Hg2+ and Cu2+ selective detection using a dual channel receptor based on thiopyrylium scaffoldings

Article abstract of DOI:10.1016/j.tetlet.2009.04.060

2,4,6-Triphenylthiopyrylium functionalized with an aza-oxa-thia macrocycle is able to selectively recognize Hg²⁺ cation by a color change and Cu²⁺ cation by a remarkable significant emission enhancement.

Full text of DOI:10.1016/j.tetlet.2009.04.060

Tetrahedron Letters 50 (2009) 3885–3888
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Hg2+ and Cu2+ selective detection using a dual channel receptor based
on thiopyrylium scaffoldings
a
a,b,c
Tatiana Ábalos a,b,c, Diego Jiménez b, Ramón Martínez-Máñez a,b,c, , Jose Vicente Ros-Lis , Santiago Royo
,
*
Félix Sancenón a,b,c, , Juan Soto a,b, Ana M. Costero a,d, Salvador Gil a,d, Margarita Parra a,d
*
a Instituto de Reconocimiento Molecular y Desarrollo Tecnológico, Centro Mixto Universidad Politécnica de Valencia-Universidad de Valencia, Spain
b Departamento de Química, Universidad Politécnica de Valencia, Camino de Vera s/n, 46022 Valencia, Spain
c CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN)
d Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universitat de Valencia, 46100 Burjassot, Valencia, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
2,4,6-Triphenylthiopyrylium functionalized with an aza-oxa-thia macrocycle is able to selectively recog-
nize Hg2+ cation by a color change and Cu2+ cation by a remarkable significant emission enhancement.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 24 February 2009
Revised 11 April 2009
Accepted 15 April 2009
Available online 20 April 2009
Keywords:
Dual channel receptor
Chromogenic Hg2+ recognition
Fluorogenic Cu2+ recognition
Thiopyrylium derivative
One of the more promising fields within supramolecular chem-
istry deals with the preparation of optical probes for target guest.1
The chemosensors are generally formed by two moieties, namely a
binding site and a signaling subunit connected through a covalent
bond. The binding site is responsible for the interaction with the
host and is designed bearing in mind supramolecular chemistry
principles in order to achieve a high degree of complementarity be-
tween both components. In the probes, this interaction between
the binding site and the host is transformed in an easy-to-observe
output by the signaling subunit. Three main groups have been
extensively employed as reporter subunits: fluorescent groups,2
organic dyes,3 and redox-active moieties.4
The coupling of several binding sites, generally of macrocyclic
nature, and certain optical signaling subunits has led to the devel-
opment of a number of receptors for the selective recognition and
for sensing of metal cations.5 In spite of this work it is noticeable
that there are relatively few examples of receptors capable of dis-
playing two or more output signals (different signaling channels)
upon cation binding. This could be achieved by the use of two or
more signaling subunits attached near the binding site6 or by the
use of one unique signaling group capable of displaying two or
more observable events (usually fluorescence, color changes, or
electrochemical modulations).7 Additionally, it is remarkable that
receptors that are able to display sensing abilities to different cat-
ions when using different signaling channels are very rare. How-
ever, these systems can be of interest for designing future probes
that are able to signal, not just one, but multiple analytes.
In this Letter, we show the synthesis, metal coordination ability,
and dual sensing features of a 2,4,6-triphenylthiopyrylium deriva-
tive functionalized with a macrocycle containing nitrogen, oxygen,
and sulfur atoms. Thiopyrylium salts have been extensively used as
photosensitizers in a great range of photochemical transforma-
tions.8 However, as far as we know, the thiopyrylium moiety has
never been used as signaling subunit for the development of opti-
cal chemosensors and only recently our research group used the
pyrylium-to-thiopyrylium transformation for the development of
a novel chromogenic chemodosimeter for sulfide anion that dis-
played sensing features in aqueous environments.9
The synthesis of receptor L1 was achieved following a four-step
procedure from N-phenyldiethanolamine (1) (see Scheme 1). The
first step consists of the mesylation of 1 with mesyl chloride in
dichloromethane and triethylamine. The obtained dimesylated
derivative (2) was reacted with 3,6-dioxaoctane-1,8-dithiol (3) to
give the macrocycle 10-phenyl-10-aza-1,4-dioxa-7,13-dithiacycl-
opentadecane (4) in 40% yield.7c Electrophilic aromatic substitu-
tion reaction between 4 and 2,6-diphenylpyrylium perchlorate
(5) yields the pyrylium salt derivative 6 in a 40% yield. Finally
receptor L1 was obtained upon reaction of compound 6 with
Na2S in acetone and subsequent acidification.10
* Corresponding authors.
