Synthesis and antimicrobial activity of a perfluoroalkyl-containing quaternary ammonium salt

Article abstract of DOI:10.1016/S0022-1139(03)00193-3

A novel perfluoroalkyl-containing quaternary ammonium salt 5 was designed and synthesized. Consequently, the antimicrobial activities of compound 5 were measured with Escherichia coli 8099 as a Gram-negative strain and Staphylococcus aureus ATCC 6538 as a

Full text of DOI:10.1016/S0022-1139(03)00193-3

Journal of Fluorine Chemistry 124 (2003) 89–91
Synthesis and antimicrobial activity of a perfluoroalkyl-containing
quaternary ammonium salt
a
Hui Shao , Li Jiang , Wei-Dong Meng , Feng-Ling Qing
College of Chemistry and Chemical Engineering, Donghua University, 1882 West Yanan Road, Shanghai 200051, China
b
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
a
a
a,b,*
a
3
54 Fenglin Lu, Shanghai 200032, China
Received 9 May 2003; received in revised form 4 July 2003; accepted 9 July 2003
Abstract
A novel perfluoroalkyl-containing quaternary ammonium salt 5 was designed and synthesized. Consequently, the antimicrobial activities of
compound 5 were measured with Escherichia coli 8099 as a Gram-negative strain and Staphylococcus aureus ATCC 6538 as a Gram-positive
strain. Both the minimum inhibitory concentration (MIC, the lowest concentration of compound 5 that inhibits microbial growth) values of
quaternary ammonium salt 5 against Escherichia coli 8099 and Staphylococcus aureus ATCC 6538 were 7.8 mg/ml.
#
2003 Elsevier B.V. All rights reserved.
Keywords: Perfluoroalkyl-containing quaternary ammonium salt; Textile finishing; Antimicrobial activity
1
. Introduction
should prevent to minimize infection or transmission of
disease [10]. Especially for surgical gowns, there is an
increasing need to protect medical staff from infection by
blood borne pathogens such as HIV and HBV [11]. Gowns
should be able to prevent ‘‘strike through’’ of ‘‘wetting
out’’ of the fabric, and so surgical gown materials should
have not only antimicrobial properties but also blood
barrier properties [12].
Perfluoroalkyl-containing chemicals and fluoropolymers
most abundantly used as repellent agents in textile finishing,
not only satisfy the demand for high water repellency but
also impart oil and soil repellency to finished textiles. Water
and oil repellency is achieved by reducing the critical sur-
face energy of fabrics [13].
In the light of the facts above mentioned, we envisaged
that a novel quaternary ammonium salt, which contains both
perfluoroalkyl group and diallyl groups, should be suitable a
finishing agent for providing the fabrics with barriers against
microorganisms, water, oil, soil and blood. Moreover, the
introduction of diallyl groups into the quaternary ammo-
nium salt not only can enhance the antimicrobial activity, but
also extend its application fields. It can be applied in two
categories of antimicrobial finishes: one category is part of
the fiber-forming process and the other category is the one
incorporated in the finishing process. It can also be used as a
perfluoroalkyl-containing monomer in the polymer field,
which is a convenient method incorporating perfluoroalkyl
chain in the polymer. We describe herein the synthesis and
Textile materials are excellent media for growing micro-
organisms. In the last few decades, the prevention of
microbial attack on textile and wearers of textile materials
has become increasingly important to consumers and tex-
tile producers [1]. A market study in Germany revealed a
steady increase in the demand for antimicrobial fabrics.
The potential market for antimicrobial fabrics is 28,000 t in
Europe and 40,000 t in the United States and Japan [2]. So
far, various antimicrobial agents have been applied to
impart antimicrobial properties to textile [3–6]. Among
them, the quaternary ammonium halide cationic surfactants
are widely used in antimicrobial finishing of textile, since
Domagk developed an important class of antimicrobial
agents based on quaternary ammonium salts in 1935 [7].
Quaternary ammonium salts exhibit marked antimicrobial
activity against a wide range of bacteria, fungi, and viruses
[
8]. The introduction of unsaturated alkyl groups into
quaternary ammonium salts can enhance its antimicrobial
activity [9].
Hospital materials such as theater drapes, gowns, mask,
sheets, and pillowcases are known to be major sources of
cross-infection, so all textile materials used in hospitals
*
Corresponding author. Tel.: þ86-216-416-3300;
fax: þ86-216-416-6128.
