Na+ triggered fluorescence sensors for Mg2+ detection based on a coumarin salen moiety

Article abstract of DOI:10.1021/ol200530g

Chemical equations presented. Two coumarin salen-based sensors CS1 and CS2 can exhibit a pronounced fluorescence enhancement response toward Mg ²⁺ as high as 36-fold (CS1) and 111-fold (CS2) in the presence of Na⁺ as a synergic trigger. More importantly, the fluorescent color of CS1 was bright green instead of weak yellow after the addition of Mg ²⁺ and Na⁺ together, which can be easily detected by the naked eye.

Full text of DOI:10.1021/ol200530g

ORGANIC
LETTERS
Naþ Triggered Fluorescence Sensors for
Mg2þ Detection Based on a Coumarin
Salen Moiety
2011
Vol. 13, No. 9
2252–2255
Yu Dong, Junfeng Li, Xiaoxiang Jiang, Fengyan Song, Yixiang Cheng,* and
Chengjian Zhu*
Key Laboratory of Mesoscopic Chemistry of MOE, School of Chemistry and
Chemical Engineering, Nanjing University, Nanjing 210093, China
yxcheng@nju.edu.cn; cjzhu@nju.edu.cn
Received February 27, 2011
ABSTRACT
Two coumarin salen-based sensors CS1 and CS2 can exhibit a pronounced fluorescence enhancement response toward Mg2þ as high as 36-fold
(CS1) and 111-fold (CS2) in the presence of Naþ as a synergic trigger. More importantly, the fluorescent color of CS1 was bright green instead of
weak yellow after the addition of Mg2þ and Naþ together, which can be easily detected by the naked eye.
The magnesium ion (Mg2þ) is one of the most abundant
divalent cations in cells and can play vital roles in many
cellular processes, such as enzyme-driven biochemical
reactions, proliferation of cells, and stabilization of
DNA conformation.1 Moreover, Mg2þ is also believed
to be an etiological factor in many pathological processes,
such as congestive heart failure, cerebral infarction, lung
cancer, and muscle dysfunction.2 Consequently, the detec-
tion of Mg2þ has attracted increasing interest in the areas of
chemical and biological sciences. In the past few years, many
analytical methods have been developed for the detection of
Mg2þ, including atomic absorption, ion-selective electrodes
(ISEs), and NMR.3 Optical detection, following changes of
fluorescence or UVꢀvis spectroscopy arisen from the Mg2þ
-
induced perturbation of the chromophore, is best suitable for
Mg2þ detection in biological systems.
Recently, investigations on highly sensitive and selective
fluorescent sensors have drawn considerable attention due
to its convenience and real-time response. In particular,
numerous efforts have been devoted to the design of
chemosensory systems with unique electrical and optical
properties that are capable of detecting metal ions in both a
real-time and reversible fashion. A number of fluorescent
sensors for Mg2þ detection have been reported in previous
(1) (a) Rubin, H. Arch. Biochem. Biophys. 2007, 458, 16–23. (b)
Cowan, J. A. Biometals 2002, 15, 225–235. (c) Shoda, T.; Kikuchi, K.;
Kojima, H.; Urano, Y.; Komatsu, H.; Suzuki, K.; Nagano, T. Analyst
2003, 128, 719–723. (d) Wolf, F. I.; Torsello, A.; Fasanella, A.; Cittadini,
A. Mol. Aspects Med. 2003, 24, 11–25. (e) Saris, N. E. L.; Mervaala, E.;
Karppanen, H.; Khawaja, J. A.; Lewenstam, A. Clin. Chem. Acta 2000,
294, 1–26. (f) Rubin, H. Bioessays 2005, 27, 311–320. (g) Moll, J. R.;
Acharya, A.; Gal, J.; Mir, A. A.; Vinson, C. Nucleic Acids Res. 2002, 30,
1240–1246.
(3) (a) Zmozinski, A. V.; de Jesus, A.; Vale, M. G. R.; Silva, M. M.
Talanta 2010, 83, 637–643. (b) de Jesus, A.; Zmozinski, A. V.; Barbar,
J. A.; Vale, M. G. R.; Silva, M. M. Energy Fuels 2010, 24, 2109–2112. (c)
Kilic, Z.; Acar, O.; Ulasan, M.; Ilim, M. Food Chem. 2002, 76, 107–116.
