Design and synthesis of intramolecular hydrogen bonding systems. Their application in metal cation sensing based on excited-state proton transfer reaction

Design and synthesis of intramolecular hydrogen bonding

systems. Their application in metal cation sensing based on

excited-state proton transfer reaction

Kun-Chan Wu,

Yu-Shan Lin,

Yu-Shan Yeh,

Chun-Yen Chen,

Moawia O. Ahmed,

Pi-Tai Chou

* and Yung-Son Hon

*

a

Department of Chemistry, National Taiwan University, Taipei 106, Taiwan

b

Department of Chemistry and Biochemistry, National Chung Cheng University, Chia-Yi 621, Taiwan

Received 14 July 2004; revised 22 September 2004; accepted 24 September 2004 Available online 18 October 2004

Abstract—We reported the design and synthesis of a new type of metal-cation probes, 3-hydroxy-4-(1,4,7,10-tetraoxa-13-azacyclopentadec-13-ylmethyl)naphthalene-2-carbaldehyde (1a) and its single hydrogen-bond analogue 1-(1,4,7,10-tetraoxa-13-azacylo-pentadec-13-ylmethyl)-2-naphthol (2a), in which 1-aza-15-crown-5 ether in combination with the naphthol oxygen acts as a receptor, while the mechanism of excited-state intramolecular proton transfer (ESIPT) is exploited as a signal transducer. The association constant of (2.5G0.5)!104, (3.8G0.4)!104, (5.5G0.5)!103and (1.2G0.3)!104MK1for the formation of 1a/NaC

, 1a/Ca2C, 2a/NaC

and 2a/Ca2C complexes, respectively, in CH3CN plus drastic fluorescence changes due to the fine-tuning of ESIPT reaction upon complexation, lead 1a

and 2a to be highly sensitive fluorescent sensors. The results add a new class into the category of metal-cation probes, with the perspective of designing ESIPT systems capable of sensing bio-analytes.

q2004 Elsevier Ltd. All rights reserved.

1. Introduction

Due to its importance in fundamental research, the excited state intramolecular proton transfer (ESIPT) process has received considerable attention.1 The ESIPT reaction generally incorporates transfer of a hydroxyl (or amino) proton to the carbonyl oxygen (or pyridinic nitrogen) through a pre-existing six or five membered ring hydrogen bonding (HB) configuration. The resulting proton-transfer tautomer, which generally possesses a vast difference in electronic configuration from its corresponding normal species, exhibits a large Stokes shifted fluorescence. This unusual photophysical property has led to versatile applications such as the development of laser dyes,2,3 probes for solvation environments,4,5ultraviolet stabilizers6 and radiation hard-scintillator counters,7etc.

Recently, we have applied 1-[(diethylamino)methyl]-3-hydroxy-2-naphthaldehyde (DMHN) possessing dual HB

sites (conformers A and B, see Scheme 1) to study the competitive ESIPT dynamics.8Despite a near degeneracy in the ground electronic state, conformers A and B undergo entirely different ESIPT dynamics, resulting in a zwitterion (lmaxw485 nm) and a keto-tautomer (lmaxw730 nm) emission, respectively. From the application viewpoint, one intriguing concept is to design ESIPT systems capable of capturing analytes and selectively blocking one HB site. The result may drastically alter the ESIPT pathway, and the associated photophysics can thus be exploited as a new type of sensor for molecule/metal-ion recognition. On this basis, we have designed 3-hydroxy-4-(1,4,7,10-tetraoxa-13-aza-cyclopentadec-13-ylmethyl)naphthalene-2-carbaldehyde (1a) and its single HB analogue 1-(1,4,7,10-tetraoxa-13-azacylopentadec-13-ylmethyl)-2-naphthol (2a). 1a and 2a were synthesized from the condensation between 3-hydroxy-naphthalene-2-carbaldehyde (3HN) (or 2-naphthol for 2a) and 1-aza-15-crown-5 ether via a modified Mannich reaction depicted in Scheme 2, in which 3HN was prepared from the reduction of 3-hydroxy-2-naphthoic acid methyl ester. Both prove to be highly sensitive fluorescent sensors based on the mechanism incorporating metal cation fine-tuning ESIPT reaction, adding a new class into the category of metal-cation probes.9,10

0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2004.09.102

Tetrahedron 60 (2004) 11861–11868

Keywords: Hydrogen bonding; Metal-cation probes; Excited state intra-molecular proton transfer reaction; Receptors.

