Fluorescent phosphane selenide as efficient mercury chemodosimeter

Article abstract of DOI:10.1021/ol200066p

The synthesis and photophysical properties of a novel fluorescent sensor are described. The phosphorus-selenium moiety allowed a selective mercury salt complexation, followed by the formation of phosphane oxide, which leads to a turn-on of the fluorescence. The sensibility and selectivity toward mercury cations were evaluated (0.18 ppb) and found to be in complete adequation with the targeted level of the World Health Organization, which makes the dye an efficient dosimeter for mercury cations.(Figure Presented)

Full text of DOI:10.1021/ol200066p

ORGANIC
LETTERS
2011
Vol. 13, No. 5
1182–1185
Fluorescent Phosphane Selenide As
Efficient Mercury Chemodosimeter
†
‡
†
,†
ꢀ ꢀ
ꢀ
Issa Samb, Jeremy Bell, Patrick Y. Toullec, Veronique Michelet,* and
Isabelle Leray*,‡
E.N.S.C.P., Chimie ParisTech, UMR 7223, Laboratoire Charles Friedel 11 rue P. et M.
Curie, 75231 Paris Cedex 05, France, and PPSM, ENS Cachan, CNRS, 61, avenue du
ꢀ
President Wilson 94230 Cachan, France
veronique-michelet@chimie-paristech.fr; icmleray@ppsm.ens-cachan.fr
Received January 10, 2011
ABSTRACT
The synthesis and photophysical properties of a novel fluorescent sensor are described. The phosphorus-selenium moiety allowed a selective
mercury salt complexation, followed by the formation of phosphane oxide, which leads to a turn-on of the fluorescence. The sensibility and
selectivity toward mercury cations were evaluated (0.18 ppb) and found to be in complete adequation with the targeted level of the World Health
Organization, which makes the dye an efficient dosimeter for mercury cations.
Heavy metal ions such as mercury represent highly toxic
pollutants to the environment and are extremely danger-
ous for human health.1 A wide variety of symptoms
including digestive, cardiac, kidney, and especially neuro-
logical diseases result from a series of biological effects.1,2
Thus, the level of this detrimental ion is the object of
several official norms; the World Health Organization
established in 2004 a guideline for drinking water quality
developed, the development of new, inexpensive, and real-
time monitoring methods for the detection of Hg2þ still
instigates interest. In this context, optical methods based
on chromogenic and fluorogenic molecular chemosen-
sors have attracted ever increasing attention.4 The chalco-
genophilicity of mercury5 has been extensively exploited by
(4) (a) Valeur, B.; Leray, I. Coord. Chem. Rev. 2000, 205, 3–40. (b)
Nolan, E. M.; Lippard, S. J. Chem. Rev. 2008, 108, 3443–3480. (c)
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1997, 97, 1515–1566. (d) Nolan, E. M.; Lippard, S. J. Chem. Rev. 2008,
108, 3443–3480. (e) Leray, I.; Valeur, B. Eur. J. Inorg. Chem. 2009, 3525–
3535.
which included a mercury maximal value of 1 μg L-1 3
.
Whereas a wide set of analytical methods including induc-
3
tively coupled plasma spectroscopy, atomic absorption,
atomic emission, and electrochemical detection have been
(5) Melnik, J. G.; Yurkervich, K.; Parkin, G. J. Am. Chem. Soc. 2010,
132, 647–655.
† E.N.S.C.P., Chimie ParisTech.
‡ PPSM, ENS Cachan.
(6) For selected examples of fluorescent chemodosensors exploiting
the thiophilicity of mercury, see: (a) J Ros-Lis, J. V.; Marcos, M. D.;
Martinez-Manez, R.; Rurack, K.; Soto, J. Angew. Chem. 2005, 44, 4405–
4407. (b) Yang, Y.-K.; Yook, K.-J.; Tae J. Am. Chem. Soc. 2005, 127,
16760–16761. (c) Liu, B.; Tian, H. Chem. Commun. 2005, 3156–3158. (d)
Song, K. C.; Kim, J. S.; Park, S. M.; Chung, K. C.; Ahn, S.; Chang, S. K.
Org. Lett. 2006, 8, 3413–3416. (e) Shi, W.; Ma, H. M. Chem. Commun.
2008, 1856–1858. (f) Lee, M. H.; Lee, S. W.; Kim, S. H.; Kang, C.; Kim,
J. S. Org. Lett. 2009, 11, 2101–2104. (g) Tian, M. Q.; Ihmels, H. Chem.
Commun. 2009, 3175–3177. (h) Yoon, S.; Albers, A. E.; Wong, A. P.;
Chang, C. J. J. Am. Chem. Soc. 2005, 127, 16030–16031. Lin, W. Y.; Cao,
X. W.; Ding, Y. D.; Yuan, L.; Long, L. L. Chem. Commun. 2010, 46,
3529–3531.
(1) (a) Hutchinson, T. C.; Meena, K. M. In Lead, Mercury, Cadmium
and Arsenic in the Environment; John Wiley: New York, 1987. (b) Scoullos,
G. H.; Vonkeman, M. J.; Thorton, L.; Makuch, Z. In Mercury, Cadmium,
Lead: Handbook for Sustainable Heavy Metals Policy and Regulation
(Environment and Policy, V. 31); Kluwer Academic: Norwell, MA, 2001.
(c) Koester, C. J.; Moulik, A. Anal. Chem. 2005, 77, 3737–3754. (d)
Richardson, S. D.; Temes, T. A. Anal. Chem. 2005, 77, 3807–3838.
(2) (a) Clarkson, T. W.; Magos, L.; Myers, G. J. N. Engl. J. Med.
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(3) Guidelines for drinking-water quality, 3rd ed.; World Health Orga-
nization: Geneva, 2004; p 188.
r
10.1021/ol200066p
Published on Web 02/09/2011
2011 American Chemical Society

