HETEROCYCLES

Paper | Special issue | Vol. 82, No. 1, 2010, pp. 473-478
Received, 15th April, 2010, Accepted, 31st May, 2010, Published online, 2nd June, 2010.
DOI: 10.3987/COM-10-S(E)20

■ Unexpected Fluorescent Behavior of a New pH Chemosensor Based upon Bis-4-piperidine-1,8-naphthalimide Linked by the Diethylenetriamine

Hui Xu,* Huiling Dai, and Junqiang Ran

Laboratory of Pharmaceutical Design & Synthesis, College of Life Sciences, Northwest A & F University, Yangling, Shaanxi, 712100, China

Abstract

A new fluorescent chemosensor 3 based upon bis-4-piperidine-1,8-naphthalimide linked by the diethylenetriamine was synthesized, and its fluorescent properties were also investigated. Different from other bis-1,8-naphthalimides, no changes in the fluorescence spectra of 3 in the presence of metal cations was observed, and it displayed an unexpectedly strong fluorescence quench in weakly acidic aqueous solutions. Its pKa value (7.25) indicated that it would be suited as a new pH fluorescent chemosensor to monitor changes at the physiological pH range.

INTRODUCTION
Currently, the design and synthesis of fluorescent devices for the sensing and reporting chemical speciesis of very importance for biological and environmental applications.1-5 Due to their fluorescent properties and special interactions with some biomolecules, mono-1,8-naphthalimides are frequently used as the fluoroionophores to prepare fluorescent chemosensors for metal cations and protons.6-9 To the best of our knowledge, however, little attention has been paid to the fluorescent properties of the bis-1,8-naphthalimides. Chovelon et al. described the changes in the fluorescence spectra of bis-1,8-naphthalimide analog 1 (Figure 1) in the presence of metal cations (Zn2+, Ni2+ and Ce3+) and protons.10 Staneva et al. reported Fe3+ and Cr3+-induced fluorescence spectra changes of bis-1,8-naphthalimide (Zn2+, Ni2+ and Ce3+) and protons.10 Staneva et al. reported Fe3+ and Cr3+-induced fluorescence spectra changes of bis-1,8-naphthalimide analog 2 (Figure 1).11 Obviously, introducing the different groups (e.g., N,N-dimethylaminoethylamino group) on the 4-position of 1 could lead to compound 2 with different photophysical properties. Therefore, in this paper we want to introduce the piperidine group on the 4-position of 1, and investigate the fluorescent properties of a new bis-1,8-naphthalimide analog 3 (Figure 1) based on bis-4-piperidine-1,8-naphthalimide linked by the diethylenetriamine.

RESULTS AND DISCUSSION
As shown in Scheme 1, 4-bromo-1,8-naphthalic anhydride firstly reacted with piperidine in 2-methoxyethanol to give 4-piperidine-1,8-naphthalic anhydride 4 in a 86% yield.5 Then compound 3 was obtained in a 95% yield by treating compound 4 with diethylenetriamine in ethanol. The structure of compound 3 was well characterized by 1H NMR, 13C NMR, HR-MS and mp.

The data of absorption (λA), fluorescence (λF), quantum yield of fluorescence (ΦF), and Stokes shift (νA-νF) of 3 in the different organic solvents were listed in Table 1. Due to the good solubility for the HTM ions and the fluorescent quantun yields (ΦF), tetrahydrofuran (THF) was chosen as the solvent for all the measurements. Firstly, the metal-induced fluorescence changes of 3 in THF solution were investigated. As shown in Figure 2, an enhancement or reducement of fluorescent intensity of 3 in the presence of different metal cations (such as Zn2+, Fe3+, Cd2+, Pb2+, Ca2+, Cu2+, Mg2+, and Ba2+) has not been observed. Then the influence of protons on the fluorescent intensity of 3 was also tested in water over a pH range of 3.04-9.34. The parameters of absorption and fluorescent spectra of 3 in water of different pH were listed in Table 2. As outlined in Figure 3, compound 3 exhibited high sensitivity to the presence of protons. For example, from pH 8.20 to 4.88, a dramatic decrease in the fluorescent intensity of 3 was observed. That is, the fluorescent intensity of 3 was greatly reduced when the solution became acidic. Meanwhile, the fluorescent intensity of 3 at pH 8.20 was more than 17 times of that at pH 3.04. It should be noteworthy that the fluorescent intensity of 3 was absolutely observed in water, while the fluorescent intensity of 1 and 2 was observed in mixture solution (e.g., MeCN/H2O or MeOH/H2O).10,11 The pH dependence of fluorescent intensity could be analyzed with below equation to give the pKa value.
log[(IFmax- IF)/(IF-IFmin)] = pH-pKa

