Synthesis, Characterization and Evaluation of a Carbazolyl-BODIPY as a Fluorimetric Chemosensor for F^-  †

Abstract

BODIPY dyes have received great attention in the last few years as optical chemosensors since they can recognize metal ions in solutions through optical signals (colorimetric and/or fluorimetric). In this context, our research group reports the synthesis of a carbazolyl-BODIPY derivative and its respective characterization by ¹H NMR spectroscopy and mass spectrometry. Furthermore, a preliminary study of the chemosensory capacity of this BODIPY derivative was carried out in acetonitrile solution in the presence of several anions and a highly selective fluorimetric response was obtained for F^-.

1. Introduction

The development of probes capable of recognizing ions with biological and environmental importance through optical signals (colorimetric and/or fluorimetric) is an attractive goal nowadays. Fluoride is an example of an anion harmful to human health at certain levels, since its high intake can lead to chronic diseases such as dental and skeleton fluorosis, and metabolic dysfunctions [1,2]. Thus, simple and rapid sensing tools to monitor fluoride levels in biological samples are of great importance. Boron-dipyrromethene (BODIPY) derivatives have received great attention for chemosensory applications due to their remarkable physical–chemical properties, such as high molar absorption coefficients, high quantum fluorescence yields, intense and narrow absorption/emission bands in the visible region of the electromagnetic spectrum, and good photochemical stability. Additionally, the BODIPY core can be easily functionalized to be used as a selective chromo-fluorogenic chemosensor for various analytes [3,4,5].

In continuation of the work developed in our research group [6,7,8,9,10,11,12], regarding the synthesis and evaluation of the optoelectronic properties of BODIPY derivatives for several applications, namely, as chromofluorogenic chemosensors, we report the synthesis, spectroscopic characterization, and evaluation of the chemosensory ability of a novel BODIPY derivative functionalized with a carbazolyl group at the meso position as a fluorimetric chemosensor for the selective detection of fluoride.

2. Experimental Section

2.1. Methods and Materials

All reagents were purchased from Sigma-Aldrich, Acros, and Fluka and used as received. Thin-layer chromatography (TLC) analysis were carried out on 0.25 mm thick precoated silica plates (Merck Fertigplatten Kieselgel 60F254) and the spots were visualized under UV light. Dry flash chromatography was performed using silica gel 60 with a diameter between 230 and 400 mesh (Merck, Kenilworth, NJ, USA). The ¹H NMR spectra were recorded on a Bruker Avance III device at 400 MHz, using the solvent peak as an internal reference. Mass spectrometry analyses were performed at the “C.A.C.T.I.-Unidad de Espectrometria de Masas” at the University of Vigo, Spain. The deuterated solvent used in nuclear magnetic resonance spectroscopy was CDCl₃ with a 99.8% deuteration degree, containing 0.03% v/v TMS (Sigma Aldrich, Av. Alm. Gago Coutinho 132, 1950-037 Lisboa, Portugal). The absorption spectra were obtained using a Shimadzu UV/2501PC spectrophotometer and fluorescence spectra were collected using a Horiba FluoroMax-4 spectrofluorometer.

2.2. Synthesis of BODPY Derivative 1 

2,4-Dimethylpyrrole (170 mg, 1.8 mmol) and N-ethylcarbazolyl-4-carbaldehyde (200 mg, 0.89 mmol) were dissolved in dry DCM (100 mL) and this reaction mixture was stirred for 50 min, at room temperature, after adding a drop of TFA. Subsequently, a solution of DDQ (406 mg, 1.8 mmol) dissolved in dry DCM (100 mL) was added and the stirring time was extended for another 50 min. Then, triethylamine (2 mL, 15 mmol) was added and, after 15 min, we added BF₃.OEt₂ (3 mL, 25 mmol) to the reaction mixture, which was further stirred for 30 min at room temperature. The crude product obtained after the evaporation of the solvent under reduced pressure was purified by dry flash chromatography using a petroleum ether/AcOEt (4:1) mixture as eluent. The pure BODIPY derivative 1 (Figure 1) was obtained as a dark red solid (65 mg, 17%).

Figure 1. Structure of BODIPY derivative 1.

¹H RMN (400 MHz, CDCl₃): δ = 1.27 (s, 6H, CH₃-1 and CH₃-7), 1.51 (t, 3H, N(CH₂CH₃)), 2.59 (s, 6H, CH₃-3 and CH₃-5), 4.45 (q, 2H, N(CH₂CH₃)), 5.99 (s, 2H, H-2 and H-6), 7.26–7.30 (m, 1H, H6’ or H7’), 7.30 (dd, J = 1.6 and 8.4 Hz, 1H, H3’), 7.48–7.56 (m, 3H, H8’, H4’, H6’ or H7’ ), 8.01 (d, J = 7.6 Hz, 1H, H1’), 8.08 (dd, J = 0.8 and 1.6 Hz, 1H, H5’), ppm.

