Microwave-assisted Synthesis and Molecular Docking Study of Heteroaromatic Chalcone Derivatives as Potential Antibacterial Agents

Article abstract of DOI:10.1002/bkcs.12088

In this study, a series of chalcone derivatives (1a–c) were synthesized via Claisen-Schmidt condensation, followed by aza-Michael addition to form pyrazoline derivatives (2a–c and 3a–c). The reaction was performed via microwave radiation to give excellent

Full text of DOI:10.1002/bkcs.12088

Article
DOI: 10.1002/bkcs.12088
BULLETIN OF THE
S. Farooq et al.
KOREAN CHEMICAL SOCIETY
Microwave-assisted Synthesis and Molecular Docking Study of
Heteroaromatic Chalcone Derivatives as Potential Antibacterial Agents
*
*
Saba Farooq , Zainab Ngaini , and Nur Arif Mortadza
Faculty of Resource Science and Technology, Universiti Malaysia Sarawak, Kota Samarahan, Sarawak,
94300, Malaysia. *E-mail: sabafarooq61@yahoo.com; nzainab@unimas.my
Received May 22, 2020, Accepted July 23, 2020
In this study, a series of chalcone derivatives (1a–c) were synthesized via Claisen-Schmidt condensation,
followed by aza-Michael addition to form pyrazoline derivatives (2a–c and 3a–c). The reaction was per-
formed via microwave radiation to give excellent yields (77–93%) in 1–3.5 min. Microwave-assisted reac-
tion of Fischer esterification of pyrazolines (2a–c and 3a–c) afforded heteroaromatic pyrazoline esters
(4a–c) in high yield (83–96% in <2 min) compared to conventional reflux (55–79% in 30 min). Com-
pounds 1a–c and 3a–c demonstrated excellent antibacterial activity against Staphylococcus aureus via
disc diffusion assay with inhibition zone with 13 and 19 mm compared to a standard drug, ampicillin
(11 mm). Structure activity relationship of 1b and 3b were visualized via molecular docking interaction
against 4pql protein of S. aureus with binding free energy −7.0 and −8.0 kcal/mol, respectively. This
study is significant in drug discovery process particularly for pharmaceutical industries.
Keywords: Condensation, Acetophenone, Pyrazoline
Introduction
Alzheimer, Huntington, and Parkinson’s diseases.25 Inter-
estingly, the presence of natural product moiety offers
strong binding interactions with the target receptors during
inhibition due to the availability of numerous active sites in
Chalcone is a biologically active molecule derived from
natural products. Chalcone and their derivatives can be eas-
ily prepared via Claisen-Schmidt condensation.1 It has a
distinctive open chain flavonoid with two aromatic rings
and three carbon atoms. Chalcone is a stable intermediate2
for the synthesis of various heterocyclic compounds such
as isoxazole,3 pyrazoline,4 epoxide,5 thiazine,6 indazole,7
and pyrimidine8 valuable in pharmaceutical industries.9 A
recent study disclosed a series of heterocyclic chalcones
especially pyrazoline10 derivatives with remarkable biologi-
cal properties such as antioxidant,11 antibacterial,12
antidepressant,13 anticancer,14 antipyretic,15 antimalarial,16
antitubercular17 as well as non-biological applications in
solar dyes, chemosensors,18 photo-conductors,19 and opto-
electronic devices.20 Pyrazolines are well known heterocy-
clic compounds with aromaticity. Heterocyclic compounds
(i.e., pyrazoles, pyrazolines, oxazoles, pyrrolidinone) are
significant in organic chemistry and pharmaceutical indus-
try to achieve unique drugs with excellent potential against
microbial diseases.21
Utilizing natural product-based compounds as potential
antibacterial drugs has grown interest among researchers.
The incorporation of chalcone with heterocyclic natural
product based compounds such as kojic acid and
dihydroartemisinin via ester linkage has been reported to
produce kojic ester22 and dihydroartimisinyl ester,23 respec-
tively, with excellent antibacterial and anticancer activities.
Similarly, chalcone-derived carboxylate pyrazoline24 has
also been reported to cure neurological diseases such as
the molecular network.
