Cu2+-induced intermolecular static excimer formation of pyrenealkylamine

Article abstract of DOI:10.1021/ol800475d

Synthesis of monopyrenylalkylamine derivative 1 and its fluorescence behavior for Cu²⁺ in H₂O/CH₃CN (1:1, v/v) were investigated. Upon Cu²⁺ binding, 1, bearing a sulfonamide group, exhibited a marked excimer emission at 455 nm along with a weak monomer emission at 375 nm. The excimer emission, driven by formation of an intermolecular pyrenyl static excimer upon Cu²⁺ binding to the sulfonamide group, is rationalized by experimental and theoretical DFT calculation results.

Full text of DOI:10.1021/ol800475d

ORGANIC
LETTERS
Cu2+-Induced Intermolecular Static
Excimer Formation of Pyrenealkylamine
2008
Vol. 10, No. 10
1963-1966
Hyun Jung Kim,† Jooyeon Hong,‡ Areum Hong,‡ Sihyun Ham,*,‡ Joung Hae Lee,§
and Jong Seung Kim*,†
Department of Chemistry, Korea UniVersity, Seoul 136-701, Korea, Department of
Chemistry, Sookmyung Womens UniVersity, Seoul 140-742, Korea, and Korea
Research Institute of Standards and Science, Taejon 305-600, Korea
jongskim@korea.ac.kr; sihyun@sookmyung.ac.kr
Received March 3, 2008
ABSTRACT
Synthesis of monopyrenylalkylamine derivative 1 and its fluorescence behavior for Cu2+ in H2O/CH3CN (1:1, v/v) were investigated. Upon Cu2+
binding, 1, bearing a sulfonamide group, exhibited a marked excimer emission at 455 nm along with a weak monomer emission at 375 nm.
The excimer emission, driven by formation of an intermolecular pyrenyl static excimer upon Cu2+ binding to the sulfonamide group, is rationalized
by experimental and theoretical DFT calculation results.
Recently, the development of fluorescent chemosensors
capable of selective recognition and sensing of metal ions
is one of the most challenging fields from the vantage of
organic and supramolecular chemistry.1,2 The best effective
fluorescence chemosensor must convert the event of metal
ion recognition by the ionophore into light signals over the
fluorophore with high sensitivity and ease of monitoring.3,4
In designing sensors, therefore, the recognition moiety linked
to the fluorophore should be preliminarily considered because
they are responsible for the selectivity and binding efficiency
of the whole chemosensors.
Over the last few decades, considerable attention has been
paid to the development of heavy metal ion sensors, because
of their essential and/or deleterious roles, for one species.1,5–7
Over other metal ions, Cu2+ is an essential trace element
for humans, and plays an important role in various biological
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† Korea University.
Yamaguchi, M. Anal. Chem. 2000, 72, 4199
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‡ Sookmyung Womens University.
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§ Korea Research Institute of Standards and Science.
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A. J. M.; McCoy, C. P.; Rademacher, J. T.; Rice, T. E. Chem. ReV. 1997,
97, 1515. (b) Valeur, B.; Leray, I. Coord. Chem. ReV. 2000, 205, 3. (c)
Prodi, L.; Bolletta, F.; Montalti, M.; Zaccheroni, N. Coord. Chem. ReV.
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10.1021/ol800475d CCC: $40.75
Published on Web 04/15/2008
2008 American Chemical Society

