A coumarin based chemodosimetric probe for ratiometric detection of hydrazine

Article abstract of DOI:10.1016/j.tetlet.2014.03.041

A coumarin-based sensor containing trifluoroacetyl acetonate moiety was designed, synthesized, and applied for hydrazine detection. Hydrazinolysis of the chemodosimeter results in a prominent chromogenic and fluorescence ratiometric response toward hydrazine within 3 min. The probe is highly selective toward hydrazine over other important amines and other biologically and environmentally abundant analytes. The limit of detection (LOD) of the probe is in 10^-6 M range. The sensing mechanism was supported by NMR and HRMS analysis. The experimentally observed change in structure and electronic properties of the sensor after reaction with hydrazine was modeled by Density Functional Theory (DFT) and Time Dependent Density Functional Theory (TDDFT) computational calculations, respectively.

Full text of DOI:10.1016/j.tetlet.2014.03.041

Tetrahedron Letters 55 (2014) 2695–2699
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A coumarin based chemodosimetric probe for ratiometric detection
of hydrazine
a
a
b
b
Shyamaprosad Goswami a, , Sangita Das , Krishnendu Aich , Deblina Sarkar , Tapan Kumar Mondal
⇑
a Bengal Engineering and Science University, Shibpur, Howrah 711 103, India
b Jadavpur University, Jadavpur, Kolkata 700 032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A coumarin-based sensor containing trifluoroacetyl acetonate moiety was designed, synthesized, and
applied for hydrazine detection. Hydrazinolysis of the chemodosimeter results in a prominent chromo-
genic and fluorescence ratiometric response toward hydrazine within 3 min. The probe is highly selective
toward hydrazine over other important amines and other biologically and environmentally abundant
analytes. The limit of detection (LOD) of the probe is in 10À6 M range. The sensing mechanism was
supported by NMR and HRMS analysis. The experimentally observed change in structure and electronic
properties of the sensor after reaction with hydrazine was modeled by Density Functional Theory (DFT)
and Time Dependent Density Functional Theory (TDDFT) computational calculations, respectively.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 16 January 2014
Revised 6 March 2014
Accepted 7 March 2014
Available online 17 March 2014
Keywords:
Sensor
Chemodosimeter
Ratiometric
Colorimetric & fluorimetric
Hydrazine
In recent era, the development of chemosensors as well as
chemodosimeters for the recognition of environmentally impor-
tant and hazardous analytes has been receiving considerable
attention.1 Hydrazine pollution is a global problem and creates a
significant damage to human health. Hydrazine is extensively used
as a high energetic fuel in missile propulsion systems.2,3 It is a
highly explosive base and a robust reducing mediator and is used
as a key reactant in the preparation of pharmaceuticals, photogra-
phy chemicals, pesticides, dyes, and emulsifiers.4 Nevertheless,
hydrazine has considerable effects that can potentially lead to
serious environmental pollution during its production, use,
conveyance, and clearance. Hydrazine is routinely determined by
electrochemical analysis5 and chromatography,6 including gas
chromatography,7 HPLC,8 and capillary electrophoresis.9 Due to
its extensive applications and poisonous effects, it is highly desir-
able to develop consistent and sensitive analytical methods for
the selective detection of hydrazine. However, there are only a
few reports regarding hydrazine-assisted fluorescent probes.10
In continuation of our research work in the development of
fluorescence sensors11 for important analytes, herein, we disclose
the design and synthesis of a fluorescence sensor based on
coumarin-trifluoroacetyl acetonate moiety (CTF; C = coumarin,
TF = trifluoroacetyl acetonate) which can selectively detect hydra-
zine ratiometrically in acetonitrile media. Hydrazine plays here the
key role to affect the ICT distribution of CTF through the formation
of a five-membered ring in its side chain, therefore a subsequent
ICT-induced ratiometric response was observed both in absorption
and fluorescence changes toward hydrazine. As depicted in
Scheme 1, compound 1 [3-acetyl-7-(diethylamino)coumarin] was
synthesized by following a similar procedure reported earlier.12
Compound 1 was converted to the target sensor CTF [1-(7-(diethyl-
amino)-2-oxo-2H-chromen-3-yl)-4,4,4-trifluorobutane-1,3-dione]
by treatment with ethyl trifluoroacetate through Claisen condensa-
tion in 64% yield. The structure of CTF was confirmed by 1H NMR,
13C NMR, (1HÀ13C) HMBC NMR, and HRMS spectroscopy (Supple-
mentary data Figs. S7–S11).
