Two-stage sensing property via a conjugated donor-acceptor-donor constitution: Application to the visual detection of mercuric ion

Article abstract of DOI:10.1021/jo050389e

A conjugated donor-acceptor-donor molecule incorporating a central moiety of naphthyridine and two terminal moieties of di(hydroxyethyl)aniline connected by ethynyl bridges shows two-stage color changes on binding with mercury(II) ion in Me₂SO/

Full text of DOI:10.1021/jo050389e

Two-Stage Sensing Property via a Conjugated
Donor-Acceptor-Donor Constitution: Application to the Visual
Detection of Mercuric Ion
Ju-Hui Huang,† Wen-Hsien Wen,† Yueh-Yang Sun,† Pi-Tai Chou,† and Jim-Min Fang*,†,‡
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan, and Genomics Research
Center, Academia Sinica, Taipei 115, Taiwan
jmfang@ntu.edu.tw
Received March 2, 2005
A conjugated donor-acceptor-donor molecule incorporating a central moiety of naphthyridine and
two terminal moieties of di(hydroxyethyl)aniline connected by ethynyl bridges shows two-stage
color changes on binding with mercury(II) ion in Me2SO/H2O (1:1) solution with a bathochromic
shift from 450 to 498 nm, and then an extraordinarily large hypsochromic shift to 378 nm. In
comparison, the corresponding donor-acceptor molecule weakly binds mercury(II) ion with a
hypsochromic shift from 408 to 375 nm. Our designed sensor of the donor-acceptor-donor system
shows high selectivity toward mercury(II) ion over other competing metal ions.
Introduction
We have previously explored that 2,7-bis(1H-pyrrol-2-
yl)ethynyl-1,8-naphthyridine (BPN), a push-pull conju-
gated molecule, exhibits a very large Stokes shift of
fluorescence upon complexation with glucopyranoside.3
Along this line, we herein designed the molecule 2 of
D-A-D assembly, in comparison with molecule 1 of A-D
constitution, as a simple model to demonstrate the
concept of the two-stage sensing with enhanced signal
transduction.4 As shown by the schematic drawing
(Scheme 1), the naphthyridine moiety acts as the acceptor
site, whereas the di(hydroxyethyl)amino moiety functions
A molecule bearing conjugated electron acceptor (A)
and electron donor (D) usually undergoes an intramo-
lecular charge transfer (ICT) upon electronic excitation.1
The ICT and hence an elongation of the π electron
conjugation occurring upon Franck Condon excitation
contributes considerably to the absorption profile. If the
A-D molecule binds a metal ion at the acceptor site, a
bathochromic shift occurs to account for the enhanced
ICT.1,2 However, in most cases, a metal ion tends to bind
at the electron-rich donor site to cause a hypsochromic
shift, often making visual detection difficult.1,2 To extend
the A-D recognition concept, the optical properties and
binding behavior of D-A-D molecules are of interest to
investigate, because they may be employed in multiple-
stage sensing of appropriate analytes over a large
dynamic range of concentration.1,2
(2) (a) Wang, S.-L.; Ho, T.-I. Chem. Phys. Lett. 1997, 268, 434-438.
(b) Gao, C.; Bru¨mmer, O.; Mao, S.; Janda, K. D. Org. Lett. 1999, 1,
415-418. (c) Rurack, K.; Sczepan, M.; Spieles, M.; Resch-Genger, U.;
Rettig, W. Chem. Phys. Lett. 2000, 320, 87-94. (d) Crochet, P.; Malval,
J.-P.; Lapouyade, R. Chem. Commun. 2000, 289. (e) Bru¨mmer, O.; La
Clair, J. J.; Janda, K. D. Bioorg. Med. Chem. 2001, 9, 1067-1071. (f)
Palomares, E.; Vilar, R.; Durrant, J. R. Chem. Commun. 2004, 362-
363. (g) Gunnlaugsson, T.; Leonard, J. P.; Murray, N. S. Org. Lett.
2004, 6, 1557-1560. (h) El-Gezawy, H.; Rettig, W.; Lapouyade, R.
Chem. Phys. Lett. 2005, 401, 140-148.
(3) (a) Liao, J.-H.; Chen, C.-T.; Chou, H.-C.; Cheng, C.-C.; Chou, P.-
T.; Fang, J.-M.; Slanina, Z.; Chow, T. J. Org. Lett. 2002, 4, 3107-3110.
(b) Fang, J.-M.; Selvi, S.; Liao, J.-H.; Slanina, Z.; Chen, C.-T.; Chou,
P.-T. J. Am. Chem. Soc. 2004, 126, 3559-3566.