(d) Luo, Y.; Zhang, B.; Chen, M.; Wang, J.; Zhang, X.; Gao, W. Y.;
Huang, J. F.; Fu, W. L. J. Agric. Food Chem. 2010, 58, 9396–9400. (e)
Shim, J. H.; Jeong, I. S.; Lee, M. H.; Hong, H. P.; On, J. H.; Kim, K. S.;
Kim, H. S.; Kim, B. H.; Cha, G. S.; Nam, H. Talanta 2004, 63, 61–71. (f)
Zhu, J. W.; Qin, Y.; Zhang, Y. H. Anal. Chem. 2010, 82, 436–440. (g)
(2) (a) Stepura, O. B.; Martynow, A. I. Int. J. Cardiol. 2009, 134, 145–
€
€
ꢀ
147. (b) Larsson, S. C.; Virtanen, M. J.; Mars, M.; Mannisto, S.;
Pietinen, P.; Albanes, D.; Virtamo, J. Arch. Intern. Med. 2008, 168,
459–465. (c) Mahabir, S.; Wei, Q. Y.; Barrera, S. L.; Dong, Y. Q.; Etzel,
C. J.; Spitz, M. R.; Forman, M. R. Carcinogenesis 2008, 29, 949–956. (d)
Nielsen, F. H.; Lukaski, H. C. Magnesium Res. 2006, 19, 180–189.
Hamdi, A.; Kim, S. H.; Abidi, R.; Thuery, P.; Kim, J. S.; Vicens, J.
Tetrahedron 2009, 65, 2818–2823. (h) Hifumi, H.; Tanimoto, A.; Citterio,
D.; Komatsu, H.; Suzuki, K. Analyst 2007, 132, 1153–1160. (i) Ishida, M.;
Naruta, Y.; Tani, F. Angew. Chem., Int. Ed. 2010, 49, 91–94. (j) Patra, S.;
Paul, P. Dalton Trans. 2009, 8683–8695.
r
10.1021/ol200530g
Published on Web 04/05/2011
2011 American Chemical Society

works, such as diketone,4 crown ether,5 polymer based
ligands,6 and nanoparticles.7 However, some available
Mg2þ sensors have difficulty in distinguishing Mg2þ and
Ca2þ,8 so it is still interesting and of importance to design a
highly selective and sensitive fluorescent sensor that can
recognize Mg2þ without the interference from other metal
prepared according to reported procedures.11 CS1 and CS2
could be obtained by condensation of o-phenylenediamine
and (R,R)-1,2-diaminocyclohexane with 8-formyl-7-hydro-
xyl-4-methyl-coumarin via a nucleophilic additionꢀelimina-
tion reaction in 81.9% and 86.8% yields, respectively.
The fluorescence response behaviors of sensors CS1 and
CS2 on various metal ions have been investigated. CS1 and
CS2 can display weak and broad emission bands centered
at 550 and 510 nm, respectively. Figure 1a and 1b show the
fluorescencespectra of CS1 and CS2 (10 μM in THF) upon
the addition of various metal ions in aqueous solution with
the excitation at 360 and 352 nm. As shown in Figure 1a,
obvious fluorescence enhancement could be observed as
high as 4.7-fold (SI 4a) upon the addition of Mg2þ at a 1:1
molar ratio, and the addition of other selected metal ions,
ions, especially Ca2þ
.
Salen-based ligands have the potentially tetradentate
N2O2 donor and can form stable complexes with various
metal ions. There are many reports on these salen-based
fluorescent sensors for metal ions detection.9 As a better
fluorophore, coumarin derivatives have been widely used
for constructing sensory systems due to their desirable
photophysical properties with a large Stock shift and
visible emission wavelength.10 In this paper, we designed
two coumarin salen-based ligands as fluorescence sensors
for Mg2þ recognition. The fluorescence intensities of the
two sensors are enhanced by mixing Naþ and Mg2þ
together, and the fluorescence color is bright green, which
can be easily detected by the naked eye. The results indicate
that two coumarin salen-based sensors can exhibit high
sensitivity and selectivity for Mg2þ recognition in the
presence of Naþ as the coexisting cation.
