3, has the highest reactivity (ꢁE= 0.38 eV) fol-
lowed by L1 (ꢁE= 2.24 eV) and L2 (ꢁE= 2.34 eV). In Table 3. we
can see all the calculated energy features of the three molecules
including, enthalpy, entropy and Gibbs energy. Any process in
which the number of particles in the system increases conse-
quently results in an increase in disorder. This is why we can ob-
serve an increase in the entropy of the molecules.
Fig. 5. IR spectra of L1, L2 and L3 chalcone derivatives calculated in aqueous phase.
is responsible for the t(H-O-C-C) vibration at 800cm−1 which is
absent for L1 and L2. The 1700 cm-1 peak is responsible for the
s(N-C) of the molecules, while the 1500 cm−1 peak is responsible
for s(N-O) that is why it is absent from L2 [38].
The individual charge on each atom on the molecule, it is an-
other factor used to characterised molecular structures and it is
presented by the Mulliken population study [39]. The Mulliken
atomic charges have been calculated by DFT method and presented
in Table 4.
Molecular Orbital Studies
The molecular orbital studies revealed the energy gap between
the highest molecular orbital (HOMO) and the lowest molecu-
lar orbital (LUMO). The value of the energy difference between
HOMO and LUMO as well as the highest occupied molecular or-
The O20 atom has the highest negative charge for L1, while for
L2 the highest negative charge belongs to C2 atom. For L3 the high-
est negative charge is that of C2 atom as well. On the other hand,
N18 and H33 atoms are having the highest electropositive charge
Table 4
Calculated Mulliken atomic structures of the synthesised structures.
L1
L2
L3
L1
L2
L3
0
C
C
C
C
C
O
C
C
C
C
C
C
C
C
C
C
C
O
N
O
O
0.063637
-0.01498
0.006626
0.005301
-0.01552
-0.18649
-0.03756
-0.03731
-0.01681
-0.07558
0.139354
-0.02794
0.039388
0.010727
-0.03116
0.178551
0.037741
-0.16188
0.184202
-0.21708
-0.19531
C
C
C
C
C
O
C
C
C
C
C
C
C
C
C
C
N
C
O
C
C
0.129145
-0.06418
-2.15955
0.145811
0.086392
-0.37377
-0.31097
0.221231
-0.14285
-0.21923
0.108108
-0.26177
-0.11634
-0.15529
-0.17493
0.023324
-0.11198
-0.3699
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
O
O
O
C
N
O
0.196881
-0.16668
-0.20199
0.216942
-0.01596
0.011232
0.186225
-0.19805
0.219312
-0.06535
-0.1448
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
H
H
H
H
H
H
H
H
H
H
H
H
H
0.016168
0.055123
-0.0143
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
-0.12029
-0.66633
0.131908
0.111987
0.120226
0.092538
0.086498
0.0899
O
H
H
H
H
H
H
H
H
H
H
H
H
H
-0.45753
0.121061
0.126387
0.174554
-0.809
1
2
3
-0.01752
-0.02783
0.007255
0.011455
0.011051
0.018982
0.023503
0.048161
0.034461
0.185554
4
5
-0.40756
0.08526
6
7
0.108883
0.124392
0.152466
0.341468
0.134882
0.100239
0.13827
8
0.08746
9
0.116634
0.116973
0.116384
1.869932
0.176557
0.078148
0.219539
0.141291
0.111857
0.125495
10
11
12
13
14
15
16
17
18
19
20
-0.15484
-0.05795
-0.17958
0.081493
-0.40831
-0.38967
-0.26285
-0.17764
0.220938
1.356872
0.922754
0.07014
-0.25285
6

M.C. Vlasiou and A.A. Hatahta
Journal of Molecular Structure 1232 (2021) 130052
Fig. 6. HOMO-LUMO orbitals of L1, L2 and L3 molecules.
Table 5
Interaction types of the chalcone molecules and their zinc complexes.
