Metal ion induced FRET OFF-ON in tren/dansyl-appended rhodamine

Article abstract of DOI:10.1021/ol702558p

(Figure Presented) A series of new fluorescent probes bearing tren-spaced rhodamine B and dansyl groups have been synthesized. Compound 1 exhibits selective changes in the absorption and the emission spectra toward Cu ²⁺ ion over miscellaneous

Full text of DOI:10.1021/ol702558p

ORGANIC
LETTERS
2008
Vol. 10, No. 2
213-216
Metal Ion Induced FRET OFF−ON in
Tren/Dansyl-Appended Rhodamine
Min Hee Lee,† Hyun Jung Kim,§ Sangwoon Yoon,*,† Noejung Park,*,‡ and
Jong Seung Kim*,§
Department of Chemistry and Department of Applied Physics, Dankook UniVersity,
Seoul 140-714, Korea, and Department of Chemistry, Korea UniVersity,
Seoul 136-701, Korea
sangwoon@dankook.ac.kr; noejung@dankook.ac.kr; jongskim@korea.ac.kr
Received October 20, 2007
ABSTRACT
A series of new fluorescent probes bearing tren-spaced rhodamine B and dansyl groups have been synthesized. Compound 1 exhibits selective
+
changes in the absorption and the emission spectra toward Cu2 ion over miscellaneous metal cations. Among 1
−3, 1 shows the best FRET
efficiency through dansyl emission to rhodamine absorption for the Cu2 ion.
+
Selective detection of target metal ions has been of great
interest because of their importance in biological and
environmental processes.1-3 Many detection schemes rely
on fluorescence changes upon sensing specific metal ions.4-6
We report here a novel fluorescent probe for copper(II) cat-
ion, based on fluorescence resonance energy transfer (FRET).
The FRET is defined as an excited-state energy interaction
between two fluorophores in which excited donor energy is
nonradiatively transferred to an acceptor unit. The metal ion
induced FRET ONfOFF has been observed in previous
studies.5 To the best of our knowledge, however, the FRET
OFFfON module, inherently more sensitive owing to its
zero background, is reported here for the first time.
We have synthesized a series of rhodamine/dansyl fluo-
rophores (1-3) incorporated into a tren spacer (Scheme 1)
and measured their optical properties upon the metal cations.
The absorption and the emission spectra of individual
constituents of 1 are shown in Figure 1a. Rhodamine has
two constitutional isomers with distinctively different absorp-
tion properties. The spirolactam form (4) absorbs the UV
light and shows a band at ∼250 nm, and thus it is colorless
and nonfluorescent. Upon adding Cu2+ ion, 4 changes its
color to pink, indicating that the absorption shifts to the
visible region. The tetraaza group has been reported to show
high affinity to Cu2+ ion, and the complexation of Cu2+ leads
to opening of the spirolactam ring.7 Notably, the resulting
absorption spectrum of the 4•Cu2+ complex overlaps with
the emission spectrum of dansyl chloride (6), fulfilling a
favorable condition for the FRET.
† Department of Chemistry, Dankook University.
‡ Department of Applied Physics, Dankook University.
§ Korea University.
(1) (a) Choi, M. J.; Kim, M. Y.; Chang, S.-K. Chem. Commun. 2001,
1664. (b) Kra¨mer, R. Angew. Chem., Int. Ed. 1998, 37, 772. (c) Brummer,
O.; La Clair, J. J.; Janda, K. D. Org. Lett. 1999, 1, 415. (d) Kim, J. S.;
Quang, D. T. Chem. ReV. 2007, 107, 3780.
(2) Woodroofe, C. C.; Lippard, S. J. J. Am. Chem. Soc. 2003, 125, 11458.
(3) (a) Kimura, E.; Aoki, S.; Kikuta, E.; Koike, T. Proc. Natl. Acad.
Sci. U.S.A. 2003, 100, 3731. (b) Royzen, M.; Durandin, A.; Young, V. G.,
Jr.; Geacintov, N. E.; Canary, J. W. J. Am. Chem. Soc. 2006, 128, 3854.
(4) (a) Jin, T.; Ichikawa, K.; Koyama, T. J. Chem. Soc., Chem. Commun.
1992, 499. (b) Ji, H.-F.; Brown, G. M.; Dabestani, R. Chem. Commun.
1999, 609. (c) Kim, J. S.; Noh, K. H.; Lee, S. H.; Kim, S. K.; Kim, S. K.;
Yoon, J. J. Org. Chem. 2003, 68, 597.
(5) (a) Lee, S. H.; Kim, S. K.; Bok, J. H.; Lee, S. H.; Yoon, J.; Lee, K.;
Kim, J. S. Tetrahedron Lett. 2005, 46, 8163. (b) Bolletta, F.; Costa, I.;
Fabbrizzi, L.; Licchelli, M.; Montalti, M.; Pallavicini, P.; Prodi, L.;
Zaccheroni, N. J. Chem. Soc., Dalton Trans. 1999, 1381.
The absorption spectrum of 1, shown in Figure 1b, closely
resembles that of the combination of 4 and 6, suggesting
(6) Valeur, B.; Leray, I. Coord. Chem. ReV. 2000, 205, 3.
10.1021/ol702558p CCC: $40.75
© 2008 American Chemical Society
Published on Web 12/14/2007

