CN103183697A - 基于二联杂环并吡咯基团的近红外氟硼二吡咯化合物及其制法和用途 - Google Patents
基于二联杂环并吡咯基团的近红外氟硼二吡咯化合物及其制法和用途 Download PDFInfo
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Abstract
一类基于二联噻吩并吡咯基团的近红外氟硼二吡咯化合物(BODIPY),它有如下结构:其中取代基M、N、P、E、F、M’、N’、P’、E’或F’=H或Br。本发明首次合成了二联噻吩并吡咯为母体的大共轭的BODIPY光敏剂,两个噻吩基团的引入使得这类光敏剂的吸收光谱红移到了680-720nm,发射峰716n-750nm,处于生物窗口的范围内(650-900nm),同时该染料的荧光量子效率较高。另外该光敏剂在溶液中的摩尔吸光系数高达200000M-1cm-1。而且,两个噻吩基团中的S是重原子,这就使得该光敏剂的三重态效率增大了,进而提高了其产生单线态氧的效率,因此,它在生物成像和光动力治疗方面有着诱人的应用前景。
Description
技术领域
本发明涉及一系列基于二联杂环并吡咯基团的近红外BODIPY及其制法和在制备光动力治疗中的光敏剂中的应用。
背景技术
近年来,光动力治疗(PDT)作为一种治疗各种癌症的微创手段和方法越来越的得到人们的关注。这是一种有氧分子参与的伴随生物效应的光敏化反应。其过程是,特定波长的激光照射使组织吸收的光敏剂受到激发,而激发态的光敏剂通过系间窜越过程(ISC)由单重态跃迁到三重态,而后再把能量传递给周围的氧气分子,生成活性很强的单线态氧,单线态氧和相邻的生物大分子发生氧化反应,产生细胞毒性作用,进而导致细胞受损乃至死亡。[参见:(a)Dolmans,D.E.J.G.J.;Fukumura,D.R.;Jain,K.Nat.Rev.Cancer2003,3,380.(b)Bonnett,R.Chem.Soc.Rev.1995,24,19.(c)Sharman,W.M.;Allen,C.M.;van Lier,J.E.Drug Discovery Today 1999,4,507.(d)MacDonald,I.J.;Dougherty,T.J.J.Porphyrins Phthalocyanines.2001,5,105.(e)Brown,S.B.;Brown,E.A.;Walker,I.Lancet Oncol.2004,5,497.(f)Celli,J.P.;Spring,B.Q.;Rizvi,I.;Evans,C.L.;Samkoe,K.S.;Verma,S.;Pogue,B.W.;Hasan,T.Chem.Rev.2010,110,2795.]第一代光敏剂有血卟啉衍生物(HpD)、Porfimer Sodium,二血卟啉酯(DHE)等。但是这类光敏剂存在着很多的不足:(1)结构复杂不易合成分离;(2)在生物组织的透明窗口范围(650-900nm)吸收强度很低;(3)从体内排除较慢,而且对皮肤有持久的光敏反应伤害。[参见:(a)MacDonald,I.J.;Dougherty,T.J.J.Porphyrins Phthalocyanines.2001,5,105.(b)Ochsner,M.Drug Res.1997,47,1185.(c)Dougherty,T.J.;Gomer,C.J,;Henderson,B.W.;Jori,G.;Kessel,D.;Korbelik,M.;Moan,J.;Peng,Q.J.Natl.Cancer Inst.1998;90,889.]目前,已有一组第二代光敏剂问世,包括5-氨基酮戊酸(5-ALA)、mTHPC、初卟啉锡(SnEtz)、亚甲基兰和亚甲苯兰、苯卟啉衍生物,以及lutelium texaphyrins(Lu-Tex)。第二代光敏剂部分地克服了第一代光敏剂的缺点,表现为光敏期短,作用的光波波长较长,因而增加作用的深度,产生的单态氧也较多,对肿瘤更有选择性。但是这类化合物还存在以下不足:(1)单线态氧产生效率不是很高;(2)化合物光稳定性极差;(3)暗毒性较大。所以,寻求一种更好的光敏剂仍是人类研究一个的热点和任务。好的光敏剂要满足一下几个要求:(1)光敏剂的最大吸收峰要处在生物的光学窗口(650-900nm),这个区域 的光对生物组织有更好的穿透性;(2)较高的三重态效率,进而提高单线态氧效率;(3)没有暗毒性,只有较高的光毒性。
因此,作为卟啉类家族的近亲---氟硼二吡咯类化合物(BODIPY或者BDP),得到了人们的广泛关注。氟硼二吡咯亚甲基类化合物是由两个吡咯环通过硼桥键和亚甲基桥键连接起来,这种连接方式把该类染料的母体部分固定在同一平面上,使分子具有高度的刚性。BODIPY的分子母核结构如下:
根据国际纯粹与应用化学联合会(IUPAC)按惯例以阿拉伯数字命名了BODIPY母核的各原子,但是在实际工作中我们通常选用更方便有效的方式认识BODIPY母核中的各原子:meso-位,α-位,β-位。氟硼二吡咯类化合物早在1968年就由Treibs和Keuzer发现了,发展至今仍被人们视为研究热点,这主要是因为这类化合物具有非常优越的光学特性:(1)极高的摩尔吸光系数和荧光量子产率;(2)对外界环境和光源都表现出很好的稳定性,在生理环境下非常稳定;(3)容易合成和进行各种结构修饰。[参见:(a)Loudet,A.;Burgess,K.Chem.Rev.2007,107,4891.(b)Ulrich,G.;Ziessel,R.;Harriman,A.Angew.Chem.2008,120,1202;Angew.Chem.Int.Ed.2008,47,1184.(c)Ziessel,R.;Ulrich,G.;Harriman,A.New J.Chem.2007,31,496.(d)Boens,N.;Leen,V.;Dehaen,W.Chem.Soc.Rev.2012,41,1130.(d)Qu,X.;Liu,Q.;Ji,X.;Chen,H.;Zhou,Z.;Shen,Z.Chem.Commun.2012,48,4600.(e)Shen,Z.;Rohr,H.;Rurack,K.;Uno,H.;Spieles,M.;Schulz,B.;Reck,G.;Ono,N.Chem.Eur.J.2004,10,4853.]因此这类化合物在各领域的应用也得到了全面的研究,例如,其可以用于激光光学记录,光学成像,生物成像,生物光学传感器,荧光探针等等。[参见:(a)Lavis,L.D.;Raines,R.T.ACSChem.Biol.2008,3,142.(b)Mishra,A.;Behera,R.K.;Behera,P.K.;Mishra,B.B.;Behera,G.B.;Chem.Rev.2000,100,1973.(c)Wagner,R.W.;Lindsey,J.S.Pure Appl.Chem.1996,68,1373.(d)Malinin,V.S.;Haque,Md.E.;Lentz,B.R.Biochemistry 2001,40,8292.(e)Luedtke,N.W.;Carmichael,P.;Tor,Y.J. Am.Chem.Soc.2003,125,12374.(e)Rurak,K.;Resch-Genger,U.Chem.Soc.Rev.2002,31,116.]但是,BODIPY类染料的三重态效率很低,不利于单线态氧的产生,因此,科学家们想到了重原子效应,通过在BODIPY结构上引入溴、碘等重原子来增加其三重态效率,进而提高单线态氧的效率。目前这类BODIPY染料用于PDT主要集中于简单的 BODIPY,苯乙烯基修饰的BODIPY,氮杂BODIPY,然而这些光敏剂也存着很多缺陷:(1)简单的BODIPY吸收光集中在500nm左右,光在组织内的渗透性不好,而且单线态氧效率较低;(2)苯乙烯基取代的BODIPY效率比较低;(3)氮杂BODIPY不易合成和分离,水溶性较差而且在稍高的浓度下有很强的细胞暗毒性。[参见:(a)Gorman,A.;Killoran,J.;O’Shea,C.;Kenna,T.;Gallagher,W.M.;O’Shea,D.f.;J.Am.Chem.Soc.2004,126,10619.(b)McDonnell,S.O.;Hall,M.J.;Allen,L.T.;Byrne,A.;Gallagher,W.M.;O’Shea,D.F.J.Am.Chem.Soc.2005,127,16360.(c)Yogo,T.;Urano,Y.;Ishitsuka,Y.;Maniwa,f.;Nagano,T.J.Am.Chem.Soc.2005,127,12162.(d)Atilgan,S.;Ekmekci,Z.;Dogan,A.L.;Guc,D.;Akkaya,E.U.Chem.Commun.2006,4398.(e)Erbas,S.;Gorgulu,A.;Kocakusakogullari,M.;Akkaya,E.U.Chem.Commun.2009,4956.(f)Ozlem,S.;Akkaya,E.U.J.Am.Chem.Soc.2009,131,48.(g)Lim,S.H.;Thivierge,C.;Nowak-Sliwinska,P.;Han,J.;van den Bergh,H.;Wagnières,G.;Burgess,K.;Lee,H.B.J.Med.Chem.2010,53,2865.(h)Adarsh,N.;Avirah,R.R.;Ramaiah,D.Org.Lett.2010,12,5720.(i)He,H.;Lo,P.C.;Yeung,S.L.;Fong,W.P.;Ng,D.K.P.Chem.Commun.2011,47,4748.(j)He,H.;Lo,P.C.;Yeung,S.L.;Fong,W.P.;Ng,D.K.P.J.Med.Chem.2011,54,3097.(k)Awuah,S.G.Polreis,J.;Biradar,V.;You,Y.Org.Lett.2011,13,3884.(l)Jiao,L.;Pang,W.;Zhou,J.;Wei,Y.;Mu,X.;Bai,G.;Hao,E.J.Org.Chem.2011,76,9988.]
