Coupling selectivity with sensitivity in an integrated chemosensor framework: Design of a Hg2+-responsive probe, operating above 500 nm

Article abstract of DOI:10.1021/ja0290779

For the highly selective and sensitive sensing of Hg²⁺ in water, a new design concept was realized where the selectivity of the probe's binding site is amplified by electronic properties of the chromophore. The molecular architecture of this ph

Full text of DOI:10.1021/ja0290779

Published on Web 02/27/2003
Coupling Selectivity with Sensitivity in an Integrated Chemosensor
2+
Framework: Design of a Hg -Responsive Probe, Operating above 500 nm
Ana B. Descalzo, Ram o´ n Mart ´ı nez-M a´ n˜ ez,* Reiner Radeglia, Knut Rurack,* and Juan Soto†
†
,†
‡
,‡
GDDS, Departamento de Qu ´ı mica, UniVersidad Polit e´ cnica de Valencia, Camino de Vera s/n,
E-46071 Valencia, Spain, and Department I.3, Bundesanstalt f u¨ r Materialforschung und -pr u¨ fung (BAM),
Richard-Willst a¨ tter-Strasse 11, D-12489 Berlin, Germany
Received October 24, 2002; E-mail: knut.rurack@bam.de
1
carbonyl group for coordination, ions such as Fe3+ that often
interfere due to electrostatic attraction at electron-rich binding sites
should be engaged at this end of the ditopic receptor framework.
Mercury is a highly toxic element. However, despite its toxicity
mercury and mercuric salts are used in a large number of industrial
processes and products. For instance, inorganic mercury compounds
can be found in electrical equipment, catalysts, paints, or as mining
3c
2
byproducts. Due to its wide use, a high percentage of mercury
contamination can be attributed to anthropogenic sources. Apart
from intensifying efforts to curtail mercury release into the
environment an important aspect in pollutant management is the
development of new or improved sensing methods, applicable in a
wide range of different sites and environments.
Among newer methodologies for chemical sensing, spectroscopic
techniques employing chromo- or fluorogenic molecular sensors
3
are especially appealing. They allow the monitoring of weakly
colored or nonfluorescent species such as many heavy- and
transition-metal ions with the advantageous features of optical
spectroscopy. Besides targeting biologically important cations such
The favorable spectroscopic properties of 1 and model compound
are directly obvious from Table 1. In highly polar aprotic as well
2
as Zn2 and Cu , considerable effort has been devoted to the
+
2+ 4
as aqueous media, the absorption and emission bands are centered
above 500 and 600 nm, respectively, and are well separated by
5
6
2+
design of new chromo- and fluoroionophores for Hg . However,
many of these molecules display drawbacks in terms of actual
applicability such as the lack of water solubility, cross-sensitivities
toward other metal ions, or optical signals in wavelength ranges
where matrix interference can occur.
-
1
Stokes shifts >1300 cm . The fluorescence quantum yields in
acetonitrile are typically high (φ > 0.6), and although changing to
water reduces the fluorescence yield, φ ) 0.08 for 1 is still
f
f
reasonable and substantially higher than for most other fluoroiono-
phores in mixed or neat aqueous media.3 Furthermore, these
properties are accompanied by high molar extinction coefficients,
To circumvent these problems, we followed a different strategy
for the design of title compound 1, conceived to give a highly