E-mail address: fsanceno@upvnet.upv.es (F. Sancenón).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.04.060

3886
T. Ábalos et al. / Tetrahedron Letters 50 (2009) 3885–3888
L1
O
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
O
OH
OH
OMs
OMs
O
O
L1+ Al3+
L1+ Fe3+
L1+ Cu2+
N
N
3
S
S
SH
HS
MsCl
Et3N / CH2Cl2
N
K2CO3 / acetonitrile
High dilution
4
1
2
L1+ Hg2+
DMF
O
O
O
O
O
Aosrbance
S
N
S
S
S
5
N
O
Na2S / acetone
HClO4
L1
6
300
400
500
Wavelength (nm)
600
700
S
Figure 1. UV–visible spectra of receptor L1 in acetonitrile (1.0 Â 10À5 mol dmÀ3) and
L
1 in the presence of 10 equiv of Hg2+, Al3+, Fe3+, and Cu2+. The inset shows the color
Scheme 1. Reagents and conditions for the synthesis of receptor L1.
changes observed for acetonitrile solutions of receptor L1 (1.0 Â 10À5 mol dmÀ3) in
the presence of 10 equiv of the corresponding metal cations. From left to right:
receptor alone, Ag+, Al3+, Cd2+, Cu2+, Fe3+, Hg2+, Ni2+, Pb2+, and Zn2+
.
Acetonitrile solutions of L1 showed a blue coloration due to the
presence of a broad structureless intense band in the visible zone
centered at 575 nm. The optical behavior can be tentatively attrib-
uted to allowed internal charge transfer (ICT) transitions due to the
presence of an electron donor aniline group and an electron
acceptor thiopyrylium moiety in the molecular skeleton.11 Also a
relatively less intense band in the near-UV zone centered at ca.
400 nm was observed.
cent and excitation of acetonitrile solutions of receptor L1 at the
bands of 575 or 400 nm resulted in no significant emission in the
range of 460–600 nm due to the existence of a very effective
non-radiative deactivation of the excited state most likely due to
the presence of the anilinium group. However, in the presence of
protons there is appearance of a new emission at 500 nm attrib-
uted to the protonated L1. The intensity of this emission band
reaches the highest intensity upon addition of 50 equiv of protons
as could be seen in Fig. 2. This emission, and also the absorption
band at 400 nm, correspond well with the optical properties of
the parent 2,4,6-triphenylthiopyrylium neat dye that lacks any
donor in the 4-position (kab = 400 nm and kem = 502 nm in
acetonitrile).13
Protonation studies suggest that the engagement of aniline
nitrogen lead to a partial suppression of the non-radiative deacti-
vation path resulting in a restoration of the 2,4,6-triphenylthio-
pyrylium emission. Therefore, further fluorescence studies
involving metal cations and L1 were carried out. The addition of
up to 10 equiv of Cd2+, Ni2+, Pb2+, and Zn2+ did not induce the
appearance of any significative emission band in the range of
460–600 (kex = 400 nm). In contrast, the addition of Al3+ and Fe3+
to L1 induced a 3.2- and 4.6-fold emission enhancement of the
band centered at 500 nm, respectively. At the same time addition
In a first step the chromogenic behavior of acetonitrile solutions
of receptor L1 (1.0 Â 10À5 mol dmÀ3) was tested in the presence
(10 equiv) metal cations (Ag+, Al3+, Cd2+, Cu2+, Fe3+, Hg2+, Ni2+
,
Pb2+, and Zn2+). Since the cation binding unit is in the donor side
of the molecule, it would be expected that coordination of cations
would reduce the donor character and produce a hypsochromic
shift through a modulation of the energetic positions of the HOMO
and LUMO orbitals. The presence of Ag+, Cd2+, Ni2+, Pb2+, and Zn2+
resulted in negligible changes in the visible spectra of L1 indicating
no coordination, whereas Al3+, Cu2+, and Fe3+ gave a small hypo-
chromic effects of the charge transfer band that does not induce
any remarkable change in the color of the solutions. Moreover,
the most remarkable outcome was the selective chromogenic re-
sponse observed in the presence of Hg2+ cation; a large hypochro-
mic effect on the band centered at 575 nm together with a
hypsochromic shift of 40 nm was observed, resulting in a color
modulation from blue to faint yellow (see Fig. 1). The response is
fully consistent with coordination of Hg2+ to the macrocycle.
