Silver–N-Heterocyclic Carbene Complexes: Synthesis, Characterization, and Antimicrobial Properties

Article abstract of DOI:10.1002/jccs.201700024

Six new silver complexes containing symmetrical N-heterocyclic carbene (NHC) ligands were synthesized by the reaction of azolium salts with Ag₂O in CH₂Cl₂. These complexes were tested against Gram-negative bacterial strain

Full text of DOI:10.1002/jccs.201700024

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Article
Silver–N-Heterocyclic Carbene Complexes: Synthesis, Characterization,
and Antimicrobial Properties
a,b
a,b
a
c
a,b
_
_
*
ꢀ
ꢀ
Nazan Kaloglu, Murat Kaloglu, Ilknur Özdemir, Selami Günal and Ismail Özdemir
a
_
Department of Chemistry, Faculty of Science and Arts, Inönü University, Malatya 44280, Turkey
b
_
Catalysis Research and Application Center, Inönü University, Malatya 44280, Turkey
c
_
Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Inönü University, Malatya 44280, Turkey
(Received: January 19, 2017; Accepted: January 25, 2017; DOI: 10.1002/jccs.201700024)
Six new silver complexes containing symmetrical N-heterocyclic carbene (NHC) ligands were
synthesized by the reaction of azolium salts with Ag2O in CH2Cl2. These complexes were tested
against Gram-negative bacterial strains (Escherichia coli and Pseudomonas aeruginosa), Gram-
positive bacterial strains (Enterococcus faecalis and Staphylococcus aureus), and fungal strains
(Candida albicans and Candida tropicalis), and all tested complexes showed good activity against
the different microorganisms.
Keywords: N-Heterocyclic carbene; Azolium salts; Silver–N-heterocyclic carbene complexes;
Antimicrobial activity.
INTRODUCTION
N-Heterocyclic carbenes (NHCs) are neutral two-
Most of the biomedical studies on silver–NHC
complexes have been conducted with regard to their
antimicrobial properties.31–36 Although the cytotoxic
effects of silver compounds against bacteria have long
been established, the mechanisms of action are not
completely understood. Sporadic studies of the cell tox-
icity mechanisms of silver compounds suggest that sil-
ver ions kill organisms through a variety of ways.37–44
In this area, many articles have been recently published
on the synthesis and applications of silver–NHC com-
plexes. Recently we reported the bioorganometallic
studies by silver and gold complexes of imidazolin-2-
ylidene and benzimidazol-2-ylidene ligands for antimi-
crobial applications.45–49
electron donors and are known to be strong Lewis
bases and excellent nucleophiles that bind metals bet-
ter than phosphines.1,2 NHCs have been widely stud-
ied for their intriguing structural properties. These
properties make these ligands desirable for a range of
catalytic applications. NHCs have been employed
widely as very important ligands in many
applications.3–8 Transition-metal complexes of NHCs,
which serve as catalysts for a variety of useful syn-
thetic reactions in organometallic chemistry and homo-
geneous catalysis, have attracted much attention in
recent years.9–17
Over the last few years, transition-metal com-
plexes of NHCs have gained real practical importance
as antimitochondrial, antimicrobial, and anticancer
agents for medicinal applications.18–26 Silver–NHC
complexes are the most studied metal–NHC complexes
because of their easy preparation. Although many
silver–NHC complexes have been reported, their
catalytic properties have rarely been investigated.
Therefore, silver–NHC complexes have been used
as bioactive compounds in bioorganometallic
applications.27–30
Here we describe the synthesis, characterization,
and antimicrobial applications of the new silver com-
plexes containing symmetrical NHC ligands (3a,b and
4a–d). The structures of all silver–NHC complexes were
1
characterized by elemental analysis as well as by H-
NMR, 13C-NMR, and IR spectroscopic techniques.
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 microorganism.
*Corresponding author. Email: ismail.ozdemir@inonu.edu.tr
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Kaloglu et al.
