CN109232624A - 一种不对称氮杂氟硼烷染料及其制备方法和应用 - Google Patents
一种不对称氮杂氟硼烷染料及其制备方法和应用 Download PDFInfo
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- 229910000085 borane Inorganic materials 0.000 title claims abstract description 28
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 239000000975 dye Substances 0.000 title claims abstract description 26
- GQFIUXKQHAQQHA-UHFFFAOYSA-N [F].N1C=CC=CC=C1 Chemical compound [F].N1C=CC=CC=C1 GQFIUXKQHAQQHA-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 238000006467 substitution reaction Methods 0.000 claims abstract description 5
- 238000006116 polymerization reaction Methods 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 12
- 230000015572 biosynthetic process Effects 0.000 claims description 11
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- 229910015900 BF3 Inorganic materials 0.000 claims description 7
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- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 claims description 4
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- 239000005695 Ammonium acetate Substances 0.000 claims description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 3
- 229940043376 ammonium acetate Drugs 0.000 claims description 3
- 235000019257 ammonium acetate Nutrition 0.000 claims description 3
- 238000006555 catalytic reaction Methods 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 3
- 238000007626 photothermal therapy Methods 0.000 claims description 3
- 150000001299 aldehydes Chemical class 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 238000003379 elimination reaction Methods 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
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- 125000000168 pyrrolyl group Chemical group 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- 230000000694 effects Effects 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 11
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- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
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- 238000012512 characterization method Methods 0.000 description 4
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- FBUZNPORDKVYFD-UHFFFAOYSA-N 1-bromohex-1-ene Chemical class CCCCC=CBr FBUZNPORDKVYFD-UHFFFAOYSA-N 0.000 description 2
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
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- MOFVSTNWEDAEEK-UHFFFAOYSA-M indocyanine green Chemical compound [Na+].[O-]S(=O)(=O)CCCCN1C2=CC=C3C=CC=CC3=C2C(C)(C)C1=CC=CC=CC=CC1=[N+](CCCCS([O-])(=O)=O)C2=CC=C(C=CC=C3)C3=C2C1(C)C MOFVSTNWEDAEEK-UHFFFAOYSA-M 0.000 description 2
- 229960004657 indocyanine green Drugs 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