E-mail address: flq@pub.sioc.ac.cn (F.-L. Qing).
0022-1139/$ – see front matter # 2003 Elsevier B.V. All rights reserved.
doi:10.1016/S0022-1139(03)00193-3

90
H. Shao et al. / Journal of Fluorine Chemistry 124 (2003) 89–91
AIBN
5%
Bu SnH / AIBN
OH
3
CF (CF )
2 7
OH
CF (CF )
2 7
OH
3
CF (CF ) I
+
3
3
2
7
7
70%
I
1
2
8
5% TsCl / NaOH
CH3I
N
/ K CO
2 3
+
N
H
N
CF (CF )
2 7
I
OTs
3
84%
67%
3
5
4
(
CF ) CF
(CF ) CF
3
2
7
3
2
7
Scheme 1.
antimicrobial activity of a perfluoroalkyl-containing qua-
ternary ammonium salt.
3. Experimental section
Melting points were determined on a Pai-ke melting point
apparatus and were uncorrected. 1HNMR spectra were
recorded on a Bruker AM 300 (300 MHz) spectrometer
2
. Results and discussion
The target molecule 5 was designed to be a multifunc-
with Me Si as internal standard. 19F NMR spectra were
4
tional textile finishing agent capable of being attached to
fiber by ionic interactions and providing them with barriers
against microorganisms, water, oil, soil and blood. The
synthesis of 5 was outlined in Scheme 1. The first step
proceeded by a free radical addition of a perfluorooctyl
iodide to allyl alcohol that was initiated with AIBN to
provide the perfluoroalkylated iodohydrin 1 in 75% yield.
Compound 1 was then reduced to the perfluoroalkyl alcohol
obtained on Bruker AM 300 (282 MHz) spectrometer in
CDCl with CFCl as external standard, downfield shifts
3
3
being designated as negative. All chemical shifts (d) are
expressed in ppm, coupling constants (J) are given in Hz.
Mass spectra were recorded on a Finnigan-MAT-8430
instrument using EI ionization at 70 eV. IR spectra were
recorded on a Shimadzu IR-440 spectrometer.
2
in 70% yield by using tributyltin hydride [14]. Subsequent
3.1. 1H,1H,2H,2H,3H,3H-perfluoro-1-undecanol (2)
tosylation of compound 2 provided the intermediate 3 in 85%
yield. The alkylation of diallylamine with 3 in the presence
of K CO afforded the key material 4 in 67% yield [15].
Allyl alcohol (3.73 g, 64.2 mmol) was added dropwise
slowly to a mixture of perfluorooctyl iodide (27.1 g,
2
3
o
49.7 mmol) and AIBN (0.166 g, 1.01 mmol) at 95 C.
Finally, treatment of 4 with CH I in anhydrous CH CN gave
3
3
o
The reaction mixture was stirred for 24 h at 95 C. Then
the target molecular 5 in 84% yield. The perfluoroalkyl-
containing quaternary ammonium salt 5 is soluble in water.
Consequently, the antimicrobial activities of the target
molecule 5 were measured with Escherichia coli 8099 as a
Gram-negative strain and Staphylococcus aureus ATCC
the excessive allyl alcohol was removed in vacuo. Purifica-
tion of the yellow residue by column chromatography on
silica gel (petroleum ether:ethyl acetate ¼ 10:1) gave com-
pound 1 (22.5 g, 75% yield ) as a white solid. Then to a
mixture of 1 (22.0 g, 36.5 mmol) and AIBN (0.041 g,
0.24 mmol) was added dropwise tributyltin hydride
6538 as a Gram-positive strain on the basis of MIC values,
defined as the lowest concentration of antimicrobial agent
o
that results in inhibiting of growth of the test organism after
2
(10.6 g, 36.5 mmol) at 100 C for 4 h under nitrogen atmo-
o
sphere. The reaction mixture was stirred at 80 C for 24 h.
o
4 h of incubation at 37 C. The MIC values were shown in
the Table 1. This result showed compound 5 possessed good
antimicrobial activities against both Gram-positive S. aureus
and Gram-negative E. coli.
