Silver–N-heterocyclic carbene complexes-catalyzed multicomponent reactions: Synthesis, spectroscopic characterization, density functional theory calculations, and antibacterial study

Article abstract of DOI:10.1002/ardp.202100111

Nowadays, silver–N-heterocyclic carbene (silver–NHCs) complexes are widely used in medicinal chemistry due to their low toxic nature toward humans. Due to the success of silver–NHCs in medicinal applications, interest in these compounds is rapidly increas

Full text of DOI:10.1002/ardp.202100111

Received: 23 March 2021
Revised: 27 April 2021
Accepted: 30 April 2021
|
|
DOI: 10.1002/ardp.202100111
F U L L P A P E R
Silver–N‐heterocyclic carbene complexes‐catalyzed
multicomponent reactions: Synthesis, spectroscopic
characterization, density functional theory calculations, and
antibacterial study
1
,2
1
3
4
Aziza Mnasri
| Amal Mejri | Sadok M. Al‐Hazmy | Youssef Arfaoui
|
2
,5
2,5
1,6
Ismail Özdemir
| Nevin Gürbüz
| Naceur Hamdi
1
Research Laboratory of Environmental
Sciences and Technologies (LR16ES09),
Higher Institute of Environmental Sciences
and Technology, University of Carthage,
Tunis, Tunisia
Abstract
Nowadays, silver–N‐heterocyclic carbene (silver–NHCs) complexes are widely used
in medicinal chemistry due to their low toxic nature toward humans. Due to the
success of silver–NHCs in medicinal applications, interest in these compounds is
rapidly increasing. Therefore, the interaction of N,N‐disubstituted benzimidazolium
2
Catalysis Research and Application Center,
İnönü University, Malatya, Turkey
3
Department of Chemistry, College of
salts with Ag O in dichloromethane to prepare novel Ag(I)–NHCs complexes was
Science, Qassim University, Buraidah, Saudi
Arabia
2
carried out at room temperature for 120 h in the absence of light. The obtained
4
Laboratory of Characterizations,
1
13
complexes were identified and characterized by H and C nuclear magnetic re-
sonance, Fourier‐transform infrared, UV–Vis, and elemental analysis techniques.
Then, the silver complexes were applied for three‐component coupling reactions of
aldehydes, amines, and alkynes. The effect of changing the alkyl substituent on the
NHCs ligand on the catalytic performance was investigated. In addition, it has been
found that the complexes are antimicrobially active and show higher activity than
the free ligand. The silver–carbene complexes showed antimicrobial activity against
specified microorganisms with MIC values between 0.24 and 62.5 μg/ml. These
results showed that the silver–NHC complexes exhibit an effective antimicrobial
activity against bacterial and fungal strains. A density functional theory calculation
study was performed to identify the stability of the obtained complexes. All geo-
metries were optimized employing an effective core potential basis, such as
LANL2DZ for the Ag atom and 6‐311+G(d,p) for all the other atoms in the gas
phase. Electrostatic potential surfaces and LUMO–HOMO energy were computed.
Transition energies and excited‐state structures were obtained from the time‐
dependent density functional theory calculations.
Applications & Modeling of Materials
(
LR18ES08), Department of Chemistry,
Faculty of Sciences, University of Tunis El
Manar, Tunis, Tunisia
5
Department of Chemistry, Faculty of Science
and Art, İnönü University, Malatya, Turkey
6
Department of Chemistry, College of Science
and Arts, Qassim University, Ar Rass, Saudi
Arabia
Correspondence
Naceur Hamdi, Research Laboratory of
Environmental Sciences and Technologies
(
LR16ES09), Higher Institute of
Environmental Sciences and Technology,
University of Carthage, Hammam‐Lif, Tunisia,
PB 77‐P.O. Box 77, 1054 Amilcar, Tunisia.
Email: naceur.hamdi@isste.rnu.tn
K E Y W O R D S
antimicrobial activity, antitumor activity, benzimidazolium salt, DFT calculations,
multicomponent reactions, silver catalysis, structural characterization
©
2021 Deutsche Pharmazeutische Gesellschaft
Arch Pharm. 2021;e2100111.
wileyonlinelibrary.com/journal/ardp
|
1 of 16
https://doi.org/10.1002/ardp.202100111

2
of 16
MNASRI ET AL.
|
1
|
INTRODUCTION
review by Tacke et al. covered the anticancer and antibiotic activities
[
37]
of benzyl‐substituted metal–NHC complexes.
Recently, a review
N‐Heterocyclic carbenes (NHCs) are neutral two‐electron donors
by Hecel focused on antimicrobial and anticancer applications of
silver complexes as potential therapeutic agents. Hecel's review also
and are known to be strong Lewis bases and excellent nucleophiles
[
1]
+
that bind metals better than phosphines. NHCs have been widely
studied for their intriguing structural properties. Since then, the
number of studies in this area have increased considerably. NHCs
have emerged as an important building block in coordination
chemistry. Due to their good σ‐donating property, NHCs form bonds
with metals at a greater stability than phosphines, and the lone pair
of electrons on the carbene carbon, and they are stabilized by ad-
summarized the pharmacological applications of Ag nanoparticles in
[
38]
medicine and pharmacy.
Also, it is seen that the number of studies
in the field of examining the antimicrobial properties of silver–NHCs
[
39]
against bacteria and fungi is increasing rapidly.
Here, we describe
the synthesis, characterization, and antimicrobial applications of new
silver complexes containing unsymmetrical NHC ligands. The struc-
tures of all silver–NHC complexes were characterized by elemental
[2–6]
1
13
jacent nitrogen atoms via inductive effect.
The variability of the
analysis as well as by H nuclear magnetic resonance (NMR),
C
biological activities of NHCs greatly depends on the ring size and
NMR, and infrared (IR) spectroscopic techniques. The silver com-
plexes were applied in three‐component coupling reactions of alde-
hydes, amines, and alkynes. In addition, the antimicrobial activities of
these complexes were tested against Gram‐negative bacteria, Gram‐
positive bacteria, and fungi. We show that these new silver–NHC
complexes are efficient antimicrobial agents against different mi-
croorganisms. Density functional theory (DFT) and time‐dependent
density functional theory (TD‐DFT) calculations were reported to
carry out correlations between experimental and theoretical para-
meters and physical properties.
[
7–9]
[10]
structure of the substitutions over the ring.
In 1944, Wooley
reported that benzimidazole can act similarly as purines. Following
that study, it was demonstrated that benzimidazole derivatives
possess several biological activities, such as antihypertensive, anti‐
inflammatory, antimicrobial, antiviral, antioxidant, antitumor, lipid
[
11–13]
modulator, and anticoagulant activities.
Silver salts have his-
torically been used as antimicrobial agents for the prevention of eye
infections in newborns and the purification of drinking water, as well
[
14,15]
as in wound healing.
Also, it is clear that the number of silver
centers plays a crucial role in bioactivity. As the number of silver
+
centers in a complex increases, the concentration of Ag ions in
target site also increases. This enhances the cytotoxicity of the
complex. The presence of lipophilic groups such as alkyl chains on
NHC ligand increases the lipophilic nature of the complex, which
helps easy penetration of the complex into the cell wall. On the
contrary, the disadvantage of existing well‐known silver‐based drugs
is that they lose their effects rapidly due to the quick release of the
2
|
RESULTS AND DISCUSSION
2.1
|
Preparation and structural properties of
benzimidazolium salts 2a–f
Target benzimidazole salts 2a–f were achieved via a two‐step
N‐alkylation process, as depicted in Scheme 1. The first step involves
the addition of an N‐alkyl chlorane group in the presence of KOH in
dimethyl sulfoxide (DMSO) at 80°C for 72 h to the corresponding
benzimidazole or 5,6‐dimethylbenzimidazole, enhancing the re-
activity of the other nitrogen atom. The addition of the appropriately
substituted benzyl chloride in dimethylformamide (DMF) at 80°C for
72 h to the remaining nitrogen atom gives desired N,Nʹ‐disubstituted
benzimidazolium salts 2a–f. The salts obtained were soluble in polar
solvents such as methanol, ethanol, DMSO, and DMF but remained
insoluble in nonpolar solvents such as diethyl ether, di-
chloromethane, and chloroform. Salts 2a–f were stable in air and
moisture environments in the solid state and in solution. Benzimi-
dazolium salts 2a–f were characterized by Fourier‐transform infra-
+
Ag ions. Therefore, the synthesis of silver complexes having strongly
coordinating ligands such as NHCs is very important for medicinal
[
16]
applications.
Propargylamines were prepared by the addition of a
[
17]
metal acetylide to an imine group.
However, this traditional
method has some drawbacks, such as the use of stoichiometric
amounts of strong bases and the high moisture sensitivity of the
organometallic reagents formed. The metal‐catalyzed coupling re-
3
action of aldehydes, amines, and alkynes (A coupling) to give pro-
[
18–20]
pargyl amines has been improved in recent years.
The only by‐
product is water in this method, which is a one‐pot multicomponent
reaction. Most biomedical studies on silver–NHC complexes have
[
21–25]
been conducted concerning their antimicrobial properties.
Al-
though the cytotoxic effects of silver compounds on bacteria have
long been established, the mechanisms of action are not completely
understood. Sporadic studies of the cell toxicity mechanisms of silver
compounds suggest that silver ions kill organisms in a variety of
1
13
red (FTIR) spectroscopy, H and
C NMR spectroscopy, and
elemental analysis.
1
13
The FTIR spectroscopy, H and C NMR spectroscopy, and
elemental analysis data of the title compounds confirm the proposed
[
26–30]
ways.
In this area, many articles have been recently published
on the synthesis and applications of silver–NHC complexes. Re-
cently, we reported bio‐organometallic studies of silver and gold
complexes of imidazolin‐2‐ylidene and benzimidazole‐2‐ylidene li-
structures. NMR spectra of all the compounds were analyzed in
1
CDCl
3
. In the H NMR spectra, acidic protons (NCHN) for benzimi-
dazolium salts 2a–f were observed at 11.00, 11.21, 10.63, 11.08,
[
31–35]
gands for antimicrobial applications.
The presence of a strong
11.19, and 11.09 ppm, respectively, as characteristic sharp singlets.
13
metal–ligand bond has attracted the attention of medicinal chemists
In the C NMR spectra of benzimidazole salts 2a–f, the NCHN
[
36]
toward the anticancer activity of Ag–NHC complexes.
A mini‐
carbon was detected as typical singlets at 143.2, 143.3, 143.7, 143.8,