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- 150000004032 porphyrins Chemical class 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 2
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- KJNCZGIIEWUVKZ-UHFFFAOYSA-N B.[F] Chemical class B.[F] KJNCZGIIEWUVKZ-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- YPDSOAPSWYHANB-UHFFFAOYSA-N [N].[F] Chemical compound [N].[F] YPDSOAPSWYHANB-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
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- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
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- 238000000799 fluorescence microscopy Methods 0.000 description 1
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- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
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- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
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- 238000001931 thermography Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
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- 230000009466 transformation Effects 0.000 description 1
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- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
- C07F5/02—Boron compounds
- C07F5/022—Boron compounds without C-boron linkages
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Abstract
本发明公开了一种不对称的氮杂氟硼烷染料及其制备方法和应用。所述染料由氮杂氟硼烷骨架以及链长不等的烷基链和末端带烯基的烷基链构成,所述染料主要经由不同链取代醛或者酮‑烯酮的合成‑加成反应‑成环反应‑配位取代反应等多步反应最终完成。所述染料在近红外波长区域有较强的吸收和发射,光热性质和化学稳定性都有提高,有着烯基和吡咯环上的可修饰位点,可以用于取代、加成、聚合反应,在特殊官能团检测和水溶性生物等领域均有较好的应用。
Description
技术领域
本发明属于有机光电材料技术领域。具体涉及一种基于氮杂氟硼烷的具有近红外吸收的光热染料和其制备方法及其在荧光成像、光热成像、光声成像、光热治疗以及光动力治疗等领域中的应用。
背景技术
肿瘤一直是难以攻克的致死性疾病,目前对肿瘤的治疗方法还停留在传统的手术疗法、化疗或放射疗法;这些治疗方式往往会伴随着毒副作用的产生,治疗效果不佳。探索新的、毒副作用小的治疗方法,或者在已有治疗方法的基础上增加一些辅助手段,进而提高疗效、减轻毒副作用,是目前肿瘤治疗亟待解决的问题。
随着科学技术的不断发展,科研工作者逐渐开发出了多种新型治疗方案,其中光热光动力治疗作为一种非侵入性的肿瘤治疗手段,可以实时的进行肿瘤部位精确治疗,大大的提高了肿瘤治疗的效果。主要是将吲哚菁绿(ICG)、卟啉衍生物和二氢卟吩-e6(Ce6)等光敏剂呈递到肿瘤部位,在外部光源照射下,光敏剂能够吸收光能,并将氧气转化为有细胞毒性的活性氧。但是,光热光动力作为一个整体,其能量分配方式存在相互竞争的关系,如何选择合适的光敏剂已经成为人们研究的重点。
近年来陆续报道了氟硼烷、花菁、卟啉等染料,根据不同的需求被广泛的设计和合成。其中,氟硼烷类染料作为一种常用的染料具有好的光稳定性、高的量子产率、大的摩尔消光系数并且易修饰。这也使得其广泛应用于荧光标记、光学成像、光学肿瘤治疗等领域。与具有相似结构的氟硼烷相比,氮杂氟硼烷具有更长的吸收波长,在活体应用中独具优势,且其展现出不可忽略的辐射跃迁,这部分辐射跃迁会削弱单线态到三线态的转变使其不仅有良好的光热效应,还拥有了一定的光动力效果。但是如何实现其光热光动力效果的平衡依然是一个需要重点突破的问题。
氮杂氟硼烷染料一般用于生物标记、成像、光动力治疗等领域,目前为止,关于如何平衡其光热光动力效果以使其能量利用效率达到最好的报道还较少,本发明将原子连接到具有近红外吸收的氮氟硼烷染料上,从而使其具有良好的光声成像、光热成像及生物肿瘤的光热和光动力相结合的治疗效果。
发明内容
本发明的目的在于解决现有技术中的不足,设计并合成一种不对称氮杂氟硼烷染料,在氮杂BODIPY上引入原子,使其不仅具有良好的光声成像和光热成像效果,而且具有很好的光热性能,不仅对在成像引导下的治疗具有重要意义,对在指导设计、合成具有良好光热性能的光热材料方面也具有重要的指导意义。
本发明的技术方案为:本发明提供了一种不对称氮杂氟硼烷染料,其特征在于,所述染料的结构通式如下:
其中,R1为具有1至16个碳原子的直链且末端带有烯基,
R2、R3和R4选自下列中的任一个:
其中,R5为1至16个碳原子的烷基链,
X为Cl、Br或者I。
所述不对称氮杂氟硼烷染料的具体合成路线如下:
进一步地,所述不对称氮杂氟硼烷染料的具体合成步骤为:
对羟基苯甲醛经过带烯基的烷基链的取代,取代所得的带烯基的烷基链的醛和烷基链取代的对乙酮在乙醇中由氢氧化钠溶液催化经过加成消除反应生成酮烯,然后酮烯和硝基甲烷在二乙胺的催化下发生加成后,和另一种同样方法得到硝基加成的酮在正丁醇中和乙酸铵110℃下反应成环;成环后的产物和三氟化硼乙醚在二氯甲烷中加成得到氮杂氟硼烷。
进一步地,所述不对称氮杂氟硼烷染料可应用在聚合加成取代反应中。
进一步地,所述不对称氮杂氟硼烷染料可应用在肿瘤的光动力和光热治疗中。
本发明的有益效果是:
1.本发明所述不对称氮杂氟硼烷染料由近红外光激发,削弱了激发光源对生物组织的伤害,削弱背景荧光对检测信号的影响,具有较深的组织穿透深度;
2.本发明所述不对称氮杂氟硼烷染料由光致电子转移理论进行指导,很好的实现发光的猝灭和光热的转换及其吸收发射光谱的红移;
3.本发明所述不对称氮杂氟硼烷染料可用于光热成像、光声成像引导下的肿瘤治疗,是很好的生物光热光动力治疗材料;
4.本发明所述不对称氮杂氟硼烷染料制备方法工艺简单,原料丰富,便于工业化生产。
附图说明
图1是本发明实施例1中测定的化合物B1的MALDI-TOF图;
图2是本发明实施例1中测定的化合物B1的1H-NMR图;
图3是本发明实施例1中测定的化合物B1的13C-NMR图;
图4是本发明实施例2中测定的化合物B1的紫外-可见光谱图;
图5是本发明实施例3中测定的化合物B1的发射光谱图;
图6是本发明实施例4中测定的不同浓度的化合物B1的光热效果图;
图7是本发明实施例5中测定的不同浓度的化合物B1的光动力效果图。
具体实施方式
以下实施例进一步说明本发明的内容,但不应理解为对本发明的限制,在不背离本发明实质的情况下,对本发明方法、步骤或条件所作的修改和替换,均属于本发明的范围。
实施例1:不对称氮杂氟硼烷的合成,具体的合成路线如下:
F的合成:为保证实验的结果,对羟基苯乙酮和6溴-1-己烯的反应量为1:5,在一个100mL的圆底烧瓶,加入磁子。用电子天平称取0.2g的对羟基苯乙酮加入到圆底烧瓶中称取1g的碳酸钾同样加入到圆底烧瓶中,用注射器吸取并在天平上称量约1g的6溴-1-己烯注入圆底烧瓶,加入溶剂DMF淹没固体颗粒即可,插气球保护。将烧瓶安装在油浴锅上,将温度升至80℃隔夜反应。。
N的合成:第三步实验的实验原料比例依然按照对羟基苯乙酮:溴辛烷为1:5的比例加入反应。在一个100mL的圆底烧瓶,加入磁子。用电子天平称取0.2g的对羟基苯乙酮加入到圆底烧瓶中称取1g的碳酸钾同样加入到圆底烧瓶中,用注射器吸取并在天平上称量约1g的溴辛烷注入圆底烧瓶,加入溶剂DMF淹没固体颗粒即可,插气球保护。将烧瓶安装在油浴锅上,将温度升至80℃隔夜反应。
产物S和H的合成:步骤以及处理过程大致相同,以H的合成为例:将对甲氧基苯乙酮和得到的产物和N按照1:1的比例混合在常温下搅拌加入适量的饱和氢氧化钠溶液,直至反应瓶中的固体全部溶解,进行搅拌反应,由于实验一和实验三的产率都很高可以近似看做是1:1反应,实验过程中原料的颜色由澄清溶液变为淡黄色的浑浊液体,有微黄色的固体出现。反应时间为隔夜反应。
S的结构表征为:1H NMR(400MHz,CDCl3)d(ppm)δ8.06(d,J=8.8Hz,2H),7.80(d,J=15.6Hz,1H),7.61(d,J=8.8Hz,2H),7.45(d,J=15.6Hz,1H),7.01–6.99(m,2H),6.95–6.93(m,2H),5.91–5.81(m,1H),5.09–5.00(m,2H),4.03(t,J=6.4Hz,2H),3.91(s,3H),2.19–2.13(m,2H),1.88–1.81(m,2H),1.64–1.57(m,2H).13C NMR(100MHz,CDCl3)d(ppm):δ188.81,163.27,161.10,143.93,138.44,131.40,130.71,130.13,127.63,119.41,114.88,113.79,67.95,55.50,33.41,28.61,25.29.
H的结构表征为1H NMR(400MHz,CDCl3)d(ppm)δ8.10–7.94(m,2H),7.77(d,J=15.6Hz,1H),7.64–7.51(m,2H),7.43(d,J=15.6Hz,1H),7.03–6.94(m,4H),4.04–3.97(m,4H),1.88–1.74(m,4H),1.49–1.25(m,20H),0.89(t,J=13.6Hz,6H).13C NMR(100MHz,CDCl3)d(ppm):δ188.76,162.92,161.15,143.85,131.14,130.70,130.11,127.60,119.38,114.88,114.24,68.19,31.83,29.24,26.03,22.68,14.13.
产物G和I的合成:准备一个250mL的圆底烧瓶,加入干净的磁子。用电子天平准确称取2g的黄色粉末S,倒入圆底烧瓶中,依次用量筒分别量取50mL的硝基甲烷,70mL的二乙胺加入到烧瓶中,随后加入适量的乙醇溶剂,只要使固体颗粒溶解即可。将烧瓶安装在油浴锅上,加热至90℃,搭建冷凝回流装置,尽量使反应在密闭的条件下反应。充氮气保护进行反应,反应时间为16小时。
G的结构表征如下:1H NMR(400MHz,CDCl3)d(ppm):δ7.89(d,J=8.4Hz,2H),7.18(d,J=8.4Hz,2H),6.91(d,J=8.8Hz,2H),6.83(d,J=8.4Hz,2H),5.87–5.77(m,1H),5.05–4.95(m,2H),4.81–4.60(m,1H),4.18–4.10(m,1H),3.91(t,J=6.4Hz,2H),3.85(s,3H),3.41–3.28(m,1H),2.14-2.09(m,2H),2.04(s,2H),1.80–1.73(m,2H).13C NMR(100MHz,CDCl3)d(ppm):δ195.51,163.81,158.58,138.54,130.96,130.37,129.51,128.4,114.84,113.88,79.94,67.73,55.54,41.31,38.79,33.43,28.68,25.31.