MS (ESI) m/z (%): 443 ([M+2]^+•, 33), 442 ([M+1]^+•, 100), 441 ([M]^+•, 29), 394 (54), 291 (3), 239 (8), 102 (6); HRMS (ESI) m/z: [M+1]^+• calcd for C₂₇H₂₇BF₂N₃, 442.2261; found 442.2263.

2.3. Photophysical Characterization of BODIPY Derivative 1 

The photophysical characterization of BODIPY derivative 1 in acetonitrile (1 × 10⁻⁵ M) was carried out using quartz cells. A 1 × 10⁻⁵ M Rhodamine 6G (Φ_F = 0.95) solution in ethanol was used as the fluorescence standard [13]. The compound and the standard were excited at the maximum absorption wavelength of BODIPY 1. After plotting the fluorescence spectra of compound 1 and Rhodamine 6G, the area under the curve was determined and the relative quantum fluorescence yield of BODIPY 1 was calculated through Equation (1).

$${\Phi }_{F_{comp}}=\frac{A_s\times F_{comp}\times n_s^2}{A_{comp}\times F_s\times n_{comp}^2}\times {\Phi }_{F_s}$$

(1)

A_s and A_comp, F_s and F_comp, and n_s and n_comp correspond to the absorbances, areas under the fluorescence curve, and refractive index value of the solvent of the standard and compound 1, respectively.

2.4. Chemosensing Studies of BODIPY Derivative 1 

The evaluation of BODIPY derivative 1 as an optical chemosensor was carried out in the presence of several anions (H₂PO₄^-, HSO₄^-, CN^-, F^-, I^-, NO₃^-, CH₃COO^-, Br^-, ClO₄^-, BzO^-). For this study, solutions of compound 1 (1 × 10⁻⁵ M) and the various anions (1 × 10⁻² M) were prepared in acetonitrile, and the preliminary study was carried out by the addition of 50 equivalents of each anion to the BODIPY derivative 1 solution. Solutions were visualized under natural light and in a UV-chamber under a lamp at 365 nm.

3. Results and Discussion

3.1. Synthesis of BODPY Derivative 1 

Carbazolyl-BODIPY 1 was synthesized in two reactional steps at room temperature. The first step consisted in the condensation reaction of 2,4-dimethylpyrrole and N-ethylcarbazolyl-4-carbaldehyde in dichloromethane (DCM), in the presence of trifluoroacetic acid (TFA) as catalyst. The second reactional step involved oxidation of the dipyrromethane to dipyrromethene, through addition of a solution of 2,3-dichloro-5,6-diciano-p-benzoquinone (DDQ), followed by a complexation reaction with BF₃OEt₂ in presence of triethylamine (Scheme 1). Finally, the purification of the crude product by dry flash chromatography, using petroleum ether/ethyl acetate (4:1) as eluent, gave the pure BODIPY derivative 1 as a dark red solid at a 17% yield.

Scheme 1. Synthesis of BODIPY derivative 1.

Through the ¹H NMR spectrum, it was possible to confirm the presence of the carbazolyl group in the meso position of the BODIPY core, with the characteristic proton signals appearing in the aromatic zone of the spectrum. Additionally, the data obtained by mass spectrometry is in agreement with the expected structure.

3.2. Photophysical Characterization of BODIPY Derivative 1 

The photophysical characterization of BODIPY derivative 1 was investigated in acetonitrile solution. The compound showed an intense absorption band (log ε = 4.9) at 496 nm. Upon excitation at 480 nm, the compound exhibited an emission band at 507 nm (Figure 2). The relative fluorescence quantum yield, determined by using Rhodamine 6G in ethanol as fluorescence standard (Φ_F = 0.95), was found to be low (Φ_F = 0.019).

Figure 2. Normalized absorption and fluorescence spectra of BODIPY 1 in acetonitrile (λ_max = 480 nm).

3.3. Chemosensing Studies of BODIPY Derivative 1 

Preliminary evaluation of carbazolyl-BODIPY 1 as an optical chemosensor was performed in the presence of several anions in acetonitrile solution. The study was carried out by addition of 50 equivalents of each anion to the compound’s solution and, as can be seen in Figure 3, there was a selective increase in the fluorescence of the compound upon addition of F^-.

Figure 3. BODIPY derivative 1 solutions in the presence of various anions, in acetonitrile, under natural light (above) and UV radiation at λ_max = 365 nm (below).

4. Conclusions

The BODIPY derivative 1 functionalized at the meso position with a carbazolyl group was synthesized through a condensation reaction between 2,4-dimethylpyrrole and N-ethylcarbazolyl-4-carbaldehyde, at a 17% yield. This compound was characterized by the usual spectroscopic techniques and the photophysical properties were also determined. Additionally, the preliminary chemosensing study of BODIPY derivative 1 shows the selective recognition of F^- among several anions, through a perceptible enhancement of the fluorescence of the solution of the compound. Therefore, BODIPY 1 could be a potential selective fluorimetric chemosensor for the detection of fluoride.