selective chromo- and fluorogenic response toward Hg2 in water.
The molecular architecture of this simple fluorescent chemosensor
is based on the phenoxazinone scaffold, which is also at the heart
+
4
-1
-1
e.g., 4.2 × 10 M cm at 585 nm for 1 in water.
Coordination studies with heavy, transition- as well as repre-
sentative main-group-metal ions and 2 in acetonitrile revealed the
importance of the molecular prerequisites for the success of the
7
of widely used polarity probes of the Nile Red family. The use of
the phenoxazinone moiety guarantees sufficient water solubility in
combination with intense fluorescence in the visible spectral region.
In terms of the suitability and performance as a fluoroionophore,
however, the π-conjugated and resonant indoaniline electronic
1
5
design concept. Irrespective of the metal ion employed sand
2
+
including Hg sthe absorption band of 2 shifts nonselectively to
the red (see exemplary data of 2-Hg2 and 2-Zn in Table 1).
A similar effect was observed upon protonation. These bathochro-
mic shifts indicate an increase in acceptor strength due to interaction
at the carbonyl group. Furthermore, besides appearing at longer
wavelengths, the absorption in the presence of cations is signifi-
cantly more structured, suggesting that interaction of electrophilic
species with the acceptor change the dye’s character from less to
more polymethinic.16 When such acceptor complexes of CT
chromophores are excited, the increased charge density on the
acceptor group of the excited molecule leads to a tightening of the
coordinative bond.17 Thus, if the species bound is a heavy- or
transition-metal ion, fluorescence quenching commonly occurs due
+
2+
8
structure is essential. In this donor-acceptor ensemble, the carbo-
nyl group acts as acceptor in two important processes, intramo-
lecular charge transfer (CT) and intermolecular hydrogen bonding9
or, when integrated in a metal ion recognition unit, coordinative
bond formation.1 Thus, for instance, upon exchange of an aprotic
for an equally polar but protic solvent, a red-shift of the absorption
,10
1
10
spectrum indicative of an increased CT character is noticed. On
the other hand, depriving the chromophore of the amino donor as
in phenoxazin-3-one has an opposite effect, i.e, strongly blue-shifted
1
2
13
spectra. In equipping 1 with the dithia-dioxa-monoaza crown unit
at the 7-position,14 our aim was to couple improved Hg selectivity
with efficient signaling via the amino-keto conjugative backbone.
To obtain an optimum response toward Hg2 , we avoided the use
of polythia or polyaza crowns known to bind most thio- or
2+
3
c
to electron or energy transfer, or enhanced spin-orbit coupling.
Accordingly, 2-Hg2 shows virtually no fluorescence.
+
+
Similar spectroscopic changes are also found for 1 and the
majority of the metal ions15 and protons in acetonitrile. In contrast,
the desired opposite response is obtained when Hg2 is added to
an acetonitrile solution of 1 (Table 1). The absorption band shows
a drastic hypso- and hypochromic shift, occurring now at 446 nm,
3
aminophilic metal ions. Additionally, by offering the charge-dense
+
†
Universidad Polit e´ cnica de Valencia.
Bundesanstalt f u¨ r Materialforschung und -pr u¨ fung.
‡
3418
9
J. AM. CHEM. SOC. 2003, 125, 3418-3419
10.1021/ja0290779 CCC: $25.00 © 2003 American Chemical Society

