CN115504934A - 萘二甲酰亚胺-硝酮类化合物及其制备方法和用途 - Google Patents
萘二甲酰亚胺-硝酮类化合物及其制备方法和用途 Download PDFInfo
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Abstract
本发明属于荧光探针领域,公开了一类萘二甲酰亚胺‑硝酮类化合物及其制备方法与用途,涉及一种由下述通式(I)所示的萘二甲酰亚胺‑硝酮类化合物,及其相应的与环辛炔(BCN)、反式环辛烯(TCO)或二苯并环辛炔(DIBO)发生生物正交反应后的环加成产物(II)及其光转化产物(III)。该类化合物具有显著的生物正交荧光增强(Turn‑on)效应及优良的光物理性质,能够快速、高效、特应性标记目标生物蛋白分子,可作为荧光探针。本发明可应用于体外蛋白标记、活细胞或组织的标记成像,具有广泛的应用前景。
Description
技术领域
本发明属于荧光探针领域,涉及一种萘二甲酰亚胺-硝酮类化合物及其制备方法和用途。
背景技术
基于分子探针的荧光成像技术具有便捷、高效、直观的特点,在生物医学领域具有广泛的应用。但是,传统荧光探针大多存在体系背景高、检测灵敏度差、易产生自身荧光等问题,具有一定的应用限制。因此,开发高信噪比、高特异性、高灵敏度的荧光探针具有重大意义。
相较于传统的荧光探针,生物正交“Turn-on”型荧光增强探针是一类自身荧光信号处于淬灭状态,在与特定的反应物发生生物正交反应(Bioorthogonal Reactions)后荧光信号显著增强的小分子探针。该类小分子探针能够有效消除外界干扰引起的假阳性结果,同时可降低自身背景信号干扰。此外,在使用过程中无需洗去残余的探针分子,操作方便,灵敏度高,能够有效实现在生理条件下对生物大分子的标记与示踪,具有良好的应用前景。
1,8-萘二甲酰亚胺类化合物是一类具有内部电荷转移(ICT)效应的荧光团,化学性质稳定性,结构易于修饰,且具有较大的斯托克斯位移,目前已广泛应用于荧光探针,细胞成像,荧光传感器,生物荧光标记等领域。本发明旨在提供一类基于萘二甲酰亚胺的新型生物正交“Turn-on”型荧光探针,用于光学成像和生物标记领域。
发明内容
发明目的:本发明的目的在于提供一种新型硝酮取代的1,8-萘二甲酰亚胺类探针,且该类探针能够发生1,3-偶极环加成反应得到荧光显著增强的新型探针分子。本发明的另一个目的在于公开该类化合物的制备方法,该方法可操作性强且较为高效;此外,通过荧光性质测试阐明了所述化合物具有生物正交反应“Turn-on”效应,能够快速、高效地实现蛋白、细胞及生物组织的特异性标记。
技术方案:本发明所述萘二甲酰亚胺-硝酮类荧光探针及其相应的生物正交反应产物、光转化产物,包含结构如通式(I)、通式(II)或通式(III)所示的化合物:
其中,
X选自氢、C1-C8烷基、含卤素或杂原子取代的C1-C8烷基,其中,所述杂原子选自N、O、S,所述卤素为F、Cl、Br、I;
R1、R2独立的选自-CN、-NO2、-CF3、-CHO、-CONR8R9、-COOR10或-SO3H;其中,R8为氢、C1-C6烷基,R9为氢、C1-C6烷基;R10为氢、C1-C6烷基;
R3选自以下结构片段之一:
其中,
R4、R5独立的选自-CN、-NO2、-CF3、-CHO、-CONR11R12、-COOR13或-SO3H;其中,R11为氢、C1-C6烷基,R12为氢、C1-C6烷基;R13为氢、C1-C6烷基;
环A独立地选自以下结构片段之一:
其中,
R6、R7独立的选自-CN、-NO2、-CF3、-CHO、-CONR14R15、-COOR16或-SO3H;其中,R14为氢、C1-C6烷基,R15为氢、C1-C6烷基;R16为氢、C1-C6烷基;
优选地,所述化合物选自下述化合物(XT-DIBO,XT-TCO和XT-DIBO-UV中的波浪线代表该化合物为异构体混合物):
优选的所述化合物的制备方法,包括以下步骤:
反应条件:(a)正丁胺、乙醇,70℃,1h;(b)氯化铵、锌粉,甲醇,室温,3h;(c)三氯化铁,乙醇,室温,10min;(d)溴代物、氢氧化钠、四氢呋喃,0℃,4h;(e)烯烃或炔烃,室温,5min。
所述的化合物具有生物正交荧光增强效应。
所述的化合物在生物大分子荧光标记中的应用。
所述的化合物在活细胞荧光标记中的应用。
在一些实施例中,所述化合物选自以下化合物:
本发明具有如下优点和有益效果:
本发明所述的萘二甲酰亚胺-硝酮类化合物具有显著的荧光增强效果,具有良好的光物理性质,可以实现对目标生物分子的高效、特异性标记,为蛋白质等生物大分子以及活细胞的荧光标记和可视化研究提供了新的工具,具有广泛的应用前景。
附图说明
图1探针分子的吸收光谱曲线
图2探针分子的发射光谱曲线
图3探针分子用于蛋白特异性标记
具体实施方式
1H-NMR核磁共振由Bruker AV400型(400HZ)核磁共振仪测定(TMS为内标物),质谱分别由岛津GC/MS-QP2010型质谱仪(EI-MS)、Agilent100LC-MDS-Trans/SL型质谱仪(EI-MS)测定。
柱层析硅胶为100-200目、200-300目或300-400目硅胶(青岛海洋化工厂),洗脱剂为石油醚-乙酸乙酯体系或二氯甲烷-甲醇体系。薄层层析(TLC)用GF254薄层层析板(烟台江友硅胶开发有限公司);TLC展开体系为石油醚-乙酸乙酯体系或二氯甲烷-甲醇体系;TLC在ZF7型三用紫外分析仪(河南巩义予华仪器有限公司)下照射显示。
合成路线:
反应条件:(a)正丁胺、乙醇,70℃,1h;(b)氯化铵、锌粉,甲醇,室温,3h;(c)三氯化铁,乙醇,室温,10min;(d)溴代物、氢氧化钠、四氢呋喃,0℃,4h;(e)烯烃或炔烃,室温,5min。
实施例1
中间体1的合成
将4-硝基萘二甲酸酐(360mg,1.48mmol)加入到10ml乙醇溶液中,搅拌下加入正丁胺(108.2mg,1.48mmol),90℃回流1h,柱层析纯化得淡黄色固体270mg,收率61.2%。1H NMR(400MHz,Chloroform-d)δ8.82(d,J=8.0Hz,1H),8.72(d,J=8.0Hz,1H),8.67(d,J=8.0Hz,1H),8.39(d,J=8.0Hz,1H),8.04–7.91(m,1H),4.14(m,2H),1.71(p,J=7.6Hz,2H),1.44(m,J=14.7,7.4Hz,2H),0.97(t,J=7.3Hz,3H)。
实施例2
中间体3的合成
将中间体1(330mg,1.11mmol)溶于10ml甲醇溶液中,0℃下加入锌粉(158.4mg,2.43mmol)和氯化铵(71.28mg,1.33mmol),升至室温搅拌3h,旋干溶剂,柱层析得224.7g中间体2。
冰浴下,将三氯化铁(228mg,1.4mmol)溶于水中,搅拌下逐滴加入上述中间体2(200mg,0.7mmol)的乙醇溶液中,室温反应10min,TLC监测反应完全,加水,乙酸乙酯萃取,合并有机相,无水硫酸钠干燥,旋干溶剂,柱层析纯化得150mg淡黄色固体,收率75.5%。1HNMR(400MHz,CDCl3)δ10.16(d,J=9.6Hz,1H),8.78(d,J=7.3Hz,1H),8.62(d,J=7.9Hz,1H),8.28–8.19(m,1H),6.62(d,J=7.9Hz,1H),4.24–4.18(m,2H),1.81–1.68(m,2H),1.51–1.42(m,2H),0.99(t,J=7.3Hz,3H);13C NMR(100MHz,CDCl3)δ164.1,163.1,156.1,131.9,130.9,130.5,130.5,130.2,129.1,128.1,122.8,105.2,40.7,30.2,20.4,13.9;HRMS(ESI)m/z Calcd for[M+H]+:C16H15N2O3 283.1077,Found 283.1075.