Molecule
Energy (Kcal/mol)
Van der Waals (Kcal/mol)
Hydrogen Bonding (Kcal/mol)
Electrostatic Forces (Kcal/mol)
L1
L2
L3
C1
C2
C3
-78.63
-76.66
-84.53
-82.64
-118.05
-94.29
-65.08
-59.16
-65.31
-62.09
-102.97
-73.61
-13.55
-17.50
-19.22
-20.55
-15.08
-20.67
0
0
0
0
0
0
Table 6
for L1, and C7 and H33 atoms the highest electropositive charge
for L2. Finally, for L3, C3, N19 and H31 are the most electropositive
atoms. The negative charges are due to the electron withdrawing
groups that the atoms are attached with and the positive charges
are because of the negative charges of the adjacent groups.
Interactions formed between the studied molecules with the amino acids of the
transport protein.
Molecule
L1
Amino Acid Residue
Hydrophilic: GLN 33 (-2.5), THR 83 (-8.5) TYR 84 (-2.5)
Hydrophobic: LEU 31 (-4.8), ARG 81 (-4.1) GLU 82 (-9.6) THR
83 (-5.4)
L2
L3
Hydrophilic: TYR 140 (-4.1) GLU 141 (-3.5) ARG 144 (-9.9)
Hydrophobic: PRO 35 (-6.9) PHE 36 (-5) GLU 37 (-5) TYR 140
(-9.3)
Biological Evaluation of Chalcone Derivatives and their Zinc
Complexes
Hydrophilic: ASP 38 (-2.5) HIS 39 (-5.6) ARG 81 (-3.4) THR
83 (-6)
Molecular Docking
Hydrophobic: LEU 31(-2.5) HIS 39 (-5.6) ARG 81 (-3.4) THR
83 (-6) LEU 31 (-4.3) GLN 33 (-6.1) PRO 35 (-6.4) ASP 38
(-4.4) VAL 77 (-4.5) ARG 81 (-7) TYR 84 (-4)
Hydrophilic: ASP 38 (-11) THR 83 (-6.7) ARG 144 (-2.8)
Hydrophobic: GLN 33 (-9.3) ASP 38 (-5.8) ARG 81 (6.3) LAU
112 (-4.9) ARG 144 (-5.1)
The examination of the biological activity of the three ligand
molecules (L1, L2, L3) and their corresponding complexes (C1, C2,
C3), calculated theoretically by molecular docking studies. Using
this technique, we can predict the best drug candidate in terms
of protein inhibition, on a specific targeted protein. By molecular
docking, we can predict binding energies, types of interactions and
the amino acid profile residue of the protein that interacts with the
drug molecule. In this study, we investigated the binding affinity of
our studied molecules with HSA (human serum albumin). HSA, is
the main transport protein in human organisms, were drugs bind
and transported throughout the blood transportation. The interac-
tion types between the chalcone molecules and their zinc com-
plexes are given in Table 5. The energy function can be dissected
into the following terms:
C1
C2
Hydrophilic: GLN 33 (-3.2) PHE 36 (-3.1) TYR 140 (-5) ARG
144 (-3.9)
Hydrophobic: GLN 33 (-7.4) PRO 35 (-9) PHE 36 (-6.1) GLU
37 (-7.7) LEU 112 (-4) TYR 140 (-13.6)
C3
Hydrophilic: ASP 38 (-10.7) ARG 81 (-8.6)
Hydrophobic: GLN 33 (-11.8) PRO 35 (-7.7) ARG 81 (-11.9)
THR 83 (-12.8)
where Ebind is the empirical binding energy used during the
molecular docking; Epharma is the energy of binding-site pharma-
cophores; and Eligpre is a penalty value if the ligand unsatisfied the
Etot=Ebind+Epharma+Eligpre
(1)
7

M.C. Vlasiou and A.A. Hatahta
Journal of Molecular Structure 1232 (2021) 130052
Fig. 7. Interactions of the studied molecules in human serum albumin.
ligand preferences. Epharma and Eligpre were used to improve the
number of true positives by discriminating active compounds from
hundreds of thousands of non-active compounds.