RESULTS AND DISCUSSION
Synthesis of the azolium salts
The synthesized symmetrical NHC salts (1a,b and
2a–d) in this study have already been reported in the lit-
erature.50,51 These salts were prepared according to the
general reaction pathway shown in Scheme 1. The azo-
lium salts were air- and moisture-stable both in the
solid state and in solution. The structures of the salts
were determined by their characteristic spectroscopic
data and elemental analyses. The results are consistent
with those in the literature.50,51
Synthesis of the silver–NHC complexes
Silver–NHC complexes are readily prepared from
azolium salts and Ag2O, Ag2CO3, or Ag(OAc) and con-
tain relatively strong silver–carbon bonds. In this study,
silver–NHC complexes (3a,b and 4a–d) were prepared
by treating the azolium salts with Ag2O in dry CH2Cl2
at room temperature for 24 h (Scheme 2). All the
silver–NHC complexes are air-stable. They are soluble
in organic solvents such as acetone, dichloromethane,
chloroform, dimethylformamide (DMF), dimethyl sulf-
oxide (DMSO), ethanol, and acetonitrile.
Scheme 2. Synthesis of imidazolidin-2-ylidene (3a,b)
and benzimidazol-2-ylidene (4a–d) silver–
NHC complexes.
The structures of the silver–NHCs were determined
by their characteristic spectroscopic data and elemental
analyses. The characteristic peak of the Ag–carbene reso-
nance for the compound 4b displays a singlet at
178.6 ppm in the 13C-NMR spectra. In the 4a, 4c, and 4d
complexes, the resonances for Ag–carbene were not
observed, which has also been mentioned in the literature
and given as a reason for the fluxional behavior of the
NHC complexes.52–54 Silver–NHC complexes exhibit a
characteristic v(CN) band at 1440, 1417, 1466, 1451, 1448,
and 1463 cm−1, respectively, for 3a,b and 4a–d.
Antimicrobial applications of the silver–NHC complexes
Silver–NHC complexes were initially tested against
bacterial strains with ampicillin and ciprofloxacin as
standard drugs. The minimum inhibitory concentrations
(MICs) of the silver–NHC complexes against bacterial
strains are summarized in Table 1. 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 bacteria.
Complex 4c was found to be effective at inhibiting the
growth of all bacterial strains, with MIC values between
Scheme 1. Synthesis of imidazolidinium (1a,b) and
benzimidazolium (2a–d) salts.
2
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Silver–NHC Complexes as Antimicrobial Agents
Table 1. MIC values of compounds (3a,b and 4a–d) used against bacterial strains in antimicrobial test.
MIC (μg/mL)
Gram-negative bacteria
P. aeruginosa
Gram-positive bacteria
Silver–NHC complex
E. coli
S. aureus
E. faecalis
3a
3b
4a
4b
4c
4d
200
100
100
100
100
100
3.12
1.56
200
100
100
100
100
100
–
200
100
100
100
50
100
3.12
0.39
200
100
100
100
50
100
1.56
0.78
Ampicillin
Ciprofloxacin
3.12
50 and 100 μg/mL. These complexes were particularly
effective against Gram-positive bacterial strains.
Dorset, UK). Elemental analyses were performed at the
_
Inönü University Scientific and Technological Research
The silver–NHC complexes (3a,b and 4a–d) were
evaluated for their antifungal activity against Candida
albicans and Candida tropicalis using fluconazole as the
standard drug. The MICs of silver–NHC complexes
against fungal strains are summarized in Table 2.
The tested silver–NHC complexes showed antifun-
gal activity with a range of MICs between 12.5 and
100 μg/mL. The complexes 3b, 4a, and 4d showed simi-
lar activities against both fungi, but the compound 4c
displayed high activity with an MIC of 12.5 μg/mL.
These results show that silver–NHC complexes contain-
ing benzimidazol-2-ylidene (4a–d) are more efficient
than those with imidazolidin-2-ylidene (3a,b).