suchasLiþ, Naþ, Kþ, Ca2þ, Fe3þ, Co2þ, Ni2þ, Agþ, Hg2þ
,
and Pb2þ, causes almost no fluorescence response. But
Cr3þ, Ni2þ, and Cd2þ cause limited fluorescence quench-
ing under the same conditions (I/I0 < 0.7). Meanwhile,
Cu2þ can lead to almost complete quenching of CS1
(Supporting Information, SI 4a), which can be attributed
to the energy or electron-transfer reactions arisen from the
strong metalꢀligand orbital interaction upon the forma-
tion of binding metal complexes.12 In addition, the max-
imum emission wavelength of CS1 appears remarkably
blue-shifted from 550 to 490 nm. As shown in Figure 1b,
Mg2þ (10 μM) can lead to the pronounced fluorescence
enhancement of CS2 as high as 9.8 (SI 4b) at a 1:1 molar
ratio. Moreover, a blue shift is also observed from 510 to
The synthesis protocol of two sensors is outlined (SI,
Scheme 1). 8-formyl-7-hydroxy-4-methylcoumarin was
(4) (a) Suzuki, Y.; Komatsu, H.; Ikeda, T.; Saito, N.; Araki, S.;
Citterio, D.; Hisamoto, H.; Kitamura, Y.; Kubota, T.; Nakagawa, J.;
Oka, K.; Suzuki, K. Anal. Chem. 2002, 74, 1423–1428. (b) Shoda, T.;
Kikuchi, K.; Kojima, H.; Urano, Y.; Komatsu, H.; Suzuki, K.; Nagano,
T. Analyst 2003, 128, 719–723. (c) Komatsu, H.; Iwasawa, N.; Citterio,
D.; Suzuki, Y.; Kubota, T.; Tokuno, K.; Kitamura, Y.; Oka, K.; Suzuki,
K. J. Am. Chem. Soc. 2004, 126, 16353–16360. (d) Kim, H. M.; Yang,
P. R.; Seo, M. S.; Yi, J. S.; Hong, J. H.; Jeon, S. J.; Ko, Y. G.; Lee, K. J.;
Cho, B. R. J. Org. Chem. 2007, 72, 2088–2096. (e) Kim, H. M.; Jung, C.;
Cho, B. R. Angew. Chem., Int. Ed. 2007, 46, 3460–3463. (f) Valeur, B.;
Leray, I. Coord. Chem. Rev. 2000, 205, 3–40.
(5) (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) Liu, Y.; Han, M.; Zhang, H. Y.; Yang, L. X.;
Jiang, W. Org. Lett. 2008, 10, 2873–2876. (c) Kim, J.; Morozumi, T.;
Nakamura, H.; Nakamura, H. Org. Lett. 2007, 9, 4419–4422. (d)
Bronson, R. T.; Montalti, M.; Prodi, L.; Zaccheroni, N.; Lamb,
R. D.; Dalley, N. K.; Izatt, R. M.; Bradshaw, J. S.; Savage, P. B.
Tetrahedron 2004, 60, 11139–11144.
(6) (a) Ding, A. L.; Pei, J.; Yu, W. L.; Lai, Y. H.; Huang, W. Thin
Solid Films 2002, 417, 198–201. (b) Pei, J.; Yu, W. L.; Ding, A. L.; Yu,
W. L.; Lai, Y. H. Macromol. Rapid Commun. 2002, 23, 21–25.
(7) Park, E. J.; Brasuel, M.; Behrend, C.; Philbert, M. A. Anal. Chem.
2003, 75, 3784–3791.
(8) (a) Pesco, J.; Salmon, J.; Vigo, J.; Viallet, P. Anal. Biochem. 2001,
290, 221–231. (b) Kim, J.; Morozumi, T.; Kurumatani, N.; Nakamura,
H. Tetrahedron Lett. 2008, 49, 1984–1987. (c) Dubonosov, A. D.;
Minkin, V. I.; Bren, V. A.; Shepelenko, E. N.; Tsukanov, A. V.;
Starikov, A. G.; Borodkin, G. S. Tetrahedron 2008, 64, 3160–3167. (d)
Gromov, S. P.; Ushakov, E. N.; Fedorova, O. A. J. Org. Chem. 2003, 68,
6115–6125.
