A proton-triggered ON-OFF-ON fluorescent chemosensor for Mg(II) via twisted intramolecular charge transfer

Article abstract of DOI:10.1021/ol801048t

(Figure Presented) A novel fluorescent chemosensor has been synthesized and shows interesting fluorescent ON-OFF-ON processes through mediating its twisted intramolecular charge transfer (TICT) state. An exclusively fluorescent enhancement is observed for

Full text of DOI:10.1021/ol801048t

ORGANIC
LETTERS
2008
Vol. 10, No. 13
2873-2876
A Proton-Triggered ON-OFF-ON
Fluorescent Chemosensor for Mg(II) via
Twisted Intramolecular Charge Transfer
Yu Liu,* Min Han, Heng-Yi Zhang, Li-Xu Yang, and Wei Jiang
Department of Chemistry, State Key Laboratory of Elemento-Organic Chemistry,
Nankai UniVersity, Tianjin 300071, PRC
yuliu@nankai.edu.cn
Received May 6, 2008
ABSTRACT
A novel fluorescent chemosensor has been synthesized and shows interesting fluorescent ON-OFF-ON processes through mediating its
twisted intramolecular charge transfer (TICT) state. An exclusively fluorescent enhancement is observed for Mg2+
.
Fluorescent chemosensors are receiving increasing attention
due to their potential in analytical chemistry, the life sciences,
medical analysis, and environmental monitoring.1–3 Sensitive
magnesium ion sensors are extensively required because this
biologically most abundant divalent cation plays vital roles
in many cellular processes.4 As a result, intensive efforts
have been devoted to the design and synthesis of sensitive
and selective fluorescent sensors for Mg2+.5–7 These chemosen-
sors, which are mainly based on the fluorescence signaling
mechanisms of photoinduced electron transfer (PET) and
internal charge transfer (ICT), usually exhibit poor selectivity
for Mg2+ due to the interference of related cations, such as
Ca2+ and Ba2+.8 Herein, we report the novel fluorescent
chemosensor 1, which can signal Mg2+ selectively after its
(1) (a) Fluorescent Chemosensors for Ion and Molecule Recognition;
Czarnik, A. W., Eds.; ACS Symposium Series 538; American Chemical
Society: Washington, DC, 1993. (b) Valeur, B.; Leray, I. Coord. Chem.
ReV. 2000, 205, 3–40. (c) de Silva, A. P.; Fox, D. B.; Huxley, A. J. M.;
Moody, T. S. Coord. Chem. ReV. 2000, 205, 41–57. (d) de Silva, A. P.;
Gunaratne, H. Q. N.; Gunnlaug-sson, T.; Huxley, A. J. M.; McCoy, C. P.;
Rademacher, J. T.; Rice, T. E. Chem. ReV. 1997, 97, 1515–1566. (e) Lo¨hr,
(4) (a) Rude, G. A. Am. J. Cardiol 1989, 63, 316–321. (b) Grubb, R. D.;
Maguire, M. E. Magnesium 1987, 6, 113–127. (c) Hartwig, A. Mutat. Res.
2001, 475, 1133–1143
.
(5) Bu¨hlmann, P.; Pretsch, E.; Bakker, E. Chem. ReV. 1998, 98, 1593–
1688
.
(6) (a) Farruggia, G.; Iotti, S.; Prodi, L.; Montalti, M.; Zaccheroni, N.;
Savage, P. B.; Trapani, V.; Sale, P.; Wolf, F. I. J. Am. Chem. Soc. 2006,
128, 344–350. (b) Yang, Q.-Z.; Wu, L.-Z.; Zhang, H.; Chen, B.; Wu, Z.-
X.; Zhang, L.-P.; Tung, C.-H. Inorg. Chem. 2004, 43, 5195–5197. (c)
Arunkumar, E.; Chithra, P.; Ajayaghosh, A. J. Am. Chem. Soc. 2004, 126,
6590–6598. (d) Ajayaghosh, A.; Arunkumar, E.; Daub, J. Angew. Chem.,
Int. Ed. 2002, 41, 1766–1769. (e) Gromov, S. P.; Ushakov, E. N.; Fedorova,
O. A.; Baskin, I. I.; Buevich, A. V.; Andryukhina, E. N.; Alfimov, M. V.;
Johnels, D.; Edlund, U. G.; Whitesell, J. K.; Fox, M. A. J. Org. Chem.
H.-G.; Vo¨gtle, F. Acc. Chem. Res. 1985, 18, 65–72
.
(2) (a) Wiegmann, T. B.; Welling, L. W.; Beatty, D. M.; Howard, D. E.;
Vamos, S.; Morris, J. A. J. Physiol. 1993, 265, C1184–C1190. (b) Salvador,
J. M.; Inesi, G.; Rigaud, J. L.; Mata, A. M. J. Biol. Chem. 1998, 273, 18230–
18234. (c) Vo-Dinh, T.; Viallet, P.; Ramirez, L.; Pal, A.; Vigo, J. Anal.
Chim. Acta 1994, 295, 67–75. (d) Hirshfeld, K. M.; Toptygin, D.; Grandhige,
G.; Packard, B. Z.; Brand, L. Biophys. Chem. 1998, 71, 63–72. (e) Yuasa,
J.; Fukuzumi, S. J. Am. Chem. Soc. 2006, 128, 15976–15977. (f) Yuasa, J.;
Fukuzumi, S. J. Am. Chem. Soc. 2008, 130, 566–575
.
2003, 68, 6115–6125.
(3) New Trends in Fluorescence Spectroscopy: Applications to Chemical
and Life Sciences; Valeur, B., Brochon, J.-C., Eds.; Springer: Berlin, 2001.
More specific reviews are referenced in the various chapters
(7) (a) Liu, Y.; Duan, Z.-Y.; Zhang, H.-Y.; Jiang, X.-L.; Han, J.-R. J.
Org. Chem. 2005, 70, 1450–1455. (b) Mello, J. V.; Finney, N. S. Angew.
Chem., Int. Ed. 2001, 40, 1536–1538
.
10.1021/ol801048t CCC: $40.75
Published on Web 06/10/2008
2008 American Chemical Society