_
Center (IBTAM). Melting points were measured in open
capillary tubes with an Electrothermal-9200 melting point
apparatus. IR spectra were recorded as KBr pellets in the
range 400–4000 cm−1 on an ATI Unicam 1000 spectrome-
ter. 1H-NMR and 13C NMR spectra were recorded using a
Varian As 300 Merkur spectrometer operating at
300 MHz (1H-NMR) and at 75 MHz (13C-NMR) in
CDCl3. The NMR studies were carried out in high-quality
5 mm NMR tubes. Chemical shifts (δ) are reported in ppm
relative to CDCl3. Coupling constants (J-values) are given
1
in hertz. H-NMR spectra are referenced to residual pro-
tiated solvents (δ = 7.26 ppm for CDCl3), and 13C chemi-
cal shifts are reported relative to deuterated solvents
(δ = 77.16 ppm for CDCl3).
EXPERIMENTAL
Materials and methods
All reactions were carried out under argon using
standard Schlenk line techniques. The chemicals and sol-
vents were purchased from Sigma-Aldrich Co. (Poole,
The MIC for each compound was investigated
against standard bacterial strains: Staphylococcus aureus
(ATCC 29213), Enterococcus faecalis (ATCC 29212),
Escherichia coli (ATCC 25922), and Pseudomonas aerugi-
nosa (ATCC 27853). These were obtained from American
Type Culture Collection (Rockville, MD, USA). The fun-
gal strains C. albicans (ATCC 10231) and C. tropicalis
(ATCC 13803) were obtained from the Department of
Microbiology, Faculty of Medicine, Ege University
(Turkey). Bacterial strains were subcultured in Muller–
Hinton broth (HiMedia Laboratories Pvt. Ltd, Mumbai,
India) and fungal strains in RPMI 1640 broth (Sigma-
Aldrich Chemie GmbH, Taufkirchen, Germany).
Table 2. MIC values of compounds (3a,b and 4a–d) used
against fungal strains in antimicrobial test.
MIC (μg/mL)
Silver–NHC complex
C. albicans
C. tropicalis
3a
3b
4a
100
50
50
100
50
50
4b
4c
4d
100
25
50
100
12.5
50
General procedure for the preparation of azolium salts
Treatment of the diamine (ethylenediamine or 1,2-
phenylenediamine) (10.0 mmol) with aromatic aldehyde
Fluconazole
3.12
3.12
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Kaloglu et al.
(20.0 mmol) in methanol (25 mL) at r.t. led to the for-
mation of the corresponding diimines. The diimine was
collected as a white solid. Next, it was filtered through
a filter paper and recrystallized from an alcohol/ether
mixture (1:2 ratio). The diimine (10.0 mmol) was subse-
quently reduced by NaBH4 (30.0 mmol) in methanol
(30 mL). The solution was then treated with 1 N HCl
solution, and the organic phase was extracted with
CH2Cl2 (3 × 30 mL). After drying over MgSO4 and
evaporation, the diamine was isolated as a solid and
then treated in a large excess of triethylorthoformate
(50 mL) in the presence of NH4Cl (10.0 mmol) at
110ꢀC in a distillation apparatus until the removal of
ethanol ceased. Upon cooling to r.t., a colorless solid
precipitated, which was collected by filtration and dried
under vacuum. The crude product was recrystallized
from absolute ethanol to give colorless needles, and the
solid was washed with diethyl ether (2 × 10 mL) and
dried under vacuum.
48.14; H, 5.27; N, 4.88. Found: C, 48.16; H, 5.29;
N, 4.90.
1,3-Bis(4-ethoxy-3-methoxybenzyl)imidazolidin-2-
yli- denesilver(I) chloride (3b): Yield: 0.55 g, 88%, mp:
1
140–141ꢀC, IR (cm−1) v(CN): 1417. H-NMR (300 MHz,
CDCl3): δ 3.89 (s, 6H, NCH2C6H3((OCH3)3-3-(OCH2
CH3)-4); 4.07 (q, J = 5.0 Hz, 4H, NCH2C6H3((OCH3)3-
3-(OCH2CH3)-4); 1.47 (t, 6H, J = 5.1 Hz, NCH2C6H
3((OCH3)3-3-(OCH2CH3)-4); 4.65 (s, 4H, NCH2C6
H3((OCH3)3-3-(OCH2CH3)-4); 3.49 (t, J = 5.8 Hz, 4H,
NCH2CH2N). 13C-NMR (75 MHz, CDCl3): δ 64.4
(NCH2C6H3((OCH3)3-3-(OCH2CH3)-4); 56.2 (NCH2C6
H3((OCH3)3-3-(OCH2CH3)-4);
14.8
(NCH2C6H3-
((OCH3)3-3-(OCH2CH3)-4); 55.3 (NCH2C6H3((OCH3)3-
3-(OCH2CH3)-4); 48.4 (NCH2CH2N); 111.4, 112.7,
120.5, 127.3, 148.5, 149.5 (NCH2C6H3((OCH3)3-3-
(OCH2CH3)-4). Ag–Ccarbene: not observed. Anal. Calcd.