实施例3
化合物XT-1的合成
冰浴下,将中间体3(500mg,1.77mmol)、溴丙二酸二乙酯(423.4mg,1.77mmol)溶于四氢呋喃溶液中,氩气保护下缓慢加入氢氧化钠水溶液(71mg,1.77mmol),继续搅拌6h,旋蒸除去溶剂,柱层析纯化得黄色固体562.1mg,收率72.1%。1H NMR(500MHz,DMSO-d6)δ8.62(d,J=7.8Hz,1H),8.57(d,J=7.8Hz,1H),8.10(d,J=7.8Hz,1H),8.06(d,J=6.3Hz,2H),4.51(m,J=6.9,3.1Hz,2H),4.09(t,J=7.3Hz,2H),4.01(q,J=7.0Hz,2H),1.66(p,J=7.5Hz,2H),1.39(m,5H),0.95(m,6H).13C NMR(101MHz,CDCl3)δ163.58,162.99,159.91,157.63,147.06,132.18,130.60,128.98,128.74,127.61,124.86,124.41,123.12,121.02,63.59,63.34,62.83,40.55,30.20,20.43,14.10,13.88;HRMS(ESI)m/z calculated forC19H18O2N5[M+H]+:441.1643,found:441.1617.
实施例4
化合物XT-2的合成
冰浴下,将中间体3(500mg,1.77mmol)、2-溴丙二酰胺(320.3mg,1.77mmol)溶于四氢呋喃溶液中,氩气保护下缓慢加入氢氧化钠水溶液(71mg,1.77mmol),继续搅拌6h,旋蒸除去溶剂,柱层析得黄色油状物,收率82.6%。1H NMR(400MHz,Chloroform-d)δ9.86(s,1H),8.64(d,J=7.2Hz,1H),8.57(d,J=7.8Hz,1H),8.48(s,1H),8.11(d,J=8.4Hz,1H),7.84(d,J=7.2Hz,1H),7.57(d,J=7.8Hz,1H),6.27(s,1H),5.63(s,1H),4.16(t,2H),1.69(p,J=8.5,7.8Hz,2H),1.43(m,J=14.7,7.4Hz,2H),0.96(t,J=7.3Hz,3H);13C NMR(101MHz,DMSO)δ163.58,162.98,161.55,160.50,146.61,144.06,131.98,130.64,129.82,129.28,128.45,124.91,124.24,122.90,122.41,40.95,30.06,20.31,14.24.
实施例5
化合物XT-3的合成
冰浴下,将中间体3(500mg,1.77mmol)、2-溴丙二腈(256.6mg,1.77mmol)溶于四氢呋喃溶液中,氩气保护下缓慢加入氢氧化钠水溶液(71mg,1.77mmol),继续搅拌6h,旋蒸除去溶剂,柱层析得黄色油状物,收率82.6%。1H NMR(400MHz,Chloroform-d)δ8.75(d,J=6.4Hz,1H),8.70(d,J=7.8Hz,1H),8.08(d,J=8.5Hz,1H),8.00(d,J=7.3Hz,1H),7.95(d,J=7.8Hz,1H),4.19(t,2H),1.77–1.66(m,2H),1.43(m,J=14.7,7.4Hz,2H),0.98(t,J=7.4Hz,3H);13C NMR(101MHz,CDCl3)δ163.34,162.71,145.24,132.48,130.24,128.84,128.55,126.76,124.10,123.40,110.20,110.05,106.45,30.00,20.30,14.23.
实施例6
化合物XT-BCN的合成
将化合物XT-1(100mg,0.23mmol)加入10ml乙腈溶液中,搅拌下加入BCN(40.93mg,0.28mmol),室温反应5min,得黄色固体,收率64.2%。1H NMR(400MHz,Chloroform-d)δ8.96(dd,J=8.5,1.1Hz,1H),8.63–8.43(m,2H),7.69(dd,J=8.5,7.3Hz,1H),7.59(d,J=8.5Hz,1H),4.21–4.04(m,2H),3.97–3.81(m,2H),3.81–3.67(m,4H),2.80–2.65(m,1H),2.60–2.50(m,1H),2.50–2.41(m,1H),2.35–2.17(m,2H),1.75–1.62(m,6H),1.41(m,J=14.7,7.4Hz,2H),1.28–1.17(m,3H),0.94(dt,J=11.4,7.2Hz,9H).13C NMR(101MHz,CDCl3)δ166.68,166.46,164.34,163.76,153.56,149.83,131.63,131.43,131.36,128.60,127.11,126.33,122.25,120.30,119.65,103.67,88.79,62.29,62.82,62.25,59.96,40.34,30.36,30.26,24.96,23.76,22.57,21.25,21.08,20.47,19.00,14.27,13.92,13.66.