processes. However, it is toxic at higher concentration level,
for example, the accumulation of Cu2+ in the liver and kidney
may cause gastrointestinal, Wilson disease, hypoglycemia,
dyslexia and infant liver damage.8,9 Thus, a number of
fluorescent sensors for the Cu(II) have been prepared and
reported.10 However, the fluorescent chemosensors that
display fluorescence enhancements by the addition of the
Cu(II) ion are limited.11
reference material 3 in 61% yield. (See detailed synthetic
procedures in the Supporting Information.)
In consideration of the solvent system, related to the ra-
tiometry between monomer and excimer emissions of 1 and
of its corresponding applicability in aqueous media, we used
a mixed solvent of CH3CN/H2O (1:1). The solution of 1
displays an intensive absorption band at 342 nm, which is
for the pyrene band.
For the fluorescent copper(II) chemosensor, we previously
reported that 1,3-dipyrene-appended calix[4]arene exhibited
a decreased excimer emission in a function of [Cu2+], that
is, excimer “On-Off” system.12a In contrast, the pyrene
excimer “Off-On” system upon Cu2+ ion complexation has
been rarely reported till now.12b We report herein pyrenyl-
alkylamine derivatives that show an enhancement of the
pyrenyl excimer emission by the addition of Cu2+ ions in
an aqueous media.
Synthetic pathways of fluorogenic molecules 1-3 are
summarized in Scheme 1. The reaction of 1-pyrenemethyl-
Scheme 1. Synthetic Pathways of 1-3
Figure 1
. (a) Absorption spectra of 1 (20.0 µM) and (b) fluorescence
-
spectra of 1 (6.0 µM) with addition of ClO4 salts of Li+, Na+,
K+, Rb+, Cs+, Ag+, Cd2+, Mg2+, Ca2+, Sr2+, Ba2+, Zn2+, Hg2+
,
Pb2+, Co2+, Cu2+, and Al3+ (100 equiv, respectively) in H2O/
CH3CN (1:1, v/v) with an excitation at 342 nm.
amine hydrochloride with 1.1 equiv of p-toluenesulfonyl
chloride and pyridine in CH2Cl2 affords the desired N-tosyl
methylpyrene (1) in moderate yield. Reaction of 1 with
Cs2CO3 in CH3CN leads to N-propyl-N′-tosyl methylpyrene
(2) in 63% yield. Treatment of 1-pyrenemethylamine with
1-iodopropane in the presence of Et3N in CHCl3 produced
UV/vis spectra of 1 over other metal cations (Figure 1).
The band broadening and red-shift in the UV spectra of 1
upon the addition of Cu2+ ions are attributable to the fa-
vorable intermolecular π-π stacking dimerization of the two
pyrenes in the ground state.13
To this solution, various metal cations (Li+, Na+, K+, Rb+,
Cs+, Ag+, Cd2+, Mg2+, Ca2+, Sr2+, Ba2+, Zn2+, Hg2+, Pb2+,
Co2+, Cu2+, and Al3+) were added, and the complexation
abilities of 1 toward the metal cations were examined from
the spectral changes.
Interestingly, we have found unusual fluorescence changes
in 1 that, upon addition of Cu2+, gave a pyrene excimer
emission at 455 nm in a solution of CH3CN/H2O (1:1) as
shown in Figure 1b. In contrast, the pyrenyl monomer
emission in 1 at 375 nm declines concomitantly to show
a ratiometry. For formation of excimer emission in 1,
along with ratiometry when Cu2+ is added, we were
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S. K.; Kim, S. H.; Kim, H. J.; Lee, S. H.; Lee, S. W.; Ko, J.; Bartsch,
R. A.; Kim, J. S. Inorg. Chem. 2005, 44, 7866
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1964
Org. Lett., Vol. 10, No. 10, 2008