The calculated pKa value was 7.25 (288 K). Interestingly, the influence of protons on the fluorescent intensity of 3 was completely different from its other bis-1,8-naphthalimide analogs 1 (pKa = 7.53) and 2 (pKa = 6.85).10,11 For example, the fluorescent intensity of 3 was greatly reduced as the solution became acidic, while the fluorescent intensity of 1 and 2 were greatly reduced as the solution became alkali. The difference of the chemical structures between 3 and 1 (hydrogen atom) or 2 (N,N-dimethylaminoethylamino group) was only the different substituents on the 4-position of bis-1,8-naphthalimide. The proposed mechanism for the observed quenching process for 3 in the weakly acidic conditions was due to the formation of intramolecular hydrogen bond between the nitrogen atom of diethylenetriamine and oxygen atoms of aminonaphthalimide.
In summary, a new fluorescent chemosensor 3 based upon bis-4-piperidine-1,8-naphthalimide linked by the diethylenetriamine was synthesized, and its fluorescent properties were also investigated. Different from other bis-1,8-naphthalimides, no changes in the fluorescence spectra of 3 in the presence of metal cations was observed, and it displayed an unexpectedly strong fluorescence quench in weakly acidic aqueous solutions. It would be suited as a new pH sensor to monitor changes in the physiological pH conditions.

EXPERIMENTAL
All solvents and reagents were used as obtained from commercial sources without further purification. The solutions of metal ions were prepared from Zn(ClO4)2·6H2O, Fe(ClO4)2·6H2O, Ca(ClO4)2·4H2O, Mg(ClO4)2, Ba(ClO4)2, Pb(ClO4)2, Cd(ClO4)2, and Cu(ClO4)2, respectively, and were dissolved in distilled THF. Analytical thin-layer chromatography (TLC) and preparative thin-layer chromatography (PTLC) were performed with silica gel plates using silica gel 60 GF254 (Qingdao Haiyang Chemical Co., Ltd.). Melting points are uncorrected. Nuclear magnetic resonance spectra (NMR) were recorded on a Bruker Avance DMX 400 MHz instrument in CDCl3 (1H at 400 MHz and 13C at 100 MHz) using TMS (tetramethylsilane) as the internal standard. High-resolution mass spectra (HR-MS) and mass spectra (MS) were carried out with APEX II Bruker 4.7T AS instrument and HP 5988 instrument, respectively. All pH measurements were carried out with a pH-meter PHS-3C (Chengdu Century Fangzhou Science& technology Co., Ltd.). Fluorescent spectra were determined on a Hitachi F-4500 spectrophotometer. UV-visible spectra were determined on a Hitachi U-3310 spectrophotometer.
Synthesis of compound 4. A mixture of 4-bromo-1,8-naphthalic anhydride (2.77 g, 10.0 mmol), and piperidine (1.97 mL, 20 mmol) in 2-methoxyethanol (25 mL) was refluxed for 5 h, then the reaction mixture was cooled to room temperature to afford a yellow solid after filtration, which was purified by recrystallization from EtOH to give 2.41 g (86%) of 4 as the orange needles. Mp 170-171 °C (lit.,12 175-176 oC); 1H-NMR (400 MHz, CDCl3 ): δ 8.58 (d, J = 7.6 Hz, 1H), 8.50 (d, J = 8.4 Hz, 1H), 8.44 (d, J = 8.8 Hz, 1H), 7.73 (t, J = 7.6 Hz , 1H), 7.20 (d, J = 8 Hz, 1H), 3.31 (t, J = 5.6 Hz, 4H), 1.88-1.93 (m, 4H), 1.74-1.78 (m, 2H); EI-MS m/z: 281(M+, 83 ), 280 ([M-1]+, 100).
Synthesis of compound 3. A mixture of 4 (351mg, 1.25 mmol), and diethylenetriamine (0.054 mL, 0.5 mmol) in absolute EtOH (20 mL) was refluxed for 7.5 h under an argon atmosphere. After removal of EtOH, the residue was purified by preparative thin-layer chromatography (PTLC) using CH2Cl2/MeOH (20:1, v/v) as eluent to afford 299 mg (95%) of 3 as a yellow solid. Mp 115-116 oC; 1H-NMR (400 MHz, CDCl3): δ 8.28-8.37 (m, 6H), 7.60 (t, J = 8.4 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 4.34 (t, J = 6.4 Hz, 4H), 3.11-3.21 (m, 12H), 2.80 (s, 1H), 1.86-1.90 (m, 8H), 1.72-1.73 (m, 4H); 13C NMR (100 MHz, CDCl3): δ 164.7, 164.2, 132.5, 130.9, 130.3, 129.8, 126.1, 125.1, 122.9, 115.8, 114.5, 54.5, 47.4, 39.3, 26.2, 24.3; HRMS: Calcd. for C38H40N5O4 (M+H)+: 630.3075. Found: 630.3083.

ACKNOWLEDGEMENTS
This work has been supported by the program for New Century Excellent University Talents, State Education Ministry of China (NCET-06-0868), and the Key Project of Chinese Ministry of Education (No.107105).

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