A highly selective ratiometric chemosensor for Hg2+ based on the anthraquinone derivative with urea groups

Article abstract of DOI:10.1016/j.tet.2007.04.086

Anthraquinone derivatives with different substituents 1-3 were synthesized by introducing the urea group. Their cations' binding properties were investigated by UV-vis absorption spectroscopy. Compared with 1 and 2, 3 with electron-withdrawing group (-NO<

Full text of DOI:10.1016/j.tet.2007.04.086

Tetrahedron 63 (2007) 6732–6736
A highly selective ratiometric chemosensor for Hg2D based
on the anthraquinone derivative with urea groups
*
Hong Yang, Zhi-Guo Zhou, Jia Xu, Fu-You Li, Tao Yi and Chun-Hui Huang
*
Department of Chemistry and Laboratory of Advanced Materials, Fudan University, 200433 Shanghai, PR China
Received 17 January 2007; revised 25 April 2007; accepted 26 April 2007
Available online 3 May 2007
Abstract—Anthraquinone derivatives with different substituents 1–3 were synthesized by introducing the urea group. Their cations’ binding
properties were investigated by UV–vis absorption spectroscopy. Compared with 1 and 2, 3 with electron-withdrawing group (–NO2)
showed a remarkable absorption change for Hg2+ over the other metal ions. The anthraquinone moiety and the N–H fragment of the urea
moiety played key roles in sensing Hg2+. The different acidity of N–H fragments of the urea moiety, caused by electron push–pull properties
of the substituents on the phenyl para position, is the main reason for recognition.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
colorimetric receptors of anion sensors based on hydrogen
bond mechanism.7–8 However, urea receptors have rarely
attracted interest in recognizing heavy metal ions.9 Recently,
we have succeeded in detecting Cu2+ bearing two urea
groups as the receptor.9b In the present study, using the an-
thraquinone as chromophore, compounds 1–3 (see Scheme
1) with the urea group were synthesized to detect Hg2+.
The recognition–structure relationship was studied by intro-
ducing the electron-donating and electron-withdrawing
groups. Interestingly, 3 showed a colorimetric recognition
for Hg2+ with a high selectivity.
Design and synthesis of new chemosensors for transition and
heavy metal ions have been of interest to chemists for many
years because these ions play important roles in the areas of
biological, environmental, and chemical systems.1 As one of
the most important environmental pollutants and an essential
trace element in various biological systems, the Hg2+ recog-
nition in particular has received more attention by using the
colorimetric,2 fluorogenic,3 redox-active method,4 and che-
modosimeter.5 According to the hard–soft acid–base theory,
6 nitrogen and sulfur binding sites may be the best choice for
the selective recognition of soft heavy metal ion Hg2+. Up to
now, most receptors were still limited to be polyaza or thia-
based chromophore. As one type of important receptors,
urea groups have been widely adapted as fluoregenic and
2. Results and discussion
According to the literature, compounds 1 and 3 were synthe-
sized by the reaction of anthraquinone diamine with the cor-
responding urea.10 As shown in Scheme 2, 2 was synthesized
by the condensation of 1,2-diaminoanthraquinone and the
intermediate 5.
N
N
NO2
NO2
NO2
NO2
NH HN
NH HN
NH HN
N
N
O
O
O
O
O
O
O
O
O
NH HN
HN
HN
HN
HN
HN
HN
O
O
O
NH2
NH2
HN
HN
N
N
HN
HN
NH
NaN3
THF
O
THF
O
O
O
O
O
O
HN
1
2
3
4
COCl
CON3
5
Scheme 1. Chemical structures of 1–3 with different substituents and the
control compound 4.
2
O
* Corresponding authors. Tel.: +86 21 55664185; e-mail addresses: fyli@
fudan.edu.cn; chhuang@pku.edu.cn
Scheme 2. Synthetic routine of 2.
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.04.086

H. Yang et al. / Tetrahedron 63 (2007) 6732–6736
6733
4
3
2
1
0
1.5
0.16
0.12
0.08
0.04
0.00
1.2
0.9
0.6
Chi^2 = 0.00001
R^2
k
=
0.99364
5
6.0 × 10
0.0
0.4
[Hg ] × 10 mol.L
0.8
1.2
-1
1.6
357 nm (3)
2+
-5
422 nm (1)
490 nm (2)
0.3
0.0
300
400
Wavelength / nm
500
600
300
4
00
Wavelength / nm
50
0
600
Figure 1. Absorption spectra of 1 (---), 2 (/), and 3 (—) in solution
(5ꢁ10ꢀ5 mol Lꢀ1) at room temperature.
