Acetonitrilated Unsymmetric BODIPYs having glycine fluorescence responsive quenching: Design, synthesis and spectroscopic properties
Graphical abstract
Introduction
Boron-dipyrromethene (BODIPY) are of high concern for novel properties. The outstanding properties of high fluorescence quantum yields (Фf = 60–90%) and low-energy photo-sensitization, with large molar extinction coefficient (ε > 5000 M−1 cm−1) and unique ultraviolet and fluorescence peaks, make it good candidates as sensors in the detection [[1], [2], [3], [4], [5], [42], [43], [44]].
Glycine is an amino acid widely distributed in human body. In the central nervous system (CNS), especially in the spine, glycine acts as an inhibitory neurotransmitter [[6], [7], [8], [9], [10], [11], [12]]. Glycine has been considered as the most important inhibitory neurotransmitter other than GABA in the past. It is widely distributed in the CNS and plays an important fundamental role in the transmission of neural signals and participation in various physiological and pathological responses[[47], [48], [49], [50], [51]]. Various application from where it occupies an important position are also as an additive in the food realm, and biochemical reagent in pharmaceutical industry. In recent years, many literatures have shown that glycine plays a prominent role in cancer cell metabolism [[13], [14], [15], [16], [17], [18], [19], [20], [21]]. The study of glycine metabolism in medical microorganisms and biochemistry were growing in appeal, and getting more popular. The research value of glycine in medical metabolism makes it useful to labeling or detect it. To perform detection of glycine, more fluorescent molecules that interact with amino acids are under development. A large number of academic papers dedicated to develop BODIPY fluorescence sensors for amino acid detection [[22], [23], [24], [25], [26], [27], [28]]. In particular, BODIPY probes for sulfur-containing amino acids such as cysteine and homocysteine are common research objects [[29], [30], [31], [32], [45], [46]], nevertheless, few studies have been conducted on glycine as a research object.
In recent years, there have been many reports on the synthesis and application of BODIPY derivatives. Modification of BODIPY core 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene are often occurred at 3- and 5-positions through nucleophilic substitutions [23,33,34]. To optimize the spectroscopic and photophysical properties, the conventional method to make the bathochromic shift is to extend the conjugated system via the introduction of the aryl moieties and electron-withdrawing group. Based on the current research hot spots of glycine and BODIPY modification [[35], [36], [37], [38], [39], [40], [41]], this paper aims to design the fluorescent probes in the near-infrared region that can respond to glycine and realize its recognition. With various types of BODIPYs readily available, herein, we reported a novel series of BODIPY derivatives which introduced aromatic aldehyde group via aldol condensation reaction starting from the (Z)-5-acetyl-2-((1-(difluoroboranyl)-4-ethyl-3,5-dimethyl-1H-pyrrol-2-yl) (phenyl) methylene)-7-propyl-2,7-dihydro-6H-pyrrolo[2,3-b] pyridin-6-one in this study. Meanwhile, we also introduced the acetonitrile electron-donor group into the boron fluoride part to form an asymmetric structure N≡C-CH2-B-F system and alter the electron distribution of target compounds. The introducing of electron-donor group makes the electrons move towards electron-withdrawing group, which leads to the internal transfer of electrons and changes its spectral properties, namely: bathochromic shift effect. After a successful synthesis of three probes (Fig. 1), we tested the response of the compounds to glycine in the presence and absence of ions.
Section snippets
General information
All chemicals and reagents were purchased from commercial suppliers used as received and without further purification unless otherwise specified. Acetonitrile was distilled over calcium hydride. All glassware was dried in a flame or oven and stored in a desiccator before use. The 1H, 13C, and 19F NMR spectra were recorded on Bruker Avance spectrometer (400 MHz for 1H, 101 MHz for 13C, and 376 MHz for 19F, respectively) and chemical shifts (δ) are reported in ppm with the internal CDCl3 at δ
The spectroscopic property of BODIPY 1–3
Spectroscopic evaluation of 1–3 was performed in THF solvent with strong absorption and fluorescence spectral intensity. It is with relatively broad band that absorption and emission spectrum are in the wavelength region of 600–660 nm possessing distinctive spike-like peak (Fig. 2).
The absorption spectroscopic evaluation of BODIPY was investigated in THF solvents in different concentration to explore the optical features. The absorption of BODIPY derivatives displays a major S0-S1 absorption
Conclusions
The novel asymmetric fluoroboropyrrole compounds can significantly improve its spectral properties, adjust the push-pull ability of substituents in the BODIPY structure, and effectively change its reactivity with nucleophiles. Glycine response experiments of target compounds were also performed. It was significant discovered that the three products possessed favourable response to glycine with and without cations, and manifested as being significantly quenched by glycine, particularly 1 showing
Credit author statement
Xiao Fuyan: Investigation, Data curation, Formal analysis, Writing- Original draft preparation. Wang Yuling: Investigation, Visualization, Validation. Shao Tingyu: Investigation. Jin Guofan: Conceptualization, Methodology, Writing-Review and Editing, Project administration.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
This study was supported financially by the scientific research foundation of Jiangsu University (Grant No. 5501290005).
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