因此寻求一种吸收在近红外区域(光敏剂吸收在近红外区域可以解决光在生物组织内渗透深度的问题),效率较高且易于合成的光敏剂仍是研究的热点。
噻吩(thiophene)是含有一个硫杂原子的五元杂环化合物,分子式为C4H4S。硫原子两对孤电子中的一对与两个双键共轭,形成离域π键,其芳香性仅次于苯,但是它比苯的电子离域能垒要低,更利于分子整体的共轭,而且能够有效的提高分子的系间窜越过程(ISC)。[参见:(a)Varanasi,P.R.;Jen,A.K.Y.;Chandrasekhar,J.;Namboothiri,I.N.N.;Rathna,A.J.Am.Chem.Soc.1996,118,12443.(b)Kim,S.;Ohulchanskyy,T.Y.;Baev,A.;Prasad,P.N.J.Mater.Chem.2009,19,3181.(c)Chen,Y.;Zhao,J.;Xie,L.;Guo,H.;Li,Q.RSCAdv.2012,2,3942.]所以,把噻吩引入到光敏剂中,一方面可以增加光敏剂中电子的离域性或者共轭性,进而光敏剂的吸收也会实现显著的红移;另一方面可以增加光敏剂的系间窜越过程,提高三重态效率和产生单线态氧的效率。这两个方面对于光敏剂在光动力治疗方面都是起着促进的作用。目前,基于这种噻吩稠合吡咯的BODIPY染料报道很少,[参见:(a)Awuah,S.G.;Polreis,J.;Biradar,V.;You,Y.Org.Lett.2011,13,3884.(b)Umezawa,K.;Nakamura,Y.;Makino,H.;Citterio,D.;Suzuki,K.J.Am.Chem.Soc.2008, 130,1550.(c)Umezawa,K.;Matsui,A.;Nakamura,Y.;Citterio,D.;Suzuki,K.Chem.Eur.J.2009,15,1096.(d)Landrum,M.;Smertenko,A.;Edwards,R.;Hussey,P.k J.;Steel,P.G.Plant J.2010,62,529.(e)Matsui,A.;Umezawa,K.;Shindo,Y.;Fujii,T.;Citterio,D.;Oka,K.;Suzuki,K.Chem.Commun.,2011,47,10407.]其中只有第一篇文章用在了单线态氧方面,但是效率不是很理想而且也并没有测试细胞内的光动力治疗效果。这类BODIPY的专利也仅有一项[参见:Suzuki,K.;Umezawa,K.et al.PCT Int.Appl.(2007)154pp.],而且这项专利也并未用在光动力治疗方面。
发明内容
本发明内容是设计并提供了一系列基于二联杂环并吡咯基团的近红外氟硼二吡咯(BODIPY)及其制备方法和用途。
本发明的技术方案如下:
一类基于二联噻吩并吡咯基团的近红外氟硼二吡咯化合物(BODIPY),它有如下结构:
其中:取代基M、T、P、E、F、M’、T’、P’、E’、F’取自下列五组定义中任一组:
1.M=T=P=E=F=M’=T’=P’=E’=F’=H;
2.M=M’=Br;T=P=E=F=T’=P’=E’=F’=H;
3.M=M’=E=Br;T=P=F=T’=P’=E’=F’=H;
4.M=M’=F=F’=Br;T=P=E=T’=P’=E’=H;
5.M=T=P=E=M’=T’=P’=E’=Br;F=F’=H。
一种制备上述的基于二联噻吩并吡咯基团的近红外氟硼二吡咯化合物(BODIPY)的方法,它可以按如下反应制备,
它包括下列步骤:
在反应容器中加入2-(2-噻吩基)-噻吩并[3,2-b]吡咯,芳香醛R-CHO和无水二氯甲烷,2-(2-噻吩基)-噻吩并[3,2-b]吡咯与芳香醛摩尔比为2:1,在无水无氧避光条件下放入磁子室温搅拌,然后用微量注射器逐滴加入催化量的三氟乙酸(TFA),室温下反应12小时后,将与芳香醛R-CHO同摩尔数的2,3-二氯-5,6-二氰基-1,4-苯醌(DDQ)加入到反应溶液中,反应1小时,之后加入过量的三乙胺(TEA)和BF3·Et2O,再反应一个小时,然后用水淬灭反应,用NaHCO3、水和饱和食盐水依次洗涤,无水Na2SO4干燥,减压蒸去溶剂得黑色粉末,用100-140目硅胶装柱、乙酸乙酯-石油醚作为洗脱剂进行层析分离,蒸干溶剂后得到目标化合物:
其中M=T=P=F=E=M’=T’=P’=F’=E’=H,
经氯仿和正己烷混合溶剂重结晶后得氟硼二吡咯化合物A1的晶体。
催化剂的量对于BODIPY这一步有至关重要的影响。合成BODIPY的TFA催化反应必须在无氧条件下进行并且量要少,这是为了抑制吡咯的氧化和酸性条件下的聚合,从而提高BODIPY的产率。但是TFA的量也不宜太少,否则,反应会进行的很慢,而且产率也会降低。
一种制备上述的多溴取代的基于二联噻吩并吡咯基团的近红外氟硼二吡咯化合物(BODIPY)的方法,它包括如下步骤:
在反应容器中加入上述制得的二联噻吩并吡咯BODIPY(BODIPY-A1)和N-溴代琥珀酰亚胺(NBS)或者Br2,四氢呋喃(THF),(或者其他溶剂)及磁子,室温下搅拌,反应完后用硫代硫酸钠溶液淬灭,之后水,饱和食盐水依次洗涤,无水Na2SO4干燥,减压蒸去溶剂得金色粉未,用300-400目硅胶装柱、乙酸乙酯-石油醚作为洗脱剂进行层析分离,蒸干溶剂后得到各个多溴取代的二联噻吩并吡咯BODIPY,经氯仿和正己烷重结晶后得到各个多溴取代的二联噻吩并吡咯BODIPY晶体。
NBS或者Br2与a-d系列BODIPY的用量比例、反应时间、以及反应体系中温度都是关键。
用1H-NMR、UV-Vis、fluorescence spectral、MALDI-TOF MASS及晶体结构表征并证实了该BODIPY光敏剂的结构(见附图和附表)。检测所用仪器为:Bruker ARX500型核磁共振仪(TMS为内标,氘代CDCl3为溶剂),岛津UV-4500型紫外-可见分光光度计(扫描范围350~900nm,光路狭缝2nm),日立F-4600美国Thermo ELECTRONCORPORATION质谱工作站。
本发明所设计的这类BODIPY光敏剂,创新性的引入了两个噻吩基团,进一步提高了该类光敏剂的三重态效率,另外这样的设计使得该光敏剂的吸收峰红移到了680-720nm成功进入了生物光学窗口(650-900nm),且摩尔吸光系数更是达到了惊人的105数量级。此外,我们又引入了多个(2-,3-,4-,8-Br)溴原子,使结构由对称性变成了非对称性,这些特性从理论和实践中都证明了,我们所设计的分子是非常适合用在光动力治疗中的,该系列BODIPY有着强大的发展成为新一代光敏剂的潜力。
本发明的有益效果
本发明与现有技术相比,其显著优点是:首次合成了二联噻吩并吡咯为母体的大共轭的BODIPY光敏剂,两个噻吩基团的引入使得这类光敏剂的吸收光谱红移到了680-720nm,发射峰716nm-750nm,处于生物窗口的范围内(650-900nm)与简单的BODIPY (λmax≈500nm)染料相比,吸收红移了近180nm,成功地将最大吸收峰红移到了红光区域,同时该染料的荧光量子效率较高。另外该光敏剂在溶液中的摩尔吸光系数高达200000M-1cm-1,这是迄今光动力治疗光敏剂中摩尔吸光系数最大的化合物。而且,两个噻吩基团中的S是重原子,这就使得该光敏剂的三重态效率增大了,进而提高了其产生单线态氧的效率,因此,它在生物成像和光动力治疗方面有着诱人的应用前景。
附图说明
图1为二联噻吩并吡咯的BODIPY-A1光敏剂核磁图谱;
图2为二联噻吩并吡咯的BODIPY-A2(a),A3(b),A4(c)光敏剂核磁图谱;
图3为二联噻吩并吡咯的BODIPY-A5光敏剂核磁图谱;