Scheme 1. Rhodamine Derivatives 1-5
that the rhodamine moiety remains a ring-closed spirolactam
energy acceptor as shown in Figure 1b. FRET efficiency of
2+Cu2+ which is higher than that of 3+Cu2+ is due to the
additional presence of a sulfonamide group which presum-
ably assists in trapping the Cu2+ ion. Furthermore, extremely
weak fluorescence from the energy acceptor in the absence
of the energy donor (4+Cu2+) confirms that the FRET indeed
occurs from the dansyl to the rhodamine group.
Density functional theory (DFT) calculations provide
further structural evidence of the switching-ON of the FRET
upon addition of Cu2+ ion. We calculated the optimized
geometry of 1 and 1•Cu2+ complexes and the corresponding
electronic structures using the Vienna Ab initio Simulation
Package (VASP).10,11 The PBE-type generalized gradient
approximation is used for the exchange correlation,12 and
the plane-wave basis set is employed with the energy cutoff
of 400 eV.11
form. Upon irradiation at 420 nm, strong emission at ∼507
nm is observed, attributed to the fluorescence emitted from
the dansyl energy donor unit. When Cu2+ ion is added, the
fluorescence spectrum of 1 shifts to ∼580 nm, the region of
the energy acceptor. The binding of Cu2+ ion induces opening
of the spirolactam ring in 1, shifting the absorption spectrum
of rhodamine. Subsequently, an increased overlap8 between
emission of the energy donor and absorption of the energy
acceptor greatly enhances the intramolecular FRET, produc-
ing the fluorescence from the energy acceptor unit in 1. We
measured such FRET enhancement factors by considering
the ratio of the fluorescence intensity of the energy acceptor
at 574 nm (Frho) to that of the energy donor at 507 nm (Fdns
)
and observed 13-fold fluorescence increase in the case of
the Cu2+ ion complexation (Figure 4).
For more detailed studies of FRET occurring in 1+Cu2+,
we modified the energy donor systematically. Table 1
summarizes FRET efficiencies of 1-3 and also lists associa-
tion constants toward Cu2+ ions, respectively. Reducing the
number of the dansyl energy donor groups by one-half
(2+Cu2+, 3+Cu2+) lowers the FRET efficiency and thus
decreases the fluorescence intensity from the rhodamine
Figure 2 shows that 1 has an extended form due to the
tren spacer, while the 1•Cu2+ complex is relatively compact.
The coordination of Cu2+ with nearby oxygen and nitrogen
atoms in 1, as indicated by the dashed lines in Figure 2b,
pulls in the sulfonamide groups and brings the dansyl groups
close to the rhodamine group. The optimized location of Cu2+
ion is found between the oxygen atom of the sulfonyl group
and the nitrogen atom of the acyclic lactam group, confirming
(7) (a) Bernhardt, P. V.; Moore, E. G.; Riley, M. J. Inorg. Chem. 2001,
40, 5799. (b) Jang, Y. J.; Jun, E. J.; Lee, Y. J.; Kim, Y. S.; Kim, J. S.;
Yoon, J. J. Org. Chem. 2005, 70, 9603. (c) Santis, G. D.; Fabbrizzi, L.;
Licchelli, M.; Poggi, A.; Taglietti, A. Angew. Chem., Int. Ed. Engl. 1996,
35, 202.
(8) Lakowicz, J. R. Principles of Fluorescence Spectroscopy, 2nd ed.;
Plenum Publishers Corporation: New York, 1999.
(10) (a) Kresse, G.; Furthmu¨ller, J. Phys. ReV. B 1996, 54, 11169. (b)
Kresse, G.; Furthmu¨ller, J. Comput. Mater. Sci. 1996, 6, 15.
(11) Perdew, J. P.; Burcke, K.; Ernzerhof, M. Phys. ReV. Lett. 1996, 77,
3865.
(12) Association constants were calculated using the computer program
ENZFITTER, available from Elsevier-BIOSOFT, 68 Hills Road, Cambridge
CB2 1LA, United Kingdom.
(9) Kresse, G.; Hafner, J. Phys. ReV. B 1993, 47, 558.
214
Org. Lett., Vol. 10, No. 2, 2008