C O MMU N I C A T I O N S
Table 1: Spectroscopic Data of 1 and 2 in the Absence and
Presence of Selected Cations in Acetonitrile and Water
Acknowledgment. We thank the Spanish Ministerio de Ciencia
y Tecnolog ´ı a (AMB99-0504-C02-01 and MAT2000-1387-C02-02)
and the Fonds der Chemischen Industrie for support.
solvent
λabs/nm
λem/nm
φ
f
f
τ /ns
1
2
1
2
1
2
1
2
1
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
H2O
525
525
446
545 (583)
546 (599)
538 (588)
585
593
469
610
610
Q
0.65
0.63
3.50
3.80
n.d.
n.d.
n.d.
n.d.
0.47
0.34
Supporting Information Available: Details on synthesis and
competition studies (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
2
2
+
+
a
b
-Hg
-Hg
n.d.
n.d.
n.d.
n.d.
0.08
0.05
0.04
c
Q
2
+
+
-Zn
-Zn
613
610
634
630
615
2
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works generally agree on the underlying process of the spectroscopic
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2
+
Figure 1. Absorption and fluorescence spectra of 1 (9) and 1-Hg (O)
(
-
6
in water (c1 ) 2 × 10 M; excitation at isosbestic point at 500 nm). Inset:
2
+
spectrophotometric titration of 1 with Hg under similar conditions.
(
respectively. This color change from pink to yellow clearly indicates
2+
18
coordination of Hg at its designated receptor unit. The loss of
conjugation due to lone electron pair abstraction at the 7-position
is consistent with a step from 1 to phenoxazin-3-one. Obviously,
whereas Hg now binds to the crown, all the potentially interfering
species15 still prefer the carbonyl group as in 2 and can be trapped
2+
(10) Kolling, O. W.; Goodnight, J. L. Anal. Chem. 1974, 46, 482-485.
(11) (a) Dix, J. P.; V o¨ gtle, F. Chem. Ber. 1981, 114, 638-651. (b) Kubo, Y.;
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at this end of the π-system.19
61, 1, 3758-3765.
20
(12) Stu zˇ ka, V.; Golovina, A. P.; Alimarin, I. P. Collect. Czech. Chem.
Commun. 1969, 34, 221-228.
Most remarkable is the fact that the selective and reversible
2+
response toward Hg is preserved in water (Table 1, Figure 1).
Exclusive binding of Hg2 to the crown is now also indicated by
two other features: (i) the complex is still emissive in water,
conceivable with excited-state cation decoordination often found
for probes with a donor binding site,17 and (ii) the binding kinetics
(
13) Sancen o´ n, F.; Mart ´ı nez-M a´ n˜ ez, R.; Soto, J. Angew. Chem., Int. Ed. 2002,
41, 1416-1419.
+
(
14) For synthetic details, see Supporting Information. Detailed photophysical
and NMR studies of the functional dyes will be published separately,
Descalzo, A. B.; Mart ´ı nez-M a´ n˜ ez, R.; Radeglia, R.; Rurack, K.; Soto, J.
Manuscript in preparation.
-
-
-
2+
(
15) Metal ions (as NO
3
, SO
4
, or ClO
4
salts) besides Hg used for the
, Pb2+, Ca2+, and Na ; Cu2+, Ni2+
,
6
-1
follow a strict 1:1 model with K
S
) 1.20 × 10 M (Figure 1). In
studies in MeCN were Zn2+, Cd2+, Ag
+
+
2
+
2+
3+
3+
3+
+
2+
3+
+
+
2+
2+
Co , Mn , Fe , Cr , La , K , Mg , and Al were additionally
the presence of 2 mM Na , K , Mg , and Ca as well as 20 µM
checked for potential interference in H
2
O (for competition studies, see
of all the other metal ions,15 no significant variation of the
Supporting Information).
21
(16) D a¨ hne, S.; Moldenhauer, F. Prog. Phys. Org. Chem. 1985, 15, 1-130.
absorption or emission band of 1 was found. Furthermore, with
the probe concentrations employed in our studies, Hg could be
(
17) Rettig, W.; Rurack, K.; Sczepan, M. In New Trends in Fluorescence
Spectroscopy: Applications to Chemical and Life Sciences; Valeur, B.,
Brochon, J. C., Eds.; Springer: Berlin, 2001; pp 125-155.
2+
-
7
detected down to 10 M, i.e, at concentrations in the ppb range.
In conclusion, 1 takes advantage of an integrated design concept
where the selectivity of the Hg2 binding site is amplified by
electronic properties of the chromophore, while maintaining the
favorable spectroscopic features of the binding reaction. Fluorescent
sensor molecules showing strong absorption and weak emission
changes are suitable reporters in dual excitation wavelength
ratiometric measurements as employed in imaging-based fluorom-
etry.22 In this respect, due to its intense absorption and emission
bands centered above 500 nm, 1 is a particularly attractive candidate
for such applications. Finally, to the best of our knowledge, 1 is
the first molecular chemosensor able to selectively sense Hg2 in
the ppb range in water by using either absorption or emission
measurements.
2
+
(
18) In fact, coordination of Hg to 1 in acetonitrile appears to be more
complicated as photometric titrations in this solvent could not be fitted to
+
2+
a clear 1:1 model. This suggests that, although most of Hg binds to the
macrocycle as indicated by the colour changes, it may also partially
coordinate to the carbonyl group. Such a behavior was not observed in
water where Hg2+ exclusively coordinates to the macrocycle. Mechanistic
coordination studies will be published separately, see ref 14.
1
(
(
(
(
19) These results are supported by H NMR studies carried out for 1 and 2
2+
+
with Hg and H in acetonitrile, and which will be reported separately,
see ref 14.
20) Complex formation can reversibly be switched by acidification/ neutraliza-
tion employing HCl and NaOH. Proton-induced spectroscopic changes
occur only at pH <3.5.
21) The only exception was a 50% decrease of the absorption band at 585
+
nm upon addition of 10 µM Ag . However, no new blue-shifted band
+
appeared so that Ag+ does not interfere with the detection of Hg
2+
.
22) Silver, R. B. Methods Cell Biol. 1998, 56, 237-251.
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J. AM. CHEM. SOC.
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VOL. 125, NO. 12, 2003 3419