MNASRI ET AL.
3 of 16
|
SCHEME 1 General synthesis and structure formulas of 1,3‐dialkylbenzimidazolium salts 2a–f. DMF, dimethylformamide; DMSO, dimethyl
sulfoxide
1
41.6, and 143.1 ppm. In the IR spectra, ν(C═N) bands for salts 2a–f
chloroform, dichloromethane, DMF, DMSO, ethanol, and acetonitrile,
and insoluble in hexane, ether, and benzene.
−
1
were observed at 1549, 1550, 1559, 1558, 1560, and 1560 cm
.
Aromatic protons of benzimidazolium salts 2a–f were detected in the
range of 7.01–8.02 ppm. Methyl protons of the isopropyl group on all
benzimidazolium salts were seen as doublets in the range of
The structure of the silver complexes was elucidated by NMR
spectroscopy. In addition, it was also supported with FTIR spectro-
scopy and elemental analysis data. However, an attempt was made to
obtain a single crystal for X‐ray diffraction, but a suitable single
crystal could not be obtained from these new silver complexes for
0
.75–0.76 ppm. N–CH– protons of the isopropyl group on benzimi-
dazolium salts 2a–f resonated between 2.04 and 2.06 as multiplets;
however, methylic protons –CH –N of benzimidazolium salts 2a–f
2
X‐ray diffraction. NMR spectra of all the compounds were analyzed
1
signaled at 2.88–4.54 ppm as triplets. Methylic protons of pyrrolidine
and piperidine groups on benzimidazolium salts (2c–f) resonated
between 1.28 and 3.03 as multiplets; however, methylic
in d‐CDCl
3
. In the H NMR spectra of Ag(I)–NHC complexes 3a–f,
the acidic proton (NCHN) for NHC ligands (2a–f) was not observed,
and its absence is proof of the formation of complexes 3a–f. The
characteristic signals (NCN) on the Ag(I)–NHC complexes 3a–f were
not detected exactly, which has also been mentioned in the literature
protons –CH
2
–N of benzimidazolium salts (2c–f) signaled at
1
2
.72–5.01 ppm as triplets. In the H NMR spectra of (2a–f),
[
40]
H
1″ protons were detected as typical singlets between 5.47 and
and is a reason for the fluctuating behavior of NHC complexes.
5
.82 ppm. The Ag–NHC complexes (3a–f) were prepared by in situ
These values are in agreement with reported data for similar Ag
[
41]
deprotonation of corresponding benzimidazolium salts (2a–f) using
silver(I) oxide as the both metal source and base. The reactions were
carried out in the dark in the presence of dichloromethane as the
solvent at room temperature for 120 h, and the target complexes
were obtained as white solids between 65% and 85% yields
(I)–NHC complexes.
2
Aliphatic –CH – protons of benzyl sub-
stituents for benzimidazolium salts were detected as a singlet at
1
3
δ = 4.54–5.77 ppm. C NMR chemical shifts provide a useful diag-
13
nostic tool for Ag–carbene complexes. In the C NMR spectra of
Ag–NHCs, characteristic signals of C(2) carbon of benzimidazolium
salts 2a–f completely disappeared. In our case for the complexes
(
Scheme 2). Complex 3 is an air‐stable solid soluble in acetone,

4
of 16
MNASRI ET AL.
|
SCHEME 2 General synthesis and
structure formulas of silver(I)–NHC
complexes (3a–f). DCM, dichloromethane;
NHC, N‐heterocyclic carbene
3
a–f, the resonances for AgC(carbene) bond were not observed,
medium is enhanced by the heavy atom effect of silver ion. This
explanation is supported by the higher absorbance at 286 nm and
much higher at 241 nm in chloroform, which is a nonpolar solvent;
which has also been mentioned in the literature and given as a
[
40–42]
reason for the fluxional behavior of the Ag–NHCs.
In the FTIR
+
spectra, benzimidazole ring C═N vibrations of NHC ligands (2a–f)
Ag is not solvated and exists near the emitting molecule, which
−
1
showed peaks at 1549, 1549, 1559, 1558, 1560, and 1560 cm
,
causes more concentration of triplet state molecules, leading to
higher absorbance that is confirmed by a clear increase in extinction
coefficient values. The chlorine atoms represent heavy atoms on
their own, as shown in Figure 1. It also shows the same behavior for
respectively. After the formation of the complexes, C═N vibrations
of Ag–NHC complexes 3a–f shifted to lower energy regions, such as
−1
1
484, 1445, 1473, 1486, 1474, and 1478 cm , respectively. This
negative shift was attributed to the electropositive metal center,
which pulls electron density toward itself. Also, elemental analysis
data of the Ag–NHC complexes were consistent with the expected
structures. A lot of work has been done by many groups on these
types of complexes, which are extremely stable in air and moisture.
Nolan and co‐workers also showed that silver N‐heterocyclic car-
complexes 3b and 3c with a 10‐nm red shift in a spin‐allowed S
transition for complex 3c.
0
→ S1
The triplet state of complexes 3a–c is not efficiently formed
in acetonitrile; on the contrary, in a chloroform solvent, their
[43,44]
benes are a powerful catalysts.
Also, some days later, when the
NMR of the solution in the NMR tube was taken again, the same
NMR spectrum had been observed.
2.2
|
UV–vis
The complex 3a in chloroform shows a clear strong absorbance at
41 nm, due to the spin‐allowed S → S transition. The medium in-
tensity longer wavelength bands at 286 nm indicate a spin‐allowed
→ S transition. The lower intensity longer wavelength bands at
96 nm in chloroform and at 426 nm in ethanol are attributed to the
spin‐forbidden S → T transition. Triplet state generation in the
2
0
2
S
0
1
–4
3
FIGURE 1 Absorption spectra of 1.5 × 10 M complexes (
3a, ( ) 3b, and ( ) 3c in CHCl
)
0
1
3

MNASRI ET AL.
5 of 16
|
−
5
3
FIGURE 3 Absorption spectra of 3 × 10 ml/dm of complex 3a
in CHCl fresh ( ) and irradiated solution ( ) using 365‐nm
light for 24 h
3
−
4
FIGURE 2 Absorption spectra of 1.5 × 10 M complexes (
a, ( ) 3b, and ( ) 3c in CH CN
)
3
3
Complex 3a shows great optical stability, as no change in the
emission and absorption spectra is observed on irradiation using
365‐nm light for 24 h, as shown in Figure 3. Neither the acid nor the
base affects the absorption spectra, as shown in Figure 4. An irre-
gular Stokes shift was observed, which varied between 13, 42, and
absorbance in acetonitrile at 390 nm is negligible, as the
values of the molar extinction coefficients are in the range
−
1
−1
6
0–80 M ·cm , as shown in Figures 1 and 2 and Table 1, which
may be attributed to the formation of a complex between acet-
+
onitrile and Ag .
91 nm in CHCl
3
, CH
3
CN, and ethanol of relative polarities, 0.460,
TABLE 1 Spectral data of
complexes 3a–c
λ
abs
λ
em
Solvent relative
−1
−1
Complex
Solvent
max (nm)
max (nm)
ε (M ·cm
)
ɸ
f
polarity
Complex 3a DMF
281
4337
100
0.386
3
96
438
CHCl
3
285
1973
220
0.25
3
4
96
82
438
595
433
407
0.10
CCl
4
395
2433
153
0.07 0.052
0.355
Acetone 394
i‐Butanol 281
5631
193
0.552
3
93
280
96
292
27
439
409
519
CH
3
CN
2666
100
0.460
0.03
3
Ethanol
2000
206
0.05 0.654
4
Complex 3b ETOH
392
396
394
391
1462
85
3
CH CN
DMF
4636
1277
1325
795
Complex 3c ETOH
409
–
0.02
0.02
Acetone 392
Cl 390
Glycerol 390
CH CN 396
CHCl
Abbreviation: DMF, dimethylformamide.
C
H
4 9
–
1277
80
3
409
435
3