* Corresponding authors. Tel.: C866 2 2363 0231x3988; fax: C886 2 2369 5208 (P.T.C.); e-mail addresses: [email protected]; [email protected]

2. Experimental 2.1. General

All reactions were performed under nitrogen atmosphere. Solvents were distilled from appropriate drying agents prior to use. Commercially available reagents were used without further purification unless otherwise stated. All reactions were monitored by TLC with Macherey-Nagel pre-coated

glassic sheets (0.20 mm with fluorescent indicator UV254).

Compounds were visualized with UV light at 254 and 365 nm. Flash column chromatography was carried out using silica gel from Merck (230–400 mesh).1H NMR and

13

C NMR in CDCl3were recorded using a Varian (Unity

Plus 400) spectrometer at 400 and 100 MHz, respectively. FAB-mass spectroscopy were collected on a JMS-700 double focusing mass spectrometer (JEOL, Tokyo, Japan) with a resolution of 3000 and 8000 for LR and HR

Scheme 2.The synthetic scheme for compounds 1a and 2a, and their possible conformers.

Scheme 1.The proposed competitive ESIPT mechanism for DMHN in aprotic solvents.8It should be noted that the rate of interconversion between conformers Aand B in the excited state is too slow to compete with the proton transfer process. Thus, each hydrogen-bonding conformer undergoes independent ESIPT process.

FAB-mass spectra. The source accelerating voltage was operated at 10 kV with Xe gun for FAB-mass spectra, using 3-nitrobenzyl alcohol as matrix.

2.1.1. 3-Methoxy-naphthalene-2-carboxylic acid methyl ester (4). To a suspension of potassium carbonate (2.7 g, 19.8 mmol) in acetone (10 mL) was added 2-hydroxy-3-naphthoic acid methyl ester (2.0 g, 9.9 mmol) and catalyst amount of 18-crown-6 ether (0.3 g, 1.0 mmol), followed by addition of methyl iodide (2.1 g, 14.9 mmol) under nitro-gen. The reaction mixture was subjected to reflux for 12 h. The mixture was cooled and the solvent was removed via reduced pressure. The product was then extracted with CH2Cl2. Subsequently, the organic layer was dried with

MgSO4 and filtered, and the solvent was removed in

vacuum. The residue was purified by column chromato-graphy (eluent: EtOAc/hexane (1:10 v/v)), yielding com-pound 4, (1.9 g, 89%).1H NMR (CDCl3, 400 MHz) d 3.9 (s, 3H), 3.98 (s, 3H), 7.18 (s, 1H), 7.34 (td, JZ8.0, 1.2 Hz, 1H), 7.50 (td, JZ8.0, 1.2 Hz, 1H), 7.72 (d, JZ8.4 Hz, 1H), 7.79 (d, JZ8.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 52.3 (CH3), 56.0 (CH3), 106.7 (CH), 114.9 (C), 121.6 (C), 124.3 (CH), 126.3 (CH), 127.4 (C), 128.3 (CH), 128.5 (CH), 132.6 (CH), 135.9 (C), 155.5 (C), 166.5 (C); IR (neat) 3062, 2956, 2837, 1732, 1640, 1590, 1507, 1470, 1428, 1337 cmK1; FAB-MS m/z (rel intensity) 217 (MC_{C1, 100%); HRMS}

(FAB) Calcd for C13H12O3216.0786, found 216.0788.

