氮杂氟硼荧（Aza-BODIPY）类荧光探针的研究进展

doi:10.16085/j.issn.1000-6613.2017-1184

摘要/Abstract

摘要： 氮杂氟硼荧（Aza-BODIPY）作为BODIPYs改良型荧光团，具有摩尔吸光系数高、荧光光谱半峰宽窄、荧光寿命长、光稳定性好、荧光可调等优点，是优良的近红外比色及荧光探针候选母体，然而Aza-BODIPY也存在水溶性能差、应用领域待扩展等问题。本文主要综述了近年来各类以Aza-BODIPY为荧光团的探针种类及其应用：首先，简要概括了3种通用的Aza-BODIPY合成方法，包括从查尔酮出发合成Aza-BODIPY的O'Shea法、从2，4-二取代吡咯出发的Carreira法和Lukyanets的邻苯二腈与苯基溴化镁反应的稠环合成法；然后重点对pH、H₂O₂、NH₄⁺、F^-、Hg²⁺、CN^-、蛤毒素和Cys等探针的客体识别性能、识别机理和实际应用进行了总结。提出目前以Aza-BODIPY为母体设计合成的探针数量仍较少，将来的发展方向是通过结构修饰或改造来提高探针的水溶性能、拓宽其激发发射波长到近红外区、增加识别客体的种类和范围，在生物、环境等领域将具有重要的发展前景。

关键词: 氮杂氟硼荧, 荧光探针, 识别, 生物检测

Abstract: Aza-BODIPY,developed from BODIPYs,have advantages of large molar absorption coefficients,narrow half peak widths,long fluorescence life,good optical stability and tunable fluorescence;hence they have been selected as excellent candidates for near infrared colorimetric and fluorescent probes. However,most of them are poor water solubility and the field of their application is limited. In this paper,the recent researches on Aza-BODIPY-based fluorescent probes were reviewed. Three methods of synthesis of Aza-BODIPYs are summarized briefly including the O'Shea method starting from chalcone,the Carreira method using 2,4-substituted pyrroles as starting materials and the Lukyanets method for fused-ring-Aza-BODIPYs. The sensing performances,mechanisms and practical applications of various probes for pH,H₂O₂,NH₄⁺,F^-,Hg²⁺,CN^-,damtoxin and Cys are discussed. Although there are limited reports about Aza-BODIPY-based probes,they are expected to be developed in the biological and environment areas with the improvement of water solubility,the longer excitation and emission wavelengths in the near-infrared region and the increase of the type and range of identifying species by structural modifications.

Key words: Aza-BODIPY, fluorescent probes, recognition, biological detection

中图分类号:

TP212.14

池雨, 高云玲, 潘勇, 刘孟, 赵辉. 氮杂氟硼荧（Aza-BODIPY）类荧光探针的研究进展[J]. 化工进展, 2018, 37(03): 1137-1144.

CHI Yu, GAO Yunling, PAN Yong, LIU Meng, ZHAO Hui. New progress in Aza-BODIPY-based fluorescence probes[J]. Chemical Industry and Engineering Progress, 2018, 37(03): 1137-1144.