6
of 16
MNASRI ET AL.
|
−
5
−
5
3
FIGURE 5 Normalized fluorescence spectra of 1.5 × 10
M
FIGURE 4 Absorption spectra of 3 × 10 ml/dm of complex 3a
complex 3a in ( ) acetone and ( ) ethanol, λex 365 nm
in CCl
(
4
fresh (
), alkalized solution using triethylamine
SO
), and acidified solution using H
2
4
(
)
Moreover, the energy gap (Δε) between HOMO and LUMO char-
acterizes the reactivity of the molecule. A molecule with a small Δε is
more polarizable and generally associated with a high chemical
0
.25, and 0.654, respectively, as shown in Table 1. In ethanol, the
larger Stokes shift is due to better excited state solvation in such a
polar solvent with the possibility of hydrogen bond formation. This is
substantiated by the lack of vibrational structure of the emission
spectrum of complex 3a in ethanol in comparison to acetone, as
indicated in Figure 5 and Table 1.
[
48]
reactivity.
HOMO and LUMO for complexes 3a–f (Figure 9) were
calculated from the optimized structure at the same level of
[
49]
theory.
It can be observed from Figure 10 and Table 2 that the
HOMO in compounds 3a and 3b is mainly localized on the
N‐isopropylpropan‐2‐amine part, whereas for complex 3f compounds,
the HOMO is localized around the Cl site. The LUMO for complexes
3a, 3b, and 3f is concentrated only in the benzimidazole moiety. Δε
values for the obtained complex are summarized in Table 3.
The difference between λex max and λab max of complex 3a
shown in Figure 6 is attributed to intramolecular proton transfer or
rearrangement.
Table 1 also shows no change in λabs max. It seems that the
ground states of complexes 3a–c are not influenced by changing
the relative solvent polarity and show a low molar absorptivity in the
studied solvents.
The high Δε value in the case of complex 3a refers to high
[
49]
chemical hardness and kinetic stability.
For the molecular
electrostatic potentials (MEPs), it is seen that most of the ne-
gative potentials appear to be distributed on the Cl and N29
atoms (red color), whereas the positive potentials appear to be at
Fluorescence was obtained only from complex 3a in CHCl
ethanol, and CH CN at emission maxima wavelength, 595, 433, 519,
08, and 433 nm, respectively; λex was at λab max with a low fluor-
escence quantum yield (ɸ = 0.10, 0.08, 0.05, and 0.03, respectively).
3 4
, CCl ,
3
4
8
N and N10 atoms (blue color). In the MEP surface, red color
f
refers to electron‐rich (negative) region, blue color refers to
electron‐poor (positive) region, and green color signifies zero
electrostatic potential. The charge distribution was similar in all
studied complexes and was weakly influenced by the chemical
environment (Figure 8 and Table 2).
Emission spectra of complex 3a in different solvents are shown in
Figure 7. The blue shift in the maximum absorption wavelength of 3b
in ethanol as compared with acetonitrile, shown in Figure 8, is due to
increase in solvent polarity.
2.3
|
DFT calculations
All the calculations were performed via DFT using the Gaussian 09
[
45]
set of programs.
The geometries of all products were optimized at
the B3LYP level of theory. The calculations were performed em-
ploying an effective core potential basis, such as LANL2DZ for the Ag
[
46]
atom and 6‐311+G(d,p) for all the other atoms.
Vibrational ana-
lyses confirmed that all products have zero imaginary frequencies.
[
47]
The electronic spectra were calculated using the TD‐DFT.
The frontier molecular orbitals, HOMO (highest occupied mo-
lecular orbital) and LUMO (lowest unoccupied molecular orbital),
play an important role in several chemical processes. Thus, the larger
the εHOMO, the greater is the electron‐donating ability, and the
smaller the εLUMO, the smaller is the resistance to accept electrons.
FIGURE 6 Normalized emission (
), excitation (
), and
−
4
absorption (
) spectra of 1.5 × 10 M in CHCl
3

MNASRI ET AL.
7 of 16
|
2.4
|
Catalytic activity of the silver(I)–NHC
complexes (3a–f)
The three‐component coupling reaction of alkynes, aldehydes, and
amines catalyzed by transition metals is a useful approach for the pre-
paration of propargyl amines as key intermediates in the building of
[
51]
nitrogen‐containing biologically active compounds.
Transition metal
However, there
[
52,53]
complexes are efficient catalysts for this reaction.
have been a limited number of reports related to the catalytic applica-
3
[54–56]
tions of NHC–Ag(I) complexes in A coupling reactions.
In recent
years, it has also been observed that silver compounds exhibit a highly
[57]
−5
effective catalytic activity for this three‐component coupling reaction.
FIGURE 7 Normalized fluorescence spectra of 1.5 × 10
M
Herein, preliminary catalytic studies were carried out using phenylace-
tylene, piperidine, and p‐formaldehyde at 80°C. The catalytic activity of
complex 3 was examined in different solvents (Table 4, entries 1–5).
complex 3a in (
) CHCl
3
, (
3
) CH N, (
) acetone, and
(
) ethanol, λex 365 nm
3
Moderate yields were obtained in acetone and CH CN. A good catalytic
activity was observed with complexes 3a, 3c, and 3f under neat condi-
tions (Table 4, entries 1 and 8). Whereas complexes 3b and 3e bearing
different substituents on the NHC ligand showed similar activities
(
Table 4, entries 6, 13, and 17), lower yields were obtained by complex 3e
Table 4, entries 14 and 18). It was concluded that the methyl group in
compound 3g caused a decrease in activity as compared with complex
a. It was previously reported that increasing the number of groups on
(
3
the NHC ligand led to a decrease in activity.
A tentative mechanism was proposed involving the exchange of
H of the C–H bond of alkyne by an Ag(I) species. The silver acetylide
intermediate thus generated reacted with the iminium ion generated
in situ from aldehydes and secondary amines to give the corre-
sponding propargylamine and regenerate the Ag(I) catalyst for fur-
ther reactions (Scheme 2).
FIGURE 8 Normalized absorption spectra of complex 3b,
−
4
3
−4
3
6
(
× 10 mol/dm in ethanol (
) in CH CN
) and 2.7 × 10 mol/dm
3
Herein, according to the mechanistic studies reported in the
3
literature regarding “A coupling” reactions, we proposed a likely
mechanism for the synthesis of propargylamines in the presence of 3.
In the first step of the catalytic cycle, a metal–acetylide intermediate
is created. The formation of this intermediate renders the alkyne
proton more acidic, causing its abstraction by iminium ion. Then, in
situ generated metal acetylide reacts with iminium ion to provide
propargylamine product and metal ion (Scheme 3).
To compare the experimentally obtained UV–visible and lumi-
nescence spectra with theoretical values, the TD‐DFT method was
applied to obtain a prediction of the emission spectra. Both theo-
retical emission and UV–visible spectra for 3a, 3b, and 3f complexes
are shown in Figures 11 and 12, respectively. The obtained spectra
indicate relatively strong two‐luminescence intensities with emission
maxima at 315 and 375 nm for the 3a complex, 314 and 366 nm for
the 3b complex, and 302 and 374 nm for the 3f complex. This
fluorescent maximum emission band can be attributed to the intra‐
It is well known that silver ions and silver‐based compounds are
[
58]
highly toxic to microorganisms
and show strong biocidal effects;
therefore, as an advancement of our previous studies, we now in-
vestigate the antimicrobial activity of the synthesized silver–NHC
complex 3.
[
50]
ligand π*–π charge transitions of the benzimidazole moiety.
The
calculated UV–visible spectra of complexes 3a, 3b, and 3f display
two intense bands centered at 262 and 312 nm for complex 3a, two
intense bands at 260 and 303 nm for 3b, and two bands at 252nm
and 307 nm for 3f complexes, attributed to two π–π* transitions.
DFT calculations were adopted to investigate the geometry and
spectral properties of the studied complexes. The obtained theore-
tical geometric parameters are approximately in good agreement
with the experimental parameters (Figure 13 and Table 3), and there
is approximately no effect of the substituent on the obtained geo-
metric parameter results (Table 3).
2.5
|
Antibacterial and antifungal activities
Ag–NHC complexes 3a–f and salts 2a–f were initially tested against
bacterial strains with ampicillin and nystatin as standard drugs using
the agar disc diffusion technique. In this section, the antimicrobial
activities of Ag–NHC complexes 3a–f and salts 2a–f are described
against Listeria monocytogenes, Escherichia coli, Pseudomonas aerugi-
nosa, Salmonella typhimurium, and Candida albicans. The antimicrobial

8
of 16
MNASRI ET AL.
|
FIGURE 9 The calculated energies (eV) of
the LUMO (L), HOMO (H), Δε, and plots of the
calculated frontier molecular orbitals at
isovalue = 0.02 a.u. of complexes 3a, 3b, and
3
f. The positive (blue) and negative (red)
phase distributions in molecular orbital wave
function. HOMO, highest occupied molecular
orbital; LUMO, lowest unoccupied molecular
orbital
FIGURE 10 Molecular electrostatic
potentials surface of the three complexes 3a,
3
b, and 3f mapped on the electron density
isovalue of 0.0004 a.u
activity of these complexes, measured based on a zone of inhibition
zoi) parameter, is listed in Table 5, whereas the minimum inhibitory
bacteria. It is interesting to note that S. typhimurium was not sensitive
to the silver complex 3d and salt 2c. Complexes 3c and 3b showed
higher activity (zoi = 31 mm and zoi = 25 mm, respectively) against
Staphylococcus aureus (Table 5). Likewise, the corresponding
MIC values of each of these two complexes were 0.24 and
3.9 mg/ml, respectively. The other benzimidazole salt 2 was inactive.
(
concentration (MIC) is listed in Table 6. When tested against bacteria
at concentrations of 200–50 μg/ml, the silver–NHC complexes
showed antibacterial activity. It was found that all complexes showed
high levels of activity against Gram‐negative and Gram‐positive