2.1.2. (3-Methoxy-naphthalen-2-yl)-methanol (5). To a suspension of LiAlH4 (0.7 g, 17.13 mmol) in dry THF

(40 mL) was added 3-Methoxy-naphthalene-2-carboxylic acid methyl ester (1.9 g, 8.7 mmol) in dry THF (10 mL) in ice bath. The mixture was stirred at room temperature for 6 h. The reaction was then quenched with water. The product extracted from CH2Cl2was washed with water and

dried with MgSO4. After filtration CH2Cl2was removed by

a rotavapor under reduced pressure and the residue was purified by column chromatography (eluent: EtOAc/hexane (1:5 v/v)), affording compound 5 as a white solid (1.4 g, 87%).1H NMR (CDCl3, 400 MHz) d 2.10 (s, 1H), 3.96 (s, 3H), 4.81 (s, 2H), 7.11 (s, 1H), 7.33 (td, JZ7.8, 1.0 Hz, 1H), 7.42 (td, JZ8.0, 1.0 Hz, 1H), 7.71–7.76 (m, 3H);13C NMR (CDCl3, 100 MHz) d 55.4 (CH2), 62.5 (CH3), 105.1 (CH), 123.8 (CH), 126.2 (CH), 126.3 (CH), 127.4 (CH), 127.5 (CH), 128.5 (C), 130.3 (C), 134.0 (C), 155.7 (C); IR (neat) 3590, 3406, 3058, 2952, 1644, 1608, 1512, 1465, 1436, 1401, 1340 cmK1; FAB-MS m/z (rel intensity) 188 (MC

, 100%); HRMS (FAB) Calcd for C12H12O2188.0837, found

188.0839.

2.1.3. 3-Methoxy-naphthalene-2-carbaldehyde (6). A solution of (3-methoxy-naphthalen-2-yl)-methanol (1.3 g 6.7 mmol) in CH2Cl2was added dropwise at 0 8C to

a mixture of pyridinium chlorochromate (PCC, 2.2 g 10.0 mmol), sodium acetate (0.8 g 10.0 mmol) and 4 A˚ molecular sieve (2.2 g) in CH2Cl2. The mixture was stirred

for 40 min under inert atmosphere. The solvent was removed under reduced pressure, and the residue was dissolved in ether and filtered. The product was purified by column chromatography. Elution with EtOAc/hexane (1:10 v/v) afforded compound 6 as yellow oil (1.0 g, 82%).1H NMR (CDCl3, 400 MHz) d 4.01 (s, 3H), 7.17 (s, 1H), 7.36 (td, JZ8.0, 1.0 Hz, 1H), 7.52 (td, JZ8.0, 1.0 Hz, 1H), 7.72 (d, JZ8.0 Hz, 1H), 7.86 (d, JZ7.6 Hz, 1H), 8.34 (s, 1H), 10.55 (s, 1H);13C NMR (CDCl3, 100 MHz) d 55.8 (CH3), 106.1 (CH), 124.3 (CH), 125.3 (C), 126.2 (CH), 127.4 (C), 128.8 (CH), 129.5 (CH), 130.6 (CH), 137.1 (C), 157.0 (C), 189.4 (CH); IR (KBr) 3064, 2994, 2880, 1700, 1632, 1602, 1470, 1434, 1406, 1346 cmK1; FAB-MS m/z (rel intensity), 187 (MC C1, 100%); HRMS (FAB) Calcd for C12H10O2186.0681, found 186.0684. 2.1.4. 3-Hydroxy-naphthalene-2-carbaldehyde (3HN). Under inert atmosphere, a solution of BBr3 (0.52 g,

3.2 mmol) in anhydrous CH2Cl2(5 mL) was added at 0 8C

to a solution of 3-methoxynaphthalene-2-carbaldehyde (0.5 mg, 2.7 mmol) in anhydrous CH2Cl2 (5 mL). The

mixture was stirred at room temperature for 1 h, and then the reaction was quenched with 1 N NaHCO3 aqueous