for C23H30O4N2AgCl (%): C, 50.99; H, 5.58; N, 5.17.
Found: C, 50.96; H, 5.55; N, 5.19.
These known compounds were synthesized and
1,3-Bis(2,3,4-trimethoxybenzyl)benzimidazol-2-ylide-
nesilver(I) chloride (4a): Yield: 0.53 g, 88%, mp:
1
characterized by H-NMR, 13C-NMR, IR, and elemen-
1
tal analyses. The results of the analyses were consistent
with those in the literature.50,51
232–233ꢀC, IR (cm−1) v(CN): 1466. H-NMR (300 MHz,
CDCl3): δ 3.84, 3.86 and 3.87 (s, 18H, NCH2C6
H2((OCH3)3)-2,3,4); 5.54 (s, 4H, NCH2C6H2((OCH3)3)-
2,3,4); 6.60–6.62 and 6.92–6.94 (d, 4H, J = 8.7 Hz,
NCH2C6H2((OCH3)3)-2,3,4); 7.28–7.55 (m, 4H, NC6
H4N). 13C-NMR (75 MHz, CDCl3): δ 56.0, 60.8 and
General procedure for the preparation of the silver–NHC
complexes
Silver–NHC complexes (3a,b and 4a–d) were pre-
pared by the treatment of the benzimidazolium or imi-
dazolidinium salts (1.0 mmol) with Ag2O (0.5 mmol)
and activated 4 Å molecular sieves in dry CH2Cl2
(20 mL) at r.t. for 24 h. The reaction mixture was fil-
tered through celite, and the solvent was removed under
reduced pressure. The crude product was recrystallized
from dichloromethane/diethylether (1:2 ratio).
1,3-Bis(2,4,5-trimethoxybenzyl)imidazolidin-2-
ylidene silver(I) chloride (3a): Yield: 0.49 g, 82%, mp:
61.8
(NCH2C6H2((OCH3)3)-2,3,4);
48.3
(NCH2
C6H2((OCH3)3)-2,3,4); 107.4, 112.1, 120.6, 123.7, 124.1,
133.9, 142.1, 151.2, 154.3 (NCH2C6H2((OCH3)3)-2,3,4)
and (NC6H4N). Ag–Ccarbene: not observed. Anal. Calcd.
for C27H30O6N2AgCl (%): C, 52.15; H, 4.86; N, 4.50.
Found: C, 52.17; H, 4.89; N, 4.53.
1,3-Bis(2,4,5-trimethoxybenzyl)benzimidazol-2-ylide-
nesilver(I) chloride (4b): Yield: 0.49 g, 81%, mp:
155–156ꢀC, IR (cm−1) v(CN): 1451. H-NMR (300 MHz,
1
CDCl3): δ 3.86, 3.87, and 3.88 (s, 18H, NCH2
C6H2((OCH3)3)-2,4,5); 5.55 (s, 4H, NCH2C6H2
((OCH3)3)-2,4,5); 6.52 (s, 4H, NCH2C6H2((OCH3)3)-
2,4,5); 7.28–7.57 (m, 4H, NC6H4N). 13C-NMR
(75 MHz, CDCl3): δ 56.1, 56.2, and 56.8 (NCH2
C6H2((OCH3)3)-2,4,5); 47.8 (NCH2C6H2((OCH3)3)-
2,4,5); 97.2, 112.1, 113.6, 114.7, 123.7, 134.0, 143.2,
150.1, 151.5 (NCH2C6H2((OCH3)3)-2,4,5) and (NC6
H4N); Ag–Ccarbene: 178.6. Anal. Calcd. for C27H30O6N2-
AgCl (%): C, 52.15; H, 4.86; N, 4.50. Found: C,
52.20; H, 4.90; N, 4.55.