Addition of increasing quantities of Hg2+ to acetonitrile solu-
tions of L1 allowed us to measure, through a least square treatment
of the titration profile, the logarithm of the stability constant for
the formation of [Hg(L5)]2+ complex that amounts to 6.98 0.09.
This value for the complex formation constant is of the same order
as that found for other chromo- and fluorogenic receptors reported
in the literature containing the same aza-oxa-thia macrocyclic
subunit.7c,12 As conclusion of this part, receptor L1 shows a high
selective response toward Hg2+ when the UV–visible channel is
measured.
4000
50 eq.
3500
45 eq.
3000
2500
2000
1500
1000
500
40 eq.
35 eq.
30 eq.
Analogous spectroscopic studies were also carried out upon
protonation, resulting in a similar behavior found for Hg2+, that is
the proton attacks the aniline nitrogen, reducing its donor strength
and leading to the hypochromic effect and hypsochromic shift of
the charge transfer band. This engagement of the lone pair of the
aniline nitrogen is also reflected in the hyperchromic effect and
bathocromic shift of the band at 390 nm that is tentatively attrib-
uted to the 2,4,6-triphenylthiopyrylium chromophore.
25 eq.
20 eq.
15 eq.
10 eq.
5 eq.
EomIensity(au.)
0
420 440 460 480 500 520 540 560 580 600
nm
Fluorescence measurements of L1 in the presence of protons
support the UV/vis-spectroscopic observations. L1 is poorly fluores-
Figure 2. Emission enhancement observed upon addition of increasing quantities of
protons to acetonitrile solutions of receptor L1 (1.0 Â 10À5 mol dmÀ3, kexc = 400 nm).

T. Ábalos et al. / Tetrahedron Letters 50 (2009) 3885–3888
3887
of 10 equiv of Hg2+ induced a higher 6.2-fold enhancement of the
emission band (see Fig. 3). Figure 4 shows the emission intensity
enhancement observed upon addition of increasing quantities of
Hg2+ cation to acetonitrile solutions of L1.
900
800
700
600
500
400
300
200
100
0
10 eq.
7 eq.
However the most remarkable behavior was that of Cu2+, which
was able to induce a remarkable 17.6-fold enhancement of the
emission band of L1 (see again Fig. 3). Also the spectroscopic
behavior of L1 as a function of increasing Cu2+ concentration is
shown in Figure 5. This selective emission revival in the presence
of Cu2+ contrasts with the selective colorimetric response to Hg2+
of receptor L1. We believe that this might be related to a heavy
atom effect that is more effective for Hg2+. Thus, although coordi-
nation of Hg2+ to the lone pair of the nitrogen atom of the aniline
group would restore the emission of the 2,4,6-triphenylthiopyryli-
um chromophore, at the same time Hg2+ induced a partial quench-
ing of the emission intensity. In the case of Cu2+ the strength of
coordination with the macrocycle of L1, when compared with
Hg2+, is less effective leading to moderate changes in the visible
band (only a slight hypochromic effect) whereas the emission of
the 2,4,6-triphenylthiopyrylium moiety is restored more effi-
ciently. Thus the selectivity shown by L1 toward metal cations is
easily selected by an appropriate choice of the output channel, that
is detection of Hg2+ via the color channel (from blue to pale yellow)
and signaling of Cu2+ via a remarkable enhancement of the emis-
sion intensity.
5 eq.