solution. The product was extracted with CH2Cl2, and the

resulting organic layers were dried with MgSO4. After

evaporation of the solvent under reduced pressure, the crude mixture was purified by column chromatography (eluent: EtOAc/hexane (1:20 v/v)), yielding 3HN in 0.37 mg (80%). 1_{H NMR (CDCl} 3, 400 MHz) d 7.23 (s, 1H), 7.36 (t, JZ 8.4 Hz, 1H), 7.55 (t, JZ8.4 Hz, 1H), 7.70 (d, JZ8.4 Hz, 1H), 7.85 (d, JZ8.4 Hz, 1H), 8.13 (s, 1H), 10.06 (s, 1H), 10.30 (s, 1H);13C NMR (CD3OD, 100 MHz) d 111.9 (CH), 122.1 (C), 124.3 (CH), 126.6 (CH), 127.3 (C), 129.2 (CH), 130.1 (CH), 137.7 (CH), 138.0 (C), 155.6 (C), 196.4 (CH); IR (KBr) 3256, 3064, 2985, 2856, 1674, 1518, 1458, 1417, 1388, 1358, 1308 cmK1; FAB-MS m/z (rel intensity) 172 (MC

, 100%); HRMS (FAB) Calcd for C11H8O2172.0524,

found 172.0528.

2.1.5. 3-Hydroxy-4-(1,4,7,10-tetraoxa-13-azacyclopenta-dec-13-ylmethyl)naphthalene-2-carbaldehyde (1a). A mixture of 1-aza-15-crown-5 ether (0.6 g, 2.8 mmol) and dibromomethane (1.1 g, 11.4 mmol) was stirred at room temperature for 4 h under inert atmosphere. A solution containing 3-hydroxy-naphthalene-2-carbaldehyde (0.1 g, 0.71 mmol) in CH2Cl2(2 mL) was added and the mixture

was stirred at room temperature for 6 h. The solvent was removed under reduced pressure, and the residue was dissolved in diethyl ether and filtered. The product was purified by column chromatography (eluent: methanol/ dichloromethane (2:98 v/v)), yielding compound 1a as yellow oil (203.1 mg, 0.5 mmol, 71%). 1H NMR (CDCl3,

400 MHz) d 2.90 (t, JZ5.2 Hz, 4H), 3.60–3.73 (m, 16H), 4.25 (s, 2H), 7.28 (t, JZ8.0 Hz, 1H), 7.49 (t, JZ8.2 Hz, 1H), 7.82 (d, JZ8.8 Hz, 2H), 8.23 (s, 1H), 10.58 (s, 1H); 13_{C NMR (CDCl} 3, 100 MHz) d 53.6 (CH2), 54 (CH2), 68.7 (2!CH2), 70.3 (4!CH2), 70.8 (2!CH2), 114.1 (C), 121.3 (CH), 123.2 (CH), 124.4 (C), 127.0 (C), 129.0 (CH), 130.4 (CH), 130.9 (CH), 135.9 (C), 157.4 (C), 191.6 (CH); IR (KBr) 3418, 3058, 2873, 1692, 1668, 1630, 1622, 1458, 1399, 1364 cmK1; FAB-MS m/z (rel intensity) 404 (MC

C 1, 100%); HRMS (FAB) Calcd for C22H29NO6403.1995,

found 403.1999; Anal. Calcd for C22H29NO6: C, 65.49; H,

7.24; N, 3.47. Found: C, 65.44; H, 7.29; N, 3.47.

2.1.6. 1-(1,4,7,10-Tetraoxa-13-azacyclopentadec-13-ylmethyl)-2-naphthol (2a).A mixture of 1-aza-15-crown-5 ether (0.6 g, 2.8 mmol) and dibromomethane (1.9 g, 11.0 mmol) was stirred at room temperature for 4 h under inert atmosphere. A solution of 2-naphthol (0.1 g,