In this Letter, a new signaling probe (CTF) was devised for
hydrazine, using selective hydrazinolysis at the carbonyl group of
trifluoroacetyl acetonate moiety followed by cyclization to give
ultimately a new fluorescent species (CTFÀN2H4). We observed
here that the sensor CTF can react with hydrazine to generate
CTFÀN2H4 (7-(diethylamino)-3-(3-(trifluoromethyl)-1H-pyrazol-
5-yl)-2H-chromen-2-one) with a ratiometric fluorescence response
as shown in Scheme 2.
The absorption and emission properties of the probe were
investigated by addition of very small amount of hydrazine; it
causes the signal to change rapidly. CH3CN was selected as an anal-
ysis solvent to explore the optical response of CTF toward hydra-
zine at room temperature. UV–vis spectral studies of CTF (10 lM,
CH3CN, 25 °C) exhibited the maxima around at 485 nm. Upon addi-
⇑
Corresponding author. Tel.: +91 33 2668 2961–3; fax: +91 33 2668 2916.
E-mail address: spgoswamical@yahoo.com (S. Goswami).
tion of hydrazine (2 Â 10À4 M in CH3CN), the absorption at 485 nm
http://dx.doi.org/10.1016/j.tetlet.2014.03.041
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

2696
S. Goswami et al. / Tetrahedron Letters 55 (2014) 2695–2699
800
600
Scheme 1. Synthetic scheme of the probe (CTF). Reagents and conditions: (i) ethyl
acetoacetate, EtOH, piperidine, reflux, 6 h; (ii) ethyl trifluoroacetate, NaOMe, DCM,
reflux, 1 h.
400
200
0
500
550
600
650
Wavelength (nm)
Figure 2. (a) Change of fluorescence spectra of CTF (10
l
M) upon gradual addition
of hydrazine (0–2 equiv). Inset: Visible emission observed from CTF in absence and
presence of 5 equiv of hydrazine after irradiation under UV light.
Scheme 2. Probable sensing mechanism of CTF with N2H4.
mechanism of this type of change may be explained by the
addition of hydrazine. After reaction with hydrazine the conjuga-
tion is being hampered, that is, ICT (intramolecular charge-
transfer) turning off, which is accompanied by the blue-shift in
fluorescence. In contrast, only an insignificant change was
observed upon the addition of different amines, for example, ethy-
lenediamine, dimethylamine, triethylamine, NH2OH, piperazine,
phenylhydrazine, etc. Noteworthy is that it gains much importance
that even after addition of about 10 fold excess of these test
amines, there was no perturbation of the hydrazine-induced
fluorescence response. The effect of environmentally as well as bio-
eventually decreased, whereas two new absorption peaks
gradually appeared at 445 and 395 nm with two isosbestic points
arising at 273 and 335 nm. Such a blue shift (most prominent
one) of 90 nm causes a change in the absorption behavior showing
the change in the color of the solution from orange yellow to light
green, which allows a colorimetric detection of hydrazine to the
naked eye (Fig. 1). Now, the experimental data showed that in
the presence of 1.5 equiv of hydrazine ratiometric value increases
(A395/A485, from 0.7315 to 1.9094), which was observed with
logically important ions such as Na+,ÀZn2+, Cu2+, Mn2+, Fe3+, Hg2+
,
respect to CTF itself and ratio of two absorbance intensities (A395
/
Cd2+ (as their chloride salts), S2À, HSO3 ; SO24À; NO3À and NÀ3 (as their
sodium salts) was also examined and there was no significant
change observed both in UV–vis and fluorescence titration
experiments.
A485) maintained a good linear relationship with the concentration
of hydrazine (R2 = 0.994).
Fluorogenic studies of CTF were investigated in CH3CN solution.
