近红外苊并吡嗪荧光染料的合成
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摘要
大部分生物荧光探针的主要应用障碍是荧光发射波长较短,易受到生物质荧光背景的干扰。开发红外长波长生物荧光染料,对于提高检测灵敏性具有很高的应用价值。
本论文以苊醌为原料通过硝化、缩合、取代合成了染料Ap-1c和AP-2c,其中染料AP-2c保持了1,8-萘酰亚胺的荧光性能;而以苊并吡嗪为母体的染料Ap-1c,则达到了610 nm的长波长荧光发射、127nm的大范围stokes位移的近红外荧光染料的要求。
由于利用苊醌双硝化中间体,难以得到其它衍生的苊并吡嗪化合物,本文以苊为原料,通过溴代、硝化、氧化,及合成条件优化,合成一个新的荧光染料中间体4-溴-5-硝基苊醌(P1)。基于该染料中间体合成出苊并吡嗪Ap-1系列的6个新化合物Ap-1a,Ap-1b,Ap-1c,Ap-1d,Ap-1e和Ap-1f。通过系列的性能测试,发现这些苊并吡嗪类荧光染料Ap-1普遍具有荧光发射波长较长,stokes位移大的优点。具有4-(N-苯基乙二胺)基团的染料Ap-1d,在乙腈:水=80:20的体系中,荧光发射波长达632 nm,stokes位移达172 nm,加入Cu~(2+)离子能使荧光强度增大。通过模型化合物Ap-1d的性能可以预测,具有4,5-二(N-苯基乙二胺基团)染料Ap-1f可作为Cu~(2+)荧光增强型近红外荧光探针。染料Ap-1f的合成、分离纯化及其特性需进一步研究。
本文第三节以萘酰亚胺为母体,设计合成了Co~(2+)离子荧光探针CoProbe,并对其性能进行了系统的测试,发现该探针在生物环境的pH=6-8范围内,对Co~(2+)具有荧光淬灭和吸收波长红移的双通道模式高度专一的识别。由于探针CoProbe结构不稳定,荧光发射波长较短,结合Co~(2+)离子后荧光淬灭严重等因素,限制了其实用性。但是,探针CoProbe中对Co~(2+)的高选择性受体,对设计功能优异的钴离子荧光探针提供了可能。
The main applicative problems with most biolocal fluorecent probe were short emission fluorescence wavelength that would be strongly disturbed by the background fluorecence from biomass in ordinary fluorecence zone. So the exploiture of near-infrared biological dyes withlong emission wavelength was of great value for the improvement on testing sensitivity.
Novel fluorescent dye Ap-1c and dye Ap-2c were designed and synthesized through 3-step reaction including intration, condensation and substitution with acenaphthrenequinone as a raw material. Ap-2c retained the fluorescence performance of 1, 8-naphthaIimide, while Ap-1c had 610 nm near-infrared fluorecent emission wavelength and stokes shift as large as 127 nm which made Ap-1c a qualified near-infrared flurescence dye.
As the method diintration of acenaphthrenequinone did not work out for the synthesis of other acenaphtho-pyrazine compounds, a new intermedia 4-bromo-5-nitro acenaphthrenequinone (P1) was designed, synthesised and optimized as well. Based on P1, a series of 6 new acenaphtho-pyrazine compounds named as Ap-1a to Ap-1f were designed and synthesized. Through series of test, common adventages like long emission wavelength and large stokes shift were found among acenaphtho-pyrazine dyes. Especially, the 2-phenylamino acenaphtho-pyrazine dye Ap-1d was found emission wavelength as long as 632 nm , stokes shift as large as 172 nm in acetonitrile-water (80:20, v/v) solution and fluorescence intensity enhanced by Cu~(2+) ion which concluded that Ap-1f would be proper as near-infrared fluorescent probe for Cu~(2+) ion. However, as was difficult to seperate, Ap-1f could not be tested right now.
Fluorecence probe CoProbe was designed and synthsised based on naphthalimide, the testing result showed that CoProbe had altitudinal recognise property for Co~(2+) ion through 2 channel changes in UV-absorbance and fluorescence intensity. However, with objection like unstable structure and performance, short fluorecence wavelength, quenched fluorescent wavelength after coupling with Co~(2+) ion, CoProbe was not suitable for practical application. However, the highly selective acceptor of CoProbe made the design of better probe for Cobalt ion possible.