0.69 mmol) in CH2Cl2(1 mL) was added and the mixture

was stirred at room temperature for 5 h. After removing CH2Cl2under reduced pressure, the residue was dissolved

in diethyl ether and filtered. The product was then purified by column chromatography (eluent: ethyl acetate/hexane (1:1 v/v)), yielding compound 2a (194.1 mg, 74%). 1H NMR (CDCl3, 400 MHz) d 2.93 (t, JZ5.2 Hz, 4H), 3.60– 3.71 (m, 16H), 4.27 (s, 2H), 7.08 (d, JZ8.8 Hz, 1H), 7.25 (t, JZ6.8 Hz, 1H), 7.41 (td, JZ7.6, 1.2 Hz, 1H), 7.65 (d, JZ 8.4, 1.6 Hz, 1H), 7.72 (d, JZ8.4 Hz, 1H), 7.82 (d, JZ 8.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d 54.3 (CH2), 54.7 (CH2), 68.8 (CH2), 70.3 (CH2), 70.3 (4!CH2), 70.7 (CH2), 111.9 (C), 119.3 (CH), 120.8 (CH), 122.2 (CH), 126.1 (CH), 128.3 (C), 128.7 (CH), 128.0 (CH), 132.6 (C), 156.4 (C); IR (KBr, neat) (cmK1): 3488, 3060, 2874, 1676, 1626, 1602, 1526, 1474, 1410, 1353, 1272, 1238, 1128; FAB-MS m/z (rel intensity) 376 (MC

C1, 100%); HRMS (FAB) Calcd for C21H29NO5 375.2046, found 375.2049;

Anal. Calcd for C21H29NO5: C, 67.18; H, 7.79; N, 3.73.

Found: C, 65.15; H, 7.76; N, 3.77.

2.2. Spectroscopy and dynamics measurements

Steady-state absorption and emission spectra were recorded by a Hitachi (U-3310) spectrophotometer and an Edinburgh (FS920) fluorimeter, respectively. The excitation light source of the fluorimeter has been corrected by the Rodamine B spectrum. In addition, the wavelength-dependent characteristics of the monochromator and photomultiplier have been calibrated by recording the scattered light spectrum of the corrected excitation light from a diffused cell in the range of 220–700 nm.

For determining fluorescence quantum yields and relaxation dynamics of the studied compounds, sample solutions were degassed by three freeze-pump-thaw cycles under vigorous stirring condition. Quinine sulfate/1.0 N H2SO4was used as

a reference for the quantum yield measurement, assuming a yield of 0.564 with 360 nm excitation. Nanosecond lifetime studies were performed by an Edinburgh FL 900 photon-counting system with a hydrogen-filled/or a nitrogen lamp as the excitation source. Data were analyzed using the nonlinear least squares procedure in combination with an iterative convolution method, which allows partial removal of the instrument time broadening and consequently renders a temporal resolution of w200 ps. A Suntex SP-701 pH-meter was used for the pH titration study.

3. Results and discussion

Similar to that of conformer A in DMHN,8the emission of 1arevealed strong solvent-polarity dependence, being red shifted from 505 nm in cyclohexane to 585 nm in CH3CN.

The spectral shift of the fluorescence upon increasing solvent polarity depends on the difference in permanent dipole moments between ground (mg) and excited (me)

states, which can be quantitatively expressed based on Lippert equation11expressed in Eq. 1

~nf Z ~n vac f K 2j~meK~mgj 2 hca3 0 ! 3 K 1 23 C 1
 (1)

where a0 and 3 denote the cavity radius and solvent

dielectric constant, respectively, ~nf and ~nvacf represent the

fluorescence peak frequency (in cmK1) in solvent studied and in vacuum, respectively. In this study, ~nvac_f can be replaced by the peak frequency in cyclohexane ð ~ncyc_f Þ if one neglects the induced dipole interaction. As shown in the insert ofFigure 1, the plot of ~ncyc_f Knf versus f(3)Z(3K1)/

(23C1) is sufficiently linear, and a slope of as large as 11,200 cmK1is deduced. a0 in Eq. 1 was estimated to be

6.4 A˚ via the Hartree Fock theories with 6-31G(d0,p0) basis sets. Accordingly, the change in dipole moment between ground and excited states was deduced to be as large as 17.2 debye.