Here also the spectral property of CTF was found to perturb only by
Now the reaction of CTF with hydrazine might proceed through
the formation of a five-membered cyclized product (CTFÀN2H4)
(Scheme 2, Figs. 3 and 4). Here the trifluoroacetyl acetone moiety
hydrazine. Upon excitation at 450 nm CTF (10
shows a maxima at 545 nm ( = 0.01) in the absence of any ana-
lyte. Upon incremental addition of hydrazine the peak at 545 nm
decreases regularly and new peak at 500 nm increases
= 0.11) rapidly and consequently it leads to a blue-shift from
lM, CH3CN, 25 °C)
u
a
(u
545 to 500 nm (Fig. 2). The experimental data showed that the
emission intensity ratio (I500/I545) of CTF after addition of hydrazine
fits linearly with hydrazine concentration, having a good R2 value
of 0.995. The detection limit was found to be 3.38 Â 10À6 M. The
1.0
0.8
0.6
0.4
0.2
0.0
250 300 350 400 450 500 550 600
Wavelength (nm)
Figure 1. (a) Change of UV–vis spectra of CTF (10 lM) upon gradual addition of
hydrazine (0–2 equiv). Inset: Visible color change observed in CTF in absence and
presence of 2 equiv of hydrazine.
Figure 3. Partial HRMS spectra (a) of CTF and (b) [CTFÀN2H4] the product resulting
from reaction of CTF with hydrazine.

S. Goswami et al. / Tetrahedron Letters 55 (2014) 2695–2699
2697
0 S
10 S
800
600
400
200
0
20 S
30 S
40 S
50 s
60 S
70 S
80 S
90 S
100 S
110 S
120 S
130 S
140 S
150 S
160 S
170 S
180 s
500
550
600
650
Wavelength (nm)
Figure 5. Change of emission spectra of CTF (10
equiv) with time interval.
lM) after addition of hydrazine (2
recorded with change in time (Fig. 5). These results are satisfactory
to indicate that CTF is an efficient sensor for hydrazine and it reacts
chemodosimetrically with the probe. This experiment showed a ra-
pid decrease in the fluorescence intensity at 545 nm within 50 s and
a new peak at 500 nm increased regularly. The hydrazine induced
reaction was completed within 180 s. We also studied the reaction
kinetics of this reaction (Supplementary data, Fig. S1). The time vs.
emission ratio (I500/I545) plot was obtained by using first order
rate equation. We get the rate constant = k = slope  2.303 = 20
Figure 4. Partial 1H NMR spectra of (a) CTF and (b) [CTFÀN2H4], the product
resulting from reaction of CTF with hydrazine.
plays a key role in the chemodosimetric approach of hydrazine in
our design.
Noticeably the inhibition in the fluorescence signature was
caused only by hydrazine and not by any other tested amines. This
indicates that the five-membered ring formation was assisted only
by hydrazine induced chemodosimetric approach. The proposed
product (CTFÀN2H4) was isolated and it was observed that the
dehydrated product was formed simultaneously and its structure
was characterized by 1H NMR, 13C NMR, and HRMS spectroscopic
analyses (Supplementary data, Figs. S12–S14).
Time dependent fluorescence change of CTF upon addition of
hydrazine and its reaction kinetics was studied in acetonitrile
solution. To understand this time dependent experiment with
CTFÀN2H4 system, the fluorescence spectra of this system were
 10À3 sÀ1
.
To further understand the relationship between the structural
changes of CTF and its complex with hydrazine and the optical re-
sponse of CTF to hydrazine, a theoretical calculation was carried
out by Density Functional Theory (DFT) and Time Dependent Den-
sity Functional Theory (TDDFT) with the B3LYP/6-31+G(d,p) meth-
od basis set using the Gaussian 03 program.
The optimized geometry and the highest occupied molecular
orbital (HOMO) and lowest unoccupied molecular orbital (LUMO)
of CTF and its hydrazine complex are presented in Figure 6. UV–
vis spectra of CTF and its hydrazine complex were calculated using
Figure 6. Energy diagrams of HOMO and LUMO orbitals of CFT and CTF-hydrazine complex calculated at the DFT level using a B3LYP/6-31+G(d,p) basis set.

2698
S. Goswami et al. / Tetrahedron Letters 55 (2014) 2695–2699
calculated. For CTF,
s = 0.646 ns (,
2 = 0.969) and CTF+N2H4,
s
= 2.867 ns (
The fluorescence decay curves of CTF and the CTFÀN2H4 com-
pounds were fitted by utilizing the bi-exponential functions with
,
2 = 1.029).
1000
100
10
2
the acceptable
, values (Supplementary data, Table S2). The
changes in kr and knr values are attributed to the reaction of hydra-
zine with CTF to form a new fluorescent compound CTFÀN2H4.