In conclusion, we have designed and synthesized a novel
perfluoroalkyl-containing diallyl quaternary ammonium salt
The phase separation phenomenon occurred. The lower
liquid phase was collected and chromatographed on silica
gel (petroleum ether:ethyl acetate ¼ 10:3) to afford com-
1
pound 2 as a white solid (12.2 g, 70% yield). H NMR
(300 MHz, CDCl ) d 3.70 (t, J ¼ 6:0 Hz, 2H), 2.20 (m, 2H),
3
1
9
5
. It shows good antimicrobial activities against both Gram-
1.88 (m, 2H), 1.50 (s, 1H). F NMR (282 MHz, CDCl ) d
3
positive S. aureus and Gram-negative E. coli. The applica-
tion of the compound 5 for textile multifunctional finishing
and polymerization will be reported in due course.
80.72 (t, J ¼ 9:9 Hz, 3F), 114.24 (m, 2F), 121.66–121.87
(m, 6F), 122.65 (s, 2F), 123.46 (s, 2F), 126.06 (s, 2F).
3.2. Toluene-4-sulfonic acid 4,4,5,5,6,6,7,7,8,8,9,9,10,
10,11,11,11-heptadecafluoro-undecyl ester (3)
Table 1
The minimum inhibitory concentration (MIC) for compound 5
Alcohol 2 (8.10 g, 16.9 mmol) and toluene-4-sulfonyl
chloride (3.84 g, 20.2 mmol) were dissolved in CH Cl
Bacterium
Gram
MIC (mg/ml)
2
2
Staphylococcus aureus ATCC 6538
Escherichia coli 8099
(þ)
(ꢀ)
7.8
7.8
(
(
50 ml). A 50% (w/w) aqueous sodium hydroxide solution
25 ml) was then added, and the reaction mixture was heated

H. Shao et al. / Journal of Fluorine Chemistry 124 (2003) 89–91
91
o
at 40 C for 2 h. The suspension was cooled and decanted.
2F), 125.32 (s, 2F). IR (KBr) 3005, 2974, 1478, 1253, 1204,
ꢀ
1
1153, 1116, 954, 887, 703, 657 cm ; MS m/z 531(3 M –I–
þ
The organic phase was washed three times with water
(
30 ml), brine, dried over anhydrous MgSO and filtration,
4
C H ), 504 (7), 168 (5), 127 (3), 110 (5), 84 (100), 41 (31),
3 5
the solvent was removed in vacuo. Purification of the residue
by column chromatography on silica gel (petroleum ether:-
ethyl acetate ¼ 10:1) gave compound 3 (9.07 g, 85% yield)
69 (9); Anal. Calcd. for C H F NI: C, 30.92; H, 2.74; N,
18 19 17
2.00. Found: C, 31.17; H, 2.74; N, 1.84%.
o
1
as a white solid. m.p. 60 C. H NMR (300 MHz, CDCl ) d
3.5. Antimicrobial activity
3
1
2
.99 (m, 2H), 2.22 (m, 2H), 2.46 (s, 3H), 4.12 (t, J ¼ 6:0 Hz,
19
H), 7.37 (d, J ¼ 8:1 Hz, 2H), 7.80 (d, J ¼ 8:1 Hz, 2H).
F
The antimicrobial activity was tested against Escherichia
coli 8099 and Staphylococcus aureus ATCC 6538. The
minimum inhibitory concentration (MIC) of compound 5
against selected bacterium was determined by a standard
NMR (282 MHz, CDCl ) d 80.75 (t, J ¼ 9:9 Hz, 3F), 114.43
3
(
2
m, 2F), 121.90–121.94 (m, 6F), 122.69 (s, 2F), 123.46 (s,
F), 126.08 (s, 2F).
5
broth dilution method [16]. Bacterial suspensions (5 ꢁ 10
6
o
3.3. N-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-
Heptadecafluoroundecyl)-N,N-diallylamine (4)
to 5 ꢁ 10 CFU/ml) were incubated for 24 h at 37 C in the
presence of different concentrations of compound 5. The
MIC values were defined as the lowest concentration of
compound 5 that resulted in complete inhibition of growth of
the test bacterium.
A
suspension of toluene-4-sulfonate
3
1.1 mmol), diallylamine (1.45 g, 14.9 mmol), and potas-
(7.00 g,
1
sium carbonate (2.54 g, 18.4 mmol) in CH CN (35 ml) was
3
heated to reflux for 24 h under nitrogen. The reaction
mixture was filtered. The filtrates were concentrated in
vacuo. The residue was purified by column chromatography
on silica gel (petroleum ether:ethyl acetate ¼ 14:1) to give
Acknowledgements
We thank the Ministry of Education of China for financial
support.