1
141–142ꢀC, IR (cm−1) v(CN): 1440. H-NMR (300 MHz,
CDCl3): δ 3.49 (t, J = 5.8 Hz, 4H, NCH2CH2N); 3.84,
3.85 and 3.89 (s, 18H, NCH2C6H2((OCH3)3)-2,4,5); 4.62
(s, 4H, NCH2-C6H2((OCH3)3)-2,4,5); 6.52 and 6.83
(s,
4H,
NCH2C6H2-((OCH3)3)-2,4,5).
13C-NMR
(75 MHz, CDCl3): δ 56.2, 56.5, and 57.0 (NCH2
C6H2((OCH3)3)-2,4,5); 49.6 (NCH2C6H2-((OCH3)3)-
2,4,5); 48.7 (NCH2CH2N); 143.0, 143.4, 148.7, 150.0,
152.2, 152.3 (NCH2C6H2((OCH3)3)-2,4,5). Ag–Ccarbene
:
not observed. Anal. Calcd. for C23H30O6N2AgCl (%): C,
4
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Silver–NHC Complexes as Antimicrobial Agents
1,3-Bis(2-ethoxybenzyl)benzimidazol-2-ylidene silver(I)
Germany). Their turbidities matched that of a McFar-
land no. 0.5 turbidity standard.57 The stock solutions of
all compounds were prepared in DMSO. All dilutions
were done with distilled water. The concentrations of
the tested compounds were 800, 400, 200, 100, 50, 25,
and 12.5 μg/mL. Ampicillin and ciprofloxacin were
used as standard antimicrobial drugs, while fluconazole
was used as a standard antifungal drug, with known
MIC values. A loopful (0.01 mL) of the standardized
inoculum of the bacteria and yeasts (106 CFU/mL) was
spread over the surfaces of agar plates. All inoculated
plates were incubated at 35ꢀC, and the results were
evaluated after 16–20 h of incubation for bacteria and
48 h for yeasts. The lowest concentrations of the com-
pounds that prevented visible growth were taken as
the MICs.
chloride (4c): Yield: 0.58 g, 92%, mp: 216–217ꢀC, IR
1
(cm−1) v(CN): 1448. H-NMR (300 MHz, CDCl3): δ 1.44
(t, 6H, J = 6.9 Hz, NCH2C6H4((OCH2CH3)-2); 4.12 (q,
4H, J = 6.6 Hz, NCH2C6H4((OCH2CH3)-2); 5.65 (s, 4H,
NCH2C6H4-((OCH2CH3)-2); 7.26–7.43 (m, 12H, NC6H4N
and NCH2C6H4((OCH2CH3)-2). 13C-NMR (75 MHz,
CDCl3):
δ
15.0 (NCH2C6H4-((OCH2CH3)-2); 63.7
(NCH2C6H4((OCH2CH3)-2); 49.6 (NCH2C6H4((OCH2
CH3)-2); 111.4, 112.2, 120.6, 123.2, 123.9, 128.5, 129.7,
134.0, 156.2 (NC6H4N and NCH2C6H4((OCH2CH3)-2);
Ag–Ccarbene: not observed. Anal. Calcd. for C25H26O2N2-
AgCl (%): C, 56.67; H, 4.95; N, 5.29. Found: C, 56.70; H,
4.93; N, 4.31.