† National Taiwan University.
‡ Academia Sinica.
(1) (a) de Silva, A. P. H.; Gunaratne, Q. N.; Gunnlaugsson, T.;
Huxley, A. J. M.; McCoy, C. P.; Rademacher, J. T.; Rice, T. E. Chem.
Rev. 1997, 97, 1515-1566. (b) Valeur, B.; Leray, I. Coord. Chem. Rev.
2000, 205, 3-40. (c) Rurack, K. Spectrochim. Acta Part A 2001, 57,
2161-2195.
10.1021/jo050389e CCC: $30.25 © 2005 American Chemical Society
Published on Web 06/24/2005
J. Org. Chem. 2005, 70, 5827-5832
5827

Huang et al.
SCHEME 1. Design of Metal Ion Sensor with
Conjugated A-D and D-A-D Assemblies
anism can be drawn by focusing on the two major stages
(the early and late stages) as shown in Scheme 1b. At
the early stage, the D-A-D molecule may bind with a
metal ion, either at the acceptor or at the donor sites, to
form 1:1 complexes. An increase of ICT is obvious in the
binding at the acceptor site, forming D-AM-D, due to
the enhanced acceptor strength. When a metal ion binds
at one of the donor sites, the resulting A-DM unit may
also function as an enhanced electron-withdrawing group
to facilitate ICT, a consequence differing from the binding
of the A-D molecule at the donor site. Therefore, one
can predict that the binding of the D-A-D molecule with
a metal ion at the early stage will cause a bathochromic
spectral shift, regardless of the binding at the acceptor
or donor site. When the D-A-D molecule is saturated
with metal ions at the late stage, all the acceptor and
donor sites are bound to metal ions to form a 1:3 complex
(MD-AM-DM). A hypsochromic spectral shift thus
occurs to account for the great decrease of dipole at this
stage.
Results and Discussion
Two consecutive Sonogashira coupling reactions were
applied to synthesize sensor molecules 1 and 2 (Scheme
2). The coupling reaction of N,N-di(2-hydroxyethyl)-4-
iodoaniline with (trimethylsilyl)acetylene was promoted
by 10 mol % of PdCl2(PPh3)2 and CuI in the presence of
Et3N to give 3, after a subsequent removal of the
trimethylsilyl group by K2CO3. Under similar conditions,
coupling of 3 with 1 equiv of 2-chloro-1,8-naphthyridine
gave sensor 1, whereas that with 0.5 equiv of 2,7-dichloro-
1,8-naphthyridine afforded sensor 2.
as the donor site. The acceptor and donor moieties are
connected by ethynyl bridges to form a conjugated
scaffold.
The solution of molecule 1 in Me2SO/H2O (1:1) solution
showed the absorption maximum at 408 nm (ꢀ ) 45 000
M-1 cm-1) (Figure 1), whereas the dual-armed molecule
2 exhibited the absorption maximum at a much longer
wavelength, λmax ) 450 nm (ꢀ ) 54 000 M-1 cm-1) (Figure
2). The large red-shift (42 nm) from 1 of the A-D
constitution to 2 of the D-A-D constitution may be
tentatively rationalized by the ethynyl substituent effect
in one of the arms of 2, which, in part, elongates the π
conjugation upon exciting the other A-D chromophore.
However, the possibility of exciton coupling due to the
crosstalk of two chromophores cannot be excluded at this
stage.
Both the naphthyridine5 and di(hydroxyethyl)aniline6
moieties are known to have affinity toward metal ions.
During our preliminary screening, molecules 1 and 2
were found to bind Hg2+ ions in aqueous media (e.g. Me2-
SO/H2O ) 1:1). The pollution of mercury and its deriva-
tives has posed severe problems for human health and
the environment.7 Many methods have been developed
to detect Hg2+ ion.2,8 In our study, the stock solutions of
1 and 2 (1 × 10-5 M) in Me2SO/H2O (1:1) were prepared,
In general, several binding states may exist in equi-
librium. The degree of π electron conjugation induced by
ICT, in a qualitative sense, can be designated by the
dipolar vector depicted in Scheme 1. For example, the
binding of the A-D molecule with a metal ion at the
acceptor site, forming MA-D, would enhance the accep-
tor strength to facilitate ICT, whereas the binding at the
donor site, forming A-DM, would reduce ICT. When both
the acceptor and donor sites are bound to metal ions, the
original donor group D is changed to an electron-
withdrawing group DM, and the dipole would diminish.