实施例7
化合物XT-BCN-UV的合成
将化合物XT-BCN(100mg,0.23mmol)加入10ml乙腈溶液中,365nm紫外照射30min得黄色固体(混合物),收率44.2%。1H NMR(400MHz,Chloroform-d)δ8.57(s,1H),8.51(t,J=6.6Hz,1H),8.05(d,J=8.3Hz,1H),7.57(q,J=7.8,5.8Hz,1H),6.13(s,1H),4.31(p,J=7.1,6.1Hz,2H),4.21–4.04(m,4H),3.79(d,J=6.9Hz,2H),2.96–2.82(m,1H),2.69(m,J=11.4,5.5Hz,1H),2.28(tq,J=15.1,10.6,9.9Hz,3H),2.06–1.94(m,2H),1.86(m,2H),1.64(p,J=7.7Hz,2H),1.39(p,J=7.2Hz,2H),1.28(t,J=7.0Hz,3H),1.19(q,J=7.1Hz,5H),0.92(t,J=7.5Hz,3H).13C NMR(101MHz,CDCl3)δ210.52,168.18,167.40,164.33,164.11,150.33,131.99,129.54,128.70,128.06,125.66,125.25,123.14,117.47,113.71,82.36,68.82,63.00,62.82,59.52,40.29,40.07,35.85,30.36,21.95,20.51,20.39,19.86,18.87,14.27,14.11,13.95,13.91;HRMS(ESI)m/z calculated for C19H18O2N5[M+H]+:591.2708,found:591.2628.
实施例8
化合物XT-TCO的合成
将化合物XT-1(100mg,0.23mmol)加入10ml乙腈溶液中,搅拌下加入TCO(34.77mg,0.28mmol),室温反应5min,柱层析得黄色固体(混合物),收率92.1%。1H NMR(400MHz,Chloroform-d)δ8.91–8.82(m,2H),8.59–8.53(m,2H),8.49(dd,J=8.2,1.4Hz,2H),7.70(dd,J=8.1,4.7Hz,2H),7.65(dd,J=8.5,7.4Hz,2H),4.34–4.21(m,2H),4.18–4.04(m,8H),3.85(m,J=10.7,7.2Hz,2H),3.58–3.47(m,1H),3.44(dd,J=10.8,7.2Hz,1H),3.27(t,J=10.5Hz,2H),2.43–2.32(m,1H),2.27(d,J=11.7Hz,1H),2.16–2.06(m,3H),2.01(d,J=24.2Hz,3H),1.95(d,J=9.0Hz,2H),1.91(s,2H),1.87–1.78(m,2H),1.68(q,J=7.7Hz,6H),1.63–1.52(m,4H),1.50(d,J=7.8Hz,1H),1.47(m,1H),1.45–1.37(m,4H),1.14(q,J=7.0Hz,6H),0.95(t,J=7.4Hz,6H),0.75(t,J=7.1Hz,3H),0.67(t,J=7.2Hz,3H).13C NMR(101MHz,CDCl3)δ167.17,166.95,166.73,166.69,164.46,163.89,149.95,149.65,131.90,131.82,131.51,131.20,131.14,128.80,127.65,125.96,125.89,122.33,119.85,119.78,119.67,119.58,83.34,81.89,77.43,62.14,55.69,40.31,30.28,26.96,25.18,22.81,20.47,19.79,14.06,13.39;HRMS(ESI)m/z calculated for C19H18O2N5[M+H]+:567.2662,found:567.2728.
实施例9
化合物XT-DIBO-UV的合成
将化合物XT-1(100mg,0.23mmol)加入10ml乙腈溶液中,搅拌下加入TCO(61.67mg,0.28mmol),室温反应5min,柱层析得黄色固体,收率89.6%。1H NMR(400MHz,DMSO-d6)δ9.28(s,1H),8.87(d,J=8.3Hz,1H),8.46(d,J=7.3Hz,1H),7.75(t,J=7.8Hz,1H),7.46(d,J=7.7Hz,1H),7.37–7.24(m,3H),7.14–7.02(m,1H),6.94–6.81(m,2H),6.71(d,J=8.0Hz,1H),5.88(d,J=7.7Hz,1H),4.73(dd,J=11.7,4.9Hz,1H),4.41–4.20(m,2H),4.07(dd,J=14.9,11.8Hz,1H),3.88(t,J=7.7Hz,2H),3.65(m,J=10.8,7.0Hz,1H),3.38–3.30(m,1H),3.20(dd,J=14.9,4.6Hz,1H),1.48(m,J=8.5,4.1Hz,2H),1.29(t,J=7.0Hz,3H),1.26–1.13(m,2H),0.84(t,J=7.3Hz,3H),0.65(t,J=7.1Hz,3H);13C NMR(101MHz,CDCl3)δ200.50,167.91,167.35,164.01,162.96,154.35,154.27,139.95,139.87,135.05,133.76,132.74,132.52,132.40,132.23,131.95,131.40,130.65,130.45,130.37,129.55,126.99,126.34,125.77,122.69,121.27,116.99,109.59,83.98,75.68,75.61,62.92,62.14,30.22,20.30,14.34,14.22,13.69;HRMS(ESI)m/z calculated for C19H18O2N5[M+H]+:661.2543,found:661.2505.