BSA Binding
The structural changes of the protein and the complexation
with the studied molecules has been done using UV-vis absorption
measurements. The compounds interacted on the site I of the pro-
tein. We performed binding studies on the BSA protein because it
has a similar shape with the HSA. The UV-vis absorption spectrums
in Fig. 8 shows the effect of L1, L2, L3, C1, C2 and C3 molecules
on the BSA spectrum. Strong absorption peaks at 250 nm and 350
nm can be seen for L1, L2, L3 which are increased in intensities
as the concentration of the molecules increases. The red shift ob-
served at 250-255 nm indicates the complex formation of the pro-
tein with the ligands. When the L1, L2 and L3 complexed with Zn
(II), we observe in the spectrum of the protein only one strong ab-
sorption peak at 210-220 nm depending on the complex molecule.
Again, the red shift of 1-5 nm corresponds to the ligation of the
molecules in the protein structure. The Zn (II) ions are responsible
for the loosening and unfolding of the protein backbone with an
increase of the hydrophobicity of its environment, more drastically
than the of L1, L2, L3 molecules which Zn is absent [40]. Thus, the
It can be seen that C2, exhibit the highest binding affinity on
the transport protein, followed by C3 and L3. The highest binding
affinity exhibited by C2 is because of the CH3-N-CH3 group which
seems to interact better with the protein with van der Waals
forces. The lowest binding affinity exhibited by L2, which means
that in general, the complexed zinc (II) molecules are more active
molecules with only exception the C1. In Table 6. the amino acid
residue of the protein that interact with the studied molecules can
be seen.
The best drug candidate of the six studied molecules with
molecular docking (C2), interacts both with hydrophilic and hy-
drophobic interactions. More specifically, C2 exhibits hydrogen
bonds with GLN 33, PHE 36, TYR 140 and ARG 144 amino acids.
Additionally, C2, exhibits van der Waals interactions with GLN 33,
PRO 35, PHE 36, GLU 37, LEU 112 and TYR 140 amino acids. Dock-
ing poses are depicted in Fig. 7.
8

M.C. Vlasiou and A.A. Hatahta
Journal of Molecular Structure 1232 (2021) 130052
Fig. 8. UV-vis spectra of L1, L2, L3, C1, C2, C3 (1-9 μM) interactions with BSA (5 μM).
Fig. 9. Conductivity graphs of the interactions between the Zn(II)-complexes and BSA.
drastic change in the spectrum was happened by the complexed
C1, C2, C3 molecules. Additionally, the results indicated that the
interaction of the Zn (II) complexed chalcones with BSA molecule
has caused some conformational changes in the microenvironment
around chromophore of BSA, that is why we cannot observe any
peak at the 300 nm.
protein-ligand complex formation. Based on the graph of the mo-
lar conductivity versus 1/C we were able to calculate the binding
constants Kb (M−1) of the complexes. The sigmoid curve allows to
calculate for the binding constant (Kb) in the following manner.
Assuming that a free Zinc complex molecule (S) and a free protein
(D) form 1:1 complex (X), Kb is expressed as K=CX/CS∗CD whereas
C corresponds to their concentrations.
It seems that C1 molecule has the higher binding constant
(0.51), followed by C3 (0.43) and then by C2 (0.30). these results
are in agreement both with the results taken by the UV-vis spec-
troscopy and the theoretical ones taken by the molecular docking
studies. Again here, the two methyl groups that C2, has were re-
sponsible for the increase of the van der Waals interactions of the
molecule with the binding site of the protein [41].
