CN109486235B - DNA dye compound with nucleus targeting function and application thereof - Google Patents

DNA dye compound with nucleus targeting function and application thereof Download PDF

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CN109486235B
CN109486235B CN201811334907.6A CN201811334907A CN109486235B CN 109486235 B CN109486235 B CN 109486235B CN 201811334907 A CN201811334907 A CN 201811334907A CN 109486235 B CN109486235 B CN 109486235B
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hrms
dna
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CN109486235A (en
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肖义
张晓东
张新富
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Dalian University of Technology
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    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B57/00—Other synthetic dyes of known constitution
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6402—Atomic fluorescence; Laser induced fluorescence
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C09K2211/1018—Heterocyclic compounds
    • C09K2211/1025—Heterocyclic compounds characterised by ligands
    • C09K2211/1059—Heterocyclic compounds characterised by ligands containing three nitrogen atoms as heteroatoms
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C09K2211/1018—Heterocyclic compounds
    • C09K2211/1025—Heterocyclic compounds characterised by ligands
    • C09K2211/1088—Heterocyclic compounds characterised by ligands containing oxygen as the only heteroatom

Abstract

A DNA dye compound with a cell nucleus targeting function and application thereof belong to the field of fine chemical engineering. In the field of biological imaging, visual study of genetic material is of great significance for studying cellular activities. However, the excitation light wavelength required by the traditional dyes Hoechst and DAPI targeting the cell nucleus is short, which can cause serious cell damage in imaging, and in addition, Hoechst and DAPI can only target the cell nucleus simply but cannot realize other functions. In order not to influence the normal physiological function of cells, the invention provides a DNA dye compound with a cell nucleus targeting function, which has higher biocompatibility, can be specifically combined with DNA and has the function of cell nucleus targeting.