实施例10
化合物XT-BEN的合成
将XT-1(100mg,0.91mmol)加入到乙腈溶液中,随后加入2-(三甲基甲硅烷基)苯基三氟甲磺酸酯(82mg,1.1mmol),氟化铯(70mg,1.82mmol),室温搅拌4h,旋干溶剂,柱层析纯化得黄色固体293.1mg,收率62.4%。1H NMR(400MHz,Chloroform-d)δ8.63–8.57(m,2H),8.36–8.31(m,1H),7.99(d,J=7.9Hz,1H),7.66(dd,J=8.5,7.4Hz,1H),7.00(d,J=7.8Hz,1H),6.87–6.79(m,1H),6.77–6.71(m,1H),6.09–6.03(m,1H),4.31–4.12(m,4H),4.01(m,J=10.9,7.2Hz,1H),3.91(m,J=10.8,7.2Hz,1H),1.77–1.66(m,2H),1.45(m,J=7.4Hz,2H),1.17(t,J=7.1Hz,3H),0.98(t,J=7.3Hz,3H),0.86(t,J=7.1Hz,3H).
实验例1
探针分子的光物理性质测试
1.探针分子的吸收和发射光谱测定
将实施例中化合物配置为10mM的DMSO储备液,然后用乙腈将其稀释至终浓度为10μM。将稀释后的化合物加入96孔板中,两个复孔,每孔200μL;用Tecan SparkTM 10MMultimode Microplate Reader多模式酶标仪测试化合物的吸收光谱,并记录每个探针分子的最大吸收波长,如图1所示。根据上述所得探针分子的最大吸收波长测试探针分子的发射光谱,并记录每个探针分子的最大发射波长,如图2所示。
2.探针分子的摩尔消光系数和荧光量子产率的测定
将浓度为10μM的探针分子加入到荧光石英比色皿中,使用酶标仪测试其吸光度,根据朗博-比尔定律计算探针分子的摩尔消光系数;以3μg/ml的硫酸奎宁(0.1N硫酸溶液)为标准品,测试探针分子的吸光度(A<0.05)及峰面积,通过参比法计算各探针分子的荧光量子产率,计算结果如表1所示。
表1探针分子的光物理性质
实验例2
探针分子的生物学应用
将3μl XT-1(10mM)加入到10μl BSA-BCN或BSA-DIBO溶液中,室温孵育30min,加入5μl的5x SDS loading buffer,95℃加热变性5min;在BeyogelTM SDS-PAGE预制胶中加入上述样品,60V,电泳30min后升压120V跑胶至溴酚蓝跑至底部,水洗,进行胶内荧光观察,随后用考马斯亮蓝染色,脱色后观察蛋白条带,如图3所示。
Claims (7)
1.如通式(I)、(II)/(III)所示的萘二甲酰亚胺类化合物:
其中,
X选自氢、C1-C8烷基、含卤素或杂原子取代的C1-C8烷基,其中,所述杂原子选自N、O、S,所述卤素为F、Cl、Br、I;
R1选自氢、C1-C8烷基、氰基、硝基、三氟甲基、甲酰基、氨基甲酰基、C1-C6烷基取代的氨基甲酰基、羧基、C1-C6烷基取代的氧甲酰基、磺酸基;
R2选自氢、C1-C8烷基、氰基、硝基、三氟甲基、甲酰基、氨基甲酰基、C1-C6烷基取代的氨基甲酰基、羧基、C1-C6烷基取代的氧甲酰基、磺酸基;
R3选自以下结构片段之一:
其中,
R4选自氢、C1-C8烷基、氰基、硝基、三氟甲基、甲酰基、氨基甲酰基、C1-C6烷基取代的氨基C1-C8烷基、氰基、硝基、三氟甲基、甲酰基、氨基甲酰基、C1-C6烷基取代的氨基甲酰基、羧基、C1-C6烷基取代的氧甲酰基、磺酸基;
环A独立地选自以下结构片段之一:
甲酰基、羧基、C1-C6烷基取代的氧甲酰基、磺酸基;
R5选自氢、
其中,
R6选自氢、C1-C8烷基、氰基、硝基、三氟甲基、甲酰基、氨基甲酰基、C1-C6烷基取代的氨基甲酰基、羧基、C1-C6烷基取代的氧甲酰基、磺酸基;
R7选自氢、C1-C8烷基、氰基、硝基、三氟甲基、甲酰基、氨基甲酰基、C1-C6烷基取代的氨基甲酰基、羧基、C1-C6烷基取代的氧甲酰基、磺酸基。
2.根据权利要求1所述的化合物,其特征在于:
其中,
X选自氢、C1-C8烷基、含卤素或杂原子取代的C1-C8烷基,其中,所述杂原子选自N、O、S,所述卤素为F、Cl、Br、I;