Various methods have been reported in the synthesis of
chalcone derivatives. The nature of reagents and substitu-
ents in the chalcone synthesis sometimes requires harsh
reaction condition, such as vigorous stirring and heating.1
The conventional heating method is practically slow and
time consuming, which lead to low yield and product
decomposition.26 Microwave-assisted reaction of chalcone
derivatives has become a current choice as it provides uni-
form heating and offers good yield of products in shorter
reaction time.27 Microwave strategy is fascinating for a
variety of reactions cycloaddition, condensation and cou-
pling reactions to achieve wide-range of heterocyclic
compounds.28
Herein, we reported on a green and efficient synthesis of
heteroaromatic chalcone derivatives (2a–c and 3a–c) from
chalcone (1a–c), followed by Fischer esterification to pro-
duce (4a–c) via microwave-assisted reaction. These com-
pounds were evaluated against Escherichia coli and
Staphylococcus aureus. The effect on Structure Activity
Relationship (SAR) of various substituents presence in the
molecular network toward biological activities were studied
via molecular docking interaction using AutoDock Vina
1.1.2 program and AutoDock Tools 1.5.6.
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Experimental
(3 M). The precipitate was filtered and purified in ethanol
to achieve 3a–c.
All chemical analytical grade reagents and solvents were
used without further purification. Experiments reactions
were performed in via microwave radiation using Anton
Paar Microwave Synthesis Reactor, Monowave 300. Melt-
ing points were analyzed using Stuart SMP3 via open tube
capillary method. FTIR spectra were obtained through
Perkin Elmer Thermoscientific Smart Omni Transmission
Nicolet IS10 FTIR Spectrophotometer. 1HNMR and
13CNMR spectra were recorded on JEOL ECA 500 spec-
trometer, with chemical shift relative to deuterated dimethyl
sulfoxide (DMSO-d6) as reference. Elemental analysis was
recorded by using CHN analyzer THERMOFLASH EA
1112 Series. The transmittance of synthesized compounds
was noted through Optima SP-300 Spectrophotometer for
antibacterial evaluation. All spectra are reported in the sup-
plementary information (Figure S1–S3 and Table S1).
Via Microwave-assisted Synthesis. Chalcone (1a–c)
(0.001 mol) and sodium hydroxide (0.04 g, 0.001 mol)
were dissolved in ethanol (15 mL). Then the reaction mix-
ture was irradiated in the microwave in a suitable reaction
time (depicted in Table 1) at 160ꢀC. After the reaction
come to completion, the mixture was neutralized with 3 M
HCl acid to form a precipitate. The solid was filtered and
recrystallized in ethanol to afford 3a–c.
General Procedure for the Synthesis of Phenyl
Pyrazoline Ester (4a–c)
Via Conventional Method. Pyrazoline (3a–c) (0.0005 mol)
was stirred in methanol (20 mL) at room temperature for
10 min. Sulfuric acid (1 mL) was added into the reaction
mixture and refluxed for 30 min. The reaction was cooled
to room temperature, neutralized with 2% potassium car-
bonate, organic layer was extracted with ethyl acetate and
dried in vacuo and recrystallized in ether.
Via Microwave-assisted Synthesis Method. Pyrazoline
(3a–c) (0.0005 mol) was stirred at room temperature in
methanol (10 mL) for 10 min. Sulfuric acid was added five
to six drops and irradiated mixture in the microwave for a
suitable time (reported in Table 1) at 120ꢀC. After the com-
pletion of reaction, mixture was cool down, neutralized
with 2% K2CO3, organic layer extracted with ethyl acetate,
dried in vacuo, and recrystallized in ether.
General Procedure for the Synthesis of Chalcones (1a–c).
The synthesis of chalcones (1a–c) was performed following
Sie22 with slight modifications. 4-Carboxybenzaldehyde
(0.15 g, 0.001 mol) and acetophenone derivatives
(0.001 mol) were added to ethanolic solution of sodium
hydroxide (0.17 g, 0.001 mol) and the mixture was stirred
overnight at room temperature. The reaction completion
was monitored by thin-layer chromatography. The mixture
was neutralized with hydrochloric solution (3 M) and the
precipitate was formed, filtered, and recrystallized from eth-
anol to afford the title compounds.
Antibacterial Study
General Procedure for the Synthesis of Acetyl
Pyrazolines (2a–c)
Kirby Bauer Disc Diffusion Method.