According to the preference of binding states in equilib-
rium, a bathochromic shift might be attributed to the ICT
increase, and a hypsochromic shift might be attributable
to the ICT diminution.
The binding event of the D-A-D molecule with metal
ions would be much more complicate than that for the
A-D molecule. However, a simplified book-keeping mech-
(5) (a) Boelrijk, A. E. M.; Neenan, T. X.; Reedijk, J. J. Chem. Soc.,
Dalton Trans. 1997, 4561-4570. (b) He, C.; Lippard, S. J. Inorg. Chem.
2000, 39, 5225-5231. (c) Catalano, V. J.; Kar, H. M.; Bennett, B. L.
Inorg. Chem. 2000, 39, 121-127. (d) He, C.; Lippard, S. J. Inorg. Chem.
2001, 40, 1414-1420.
(6) Kubo, K.; Sakurai, T.; Mori, A. Talanta 1999, 50, 73-77.
(7) (a) Morel, F. M. M.; Kraepiel, A. M. L.; Amyot, M. Annu. Rev.
Ecol. Syst. 1998, 29, 543-566. (b) Guidelines for Drinking-Water
Quality, 2nd ed.; World Health Organization: Geneva, 1996; Vol. 2, p
940.
(4) (a) Fery-Forgues, S.; Le Bris, M.-T.; Guette´, J.-P.; Valeur, B. J.
Phys. Chem. 1988, 92, 6233-6237. (b) Rurack, K.; Rettig, W.; Resch-
Genger, U. Chem. Commun. 2000, 407-408. (c) Rurack, K.; Koval’chuck,
A.; Bricks, J. L.; Slominskii, J. L. J. Am. Chem. Soc. 2001, 123, 6205-
6206. (d) Marcotte, N.; Plaza, P.; Lavabre, D.; Fery-Forgues, S.; Martin,
M. M. J. Phys. Chem. A 2003, 107, 2394-2402.
5828 J. Org. Chem., Vol. 70, No. 15, 2005

Visual Detection of Mercuric Ion
SCHEME 2. Synthesis of Conjugated A-D and D-A-D Sensors 1 and 2a
a Reagents and reaction conditions: (i) PdCl2(PPh3)2, CuI, Et3N, 1,4-dioxane, 50 °C, 14 h. (ii) K2CO3, MeOH, rt, 1 h; 82% yield for two
steps. (iii) PdCl2(PPh3)2, CuI, Et3N, DMF, 80 °C, 18 h; 82% yield for 1 and 13 h; 77% yield for 2.
complexation at both the acceptor and donor sites, as the
MA-DM species with diminution of ICT. When e1 equiv
of Hg2+ ions was added to 1, a very weak absorption
occurring at ∼500 nm might be attributable to a transient
binding of Hg2+ ion at the acceptor (naphthyridine) site,
as the enhanced ICT species of AM-D in Scheme 1a.
The 1H NMR titration study of 1 in Me2SO-d6 solution
(see Figure S1 in the Supporting Information) indicated
that the initial addition of Hg2+ ions (<0.5 equiv in CD3-
CN) caused the disappearance of the hydroxyl protons
and significant downfield shifts of the protons on the
naphthyridine ring, but no apparent change of the
1
protons on the di(hydroxyethyl)aniline moiety. The H
FIGURE 1. UV-vis titration of the A-D receptor 1 (1 × 10-5
M) in Me2SO/H2O (1:1) solution with various amounts of Hg2+
ions (1 × 10-2 M in distilled water).
NMR spectra became complicated on further addition of
Hg2+ ions (1-4 equiv in this study), presumably due to
existence of several complexation species. According to
the chemical-shift changes of H-7, from δ 9.08 to 9.20
during the titration, the association constant (Kass) of
1490 ( 31 for 1-Hg2+ (1:1 complex) at 298 K in Me2SO-
d6 solution was deduced by the nonlinear regression
method.9
(8) (a) Chae, M.-Y.; Czarnik, A. W. J. Am. Chem. Soc. 1992, 114,
9704-9705. (b) Hennrich, G.; Sonnenschein, H.; Resch-Genger, U. J.
Am. Chem. Soc. 1999, 121, 5073-5074. (c) Rurack, K.; Resch-Genger,
U.; Bricks, J. L.; Spieles, M. Chem. Commun. 2000, 2103-2104. (d)
Sakamoto, H.; Ishikawa, J.; Nakao, S.; Wada, H. Chem. Commun.