Figure 2. Changes in absorption spectra of 3 (50 mM) in CH3CN/DMSO
(9:1, v/v) upon addition of Hg2+ (0–6 equiv).
To explore practical applicability of 3 as a Hg2+-selective
naked eye chemosensor, the titration experiments were
also investigated in the mixed solvent of DMSO/H2O¼1:1.
The similar spectral changes of 3 were observed upon addi-
tion of Hg2+. The association constant for 3–Hg2+ complex
at 298 K was calculated to be 4.2ꢁ105 Mꢀ1. This fact indi-
cated that this system could be used in semi-aqueous system.
The absorption spectra of 1–3 in the mixed solution of
DMSO/CH3CN (v/v¼1:9) are shown in Figure 1. Com-
pounds 1 and 2 exhibited strong absorbance at 422 and
490 nm with the molar extinction coefficients (3) of w105,
respectively, which were ascribed to the charge-transfer
interaction (CT1) between the electron-rich urea moiety
and the electron-deficient anthraquinone moiety. Compound
3 had a strong absorbance maximum around 357 nm and a
weaker absorbance at 420 nm. The former was assigned to
the intramolecular charge-transfer transition (CT2) between
the strong electron-withdrawing ability of nitro group and
the electron-rich urea groups and the later was consistent
with the CT1 band. Obviously, 2 with electron-donating
group (–N(CH3)2) and 3 with electron-withdrawing group
(–NO2) showed red-shifted and blue-shifted CT1 band in
comparison with 1, respectively. Therefore, the introduction
of push–pull substituents affected obviously the photo-phys-
ical properties of compounds 1–3. The shift evidently was
arisen from the different push–pull substituent. Especially,
the stronger electron-donating ability of N,N-dimethylamino
group in compound 2 induced a large red shift of 68 nm com-
pared with 1.
For an excellent chemosensor, high selectivity is a matter of
necessity. To examine the selectivity of 3, we investigated its
affinity for other metal cations. The experimental results
suggested that 3 showed a high selectivity in colorimetric
sensing Hg2+. As depicted in Figure 3, 3 showed scarcely
any response with other metal ions, such as Cu2+, Ag+,
Cd2+, Cr3+, Fe3+, Ni2+, and Zn2+.
Furthermore, competition experiments were also performed
for 3 in the presence of Hg2+ at 50 mM mixed with 200 mM
background metal cations such as Fe3+, Co2+, Ni2+, and Zn2+
(Fig. 3). In the presence of other metal ions, no obvious
variation in the absorption was observed in sensing Hg2+.
Importantly, the presence of Ag+ and Cd2+ did not affect
the selectivity of 3 for Hg2+. All these results implied that
The complexation abilities of 1–3 with Hg2+ ion were inves-
tigated by the UV–vis absorption techniques. In our present
experiments, Hg(ClO4)2 as a Hg2+ source was gradually
added to the CH3CN/DMSO (9:1, v/v) solution of 1–3.
The changes in the UV–vis spectra of 3 upon addition of
Hg2+ are presented in Figure 2. Notably, the CT1 band at
420 nm decreased gradually, and the new band at 488 nm
appeared and concomitantly grew with increasing Hg2+ con-
centration with a isosbestic point of 456 nm, indicating an
interaction between Hg2+ and 3 in the ground state. Of
course, the above results were not due to the presence of
ClOꢀ4 (see the Supplementary data). The facts suggested
that the presence of Hg2+ influenced the charge-transfer
from the electron-rich urea groups to the electron-deficient
anthraquinone moiety. A Job’s plot (see Supplementary
data) indicated that 3 formed a 1:1 complex with Hg2+ ion
in CH3CN/DMSO (9:1, v/v) solution. The association con-
stant for 3–Hg2+ complex at 298 K was estimated to be
6.0ꢁ105 Mꢀ1, which could be comparable to those of the
Hg2+-sensor reported previously.11
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
Figure 3. Absorption ratiometric responses of 3 (50 mM) to various metal
ions (200 mM) in CH3CN/DMSO (9:1, v/v). Bars represent the intensity ra-
tios of absorption at 488 nm to that at 425 nm. Black bars represent response
of 3 to different metal ions; blank bars responses of 3 containing 50 mM
Hg2+ to different metal ions.

