NJC
Letter
À1
Table 3 Comparison of the MIC (mmol l ) of organisms to [C14mim]Cl, [C14quin]Br, [C14mim][AgBr
2
] and [C14mim]
2
[CuCl
4
]. The numbers in brackets are the anion
effect ratios, when compared to that of [C14mim]Cl
Organism
[C14mim]Cl
[C14quin]Br
[C14mim][AgBr
2
]
2 4
[C14mim] [CuCl ]
MRSA
MRSE
P. aeruginosa
E. coli
K. aerogenes
P. mirabilis
C. tropicalis
16
33
264
33
33
530
66
5.8
5.8
24
11.6
5.8
5.8
3
7.5 (2.1)
15 (2.2)
30 (8.8)
15 (2.2)
15 (2.2)
18 (29)
36 (1.8)
40 (0.4)
40 (0.8)
80 (3.3)
40 (0.8)
40 (0.8)
40 (14)
20 (3.3)
28
significantly less potent against Gram positive organisms than respiratory pathways in E. coli. We confirm that, by utilising
1
0
n
the corresponding [C mim]Cl salts. This apparent antagonism anions and cations which are both inherently antimicrobial,
of antimicrobial activity has precedent, since recent studies enhancement of overall antimicrobial activity may be achieved, thus
have demonstrated that copper ions in certain biocide compo- facilitating the preparation of ‘designer’ antimicrobial ionic liquids.
1
3
sitions may exert an overall antagonistic effect. Furthermore,
Pennanen (2001) indicates that fungi are relatively more
susceptible to copper toxicity than bacteria. In contrast, the
overall antimicrobial activity was enhanced against Gram
Experimental
2
3
1-Alkyl-3-methylimidazolium chlorides and bromides were
negative bacteria and C. tropicalis, with [C14mim]
the most potent copper compound tested). Average MIC values
for Gram negative and C. tropicalis were reduced three-fold
2 4
[CuCl ]
prepared via the reaction of 1-methylimidazole with a slight
excess of the corresponding 1-haloalkane based on published
(
2
9–31
protocols.
A series of 1-alkyl-3-methylimidazolium salts of
1
0
À
À
2À
compared with [C mim]Cl. The substitution of the [AgBr ]
1
4
2
[AgBr2] and [CuCl4] (Fig. 1) were synthesised. These are
binary ionic liquids simply made by fusing the imidazolium
halide with the metal halide at elevated temperature, as
described in the ESI.† For calculation of minimum inhibitory
concentrations (MIC) and minimum bactericidal/fungicidal
concentrations (MBC or MFC), broth microdilution tests were
anion with [AgCl2]À
14
+
16
+
in both [C mim] and [C mim] ionic
liquids resulted in further enhancement of antibacterial activity
against both MRSA and P. aeruginosa, whereas no further
improvement in antibacterial activity could be achieved by
2
À
2À
substitution of [CuCl
4
]
with [CuBr
4
]
anions in both
3
2
[C
14mim] and [C16mim] ionic liquids (data not shown).
performed according to NCCLS guidelines, and as described
1
0
Finally, the antimicrobial activities of the silver(I) and
previously.† It should be noted that in the case of silver
containing ionic liquids, there was some precipitation of silver
halide when in contact with the growth media. With this
however, the ionic liquids in question were still more active
than compared to the imidazolium halide.
1
0
copper(II) ionic liquids were compared with [C mim]Cl and
[
1
4
2
4
C quin]Br (quin = 1-quinolinium) for seven microorganisms
14
(Table 3). As can be seen, the silver(I) anionic ionic liquids
appear to be more active than the imidazolium chloride ionic
liquids, and can be seen in anion effect ratios. The copper(II)
anionic ionic liquids are in generally similar in antimicrobial
activity to the corresponding chloride salts, except in the case of
Acknowledgements
P. aeruginosa and P. mirabilis, and more active than the corres- We are grateful to the Society for Applied Microbiology for
ponding chloride salts. However, the recently published 1-tetra- support of AFL through a ‘Students into Work’ grant, to the
decylquinolinium bromide ionic liquids are considerably more Marie Curie Foundation for support of GB, to the Industrial
2
4
potent than all the imidazolium ionic liquids so far tested.
Advisory Board of QUILL and the EPSRC (Portfolio Partnership
Although the exact mechanism by which antimicrobial Scheme, grant number EP/D029538/1) and to Invest Northern
ionic liquids exert microbiological toxicity has yet to be fully Ireland for their continuing support.
elucidated, their structural similarity to common biocidal
agents such as the quaternary ammonium compounds and
Notes and references
dependence on alkyl chain length for toxicity suggest
4
–10
membrane disruption as a likely mechanism of action.
1 K. R. Seddon, J. Chem. Technol. Biotechnol., 1997, 68, 351–356.
2 A. Stark and K. R. Seddon, in Kirk-Othmer Encyclopaedia of
Chemical Technology, ed. A. Seidel, John Wiley & Sons, Inc.,
Hoboken, New Jersey, 2007, vol. 26, pp. 836–920.
3 P. J. Scammells, J. L. Scott and R. D. Singer, Aust. J. Chem.,
2005, 58, 155–169.
The mode of action of metal ions, such as copper, is generally
via their ability to produce reactive oxygen species, thus target-
ing numerous biochemical pathways within the cell, resulting
in oxidation of thiol groups in proteins, DNA damage, lipid
peroxidation and the binding-site displacement of similar
1
3,25
transition metals.
In addition, silver ions cause protein
4 K. M. Docherty and C. F. Kulpa Jr., Green Chem., 2005, 7,
185–189.
denaturation via interaction with thiol, amino, imidazole,
phosphate and carboxyl groups of membrane proteins and
5 J. Pernak, K. Sobaszkiewicz and I. Mirska, Green Chem.,
2003, 5, 52–56.
2
6,27
enzymes
and cause metabolite efflux and inhibition of
This journal is c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2013
New J. Chem., 2013, 37, 873--876 875
Gilmore, Brendan F.