Conductance studies on the Zn-complexes interaction with BSA
The values of molar conductivity ꢂ (s m2 mol−1) in corelation
√
of the C are shown in Fig. 9. In the same figure we can see the
conductivity K (μs/cm2) values in corelation with the added vol-
ume of the zinc derivative to the BSA. On this graph it is signifi-
cant the change of the slope of the plot which corresponds to the
9

M.C. Vlasiou and A.A. Hatahta
Journal of Molecular Structure 1232 (2021) 130052
4. Conclusions
[13] Long Fan, Jing-can Qin, Chao-rui Li, Zheng-yin Yang, Two similar Schiff-base
receptor based quinoline derivate: Highly selective fluorescent probe for Zn(II),
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy (2018),
doi:10.1016/j.saa.2020.118347.
In this work, the synthesis of three chalcone derivatives and
their corresponding Zn (II) molecules was presented and their
structures evaluated spectroscopically and theoretically. Their spec-
troscopic and theoretical evaluation indicated that the Zn-chalcone
molecules exhibited higher binding activity than their correspond-
ing chalcone ligands. The binding activity was predicted with
molecular docking studies and confirmed by spectroscopic BSA in-
teractions of L1, L2, L3, C1, C2 and C3. From the highest to lowest
activity the molecules are C2>C3>L3>C1>L1>L2. Chalcones are bi-
ological active molecules and their interactions with Zn metal ion
increases their binding activity on transport proteins. Additionally,
these chalcone derivatives could be used in a study as biological
chelators to reduce the toxic zinc concentrations in biological sys-
tems.
[14] Chenxiang Wang, Dawei Shi, Fangfang Zhang, Xuben Yu, Guanyang Lin,
Ziye Zhou, Characterization of binding interaction between magnesium isogly-
cyrrhizinate and human serum albumin, Spectrochimica Acta Part A: Molecular
and Biomolecular Spectroscopy 234 (2020) 118245.
[15] Ankita Varshney, Priyankar Sen, Ejaz Ahmad, Mohd. Rehan, Naidu Subbarao,
Rizwan Hasan Khan, Ligand Binding Strategies of Human Serum Albumin: How
Can the Cargo be Utilized? CHIRALITY 22 (2010) 77–87.
[16] Rachana Srivastava, Md. Sayem Alama, Spectroscopic studies of the aggregation
behavior of Human Serum Albumin and cetyltrimethylammonium bromide, In-
ternational Journal of Biological Macromolecules 158 (2020) 394–400.
[17] Tanveer A. Wani, Ahmed H. Bakheit, M. A. Abounassif and Seema Zargar, Study
of Interactions of an Anticancer Drug Neratinib With Bovine Serum Albu-
min: Spectroscopic and Molecular Docking Approach, Front. Chem. 6:47. doi:
10.3389/fchem.2018.00047.
[18] Fang Shen, Ya-Xian Liu, Shu-Min Li, Chi-Kun Jiang, Bing-Feng Wang,
Ya-Hong Xiong, Zong-Wan Mao, Xue-Yi Le, Synthesis, crystal structures, molec-
ular docking and in vitro cytotoxicity studies of two new copper (II) com-
plexes: special emphasis on their binding to HAS, NewJ.Chem 41 (2017) 12429.
[19] Serpil Kaya, Sultan Erkan, Duran Karakas¸ , Computational investigation of
molecular structures, spectroscopic properties and antitumor-antibacterial ac-
tivities of some Schiff bases, Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy 244 (2021) 118829.
Declaration of competing interest
The author declares that they have no known competing finan-
cial interests or personal relationships that could have appeared to
influence the work reported in this paper.
[20] Prateek Tyagi, Sulekh Chandra, B.S. Saraswat b, Deepansh Sharma, Design,
spectral characterization, DFT and biological studies of transition metal com-
plexes of Schiff base derived from 2-aminobenzamide, pyrrole and furan alde-
hyde, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy
143 (2015) 1–11.