Figure 2. Optimized geometries of (a) 1 and (b) 1•Cu2+ complex
and the calculated partial density of states (PDOS) of (c) 1 and (d)
1•Cu2+ complex obtained by the density functional calculations.
Dashed lines and dotted lines in (c) and (d) indicate the energy
states of two dansyl groups. Solid lines represent the states of the
rhodamine group. The energy in the horizontal axis refers to the
Fermi level, and thus the first state appearing below and above 0
eV is defined as HOMO and LUMO, respectively. Double-sided
arrows in (c) and (d) indicate the HOMO-LUMO energy gap of
the dansyl and the rhodamine group.
Figure 1. (a) Normalized absorption and emission spectra of dansyl
chloride (6) and rhodamine (4)•Cu2+ complex. Shaded area indicates
the spectral overlap between the emission of the former and the
absorption of the latter. (b) Fluorescence changes of 1-4 (15.0
µM) upon addition of 7.5 mM of Cu(ClO4)2 in H2O/CH3CN (1/9,
v/v) buffered at pH 7.0 with Tris buffer-HCl with an excitation at
420 nm marked by a downward arrow.
Cu2+ ion, Job’s plot analysis was also executed (Figure S1,
Supporting Information).
To gain insight into the metal ion selectivity related to
the FRET, we performed similar fluorescence measure-
ments for a series of metal ions. We then found that the Cu2+
ion exclusively exhibits such a high FRET enhancement
(defined above as Frho/Fdns) (Figures 4 and S2-S7, Support-
ing Information). The contrast in visual color changes, shown
in Figures S8 and S9, confirms the Cu2+ ion selectivity as
well.
In conclusion, we herein for the first time report a
rhodamine/dansyl ionofluorophore showing metal ion in-
duced FRET OFFfON behavior. The complexation of Cu2+
ion opens the spirolactam ring of the rhodamine to give a
specific color change as well as a fluorescence enhancement
at ∼580 nm. Theoretical studies support that the Cu2+
that the complexation indeed requires the participation of
sulfonamide and opening of the spirolactam ring. These
structural changes are found to affect the HOMO/LUMO
energy levels of dansyl and rhodamine chromophores.
When the lactam ring is closed, the HOMO-LUMO
energy gap of the rhodamine energy acceptor is greater than
that of the dansyl energy donor, suppressing the energy
transfer from dansyl to rhodamine. As the Cu2+ is bound
and the spirolactam ring opens, the energy gap of rhodamine
is markedly reduced just to match that of the dansyl group,
enabling the intramolecular FRET.
Experimental observations and theoretical calculations
consistently explain how the addition of Cu2+ turns on the
FRET from the energy donor to the energy acceptor. Figure
3 summarizes this process along with the visual fluorescence
changes. In the absence of Cu2+ ion, the energy mismatch
between the energy donor and the acceptor blocks the energy
transfer, hence fluorescence is observed only from the energy
donor. The binding of Cu2+ to the sulfonamide and the
spirolactam moieties drives the structural changes, most
importantly the spirolactam ring opening, and accordingly
changes absorption and fluorescence spectra. Then, the
enhanced spectral overlap between the donor and the acceptor
turns FRET on to give the rhodamine fluorescence ON. On
the other hand, to confirm 1:1 stoichiometry between 1 and
Figure 3. Cu2+-induced FRET OFFfON along with visual color
changes upon irradiation at 420 nm.
Org. Lett., Vol. 10, No. 2, 2008
215

Table 1. Summarized Photochemical Properties of 1, 2, and 3
(15.0 µM) for Cu2+ Ion (7.5 mM), Such as FRET Efficiency
(Efret),8 Association Constants (Ka)9
Efret
(%)
Ka
(M-1
compound
)
1•Cu(II)
2•Cu(II)
3•Cu(II)
0.93
0.69
0.56
7.0 × 103
7.0 × 103
5.1 × 103
gap between the donor and the acceptor to provide an
enhanced FRET efficiency. The FRET technology on the
basis of tren/dansyl-appended rhodamine has a great potential
as a novel detection method for Cu2+ ion over other metal
cations.
Figure 4. In the presence of a various metal ions (7.5 mM), 1
(black), 2 (gray), and 3 (white) (15.0 µM of each) show emission
intensity ratios (Frho/Fdns) in H2O/CH3CN (1/9, v/v) buffered at pH
7.0 with Tris buffer-HCl with an excitation at 420 nm. Frho and
Acknowledgment. This work was supported by the SRC
program (R11-2005-008-02001-0(2007)) and Basic Science
Research of KOSEF (R01-2006-000-10001-0).
F
dns denote the fluorescence intensity of rhodamine at 574 nm and
Supporting Information Available: Synthetic details,
NMR copies, and additional spectra data. This material is
available free of charge via the Internet at http://pubs.acs.org.
that of the dansyl unit at 507 nm, respectively.
binding to sulfonamide and acyclic amide drives the struc-
tural changes, leading to the well-matched HOMO-LUMO
OL702558P
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