Antibacterial
screening of 1a–c, 2a–c, 3a–c, and 4a–c was performed
against E. coli (ATCC25922) and S. aureus (N5923) via
Kirby Bauer Disc Diffusion Method by following earlier
reported methodology.29 E. coli and S. aureus were cul-
tured in Mueller-Hinton Broth (MHB) as inoculum and
Via Conventional Method. Chalcone (1a–c) (0.0005 mol,
0.146) and hydrazine (20 mmol) in acetic acid (30 mL)
were refluxed for 24 h until chalcone consumed into prod-
uct. The reaction mixture was poured into crushed ice and
left overnight. The precipitate was separated by filtration,
washed well with water, dried, and recrystallized from etha-
nol to afford white colored precipitate of 2a–c.
ꢀ
incubated at 37.5 C with continuous shaking at 150 rpm
for 20 h. Mueller-Hinton Agar (MHA) plates were used to
grow bacteria by using bacteria suspension with sterilized
cotton-tipped swab. Sterilized filter paper disc placed on
the bacteria surface of MHA plate with sterilized forceps
and soaked with 10 μL of synthesized compounds in
DMSO. The plates were incubated at 37.5ꢀC for 24 h. The
zone of inhibition was measured in millimeter to estimate
the potency of prepared compounds.
Turbidimetric Kinetic Method. All successfully achieved
synthesized compounds 1a–c, 2a–c, 3a–c, and 4a–c were
evaluated against S. aureus bacteria. S. aureus was cultured
on Mueller-Hinton Broth and incubated at 37ꢀC with stir-
ring at 250 rpm overnight. Inoculums were inoculated with
a culture medium treated with increasing concentration (50,
80, and 100 ppm) of synthesized compounds in DMSO.
The mixture was shaken at 37ꢀC. Inoculum with only
DMSO was used as negative control and ampicillin used as
positive control. The transmittance (T) was recorded using
UV–Visible Spectrophotometer Optima SP-300, Japan after
Via Microwave-assisted Synthesis. A mixture of chalcone
(1a–c) (0.0005 mol, 0.146) and hydrazine hydrazine
(20 mmol) was added in acetic acid (17 mL) and irradiated
in microwave for suitable times (reported in Table 1) at
300ꢀC. The reaction mixture was poured into chilled water
and stand overnight. The precipitate was formed, filtered,
washed well with water, dried and recrystallized with etha-
nol to afford 2a–c.
General Procedure for the Synthesis of 1H- and Phenyl
Pyrazolines (2d and 3a–c)
Via Conventional Method. Sodium hydroxide (0.04 g,
0.001 mol) and chalcone (1a–c) (0.001 mol) were added in
ethanol (20 mL) and stirred until both dissolved. Hydrazine
hydrate or phenyl hydrazine (0.04 mL, 0.01 mol) was
added dropwise to the mixture and refluxed for 4 h. The
mixture was cooled to room temperature and the solution
was poured into ice-cold water and neutralized with HCl
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Table 1. Conventional and microwave methodologies for heteroaromatic chalcones.
Conventional method
Condition
Microwave method
Time (min)
Codes
Time
Yield (%)
Yield (%)
1a
1b
1c
2a
2b
2c
3a
3b
3c
4a
4b
4c
18 h
18 h
18 h
24 h
24 h
24 h
6 h
6 h
6 h
30 min
30 min
30 min
rt
rt
rt
90.6
80.2
83.3
84.1
75.5
88.5
83.9
70.4
79.7
55.9
64.8
78.9
—
—
—
3
3
3.5
2.5
3
2.5
1.5
2
—
—
—
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
89.4
80.8
93.8
88.7
77.7
82.6
83.8
95.6
96.8
1.5
Note: rt = room temperature.
1 h interval. The antibacterial activity was examined by
plotting graph of ln Nt vs. time which the ln Nt value
describe the number of colony-forming units/mL.29
Molecular Docking Study
The molecular docking interaction study was carried out
using AutoDock Vina 1.1.2 program, AutoDock Tools is
software,30 The cubic grid box of 40 Å size (x, y, and z)
with a spacing of 0.375 Å were centered on the active sites
of the protein. The X-ray structure of S. aureus DNA bind-
ing protein (PDB entry: 4pql) was retrieved from Protein
Data Bank.31
Scheme 1. Synthesis of heteroaromatic chalcone derivatives.