[21] Gao-Jun Zhang, Shao-Yi Wu, Chen-Hao Liang, Yi-Mei Fan, Ying-Jie Luo, Jia-X-
ing Guo, Xiao-Yu Li, DFT calculations of the local structures and the EPR pa-
rameters for Rh2+ doped AO (A = Mg, Ca) crystals, Chemical Physics 534
(2020) 110734.
Acknowledgements
The author wants to acknowledge the Pharmacy Programme of
the University of Nicosia and Dr. Demetris Apostolides of the De-
partment of Chemistry, of the University of Cyprus for the NMR
experiments.
[22] G. Kirishnamaline, J. Daisy Magdaline, T. Chithambarathanu, D. Aruldhas,
A. Ronaldo Anuf, Theoretical investigation of structure, anticancer activity and
molecular docking of thiourea derivatives, Journal of Molecular Structure 1225
(2021) 129118.
[23] M.K. Tripathi, P. Sharma, A. Tripathi, et al., Computational exploration and ex-
perimental validation to identify a dual inhibitor of cholinesterase and amy-
loid-beta for the treatment of Alzheimer’s disease, J Comput Aided Mol Des
34 (2020) 983–1002.
References
[24] J. Hu, C. Yan, A tool for calculating binding-site residues on proteins from PDB
structures, BMC Struct Biol 9 (2009) 52, doi:10.1186/1472-6807-9-52.
[25] Jingwei Zhou, Min Li, Nanhao Chen, Shenglong Wang, Hai-Bin Luo,
Yingkai Zhang, Ruibo Wu, Computational Design of a Time-Dependent Histone
Deacetylase 2 Selective Inhibitor, ACS Chem. Biol. 10 (2015) 687–692.
[26] S. Syed Ali Fathima, M.Mohamed Sahul Meeran, E.R. Nagarajana, Synthesis
of novel (E)-2-((anthracen-9-ylmethylene) amino) pyridin-3-ol and its transi-
tion metal complexes: Multispectral characterization, biological evaluation and
computational studies, Journal of Molecular Liquids 279 (2019) 177–189.
[27] R.N.S. Santiagoa, P.T.C. Freirea, A.M.R. Teixeirac, P.N. Bandeirae, H.S. Santose, T
L.G. Lemosf, C.A.N. Ferrazc, FT-Raman and FT-IR spectra and DFT calculations of
chalcone (2E)-1-(4-aminophenyl)-3-phenyl-prop-2-en-1-one, Vibrational Spec-
troscopy 97 (2018) 1–7.
[1] S Verma, AK Srivastava, OP Pandey, A Review on Chalcones Synthesis and their
Biological Activity, PharmaTutor 6 (2) (2018) 22–39 10.29161/PT.v6.i2.2018.22.
[2] M. Asad, M. Arshad, S. Khan, M. Oves, M. Khalid, A. Asiri, et al., Cyclization of
chalcones into N-propionyl pyrazolines for their single crystal X-ray, compu-
tational and antibacterial studies, Journal Of Molecular Structure 1201 (2020)
127186, doi:10.1016/j.molstruc.2019.127186.
[3] S.W. Khor, Y.K. Lee, M.R.B. Abas, et al., Application of chalcone-based dithiocar-
bamate derivative incorporated sol–gel for the removal of Hg (II) ion from wa-
ter, J Sol-Gel Sci Technol 82 (2017) 834–845, doi:10.1007/s10971-017-4362-7.
[4] R. Kamal, R. Kumar, V. Kumar, V. Bhardwaj, Synthetic Utilization of α,β-
Chalcone Dibromide In Heterocyclic Chemistry and Stereoselective Debromi-
nation, Chemistryselect 4 (2019) 11578–11603, doi:10.1002/slct.201902262.
[5] Xu Zhanga, K.P. Rakesha, S.N.A. Bukharia, Moku Balakrishnaa, H.M. Manuku-
marb, Hua-Li Qina, Multi-targetable chalcone analogs to treat deadly
Alzheimer’s disease: Current view and upcoming advice, Bioorganic Chemistry
80 (2018) 86–93.