本论文以苊醌为原料通过硝化、缩合、取代合成了染料Ap-1c和AP-2c,其中染料AP-2c保持了1,8-萘酰亚胺的荧光性能;而以苊并吡嗪为母体的染料Ap-1c,则达到了610 nm的长波长荧光发射、127nm的大范围stokes位移的近红外荧光染料的要求。
由于利用苊醌双硝化中间体,难以得到其它衍生的苊并吡嗪化合物,本文以苊为原料,通过溴代、硝化、氧化,及合成条件优化,合成一个新的荧光染料中间体4-溴-5-硝基苊醌(P1)。基于该染料中间体合成出苊并吡嗪Ap-1系列的6个新化合物Ap-1a,Ap-1b,Ap-1c,Ap-1d,Ap-1e和Ap-1f。通过系列的性能测试,发现这些苊并吡嗪类荧光染料Ap-1普遍具有荧光发射波长较长,stokes位移大的优点。具有4-(N-苯基乙二胺)基团的染料Ap-1d,在乙腈:水=80:20的体系中,荧光发射波长达632 nm,stokes位移达172 nm,加入Cu~(2+)离子能使荧光强度增大。通过模型化合物Ap-1d的性能可以预测,具有4,5-二(N-苯基乙二胺基团)染料Ap-1f可作为Cu~(2+)荧光增强型近红外荧光探针。染料Ap-1f的合成、分离纯化及其特性需进一步研究。
本文第三节以萘酰亚胺为母体,设计合成了Co~(2+)离子荧光探针CoProbe,并对其性能进行了系统的测试,发现该探针在生物环境的pH=6-8范围内,对Co~(2+)具有荧光淬灭和吸收波长红移的双通道模式高度专一的识别。由于探针CoProbe结构不稳定,荧光发射波长较短,结合Co~(2+)离子后荧光淬灭严重等因素,限制了其实用性。但是,探针CoProbe中对Co~(2+)的高选择性受体,对设计功能优异的钴离子荧光探针提供了可能。
The main applicative problems with most biolocal fluorecent probe were short emission fluorescence wavelength that would be strongly disturbed by the background fluorecence from biomass in ordinary fluorecence zone. So the exploiture of near-infrared biological dyes withlong emission wavelength was of great value for the improvement on testing sensitivity.
Novel fluorescent dye Ap-1c and dye Ap-2c were designed and synthesized through 3-step reaction including intration, condensation and substitution with acenaphthrenequinone as a raw material. Ap-2c retained the fluorescence performance of 1, 8-naphthaIimide, while Ap-1c had 610 nm near-infrared fluorecent emission wavelength and stokes shift as large as 127 nm which made Ap-1c a qualified near-infrared flurescence dye.
As the method diintration of acenaphthrenequinone did not work out for the synthesis of other acenaphtho-pyrazine compounds, a new intermedia 4-bromo-5-nitro acenaphthrenequinone (P1) was designed, synthesised and optimized as well. Based on P1, a series of 6 new acenaphtho-pyrazine compounds named as Ap-1a to Ap-1f were designed and synthesized. Through series of test, common adventages like long emission wavelength and large stokes shift were found among acenaphtho-pyrazine dyes. Especially, the 2-phenylamino acenaphtho-pyrazine dye Ap-1d was found emission wavelength as long as 632 nm , stokes shift as large as 172 nm in acetonitrile-water (80:20, v/v) solution and fluorescence intensity enhanced by Cu~(2+) ion which concluded that Ap-1f would be proper as near-infrared fluorescent probe for Cu~(2+) ion. However, as was difficult to seperate, Ap-1f could not be tested right now.
Fluorecence probe CoProbe was designed and synthsised based on naphthalimide, the testing result showed that CoProbe had altitudinal recognise property for Co~(2+) ion through 2 channel changes in UV-absorbance and fluorescence intensity. However, with objection like unstable structure and performance, short fluorecence wavelength, quenched fluorescent wavelength after coupling with Co~(2+) ion, CoProbe was not suitable for practical application. However, the highly selective acceptor of CoProbe made the design of better probe for Cobalt ion possible.
引文
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