1664 cm−1 attributed to υC═O and υC═O
in the
carboxyl
chalcone network. The presence of sharp peaks was
22
observed at 1601–1583 cm−1 attributed to υC═C
.
1H
Results and Discussion
NMR spectra displayed aromatic protons of 1a–c at δ
8.27–7.37 ppm with coupling constant J = 8.8–7.2 Hz,
while two doublets of vicinal protons (CHα = CHβ) were
observed at δ 7.79–7.76 ppm and 8.06–8.03 ppm with
J = 15.5–15.7, respectively, which corresponded to trans
configuration. 13C NMR spectra displayed sharp signals at
167.3 and 189.6 ppm attributed to (C═O) moiety of car-
boxylic group and ketone respectively. Although CHα and
CHβ appeared at 124.8 and 143.3, respectively.
Chemistry. Chalcone derivatives 1a–c were synthesized
via Claisen-Schmidt condensation of 4-formylbenzoic acid
with a series of acetophenone derivatives in the presence of
ethanolic NaOH. The formation of heterocyclic chalcones
namely pyrazolines (2a–c, 3a–c) from the reaction of
chalcone 1a–c with hydrazine derivatives has been success-
fully performed following aza-Michael reaction with excel-
lent yield (77–93%) in 1–3.5 min. The introduction of ester
moiety onto pyrazoline derivatives (2a–c, 3a–c) via Fischer
esterification afforded 4a–c in higher yields (83–96% in
<2 min). The synthetic reaction is outlined in Scheme 1.
The microwave-assisted reaction gave higher yields and
shorter time as compared to conventional method with
yields (55.9–88.5%) in longer time (30 min–24 h). The effi-
ciency of microwave-assisted synthesis over conventional
method for all compounds is depicted in Table 1. The pro-
posed mechanism is illustrated in Figure 1.
The FTIR spectra of 2a–c, 3a–c showed absorption
peaks of υC═N and υC─N at 1602–1593 cm−1, while the
peaks at 1346–1300 cm−1 corresponded to the formation of
pyrazoline. The peaks presence at 1669–1716 cm−1 were
attributed to υC═O of acetyl moiety in the molecular net-
1
work. The H NMR spectra of 2a–c, 3a–c displayed ─CH2
as three doublet of doublets at 3.02–5.85 ppm, which cor-
responded to the formation of pyrazolines via cyclization of
chalcone derivatives. Compound 2a–c displayed protons of
acetyl group at 2.3 ppm and aromatic region at 8.31–
6.70 ppm.32 The 13C NMR spectra showed prominent sig-
nals of 147.7–154.7 ppm and 167.1–167.5 ppm cor-
responded to C═O and C═N. The resonance observed at
63.09–59.8 ppm attributed to CH pyrazoline and 43.0–
The chemical structures of all synthesized compounds
1
were characterized using FTIR, H NMR and 13C NMR.
The FTIR spectra of 1a–c showed characteristic bands at
2988–2944 cm−1 attributed to a υCH while peaks at 1674–
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Figure 1. Proposed mechanism for the synthesis of pyrazline
ester.
Figure 3. Comparative 1H NMR spectra of 1a, 2a, 3a, and 4a.
42.4 ppm corresponded to CH2 in pyrazolines 2a–c and
neutralization able to protonate nitrogen atom and form
unstable quaternary ammonium salt, which eventually cau-
sed ring opening in the presence of sodium ethoxide.36
Hydrazine hydrate is stable in ethanolic base media, but
unstable in ethanolic solution due to atmospheric oxida-
tion.37–39 The hydrazone intermediate was easily cleaved
during neutralization due to free proton and reversibility of
reaction factors.40,41
The presence of carboxylic group and massive Szmant’z
solvent shell around hydrazone moiety has caused steric
hindrance, therefore it retards the cyclization of hydrazone.
This is due to the presence of hydrogen bonding with sol-
vent molecular cage and dimer formation with strong
hydrogen bonding (Figure 4). In solution phase, self-assem-
bled units offer informative supramolecular architecture
which appeared in the resulting macroscopic crystal struc-
tures. Mutual intermolecular hydrogen-bonded dimer of
carboxylic acid forms closed packing in crystal in the
3a–c.