I的结构表征如下:1H NMR(400MHz,CDCl3)d(ppm):δ7.88(d,J=8.0Hz,2H),7.17(d,J=8.0Hz,2H),6.90(d,J=8.3Hz,2H),6.83(d,J=7.6Hz,2H)4.81–4.60(m,2H),4.18–4.11(m,1H),4.00(t,J=12.8Hz,2H),3.90(t,J=12.8Hz,2H),3.41–3.28(m,2H),1.82–1.72(m,4H),1.50–1.28(m,20H),0.88(t,J=10.8Hz,6H).13C NMR(100MHz,CDCl3)d(ppm):δ195.53,163.47,158.64,130.94,130.36,129.28,128.46,114.93,114.31,79.94,68.35,68.00,41.29,38.82,31.82,29.72,29.48,28.97,26.02,22.67,14.12.
O的合成:将上几步实验得到的G和I用于制备O,用于制备I和G的实验中实验的产率大致相当,所以I和G可以大致按照1:1的比例进行实验。准备一个100mL的烧瓶,将制备得到的I和G混合加入烧瓶中,加入磁子,加入正丁醇至淹没反应药品即可,要保证原料完全溶解,加入300~400倍的醋酸铵,安装冷凝回流管,在120℃的条件下进行冷凝回流。将装置密封,充氮气保护。反应的温度必须要达到冷凝回流的温度。
B1的制备:将得到的产物O,用少量的二氯甲烷溶解。准备一个100mL的圆底烧瓶,放入磁子,将溶解的原料转移入烧瓶中,加入25mL的N,N-二异丙基乙胺,塞子塞紧,用注射器抽取10mL的三氟化硼乙醚,缓慢的加入瓶中。将烧瓶放在旋转搅拌器上,在室温的条件下反应隔夜处理。实验要注意三氟化硼乙醚的加入要缓慢,由于在加入过程中会有大量的乙醚蒸汽,加入的过程要慢,尽量减少瓶内的压力,以防发生危险。该步实验的原理为配位反应,三氟化硼乙醚的量可以稍微多一些。三氟化硼乙醚的主要作用是拔氢,为使实验的反应更加充分,三氟化硼乙醚的量可以稍微多一些。
实施例2:B1的紫外-可见光谱测试:
配置实施例1中的B1的稀溶液(10-5M,二氯甲烷为溶剂),移取2mL溶液于比色皿中进行紫外-可见发光谱测试,结果如图4,从图4中可以看出B1在二氯甲烷溶液中实现了更大的近红外吸收。
实施例3:B1的发射光谱测试:
配置实施例1中的B1的稀溶液(10-5M,二氯甲烷为溶剂),移取2mL溶液于比色皿中进行发射光谱测试。结果如图5,从图5中可以看出B 1在二氯甲烷溶液中具有很好的近红外发射,最大发射波长745nm。
实施例4:B1的光热效果测试:
将实施例1中的化合物B1用二氯甲烷溶解,二氯甲烷溶液将其稀释成不同浓度梯度的溶液(0、10、30μM),用690nm激光器照射5min(0.5W/cm2),用光热成像仪记录不同时间、不同浓度下,溶液温度的变化。结果如图6,从图6中可以看出,随着浓度增加,B1溶液的温度变化高达22℃,说明该化合物具有很好的光热效果。
实施例5:B1的光动力效果测试:
将实施例1中的化合物B1用二氯甲烷溶解,并向其中加入DPBF作为指示剂证明其活性氧的产生,每次用690nm激光器照射8min(0.5W/cm2),并记录其吸收度的变化。结果如图7,从图7中可以看出,DPBF吸收值随着光照次数的增加而下降,说明该化合物具有很好的光动力效果。
以上显示和描述了本发明的基本原理、主要特征及优点。但是以上所述仅为本发明的具体实施例,本发明的技术特征并不局限于此,任何本领域的技术人员在不脱离本发明的技术方案下得出的其他实施方式均应涵盖在本发明的专利范围之中。
Claims (5)
1.一种不对称氮杂氟硼烷染料,其特征在于,该染料的结构通式如下:
其中,R1为具有1至16个碳原子的直链且末端带有烯基,
R2、R3和R4选自下列中的任一个:
其中,R5为具有1至16个碳原子的烷基链,
为Cl、Br或者I。
2.如权利要求1所述的一种不对称氮杂氟硼烷染料的制备方法,其特征在于,具体合成路线如下:
3.如权利要求2所述的一种近红外氮杂氟硼烷染料的制备方法,其特征在于,具体合成步骤为:对羟基苯甲醛经过带烯基的烷基链的取代,取代所得的带烯基的烷基链的醛和烷基链取代的对乙酮经过加成消除反应生成酮烯,然后酮烯和硝基甲烷在二乙胺的催化下发生加成后,和另一种同样方法得到硝基加成的酮乙酸铵在110℃下反应成环;成环后的产物和三氟化硼乙醚在二氯甲烷中加成得到氮杂氟硼烷。
4.如权利要求1-3中任一项所述的不对称氮杂氟硼烷染料在聚合加成取代反应中的应用。