2000, 2395-2396. (e) Rurack, K.; Kollmannsberger, M.; Resch-Genger,
U.; Daub, J. J. Am. Chem. Soc. 2000, 122, 968-969. (f) Prodi, L.;
Bargossi, C.; Montalti, M.; Zaccheroni, N.; Su, N.; Bradshaw, J. S.;
Izatt, R. M.; Savage, P. B. J. Am. Chem. Soc. 2000, 122, 6769-6770.
(g) Hassan, S. S. M.; Saleh, M. B.; Abdel, G.; Ahmed, A.; Mekheimer,
R. A. H.; Abdel, K.; Nahed, A. Talanta 2000, 53, 285-293. (h) Al
Shihadeh, Y.; Benito, A.; Lloris, J. M.; Martinez-Manez, R.; Pardo, T.;
Soto, J.; Marcos, M. D. J. Chem. Soc., Dalton Trans. 2000, 7, 1199-
1205. (i) Das, A. K.; de la Guardia, M.; Cervera, M. L. Talanta 2001,
55, 1-28. (j) Sancenon, F.; Martynez-Manez, R.; Soto, J. Chem.
Commun. 2001, 2262-2263. (k) Padilla-Tosta, M. E.; Lloris, J. M.;
Martinez-Manez, R.; Marcos, M. D.; Miranda, M. A.; Pardo, T.;
Sancenon, F.; Soto, J. Eur. J. Inorg. Chem. 2001, 1475-1482. (l)
Sancenon, F.; Martynez-Manez, R.; Soto, J. Tetrahedron Lett. 2001,
42, 4321-4323. (m) Cha, N. R.; Kim, M. Y.; Kim, Y. H.; Choe, J.-I.;
Chang, S.-K. J. Chem. Soc., Perkin Trans. 2 2002, 1193-1196. (n)
Descalzo, A. B.; Martinez-Manez, R.; Radeglia, R.; Rurack, K.; Soto,
J. J. Am. Chem. Soc. 2003, 125, 3418-3419. (o) Nolan, E. M.; Lippard,
S. J. J. Am. Chem. Soc. 2003, 125, 14270-14271. (p) Caltagirone, C.;
Bencini, A.; Demartin, F.; Devillanova, F. A.; Garau, A.; Isaia, F.;
Lippolis, V.; Mariani, P.; Papke, U.; Tei, L.; Verani, G. J. Chem. Soc.,
Dalton Trans. 2003, 901-909. (q) Moon, S. Y.; Cha, N. R.; Kim, Y. H.;
Chang, S.-K. J. Org. Chem. 2004, 69, 181-183. (r) Guo, X.; Qian, X.;
Jia, L. J. Am. Chem. Soc. 2004, 126, 2272-2273. (s) Metivier, R.; Leray,
I.; Valeur, B. Chem. Eur. J. 2004, 10, 4480-4490. (t) Palomares, E.;
Vilar, R.; Durrant, J. R. Chem. Commun. 2004, 362-363.
FIGURE 2. UV-vis titration of the D-A-D receptor 2 (1 ×
10-5 M in Me2SO/H2O, 1:1) with various amounts of Hg2+ ion
(1 × 10-2 M in distilled water).
and the binding event was monitored by the UV-vis
spectroscopic method. The titrations were carried out by
using various amounts of Hg2+ ion as the aqueous
solution of perchlorate salt.
The binding of 1 with Hg2+ was rather weak; only after
addition of more than 1 equiv of Hg2+ ions did a new blue-
shifted absorption band at λmax ) 375 nm appear and
increase at the expense of the 408 nm band (Figure 1).
This hypsochromic shift is ascribed to the preferable
binding of Hg2+ ion at the donor site of di(hydroxyethyl)-
aniline, as the A-DM species in Scheme 1a,1,2,8 or
J. Org. Chem, Vol. 70, No. 15, 2005 5829

Huang et al.
FIGURE 3. 1H NMR titration of 2 (2.5 × 10-3 M in Me2SO-d6) by incremental additions of MsOH (1.25 M in Me2SO-d6).
On the other hand, titration of 1 with methanesulfonic
acid (MsOH) gave a red-shift absorption band at 489 nm
with an isosbestic point occurring at 442 nm throughout
the titration (see Figure S2 in the Supporting Informa-
tion). This result indicated that the A-D molecule 1 was
protonated at the naphthyridine site to form a 1:1
complex with prominent ICT, which prevented further
protonation of the di(hydroxyethyl)aniline moiety. The
association constant for protonated 1 (1:1 complex of
1-H+) was determined to be 355 ( 70 in Me2SO/H2O (1:
1) solution.