The successful esterification of pyrazolines 2a–c and 3a–
c has produced 4a–c, which was confirmed by the presence
of strong peaks at 1719 cm−1 corresponded to υC═O of ester
1
group. The H NMR spectra of 4a–c showed resonance as
singlet at 3.80 ppm corresponded to CH3 of ester (Figures 2
and 3). The formation of the desired product was also phys-
ically confirmed via sulfuric acid (H2SO4) test for chalcone
and pyrazoline with reddish brown and green color, respec-
tively. Acetyl pyrazoline, however, did not show green
color as of phenyl pyrazoline. This is because the acetyl
group in pyrazoline is sensitive toward acid and base and
more labile toward cleavage to form complexes with differ-
ent colors (Table S2).13CNMR spectra have also exhibited
resonance at 52.4–52.5 ppm (CH3) and 166.3 ppm
(C═OOR ester), which corresponded to the target
compounds.
Several strategies were applied for the synthesis 1H-
pyrazoline (2d), i.e., in base33 and acid conditions.34 Many
studies have been reported on the formation of (2d) under
ethanolic base conditions.34,35 However, attempted synthe-
sis of 1H-pyrazoline (2d) was not availed due to the revers-
ible reaction.34 The presence of free proton in 2d is
believed to form interaction with carboxylic group, which
eventually retard the formation of pyrazoline. Acid
H
O
Hydrogen Bonding
with solvent
O
H
N
H
O
O
H
H
O
H
N
H
Intermolecular Hydrogen
Bonding of Dimer
O
280
260
240
220
200
180
160
140
120
100
80
H
O
O
H
O
H
N
O
H
H
O
O
H
N
H
O
H
O
60
40
H
20
4000
3500
3000
2500
2000
1500
1000
Wavenumbers (cm-1)
Figure 4. Solvent molecular cage and dimer packing hindrance
Figure 2. Comparative FTIR results of 1a, 2a, 3a, and 4a.
for 1H-pyrazoline formation.
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enhancement of activity. Phenyl pyrazoline ring 3b showed
higher antibacterial activity compared to chalcone
derivatives 1b.
The antibacterial kinetics studies were also kinetically
analyzed against S. aureus via turbidimetric kinetics
method.46 The inhibition activity of 1a–c, 2a–c, 3a–c, and
4a–c was evaluated against S. aureus at three different con-
centrations (50, 80, and 100 ppm).31 The MIC values were
determined by extrapolating concentration toward the zero
growth rate (Figures S4 and S5). Compounds 1a–c and 3a
showed excellent inhibition with MIC values of 88–93 ppm
and 80–101 ppm, respectively. Compound 3b and 3c, how-
ever, showed no antibacterial activity and experienced the
Figure 5. Docking image of 1b (a), 3b (b) illustrated binding
interaction with targeted protein.
presence of ethanol as solvent.42 A solute–solvent interac-
tion has also played an important role in the process of
internal rearrangements. Fortunately, phenyl pyrazoline
derivatives 3a–c and 4a–c were stable under basic condi-
tion and successfully synthesized via aza-Michael reaction
of chalcones and Fischer esterification, respectively.
Antibacterial Activities. Antibacterial activities of all syn-
thesized compounds 1a–c, 2a–c, 3a–c, and 4a–c have been
performed via both disc diffusion method against Gram-
positive S. aureus and Gram-negative E. coli. The ampicil-
lin was used as standard drugs and DMSO as negative con-
trol against bacterial strains.
formation of precipitate during administration into the
media. Similarly, 4a–c was also precipitated in broth solu-
tion due to poor solubility and solvent incompatibility
which refrained the kinetic study of antibacterial activity.
Overall, the microbial activity via turbidimetric kinetic
method was not conclusively promising for comparative
analysis in this study compared to disc diffusion method.
Solubility is an essential factor in drug discovery process,
in addition to other factors such as the nature of compound
(lithophilic and hydrophilic sites47), dilution rate, tempera-
ture, time, and concentration.48,49
All compounds were evaluated via disc diffusion assay
against S. aureus and E. coli. Zone of inhibitions of all
compounds is depicted in Table S3. Compounds 1a–c and
3a–c demonstrated excellent zone inhibition with 9–19 mm
against S. aureus. This phenomenon could be due to the
morphology of the bacteria cell wall.22 The antibacterial
potential of the synthesized compounds was varied with the
nature and position of substituents, and types of bacterial
strain.