5.如权利要求1-3中任一项所述的不对称氮杂氟硼烷染料在肿瘤的光热治疗中的应用。
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111643482A (zh) * | 2020-07-28 | 2020-09-11 | 南京邮电大学 | 一种在乏氧条件下释放硫化氢的纳米粒子及其制备方法和应用 |
CN111777711A (zh) * | 2020-07-29 | 2020-10-16 | 南京邮电大学 | 一种光热控制释放硫化氢的聚合物及其制备方法和应用 |
CN112592360A (zh) * | 2020-11-30 | 2021-04-02 | 天津大学 | 一类两亲性氮杂氟硼二吡咯近红外染料及其制备方法 |
CN113912762A (zh) * | 2021-09-24 | 2022-01-11 | 复旦大学 | 水溶性的近红外二区大分子荧光探针及其制备方法和应用 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106543213A (zh) * | 2016-09-27 | 2017-03-29 | 苏州百源基因技术有限公司 | 一种红外bodipy荧光染料及其制备方法和应用 |
CN107501313A (zh) * | 2017-08-24 | 2017-12-22 | 南京邮电大学 | 一种基于氮杂氟硼烷的近红外光热染料及制备和应用 |
CN108102408A (zh) * | 2017-12-26 | 2018-06-01 | 南京邮电大学 | 一种基于氮杂氟硼烷的近红外染料的制备及应用 |
CN108503658A (zh) * | 2018-04-28 | 2018-09-07 | 南京邮电大学 | 一种近红外氯化氮杂氟硼烷染料及其制备方法和应用 |
-
2018
- 2018-10-24 CN CN201811241614.3A patent/CN109232624A/zh active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106543213A (zh) * | 2016-09-27 | 2017-03-29 | 苏州百源基因技术有限公司 | 一种红外bodipy荧光染料及其制备方法和应用 |
CN107501313A (zh) * | 2017-08-24 | 2017-12-22 | 南京邮电大学 | 一种基于氮杂氟硼烷的近红外光热染料及制备和应用 |
CN108102408A (zh) * | 2017-12-26 | 2018-06-01 | 南京邮电大学 | 一种基于氮杂氟硼烷的近红外染料的制备及应用 |
CN108503658A (zh) * | 2018-04-28 | 2018-09-07 | 南京邮电大学 | 一种近红外氯化氮杂氟硼烷染料及其制备方法和应用 |
Non-Patent Citations (1)
Title |
---|
CHRISTOPHER J. REINHARDT ET AL: "A Ratiometric Acoustogenic Probe for in Vivo Imaging of Endogenous Nitric Oxide", 《J. AM. CHEM. SOC.》 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111643482A (zh) * | 2020-07-28 | 2020-09-11 | 南京邮电大学 | 一种在乏氧条件下释放硫化氢的纳米粒子及其制备方法和应用 |
CN111777711A (zh) * | 2020-07-29 | 2020-10-16 | 南京邮电大学 | 一种光热控制释放硫化氢的聚合物及其制备方法和应用 |
CN112592360A (zh) * | 2020-11-30 | 2021-04-02 | 天津大学 | 一类两亲性氮杂氟硼二吡咯近红外染料及其制备方法 |
CN113912762A (zh) * | 2021-09-24 | 2022-01-11 | 复旦大学 | 水溶性的近红外二区大分子荧光探针及其制备方法和应用 |
CN113912762B (zh) * | 2021-09-24 | 2023-02-10 | 复旦大学 | 水溶性的近红外二区大分子荧光探针及其制备方法和应用 |
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