MNASRI ET AL.
9 of 16
|
TABLE 2 Values of local minimum and maximum electrostatic
potential (Vs, min and Vs, max in kcal/mol) of complexes 3a, 3b, and 3f
obtained at the electron density isosurface value of 0.0004 au
necessary to inhibit the growth of a bacterial strain. A preliminary
study of silver complex 3 was done to determine its MIC. The results
of this compound were compared with that of silver nitrate, which
was used as a positive control based on its established antimicrobial
Complex 3a
Complex 3b
Complex 3f
[
24]
V
s, min
V
s, max
V
s, min
V
s, max
V
s, min
V
s, max
properties.
(
kcal/
(kcal/
mol)
(kcal/
mol)
(kcal/
mol)
(kcal/
mol)
(kcal/
mol)
The compounds were incubated for 24 h with the nonvirulent
strains of P. aeruginosa, S. aureus, and E. coli in growth media.
Complex 3 showed antimicrobial activity at the concentrations
tested (Table 6). Although there is evidence of silver complexes that
mol)
N
N
N
8
11.41
8.92
7.25
6.85
10.22
8.81
10
19
[
25,26]
have shown antimicrobial activity,
the results from the study of
−6.77
−7.02
−10.99
−44.35
silver complex 3 are consistent with studies on other silver carbene
Cl
−44.02
−44.23
complexes (SCCs) synthesized in our research group in which anti-
[
12,15,16]
microbial activity is observed.
The silver complexes 3c and
3
a, however, showed inhibition of bacterial growth with MICs of 0.24
TABLE 3
complexes
εHOMO, εLUMO, Δε (eV), and geometric data of the 3a–f
and 1.95 mg/ml, respectively, against L. monocytogenes ATCC 19117
and S. typhimurium ATCC 14028. These values were comparable to
the MIC of silver nitrate (42.5 mg/ml), indicating that these new
silver complexes are equally effective. Complex 3c showed better
activity than ampicillin against Micrococcus luteus with an MIC of
Complexes
3a
3b
3c
3d
3e
3f
ε
HOMO (eV)
LUMO (eV)
−5.770 −5.754 −6.082 −6.021 −6.019 −6.059
−1.546 −1.512 −1.635 −1.574 −1.470 −1.602
ε
0
.0025 mg/ml, whereas an MIC of 0.0045 mg/ml was observed in the
Δε (eV)
4.224
2.368
2.119
1.362
1.360
4.242
2.369
2.119
1.362
1.360
4.447
2.367
2.123
1.361
1.359
4.447
2.367
2.120
1.362
1.360
4.549
2.368
2.122
1.361
1.359
4.457
2.367
2.123
1.361
1.358
case of S. typhimurium for complex 3c. The MICs of other compounds
remained within the tested range. Further studies are necessary to
determine the efficacy of these compounds, compared with other
SCCs, and their effectiveness against more virulent strains, but
preliminary results demonstrate the potential of 3 in the treatment
of bacterial infections.
dAg–Cl (Å)
dC–Ag (Å)
dC
9
9
–N
8
(Å)
dC
–N10 (Å)
ˆ
CAgCl (°)
177.72 178.79 179.34 178.02 179.36 179.44
316.0 315.9 317.5 317.8 316.0 316.8
ν
̅
(Ag–Cl)
−
1
(cm )
3
|
CONCLUSIONS
Five benzimidazolium salts and their Ag(I)–NHC complexes were
1
synthesized using appropriate methods. The combination of FTIR, H,
13
and C NMR spectral and elemental analyses suggested the for-
mation of these complexes. The in vitro antimicrobial activities of the
silver complexes were studied against four bacteria and two fungi to
determine their inhibitory effects. Various substituents on nitrogen
atom have a different effect on antimicrobial activity. A simple in-
spection of Table 2 indicated that the presence of sterically bulky
groups directly grafted on the nitrogen atom of the benzimidazol‐2‐
ylidene ligand has a positive effect on the antimicrobial activity.
Especially, some of the complexes exhibited remarkable inhibitory
activity against the growth of bacterial and fungal strains. These
results clearly prove the potential of the complexes as antimicrobial
drugs. Moreover, further studies focused on the synthesis of new
(benz)imidazol‐2‐ylidene‐linked silver complexes, and their biological
and medical applications as potential metallopharmaceutical agents
are currently underway by our research group. Preliminary catalytic
studies revealed that complexes 3a and 3c catalyzed the
three‐component reaction of piperidine, phenylacetylene, and
formaldehyde in good yields under neat conditions. Experimental
studies on 3a–f complexes were accompanied computationally by
DFT when the calculated UV–visible and photoluminescence spectra
are in good agreement with the experimental data. TD‐DFT
FIGURE 11 Luminescence spectra of the 3a, 3b, and 3f
complexes
Furthermore, it may be noted that the activity of the present com-
plexes was better than that of the previously reported silver nitrate
[
59]
complexes.
The microorganism C. albicans was found to be sen-
sitive to all of the salts 2 and their complexes studied 3, with an
activity varying in the range of 16–28 mm (zoi). Complex 3c and salt
2
c showed the highest activities of 28 and 24 mm, respectively,
against C. albicans.
To determine the efficacy of the complexes, MICs are de-
termined. The MIC is the minimum concentration of compound

10 of 16
MNASRI ET AL.
|
FIGURE 12 UV–visible spectra of the 3a, 3b,
and 3f complexes
pentoxide and were transferred under argon atmosphere. Melting points
were measured in open capillary tubes with an Electrothermal‐9200
melting point apparatus. FTIR spectra were obtained in the range
−1
1
4
50–4000 cm on a PerkinElmer Spectrum 100 spectrophotometer. H
13
NMR and C NMR spectra (see Supporting Information) were recorded
using a Bruker Avance AMX and a Bruker Avance III spectrometer op-
1
13
3
erating at 400 MHz ( H NMR) and at 100 MHz ( C NMR) in CDCl . The
NMR studies were carried out in high‐quality 5‐mm NMR tubes. The
1
chemical shifts (δ) are reported in ppm, relative to CDCl
3
. H NMR peaks
were labeled as singlet (s), doublet (d), triplet (t), pentet (p), and multiplet
1
(
m). H NMR spectra are referenced to residual protiated solvents
13
(
δ = 7.26 ppm for CDCl
3
), and C NMR chemical shifts are reported
relative to deuterated solvents (δ = 77.16 ppm for CDCl
3
).
The InChI codes of the investigated compounds are provided as
Supporting Information.
Organic solvents (Fluka, puriss) were of spectroscopic grade. UV–vis
absorption spectra were recorded on a Shimadzu 1600 spectro-
photometer using matched 1‐cm quartz cells. Steady‐state emission and
excitation spectra were recorded using a Jasco FP‐8200 spectro-
fluorometer (Ex bandwidth of 5 nm, Em bandwidth of 5 nm) with a Xe
lamp light source. Fluorescence quantum yields (ɸ
f
) were measured
in basic media using an absorbance of
0.06 to avoid reabsorption of the emitted light. The following relation
has been applied to calculate the fluorescence quantum yields relative to
[60]
relative to merocyanine dye
<
FIGURE 13 Molecular structure of complex 3a
[61]
those of the merocyanine dye in basic media
:
calculations were also performed to assign the bands observed in the
2
ϕf (s)
ϕf (r)
∫Is ( v¯ )d v¯
Ir ( v¯ )d v¯
Ar
As
ns
=
×
×
.
electronic spectra of the 3a–f complexes.
nr2
The integral represents the corrected fluorescence peak areas, A is
the absorbance at the excitation wavelength, n is the solvent refractive
index, and the subscripts s and r refer to the sample and reference,
respectively.
4
4
4
|
EXPERIMENTAL
|
Chemistry
.1
.1.1
|
General
4.1.2 Preparation of benzimidazolium salts 2
|
All reactions were carried out under argon using standard Schlenk line
techniques. All chemicals and solvents, including Ag O, were purchased
from Sigma‐Aldrich and Merck. The solvents such as DMF and CH Cl
were purified by distillation over the drying agents such as phosphorus
2
The reaction of 1‐alkyl‐benzimidazole (1a,b) (1 mmol) (1) with
various alkyl chlorides (1 mmol) in DMF (5 ml) at 80°C for 72 h
afforded benzimidazole salts 2a–f. A white crystalline solid was
2
2

MNASRI ET AL.
11 of 16
|
3
a
TABLE 4
A
coupling reactions catalyzed by 3a–f
b,c
Entry
Catalyst
3a
Solvent
Conversion (%)
1
2
3
4
5
6
7
8
Neat
85
65
70
45
55
75
55
80
60
80
62
75
45
80
60
3a
3
CH CN
3a
DMSO
Acetone
DMF
3a
3a
3b
3b
3c
Neat
CH
Neat
CH CN
Neat
CH CN
Neat
CH CN
Neat
CH CN
3
CN
1
1
1
1
1
1
1
0
1
2
3
4
5
6
3c
3
3d
3d
3e
3
3e
3
3f
3f
3
Abbreviations: DMF, dimethylformamide; DMSO, dimethyl sulfoxide.
a
Reaction conditions: aldehyde (1.0 mmol), amine (1.2 mmol), phenylacetylene (1.5 mmol), catalyst (3 mol %), solvent (2 ml), 18 h, 80°C, in air.
b
Isolated yields.
c
Average of two runs.
SCHEME 3 The proposed reaction
mechanism for NHC–AgCl‐catalyzed A
coupling reactions
3