R1、R2独立的选自-CN、-NO2、-CF3、-CHO、-CONR8R9、-COOR10或-SO3H;其中,R8为氢、C1-C6烷基,R9为氢、C1-C6烷基;R10为氢、C1-C6烷基;
R3选自以下结构片段之一:
其中,
R4、R5独立的选自-CN、-NO2、-CF3、-CHO、-CONR11R12、-COOR13或-SO3H;其中,R11为氢、C1-C6烷基,R12为氢、C1-C6烷基;R13为氢、C1-C6烷基;
环A独立地选自以下结构片段之一:
其中,
R6、R7独立的选自-CN、-NO2、-CF3、-CHO、-CONR14R15、-COOR16或-SO3H;其中,R14为氢、C1-C6烷基,R15为氢、C1-C6烷基;R16为氢、C1-C6烷基。
5.权利要求1~4任一项所述的化合物在制备荧光探针中的应用。
6.权利要求1~4任一项所述的化合物在制备生物大分子荧光标记物中的应用。
7.权利要求1~4任一项所述的化合物在制备活细胞荧光标记物中的应用。
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106867515A (zh) * | 2015-12-11 | 2017-06-20 | 中国科学院大连化学物理研究所 | 一种用于蛋白标记及检测的荧光探针及其合成方法与应用 |
CN107540608A (zh) * | 2017-07-17 | 2018-01-05 | 大连理工大学 | 4‑取代萘酰亚胺类化合物及其应用 |
CN110105280A (zh) * | 2019-03-29 | 2019-08-09 | 佛山市格瑞芬新能源有限公司 | 一种基于1,8-萘二甲酰亚胺的水溶性荧光探针及其制备方法和应用 |
CN110286105A (zh) * | 2019-03-08 | 2019-09-27 | 华南农业大学 | 一种荧光探针及其制备方法 |
CN111333642A (zh) * | 2018-12-18 | 2020-06-26 | 中国科学院大连化学物理研究所 | 一类高亮度、高稳定性、环境不敏感的细胞膜荧光探针 |
-
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- 2021-06-22 CN CN202110689926.6A patent/CN115504934A/zh active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106867515A (zh) * | 2015-12-11 | 2017-06-20 | 中国科学院大连化学物理研究所 | 一种用于蛋白标记及检测的荧光探针及其合成方法与应用 |
CN107540608A (zh) * | 2017-07-17 | 2018-01-05 | 大连理工大学 | 4‑取代萘酰亚胺类化合物及其应用 |
CN111333642A (zh) * | 2018-12-18 | 2020-06-26 | 中国科学院大连化学物理研究所 | 一类高亮度、高稳定性、环境不敏感的细胞膜荧光探针 |
CN110286105A (zh) * | 2019-03-08 | 2019-09-27 | 华南农业大学 | 一种荧光探针及其制备方法 |
CN110105280A (zh) * | 2019-03-29 | 2019-08-09 | 佛山市格瑞芬新能源有限公司 | 一种基于1,8-萘二甲酰亚胺的水溶性荧光探针及其制备方法和应用 |
Non-Patent Citations (1)
Title |
---|
YULIN TIAN等: "Design of Nitroso-Modified Naphthylene-Based Fluorophores as Photoactivatable Bioorthogonal Turn-On Probes", 《ORGANIC LETTERS》, vol. 23, no. 9, pages 3783 * |
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