synthetic chemists to design “OFF-ON” fluorescent
chemodosimeters.6,7 Considering the stability of HgSe
and some naturally occurring detoxification systems based
on selenium,8 we hypothesized that selenide phosphane
would be a suitable template for the capture of mercury
cations. In line with our recent investigations regarding the
use of phosphane oxides and phosphane sulfides bearing
polyphenylethynyl fluorophores as highly selective and
sensitive sensors,9 we therefore engaged in a study of
phosphane selenide as potential candidates for the detec-
tion of mercury ions. In this paper, we report the synthesis,
the spectroscopic properties, and a thorough investigation
of cation-induced photophysical changes of a new fluor-
escent dosimeter.
Scheme 2. Synthesis of Phosphane Selenide 1 and Oxide 2
In order to make a comparison between phosphane
oxide and phosphane selenide push-pull fluorescent sen-
sors, we engaged in the synthesis of the polar phosphorus
derivatives 1 and 2. The corresponding phosphane oxide
derivative 2 was usedasa comparison for the spectroscopic
measurements (Scheme 1).
selenide 5 in 95% yield. Sonogashira coupling10 between 5
and the aryl iodide 611 was performed in the presence of
15 mol % of PdCl2(PPh3)2 and 30 mol % CuI in the pres-
ence of diisopropylamine in toluene at room temperature
and led to the phosphane selenide 1 in 44% isolated yield.
The phosphane oxide analogue 2 was prepared starting
from known compound 79 according to the same cross-
coupling methodology and was isolated in 67% yield.
Scheme 1. Fluorescent Phosphane Selenide Chemodosimeter 1
and Phosphane Oxide 2
The preparation of 1-2 was realized according to pre-
vious methodologies.9 Reaction of the Grignard derivative
of 4-bromotrimethylsilylphenylacetylene 3 with PCl3 af-
forded the corresponding triarylphosphane (Scheme 2).
Treatment with an equimolar amount of selenium gave the
corresponding phosphine selenide 4 in 44% yield over two
steps. Desilylation was accomplished using K2CO3 in a
CH3OH/CH2Cl2 (2:1) solvent mixture to give phosphane
(7) For two recent examples of fluorescent chemodosimeters exploit-
ing the selenophilicity of mercury, see: (a) Tang, B.; Ding, B.; Xu, K.;
Tong, L. Chem.;Eur. J. 2009, 15, 3147–3151. (b) Chen, X.; Baek,
K.-H.; Kim, Y.; Kim, S.-J.; Shin, I.; Yoon, J. Tetrahedron 2010, 66,
4016–4021.
(8) (a) Miksa, I. R.; Buckley, C. L.; Carpenter, N. P.; Poppenga,
R. H. J. Vet. Diagn. Invest. 2005, 17, 331–340. (b) Arai, T.; Ikemoto, T.;
Hokura, A.; Terada, Y.; Kunito, T.; Tanabe, S.; Nakai, I. Environ. Sci.
Technol. 2004, 38, 6468–6474.
(9) (a) Ha-Thi, M. H.; Souchon, V.; Hamdi, A.; Metivier, R.; Alain,
V.; Nakatani, K.; Lacroix, P. G.; Genet, J. P.; Michelet, V.; Leray, I.
Chem.;Eur. J. 2006, 12, 9056–9065. (b) Ha-Thi, M. H.; Penhoat, M.;
Michelet, V.; Leray, I. Org. Lett. 2007, 9, 1133–1136. (c) Ha-Thi, M. H.;
Souchon, V.; Penhoat, M.; Miomandre, F.; Genet, J. P.; Leray, I.;
Michelet, V. Lett. Org. Chem. 2007, 4, 185–188. (d) Ha-Thi, M. H.;
Penhoat, M.; Drouin, D.; Blanchard-Desce, M.; Michelet, V.; Leray, I.
Chem.;Eur. J. 2008, 14, 5941–5950. (e) Ha-Thi, M. H.; Penhoat, M.;
Michelet, V.; Leray, I. Org. Biomol. Chem. 2009, 7, 1665–1673.
(10) (a) Chinchilla, R.; Najera, C. Chem. Rev. 2007, 107, 874–922. (b)
Doucet, H.; Hierso, J.-C. Angew. Chem., Int. Ed. 2007, 46, 834–871.
(11) Hajduk, P. J.; Sheppard, G.; Nettesheim, D. G.; Olejniczak, E. T.;
Shuker, S. B.; Meadows, R. P.; Steinman, D. H.; Carrera, G. M., Jr.;
Marcotte, P. A.; Severin, J.; Walter, K.; Smith, H.; Gubbins, E.; Simmer,
R.; Holzman, T. F.; Morgan, D. W.; Davidsen, S. K.; Summers, J. B.;
Fesik, S. W. J. Am. Chem. Soc. 1997, 119, 5818–5827.
Figure 1. Absorption spectra and corrected normalized emission
spectra of phosphane selenide 1 and phosphane oxide 2 in
CH3CN/H2O 80:20 at pH = 7 (MES-NaOH buffer, 50 mM).
The absorption and fluorescence spectra of the phos-
phane selenide 1 and oxide 2 ligands are shown in Figure 1,
and their photophysical characteristics are summarized in
Table 1. The fluorophore 1 shows an intense absorption
band in the near-UV region, and the absorption maximum
of 1 is blue-shifted by comparison of the phosphane oxide
Org. Lett., Vol. 13, No. 5, 2011
1183