2 eq.
1.5 eq.
1.2 eq.
Eomensity(au.)
1 eq.
0.5 eq.
420 440 460 480 500 520 540 560 580 600
nm
Figure 5. Emission enhancement observed upon addition of increasing quantities
of Cu2+ to acetonitrile solutions of receptor L1 (1.0 Â 10À5 mol dmÀ3, kexc = 400 nm).
Signaling of metal cations through changes in color or in emis-
sion intensity in organic solvents is not as appealing as signaling
events in water or in mixed organic solvent-water mixtures. For
this reason we studied the color and the emission intensity
changes of receptor L1, in the presence of Hg2+ and Cu2+ cations,
in acetonitrile-water mixtures with water contents ranging from
5% to 20%. Unfortunately the presence of water, in a content as
low as 5%, inhibited the colorimetric and the fluorimetric re-
sponses of L1 toward Hg2+ and Cu2+ cations.
In summary, for the first time we have used the 2,4,6-triphenyl-
thiopyrylium moiety for the design of intrinsic chemosensors. In
particular, we have prepared L1 that is a chromo-fluorogenic probe
based on the thiopyrylium scaffolding functionalized with an aza-
oxa-thia macrocycle. This new receptor has the ability to selec-
tively recognize Hg2+ through a change in color whereas this is able
to give strong emission enhancements in the presence of Cu2+ cat-
ion. This dual signaling is of significance because, as stated above,
there are few examples in the literature of optical receptors show-
ing a modulation of the selectivity by the choice of the output sig-
nal. We believe that the design of multi-channel probes could be a
suitable mode to enhance recognition features in single chemosen-
sors via signaling of multiple guests but using a unique molecular
entity.
600
L1+Cu2+
500
400
300
L1+Hg2+
200
L1+Fe3+
L1+Al 3+
L1
Emoensity(au.)
100
0
475
500
525
550
575
600
nm
Figure 3. Fluorescence enhancements observed upon addition of 10 equiv of the
corresponding metal cations to acetonitrile solutions of receptor L1 (1.0 Â 10À5
mol dmÀ3, kexc = 400 nm).
Acknowledgments
The authors wish to express their gratitude to the Spanish Gov-
ernment for financial support (Projects CTQ2006-15456-C04-01).
T.A. and S.R. would like to thank the Spanish Government and
the Generalitat Valenciana, respectively, for her/his fellowship.
Also J.V.R.-L. would like to thank Generalitat Valenciana for his
post-doctoral fellowship.
10 eq.
7 eq.
300
250
200
5 eq.
150
2 eq.
Supplementary data
100
oensity(au.)
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.04.060.
m
E
1 eq.
50
0.5 eq.
References and notes
0
420 440 460 480 500 520 540 560 580 600
nm
1. (a) Anslyn, E. V. J. Org. Chem. 2007, 72, 687–699; (b) Martínez-Máñez, R.;
Sancenón, F. Chem. Rev. 2003, 103, 4419–4476.
2. (a) de Silva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson, T.; Huxley, A. J. M.; Mc
Coy, C. P.; Rademacher, J. T.; Rice, T. E. Chem. Rev. 1997, 97, 1515–1566; (b)
Martínez-Máñez, R.; Sancenón, F. J. Fluoresc. 2005, 15, 267–285.
Figure 4. Emission enhancement observed upon addition of increasing quantities
of Hg2+ to acetonitrile solutions of receptor L1 (1.0 Â 10À5 mol dmÀ3, kexc = 400 nm).

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T. Ábalos et al. / Tetrahedron Letters 50 (2009) 3885–3888
3. (a) Löhr, H.-G.; Vögtle, F. Acc. Chem. Res. 1985, 18, 65–72; (b) Takagi, M.; Ueno,
K. Top. Curr. Chem. 1984, 121, 39–65.
4. (a) Beer, P. D. Chem. Commun. 1996, 689–696; (b) Beer, P. D. Coord. Chem. Rev.
2000, 205, 131–155; (c) Martínez-Máñez, R.; Soto, J.; Lloris, J. M.; Pardo, T.
Trends Inorg. Chem. 1998, 5, 183–203.