1,3-Bis(4-acetoxy-3,5-dimethoxybenzyl)benzimida-
zol-2-ylidenesilver(I) chloride (4d): Yield: 0.48 g, 81%,
mp: 172–173ꢀC, IR (cm−1) v(CN): 1463. 1H-NMR
(300 MHz, CDCl3): δ 2.32 (s, 6H, NCH2C6H2((OCO
CH3)-4-(OCH3)2-3,5); 3.76 (s, 12H, NCH2C6H2((OC
OCH3)-4-(OCH3)2-3,5); 5.56 (s, 4H, NCH2C6H2((OCO
CH3)-4-(OCH3)2-3,5); 6.64 (s, 4H, NCH2C6H2((OCO
CH3)-4-(OCH3)2-3,5); 7.28–7.49 (m, 4H, NC6H4N). 13C-
NMR (75 MHz, CDCl3): δ 20.5 (NCH2C6H2((OCO
CH3)-4-(OCH3)2-3,5); 56.4 (NCH2C6H2-((OCOCH3)-4-
(OCH3)2-3,5); 53.6 (NCH2C6H2((OCOCH3)-4-(OCH3)2-
3,5); 168.6 (NCH2C6H2((OCOCH3)-4-(OCH3)2-3,5);
104.3, 112.0, 124.5, 128.7, 133.5, 133.9, 152.6 (NCH2
C6H2((OCOCH3)-4-(OCH3)2-3,5) and (NC6H4N). Ag–
Ccarbene: not observed. Anal. Calcd. for C29H30O8N2-
AgCl (%): C, 51.38; H, 4.46; N, 4.13. Found: C,
51.41; H, 4.49; N, 4.16.
CONCLUSIONS
A series of new silver complexes containing sym-
metrical NHC ligands were synthesized and character-
ized by spectroscopic and analytical techniques.
Antimicrobial activities of these new silver complexes
were reported. The silver–NHC complex 4c showed bet-
ter antimicrobial activity against the bacteria and fungi
than other complexes, even at the much lower concen-
trations. The obtained results are helpful for the synthe-
sis of silver–NHC complexes possessing high
antimicrobial activity.
ACKNOWLEDGMENTS
This work was financially supported by the Tech-
nological and Scientific Research Council of Turkey
Antimicrobial activities of the silver–NHC complexes
The antimicrobial activities of the silver–NHC
complexes were determined using the agar dilution pro-
cedure recommended by the Clinical and Laboratory
Standards Institute.55,56 The MICs for each compound
were investigated, and the antimicrobial activity of
silver–NHC complexes was tested against the standard
bacterial strains S. aureus (ATCC 29213), E. faecalis
ATCC (29212), E. coli (ATCC 25922), and P. aerugi-
nosa (ATCC 27853) and the fungal strains C. albicans
(ATCC 10231) and C. tropicalis (ATCC 13803). Bacte-
rial strains were subcultured in Mueller–Hinton broth
(HiMedia Laboratories Pvt. Ltd., Mumbai, India), and
the fungal strains were also cultured in RPMI 1640
broth (Sigma-Aldrich Chemie GmbH, Taufkirchen,
_
_
(TÜBITAK) [TBAG-(108T411)] and Inönü University
_
Research Fund (I.Ü.-B.A.P: 2015/41-Güdümlü).
Supporting information
1H-NMR and 13C-NMR of silver–NHC
complexes.
REFERENCES
1. F. Glorius Ed., Topics in Organometallic Chemistry: N-
Heterocyclic Carbenes in Transition Metal Catalysis, Vol.
21, Springer, Heidelberg, 2007.
2. S. P. Nolan Ed., N-Heterocyclic Carbenes in Synthesis,
Wiley, Weinheim, 2006.
3. G. C. Fortman, S. P. Nolan, Chem. Soc. Rev. 2011,
40, 5151.
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5

Article
ꢀ
Kaloglu et al.
4. M. N. Hopkinson, C. Richter, M. Schedler, F. Glorius,
Nature 2014, 510, 485.
5. L. Delaude, Eur. J. Inorg. Chem. 2009, 13, 1681.
6. R. H. Crabtree, The Organometallic Chemistry of the
Transition Metals, 4th ed., John Wiley & Sons, Hobo-
ken, 2005.