Table 1. Photophysical Properties of Phosphane Selenide 1 and
Oxide 2 Derivatives in CH3CN/H2O 80:20a
Scheme 3. Deselenation Reaction Proposed Mechanism of 1
with Hg2þ
λabs
nm
/
ε/
λem/
nm
b
product
104 M-1 cm-1
ΦF
1
2
319
326
13.5
8.0
405
406
2 ꢀ 10-3
0.20
a Maxima of the absorption λabs (nm) and of steady-state emission
λem (nm), molar absorption coefficient ε (104 M-1 cm-1), and fluores-
cence quantum yield ΦF. b With 10% error.
derivative 2 which means that the electron-withdrawing
character of the phosphane is reduced in the case of 1. A
significant difference of the fluorescence quantum yield
between 1 and 2 was observed, 0.002 for 1 versus 0.2 for 2.
perchlorate in an acetonitrile/water mixture at pH = 7
afforded the corresponding oxide in 4 h in 99% yield
(Scheme 3).
Afteroptimization of the conditions, the evolutionof the
fluorescence upon addition of increasing quantities of
Hg2þ is displayed in Figure 3.
Figure 2. Time evolution of the fluorescence of 1 alone and after
addition of 1 equiv of mercury under the same conditions ([1] =
0.74 μM CH3CN/H2O 80:20, 40 °C, pH = 7, λexc = 330 nm).
Upon addition of mercury salt to a solution of 1 in
CH3CN/H2O 80:20 at pH = 7 (MES-NaOH,12 50 mM) a
100-fold enhancement of the fluorescence is observed as
displayed in Figure 2. The inset of Figure 2 illustrates the
increase of the fluorescence upon addition of Hg2þ. Such
an effect can be explained by a mercury-induced irrever-
sible deselenization reaction (Scheme 3), which leads to the
formation of the fluorescent phosphane oxide derivative
(ΦF = 0.2). The proposed mechanism is in full agreement
Figure 3. Corrected emission spectra of 1 (3.2 μM) in the pre-
sence of increasing concentration of Hg2þ in CH3CN/H2O
80:20 at pH = 7 at 40 °C after 20 min of equilibrium time.
λexc = 330 nm. Inset: Calibration curve as a function of
mercury concentration.
The variation of the fluorescence intensity versus the
mercury complexation is shown in the inset of figure 3. A
linearresponseofthefluorescenceintensity asa function of
mercury concentration was observed from 0 to 0.8 μM.
The detection limit calculated as three times the standard
deviation of the background/noise ratio was found to be
0.9 nM (0.18 ppb) which to the best of our knowledge
corresponds with one of the lowest reported sensitive
systems for the detection of mercury.4d,14
with various spectroscopic and analytical data such as 31
P
NMR spectra and HRMS data. To further probe the
chemical transformation of phosphane selenide to oxide,
we prepared the known triphenylphosphane selenide 313
and submitted this derivative to mercury salt. As antici-
pated we easily detected by 31P NMR spectroscopy the
formation of phosphane oxide 4. The reaction of phos-
phane selenide 3 in the presence of 1.2 equiv of mercury
(14) (a) Ye, B. C.; Yin, B. C. Angew. Chem., Int. Ed. 2008, 47, 8386–
8389. (b) Wegner, S. V.; Okesli, A.; Chen, P.; He, C. J. Am. Chem. Soc.
2007, 129, 3474–3475. (c) Nolan, E. M.; Racine, M. E.; Lippard, S. J.
Inorg. Chem. 2006, 45, 2742–2749.
(12) MES: 2-(N-morpholino)ethanesulfonic acid.
(13) Gulyas, H.; Bacsik, Z.; Szollosy, A.; Bakos, J. Adv. Synth. Catal.
2006, 348, 1306–1310 and references cited therein.
1184
Org. Lett., Vol. 13, No. 5, 2011