7. (a) Boiocchi, M.; Fabbrizzi, L.; Licchelli, M.; Sacchi, D.; Vázquez, M.; Zampa, C.
Chem. Commun. 2003, 1812–1813; (b) de Silva, A. P.; Gunaratne, H. Q. N.; Lynch,
M. J. Chem. Soc., Perkin Trans. 2 1995, 685–690; (c) Jiménez, D.; Martínez-
Máñez, R.; Sancenón, F.; Ros-Lis, J. V.; Soto, J.; Benito, A.; García-Breijo, E. Eur. J.
Inorg. Chem. 2005, 2393–2403; (d) Yuan, M.; Li, Y.; Li, J.; Li, C.; Liu, X.; Lv, J.; Xu,
J.; Liu, H.; Wang, S.; Zhu, D. Org. Lett. 2007, 9, 2313–2316; (e) Zhu, M.; Yuan, M.;
Liu, X.; Xu, J.; Lv, J.; Huang, C.; Liu, H.; Li, Y.; Wang, S.; Zhu, D. Org. Lett. 2008, 10,
1481–1484.
5. (a) Rurack, K. Spectrochim. Acta, Part A 2001, 57, 2161–2195; (b) Unger, B.;
Rurack, K.; Müller, R.; Jancke, H.; Resch-Genger, U. J. Mater. Chem. 2005, 15,
3069–3083; (c) Rurack, K.; Koval’chuck, A.; Bricks, J. L.; Slominskii, J. L. J. Am.
Chem. Soc. 2001, 123, 6205–6206; (d) García-Acosta, B.; Martínez-Máñez, R.;
Sancenón, F.; Soto, J.; Rurack, K.; Spieles, M.; García-Breijo, E.; Gil, L. Inorg.
Chem. 2007, 46, 3123–3135; (e) Nolan, E. M.; Lippard, S. J. Chem. Rev. 2008, 108,
3443–3480; (f) Fabbrizzi, L.; Poggi, A. Chem. Soc. Rev. 1995, 197–202; (g) Lee, S.
J.; Jung, J. H.; Seo, J.; Yoon, I.; Park, K.-M.; Lindoy, L. F.; Lee, S. S. Org. Lett. 2006, 8,
1641–1643; (h) Lee, S. J.; Lee, J. –E.; Seo, J.; Jeong, I. Y.; Lee, S. S.; Jung, J. H. Adv.
Funct. Mater. 2007, 17, 3441–3446; (i) Park, C. S.; Lee, J. Y.; Kang, E.-J.; Lee, J.-E.;
Lee, S. S. Tetrahedron Lett. 2009, 50, 671–675.
6. (a) Maynadie, J.; Delavaux-Nicot, B.; Fery-Forgues, S.; Lavabre, D.; Mathieu, R.
Inorg. Chem. 2002, 41, 5002–5004; (b) Delavaux- Nicot, B.; Fery-Forgues, S. Eur.
J. Inorg. Chem. 1999, 1821–1825; (c) Beer, P. D.; Graydon, A. R.; Sutton, L. R.
Polyhedron 1996, 15, 2457–2461; (d) Beer, P. D.; Szemes, F. J. J. Chem. Soc., Chem.
Commun. 1995, 2245–2247; (e) Beer, P. D.; Graydon, A. R. G.; Johnson, A. O. M.;
Smith, D. K. Inorg. Chem. 1997, 36, 2112–2118; (f) Saika, T.; Iyoda, T.; Honda, K.;
Shimidzu, T. J. Chem. Soc., Perkin Trans. 2 1993, 1181–1186; (g) Iyoda, T.; Saika,
T.; Honda, K.; Shimidzu, T. Tetrahedron Lett. 1989, 30, 5429–5432; (h) Shimidzu,
T.; Iyoda, T.; Honda, K. Pure Appl. Chem. 1988, 60, 1025–1032; (i) Funeriu, F. P.;
Lehn, J- -M.; Fromm, K. M.; Fenske, D. Chem. Eur. J. 2000, 6, 2103–2111; (j) Lehn,
J.-M. Chem. Eur. J. 2000, 6, 2097–2102; (k) Sancenón, F.; Benito, A.; Hernández,
F. J.; Lloris, J. M.; Martínez-Máñez, R.; Pardo, T.; Soto, J. Eur. J. Inorg. Chem. 2002,
866–875; (l) Otón, F.; Tárraga, A.; Velasco, M. D.; Espinosa, A.; Molina, P. Chem.