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H. Yang et al. / Tetrahedron 63 (2007) 6732–6736
Figure 4. Optimized geometries for the free receptor 3 (a) and its complexes with Hg2+(b).
3 could be used as a potential candidate of Hg2+ chemosen-
sor with very high selectivity.
The acidity of N–H fragments in urea moiety of 3 is en-
hanced for the existence of nitro-group and anthraquinone
ring, and the deprotonation of 3 becomes easier in compar-
ison with that of 1. At this point, the coordinating ability
of 3 can be improved between nitrogen of N–H fragments
and Hg2+. On the contrary, for 2, the introduction of the
electron-donating group can enhance the electron density
of N–H fragments and consequently increases the basicity,
and the deprotonation becomes more difficult. So no obvious
new peak in the UV–vis absorption spectrum for 2 was
observed.
For comparison, the recognition of 1 and 2 to Hg2+ were also
investigated. However, few changes were observed for 1 and
2 upon addition of Hg2+ (see Supplementary data), indicat-
ing weak complexation ability of 1 and 2 with Hg2+. In the
light of the observation of strong complexation of 3 with
Hg2+, we can conclude that the electron-withdrawing sub-
stituent (–NO2) plays an important role in reorganization
of 3 to Hg2+.
Accordingly, on the basis of the evidence mentioned above,
we can conclude that the bis-urea group attached electron-
withdrawing group (–NO2) plays a key role in sensing
Hg2+. To explore the complexation site, the structure of 3
and 3–Hg2+ were optimized at the B3LYP density function
theory and the results are shown in Figure 4. The SDD basis
set was used to treat the Hg atom, whereas 3-21G** basis set
was used to treat all other atoms for 3–Hg2+. The urea groups
in 3 orient almost perpendicular to the anthraquinone ring.
Upon complexation of 3 with Hg2+, one of the amide units
(no interaction with Hg2+) lies in the plane of anthraquinone
ring, but the other amide group (the interaction with Hg2+)
derived from planarity by w49ꢂ. The intramolecular
N–H/O hydrogen bond distance of 3 calculated at
3. Conclusions
In conclusion, we developed a highly selective ratiometric
Hg2+ chemosensor. The recognition of Hg2+ gave rise to
the ratiometric change at the ratio of the absorption intensity
of 420 and 488 nm for the complexation. Anthraquinone
moiety is not only the signaling subunits but also plays a re-
ceptor role. For urea moiety as a receptor, the acidity of N–H
fragments is a key point to detect Hg2+ selectively. Such a de-
sign strategy would be of great interest in the development of
other chemosensors for heavy and transition metal cations.
˚
B3LYP/6-31G** is 1.782 A between the anthraquinone
oxygen and the amide carbonyl group (see Fig. 4a). After
4. Experimental
4.1. General
addition of Hg2+, the N/Hg and O/Hg bond distances
˚
were calculated to be 2.575 and 2.397 A, respectively (see
Fig. 4b), and the N–H/O bond is much longer than that
in the absence of Hg2+, which are significantly deviated
from the presence of the interaction between Hg2+ and an-
thraquinone oxygen. That is, Hg2+ breaks the intramolecular
N–H/O hydrogen bond between the anthraquinone oxygen
and the N–H group, and the carbonyl group of anthraquinone
in 3 participates in the coordination of Hg2+. As a similar
urea derivative of 3, 4 was synthesized, and the calculated re-
sults prompted us to investigate the complexation of 4 with
Hg2+. No change in UV–vis spectra was observed upon ad-
dition of Hg2+ and other metal ions (see Supplementary
data). This fact indicated that the carbonyl group of anthra-
quinone in 3 played an important role in complexation of
Hg2+. Therefore, we can conclude that both the anthraqui-
none moiety and the urea moiety in conjugation with strong
electron-withdrawing groups are necessary bonding-site for
detecting Hg2+.
The 1H NMR spectrum was recorded at 400 MHz on a Varian
Gemin-400. UV–vis spectra were measured on UV–vis 2550
spectroscope (Shimadzu). The titration experiments were
carried out in CH3CN/DMSO mixture (9:1, v/v) by adding
aliquots of metal ion solution.