In sharp contrast, the D-A-D molecule 2 was much
more responsive to the Hg2+ ion than the A-D molecule
1 in the UV-vis titration. The initial addition of Hg2+
ions to 2 caused a prominent new absorption band at λmax
) 498 nm (Figure 2). The yellow solution of 2 im-
mediately changed to magenta in accordance with this
large red-shift (∆λ ) 48 nm). As predicted in Scheme 1b,
the Hg2+ ion might either bind to the acceptor site at the
early stage of titration to facilitate ICT or bind to one of
the donor sites to form an enhanced A-D-Hg2+ electron-
withdrawing unit that also facilitates the net ICT,
resulting in an additive effect in the dipolar change.
The magenta color of the mixture solution faded when
more than 10 equiv of Hg2+ ions were added. Accordingly,
an extraordinarily large hypsochromic shift (∆λ ) 120
nm) from 498 to 378 nm was observed. By addition of
more than 10 equiv of Hg2+ ions, all the acceptor and
donor sites in molecule 2 were likely saturated to reach
a late stage of complexation (as the MD-AM-DM species
in Scheme 1b), in which the saturated complex would
only possess the least ICT property. The prohibition of π
conjugation thus results in a great hypsochromic shift of
the absorption band.
Calculations with Specfit global analysis software
(Specfit/32) supported our experimental results of com-
plex formation, i.e., the primary formed 1:1 complex (2-
Hg2+) decreased after addition of 10 equiv of Hg2+ ions,
along with the growth of the 1:3 complex, 2-(Hg2+)3. The
association constants for 2-Hg2+ and 2-(Hg2+
) com-
3
plexes at 298 K were estimated to be (2.82 ( 0.17) × 105
M-1 and (8.91 ( 0.24) × 1011 M-3, respectively. The
binding strength of receptor 2 toward Hg2+ (1:1 complex)
is comparable to that of azatetrathia-15-crown-5,8c,e
though a precise comparison is not possible due to the
nature of different receptors and variation of measure-
ment methods and media. Furthermore, the association
constant of (2.82 ( 0.17) × 105 M-1 for 2-Hg2+ in Me2-
SO/H2O (1:1 complex) is more than 2 orders of magnitude
stronger than that (1490 ( 31 M-1) for 1-Hg2+ at 298
K. The results can be tentatively rationalized by the fact
that the D-A-D molecule 2 possesses two ICT sites, the
sum of which doubly increase the electron density at
naphthyridine in comparison to that of the A-D molecule
1. As a result, the binding strength in system 2 is
expected to be appreciably higher than that in system 1.
A different feature was observed in protonation of 2
by adding MsOH. The protonation caused a red-shift of
absorption to 560 nm with an isosbestic point occurring
at 483 nm throughout the titration. Calculations with
both Specfit/32 software and nonlinear regression analy-
sis9 concluded the 1:1 stoichiometry of 2-H+ formation.
Unlike the two-stage sensing event on titration with
Hg2+, addition of excess MsOH (e.g., 1000 equiv) did not
show blue-shifted absorption. It appeared that protona-
tion at the naphthyridine site induced a prominent ICT,
which prevented further protonation of the di(hydroxy-
ethyl)aniline moieties. The 1H NMR titration with MsOH
(Figure 3) also clearly showed that the naphthyridine
protons H-3/H-6 and H-4/H-5 shifted to lower fields,
(9) Connors, K. A. Binding Constants; Wiley: New York, 1987.
5830 J. Org. Chem., Vol. 70, No. 15, 2005

Visual Detection of Mercuric Ion
mmol), 2-chloroethanol (10 mL), and K2CO3 (4 g, 30 mmol) was
heated at 55 °C for 10 h. The mixture was concentrated, brine
was added (40 mL), and the solution was extracted with CH2-
Cl2. The combined organic phase was dried (Na2SO4), filtered,
and concentrated under reduced pressure to give a crude
product. After recrystallization from EtOAc, N,N-di(2-hydroxy-
ethyl)-4-iodoaniline (1.3 g, 71% yield) was obtained as yellow
crystals, mp 71-72 °C.
Under an atmosphere of argon, a mixture of N,N-di(2-
hydroxyethyl)-4-iodoaniline (370 mg, 1.2 mmol), (trimethylsi-
lyl)acetylene (0.2 mL, 1.44 mmol), Et3N (2 mL), PdCl2(PPh3)2
(10 mg, 0.014 mmol), and CuI (3 mg, 0.016 mmol) in 1,4-
dioxane (2 mL) was heated at 50-55 °C for 14 h. The mixture
was concentrated, taken by MeOH/CH2Cl2 (1:9), and passed
through a short column of Celite by elution with MeOH/CH2-
Cl2. The organic phase was concentrated, and the crude
product was purified by silica gel chromatography (MeOH/CH2-
Cl2 (1:9)) to give N,N-di(2-hydroxyethyl)-4-(trimethylsilyl)-
ethynylaniline (303 mg, 91% yield) as yellow solids, mp 96-
97 °C.
whereas the protons H-2′, H-3′, H-1′′, and H-2′′ on the
di(hydroxyethyl)aniline moieties were insensitive.