图4为二联噻吩并吡咯的BODIPY-A1(a)和A3(b)的晶体结构,图b中Br3a原子和Br3b原子在结构中是无序的,占有率各均为50%,就是说只有一个Br占在其中一个位置;
图5为二联噻吩并吡咯的BODIPY-A1(a),A2(b),A3(c)和A5(d)的质谱;
图6为二联噻吩并吡咯的BODIPY-A3的光毒性测试结果。
具体实施方式
实施例1.BODIPY-A1的合成:
在100ml圆底烧瓶中加入1mmol(164mg)对甲氧甲酰基苯甲醛、2mmol(410mg)二联噻吩并吡咯,和40ml无水二氯甲烷,放入磁子开始搅拌,避光且氩气保护下注射器注入一滴三氟乙酸(TFA),室温反应12小时后。之后,加入1mmol DDQ(227mg), 在反应1小时,之后每隔十分钟加入2ml三乙胺(TEA)和2ml BF3·Et2O,共3次,然后搅拌1小时。水淬灭反应,NaHCO3和水,饱和食盐水依次洗涤,无水Na2SO4干燥,减压蒸去溶剂得黑色粉未,用100-140目硅胶装柱、乙酸乙酯-石油醚作为洗脱剂进行层析分离,蒸干溶剂金色固体,产率95%,经氯仿和正己烷重结晶后得到金色晶体。产率:87%。紫外684nm,发射716nm。MALDI-MS m/z:calcd602.526,found:600.832[M-H]+,581.806[M-F]+。核磁图谱见附图1。A1晶体结构见附图4,其参数见表1。质谱见附图5(a)。
表1
BODIPY-A1 | Length | Angle | |
B1F2 | 1.354 | F2B1F1 | 106.5 |
B1F1 | 1.383 | F2B1N1 | 113.4 |
B1N1 | 1.484 | F1B1N1 | 113.1 |
B1N2 | 1.545 | F2B1N2 | 109.9 |
C5S2 | 1.748 | F1B1N2 | 108.3 |
C1S1 | 1.684 | N1B1N2 | 105.5 |
C7N1 | 1.362 | C2C1S1 | 114.4 |
C10N1 | 1.389 | C4C5S2 | 115.96 |
C12N2 | 1.399 | S1C1H1 | 122.8 |
C14S3 | 1.700 | C9C8S2 | 139.2 |
C15N2 | 1.366 | C7C8S2 | 111.43 |
C17S3 | 1.741 | C11C10N1 | 123.2 |
C18S4 | 1.633 | C11C12N2 | 118.2 |
C21S4 | 1.651 | N2C12C13 | 110.8 |
实施例2.BODIPY-A2,A3,A4的合成:
在100ml底烧瓶中加入0.17mmol(100mg)实施例1制得的BODIPY-A1,1.02mmol(182mg)NBS和30ml四氢呋喃(THF),室温下搅拌6小时。硫代硫酸钠溶液淬灭反应,水,饱和食盐水依次洗涤,无水Na2SO4干燥,减压蒸去溶剂得黑色粉未,用100-140目硅胶板、20%乙酸乙酯/石油醚进行层析分离,得到BODIPY-A2,A3,A4产率分别是23%,57%,20%。BODIPY-A2紫外693nm,发射728nm。MALDI-TOF-MS m/z:calcd760.842,found:758.402[M-2H]+,737.428[M-H3F]+。BODIPY-A3紫外698nm,发射724nm。MALDI-TOF-MS m/z:calcd839.213,found:838.219[M-H]+,821.072[M-F]+。BODIPY-A4紫外692nm,发射727nm。MALDI-TOF-MS m/z:calcd 918.110,found:917.235[M-H]+,898.676[M-HF]+。核磁图谱见附图2(a)、(b)、和(c),A1和A3晶体结构见附图4,其参数见表2。A3的光毒性测试结果见图6。质谱见附图5(c)。