protonation. For the first time, the proton-triggered ON-OFF
and the OFF-ON response induced by Mg2+ are based on
the TICT mechanism. The concept of twisted intramolecular
charge transfer (TICT), first suggested by Lippert and co-
workers for explaining the dual fluorescence phenomenon
of p-(N,N-dimethylamino)-benzonitrile,9 has frequently been
invoked to interpret the photophysical properties of fluoro-
phores.10 The degree of electron transfer and the change of
molecular geometry are two crucial factors for the resulting
TICT state. If one could control these factors by molecular
recognition, the TICT theory might become another impor-
tant tool for designing novel chemosensors in addition to
PET and ICT.8c,11
cantly changed in both intensity and location, and the relative
emission intensity also decreased accompanied by a blue shift
(Figure 1a). The replacement of 1 by either 2a or 2b did not
The biarylpyridine signaling unit presents an attractive
fluorophore because of its visible emission from a locally excited
(LE) state and a longer-wavelength visible emission band arising
from a charge transfer (CT) state which can be induced by
coordination of an ion to the pyridine nitrogen.7b,12,13 The
synthetic pathways for the target compound 1 and the
reference compounds 2a/2b are shown in Scheme 1. The
Scheme 1. Synthetic Routes for 1 and 2
Figure 1. Emission spectra of (a) 1 (0.02 mM) with various alkali
and alkaline earth cations and (b) 1 (0.02 mM) with various alkali
and alkaline earth cations in the presence of 15 equiv of HClO4,
λex ) 312 nm.
result in significant changes in both absorption and emission
spectra under the same conditions, suggesting that charac-
teristic spectral responses are the complexation between the
crown ether moiety in 1 and the cations.14 This complexation
was validated by 1H NMR experiments (Supporting Informa-
tion). The data of the association constants15 for complex-
ation of 1 with the cations indicate that the compound does
not show the significant selectivity against these alkali and
alkaline earth cations estimated.
intermediates 3 and 4 were prepared by heating a mixture
of 4-formylbenzo-15-crown-5 and 4-methoxybenzaldehyde
or 3,4-dimethoxybenzaldehyde with acetophenone in the
presence of POCl3. The products reacted with ammonium
acetate in glacial acetic acid to give 1 and 2a/2b.
Upon addition of HClO4 to the CH3CN solution of 1, a
remarkable bathochromic shift of the absorption maximum
When alkali and alkaline earth cations were added to a
CH3CN solution of 1, its original absorption bands signifi-
(12) (a) Mello, J. V.; Finney, N. S. J. Am. Chem. Soc. 2005, 127, 10124–
10125. (b) McFarland, S. A.; Finney, N. S. J. Am. Chem. Soc. 2001, 123,
1260–1261. (c) Fang, A. G.; Mello, J. V.; Finney, N. S. Org. Lett. 2003, 5,
967–970. (d) Fang, A. G.; Mello, J. V.; Finney, N. S. Tetrahedron 2004,
60, 11075–11087.
(8) (a) Mashraqui, S. H.; Sundaram, S.; Bhasikuttan, A. C.; Kapoor, S.;
Sapre, A. V. Sens. Actuators, B 2007, 122, 347–350. (b) Hama, H.;
Morozumi, T.; Nakamurab, H. Tetrahedron Lett. 2007, 48, 1859–1861. (c)
Yang, J.-S.; Hwang, C.-Y.; Chen, M.-Y. Tetrahedron Lett. 2007, 48, 3097–
3102. (d) Farruggia, G.; Iotti, S.; Prodi, L.; Montalti, M.; Zaccheroni, N.;
Savage, P. B.; Trapani, V.; Sale, P.; Wolf, F. I. J. Am. Chem. Soc. 2006,
128, 344–350.
(13) Kollmannsberger, M.; Rurack, K.; Resch-Genger, U.; Rettig, W.;
Daub, J. Chem. Phys. Lett. 2000, 329, 363–369.
(14) (a) Cielen, E.; Tahri, A.; Heyen, K. V.; Hoornaert, G. J.; de
Schryver, F. C.; Boens, N. J. Chem. Soc., Perkin Trans. 2 1998, 1573–
1580. (b) Ushakov, E. N.; Gromov, S. P.; Fedorova, O. A.; Pershina, Y. V.;
Alfimov, M. V.; Barigelletti, F.; Flamigni, L.; Balzani, V. J. Phys. Chem.
A 1999, 103, 11188–11193.
(9) Lippert, E.; Lu¨der, W.; Moll, F.; Nagele, H.; Boos, H.; Prigge, H.;
Siebold-Blankenstein, I. Angew. Chem. 1961, 73, 695–706.
(10) (a) Grabowski, Z. R.; Rotkiewicz, K. Chem. ReV. 2003, 103, 3899–
4031. (b) Rurack, K.; Resch-Genger, U. Chem. Soc. ReV. 2002, 31, 116–
127.
(15) The association constants are measured by means of titration
fluorimetry with a 1:1 binding stoichiometry, and the values obtained are
respectively 3.50 × 104 M-1 for 1·Li+, 1.19 × 104 M-1 for 1·Na+, 3.83 ×
103 M-1 for 1·K+, 8.55 × 104 M-1 for 1·Mg2+, and 1.64 × 105 M-1 for
1·Ca2+.
(11) (a) Aoki, S.; Kagata, D.; Shiro, M.; Takeda, K.; Kimura, E. J. Am.
Chem. Soc. 2004, 126, 13377–13390. (b) Morozumi, T.; Anada, T.;
Nakamura, H. J. Phys. Chem. B 2001, 105, 2923–2931
.
2874
Org. Lett., Vol. 10, No. 13, 2008