28. K. M. Hindi, A. J. Ditto, M. J. Panzner, D. A. Medvetz,
D. S. Han, C. E. Hovis, Biomaterials 2009, 30, 3771.
29. J. C. Garrison, C. A. Tessier, W. J. Youngs,
J. Organomet. Chem. 2005, 690, 6008.
30. J. C. Garrison, W. J. Youngs, Chem. Rev. 2005, 105, 3978.
31. R. Sakamoto, S. Morozumi, Y. Yanagawa, M. Toyama,
A. Takayama, N. C. Kasuga, K. Nomiya, J. Inorg. Bio-
chem. 2016, 163, 110.
7. M. C. Perry, K. Burgess, Tetrahedron: Asymmetry 2003,
14, 951.
8. D. S. Clyne, J. Jin, E. Genest, J. C. Gallucci,
T. V. RajanBabu, Org. Lett. 2000, 2, 1125.
9. M. Albrecht, Angew. Chem., Int. Ed. 2015, 54, 5822.
10. L. Faraji, K. Jadidi, B. Notash, Tetrahedron Lett. 2014,
55, 346.
11. W. A. Herrmann, Angew. Chem., Int. Ed. 2002, 41, 1290.
12. V. Paradiso, C. Costabile, F. Grisi, Molecules 2016,
21, 117.
32. M. O. Karatas¸, S. Günal, A. Mansur, B. Alıcı,
E. Çetinkaya, Heterocycl. Commun. 2016, 22, 357.
33. A. M. Al-Majid, S. Yousuf, M. I. Choudhary, F. Nahra,
S. P. Nolan, ChemistrySelect 2016, 1, 76.
34. S. Patil, A. Deally, B. Gleeson, H. Müller-Bunz,
F. Paradisi, M. Tacke, Metallomics 2011, 3, 74.
35. A. Melaiye, Z. Sun, K. Hindi, A. Milsted, D. Ely,
D. H. Reneker, J. Am. Chem. Soc. 2005, 127, 2285.
36. A. Melaiye, R. S. Simons, A. Milsted, F. Pingitore,
C. Wesdemiotis, C. A. Tessier, W. J. J. Youngs, J. Med.
Chem. 2004, 47, 973.
13. F. Nahra, A. Gómez-Herrera, C. S. J. Cazin, Dalton
Trans. 2017, 46, 628.
_
ꢀ
ꢀ
14. I. Özdemir, N. Gürbüz, N. Kaloglu, Ö. Dogan,
ꢀ
37. A. B. Lansdown, J. Wound Care 2002, 11, 125.
38. Q. L. Feng, J. Wu, G. Q. Chen, F. Z. Cui, T. N. Kim,
J. O. Kim, J. Biomed. Mater. Res. 2000, 52, 662.
39. S. M. Modak, C. L. Fox, Biochem. Pharmcol. 1973,
22, 2391.
M. Kaloglu, C. Bruneau, H. Doucet, Beilstein J. Org.
Chem. 2013, 9, 303.
_
ꢀ
ꢀ
15. I. Özdemir, Y. Gök, Ö. Özeroglu, M. Kaloglu,
H. Doucet, C. Bruneau, Eur. J. Inorg. Chem. 2010,
12, 1798.
40. C. Fox, S. Modak, Antimicrob. Agents Chemother. 1974,
5, 582.
41. K. Holt, A. Bard, Biochemistry 2005, 44, 13214.
42. P. D. Bragg, D. J. Rainnie, J. Can, Microbiology 1974,
20, 883.
ꢀ
16. M. Kaloglu, D. Sémeril, E. Brenner, D. Matt,
_
I. Özdemir, L. Toupet, Eur. J. Inorg. Chem. 2016,
7, 1115.
ꢀ
17. M. Kaloglu, N. Şahin, D. Sémeril, E. Brenner, D. Matt,
_
I. Özdemir, C. Kaya, L. Toupet, Eur. J. Org. Chem.
2015, 33, 7310.
18. J. L. Hickey, R. A. Ruhayel, P. J. Barnard, M. V. Baker,
S. J. Berners-Price, A. Filipovska, J. Am. Chem. Soc.
2008, 130, 12570.
43. W. J. Schreurs, H. Rosenberg, J. Bacteriol. 1982, 152, 7.
44. A. D. Russell, W. B. Hugo, Prog. Med. Chem. 1994, 31, 351.
_
_
ꢀ
45. I. Özdemir, N. Gürbüz, Ö. Dogan, S. Günal, I. Özdemir,
Appl. Organomet. Chem. 2010, 24, 758.