4.1.1. Urea(N,N0-(9,10-dihydro-9,10-dioxo-1,2-anthra-
cenediyl)bis[N0-phenyl]) (1). 1,2-Diaminoanthraquinone
(238 mg, 1.0 mmol) was dissolved in a solvent mixture of
dry DMF and THF (1:5 v/v) .To this solution was added
phenylisocyanate (357 mg, 3.0 mmol) and stirred under inert
atmosphere at 80 ꢂC for 6 h. The reaction mixture was cooled
to room temperature. Precipitate formed was filtered and
washed thoroughly with THF and acetonitrile, respectively.10a
Compound 1: 1H NMR: (400 MHz, DMSO-d6, ppm) d 9.77
(s, 1H), 9.70 (s, 1H), 9.10 (s, 1H), 8.60 (s, 1H), 8.65 (d,

H. Yang et al. / Tetrahedron 63 (2007) 6732–6736
6735
J¼8.0, 1H), 8.15–8.17 (m, 3H), 7.90–7.91 (m, 2H), 7.54 (d,
J¼8.0, 2H), 7.47 (d, J¼8.0, 2H), 7.28–7.30 (m, 4H), 6.98–
7.00 (m, 2H). 13C NMR: (100 MHz, DMSO-d6, ppm) d
207.8, 185.6, 182.1, 154.1, 152.7, 143.2, 140.3, 139.7,
135.1, 134.7, 133.0, 129.6, 129.5, 129.0, 128.1, 127.5,
127.3, 126.9, 126.3, 125.4, 123.1, 122.8, 119.0, 118.8.
Anal. Calcd for C28H20N4O4: C, 70.58; H, 4.23; N, 11.76.
Found: C, 70.89; H, 4.21; N, 11.69.
1H NMR: (400 MHz, DMSO-d6, ppm) d 9.82 (s, 2H), 8.83
(s, 2H), 8.18 (d, J¼8.0, 4H), 7.69 (d, J¼8.0, 4H), 7.61–
7.59 (m, 2H), 7.16–7.13 (m, 2H). 13C NMR: (100 MHz,
DMSO-d6, ppm) d 153.2, 146.9, 141.7, 131.4, 125.8,
125.5, 125.1, 118.1.
Acknowledgements
4.1.2. Azido(4-(dimethylamino)phenyl)methanone (5).
4-(Dimethylamino)benzoyl chloride (1.84 g, 0.01 mol) was
dissolved in 20 mL THF and dropped into 50 mL NaN3
solution (6.5 g, 0.1 mol) under ice bath. The reaction mixture
was stirred overnight, the precipitate was filtered and 4-(dime-
thylamino)benzoyl chloride was obtained as a yellow solid.
The crude product was purified by column chromatography
on silica gel with chloroform/petrol ether (1:1) as the eluent
to obtain pure 5. The product was obtained in 70% yield.10b
The authors thank the National Science Foundation of China
(20490210, 20501006 and 20571016), Shanghai Science
Technology Committee (05DJ14004) and the China
Postdoctoral Science Foundation for financial support.
Supplementary data
UV–vis spectra of 1, 2, and 4 with different metal ions;
UV–vis spectra of 3 with [(Bu)4N]ClO4; UV–vis spectra
of 3 with different content of Hg2+ in H2O/DMSO (1:1,
v/v) solution; Job’s plot of 3; calculation methods and results
of the energy minimized structure; NMR spectra of com-
pound 1–4. Supplementary data associated with this article
can be found in the online version, at doi:10.1016/
j.tet.2007.04.086.
1
Compound 5: H NMR: (CDCl3-d, ppm) d 7.87 (d, J¼8.0,
2H, ArH), 6.61 (d, J¼8.0, 2H, ArH), 3.01 (s, 6H, –N(CH3)2).
4.1.3. Urea(N,N0-(9,10-dihydro-9,10-dioxo-1,2-anthra-
cenediyl)bis[N0-4-dimethylamino-phenyl]) (2). The proce-
dure followed was the same as that for receptor 1. To a
solution of 0.36 g (1.5 mmol) 1,2-diaminoanthraquinone in
a 40 mL DMF solution was slowly added 1.14 g (6.0 mmol)
5 in 20 mL of THF over 30 min and refluxed for 6 h in a
nitrogen atmosphere. The solid product was collected by fil-
tration and washed with acetone. The product was obtained
in a 65% yield.