Commun. 2004, 1658–1659; (m) Otón, F.; Tárraga, A.; Espinosa, A.; Velasco, M.
D.; Molina, P. J. Org. Chem. 2006, 71, 4590–4598; (n) Otón, F.; Espinosa, A.;
Tárraga, A.; Ramírez de Arellano, C.; Molina, P. Chem. Eur. J. 2007, 13, 5742–
5752; (o) Zapata, F.; Caballero, A.; Espinosa, A.; Tárraga, A.; Molina, P. Org. Lett.
2008, 10, 41–44; (p) Ghosh, T.; Maiya, B. G.; Wong, M. W. J. Phys. Chem. A 2004,
108, 11249–11259; (q) Schmittel, M.; Lin, H.-W. Angew. Chem., Int. Ed. 2007, 46,
893–896.
8. Miranda, M. A.; García, H. Chem. Rev. 1994, 94, 1063–1089.
9. Jiménez, D.; Martínez-Máñez, R.; Sancenón, F.; Ros-Lis, J. V.; Benito, A.; Soto, J. J.
Am. Chem. Soc. 2003, 125, 9000–9001.
10. Synthesis of L1: N-phenyl macrocycle (4, 2 mmol) was reacted with 2,6-
diphenylpyrylium perchlorate (5, 4 mmol) in dry DMF (20 mL) at 150 °C for
3 h. Pyrylium derivative 6 (1 mmol, yield 50%) was precipitated from the crude
reaction by addition of dimethyl ether (25 mL). Then, compound
6 was
dissolved in acetone (50 mL), Na2S (2 mL, 20% water solution) was added, and
the crude reaction was allowed to react for 20 min at room temperature.
Finally perchloric acid (2 mL, 20% water solution) was added and the crude
reaction mixture was stirred for 40 another minutes at the same temperature.
The final thiopyrylium derivative L1 (0.48 mmol, 48% yield) was isolated by
vacuum filtration and successive washings with water and diethyl ether as
dark blue solid. 1H NMR (300 MHz, DMSO-d6): d 2.76 (4H, t, N–(CH2)2–S), 2.93
(4H, t, O–(CH2)2–S), 3.63 (4H, s, O–(CH2)2–O), 3.80 (8H, m, S–(CH2)2–N, O–
(CH2)2–S), 6.92 (2H, d, C6H4), 7.57 (6H, m, C6H5), 7.86 (4H, m, C6H5), 8.14 (2H, d,
C6H4), 8.43 (2H, s, C5H2S). 13C {1H} NMR (75 MHz, CDCl3): d 30.1, 32.1, 52.7,
70.6, 73.6, 114.1, 122.5, 125.6, 127.9, 130.2, 132.8, 133.4, 134.6, 153.8, 157.5,
162.0. HRMS calcd. for C33H36NS3O2, 574.1908, found: 574.1867.
11. Valeur, B.; Leray, I. Coord. Chem. Rev. 2000, 205, 3–40.
12. (a) Descalzo, A. B.; Martínez-Máñez, R.; Radeglia, R.; Rurack, K.; Soto, J. J. Am.
Chem. Soc. 2003, 125, 3418–3419; (b) Ros-Lis, J. V.; Martínez-Máñez, R.;
Sancenón, F.; Soto, J.; Spieles, M.; Rurack, K. Chem. Eur. J. 2008, 14, 10101–
10114.
13. (a) Parret, S.; Morlet-Savary, F.; Fouassier, J.-P.; Inomata, K.; Matsumoto, T.;
Heisel, F. Bull. Chem. Soc. Jpn. 1995, 68, 2791–2795; (b) Akaba, R.; Kamata, M.;
Koike, A.; Mogi, K.; Kuriyama, Y.; Sakuragi, H. J. Phys. Org. Chem. 1997, 10, 861–
869.