Dip-stick is a very simple but very important experiment be-
cause it gives instant qualitative information without resorting to
the instrumental analysis. In order to perform this experiment
we prepared TLC plates which were further immersed into the
solution of CTF (2 Â 10À4 M) in acetonitrile, and then evaporating
the solvent to dryness. We immersed the TLC plate in N2H4
(2 Â 10À3 M) solution and then exposed it in air to evaporate the
solvent. The color of the TLC plates changes from brownish-yellow
to greenish yellow (Fig. 8). Now this experiment evokes a real time
monitoring and it is devoid of using any instrumental analysis. Just
by naked-eye detection and use of TLC plates we can easily inves-
tigate a qualitative instant detection of N2H4.
1
0
10
20
30
40
50
60
Life time τ (ns)
Figure 7. Time-resolved fluorescence decay of CTF (Red), CTF+N2H4 (green), and
prompt (black) (kex = 450 nm).
Selectivity and interference are the two very vital constraints to
estimate the performance of a receptor. The interference of other
competing analytes was investigated by the competition experi-
ment which is demonstrated in Figure 9. When CTF is treated with
2.0 equiv of hydrazine in the presence of other analytes in the same
concentration, the detection of hydrazine in the presence of other
analytes is not troubled, that is, the interference in the detection of
the hydrazine is not observed. So CTF can be used as a selective and
sensitive sensor for the hydrazine.
In summary, in this Letter a coumarin functionalized fluoro-
phore linked with trifluroacetyl acetone has been designed and
synthesized for the chemodosimetric detection of hydrazine. The
photophysical properties of CTF in CH3CN solution were observed
and the changes are remarkably different from those of other ana-
lytes. It shows a high selectivity toward hydrazine at the molecular
level (solution) and in solid material (absorbed in TLC plates). The
spectroscopic studies are further supported by DFT and TDDFT
calculations. The detection limit of our probe CTF is in micro molar
range.
Figure 8. Photographs of TLC plates after immersion in a CTF-acetonitrile solution
(a and c) and after immersion in a CTFÀN2H4–acetonitrile solution (b and d) taken
in ambient light (left) and under hand-held UV light (right).
0.8
0.6
0.4
0.2
0.0
Acknowledgments
The authors thank the CSIR and DST, Government of India for
financial support. S.D., K.A. and D.S. acknowledge CSIR for provid-
ing them with fellowships.
-
-
-
+
-
-
Supplementary data
+
2
+
2
2
2+
2+
2+
2-
3
3
2
3
4
en
S
N
SO
Na
Zn
Cd Hg
Cu
NO
TEA
NO
Mn
SO
H
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.03.
041.
Figure 9. Change of absorbance of CTF after adding 2.0 equiv of each of the
investigated guest analytes in CH3CN at 485 nm.
References and notes
the TDDFT method in acetonitrile medium. Calculated absorption
peaks had agreed well with the experimentally observed peaks
(Supplementary data, Table S1). In case of CTF, the transition from
HOMO to LUMO and HOMO—2 to LUMO had contributed mainly to
the excitation at 459 and 298 nm, respectively. For the CTFÀN2H4,
main absorption peaks in the short wavelength region were at 394
and 283 nm generated from the transition of HOMO to LUMO and
HOMO—1 to LUMO, respectively (Supplementary data, Table S1).
A nano second time-resolved fluorescence technique has been
adapted in order to examine the excited state behavior of
our probe CTF sensor and its reaction based product with hydra-
1. (a) Wang, R.; Yu, C.; Yu, F.; Chen, L. Trends Anal. Chem. 2010, 29, 1004–1013; (b)
Chen, X.; Tian, X.; Shin, I.; Yoon, J. Chem. Soc. Rev. 2011, 40, 4783–4804.
2. (a) Hydrazine and Its Derivatives, 5th ed. In Kirk-Othmer Encyclopedia of
Chemical Technology; Kroschwitz, J. I., Seidel, A., Eds.; Wiley: NewYork, 2005;
13, pp 562–607; (b) Mo, J.-W.; Ogorevc, B.; Zhang, X.; Pihlar, B. Electroanalysis
2000, 12, 48–54; (c) Zelnick, S. D.; Mattie, D. R.; Stepaniak, P. C. Aviat. Space
Environ. Med. 2003, 74, 1285–1291.
3. Serov, A.; Kwak, C. Appl. Catal., B 2010, 98, 1–9.
4. (a) Ragnarsson, U. Chem. Soc. Rev. 2001, 30, 205–213; (b) Garrod, S.; Bollard, M.