was observed, and an isobestic points appeared at 312 nm
(Supporting Information). Obviously, the new long-wave-
length absorption band originates from the ICT process.
Protonation of the pyridine group by HClO4 leads to a
decrease in the oxidation potential of the pyridine receptor,
which triggers charge transfer from the benzocrown ether
to the pyridine moiety.16 It is noteworthy that the emission
spectra of both 1 and 2b were almost quenched upon addition
of acid (Φ1 ) 0.387, Φ2b ) 0.405 vs Φ1·H(I) ) 0.039 and
Φ2b·H(I) ) 0.037), while that of 2a significantly shifted from
356 to 469 nm (Φ2a ) 0.273, Φ2a·H(I) ) 0.495). The combined
results can be due to a TICT fluorescence quenching process
occurring between the biarylpyridine moiety and the phenyl
groups for 1·H+ and 2b·H+, but for 2a·H+, a simple ICT
process occurs for 2a. In fact, the very weak emission in
the 1·H+ or 2b·H+ system is a combination of the LE state
of the biphenylpyridine fluorophore and the TICT state, as
confirmed by fluorescence lifetime measurements.
we performed time-resolved fluorescence experiments. As
can be seen from Table 1, prior to the addition of acid, the
fluorescence decays of both 1 and its complexes are
monoexponential, and the observed lifetimes were all close
to 3 ns. The same applies for the fluorescence decay of 2a
and 2b. The minor differences between the lifetimes before
Interestingly, while the fluorescence spectrum of 1·H+ hardly
increased in the presence of Li+, Na+, K+, and Ca2+, a large
fluorescence enhancement (Φ1·H(I) + Mg(II) ) 0.610) was observed
upon addition of Mg2+ (Figure 1b). The value of the fluores-
cence enhancement factor value (FEF) is 13 times larger than
the other cations. Therefore, the protonation converts a general
alkaline and alkaline earth metal ion sensor (fluorescence
enhancement at 360 nm) into one which is highly selective to
Mg2+ (large fluorescence enhancement at 460 nm). In fact, the
complex of 1·H+ with Mg2+ can be readily distinguished by
the naked eye with a UV lamp (Supporting Information). In
contrast, the nonfluorescent 2b·H+ system did not become
fluorescent in the presence of any of the metal ions. The
exclusive selectivity for Mg2+ can be attributed to the lowest
electron-donating ability of benzocrown ether because of its
highest surface charge density.17
Figure 2.
Absorption spectra (a) and emission spectra (b) of 1·H+,
1·H+·Mg2+, and 2a·H+ in CH3CN.
Table 1. Photophysical Data of the Investigated Species in CH3CN
and after complexation with the cations are indicative for a
retention of the nature of the electronic transition and the
molecular geometry in 1. Upon addition of acid, the
fluorescence decays of 1·H+, 1·H+·Li+, 1·H+·Na+, 1·H+·K+,
and 1·H+·Ca2+ became biexponential. The two component
decays are attributed to a mechanism involving the excitation
of a single ground-state species to a fluorescent LE state
followed by a fast reaction to a weakly fluorescent TICT
state. The fast decay component (τ1) corresponds to the LE
state, and the slow one (τ2) is attributed to the TICT state.18
In sharp contrast, the fluorescence decays of both 2a·H+,
which does not form a TICT but an ICT state, and 1·H+·Mg2+
are monoexponential.
λem/nm
Φ
FEF
τ1/ns
τ2/ns
1
399
362
362
370
365
363
475
504
488
477
460
493
356
469
393
564
0.387
0.324
0.313
0.354
0.361
0.336
0.039
0.083
0.068
0.079
0.610
0.077
0.273
0.495
0.405
0.037
-
2.1
2.2
2.1
1.6
1.6
-
2.70
2.82
2.83
2.71
2.95
2.97
0.57
0.89
0.68
0.76
4.74
0.59
2.54
3.49
2.82
0.28
-
1·Li+
-
1·Na+
1·K+
-
-
1·Mg2+
1·Ca2+
1·H+
-
-
4.65
4.86
4.71
4.69
-
1·H+·Li+
1·H+·Na+
1·H+·K+
1·H+·Mg2+
1·H+·Ca2+
2a
1.4
2.1
2.9
38
2.5
-
4.55
-
2a·H+
2b
-
-
-
-
2b·H+
-
4.94
This observation suggests that the binding of Mg2+ with
the crown ether prohibits TICT formation, such that the
fluorescence occurs from an ICT state. The lifetime of 4.74
ns should correspond to an ICT state of 1·H+. The similar
To obtain in-depth mechanistic insight into the photo-
physical effects allowing the operation of the novel sensor,
(16) (a) Zucchero, A. J.; Wilson, J. N.; Bunz, U. H. F. J. Am. Chem.
Soc. 2006, 128, 11872–11881. (b) Ihmels, H.; Meiswinkel, A.; Mohrschladt,
C. J.; Otto, D.; Waidelich, M.; Towler, M.; White, R.; Albrecht, M.;
Schnurpfeil, A. J. Org. Chem. 2005, 70, 3929–3938.
(17) Geue, J. P.; Head, N. J.; Ward, A. D.; Lincoln, S. F. Dalton Trans.
2003, 521–526.
(18) Kollmannsberger, M.; Rurack, K.; Resch-Genger, U.; Daub, J. J.
Phys. Chem. A 1998, 102, 10211–10220.
Org. Lett., Vol. 10, No. 13, 2008
2875