The results lead us to ascribe the 585 nm emission in CH3CN

to a zwitterionic species resulting from O–H/N/ OK

/HNCESIPT. In contrast to the existence of conformers A and B for DMHN, as supported by the significant difference between absorption and excitation spectrum monitored at zwitterion emission,8the excitation spectrum of 1a in CH3CN is identical to the absorption spectrum. The

results indicate that the O–H/N intramolecular HB conformer A is the dominant species in 1a. Further support was given by the lack of resolution of any keto-tautomer emission at O700 nm predicted according to the ESIPT mechanism in conformer B of DMHN.8The more stable conformer A in 1a can qualitatively be rationalized by additional HB interactions between –O–H and ether oxygens. This viewpoint is also supported by a semi-empirical PM3 approach (seeFig. 2), estimating conformer A of 1a to be energetically lower than conformer B by w1.6 kcal/mol. In addition, the dipole moment of 5.52 debye calculated for conformer A of 1a is larger than that of B (3.75 debye). Accordingly, it is reasonable to expect the dominant conformer A in the strong polar solvent such as CH3CN.

The corresponding absorption and fluorescence titration spectra in CH3CN upon the addition of Na

C

to 1a are shown in Figures 3 and 4, respectively. Table 1 lists the

Figure 1.The emission spectra of 1a in cyclohexane (–&–), benzene (–C–), ethyl acetate (–:–), dichloromethane (–+–) and acetonitrile (–,–). The emission intensity has been normalized. Insert: the plot of ~ncyc_f Knfversus

photopysical properties of 1a and 2a and their associated metal ion complexes in CH3CN. Increasing the [NaC] led to

a hypsochromic shift of the absorption profile, in which the appearance of isosbestic points at w360 and 315 nm verifies a two-species equilibrium. Thus, the plot of the relationship between the measured absorbance A as a function of the added NaClO4 concentration, Cg, can be expressed by

Eq. 212 A0 A K A0 Z 3M 3cK3M
 1 Ka½Cg
C1   (2)

where 3M and 3c are molar extinction coefficients of 1a

and 1a/NaC

complex, respectively, at a selected wave-length. A0 denotes the absorbance of the free 1a at that

specific wavelength. The 1:1 1a/NaC

complexation was supported by a straight-line plot for the ratio of absorbance, A0/(A0KA), versus 1/[Na

C

] throughout the titration (insert of Fig. 3), and an association constant of as high as (2.5G0.5)!104MK1was deduced in CH3CN.

Drastic changes on the NaC

fluorescence titration spectra were also observed, in which the 585 nm zwitterion emission decreased with increasing NaC

concentrations (Fig. 4). The relationship between the measured

Figure 3.Absorption spectra of 1a (3.2!10K5M) in CH3CN by adding NaClO4concentrations (Cg) of (a) 0, (b) 1, (c) 2, (d) 4, (e) 8, (f) 16, (g) 30, (h) 60, (i) 120, (j) 240 equiv (1 equivZ2.9!10K6M). Insert: the plot of A0/A0KA against 1/Cgat 400 nm.

Figure 2.Two geometry-optimized (PM3 method) hydrogen-bonding conformers of 1a, and the respective critical bond distance (in A˚ ) and angle (in degree) involved in the intramolecular hydrogen bond.

Figure 4.Fluorescence spectra of 1a (3.2!10K5M) in CH3CN by adding NaClO4concentrations (Cg) of (a) 0, (b) 1, (c) 2, (d) 4, (e) 8, (f) 16, (g) 30, (h) 60, (i) 120, (j) 240 equiv (1 equivZ2.9!10K6M), lex: 400 nm. Insert: The spectrum of 1a at O700 nm by adding 10K3_{M NaClO4.}

fluorescence intensity F and Cgin a selected wavelength can be expressed by Eq. 312 F0 F K F0 Z FM3M ðF_C3_CKFM3MÞ 1 KaCg C1
 (3) where F0denotes the fluorescence intensity of free 1a. FM

and FCare fluorescence quantum yields of the free 1a and

complex, respectively, which are assumed to be constant throughout the titration. A linear plot for the ratio of fluorescence intensity, F0/(FKF0), versus 1/[NaC] for the