Nonetheless, MsOH did not interfere with the detection
of Hg2+ ion with receptor 2. For example, a brownish
purple mixture containing 2 (1 equiv) and MsOH (50
equiv) with λmax ) 560 nm readily changed to magenta
with λmax ) 507 nm on addition of Hg(ClO4)2 (2 equiv).
Addition of over 10 equiv of Hg(ClO4)2 resulted in the
growth of 379-nm absorption, similar to the spectra
shown in Figure 2. We also found that the sensing events
of 2 with Hg2+ ions occurred similarly in Me2SO/HEPES
buffer solutions at pH 5.55 and 7.28.
Molecule 2 was insensitive to alkaline ions (e.g., Mg2+
Ca2+, and Ba2+), transition metal ions (e.g., Mn2+ and
Fe2+), or the toxic ions (e.g., Co2+, Ni2+, Cu2+, Zn2+, Cd2+
,
,
and Pb2+). The UV-vis spectrum of 2 showed no obvious
change by treatments with any of the above-mentioned
metal ions, even in very large quantities (e.g., 200 equiv).
A mixture containing 2 (1 equiv) and metal ions (each
200 equiv) other than Hg2+ retained its yellow color (λmax
) 450 nm), but changed instantly to magenta (λmax ) 502
nm) upon addition of Hg2+ ion. When more than 10 equiv
of Hg2+ ions were added, the color faded and the absorp-
tion band also shifted to 378 nm. Thus, the two-stage
colorimetric property of 2 was unique in the detection of
the Hg2+ ion in aqueous media, e.g., Me2SO/H2O (1:1),
free from the interference of other metal ions. The unique
selectivity of Hg2+ based on the current system is truly
remarkable. At the current stage, although the actual
cause of the Hg2+ selectivity is pending resolution, we
tentatively propose that Hg2+ tends to bind molecule 2
(or 1) with the naphthyridine chromophore at the first
stage, whereas such a binding strength is rather weak
for the other metal ions studied. This viewpoint may be
rationalized by a very specific orientation of electron
density for two pyridinyl lone-pair electrons in the
naphthyridine moiety. As a result, naphthyridine favors
a complex formation with a soft metal ion of large radius
such as Hg2+. Further firm support has been given in
the NMR titration studies (vide supra), in which the
major changes of proton signals occur at the naphthyri-
dine sites in the early stage of the titration with Hg2+
ions.
A solution of N,N-di(2-hydroxyethyl)-4-(trimethylsilyl)ethy-
nylaniline (300 mg, 1.08 mmol) in MeOH (5 mL) was treated
with K2CO3 (443 mg, 3.24 mmol). The mixture was stirred at
room temperature for 1 h, then concentrated under reduced
pressure. The residue was purified by silica gel column
chromatography with elution of MeOH/CH2Cl2 (1:9) to give
compound 3 (200 mg, 90% yield) as pale yellow solids.
3: mp 107-108 °C; TLC (MeOH/CH2Cl2 (1:19)) Rf 0.20; IR
(KBr) 3300, 2929, 2098, 1517 cm-1; 1H NMR (CDCl3, 400 MHz)
δ 7.32 (2 H, d, J ) 8.9 Hz), 6.56 (2 H, d, J ) 8.9 Hz), 3.79 (4
H, t, J ) 4.8 Hz), 3.54 (4 H, t, J ) 4.8 Hz), 2.96 (1 H, s); 13C
NMR (CDCl3, 100 MHz) δ 147.9, 133.3 (2 ×), 111.9 (2 ×), 109.4,
84.4, 75.1, 60.5 (2 ×), 55.1 (2 ×); FAB-MS m/z 206.1 (M+
+
H); HRMS calcd for C12H16NO2 (M+ + H) 206.1181, found m/z
206.1180.