[28] Shui Wang, Qiaoli He, Jidong Wang, Yixin Qu, Molecular structural, IR and NMR
spectroscopic studies on the four isomers of thiotriazinone by DFT and HF cal-
culations, Spectrochimica Acta Part A 87 (2012) 179–189.
[29] Sudhir M. Hiremath, Seema S. Khemalapure, Chidanandayya S.Hiremath b,
Anil S. Pati, Mahantesha Basanagouda, Quantum chemical computa-
tional and spectroscopic (IR, Raman, NMR, and UV) studies on the
5-(5-methoxy-benzofuran-3-ylmethyl)- 3H-[1, 3, 4] oxadiazole-2-thione,
Journal of Molecular Structure 1210 (2020) 128041.
[6] Ayse Aktas Kamiloglu, Hüseyin Karaca, Gonca Celik, Irfan Acar, Halit Kantekin,
New chalcone-substituted metallophthalocyanines: Synthesis, characterization,
and investigation of their properties, Journal of Chemical Research (2020) 1–10
https://journals.sagepub.com/doi/10.1177/1747519820902684.
[30] Parutagouda Shankaragouda Patil, Neelamma B. Gummagol, Anusha Ekbote,
Qin AiWong, Ching Kheng Quah, Mohd Shkir, Shivaraj R. Maidur, S. Venugopal
Rao, Journal of Molecular Structure 1219 (2020) 128523.
[7] Mohamed Gabera, Hoda A. El-Ghamrya, Mohammed A. Mansourc, Pd(II) and
Pt(II) chalcone complexes. Synthesis, spectral characterization, molecular mod-
elling, biomolecular docking, antimicrobial and antitumor activities, Journal of
Photochemistry and Photobiology A: Chemistry 354 (2018) 163–174.
[8] Gülpınar Sarkı, Halit Kantekin, Halise Yalazan, Nuran Kahriman, Zekeriya Biyik-
lioglu, Vildan Serdaroglu, Synthesis, characterization and electrochemical stud-
ies of metal-free and metallophthalocyanines containing two different chal-
cone units substituted on peripherally positions, Journal of Molecular Structure
1196 (2019) 592e603.
[9] Chiara Sulpizio, Joscha Breibeck, Annette Rompel, Recent progress in synthesis
and characterization of metal chalcone complexes and their potential as bioac-
tive agents, Coordination Chemistry Reviews 374 (2018) 497–524.
[10] Mohammed Rayees Ahmad, V.Girija Sastry, Nasreen Bano, Syed Anwar, Syn-
thesis of novel chalcone derivatives by conventional and microwave irradiation
methods and their pharmacological activities, Arabian Journal of Chemistry 9
(2016) S931–S935.
[31] Chandra Kereyagalahally Honneshappa Narasimhamurthy, Toreshettahally
Ramesh Swaroop, Swamy Jagadish, Kanchugarakoppal Subbegowda Rangappa,
Synthesis of Piperidine Conjugated Dihydroquinazolin-4(1H)-ones and their
Antiproliferative Activity, Molecular Docking Studies and DFT Calculations, Let-
ters in Drug Design & Discovery 17 (2020) 85–93.
[32] Ajay Kumar, Kamlesh Kumari, Indra Bahadur, Prashant Singh, Temperature de-
pendent DFT studies to understand the physiochemical interaction of lithium
chloride cluster ions in presence of syringic acid, J. Chem. Thermodynamics
152 (2021) 106277.
[33] Bao-Li Wang, Dong-Qi Pan, Song-Bo Kou, Zhen-Yi Lin, Jie-Hua Shi, Exploring
the binding interaction between bovine serum albumin and perindopril as well
as influence of metal ions using multi-spectroscopic, molecular docking and
DFT calculation, Chemical Physics 530 (2020) 110641.