_
_
46. I. Özdemir, S. Demir, S. Günal, I. Özdemir, C. Arıcı,
C. Ülkü, Inorg. Chim. Acta 2010, 363, 3803.
19. R. A. Haque, S. Y. Choo, S. Budagumpi, M. A. Iqbal,
A. A. Abdullah, Eur. J. Med. Chem. 2015, 90, 82.
20. C. V. Maftei, E. Fodor, P. G. Jones, M. Freytag,
M. H. Franz, G. Kelter, H. H. Fiebig, M. Tamm,
I. Neda, Eur. J. Med. Chem. 2015, 101, 431.
21. M. A. Iqbal, M. I. Umar, R. A. Haque,
M. B. K. Ahamed, M. Z. B. Asmawi, A. M. S. A. Majid,
J. Inorg. Biochem. 2015, 146, 1.
22. L. Oehninger, R. Rubbiani, I. Ott, Dalton Trans. 2013,
42, 3269.
23. W. Liua, R. Gust, Chem. Soc. Rev. 2013, 42, 755.
24. K. M. Hindi, M. J. Panzner, C. A. Tessier,
C. L. Cannon, W. J. Youngs, Chem. Rev. 2009,
109, 3859.
_
_
ꢀ
47. S. Günal, N. Kaloglu, I. Özdemir, S. Demir, I. Özdemir,
Inorg. Chem. Commun. 2012, 21, 142.
_
ꢀ
48. B. Yigit, Y. Gök, I. Özdemir, S. Günal, J. Coord. Chem.
2012, 65, 371.
_
ꢀ
ꢀ
49. M. Kaloglu, N. Kaloglu, I. Özdemir, S. Günal,
_
I. Özdemir, Bioorg. Med. Chem. 2016, 24, 3649.
_
50. S. Yas¸ar, I. Özdemir, B. Çetinkaya, J. -L. Renaud,
C. Bruneau, Eur. J. Org. Chem. 2008, 12, 2142.
_
51. S. Yas¸ar, PhD thesis, Inönü University, Malatya, Tur-
key, 2008.
52. D. J. Nielsen, K. J. Cavell, B. W. Skelton, A. H. White,
Inorg. Chim. Acta 2003, 352, 143.
25. W. Liu, R. Gust, Chem. Soc. Rev. 2013, 42, 755.
26. L. Mercs, M. Albrecht, Chem. Soc. Rev. 2010, 39, 1903.
27. S. Medici, M. Peana, G. Crisponi, V. M. Nurchi,
J. I. Lachowicz, M. Remelli, M. A. Zoroddu, Coord.
Chem. Rev. 2016, 327, 349.
53. J. Pytkowicz, S. Roland, P. Mangeney, J. Organomet.
Chem. 2001, 631, 157.
54. H. M. Lee, P. L. Chiu, C. H. Hu, C. L. Lai, Y. C. Chou,
J. Organomet. Chem. 2005, 690, 403.
6
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© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2017

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Silver–NHC Complexes as Antimicrobial Agents
55. Clinical and Laboratory Standards Institute, Methods for
Dilution, Antimicrobial Susceptibility Tests for Bacteria
that Grow Aerobically, Approved Standard, CLSI Docu-
ment M7-A-7, 7th ed., Clinical and Laboratory Standards
Institute, Wayne, PA, 2003.
Testing of Yeasts, Approved Standard, NCCLS Docu-
ment M27-A2, 2nd ed., National Clinical and Laboratory
Standards Institute, Wayne, PA, 2002.
57. J. Hindler, L. Hochstein, A. Howell, In Clinical Microbi-
ology Procedures Handbook, Vol. 1, H. D. Isenberg Ed.,
American Society for Microbiology, Washington, DC,
1992, p. 5.19.1.
56. Clinical and Laboratory Standards Institute, Reference
Method for Broth Dilution Antifungal Susceptibility
J. Chin. Chem. Soc. 2017
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
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