7-{4-[Di(2-hydroxyethyl)amino]phenylethynyl}-1,8-
naphthyridine (1). Under an atmosphere of argon, a mixture
of 2-chloronaphthyridine (50.2 mg, 0.305 mmol), Et3N (1 mL),
PdCl2(PPh3)2 (21 mg, 0.0305 mmol), and CuI (5 mg, 0.0305
mmol) in DMF (3 mL) was heated at 80-85 °C for 10 min. A
solution of N,N-di(2-hydroxyethyl)-4-ethynylaniline (3, 74.7
mg, 0.366 mmol) in DMF (3 mL) was added dropwise, and the
mixture was heated for another 18 h. The mixture was
concentrated, and the crude product was purified by silica gel
chromatography (MeOH/CH2Cl2 (1:9)) to give compound 1 (87
mg, 82% yield) as yellow solids.
1: mp 185-185.9 °C; TLC (MeOH/CH2Cl2 (1:9)) Rf 0.31; IR
(KBr) 3421, 2931, 2202, 1594 cm-1; UV-vis (Me2SO/H2O (1:
1
1)) λmax 409 nm (ꢀ ) 45 000 M-1 cm-1); H NMR (DMSO-d6,
In conclusion, the dual-armed D-A-D molecule 2
exhibits absorptions at longer wavelengths than the A-D
molecule 1, and hence provides a more convenient
“naked-eye” colorimetric detection of the Hg2+ ion. In-
stead of the commonly used macrocycles for metal ion
detection,1,2,8 molecule 2 with the acyclic di(hydroxyethy-
l)aniline components renders a straightforward prepara-
tion and good solubility in aqueous media. The D-A-D
constitution demonstrated in this study can serve as a
protocol for the future design of a multiple-stage sensing
system, which may eventually lead to practical applica-
tion on the logic gates4c,10 based on its sensitivity and
selectivity of metal ions and other possible analytes.
400 MHz) δ 9.08 (1 H, d, J ) 8.0 Hz), 8.44 (2 H, d, J ) 8.4
Hz), 7.73 (1 H, d, J ) 8.4 Hz), 7.60 (1 H, dd, J ) 8.4, 8.0 Hz),
7.45 (2 H, d, J ) 8.7 Hz), 6.76 (2 H, d, J ) 8.7 Hz), 4.80 (2 H,
t, J ) 4.8 Hz), 3.56 (4 H, td, J ) 5.2, 4.8 Hz), 3.48 (4 H, t, J )
4.8 Hz); 13C NMR (DMSO-d6, 100 MHz) δ 155.5, 154.3, 149.2,
146.5, 138.0, 137.4, 133.5 (2 ×), 125.0, 122.3, 121.5, 111.5 (2
×), 105.9, 93.7, 88.2, 58.0 (2 ×), 53.1 (2 ×); FAB-MS m/z 368.1
(M+ + H); HRMS calcd for C20H20N3O2 (M+ + H) 334.1556,
found m/z 364.1548. Anal. Calcd for C20H19N3O2: C, 72.05; H,
5.74; N, 12.60. Found: C, 71.88; H, 5.92; N, 12.41.
2,7-Bis{4-[di(2-hydroxyethyl)amino]phenylethynyl}-
1,8-naphthyridine (2). Under an atmosphere of argon, a
mixture of 2,7-dichloronaphthyridine (48 mg, 0.24 mmol), Et3N
(1 mL), PdCl2(PPh3)2 (16 mg, 0.023 mmol), and CuI (3 mg,
0.016 mmol) in DMF (5 mL) was heated at 80-85 °C for 10
min. A solution of N,N-di(2-hydroxyethyl)-4-ethynylaniline
(105 mg, 0.51 mmol) in DMF (3 mL) was added dropwise, and
the mixture was heated for another 13 h. The mixture was
concentrated, taken by MeOH/CH2Cl2 (1:9), and passed through
a short column of Celite by elution with MeOH/CH2Cl2. The
organic phase was concentrated, and the crude product was
purified by silica gel chromatography (MeOH/CH2Cl2 (1:9)) to
give compound 2 (98 mg, 77% yield) as red solids.
Experimental Section
N,N-Di(2-hydroxyethyl)-4-ethynylaniline (3). Under an
atmosphere of nitrogen, a mixture of 4-iodoaniline (1.3 g, 6
(10) (a) de Silva, A. P.; Dixon, I. M.; Gunaratne, H. Q. N.;
Gunnlaugsson, T.; Maxwell, P. R. S.; Rice, T. E. J. Am. Chem. Soc.
1999, 121, 1393-1394. (b) de Silva, A. P.; Fox, D. B.; Huxley, A. J. M.;
Moody, T. S. Coord. Chem. Rev. 2000, 205, 41-57.
J. Org. Chem, Vol. 70, No. 15, 2005 5831

Huang et al.