References and notes
1. B}uhlmann, P.; Pretsch, E.; Bakker, E. Chem. Rev. 1998, 98,
1593.
Compound 2: 1H NMR: (400 MHz, DMSO-d6, ppm) 8.21 (s,
1H), 8.19 (s, 1H), 8.13 (s, 1H), 8.10 (s, 1H), 7.96 (d, J¼8.0,
1H), 7.83–7.89 (m, 4H), 7.52 (d, J¼8.0, 2H), 7.27 (d, J¼8.0,
3H), 6.69 (d, J¼8.0, 4H), 2.80 (s, 9H), 2.78 (s, 3H). 13C
NMR: (100 MHz, DMSO-d6, ppm) d 185.2, 182.6, 171.2,
153.2, 147.4, 144.4, 135.0, 134.9, 134.4, 133.4, 133.3,
129.5, 128.6, 127.2, 126.9, 126.0, 120.9, 117.8, 113.8,
60.5. Anal. Calcd for C32H30N6O4: C, 68.31; H, 5.37; N,
14.94. Found: C, 68.01; H, 5.69; N, 15.21.
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Ros-Lis, J. V.; Marcos, M. D.; Martınez-Manez, R.; Rurack,
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4.1.4. Urea(N,N0-(9,10-dihydro-9,10-dioxo-1,2-anthra-
cenediyl)bis[N0-4-nitrophenyl]) (3). The procedure followed
was similar to that for receptor 1. 4-Nitro-phenylisocyanate
(492 mg, 3.0 mmol) was used instead of phenylisocyanate.
Yield: 80%.
ꢀ
ꢀ
4. Lloris, J. M.; Martınez-Man˜ez, R.; Padilla-Tosta, M. E.; Pardo,
T.; Soto, J.; Beer, P. D.; Cadman, J.; Smith, D. K. J. Chem. Soc.,
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Compound 3: 1H NMR: (400 MHz, DMSO-d6, ppm) d 10.50
(s, 1H, NH), 10.28 (s, 1H, NH), 9.171 (s, 1H, NH), 8.76 (s,
1H, NH), 8.66 (d, J¼7.2, 1H), 8.19–8.23 (t, J¼8.0, 6H),
7.92–7.95 (m, 3H), 7.77 (d, J¼8.0, 2H), 7.70 (d, J¼8.0,
2H). 13C NMR: (100 MHz, DMSO-d6, ppm) d 185.3, 182.1,
171.2, 163.2, 153.7, 152.2, 146.8, 146.2, 142.5, 142.1,
141.9, 135.2, 134.7, 133.0, 128.7, 128.3, 127.7, 127.5,
127.1, 127.0, 126.8, 125.9, 118.4, 118.2. Anal. Calcd for
C28H18N6O8: C, 59.37; H, 3.20; N, 14.84. Found: C,
59.13; H, 3.22; N, 14.78.
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4.1.5. N,N0-1,2-(Phenylenebis-[N0-p-nitrophenylurea])
(4). The procedure followed was similar to that for receptor
1. 1,2-Diaminobenzene (108 mg, 1.0 mmol) was used in-
stead of 1,2-diaminoanthraquinone. Yield: 85%.
9. (a) Basabe-Desmonts, L.; Beld, J.; Zimmerman, R. S.;
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calculated from the following equation: A¼A0+((AlimꢀA0)/
2C0)(C0+[M]+1/Kꢀ((C0+[M]+1/K)2ꢀ4C0[M])0.5), where A
and A0 are the absorbance for 3 (at 488 nm) in the presence
and absence of Hg2+; C0 is half of the concentration of 3;
[M] is the concentration of the Hg2+; and Alim is the limiting
.
(Xue, H.; Tang, X. J.; Wu, L. Z.; Zhang, L. P.; Tung, C. H.
J. Org. Chem. 2005, 70, 9727).
10. (a) Jose, D. A.; Kumar, D. K.; Ganguly, B.; Das, A. Org. Lett.
2004, 6, 3445; (b) Okaniwa, M.; Takeuchi, K.; Asai, M.; Ueda,
M. Macromolecules 2002, 35, 6224.
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J. Org. Chem. 2005, 70, 5827. The binding constant (K) was
value of the absorbance in the presence of excess Hg2+