absorption and emission changes of 1·H+·Mg2+ with 2a·H+
also conformed the occurrence of the ICT state (Figure 2).
The schematic representation of the presumed coordination
mode for the proton-triggered ON-OFF and the OFF-ON
fluorescence response induced by Mg2+ is illustrated in
Figure 3.
earth cations in neutral and acidic conditions have been
investigated. In the absence of acid, the fluorescent sensor
shows an unselective blue shift upon addition of all metal
ions. Addition of acid efficiently quenches its emission
spectrum, and the subsequent addition of metal ions which
causes a fluorescent enhancement is exclusively for Mg2+.
Furthermore, we elucidated the mechanism that results in
the ON-OFF-ON fluorescence response, indicating that the
conversion to the TICT state in 1 plays an important role in
the sensing. Although the application of 1 in organic solvents
presents a drawback for direct implementation into potential
applications, the design of related TICT sensors for different
metal ions which results in improved water solubility appears
to be promising in view of the present findings.
Acknowledgment. This work was supported by the 973
Program (2006CB932900), NNSFC (Nos. 20421202 and
20772063), and the Program for New Century Excellent
Talents in University (NCET-05-0222).
Figure 3
mode for the proton-triggered ON-OFF and the OFF-ON
fluorescence response induced by Mg2+
. Schematic representation of the presumed coordination
Supporting Information Available: Experimental pro-
cedures and characterization data for the chemosensor 1 and
the reference compounds 2a and 2b, UV-vis, fluorescence
spectra, and 1H NMR spectra. This material is available free
of charge via the Internet at http://pubs.acs.org.
.
In conclusion, the novel chemosensor 1 composed of
biarylpyridine and crown ether moieties has been synthesized,
and its spectral properties upon addition of alkali and alkaline
OL801048T
2876
Org. Lett., Vol. 10, No. 13, 2008