concentration of both 1 and Cu2+ ion (Figure S2, Supporting
Information). The maximum point appears at the mole
fraction of 0.6, close to the typical ligand mole fraction (0.66)
for 2:1 ligand-to-metal complex. Mass spectrum also con-
firms the formation of the 2:1 complex (Figure S3, Support-
ing Information) where there are two major peaks at m/z
385 and 832, corresponding to [[1] + Cu]2+ and [1 · Cu2+
1], respectively.
·
Figure 2 gives detailed absorption and fluorescence
changes of 1 upon gradual titration with Cu2+ ion. As the
Cu2+ concentration increases, the excimer band at 455 nm
garadually increases. Based on this titration data in Figure
2, the association constant of 1 for Cu2+ is 2.8 × 104 M-2.14
Thus, upon Cu2+ binding, 1 is stacked together to have a
strong π-π interaction between two pyrenes, inducing an
enhanced excimer emission.
An important feature of 1 is its high selectivity toward
Cu2+ over other competitive species. Fluorescence spectral
changes of 1 were investigated with addition of miscel-
laneous cations including: Li+, Na+, K+, Rb+, Cs+, Ag+,
Cd2+, Mg2+, Ca2+, Sr2+, Ba2+, Zn2+, Hg2+, Pb2+, Co2+, Cu2+,
and Al3+ (Figure S4, Supporting Information). No changes
were observed, except in the case of the Cu2+ ions. Moreover,
in competition experiments of 1, other miscellaneous cations
did not interfere the Cu2+ selectivity, which is applicable
for the Cu(II) sensing in the industrial field.
To gain insight into the complexation mode of 1 for Cu2+
to give an excimer emission, pyrene derivative 3, bearing
no sulfonyl group, was synthesized and its fluorescence
studies with Cu2+ implemented. When the Cu2+ ion is added,
the fluorescence of 3 rarely changes, unlike 1 (Figure S5,
Supporting Information). Thus, it is notable that the sul-
fonamide group of 1 plays an important role in the Cu2+
complexation.15
To further elucidate the binding mechanism of 1 to Cu2+,
we also synthesized 2, bearing propyl groups on the nitrogen
atom. Compound 2 showed almost the same binding behavior
toward metal ions as did 1, with respect to the spectral
changes (Figure S6, Supporting Information). From the
titration experiment, association constants of 1 and 2 for Cu2+
in H2O/CH3CN (1:1, v/v) were calculated to be 2.4 × 104
and 2.3 × 103 M-2, respectively.
Figure 2. (a) Absorption titration spectra of 1 (20 µM) upon
addition of various amounts of Cu(ClO4)2 (0, 1, 2, 3, 4, 5, 10, 20,
30, and 40 equiv) and (b) fluorescence titration spectra of 1 (6 µM)
in H2O/CH3CN (1:1, v/v) upon addition of various amounts of
Cu(ClO4)2 (0, 1, 2, 3, 4, 5, 7, 10, 15, 20, 30, 50, and 100 equiv)
with an excitation at 342 nm.
motivated to elucidate the complexation mechanism in
more detail.
Pyrene is one of the most useful fluorogenic units for
fluorescent sensors because it displays not only a well-defined
monomer emission but also an efficient excimer emission.
Depending upon the origin of the pyrene dimer, there are
two kinds of excimers: a dynamic excimer and a static
excimer. The former results from a pyrene dimer formed in
the excited state, whereas the latter arises from a pyrene
dimer in the ground state. Formation of a dynamic or static
excimer depends on the distance between the two pyrene
units.12,13 A useful method to differentiate a dynamic excimer
from a static one is the excitation spectrum.12The excitation
spectra of 1•Cu2+ monitored at 455 nm are red-shifted (∆λ
) 15 nm) in comparison to that recorded at 376 nm, as well
as at decreased monomer emission. This is explicit evidence
for the formation of intermolecular pyrenyl static excimer
of 1 in the event of Cu2+ ion binding (Figure S1, Supporting
Information). Thus, the chemical species corresponding to
455 and 375 nm emissions are different.
For the latter case, the decrease in the association constant
is primarily due to two factors: (a) perturbation of electron
density over the donor N-atom by the additional propyl group
and (b) steric hindrance imposed by the propyl group.16
Therefore, it should be noteworthy that formation of the
excimer emission of 1 upon Cu(II) complexation is quite
dependent on the presence of the sulfonyl unit to bind Cu(II),
and the presence of an H atom on the nitrogen is a secondary
factor to form the dymeric pyrenes (Vide infra).
For the investigation of fluorescence spectral changes upon
Cu2+ ion binding to 1, the density functional theory (DFT)
(12) (a) Choi, J. K.; Kim, S. H.; Yoon, J.; Lee, K.-H.; Bartsch, R. A.;
Kim, J. S. J. Org. Chem. 2006, 71, 8011. (b) Yang, J.-S.; Lin, C.-S.; Hwang,
C.-Y. Org. Lett. 2001, 3, 889.
To quantify the complexation ratio between 1 and the Cu2+
ion, the Job plot measurement was executed by varying
(13) Kim, H. J.; Kim, S. K.; Lee, J. Y.; Kim, J. S. J. Org. Chem. 2006,
71, 6611.
Org. Lett., Vol. 10, No. 10, 2008
1965