2: mp >300 °C dec; TLC (MeOH/CH2Cl2 (1:9)) Rf 0.26; IR
(KBr) 3320, 2928, 2202, 1588 cm-1; UV-vis spectrum λmax 332
nm (ꢀ ) 29 000 M-1 cm-1), λmax ) 450 nm (ꢀ ) 54 000 M-1
cm-1) in Me2SO/H2O (1:1); 1H NMR (DMSO-d6, 400 MHz) δ
8.39 (2 H, d, J ) 8.3 Hz), 7.68 (2 H, d, J ) 8.3 Hz), 7.45 (4 H,
d, J ) 8.8 Hz), 6.77 (4 H, d, J ) 8.8 Hz), 4.81 (4 H, t, J ) 5.5
Hz), 3.55 (8 H, t, J ) 5.5 Hz), 3.49-3.47 (8 H, m); 13C NMR
(DMSO-d6, 100 MHz) δ 155.5, 149.2 (2 ×), 147.1 (2 ×), 137.6
(2 ×), 133.6 (4 ×), 125.0 (2 ×), 120.5, 111.5 (4 ×), 105.9 (2 ×),
94.1 (2 ×), 88.4 (2 ×), 58.1 (4 ×), 53.1 (4 ×); FAB-MS m/z 537.3
(M+ + H); HRMS calcd for C32H33N4O4 (M+ + H) 537.2502,
found m/z 537.2496. Anal. Calcd for C32H32N4O4: C, 71.62; H,
6.01; N, 10.44. Found: C, 71.55; H, 6.08; N, 10.36.
prepared by using Me2SO-d6. The Hg2+ solution was prepared
as 0.25 M by using the perchlorate salt dissolved in CD3CN.
The solution containing compound 2 (0.5 mL of stock solution)
1
was placed in an NMR tube, and the H NMR spectrum was
recorded at 298 K. The stock solution of Hg2+ ions was
introduced in an incremental fashion (0.5, 1.0, 1.5, 2.0, 2.5,
3.0, 4.0, 6.0, 10, and 16 µL; 5 µL corresponds to 1 equiv), and
1
their corresponding H NMR spectra were recorded.
The 1H NMR titration of 2 (2.5 × 10-3 M in Me2SO-d6) with
MsOH was conducted similarly by incremental additions of
MsOH (1.25 M in Me2SO-d6).
1
The H NMR titration of 1 (0.5 mL of 5 × 10-4 M solution
in Me2SO-d6) with Hg2+ ions was carried out by a procedure
similar to that for 2. The stock solution of Hg2+ ions was
introduced in an incremental fashion (0.5, 1.0, 1.5, 2.0, and
4.0 µL; 1 µL corresponds to 1 equiv).
UV-Vis Titration of Compounds 1 and 2 with Hg2+
Ions. The stock solution of compound 1 (1 × 10-5 M) was
prepared by using spectroscopic grade Me2SO and distilled
water (v/v 1:1). The solution of Hg2+ ions (1 × 10-2 M) was
prepared by using mercury(II) perchlorate hydrate dissolved
in distilled water. The solutions of 1 in the range of 1 × 10-5
to 6.25 × 10-5 M exhibited a linear dependence of absorbance.
The absorption spectrum of 1 (2 mL of 1 × 10-5 M stock
solution) in a quartz cell (1 cm width) was recorded at 298 K.
The stock solution of Hg2+ ions was introduced in an incre-
mental fashion (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14
µL; 2 µL corresponds to 1 equiv), and their corresponding UV-
vis curves were recorded.
The binding constant was calculated according to the
following equation.
y ) [d/(2c)]{K-1 + c + x - [(K-1 + c + x)2 - 4cx]0.5
}
where c is the receptor concentration, d the saturated chemical
shift, K the association constant, x the substrate concentration,
and y the chemical shift.
Acknowledgment. We thank the National Science
Council for financial support.
The UV-vis titration of 2 with Hg2+ ions was carried out
by a procedure similar to that for 1, except for a slight change
of Hg2+ increments (2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28,
32, 36, 40, 56, 64, 72, 80, 90, 100, and 120 µL; 2 µL corresponds
to 1 equiv).
Supporting Information Available: NMR spectra, UV-
vis titration curves and figures. This material is available free
of charge via the Internet at http://pubs.acs.org.
1H NMR Titration of Compounds 1 and 2 with Hg2+
Ions or MsOH. The stock solution of 2 (2.5 × 10-3 M) was
JO050389E
5832 J. Org. Chem., Vol. 70, No. 15, 2005