12 of 16
MNASRI ET AL.
|
TABLE 5 The antimicrobial activity of the complexes based on the zone of inhibition (zoi) parameter
Microorganism,
bacteria/fungi
Staphylococcus
aureus
Listeria
Pseudomonas
aeruginosa
Salmonella
Candida
albicans
monocytogenes
Escherichia coli
typhimurium
3
3
3
3
3
3
2
2
2
2
2
2
a
b
c
d
e
f
15
25
31
21
24
15
14
15
–
16
20
30
25
16
18
15
16
–
16
17
17
26
20
16
14
18
–
18
18
22
26
22
20
12
14
–
18
20
28
–
18
22
28
26
24
18
20
22
24
16
20
20
–
18
18
22
22
–
a
b
c
d
e
f
–
12
–
–
–
16
15
15
16
–
–
–
12
–
–
–
–
AMC
16
–
16
–
18
–
20
–
Nystatin
20
Abbreviation: AMC, amoxicillin/clavulanic acid.
TABLE 6 Minimal bacterial inhibitory
concentration measured in mg/ml of 3a–g
Compounds
Microorganisms
3a
3b
3c
3d
3e
3f
Ampicillin
Kanamycin
Listeria monocytogenes
3.9
3.9
0.24 15.6 31.25 62.5 3.9
12.5
ATCC 19117
Staphylococcus aureus
3.9
1.95 0.24 3.9
62.5
125 1.95
6.25
12.5
Salmonella typhimurium
1.95 3.9 0.24 1.95 15.62 62.5 3.9
ATCC 14028
obtained after adding diethyl ether (15 ml), which was subse-
quently filtered off. After washing with diethyl ether
1‐[2‐(Diisopropylamino)ethyl]‐3‐(4‐methylbenzyl)‐5,6‐
dimethylbenzimidazolium chloride (2b)
−
1
1
(
3 × 10 ml), the solid was dried under vacuum and the crude
product was recrystallized from dichloromethane/diethyl ether
1:3 ratio).
Yield 78%, Mp: 220°C, ν(CN) = 1549 cm
.
H
NMR (CDCl
3
,
400 MHz) δ (ppm) = 0.75 (s, 12H, CH3(a,b,c,d)), 2.27 (s, 3H, H
e
), 2.35 (s,
(
3H, CH3(f)), 2.38 (s, 3H, CH3(g)), 2.88 (t, 2H, H2ʹ), 2.99 (m, 2H,
CH (3ʹ,4ʹ)), 4.48 (t, 2H, H1ʹ), 5.71 (s, 2H, H1″), 7.12–7.38 (m, 6H, H7,4,2″,3″,
1
3
1
‐[2‐(Diisopropylamino)ethyl]‐3‐(2‐methylbenzyl)‐5,6‐
5″,6″), 11.21 (s, 1H, H
136.96 (d, J = 8.4 Hz, C5,6), 136.42 (C5″), 131.20 (C2″), 130.30 (C
(C ), 128.05 (C3″,7″), 126.73 (C4″ 6″), 113.22 (C ), 112.97 (C
(C3ʹ,4ʹ), 47.69 (C2ʹ), 47.26 (C1″), 44.18 (C1ʹ), 20.77 (Ca,b,c,d), 19.64 (C
(Cf,g). Anal. calc. for C25 36ClN (%): C, 72.52; H, 8.76; N, 10.15. Found
(%): C, 72.6; H, 8.9; N, 10.1.
2
). C NMR (CDCl
3
, 100 MHz) δ (ppm) = 143.30 (C
), 129.91
), 49.26
), 18.52
2
),
dimethylbenzimidazolium chloride (2a)
9
−
1
1
Yield 75%, Mp: 215°C, ν(CN) = 1549 cm
.
H
NMR (CDCl3,
8
,
7
4
4
00 MHz) δ (ppm) = 0.76 (s, 12H, CH3(a,b,c,d)), 2.33 (s, 3H, CH3(e)), 2.40
s, 6H, CH3(f,g)), 2.90 (t, 2H, H2ʹ), 3.00 (m, 2H, H3ʹ 4ʹ), 4.54 (t, 2H, H1ʹ),
4″,5″,6″), 7.43 (s, 1H, H ), 11.00 (s,
, 100 MHz) δ (ppm) = 143.22 (C ), 136.92
2″), 136.84 (C3″), 136.34 (C5,6), 131.14 (C4″), 131.112 (C7″), 130.22
5″), 129.83 (C6″), 129.04 (C ), 127.97 (C ), 113.14 (C ), 112.89 (C ),
9.18 (C3ʹ 4ʹ), 47.61 (C1″), 47.18 (C2ʹ), 44.10 (C1ʹ), 20.69
a,b,c,d), 19.56 (C ), 18.52 (Cf,g). Anal. calc. for 36ClN
%): C, 72.52; H, 8.76; N, 10.15. Found (%): C, 72.6; H,
.7; N, 10.2.
e
(
,
H
3
5
1
.77 (s, 2H, H1″), 7.15 (m, 5H, H7,3″
,
4
13
H, H
2
). C NMR (CDCl
3
2
(
(
C
1‐[2‐(Pyrrolidin‐1‐yl)ethyl]‐3‐(2,3,5,6‐tetramethylbenzyl)‐
benzimidazolium chloride (2c)
C
9
8
7
4
−1
1
4
,
Yield 70%, Mp: 205°C, ν(CN) = 1559 cm
100 MHz) δ (ppm) = 1.66 (s, 4H, H5ʹ 6ʹ), 2.22–2.24 (d, 12H, CH3(a,b,c,d)),
2.58 (m, 4H, H4ʹ,7ʹ), 3.01 (t, 2H, H2ʹ), 4.82 (t, 2H, H1ʹ), 5.82 (s, 2H, CH
.
3
H NMR (CDCl ,
(
(
C
e
C
25
H
3
,
2
,
13
8
2
H1″), 7.06–7.79 (m, 5H, H4,5,6,7,5″), 10.63 (s, 1H, H ). C NMR