(9) (a) Cozzi, P. G. Chem. Soc. Rev. 2004, 33, 410–421. (b) Pucci, D.;
Aiello, I.; Bellusci, A.; Crispini, A.; Ghedini, M.; Deda, M. L. Eur. J.
Inorg. Chem. 2009, 4274–4281. (c) Chu, Z. L.; Huang, W.; Wang, L.;
Gou, S. H. Polyhedron 2008, 27, 1079–1092. (d) Xu, Y.; Meng, J.; Meng,
L. X.; Dong, Y.; Cheng, Y. X.; Zhu, C. J. Chem.;Eur. J. 2010, 16,
12898–12903.
(10) (a) Trenor, S. R.; Shultz, A. R.; Love, B. J.; Long, T. E. Chem.
Rev. 2004, 104, 3059–3077. (b) Suresh, M.; Das, A. Tetrahedron Lett.
2009, 50, 5808–5812. (c) Komatsu, K.; Urano, Y.; Kojima, H.; Nagano,
T. J. Am. Chem. Soc. 2007, 129, 13447–13454. (d) Lim, N. C.; Schuster,
J. V.; Porto, M. C. Inorg. Chem. 2005, 44, 2018–2030. (e) Ray, D.;
Bharadwaj, P. K. Inorg. Chem. 2008, 47, 2252–2254. (f) Lim, N. C.;
Figure 1. Selectivity of sensors (a) CS1 and (b) CS2 toward Mg2þ
and other metal ions: fluorescence spectra of the ligandꢀmetal
ion complexes.
€
Bruckner, C. Chem. Commun. 2004, 1094–1095. (g) Hanshaw, R. G.;
Hilkert, S. M.; Jiang, H. Tetrahedron Lett. 2004, 45, 8721–8724.
Org. Lett., Vol. 13, No. 9, 2011
2253

430. Meanwhile, CS2 shows much more sensitivity toward
Zn2þ (39.3-fold), which is in accordance with our previous
report.9d The obvious fluorescent enhancement responses
can be attributed to two reasons: (1) the decrease of the
HOMO of the conjugated segment of the ligand when the
Salen-based N2O2 receptor coordinates with Mg2þ or Zn2þ 13
;
(2) upon binding Mg2þ or Zn2þ, a coordination-enhanced
fluorescence process happens, meanwhile the intramolecular
electron-transfer process is forbidden. So an enhancement in
the emission spectrum and a red shift in the absorption
spectrum are observed simultaneously. (SI 6).14
Inspired by the above results, we further investigated the
fluorescent response behaviors of two coumarin salen-
based sensors CS1 and CS2 toward Mg2þ under a Naþ
triggered synergistic effect. The fluorescence titration of
CS1-Naþ with Mg2þ was presented in Figure 2a. The
fluorescent intensities of a Naþꢀligand complex show a
gradual enhancement as high as 36-fold upon the addition
of Mg2þ from 0.1 to 1.2 equiv. Moreover, the maximum
emission wavelength of sensor CS1 is also blue-shifted
from 550 to 490 nm, which is induced by the well-known
ICT mechanism.14c Figure 2b shows a gradual fluores-
cence enhancement of the CS2ꢀNaþ complex upon addi-
tion of Mg2þ from 0.1 to 1.2; a much larger enhancement
efficiency that reaches 111-fold is observed when 1.0 equiv
of Mg2þ is added. Meanwhile the maximum emission
wavelength of sensor CS2 is blue-shifted from 510 to
430 nm. The interesting results suggest that the effects of
Naþ and Mg2þ ions are synergistic, because the presence of
10 μM Mg2þ alone does not induce such a large fluores-
cence enhancement in this recognition event.
