Selective signaling of peracetic acid over hydrogen peroxide by desulfurization of an anthracene-thioamide

Article abstract of DOI:10.1016/j.tetlet.2012.05.101

Selective signaling of peracetic acid by desulfurization of a thioamide was investigated. A thioamide derivative of anthracene 1 was efficiently desulfurized by peracetic acid to the corresponding amide 2, which resulted in a pronounced turn-on type fluorescent signaling. Signaling was not affected by the presence of another important oxidant hydrogen peroxide thereby providing selective signaling of the peracetic acid from its frequent contaminant hydrogen peroxide. Anthracene-thioamide 1 also provided selectivity for peracetic acid over commonly encountered metal ions and anions. The chemical transformation was confirmed by ¹H NMR, ¹³C NMR, and fluorescence measurements.

Full text of DOI:10.1016/j.tetlet.2012.05.101

Tetrahedron Letters 53 (2012) 4080–4083
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Selective signaling of peracetic acid over hydrogen peroxide
by desulfurization of an anthracene-thioamide
⇑
Suyoung Eor, Myung Gil Choi, Nayun Kim, Taihao Sun, Suk-Kyu Chang
Department of Chemistry, Chung-Ang University, Seoul 156-756, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Selective signaling of peracetic acid by desulfurization of a thioamide was investigated. A thioamide
derivative of anthracene 1 was efficiently desulfurized by peracetic acid to the corresponding amide 2,
which resulted in a pronounced turn-on type fluorescent signaling. Signaling was not affected by the
presence of another important oxidant hydrogen peroxide thereby providing selective signaling of the
peracetic acid from its frequent contaminant hydrogen peroxide. Anthracene-thioamide 1 also provided
selectivity for peracetic acid over commonly encountered metal ions and anions. The chemical transfor-
mation was confirmed by 1H NMR, 13C NMR, and fluorescence measurements.
Received 18 March 2012
Revised 16 May 2012
Accepted 23 May 2012
Available online 29 May 2012
Keywords:
Peracetic acid
Fluorogenic signaling
Desulfurization
Ó 2012 Elsevier Ltd. All rights reserved.
Anthracene-thioamide
Hydrogen peroxide
There is great interest in the development of smart molecular
systems for the selective signaling of chemically and biologically
important chemical species.1 Recently, signaling of oxidants has at-
tracted considerable research interest in the biological and envi-
ronmental chemistry fields.2 A number of probes have been
developed for signaling or visualization of biologically important
oxidants, such as hydrogen peroxide,3 peroxynitrite,4 and hypo-
chlorous acid.5 However, signaling of peracids, which have found
more practical involvement in many aspects of synthetic chemis-
try, daily living, and industrial applications such as disinfection,
food processing, and water treatment, is not so well studied.
Peracetic acid (PAA) is the peroxide of acetic acid. PAA is a
strong oxidizing agent produced by reacting acetic acid and hydro-
gen peroxide in aqueous solution.6 It is used widely as a green oxi-
dant in synthetic organic chemistry and as a safe disinfectant. The
disinfection power of PAA is known to be more efficient than chlo-
rine or chlorine dioxide, and it could be used as a safer disinfectant
in the food and beverage industry.7 For disinfection purposes,
typical concentrations of PAA range between 6.6 Â 10À4 and
1.3 Â 10À2 M.8
analysis is the most attractive due to its convenience and sensitivity.