表2
BODIPY-A3 | Length | Angle | |
C7-N1 | 1.376 | F2B1F1 | 108.6 |
C10-N1 | 1.383 | F2B1N2 | 111.8 |
C12-N2 | 1.393 | F1B1N2 | 110.8 |
C15-N2 | 1.378 | F2B1N1 | 110.2 |
C1-S1 | 1.607 | F1B1N1 | 110.0 |
C4-S1 | 1.702 | N2B1N1 | 105.4 |
C5-S2 | 1.750 | F2B1F1 | 108.6 |
C8-S2 | 1.723 | C1S1C4 | 94.6 |
C14-S3 | 1.730 | C8S2C5 | 90.3 |
C17-S3 | 1.754 | C14S3C17 | 90.0 |
C18-S4 | 1.735 | C18S4C21 | 91.6 |
C21-S4 | 1.740 | C1S1C4 | 94.6 |
实施例3.BODIPY-A5的合成:
在100ml底烧瓶中加入0.17mmol(100mg)BODIPY-A1,17.0mmol(2.72g)NBS和30ml CHCl3,室温下搅拌1小时。NaOH溶液淬灭反应,水,饱和食盐水依次洗涤,无水Na2SO4干燥,减压蒸去溶剂得黑色粉未,用100-140目硅胶装柱、氯仿作为洗脱剂进行层析分离,蒸干得到红棕色粉未。产率93%。紫外:633nm,发射:723nm。MALDI-TOF-MS m/z:calcd1233.694,found:1212.405[M-H2F]+,1152.502[M-H2Br]+。核磁图谱见附图3。质谱见附图5(d)。
Claims (5)
2.一种制备权利要求1所述的氟硼二吡咯化合物(BODIPY)的方法,其特征是它包括下列步骤:
在反应容器中加入2-(2-噻吩基)-噻吩并[3,2-b]吡咯,芳香醛R-CHO和无水二氯甲烷,2-(2-噻吩基)-噻吩并[3,2-b]吡咯与芳香醛摩尔比为2:1,在无水无氧避光条件下放入磁子室温搅拌,然后用微量注射器逐滴加入催化量的三氟乙酸(TFA),室温下反应12小时后,将与芳香醛R-CHO同摩尔数的2,3-二氯-5,6-二氰基-1,4-苯醌(DDQ)加入到反应溶液中,反应1小时,之后加入过量的三乙胺(TEA)和BF3·Et2O,再反应一个小时,然后用水淬灭反应,用NaHCO3、水和饱和食盐水依次洗涤,无水Na2SO4干燥,减压蒸去溶剂得黑色粉未,用100-140目硅胶装柱、乙酸乙酯-石油醚作为洗脱剂进行层析分离,蒸干溶剂后得到目标化合物:
其中:M=T=P=F=E=M’=T’=P’=F’=E’=H;
经氯仿和正己烷混合溶剂重结晶后得氟硼二吡咯化合物A1的晶体。
3.一种制备权利要求1所述的多溴取代的基于二联噻吩并吡咯基团的近红外氟硼二吡咯化合物的方法,其特征是它包括如下步骤:
在反应容器中加入权利要求2所述制得的二联噻吩并吡咯BODIPY和N-溴代琥珀酰亚胺或者Br2和四氢呋喃,室温下搅拌,反应完后用硫代硫酸钠溶液淬灭,之后水,饱和食盐水依次洗涤,无水Na2SO4干燥,减压蒸去溶剂得金色粉未,用300-400目硅胶装柱、乙酸乙酯-石油醚作为洗脱剂进行层析分离,蒸干溶剂后得到各个多溴取代的二联噻吩并吡咯BODIPY,经氯仿和正己烷重结晶后得到各个多溴取代的二联噻吩并吡咯BODIPY晶体。
4.根据权利要求3所述的制备方法,其特征是:N-溴代琥珀酰亚胺或者Br2与BODIPY的用量比例和反应时间不同,得到不同的溴取代的二联噻吩并吡咯BODIPY。
5.权利要求1所述的基于二联杂环并吡咯基团的近红外氟硼二吡咯化合物在制备生物成像和光动力治疗药物中的应用。
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