参考文献

[1] MCDONNELL S O,O'SHEA F.Near-infrared sensing properties of dimethlyamino-substituted BF2-azadipyrromethenes[J]. Organic Letters,2006,8(16):3493-3496.
[2] LOUDET A,BURGESS K.BODIPY dyes and their derivatives:syntheses and spectroscopic properties[J].Chemical Reviews,2007,107(11):4891-4932.
[3] GRESSER R,HARTMANN H,WRACKMEYER M.Synthesis of thiophene-substituted Aza-BODIPYs and their optical and electrochemical properties[J].Tetrahedron,2011,67(37):7148-7155.
[4] ADARSH N,AVIRAH R R,RAMAIAH D.Tuning photosensitized singlet oxygen generation efficiency of novel Aza-BODIPY dyes[J].Organic Letters,2010,12(24):5720-5723.
[5] JOSHI J,KUMARI T,DUCHANIYA Y.Chemical sciences Aza-BODIPY:as an organic photovoltaic material[J].International Journal of Engineering Technology,Management and Applied Sciences,2015,3(s1):200-211.
[6] ADARSH N,KRISHNAN M S,RAMAIAH D.Sensitive naked eye detection of hydrogen sulfide and nitric oxide by Aza-BODIPY dyes in aqueous medium[J].Analytical Chemistry,2014,86(18):9335-9342.
[7] ROGERS M A T.2:4-Diarylpyrroles.Part I.Synthesis of 2:4-diarylpyrroles and 2:2':4:4'-tetra-arylazadipyrromethines[J]. Journal of the Chemical Society,1943:590-596.
[8] O'SHEA D F,KILLORAN J,ALLEN L,et al.Synthesis of BF₂ chelates of tetraarylazadipyrromethenes and evidence for their photodynamic therapeutic behaviour[J].Chemical Communications,2002,17:1862-1863.
[9] GUPTA I,BALSUKURI N,LONE M Y,et al.Synthesis,structure and optical studies of energy donor-acceptor type NIR Aza-BODIPYs[J].Chemistry an Asian Journal,2016,11(10):1572-1587.
[10] 李翠红,沈田华,宋庆宝,等.Aza-BODIPY荧光染料的合成、表征及性能研究[J].有机化学,2011,31(9):1440-1444. LI C H,SHEN T H,SONG Q B,et al.Synthesis,characterization and properties of Aza-BODIPY fluorescent dyes[J].Chinese Journal of Organic Chemistry,2011,31(9):1440-1444.
[11] O'SHEA D F,MCDONNELL S O,HALL M J,et al.Supramolecular photonic therapeutic agents[J].Journal of the American Chemical Society,2005,127(47):16360-16361.
[12] 窦媛媛.基于BODIPY/Aza-BODIPY光敏剂的设计、合成与光谱行为研究[D].开封:河南大学,2013. DOU Y Y.Design synthesis,and spectroscopic properties of PDT-photosensitizers based on BODIPY/Aza-BODIPY[D].Kaifeng:Henan University,2013.
[13] O'SHEA D F,GORMAN A,KILLORAN J,et al.In vitro demonstration of the heavy-atom effect for photodynamic therapy[J].Journal of the American Chemical Society,2004,126(34):10619-10631.
[14] ZHAO W,CARREIRA E M. Conformationally restricted Aza-BODIPY:highly fluorescent,stable near-infrared absorbing dyes[J]. Chemistry:a European Journal,2006,12:7254-7263.
[15] LUKYANETS E A,DONYAGINA V F,SHIMIZU S,et al. Synthesis of N,N-difluoroboryl complexes of 3,3'-diarylazadiisoindolylmethenes[J]. Tetrahedron Letter,2008,49:6152-6154.
[16] JIANG X D,GUAN J,ZHAO J L,et al.Synthesis,structure and photophysical properties of NIR Aza-BODIPYs with -F/-N₃/NH₂ groups at 1,7-positions[J].Dyes and Pigments,2017,136:619-626.
[17] GE Y F,ZHU J W,ZHAO W L,et al.Ion-selective optodes based on near infrared fluorescent chromoionophores for pH and metal ion measurements[J].Sensors and Actuators B:Chemical,2012,166:480-484.
[18] STROBL M,MAYR T, BORISOV S M,et al.Photostable upconverting and downconverting pH sensors based on combination of a colorimetric NIR indicator and stable inorganic phosphors as secondary emitters[J].Sensors and Actuators B:Chemical,2017,245:972-979.