Difficulty in PAA analysis is the presence of varying amounts of
hydrogen peroxide, which is a result of the synthesis of PAA from
acetic acid as well as from decomposition of PAA via the reverse
reaction. Therefore, the discrimination of PAA from hydrogen perox-
ide is a very important property in the analysis of PAA. Simultaneous
determination of PAA, hydrogen peroxide, and acetic acid has been
carried out using far-UV absorption bands in the 180–220 nm
region.14 On the other hand, the discrimination of PAA from hydro-
gen peroxide has been investigated by potentiometry,15 reagentless
biosensor,16 and time resolved UV–vis spectrometry.17
We recently reported a convenient signaling system for the syn-
thetically useful oxidant 3-chloroperbenzoic acid (mCPBA) that re-
lied on the oxidative desulfurization of thiocoumarin.18 In this
Letter, a new simple PAA selective probe based on a thioamide
derivative of anthracene was investigated. Anthracene based thio-
amide 1 showed pronounced fluorescence turn-on type signaling
behavior toward PAA via desulfurization of the thioamide group
in the presence of common metal ions and anions as well as hydro-
gen peroxide.
Accurate determination of PAA is required to assess PAA levels in
oxidant or disinfectant solutions. A number of analytical methods
have been developed to assay PAA, including titrimetry,9 gas chro-
matography,10 liquid chromatography,11 electrochemistry,12 and
spectrophotometry.13 Among these analytical methods, optical
Compound 1 was prepared from 9-anthracenecarboxylic acid by
acid chloride formation with oxalyl chloride, amidation with dieth-
ylamine (86%), and subsequent treatment with Lawesson’s reagent
(toluene, 64%) (Scheme 1). The anthracene fluorophore was chosen
as the signaling moiety due to its relative stability to oxidation from
the targeted oxidants. A diethylthioamide was utilized as a signal-
switching moiety, due to the relative inertness of aromatic tertiary
thioamides to metal ion-induced desulfurization.19
⇑
Corresponding author. Tel.: +82 2 820 5199; fax: +82 2 825 4736.
E-mail address: skchang@cau.ac.kr (S.-K. Chang).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.05.101

S. Eor et al. / Tetrahedron Letters 53 (2012) 4080–4083
4081
100
80
60
40
20
0
100
100
80
60
40
20
0
88 88 88
87
87
87
+ PAA
1
1
86
86
83
85
85
85
83
83
80
60
40
20
0
28
+ mCPBA
only,
1.0
1.0
0.9
only +PAA
+H O +mCPBA +TBHP
2 1
1
1
1
1
2
1
1
1.0
+ H O , TBHP
2
2
360
410
460
510
560
Wavelength (nm)
+ PAA
Figure 1. Fluorescence spectra of 1 in the presence of PAA, mCPBA, TBHP, and H2O2
in a mixture of CH3CN and acetate buffer solution (pH 4.8, 10 mM), (10:90, v/v).
kex = 340 nm; [1] = 5.0 Â 10À6 M; [Oxidant] = 5.0 Â 10À4 M. Inset represents the
fluorescence intensity ratio I/Io of 1 at 409 nm for each oxidant.
Figure 3. Competitive fluorescent signaling of PAA by 1 in the presence of metal
ions and anions as background in a mixture of CH3CN and acetate buffer solution
(pH 4.8, 10 mM), (10:90, v/v). kex = 340 nm; [1] = 5.0 Â 10À6 M; [PAA] = 2.5 Â
10À4 M; [Mn+] = [AnÀ] = 5.0 Â 10À4 M.
100
thioamide 1 showed very weak fluorescence emission due to the
quenching nature of its thiocarbonyl function.20 On the other hand,
thioamide 1 revealed a large fluorescence enhancement with PAA;
the fluorescence intensity ratio in the presence and absence of
oxidant I/Io at 409 nm was 83 (Fig. 1). Another widely used peracid,
mCPBA, induced a 28-fold fluorescence enhancement. Other indus-
trially important oxidants, such as hypochlorite (I/Io = 60) and
Oxone (I/Io = 4.4) also induced significant responses (Fig. S1).21 At
the moment, we have no clear explanation for these differences
in the reactivity of 1 toward surveyed oxidants. The response of
1 toward mCPBA, hypochlorite, and Oxone is not a drawback in
the selective signaling of PAA, since PAA is usually used as a single
component oxidant in many applications. In addition, thioamide 1
had almost no response to hydrogen peroxide, a major contami-
nant in PAA as well as tert-butyl hydroperoxide (TBHP) and
di-tert-butyl peroxide (DTBP). Based on these results, the selective
signaling of probe 1 for PAA over hydrogen peroxide was further
tested. The signaling behavior of probe 1 was measured in the
presence of varying amounts of hydrogen peroxide from 100 equiv
to 7000 equiv with respect to 1 (Fig. S2) and was relatively stable
toward hydrogen peroxide up to 2000 equiv.