585 nm band reconfirmed the 1:1 complex formation, and Ka was deduced to be (2.3G0.3)!104MK1. Upon the

addition of [NaC

] of O10K3M, in which O99% of 1a/NaC

complex is formed, a weak emission band (Ff!10K4)

maximized at w730 nm was observed (see insert ofFig. 4). The mechanism of complexation can thus be rationalized by the rupture of the O–H/N hydrogen bond due to the usage of lone pair electrons on the nitrogen atom upon formation of the 1a/NaC

complex, resulting in switching the intramolecular HB sites from O–H/N (conformer A) to O–H/O]C (conformer B). ESIPT takes place in the NaC

/ conformer B complex, giving rise to a keto-tautomer 730 nm emission.

In contrast to a unique, zwitterionic emission band in 1a, 2a exhibits dual emission maximized at 355 (4.6 ns) and 432 nm (tfZ4.3 ns) (seeFig. 5). Similar to that assigned for 1-diethylaminomethyl-2-naphthol,13 the 432 nm emission can be ascribed to a zwitterion emission resulting from ESIPT. Accordingly, the 355 nm band, being a mirror image

with respect to the S0–S1(pp*) absorption of 2a, can be

unambiguously ascribed to the emission associated with the normal form of 2a in that the intramolecular hydrogen bond is ruptured due to the strong solute-solvent polar–polar interaction in CH3CN. ESIPT is thus prohibited during the

lifespan of the excited conformer C. It should be noted that the existence of conformer C is negligible in 1a due to its dual HB sites, that is, conformers A and B, providing an intact intramolecular HB environment free from solvent perturbation.

Titration of 2a by NaClO4revealed a similar hypsochromic

absorption shift with that of 1a, and an association constant of (5.5G0.5)!103MK1 was deduced in CH3CN (not

shown here). During titration the 432 nm emission band decreased, accompanied by the increase of a 355 nm normal emission (tfZ4.6 ns) with an isoemissive point at 397 nm.

The results lead us to conclude the rupture of the O–H/N hydrogen bond on the formation of the 2a/NaC

complex so that ESIPT is prohibited, giving rise to a normal Stokes shifted emission. This is quite different from 1a in that the conformation of 1a switches from the OH/N to the OH/ O]C site upon 1a/NaC

complexation, resulting in a weak keto-tautomer emission (vide supra). In comparison to 2a, the w4-folds larger Kavalue in 1a can be rationalized by the

more stable 1a/NaC _{complex due to the intramolecular}

OH/O]C hydrogen bond formation.

Attempts have also been made to titrate DMHN with NaC_.

The results revealed negligible spectral differences, verify-ing the importance of cappverify-ing NaC

with 1-aza-15-crown-5 ether in 1a and 2a. Furthermore, within the same range of concentrations, absorption and emission titration remained unchanged on adding KC_{to both 1a and 2a, and the results}

can simply be rationalized by the mismatched sizes between KC

and 1-aza-15-crown-5 ether.

The absorption and emission spectra of 1a as a function of the divalent metal ions, for example, Ca2C, in CH3CN are

shown inFigure 6. Upon an increase in [Ca2C], a decrease in the 393 nm absorption band was observed, accompanied

Figure 5.Fluorescence spectra of 2a (3.2!10K5M) in CH3CN by adding NaClO4concentrations (Cg) of (a) 0, (b) 1, (c) 5, (d) 10, (e) 20, (f) 40, (g) 80, (h) 160, (i) 230, (j) 650, (k) 1300 equiv (1 equivZ2.9!10K6M). Insert: the plot of F0/FKF0against 1/Cg, lex: 320 nm.