MNASRI ET AL.
13 of 16
|
(
CDCl
3
, 100 MHz) δ (ppm) = 143.77 (C
33.62 (C3″,7″), 131.76 (C ), 131.34 (C
26.97 (C ), 113.53 (C ), 113.27 (C ), 53.94 (C4ʹ
7.51 (C2ʹ), 46.19 (C1ʹ), 23.71 (C5ʹ 6ʹ), 20.67 (Cb,c), 16.09 (Ca,d). Anal.
32ClN (%): C, 72.43; H, 8.10; N, 10.56. Found (%): C,
2.5; H, 8.2; N, 10.6.
2
), 135.13 (C2″), 134.18 (C4″,6″),
), 127.92 (C5″), 126.99 (C ),
7ʹ), 53.62 (C1″),
temperature in the dark. The reaction mixture was filtered through
celite and the solvent was removed under reduced pressure. The
crude product was recrystallized from dichloromethane/diethyl
ether (1:3).
1
1
4
9
8
5
6
7
4
,
,
calc. for C24
H
3
7
Chloro‐{1‐[2‐(diisopropylamino)ethyl]‐3‐(2‐methylbenzyl)‐5,6‐
dimethylbenzimidazole‐2‐ylidene}silver(I) (3a)
−1
1
1
‐[2‐(Pyrrolidin‐1‐yl)ethyl]‐3‐(2‐methylbenzyl)‐5,6‐
Yield 75%, Mp: 185°C, ν(CN) = 1484 cm
.
3
H NMR (CDCl ,
dimetilbenzimidazolium chloride (2d)
400 MHz) δ (ppm) = 0.94 (s, 12H, CH3(a,b,c,d)), 2.29 (s, 3H, CH3(e)), 2.40
−1 1
3
Yield 80%, Mp: 240°C, ν(CN) = 1558 cm . H NMR (CDCl , 400 MHz) δ
(s, 6H, CH3(f,g)), 2.90 (t, 2H, H2ʹ), 3.04 (m, 2H, H3ʹ,4ʹ), 4.33 (t, 2H, H1ʹ),
1
3
(
ppm) = 1.69 (m, 4H, H5ʹ,6ʹ), 2.29 (s, 3H, CH3(c)), 2.35 (s, 3H, CH3(a)), 2.38 (s,
5.51 (t, 2H, H1″), 7.24–6.61 (m, 6H, H7,4
100 MHz) δ (ppm) = 134.00 (C2″), 133.48 (C7″), 133.28 (C5,6), 131.24
(C6″), 128.44 (C9,8), 128.24 (C3″), 126.91 (C4″,5″), 112.55 (C ), 112.34
(C ), 51.50 (C4ʹ,3ʹ), 51.07 (C1″), 49.17 (C2ʹ), 46.00 (C1ʹ), 21.41 (Ca,b,c,d),
20.94 (C ), 20.73 (C ), 19.96 (C ). Anal. calc. for C25 35AgClN (%): C,
57.65; H, 6.77; N, 8.07. Found (%): C, 57.7; H, 6.75; N, 8.1.
3
, 4″,5″, 6″,7″). C NMR (CDCl ,
3
H, CH3(b)), 2.61 (m, 4H, H4ʹ,7ʹ), 3.03 (t, 2H, H2ʹ), 4.68 (t, 2H, H1ʹ), 5.78 (s,
13
2
H, H1″), 7.01–7.46 (m, CH, H4,7,4″,5″,6″,7″), 11.19 (s, 1H, H
, 100 MHz) δ (ppm) = 143.84 (C ), 137.45 (C2″), 137.37 (C
36.98 (C ), 131.59 (C3″), 131.49 (C4″), 130.31 (C7″), 130.31 (C5″), 129.46
6″), 128.35 (C ), 126.97 (C ), 113.71 (C ), 113.09 (C ), 54.36 (C4ʹ,7ʹ),
4.08 (C1″), 50.06 (C2ʹ), 46.45 (C1ʹ), 24.01 (C5ʹ,6ʹ), 21.03 (C ), 19.83 (C ),
8.82 (C ). Anal. calc. for C23 30ClN (%): C, 71.95; H, 7.88; N, 10.94.
2
). C NMR
7
(CDCl
3
2
5
),
8
1
6
e
f
g
H
3
(C
9
8
7
4
5
1
a
b
c
H
3
Chloro‐{1‐[2‐(diisopropylamino)ethyl]‐3‐(4‐methylbenzyl)‐5,6‐
dimethylbenzimidazole‐2‐ylidene}silver(I) (3b)
Found (%): C, 72.1; H, 7.9; N, 10.8.
−1
1
Yield 78%, Mp: 290°C, ν(CN) = 1445 cm
.
3
H NMR (CDCl ,
1
‐[2‐(Pyrrolidin‐1‐yl)ethyl]‐3‐(2,3,5,6‐tetramethylbenzyl)‐5,6‐
400 MHz) δ (ppm) = 0.93 (s, 12H, CH3(a,b,c,d)), 2.31 (s, 6H, CH3(f,g)),
dimetilbenzimidazolium chloride (2e)
2.37 (s, 3H, CH3(e)), 2.88 (t, 2H, H2ʹ), 3.02 (m, 2H, H3ʹ,4ʹ), 4.31
−
1
1
13
Yield 85%, Mp: 210°C, ν(CN) = 1560 cm . H NMR (CDCl
3
, 400 MHz) δ
(t, 2H, H1ʹ), 5.49 (s, 2H, H1″), 7.07–7.22 (m, 6H, H4,7,3″,4″,6″,7″).
NMR (CDCl
(C5,6), 132.36 (C9,8), 129.79 (C4″,6″), 127.23 (C3″,7″), 112.30 (C
111.96 (C ), 53.16 (C3ʹ,4ʹ), 50.68 (C1″), 48.96 (C1ʹ), 45.68 (C2ʹ), 21.08
(Ca,b,c,d), 20.60 (C ), 20.57 (Cf,g). Anal. calc. for C25 35AgClN (%): C,
C
(ppm) = 1.72 (m, 4H, H5ʹ,6ʹ), 2.20 (d, 6H, CH3(a,d)), 2.24 (d, 6H, CH3(b,c)),
3
, 100 MHz) δ (ppm) = 138.33 (C2″), 133.56 (C5″), 133.50
),
2
.34 (s, 3H, CH3(e)), 2.40 (s, 3H, CH3(f)), 2.72 (m, 4H, H4ʹ,7ʹ), 3.14 (t, 2H,
2ʹ), 4.82 (t, 2H, H1ʹ), 5.66 (d, 2H, H1″), 7.06 (s, 1H, H5″), 7.18 (s, 1H, H ),
, 100 MHz) δ
), 134.83 (C ), 133.83
), 127.50 (C5″), 112.82
7ʹ), 52.86 (C1″), 46.63 (C2ʹ), 45.18 (C1ʹ), 23.31
5ʹ,6ʹ), 20.40–20.32 (Cb,c), 18.20 (Ce,f), 15.73 (Ca,d). Anal. calc. for
36ClN (%): C, 73.30; H, 8.52; N, 9.86. Found (%): C, 73.1; H, 8.5;
N, 9.8.
7
H
4
4
13
7
.64 (s, 1H, H
ppm) = 141.62 (C
4″,6″), 133.29 (C3″
), 112.72 (C ), 53.45 (C4ʹ
7
), 10.12 (s, 1H, H
), 137.12 (C2″), 137.00 (C
7″), 129.87 (C ), 129.52 (C
8
2
). C NMR (CDCl
3
e
H
3
(
2
5
6
57.65; H, 6.77; N, 8.07. Found (%): C, 57.7; H, 6.75; N, 8.1.
(C
,
9
(C
7
4
,
Chloro‐{1‐[2‐(pyrrolidin‐1‐yl)ethyl]‐3‐(2,3,5,6‐tetrabenzyl)‐
benzimidazole‐2‐ylidene}silver(I) (3c)
(C
−1 1
26
C H
3
Yield 80%, Mp: 180°C, ν(CN) = 1473 cm . H NMR (CDCl
(ppm) = 1.74 (m, 4H, H5ʹ,6ʹ), 2.13 (s, 6H, CH3(a,d)), 2.28 (s, 6H, CH3(b,c)), 2.56
m, 4H, H4ʹ,7ʹ), 2.90 (t, 2H, H2ʹ), 4.45 (t, 2H, H1ʹ), 5.46 (s, 2H, H1″),
3
, 400 MHz) δ
(
1
3
1
‐[2‐(Pyrrolidin‐1‐yl)ethyl]‐3‐(2,3,4,5,6‐pentamethylbenzyl)‐
7.12–7.51 (m, 5H, H4,5,6,7,5″). C NMR (CDCl
135.06 (C2″), 134.04 (C4″,6″), 133.57 (C3″,7″), 133.27 (C
129.50 (C5″), 124.06 (C ), 123.84 (C ), 111.19 (C ), 111.17 (C
(C4ʹ,7ʹ), 54.23 (C2ʹ), 49.03 (C1″), 47.24 (C ʹ), 23.37 (C5ʹ,6ʹ), 20.46 (Cb,c), 15.94
(Ca,d). Anal. calc. for C24 31AgClN (%): C, 57.10; H, 6.19; N, 8.32. Found
(%): C, 57.2; H, 6.3; N, 8.4.
3
, 100 MHz) δ (ppm) =
), 132.91 (C ),
), 55.56
benzimidazolium chloride (2f)
8
9
−
1
1
Yield 67%, Mp: 215°C, ν(CN) = 1560 cm
.
H
NMR (CDCl
3
,
5
6
7
4
4
9
5
00 MHz) δ (ppm) = 1.75 (m, 4H, H5ʹ,6ʹ), 2.25 (s, 6H, CH3(a,e)), 2.28 (s,
1
H, CH3(b,c,d)), 2.78 (m, 4H, H4ʹ,7ʹ), 3.20 (s, 2H, H2ʹ), 4.95 (s, 2H, H1ʹ),
H
3
13
.76 (s, 2H, H1″), 7.94–7.43 (m, 4H, H4,5,6,7), 10.47 (s, 1H, H
, 100 MHz) δ (ppm) = 143.12 (C ), 137.38 (C2″), 133.96
), 133.57 (C ), 131.71 (C3″,7″), 131.22 (C4″,6″), 127.13 (d,
J = 13.2 Hz, C5,6), 124.91 (C5″), 113.43 (d, J = 18.1 Hz, C7,4), 53.70
7ʹ), 53.16 (C2ʹ), 47.77 (C1″), 45.52 (C1ʹ), 23.55 (C5ʹ,6ʹ), 17.34 (Ca,e),
7.02 (d, J = 1.8 Hz, Cb,c,d). Anal. calc. for C25 34ClN (%): C, 72.88; H,
.32; N, 10.20. Found (%): C, 72.8; H, 8.4; N, 10.3.
2
).
C
NMR (CDCl
3
2
(
C
9
8
Chloro‐{1‐[2‐(pyrrolidin‐1‐yl)ethyl]‐3‐(2‐methylbenzyl)‐5,6‐
dimethylbenzimidazole‐2‐ylidene}silver(I) (3d)
−
1
1
(
C
4ʹ
,
Yield 70%, Mp: 200°C, ν(CN) = 1486 cm
.
3
H NMR (CDCl ,
1
8
H
3
400 MHz) δ (ppm) = 1.79 (m, 4H, H5ʹ,6ʹ), 2.28 (s, 3H, CH3(a)), 2.37
(s, 6H, CH3(b,c)), 2.62 (m, 4H, H4ʹ,7ʹ), 2.96 (t, 2H, H2ʹ), 4.49 (t, 2H, H1ʹ),
1
3
5
.51 (s, 2H, H1″), 7.06–7.29 (m, 6H, H7,4,4″,5″,6″,7″). C NMR (CDCl
00 MHz) δ (ppm) = 135.45 (C2″), 133.85 (C3″), 133.81 (C ), 133.18
), 132.53 (C4″), 130.93, 188.26 (C ), (C7″), 128.31 (C ), 126.61 (C ),
126.32 (C5″,6″), 112.29 (C ), 111.73 (C ), 55.97 (C4ʹ), 54.70 (C7ʹ),
1.24 (C2ʹ), 48.78 (C1″), 23.74 (C1ʹ), 20.51 (C5ʹ,6ʹ), 19.65 (Ca,b,c). Anal.
calc. for C23 29AgClN (%): C, 56.28; H, 5.96; N, 8.56. Found (%): C,
56.3; H, 6.1; N, 8.6.
3
,
1
9
4.1.3
|
General procedure for the preparation of
(C
8
2
5
6
silver(I)–NHC complexes 3a–f
7
4
5
A solution of benzimidazolium salt (1.0 mmol) (2a–f) and Ag
2
O
H
3
(
1.4 mmol) in dichloromethane (15 ml) was stirred for 120 h at room