100
83
80
80
60
40
60
20
1.5
1.3 0.9 1.3 0.9 0.8 1.1 1.0 1.0 1.3 1.1
0
40
20
0
2.0
1.5 1.6
1.4
1.6
1.0
1.3 1.1
1.3
1.0
1.0
0.9 1.0 0.9 0.9 0.8
0.9 0.9
Figure 2. Changes in fluorescence intensity ratio I/Io at 409 nm of 1 in the presence
of PAA, H2O2, metal ions, and anions in a mixture of CH3CN and acetate buffer
solution (pH 4.8, 10 mM), (10:90, v/v). kex = 340 nm; [1] = 5.0 Â 10À6 M;
[PAA] = 1.0 Â 10À4 M; [Mn+] = [AnÀ] = [H2O2] 5.0 Â 10À4 M.
Selective signaling of PAA over other commonly encountered
metal ions and anions might be an important characteristic for
the practical use of 1 as a PAA probe. Thioamide 1 exhibited almost
no response toward surveyed alkali (Li+, Na+, K+), alkaline earth
O
O
OH
O
S
N
N
i) Oxalyl chloride
ii) Diethylamine
(Mg2+, Ca2+, Ba2+), and transition metal ions (Mn2+, Fe3+, Co2+
,
Ni2+, Cu2+, Zn2+, Cd2+, Hg2+, Pb2+, Ag+) (Fig. 2). The fluorescence
intensity ratio in the presence and absence of metal ions I/Io at
409 nm varied in a limited range between 0.8 for Mn2+ and 2.0
for Zn2+ ions. Possible responses of thioamide toward notable thi-
ophilic metal ions of Cd2+, Hg2+, and Ag+ were not observed as
was similarly reported for the diethylthioamide derivative of pyr-
ene.19 The response of 1 toward common anions was also tested.
As can be seen in Figure 2, frequently encountered anions induced
negligible fluorescence signaling of 1; the I/Io at 409 nm varied
within a narrow range between 0.8 (for P2O74À) and 1.5 (for FÀ).
For practical applications, signaling of PAA under competitive
conditions in the presence of commonly encountered coexisting
metal ions and anions as background is necessary. To check the
possibility of interference, fluorescence signaling of PAA by 1 in
the presence of 20 equiv of coexisting ions with respect to PAA
was measured (Fig. 3). With metal ions as background, no
CH2Cl2
2
1
N
Lawesson's reagent
Toluene, reflux
O
2
CH3COOH
Fluorescence ON
Fluorescence OFF
90% aq CH3CN
Scheme 1. Preparation of anthracene-thioamide 1 and its peracetic acid signaling.
Initially, the response of 1 toward important peroxide and
peracid oxidants was surveyed. In 90% aqueous acetonitrile,

4082
S. Eor et al. / Tetrahedron Letters 53 (2012) 4080–4083
Figure 4. Partial 1H NMR spectra of 1, 1 upon reaction with PAA, and 2 in CDCl3. [1] = [2] = 3.0 Â 10À2 M. Middle spectrum (1 + PAA) was obtained from the purified reaction
product of 1 with PAA (10 equiv) in 90% aqueous acetonitrile.
15 min after sample preparation (Fig. S4). The time plot also
showed that the probe 1 was stable under the signaling conditions
and did not exhibit any signaling with hydrogen peroxide and tert-
butyl hydroperoxide (TBHP).