1
compound 4 (4.13 g, 67% yield) as a colorless liquid. H
NMR (300 MHz, CDCl ) d 1.75 (m, 2H), 2.08 (m, 2H), 2.50
3
(
5
t, J ¼ 6:9 Hz, 2H), 3.09 (d, J ¼ 6:9 Hz, 4H), 5.16 (m, 4H),
1
9
References
.84 (m, 2H). F NMR (282 MHz, CDCl ) d 80.75 (t,
3
J ¼ 9:9 Hz 3F), 114.16 (m, 2F), 121.99–121.94 (m, 6F),
[
[
[
1] H.S. Seong, J.P. Kim, S.W. Ko, Textile Res. J. 69 (1999) 483–488.
2] G. Tanchis, Tanctoria 99 (2002) 68–69.
1
3
7
4
2
22.76 (s, 2F), 123.46 (s, 2F), 126.12 (s, 2F). IR (thin film)
084, 2984, 2812, 1645, 1243, 1209, 1152, 1114, 997, 923,
3] T. Nakashima, Y. Sakagami, H. Ito, M. Matsuo, Textile Res. J. 71
ꢀ
1
05, 656 cm . MS m/z 557 (3), 530 (6), 110 (100), 69 (11),
1 (51). Anal. Calcd. for C H F N: C, 36.64; H, 2.89; N,
.51. Found: C, 36.57; H, 3.10; N, 2.67%.
(
2001) 688–694.
1
7
16 17
[4] K. Teraoka, T. Nonami, Y. Yokogawa, H. Taoda, T. Kameyama, J.
Mater. Res. 15 (2000) 1243–1244.
[
5] Y.H. Kim, G. Sun, Textile Res. J. 71 (2001) 318–323.
[
6] Y.J. Jeong, S.Y. Cha, W.R. Yu, W.H. Park, Textile Res. J. 72 (2002)
7
3.4. N-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-
Heptadecafluoroundecyl)-N,N-diallylmethyl ammonium
iodide (5)
0–76.
[
[
7] M. Diz, M.R. Infante, P. Erra, Textile Res. J. 71 (2001) 695–700.
8] D.L. Fredel, J. Cross, E.J. Singer, Surfactant Science Series, vol. 53,
Marcel Dekker, NY, 1994.
[
9] H. Kourai, Y. Manabe, E. Matsutan, Bokin Bobai 23 (1995) 271.
A mixture of compound 4 (0.794 g 1.42 mmol), CH3I
0.206 g, 1.45 mmol) and anhydrous CH CN (2 ml) was
3
[
[
[
10] T.L. Vigo, Textile Res. J. 51 (1981) 454–465.
(
11] K.K. Leonas, INDA J. Nonwovens Res. 5 (1993) 22–26.
12] E.A. McCullough, L.K. Schoenberger, INDA J. Nonwovens Res. 3
refluxed for 24 h. The solvent was removed in vacuo. The
residue was washed with anhydrous ether (3ꢁ 10 ml) to give
quaternary ammonium salt 5 (0.833 g, 84% yield) as a pale
(
3) (1991) 14–20.
[13] D. Lammermann, Melliand Textillber. Eng. Ed. 72 (1991) 380–383.
o
1
[
[
14] J.M. Vincent, A. Rabion, V.K. Yachandra, R.H. Fish, Angew. Chem.
Int. Ed. Engl. 36 (1997) 2346–2349.
yellow solid. m.p. 65–68 C H NMR (300 MHz, CDCl ) d
3
2
4
.18–2.40 (m, 4H), 3.34 (s, 3H), 3.71 (t, J ¼ 7:2 Hz 2H),
15] F.D. Campo, D. Last e´ cou e` res, J.M. Vincent, J.B. Verlhac, J. Org.
Chem. 64 (1999) 4969–4971.
19
.30 (d, J ¼ 6:9 Hz 4H), 5.83 (m, 4H), 6.03 (m, 2H).
F
NMR (282 MHz, CDCl ) d 79.90 (t, J ¼ 9:9 Hz 3F), 112.64
3
[16] Technical Standard For Disinfection, Broth Dilution Minimum
Inhibitory Concentration Test, Ministry of Health, PR China, 2002.
(
m, 2F), 120.78–121.08 (m, 6F), 121.90 (s, 2F), 122.31 (s,