Figure 2. Fluorescence spectra of (a) CS1 and (b) CS2 (10 μM) þ
1.0 equiv of Naþ in THF with increasing amounts of Mg2þ ((0,
1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0, 11.0, 12.0) ꢁ 10ꢀ6
mol/L) ((a): λex = 360 nm; (b): λex = 352 nm); inset: Plot of the
concentration of Mg2þ vs I/I0, where I is the fluorescence
intensity of (a) CS1 or (b) CS2 with the addition of Mg2þ at (a)
λem = 490 nm or (b) 430 nm and I0 is the fluorescence intensity
of (a) CS1 or (b) CS2 without Mg2þ at (a) 550 nm or (b) 510 nm.
So far there has been no report on the pronounced
response behavior toward Mg2þ detection based on the
fluorescence sensor under the Naþ triggered synergistic
effect. This may be due to the building blocks of salen
receptors of CS1 and CS2 fitting well for the formation of
the stable Mg2þꢀligand and Zn2þꢀligand complexes. On
the other hand, Naþ can still interact with another lone
pair of electrons on the oxygen atom of OH groups after
Mg2þ has coordinated with one lone pair of electrons on
the oxygen atom of a N2O2 group, which can reduce the
nonradiative decay of the excited state and lead to the
pronounced fluorescence enhancement.
In this paper, we proceeded to further evaluate their
selectivity of CS1 and CS2 toward Mg2þ. The results
indicate that Liþ, Kþ, Ca2þ, Zn2þ, Hg2þ, and Pb2þ can
also slightly trigger the fluorescent enhancement of CS1-
Mg2þ as high as 6.1-, 6.7-, 7.4-, 7.5-, 5.2-, and 8.5-fold
(Figure 3a). In parallel, Liþ, Kþ, Ca2þ, and Zn2þ can also
increase the fluorescence intensities of CS2-Mg2þ by 12.6-,
16.4-, 13.7-, and 47.5-fold (Figure 3b), respectively. Other
metal ions, such as Cr3þ, Cd2þ, and Cu2þ can cause
different content fluorescence quenchings of CS1-Mg2þ
and CS2-Mg2þ (see SI 3).
The optical output signals of a salen-based ligand in
response to metal ion binding have been used to develop
AND and INHIBIT logic gates.15 The AND gate is a
digital logic gate that implements logical conjunction,
which results in a HIGH output (1) only if both of
the inputs are simultaneously applied as HIGH. In
another sense, the function of AND can effectively find
the “minimum” between two binary digits, just as the OR
function finds the “maximum”. The fluorescence of CS2
(11) (a) Kulkarni, A.; Patil, S. A.; Badami, P. S. Eur. J. Med. Chem.
2009, 44, 2904–2912. (b) Kulkarni, A.; Patil1, S. A.; Badami, P. S.
J. Enzyme Inhib. Med. Chem. 2010, 25, 87–96. (c) Hu, Y.; Li, Q. Q.; Li,
H.; Guo, Q. N.; Lu, Y. G.; Li, Z. Y. Dalton Trans. 2010, 39, 11344–
:
11352. (d) Yıldırım, M.; Kaya, I. J. Fluoresc. 2010, 20, 771–777.
ꢀ
~
(12) (a) Pina, F.; Bernardo, M. A.; GarcIa-Espana, E. Eur. J. Inorg.
Chem. 2000, 2143–2157. (b) Xu, Z. C.; Yoon, J.; Spring, D. R. Chem.
Soc. Rev. 2010, 39, 1996–2006. (c) Bozdemir, O. A.; Guliyev, R.;
Buyukcakir, O. J. Am. Chem. Soc. 2010, 132, 8029–8036. (d) de Silva,
A. P.; McClenaghan, N. D. Chem.;Eur. J. 2002, 8, 4935–4945.
(13) (a) Liu, Y.; Zhang, S. W.; Miao, Q.; Zheng, L. F.; Zong, L. L.;
Cheng, Y. X. Macromolecules 2007, 40, 4839–4847. (b) Liu, Y.; Miao,
Q.; Zhang, S. W.; Huang, X. B.; Zheng, L. F.; Cheng, Y. X. Macromol.
Chem. Phys. 2008, 209, 685–694.
(15) (a) de Silva, A. P.; Gunaratne, H. Q. N.; McCoy, C. P. Nature
1993, 364, 42–44. (b) Coskun, A.; Deniz, E.; Akkaya, E. U. Org. Lett.