cations at much higher concentrations. The selectivity
diagram displayed in Figure 4 shows that the addition of
interfering cation does not alter the fluorescence response
of 1.
In conclusion, we have synthesized and characterized a
simple and efficient mercury dosimeter. The phosphorus-
selenide moiety incorporated in a push-pull chromophore
was found to be a selective complexation template for
mercury salt. We showed that the complexation was
accompanied by the chemical transformation of phos-
phane selenide to phosphane oxide, which leads to a
turn-on of the fluorescence. The sensibility and selectivity
toward mercury were evaluated (0.18 ppb) and found to be
in complete adequation with the targeted level of the
World Health Organization.
Figure 4. (Dark gray) Fluorescence intensity at 406 nm of 1
(1 μM) toward interfering metal ions (10-3 mol L-1 for Pb2þ
,
3
Cd2þ, Liþ, Mg2þ, Ca2þ, Zn2þ, Co2þ, Mn2þ; 10-4 mol L-1 for
Acknowledgment. This work was supported by the Na-
tional Research Agency program CP2D ”FLUOSEN-
SIL”. I.S. and J.B. are grateful to the National Research
Agency for their grants (2009-2011) and (2009-2012),
respectively.
3
Naþ, Kþ). (Light gray) Response toward interfering ions (same
concentration as that for part a) plus mercury (1 μM) (λexc =
330 nm). Spectra were acquired in CH3CN/H2O 80:20 at pH =
7 at 40 °C in MES buffer.
Having in hand a highly sensitive derivative, we exam-
ined the selectivity of 1 for Hg2þ with respect to other
Supporting Information Available. Experimental pro-
cedure and full analyses of 1 and 2. This material is
available free of charge via the Internet at http://pubs.
acs.org.
cations such as Kþ, Naþ Ca2þ, Liþ, Mg2þ, Zn2þ, Pb2þ
,
and Cd2þ. As shown in Figure 4, no significant changes of
the fluorescence is observed upon addition of interfering
Org. Lett., Vol. 13, No. 5, 2011
1185