120
100
80
60
40
20
0
120
100
80
60
40
20
0
[PAA]
Finally, quantitative signaling of PAA by thioamide 1 was inves-
tigated. A concentration dependent response of 1 to PAA was ob-
served with up to 10 equiv of PAA under the same experimental
conditions (Fig. 5). The reaction of 1 with PAA appears not to pro-
ceed in a 1:1 stoichiometry, possibly due to the fact that PAA fre-
quently contains varying amounts of hydrogen peroxide. That is
a result of the synthesis of PAA from acetic acid as well as from
decomposition of PAA via the reverse reaction. From this concen-
tration dependent signaling profile, the detection limit of 1 for
the determination of PAA in 90% aqueous acetonitrile was esti-
0
5
10 15 20 25 30
Equiv. of PAA
mated to be 5.7 l
M.26
In summary, a simple thioamide-based chemosignaling system
for the widely used oxidant peracetic acid was developed. A thio-
amide derivative of anthracene 1 showed selective fluorescent
turn-on type signaling behavior toward peracetic acid over com-
mon metal ions and anions. The developed probe 1 also exhibited
significant discrimination for peracetic acid over hydrogen perox-
ide, a common contaminant of commercial peracetic acid. The
probe 1 could be useful for the fluorescent determination of prac-
tical peracetic acid samples such as disinfectant in daily life and
industrial applications, which typically contain varying amounts
of hydrogen peroxide.
360
410
460
510
560
Wavelength (nm)
Figure 5. Fluorescence titration of 1 with PAA. [1] = 5.0 Â 10À6 M in a mixture of
CH3CN and acetate buffer solution (pH 4.8, 10 mM), (10:90, v/v). kex = 340 nm.
significant interference in the signaling of PAA was found with the
exception of Hg2+ and Fe3+ ions. Hg2+ ions significantly interfered
with the signaling of PAA because of a direct reaction with the ana-
lyte PAA.22 Ferric ions also considerably interfered with signaling,
possibly due to the known incompatibility of PAA with Fe3+ ions.23
With anions, except for bromide and iodide, almost no interference
with the fluorescent signaling of probe 1 with PAA was found.
Interference from bromide and iodide ions is due to the well-
known redox reaction of the oxidant PAA itself with these reactive
ions.24
Acknowledgments
This work was supported by a fund from Korea Research Foun-
dation of Korean government (2012-0002403).
Transformation of 1 into 2 by PAA was confirmed by NMR mea-
surements. The 1H NMR spectrum of the purified reaction product
of 1 after treatment with 10 equiv of PAA was almost identical to
that of 2. The ethyl proton resonances of 1 at 4.42 and 3.20 ppm
disappeared, and new resonances at 3.87 and 3.02 ppm for the
ethyl protons of 2 were observed (Fig. 4). In the 13C NMR spectrum,
particularly, the resonance of the thiocarbonyl carbon of 1 at
197.7 ppm disappeared, and a carbonyl carbon peak for 2 at
169.6 ppm was observed (Fig. S3). It has been reported that the
thiocarbonyl group is oxidized by PAA to give a sulfine, followed
by subsequent hydrolysis to give the carbonyl group.25 Fluores-
cence measurements also supported the chemical transformation
as the fluorescence spectrum of 1 in the presence of 20 equiv of
PAA was almost identical to that of 2. A time course plot for 1 in
the presence of PAA showed that signaling was complete within
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.05.
101. These data include MOL files and InChiKeys of the most
important compounds described in this article.
References and notes
1. (a) de Silva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson, T.; Huxley, A. J. M.;
McCoy, C. P.; Rademacher, J. T.; Rice, T. E. Chem. Rev. 1997, 97, 1515; (b) Jun, M.
E.; Roy, B.; Ahn, K. H. Chem. Commun. 2011, 47, 7583.