E.; Nicholls, A. W.; Connor, S. C.; Connelly, J.; Nicholson, J. K.; Holmes, E. Chem.
Res. Toxicol. 2005, 18, 115–122; (c) Narayanan, S. S.; Scholz, F. Electroanalysis
1999, 11, 465–469.
5. Batchelor-McAuley, C.; Banks, C. E.; Simm, A. O.; Jones, T. G. J.; Compton, R. G.
Analyst 2006, 131, 106–110.
zine in CH3CN solvent (Fig. 7). According to the equations13 sÀ1
kr + knr, where kr = Uf , the radiative rate constant kr and the total
non-radiative rate constant knr of CTF and CTFÀN2H4 species were
=
/s
6. Elder, D. P.; Snodin, D.; Teasdale, A. J. Pharm. Biomed. Anal. 2011, 54, 900–910.
7. Sun, M.; Bai, L.; Lui, D. Q. J. Pharm. Biomed. Anal. 2009, 49, 529–533.

S. Goswami et al. / Tetrahedron Letters 55 (2014) 2695–2699
2699
8. Bhutani, H.; Singh, S.; Vir, S.; Bhutani, K. K.; Kumar, R.; Chakraborti, A. K.; Jindal,
K. C. J. Pharm. Biomed. Anal. 2007, 43, 1213–1220.
9. Liu, J.; Zhou, W.; You, T.; Li, F.; Wang, E.; Dong, S. Anal. Chem. 1996, 68, 3350–
3353.
11. (a) Goswami, S.; Aich, K.; Das, S.; Das, A. K.; Manna, A.; Halder, S. Analyst 2013,
138, 1903–1907; (b) Goswami, S.; Das, S.; Aich, K. Tetrahedron Lett. 2013, 54,
4620–4623; (c) Goswami, S.; Aich, K.; Das, S.; Das, A. K.; Sarkar, D.; Panja, S.;
Mondal, T. K.; Mukhopadhyay, S. K. Chem. Commun. 2013, 10739–10741; (d)
Goswami, S.; Das, S.; Aich, K.; Sarkar, D.; Mondal, T. K.; Quah, C. K.; Fun, H.-K.
Dalton Trans. 2013, 42, 15113–15119; (e) Goswami, S.; Aich, K.; Das, A. K.;
Manna, A.; Das, S. RSC Adv. 2013, 3, 2412–2416; (f) Goswami, S.; Aich, K.; Sen,
D. Chem. Lett. 2012, 41, 863; (g) Goswami, S.; Das, S.; Aich, K.; Sarkar, D.;
Mondal, T. K. Tetrahedron Lett. 2013, 54, 6892–6896.
12. Liu, J.; Sun, Y.-Q.; Zhang, J.; Yang, T.; Cao, J.; Zhang, L.; Guo, W. Chem.-Eur. J.
2013, 19, 4717–4722.
13. Valeur, B. Molecular Fluorescence. Principles and Applications; Wiley-VCH:
Weinheim, Germany, 2002.
10. (a) Choi, M. G.; Hwang, J.; Moon, J. O.; Sung, J.; Chang, S.-K. Org. Lett. 2011, 13,
5260–5263; (b) Choi, M. G.; Moon, J. O.; Bae, J.; Lee, J. W.; Chang, S.-K. Org.
Biomol. Chem. 2013, 11, 2961–2965; (c) Fan, J.; Sun, W.; Hu, M.; Cao, J.; Cheng,
G.; Dong, H.; Song, K.; Liu, Y.; Sun, S.; Peng, X. Chem. Commun. 2012, 8117–
8119; (d) Chen, X.; Xiang, Y.; Li, Z.; Tong, A. Anal. Chim. Acta 2008, 625, 41–46;
(e) Zhu, S.; Lin, W.; Yuan, L. Anal. Methods 2013, 5, 3450–3453; (f) Goswami, S.;
Das, S.; Aich, K.; Pakhira, B.; Panja, S.; Mukherjee, S. K.; Sarkar, S. Org. Lett. 2013,
15, 5412–5415; (g) Lee, M. H.; Yoon, B.; Kim, J. S.; Sessler, J. L. Chem. Sci. 2013, 4,
4121–4126; (h) Hu, C.; Sun, W.; Cao, J.; Gao, P.; Wang, J.; Fan, J.; Song, F.; Sun,
S.; Peng, X. Org. Lett. 2013, 15, 4022–4025.