[34] Sudhir M. Hiremath, A. Suvitha, Ninganagouda R. Patil, Chidanandayya S. Hire-
math, Seema S. Khemalapure, Subrat K. Pattanayak, Veerabhadrayya S. Ne-
galurmath, Kotresh Obelannavar, Molecular structure, vibrational spectra, NMR,
UV, NBO, NLO, HOMO-LUMO and molecular docking of 2-(4, 6-dimethyl-1-
benzofuran-3-yl) acetic acid (2DBAA): Experimental and theoretical approach,
Journal of Molecular Structure 1171 (2018) 362e374.
[11] Mohammad Azam, Saud.I. Al-Resayes, Raghavaiah Pallepogu, Farha Firdaus,
Mohammad Shakir, Mononuclear Bis(3-aminoquinoline)Zn(II) complexes: Syn-
thesis and structural characterization, Journal of Saudi Chemical Society 20
(2016) 120–126.
[12] Artur Krezel, Wolfgang Maret, The biological inorganic chemistry of zinc ion,
Archives of Biochemistry and Biophysics 611 (2016) 3e19.4.
10

M.C. Vlasiou and A.A. Hatahta
Journal of Molecular Structure 1232 (2021) 130052
[35] Nazia Siddiqui, Saleem Javed, Quantum computational, spectroscopic investiga-
tions on ampyra (4-aminopyridine) by df t/td-df t with different solvents and
molecular docking studies, Journal of Molecular Structure 1224 (2021) 129021.
[36] Julian Tirado-Rives, William L. Jorgensen, Performance of B3LYP Density Func-
tional Methods for a Large Set of Organic Molecules, J. Chem. Theory Comput.
4 (2008) 297–306.
[39] Amit Kumar, Rajesh Kumar, Archana Gupta, Poonam Tandon, E. Deepak D’silva,
Molecular structure, nonlinear optical studies and spectroscopic analysis
of chalcone derivative (2E)-3-[4-(methylsulfanyl) phenyl]- 1-(3-bromophenyl)
prop-2-en-1-one by DFT calculations, Journal of Molecular Structure 1150
(2017) 166e178.
[40] Tiyas Pal, Pooja Patil, Abha Sharma, Synthesis, molecular docking and spectro-
scopic studies of pyridoxine carbamates as metal chelator, Journal of Molecular
Structure 1223 (2021) 128837.
[37] T.R. Garcia, T.S. de Freitas, H.S. dos Santos, P.N. Bandeira, M.S.S. Juli~ao,
J.E. Rocha, C.E.S. Nogueira, R.L.S. Pereira, A.C.H. Barreto, P.T.C. Freire,
H.D.M. Coutinho A.M.R. Teixeira, Structural, vibrational and elec-
[41] M. Manabe, H. Kawamura, H. Katuura, M. Shiomi, The Application of Differ-
ential Conductivity Method to the Determination of Binding Constant of β-
Cyclodextrin with Sodium Perfluorooctanoate, in: J.J.T. Labandeira, J.L. Vila-Jato
(Eds.), Proceedings of the Ninth International Symposium on Cyclodextrins,
Springer, Dordrecht, 1999, doi:10.1007/978-94-011-4681-4_154.
trochemical
analysis
and
antibiotic
activity
study
of
chalcone
(2E)-1-(3ʹ,-methoxy-4ʹ,-hydroxyphenyl)-3-
(3-nitrophenyl)prop-2-en-1-one,
Journal of Molecular Structure 1216 (2020) 128358.
[38] Serdal Kaya, Halil Gokce, Tayfun Arslan, Gokhan Alpaslan, Synthesis, spectro-
scopic characterization, DFT computations, nonlinear optical profile and molec-
ular docking study of a novel chalcone derivative, Journal of Molecular Struc-
ture 1202 (2020) 127270.
11