The presence of acetyl group in pyrazoline (2a–c) and
pyrazolines ester (4a–c), however, did not show
antibacterial activities against S. aureus and E. coli. This
could be no formation of hydrogen bond interaction
between acetyl group with the protein receptor.43,44
Whereas, 4a–c were inactive in disc diffusion method due
to the strong interactions of unexpected solvent cage, which
occupy the active and reactive site of the compound with
solvent. In short, poor dissolution and improper solvent
composition on both ligand-binding and protein stability
could also contribute to the antibacterial activity.45
Compound 1a–c demonstrated mild activities with the
inhibition zone of 9–13 mm. The presence of hydrophilic
moiety (COOH) able to enhance the bacterial activities via
hydrogen bonding formation.43 Compound 1b showed
good inhibition zone (13 mm) compared to 1a (11 mm)
and 1c (9 mm). Higher electronegative and lithophilic moi-
ety of fluorine substituent in 1b has contributed to the
antibacterial activity.31 Compound 3a–c exhibited good
antibacterial activities with 16–19 mm inhibition zone.
Compound 3b gave superb activity with 19 mm inhibition
zone due to the presence of heterocyclic pyrazoline with
N─N moiety and fluoro substituent, that contributed for the
Molecular Docking
Comprehensive structure activity relationship analysis of
the targeted compounds (1b and 3b) with protein docking
was performed and visualized using Autodock vina. The
selected compounds (1b and 3b) is based on strong inhibi-
tion activity against S. aureus with diameter of inhibition
zone 13 and 19 mm, respectively. S. aureus N-Terminal
domain of DNA binding protein (PDB entry: 4pql) was
selected as the active site to interact with 1b and 3b. The
docking depicted the molecular interaction between the
compound (ligand) and targeted bacteria (receptor) via, i.e.,
hydrogen bonding, Van der Waal interaction.50 The
strength of interaction between a compound to its target
receptor was determined by the binding affinity. Lower
binding free energy indicates for stronger, simultaneous,
and stable binding interaction.51 Figure 5 showed the dock-
ing modeling result of 1b and 3b with the targeted protein.
The interaction of 1b with N-terminal domain of DNA
binding protein receptor gave binding free energy of
−7.0 kcal/mol (Figure 5(a)). The dominant hydrogen bond-
ing interactions between TRY17 and unsaturated keto moi-
ety of 1b was observed as represented with green line.52
Other amino acid residues such as GLU126, PHE24,
ASN76, LEU75, and ILE42 appeared to form bonding
interaction with aromatic (Ar) group of 1b via electrostatic
interactions and aryl-alkyl interactions.31,52 Compound 3b
depicted binding free energy of −8.0 kcal/mol (Figure 5
(b)). The docking image of 3b suggested that a strong
hydrogen bond interaction (indicated by green-colored
sphere) and hydrophilic interaction occurred between the
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BULLETIN OF THE
Article Study of Heteroaromatic Chalcone Derivatives as Potential Antibacterial Agents KOREAN CHEMICAL SOCIETY
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Three series of chalcone derivatives 1a–c, heteroaromatic
chalcone derivatives of pyrazoline 2a–c, 3a–c and hetero-
aromatic chalcone esters derivatives 4a–c have been effica-
ciously synthesized via conventional and MW radiation in
excellent yield. MW-assisted synthesis demonstrated con-
venience and green route with higher yield and shorter time
than the conventional method. Compounds 1a–c, 3a, and
3b exhibited good inhibition activity against S. aureus,
where 1b and 3b demonstrated the highest inhibition zone
with 13 and 19 mm, respectively, due to the presence of
halogen, carboxylic and pyrazoline (N─N) moieties.
Molecular docking supported the experimental results of
antibacterial activity via disc diffusion method. This study
showed the convenient preparation of chalcones and
pyrazoline derivatives and their potential for antibacterial
application in pharmaceutical industries.
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Acknowledgments. The authors would like to thank the
Ministry of Higher Education Malaysia and Universiti
Malaysia Sarawak (UNIMAS) for financial support through
F07/FRGS/1883/2019 and Postgraduate Research Grant
through F07/PGRS/1794/2019. We are also thankful to
Universiti Malaysia Sarawak for the Zamalah scholarship
awarded to Saba Farooq. Publication cost of this paper was
supported by the Korean Chemical Society.
Supporting Information. Additional supporting informa-
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