14 of 16
MNASRI ET AL.
|
Chloro‐{1‐[2‐(pyrrolidin‐1‐yl)ethyl]‐3‐(2,3,5,6‐tetramethylbenzyl)‐
was purchased from HiMedia Laboratories Pvt. Ltd. and RPMI‐1640
broth was purchased from Sigma‐Aldrich (Chemie GmbH).
The bacterial strains used as indicator microorganisms for the
antibacterial activity assays were M. luteus LB 14110, S. aureus ATCC
6538, L. monocytogenes ATCC 19117, S. typhimurium ATCC 14028,
P. aeruginosa ATCC 49189, and E. coli, which were obtained from
International Culture Collections (ATCC) and local culture collection
of the Laboratory of Microorganisms and Biomolecules of the Centre
of Biotechnology of Sfax, Tunisia.
5
,6‐dimethylbenzimidazole‐2‐ylidene}silver(I) (3e)
−
1
1
Yield 75%, Mp: 212°C, ν(CN) = 1474 cm
.
3
H NMR (CDCl ,
4
00 MHz) δ (ppm) = 1.76–1.73 (m, 4H, H5ʹ,6ʹ), 2.12 (s, 6H, CH3(c,b)),
.29 (s, 6H, CH3(a,d)), 2.39–2.40 (d, J = 5.3 Hz, 6H, CH3(e,f)), 2.58–2.54
2
(
m, 4H, H4ʹ,7ʹ), 2.89–2.85 (t, 2H, H2ʹ), 4.42–4.38 (t, 2H, H1ʹ), 5.38
1
3
(
s, 2H, H1″), 7.13 (s, 1H, H5″), 7.21 (s, 1H, H
7
), 7.27 (s, 1H, H
4
).
C
NMR (CDCl3, 100 MHz) δ (ppm) = 135.40 (C2″), 133.80 (C4″, 6″),
1
1
4
33.60 (C3″,7″), 133.45 (C
30.05 (C5″), 111.69 (d, J = 8.6 Hz, C7,4), 188.04 (C
9.35 (C1″), 47.12 (C1ʹ), 23.71 (C5ʹ 6ʹ), 20.82 (Cb,c) 20.63 (Ce,f), 16.26
a,d). Anal. calc. for C26 35AgClN (%): C, 58.60; H, 6.62; N, 7.89.
Found (%): C, 58.7; H, 6.70; N, 7.9.
5
), 133.18 (C
6
), 133.04 (C
9
), 132.41 (C
8
),
2
), 54.55 (C3ʹ,7ʹ),
These bacterial strains were grown overnight in Luria–Bertani
(LB) agar medium (g/l), containing peptone 10, yeast extract 5, and
NaCl 5, at pH 7.2 under aerobic conditions and constant agitation
(200 rpm) at 30°C for M. luteus LB14110 and L. monocytogenes ATCC
,
(
C
H
3
1
9117 and at 37°C for S. aureus ATCC 6538, S. typhimurium ATCC
Chloro‐{1‐[2‐(pyrrolidin‐1‐yl)ethyl]‐3‐(2,3,4,5,6‐pentamethylbenzyl)‐
benzimidazole‐2‐ylidene}silver(I) (3f)
14028, and P. aeruginosa ATCC 49189, and then diluted, 1:100, in LB
media and incubated for 5 h under constant agitation (200 rpm) at
the appropriate temperature.
−
1
1
Yield 85%, Mp: 185°C, ν(CN) = 1478 cm
.
3
H NMR (CDCl ,
4
2
2
2
H
00 MHz) δ (ppm) = 1.77–1.73 (m, 4H, H5ʹ,6ʹ), 2.19 (s, 6H, CH3(a,e)),
.28 (s, 6H, CH3(b,d)), 2.33 (s, 3H, CH3(c)), 2.56 (m, 4H, H4ʹ,7ʹ),
.92–2.87 (t, 2H, H2ʹ), 4.48–4.44 (t, 2H, H1ʹ), 5.47 (s, 2H, H1″), 7.41 (m,
4.2.2
|
Agar well diffusion method
H, H5,6), 7.47 (d, J = 6.7 Hz, 1H, CH, H
7
), 7.53 (d, J = 8.4 Hz, 1H, CH,
, 100 MHz) δ (ppm) = 137.43 (C2″), 134.42
), 134.07 (C ), 133.09 (C4″,6″), 126.73 (C5″), 124.40
), 111.52 (d, J = 5.0 Hz, C7,4), 55.99 (C2ʹ), 54.59 (C4ʹ,7ʹ),
9.45 (C1″), 47.91 (C1ʹ), 23.73 (C5ʹ,6ʹ), 17.54 (C ), 17.28 (d, J = 2.5 Hz,
a,b,d,e). Anal. calc. for C25 33AgClN (%): C, 57.87; H, 6.41; N, 8.10.
Found (%): C, 57.9; H, 6.5; N, 8.2.
13
4
). C NMR (CDCl
3″,7″), 134.36 (C
), 124.10 (C
3
The agar well diffusion method was employed for the determination
of the antimicrobial activity of the synthesized compounds according
(
C
9
8
[
62]
(
C
5
6
to Güven et al.,
with some modifications. Briefly, the synthesized
4
c
compounds were allowed to diffuse out into the appropriate agar
medium (LB agar medium) and interact in a plate freshly seeded with
C
H
3
8
a suspension of the indicator microorganisms (0.1 ml of 10 cells per
ml). The plate was incubated at the appropriate temperature after
allowing to stand at 4°C for 2 h. The resulting zones of inhibition
would be uniformly circular as there would be a confluent lawn of
growth. The antibacterial activity was assayed by measuring the
diameter of the inhibition zone formed around the well in milli-
meters. All tests were assayed in triplicate and expressed as the
average ± SD of the measurements.
4
.1.4
|
General procedure for the Ag(I)–NHC‐
catalyzed three‐component coupling reaction
In a typical procedure, a mix of phenylacetylene (1.5 mmol, 164.7 ml),
aldehyde (1.0 mmol), piperidine (1.2 mmol, 118.7 ml), and silver
complex (3 mol%) was added to an oven‐dried Schlenk tube (15 ml)
with 1,4‐dioxane (2.0 ml). The Schlenk tube was placed in a pre-
heated oil bath (80°C). The mixture was stirred at 80°C for a given
time under an argon atmosphere. After the reaction was completed,
the mixture was cooled to room temperature and diethyl ether was
4.2.3
|
MIC
The MIC of the synthesized compounds was determined by NCCLS
added. The organic portion was dried over MgSO
4
and filtered. After
guidelines M7‐A6 and M38‐P (National Committee for Clinical La-
[
63]
the volatile components were removed in a vacuum, the residue was
purified by column chromatography on silica using ethyl acetate/
hexane (1:2).
boratory Standard, Wayne 1998).
The test was performed in
sterile 96‐well microplates with a final volume of 100 μl in each
microplate well. The synthesized compounds (20 mg/ml) were prop-
erly prepared in a solution of DMSO/water (1/9; v/v). The inhibitory
activity of each synthesized compound was transferred to each well
to obtain a two fold serial dilution of the original sample. As an
indicator of microorganism growth, 25 μl of thiazolyl blue tetra-
zolium bromide (MTT) indicator solution (0.5 mg/ml) dissolved in
sterile water was added to the wells and incubated at room tem-
perature for 30 min. This determination was performed in triplicate,
and the obtained results were very similar. The reported value is the
average of the three tests.
4.2
|
Biological assays
4.2.1
|
Bacterial strains, media, and growth
conditions
Microorganisms defined in the American Type Culture Collection
(
ATCC) were used in antimicrobial studies. Mueller–Hinton Broth