calculations were employed using the Gaussian 03 package.17
Due to the 2:1 ligand-to-metal complexation behavior de-
termined by both mass spectrum and job plot measurements,
the dimers of 1 with and without Cu2+ ion were subjected
to the energy optimization at the B3LYP hydrid functional
with 3-21G* basis set.18 Several different starting geom-
etries were used for the geometry optimization to ensure that
the optimized structures corresponded to a global minima.
The optimized geometry for the monomer of 1 is represented
in Figure S7 (see Supporting Information) and the energy
minimized structures for the dimer of 1 both with (1-Cu2+)
and without the Cu2+ ion are shown in Figure 3.
ion recognition. Overall, the major binding mode in 1-Cu2+
is the electrostatic interaction between Cu2+ and the elec-
tronegative nitrogen atoms in 1, and the van der Waals
interactions between the stacked pyrenes also stabilize the
complex. It is noted that the 1-Cu2+ complex is also stabilized
by two NH---OS hydrogen bonds with an average distance
of 1.85 Å.
In addition, a time-dependent density functional theory
(TDDFT) calculation19 was executed to characterize the
nature of the fluorescence behavior of 1 upon Cu2+ ion
complexation. The molecular orbital energies and the as-
socaited electronic transitions were calculated from the
optimized geometry of the S0 state by TDDFT/B3LYP/3-
21G* level. Several studies,20 including our recent reports,21
have shown that hybrid functionals give the best performance
for evaluating electronic transitions in organic molecules.
On the basis of the TD-B3LYP/B3LYP/3-21G* calculations,
the efficient HOMO-1 to LUMO+1 excitation from one
pyrene and to the other pyrene (Py-Py* interaction) presum-
ably contribute to the strong fluorecence excimer bands for
1-Cu2+, whereas no excimer transitions were found in the
dimer of 1 without Cu2+ ion, as shown in Figures S1 and
S2. In this regard, the experimental observation is in excellent
agreement with the theoretical DFT calculation result that
the excimer emission corresponding to the Cu2+ ion com-
plexation for 1 requires a preorganized cavity with two
proximate nitrogen atoms of the sulfonamide groups to
recognize the metal ion as well as hydrogen bonds to stabilize
the complex.
Figure 3. B3LYP/3-21G* optimized geometries for the dimer of
1 (a) and the dimer of 1 with Cu2+ion (b).
Without the Cu2+ ion, as shown in Figure 3a, two pyrene
groups interact with two benzene groups independently em-
ployed by the π-π interaction.
The resulting dipole moment is to be 0 due to the
symmetry. Two, tight NH---OS hydrogen contacts (1.81 Å)
are present, contributing to the stability of the dimer of 1,
as shown by the dashed line in Figure 3a.
Converseley, the lowest energy conformation for 1-Cu2+
is located with two pyrene groups facing each other, where
the Cu2+ ion is recognized by two nitrogen atoms with a
distance of 1.97 and 1.99Å, respectively (Figure 3b). Four
sulfonamide oxygen atoms also exhibit minor interactions
with the Cu2+ ion (3.31 Å in average).
It is observed that the distance between two nitrogens in
1-Cu2+ ion is 2.88 Å, whereas that in the dimer of 1 without
Cu2+ ion is 4.23 Å. Two nitrogen atoms in proximity of the
sulfonamide groups might be the dominant factor for Cu2+
Acknowledgment. This work was supported by the Grant
of Korea Research Foundation [KRF-2005-003-C00092], the
SRC Research Center for Women’s Diseases of Sookmyung
Women’s University, and the SRC program (R11-2005-008-
02001-0(2008)).
Note Added after ASAP Publication. The Abstract and
Table of Contents graphics contained errors in the version
published ASAP April 15, 2008; the corrected version was
published on the Web May 8, 2008.
Supporting Information Available: Additional figures of
UV/vis, fluorescence emission spectra, and optimized geometry
for the monomer of 1 (Figure S1-S10). This material is
available free of charge via the Internet at http://pubs.acs.org.
OL800475D
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