2005, 7, 5187–5189. (c) Irie, M.; Fukaminato, T.; Sasaki, T.; Tamai, N.;
Kawai, T. Nature 2002, 420, 759. (d) Montenegro, J. M.; Perez-Inestrosa,
E.; Collado, D. Org. Lett. 2004, 6, 2353–2355. (e) Joseph, R; Ramanujam,
B.; Acharya, A.; Rao, C. P. J. Org. Chem. 2009, 74, 8181–8190. (f) Pischel,
U. Angew. Chem., Int. Ed. 2007, 46, 4026–4040. (g) Saha, A.; Manna, S.;
Nandi, A. K. Soft Matter 2009, 5, 3992–3996.
(14) (a) Zhang, Y.; Guo, X. F.; Si, W. X.; Jia, L. H.; Qian, X. H. Org.
Lett. 2008, 10, 473–476. (b) Liu, Z. P.; Zhang, C. L.; Li, Y. L.; Wu, Z. Y.;
Qian, F.; Yang, X. L.; He, W. J.; Gao, X.; Guo, Z. J. Org. Lett. 2009, 11,
795–798. (c) Wang, Y. W.; Yu, M. X.; Yu, Y. H.; Bai, Z. P.; Shen, Z.; Li,
F. Y.; You, X. Z. Tetrahedron Lett. 2009, 50, 6169–6172.
2254
Org. Lett., Vol. 13, No. 9, 2011

Figure 5. Fluorescence output of ligand CS2 in the presence of
chemical inputs, Zn2þ (10 μM) and Cu2þ (10 μM), and the truth
table of the INH gate.
Figure 3. Selectivity of the CS1 (a) and CS2 (b) toward Mg2þ and
other metal ions. In these experiments, the fluorescence mea-
surement was taken at λex = 360 nm (for CS2, λex = 352 nm)
from 10 μM of the sensor in THF at room temperature and in the
absence and presence of 1.0 equiv of a metal ion. Inset: The
fluorescence image of a solution of the sensors (10 μM) plus 1.0
equiv of a metal ion excited by a commercially available UV lamp
(λex = 365 nm) (1: None; 2: Naþ; 3: Mg2þ; 4: Naþ þ Mg2þ).
Mg2þ (Input 2) are combined with CS2 in a THF solution
(Figure 4).
An INH logic gate can be basically understood as an
AND operation with oneofthe inputsbeing reversed. That
is, INH can be integrated by incorporating a NOT and an
AND gate.16 A basic two-input INHIBIT action can
be obtained for CS2 (10 μM) with Zn2þ (10 μM) and Cu2þ
(10 μM) asinputs (Figure 5). Fluorescenceenhancement of
CS2 at 450 nm is observed only in the presence of 1.0 equiv
of Zn2þ and the absence of Cu2þ, leading to the output as
“1”. Under other conditions the fluorescence of CS2 is
quenched, resulting in output “0”.
In summary, two salen-based ligands can act as excellent
fluorescent sensors for the detection of Mg2þ. Mg2þ can
producea pronouncedfluorescenceenhancement response
under a Naþ triggered synergistic effect. Two fluorescence-
based logic gates can be used as potential candidates for a
molecular logic circuit.
Acknowledgment. This work was supported by the
National Natural Science Foundation of China (No.
20832001, 20972065, 21074054) and National Basic Re-
search Program of China (2007CB925103, 2010CB923303).
Supporting Information Available. synthetic proce-
dures, characterization, and additional spectra data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Figure 4. Fluorescence output of ligand CS2 (10 μM) in the
presence of chemical inputs, Naþ (10 μM) and Mg2þ (10 μM),
and the truth table of the AND gate.
(16) (a) Kluciar, M.; Ferreira, R.; de Castro, B.; Pische, U. J. Org.
Chem. 2008, 73, 6079–6085. (b) 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.
(10 μM) at 430 nm (Output 1) would be largely enhanced
only if 1.0 equiv of Naþ (Input 1) and 1.0 equiv of
Org. Lett., Vol. 13, No. 9, 2011
2255