MNASRI ET AL.
15 of 16
|
ACKNOWLEDGMENTS
[30] K. M. Hindi, T. J. Siciliano, S. Durmus, M. J. Panzner, D. A. Medvetz,
D. V. Reddy, L. A. Hogue, C. E. Hovis, J. K. Hilliard, R. J. Mallet,
C. A. Tessier, C. L. Cannon, W. J. J. Youngs, Med. Chem. 2008, 51,
This study was supported by the İnönü University Research Fund (İÜ‐
BAP: FBG‐2019‐1594).
1
577.
[
[
[
31] M. J. Panzner, K. M. Hindi, B. D. Wright, J. B. Taylor,
D. S. Han, Youngs, W. J. C. L. Cannon, Dalton Trans. 2009, 35, 7308.
32] R. A. Haque, M. A. Iqbal, F. Mohamad, M. R. Razali, J. Mol. Struct.
ORCID
Naceur Hamdi
https://orcid.org/0000-0003-0110-9588
2
018, 1155, 362.
33] R. X. Zhao, J. Wang, D. W. Jing, H. J. Zhang, C. Feng, G. Y. Li, Inorg.
Chem. Commun. 2019, 107597.
REFERENCES
[
1] M. N. Hopkinson, C. Richter, M. Schedler, F. Glorius, Nature 2014,
10(7506), 485.
[34] S. H. Alisir, B. Sariboga, S. Caglar, O. Buyukgungor, J. Mol. Struct.
2017, 1130, 156.
5
[
2] T. Roth, V. Vasilenko, C. G. M. Benson, H. Wadepohl, D. S. Wright,
L. H. Gade, Chem. Sci. 2015, 4, 2506.
[35] R. A. Haque, M. A. Iqbal, S. Budagumpi, M. B. Khadeer Ahamed,
A. M. Abdul Majid, N. Hasanudin, App. Organomet. Chem. 2013, 4,
214.
[
3] N. Wang, J. Xu, J. K. Lee, Org. Biomol. Chem. 2018, 37, 8230.
4] V. Nesterov, D. Reiter, P. Bag, P. Frisch, R. Holzner, A. Porzelt,
S. Inoue, Chem. Rev. 2018, 19, 9678.
[
[36] (a) K. M. Hindi, M. J. Panzner, C. A. Tessier, C. L. Cannon,
W. J. Youngs, Chem. Rev. 2009, 109, 3859.; (b) M. Tacke,
J. Organomet. Chem. 2015, 782, 17.; (c) T. Samanta, R. N. Munda,
G. Roymahapatra, A. Nandy, K. D. Saha, S. S. Al‐Deyab, J. Dinda,
J. Organomet. Chem 2015, 791, 183.
[
5] Y. Liu, X. Zhang, R. Zeng, Y. Zhang, Q. S. Dai, H. J. Leng, X. J. Gou,
J. L. Li, Molecules 2017, 11, 1882.
[
6] B. S. Yun, J. H. Kim, S. Y. Kim, H. J. Son, D. W. Cho, S. O. Kang, Phys.
Chem. Chem. Phys. 2019, 13, 7155.
[37] (a) R. A. Haque, S. Y. Choo, S. Budagumpi, M. A. Iqbal,
A. A. Abdullah, Eur. J. Med. Chem. 2015, 90, 82.; (b) M. O. Karataş,
B. Olgundeniz, S. Günal, İ. Özdemir, B. Alıcı, E. Çetinkaya, Bioorg.
Med. Chem. 2016, 24, 643.
[
7] N. M. Scott, S. P. Nolan, Eur. J. Inorg. Chem. 2005, 10, 1815.
8] C. J. Collett, R. S. Massey, J. E. Taylor, O. R. Maguire,
A. C. O'Donoghue, A. D. Smith, Angew. Chem. Weinheim. Bergstr. Ger.
[
2
015, 23, 6991.
[38] (a) C. R. Shahini, G. Achar, S. Budagumpi, H. Müller‐Bunz, M. Tacke,
S. A. Patil, J. Organomet. Chem. 2018, 868, 1.; (b) C. O'Beirne,
N. F. Alhamad, Q. Ma, H. Müller‐Bunz, K. Kavanagh, G. Butler,
X. Zhu, M. Tacke, Inorg. Chim. Acta 2019, 486, 294.
[
9] C. K. Chung, R. H. Grubbs, Org. Lett. 2008, 13, 2693.
[
10] D. W. Woolley, J. Biol. Chem. 1944, 2, 225.
[
11] M. T. Khan, M. T. Razi, S. U. Jan, M. Mukhtiar, R. Gul, U. Izhar,
A. Hussain, A. M. Hashmi, M. T. Ahmad, N. A. Shahwani, I. R., Pak,
J. Pharm. Sci. 2018, 3, 1067.
[39] (a) A. Hecel, P. Kolkowska, K. Krzywoszynska, A. Szebesczyk,
M. Rowinska‐Zyrek, H. Kozlowski, Curr. Med. Chem. 2019, 26, 624.;
(b) R. Ashraf, H. N. Bhatti, M. A. Iqbal, Y. Jamil, Inorg. Chem.
Commun. 2020, 119, 108077.; (c) O. E. Palomero, A. L. Cunningham,
B. W. Davies, R. A. Jones, Inorg. Chim. Acta 2021, 517, 120152.
[40] D. J. Nielsen, K. J. Cavell, B. W. Skelton, A. H. White, Inorg. Chim.
Acta 2003, 352, 143.
[
12] G. Kaur, O. Silakari, Bioorg. Chem. 2018, 80, 24.
13] F. F. Al‐Blewi, M. A. Almehmadi, M. R. Aouad, S. K. Bardaweel,
P. K. Sahu, M. Messali, N. Rezki, E. S. H. El Ashry, Chem. Cent. J.
[
2
018, 1, 110.
[
14] H. L. Kuo, J. C. Lien, C. H. Chung, C. H. Chang, S. C. Lo, I. C. Tsai,
H. C. Peng, S. C. Kuo, T. F. Huang, Naunyn‐Schmiedeberg's Arch.
Pharmacol. 2010, 6, 495.
[41] J. Pytkowicz, S. Roland, P. Mangeney, J. Organomet. Chem. 2001,
631, 157.
[
[
[
15] B. Da Silva, M. Habibi, S. Ognier, G. Schelcher, J. Mostafavi‐Amjad,
H. R. M. Khalesifard, D. Bonn, Eur. Phys. J.: Spec. Top. 2016, 4, 707.
16] (a) C. G. Hartinger, P. J. Dyson, Chem. Soc. Rev. 2009, 2, 391.;
[42] H. M. Lee, P. L. Chiu, C. H. Hu, C. L. Lai, Y. C. Chou, J. Organomet.
Chem. 2005, 690, 403.
[43] I. Slimani, A. C. Mtiba, L. Mellouli, L. Mansour, I. Özdemir.,
N. Gürbüz, N. Hamdi, J. Braz. Chem. Soc. 2020, 10, 2058.
[44] İ. Özdemir,O. Çiftçi, E. Evren, N. Gürbüz, N. Kaloğlu, N. B. Türkmen,
Ş. Yaşar, E. Üstün, N. Hamdi, L. Mansour, İ. Özdemir, Inorg. Chim.
Acta. 2020, 506, 119530.
(
b) W. Liu, R. Gust, Chem. Soc. Rev. 2013, 2, 755.
17] S. Ajay, P. P. Saidhareddy, A. K. Shaw, Asian J. Org. Chem. 2017, 6,
03.
5
[18] V. Panwar, S. L. Jain, Mater. Sci. Eng. C 2019, 99, 191.
[19] S. Dapeng, D. Zhongyu, Chin. J. Org. Chem. 2020, 40, 1316.
[20] H. N. K. Lam, N. B. Nguyen, G. H. Dang, T. Truong, N. T. S. Phan,
Catal. Lett. 2016, 146, 2087.
[45] Gaussian 09, Revision A.1, M. J. Frisch, G. W. Trucks, H. B. Schlegel,
G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone,
B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li,
H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg,
M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida,
T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven,
J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark,
J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R.
Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant,
S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene,
J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo,
R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi,
C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma,
V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg,
S. Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz,
J. Cioslowski, D. J. Fox, Gaussian Inc., Wallingford, CT, 2009.
[46] M. A. Ben Aissa, S. Hassen, Y. Arfaoui, Int. J. Quantum Chem. 2020,
[21] A. D. Russel, F. R. C. Path, W. B. Hugo, Prog. Med. Chem. 1994, 31,
3
51.
[22] C. A. Moyer, L. Brentanol, D. L. Gravens, H. W. Margraf,
W. W. Monafo, Arch. Surg. 1965, 90, 812.
[
[
[
[
23] C. L. Fox, Arch. Surg. 1968, 96, 184.
24] A. B. J. Lansdown, J. Wound Care 2002, 11, 125.
25] S. Silver, FEMS Microbiol. Rev. 2003, 27, 341.
26] W. J. Youngs, A. R. Knapp, P. O. Wagers, C. A. Tessier, Dalton Trans.
2
012, 41, 327.
[
[
27] A. Melaiye, R. S. Simons, A. Milsted, F. Pingitore, C. Wesdemiotis,
C. A. Tessier, W. J. Youngs, J. Med. Chem. 2004, 47, 973.
28] A. Melaiye, Z. Sun, K. Hindi, A. Milsted, D. Ely, D. H. Reneker,
C. A. Tessier, W. J. Youngs, J. Am. Chem. Soc. 2005, 127,
2
285.
[
29] A. Kascatan‐Nebioglu, A. Melaiye, K. Hindi, S. Durmus,
M. J. Panzner, L. A. Hogue, R. J. Mallett, C. E. Hovis, M. Coughenour,
S. D. Crosby, A. Milsted, D. L. Ely, C. A. Tessier, C. L. Cannon,
J. Youngs, J. Med. Chem. 2006, 49, 6811.
6
, 25837.
[47] Y. L. Li, L. Han, Y. Mei, J. Z. H. Zhang, Chem. Phys. Lett. 2009, 482,
217.
[48] J. Aihara, Phys. Chem. Chem. Phys. 2000, 2, 3121.

16 of 16
MNASRI ET AL.
|
[49] J. Ralph, G. Pearson, Chem. Sci. 2005, 5, 369.
[62] J. N. Demas, G. A. Crosby, J. Phys. Chem. 1971, 75, 1001.
[50] S. Hassen, H. Chebbi, M. F. Zid, Y. Arfaoui, J. Mol. Struct. 2019,
[63] J. R. Tagg, A. R. McGiven, App Microbiol. 1971, 21, 943.
1
179, 678.
[51] V. A. Peshkov, O. P. Pereshivko, E. V. Van der Eycken, Chem. Soc.
Rev. 2012, 41, 3790.
SUPPORTING INFORMATION
[52] S. Sakaguchi, T. Kubo, Y. Ishii, Angew. Chem. Int. Ed. 2001, 40, 2534.
[53] C. M. Wei, Z. G. Li, C. J. Li, Org. Lett. 2003, 5, 4473.
[54] R. Manikandan, P. Anitha, P. Viswanathamurthi, J. G. Malecki,
Polyhedron 2016 119, 300.
Additional Supporting Information may be found online in the
supporting information tab for this article.
[
[
[
55] L. Shi, Y. Q. Tu, M. Wang, F. M. Zhang, C. A. Fan, Org. Lett. 2004, 6,
1
001.
How to cite this article: A. Mnasri, A. Mejri, S. M. Al‐Hazmy,
Y. Arfaoui, I. Özdemir, N. Gürbüz, N. Hamdi. Silver–N‐
heterocyclic carbene complexes‐catalyzed multicomponent
reactions: Synthesis, spectroscopic characterization, density
functional theory calculations, and antibacterial study. Arch.
Pharm. 2021;e2100111.
56] L. Rubio‐Perez, M. Iglesias, J. Munarriz, V. Polo, J. J. Perez‐
Torrente, L. A. Oro, Chem.–Eur. J. 2015, 21, 17701.
57] R. Kilincarslan, A. Kunduracioglu, N. Sadic, Rev. Chim. 2016, 67,
2
214.
[
58] P. Li, L. Wang, Y. Zhang, M. Wang, Tetrahedron Lett. 2008, 49, 6650.
59] I. Slimani, L. Mansour, N. Abutaha, A. Halim Harrath, J. Al‐Tamimi,
N. Gürbüz, I. Özdemir, N. Hamdi, J. King Saud Univ. 2020, 32, 1544.
60] J. Jentzsch, W. S. Koko, I. Al Nasr, T. A. Khan, R. Schobert,
K. Ersfeld, B. Biersack, Chem. Biodivers. 2019, 2, 17.
[
https://doi.org/10.1002/ardp.202100111
[
[
61] M. H. Abdel‐Kader, U. Steiner, J. Chem. Educ. 1983, 60, 160.