2. Kohen, R.; Nyska, A. Toxicol. Pathol. 2002, 30, 620.
3. Lippert, A. R.; Van de Bittner, G. C.; Chang, C. J. Acc. Chem. Res. 2011, 44, 793.
4. Peng, T.; Yang, D. Org. Lett. 2010, 12, 4932.

S. Eor et al. / Tetrahedron Letters 53 (2012) 4080–4083
4083
5. Yang, Y. K.; Cho, H. J.; Lee, J.; Shin, I.; Tae, J. Org. Lett. 2009, 11, 859.
19. Eor, S.; Hwang, J.; Choi, M. G.; Chang, S.-K. Org. Lett. 2011, 13, 370.
20. Maciejewski, A.; Steer, R. P. Chem. Rev. 1993, 93, 67.
21. By using similar desulfurization of thiocarbonyl functions, we have previously
6. Zhao, X.; Zhang, T.; Zhou, Y.; Liu, D. J. Mol. Catal. A 2007, 27, 246.
7. Alvaro, J. E.; Moreno, S.; Dianez, F.; Santos, M.; Carrasco, G.; Urrestarazu, M. J.
Food Eng. 2009, 95, 11.
reported thiocoumarin and pyrene-thioamide based signaling probe for the
19
8. Plnkernell, U.; Karst, U.; Cammann, K. Anal. Chem. 1994, 66, 2599.
9. Greenspan, F. P.; MacKellar, D. G. Anal. Chem. 1948, 20, 1061.
10. Di Furia, F.; Prato, M.; Scorrano, G.; Stivanello, M. Analyst 1988, 113, 793.
11. Pinkernell, U.; Effkemann, S.; Karst, U. Anal. Chem. 1997, 69, 3623.
12. Hua, M. Y.; Chen, H. C.; Tsai, R. Y.; Lin, Y. C. Electrochim. Acta 2011, 56, 4618.
13. (a) Pinkernell, U.; Lüke, H. J.; Karst, U. Analyst 1997, 122, 567; (b) Janotta, M.;
Vogt, F.; Voraberger, H. S.; Waldhauser, W.; Lackner, J. M.; Stotter, C.; Beutl, M.;
Mizaikoff, B. Anal. Chem. 2004, 76, 384.
practical oxidants of mCPBA18 and Oxone,
respectively. We tried to clarify
the relationship between the structural effects of the thiocarbonyl compounds
on the reactivity toward the oxidants. However, the thio-compounds showed
somewhat broad signaling behavior toward these oxidants depending on the
measuring conditions as shown in Figure S1. In fact, we optimized the signaling
conditions of 1 for a targeted oxidant by systematically varying the solvents
and pH of the solution.
22. Kojima, K.; Fujita, M. Toxicology 1973, 1, 43.
14. Higashi, N.; Yokota, H.; Hiraki, S.; Ozaki, Y. Anal. Chem. 2005, 77, 2272.
15. Awad, M. I.; Oritani, T.; Ohsaka, T. Anal. Chem. 2003, 73, 2688.
16. Sanz, V.; de Marcos, S.; Galbán, J. Anal. Chim. Acta 2007, 583, 332.
17. Pettas, I. A.; Karayannis, M. I. Anal. Chim. Acta 2004, 522, 275.
18. Cha, S.; Hwang, J.; Choi, M. G.; Chang, S.-K. Tetrahedron Lett. 2010, 51, 6663.
23. Mücke, H. Pharmazie 1977, 32, 613.
24. (a) Fortnum, D. H.; Battaglia, C. J.; Cohen, S. R.; Edwards, J. O. J. Am. Chem. Soc.
1960, 82, 778; (b) Davies, D. M.; Deary, M. E. Analyst 1988, 113, 1477.
25. Corsaro, A.; Pistarà, V. Tetrahedron 1998, 54, 15027.
26. Shortreed, M.; Kopelman, R.; Kuhn, M.; Hoyland, B. Anal. Chem. 1996, 68, 1414.