[19] LU H,SHIMIZU S,MACK J,et al.Synthesis and spectroscopic properties of fused-ring-expanded Aza-boradiazaindacenes[J]. Chemistry:an Asian Journal,2011,6(4):1026-1037.
[20] STROBL M,RAPPITSCH T,KLIMANT I,et al.NIR-emitting Aza-BODIPY dyes-new building blocks for broad-range optical pH sensors[J].Analyst,2015,140(21):7150-7153.
[21] SCHUTTING S,STROBL M,BORISOV S M,et al.NIR optical carbon dioxide sensors based on highly photostable dihydroxy-Aza-BODIPY dyes[J].Journal of Materials Chemistry C,2015,3(21):5474-5483.
[22] MOßHAMMER M,STROBL M,KOREN K,et al.Design and application of an optical sensor for simultaneous imaging of pH and dissolved O₂ with low cross-talk[J].ACS Sensors,2016,1(6):681-687.
[23] HALL M J,ALLEN L T,O'SHEA D F.PET modulated fluorescent sensing from the BF₂ chelated azadipyrromethene platform[J]. Organic & Biomolecular Chemistry,2006,4(5):776-780.
[24] KILLORAN J,O'SHEA D F.Impact of a conformationally restricted receptor on the BF₂ chelated azadipyrromethene fluorosensing platform[J].Chemical Communications,2006,14:1503.
[25] XU J J,ZHAI J Y,JIANG D C,et al.A near-infrared fluorescent Aza-BODIPY probe for dual-wavelength detection of hydrogen peroxide in living cells[J].Analyst,2016,141(8):2380-2383.
[26] LIU Y L,ZHU J W,JIANG D C,et al.Boronic acid functionalized Aza-Bodipy(azaBDPBA) based fluorescence optodes for the analysis of glucose in whole blood[J].ACS Applied Materials & Interfaces,2015,7(21):11141-11145.
[27] CHEN X Q,TIAN X Z,YOON J,et al.Fluorescent and luminescent probes for detection of reactive oxygen and nitrogen species[J].Chemical Society Reviews,2011,40(9):4783-4804.
[28] LIU H Z,MACK J,SHEN Z,et al.A selective colorimetric and fluorometric ammonium ion sensor based on the H-aggregation of an Aza-BODIPY with fused pyrazine rings[J]. Chemical Communications,2011,47(44):12092-12094.
[29] ZOU B,LIU H,SHEN Z,et al.A new Aza-BODIPY based NIR region colorimetric and fluorescent chemodosimeter for fluoride[J].RSC Advances,2014,4(96):53864-53869.
[30] LIU S J,SHIA Z J,HUANG W,et al.A class of wavelength-tunable near-infrared Aza-BODIPY dyes and their application for sensing mercury ion[J].Dyes and Pigments,2014,103:145-153.
[31] JIANG X D,ZHAO J L,XIAO L J,et al.Synthesis of NIR fluorescent thienyl-containing Aza-BODIPY and its application for detection of Hg²⁺:electron transfer by bonding with Hg²⁺[J].Dyes and Pigments,2016,125:136-141.
[32] COSKUN A,YILMAZ M D,AKKAYA E U.Bis(2-pyridyl)-substituted boratriazaindacene as an NIR-emitting chemosensor for Hg(Ⅱ)[J].Organic Letters,2007,9(4):607-609.
[33] DVIVEDI A,KUMAR S,RAVIKANTH M.Nucleophilic addition of CN^- ion to -C==N bond of Aza-BODIPY leading to turn-on fluorescence sensor[J].Sensors and Actuators B:Chemical,2016,224:364-371.
[34] BHAT H R,JHA P C. Cyanide anion sensing mechanism of 1,3,5,7-tetratolyl Aza-BODIPY:intramolecular charge transfer and partial configuration change[J].Chemical Physics Letters,2017,669:9-16.
[35] GAWLEY R E,MAO H,PHARR J S,et al.Visible fluorescence chemosensor for saxitoxin[J]. Journal of Organic Chemistry,2007,72(6):2187-2191.
[36] JIANG X D,ZHANG J,ZHAO W L,et al.A selective fluorescent turn-on NIR probe for cysteine[J]. Organic & Biomolecular Chemistry,2012,10:1966-1968.
[37] CHEN X Q,ZHOU Y,YOON J,et al.Fluorescent and colorimetric probes for detection of thiols[J].Chemical Society Reviews,2010,39(6):2120-2135.