Figure 6.Absorption and emission spectra of 1a (3.2!10K5_{M) in CH3CN} by adding Ca2Cconcentrations (Cg): (a) 0, (b) 1, (c) 2, (d) 4, (e) 6, (f) 8, (g) 18, (h) 23, (i) 28, (j) 33 equiv (1 equivZ2.9!10K6_{M), lex: 450 nm.} Table 1. The photophysical properties of ion-free 1a and 2a and the

association constants of various 1a/metal ion and 2a/metal ion complexes in CH3CN Absorption lmax(nm) Fluorescence lmax(nm), tf Association constant Ka(MK1) NaC Ca2C 1a 390 585 (4.7 ns), 730 (520 fs) 2.3!104 _3.8!104 2a 327 355 (4.6 ns), 432 (4.3 ns) 5.5!103 _1.2!104

by the gradual increase of a new band maximized at 438 nm and the appearance of an isosbestic point at 412 nm. The straight-line plot of A0/(AKA0) versus 1/[Ca2C] confirms a

1:1 1a/Ca2Ccomplexation, and an association constant of (3.8G0.4)!104MK1 was deduced. Upon 450 nm exci-tation, the increase of fluorescence intensity as a function of [Ca2C] was observed, and the emission peak wavelengths shifted from 580 to 560 nm (Fig. 6). During titration, the relaxation dynamics of the entire band could be well fitted by biexponential decay kinetics, and lifetimes were resolved to be 4.7 and 7.1 ns, indicating the existence of two distinct species. Due to its spectral similarity with that of the KOH basified 1a oxide (in MeOH), the 438 nm absorption band can be assigned to a 1a/Ca2Ccomplex absorption, in which the hydroxyl proton is detached to form oxide, along with the nitrogen atom binding to Ca2C, giving rise to a 560 nm (tfw7.1 ns) anion emission. In a comparative study,

although similar spectral change was observed upon titration of DMHN with Ca2C, the association constant of (8.0G0.3)!103MK1is smaller than that of the 1a/Ca2C complex by wfive folds. We thus conclude that in addition to oxide (OK

) and nitrogen atoms, the remaining ether

oxygens in azacrown are also incorporated in the 1a/Ca2C complexation. A similar coordination structure has been reported in a ([Ca(1-aza-15-crown-5 ether)(CH3–OH)2]

BPh4) single crystal.14

In contrast to the oxy-anion characteristic for the 1a/Ca2C complex, drastically different Ca(ClO4)2titration spectra for

2a were observed, in which increasing Ca2C resulted in a hypsochromic spectral shift with an appearance of an isosbestic point at 324 nm (Fig. 7). The lack of oxide absorption indicates that the hydroxyl group remains intact in 2a during the Ca2C titration. This viewpoint is further supported by a decrease of the 435 nm zwitterion emission during the titration, accompanied by an increase of the 360 nm normal emission with an isoemissive point appearing at 405 nm. The difference in capping Ca2Ccan be qualitatively rationalized by the stronger acidity of the hydroxyl group in 1a due to the aldehyde (CHO) electron withdrawing property (pKaw6.6 in 1a versus w7.7 in 2a according to the pH titration shown inFig. 8). The dissimilar binding property is also manifested by the association strength, in which Ka of (1.2G0.3)!10

4

MK1 for 2a is smaller than that of 1a by more than three folds.

4. Conclusion

In conclusion, we have reported the design and synthesis of a new type of metal-cation probes 1a and 2a, in which 1-aza-15-crown-5 ether in combination with a hydroxyl group acts as a receptor, while a mechanism of switch or prohibition of ESIPT upon complexation is exploited as the signal transducer. 1a is superior to 2a owing to its larger Ka

values and metal-ion-selective spectral change. It is thus conceivable to design multiple HB systems capable of sensing bio-analytes based on the ESIPT mechanism. Further work focusing on this issue is currently in progress.

Acknowledgements

We thank the National Science Council for financial support.

References and notes

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Figure 7.Absorption and emission spectra of 2a (3.2!10K5M) in CH3CN by adding Ca2C_{concentrations (Cg): (a) 0, (b) 2, (c) 4, (d) 6, (e) 10, (f)} 15 equiv (1 equivZ2.9!10K6M). lex: 320 nm.

Figure 8.The ground-state pH (NaOH) titration experiment for 1a (&) and 2a(C) in water. Data were obtained from the pH dependent absorbance at 450 nm and 350 nm for 1a and 2a, respectively.

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