Description

DNA dye compound with nucleus targeting function and application thereof
Technical Field
The invention relates to a DNA dye compound with a cell nucleus targeting function and application thereof, in particular to a dye compound for targeting cell nucleus, belonging to the field of fine chemical engineering.
Background
The nucleus is the major organelle of a eukaryotic cell that maintains gene integrity and regulates cell function, and contains a large amount of genetic material, i.e., DNA, inside. Each eukaryotic cell contains approximately two meters of DNA, which interacts with proteins to form highly structured chromatin. DNA is predominantly present in the nucleus in chromatin or chromosome form. The regulation of cellular functions by cellular nuclei is mainly achieved by the action of regulatory DNA. Therefore, the research on the highly structured chromatin or chromosomes in the cell nucleus has important significance for the research on the cell nucleus and the control of the cell life activities.
In the field of bioimaging, visual studies of genetic material are of great interest for studying cellular activity. Hoechst and DAPI are two dyes capable of being combined with DNA, but the excitation light wavelength of the Hoechst and DAPI is short, cells are affected by phototoxicity in the imaging process, so that normal physiological process is disordered or serious cell damage is caused, and the Hoechst and DAPI can only be singly targeted to cell nucleus but cannot realize other functions, such as pH value measurement and the like. In order to not influence the normal physiological function of cells, the synthesis of a functional cell nucleus targeting dye with high biocompatibility has important research value.
Disclosure of Invention
In order to search a fluorescent dye with excellent cell nucleus targeting property, realize the visualization of cell nucleus and research the function of cell nucleus genetic material, the invention provides a DNA dye compound with the cell nucleus targeting function, and the compound is a sulfamide rhodamine compound based on sulfoacid rhodamine and Hoechst which can be used for synthesizing the fluorescent dye for cell microscopic imaging. The sulfoacid rhodamine has the characteristics of higher fluorescence quantum yield and easy functional modification as common rhodamine. In addition, the excitation wavelength of the sulfoacid rhodamine is longer, and the damage to cells in the imaging process is smaller. A traditional nuclear dye Hoechst is used as a targeting group of DNA, and the Hoechst is connected with different sulfonamide rhodamine chromophores with biocompatibility through a Click reaction to obtain a DNA dye compound with a nuclear targeting function.
The technical scheme adopted by the invention is as follows: a DNA dye compound with a cell nucleus targeting function has the following structural general formula:
Figure GDA0002186023720000021
in the general formula (I), the compound is shown in the specification,
Figure GDA0002186023720000022
wherein: n is an integer of 0 to 18, m is an integer of 0 to 18, X-Is an anion, the anion being BF4 -、Cl-、Br-、I-、NO3 -、SO4 2-、ClO4 -、CH3COO-、CH3SO3 -Or CF3SO3 -；
The above-mentionedThe total number of positive charges being equal to the anion X-Total number of negative charges, R1And R2Can be different groups;
Figure GDA0002186023720000025
or
Figure GDA0002186023720000026
R3And R4Can be different groups;
Figure GDA0002186023720000027
or a six-membered ring structure consisting of N atoms on the same side and carbon atoms on a benzene ring, wherein: n is60-18, R5And R6Can be different groups;
R5and R6The structure of the six-membered ring structure formed by N atoms on the same side and carbon atoms on a benzene ring is as follows:
Figure GDA0002186023720000028
R5or R6Or a six-membered ring structure consisting of N atoms on the same side and carbon atoms on a benzene ring can be adopted on only one side.
Figure GDA0002186023720000031
Wherein: n is1N is an integer of 0 to 1120 to 5, m1N is an integer of 0 to 1130 to 11, m2N is an integer of 0 to 114Is an integer of 0 to 5, n 50 to 5, m3An integer of 0 to 11, R7And R8May be different groups.
A preparation method of a DNA dye compound with a cell nucleus targeting function is disclosed, the compound is obtained by reacting alkynyl sulfonamide rhodamine and azido Hoechst or azido sulfonamide rhodamine and alkynyl Hoechst through Click, and the preparation method is as follows:
Figure GDA0002186023720000033
wherein: r1，R2，R3，R4，R5，R6，R7，R8And Y is as defined in the general formula of claim 1,
Figure GDA0002186023720000034
X2＝N3or
The invention has the beneficial effects that: through the Click reaction of sulfonamide rhodamine with alkynyl and Hoechst with azido or sulfonamide rhodamine with azido and Hoechst with alkynyl, DNA dye compounds with different connection modes and different chain lengths and having a cell nucleus targeting function are obtained. The compound has excellent cell nucleus targeting property, solves the problem that the traditional rhodamine fluorophore cannot be positioned to the cell nucleus, simultaneously overcomes the problem that the Hoechst causes serious damage to cells in the imaging process due to short excitation light wavelength, and provides more selectable tools for imaging the cell nucleus of biological cells.
Drawings
FIG. 1 is the fluorescence spectrum of the compound HoeSR titrated with ctDNA. Inner panel a is a plot of fluorescence intensity at 590nm as a fit to ctDNA addition.
FIG. 2 is a fluorescence spectrum of the compound HoeSR-1 titrated with ctDNA. Inner panel b is a plot of fluorescence intensity at 590nm as a fit to ctDNA addition.
FIG. 3 is a confocal fluorescence imaging diagram of compound HoeSR staining HeLa and MCF-7 cells, a diagram c is a HeLa cell staining effect diagram, the left side is a fluorescence field diagram, and the right side is a fluorescence field and bright field mixed diagram; FIG. d is a graph showing the effect of staining MCF-7 cells, with a fluorescence field on the left and a mixture of fluorescence and bright fields on the right.
FIG. 4 is a confocal fluorescence imaging diagram of compound HoeSR-1 staining MCF-7 cells, wherein the channel is a 450-540nm fluorescence acquisition diagram, the channel is a 560-660nm fluorescence acquisition diagram, the bright field is a nuclear imaging bright field diagram, and the superimposed field is an overlay diagram of the channel I, the channel II and the bright field.
Detailed Description
The invention is illustrated but not limited by the following examples in which all parts and percentages are by weight unless otherwise indicated.
The following detailed description of the embodiments of the present invention is provided in conjunction with the technical solutions:
example 1
Under the protection of argon, compound A1(50mg, 98.50umol) and compound B1(55mg, 118.21umol) were added to a reaction flask, an anhydrous copper sulfate aqueous solution, an aqueous sodium ascorbate solution and 4 drops of N, N-diisopropylethylamine were added, and reacted at room temperature for 24 hours, and the solvent was evaporated under reduced pressure. Column chromatography of the crude product (distillate CH2Cl2: MeOH 8: 1) gave a purple solid (60mg, 62.04umol, 62.98%). The product structure is identified by HRMS (high resolution Mass Spectrometry) [ M + H ]]+：967.4164。
Example 2
Figure GDA0002186023720000051
Synthesis method referring to example 1, compound B2 was used in place of B1, and the product structure was identified by HRMS [ M + H ]]+：963.3864。
Example 3
Figure GDA0002186023720000052
Synthesis method referring to example 1, compound B3 was used in place of B1, and the product structure was identified by HRMS [ M + H ]]+：1019.4374。
Example 4
Under the protection of argon, compound A1(50mg, 98.50umol) and compound B4(63.79mg, 118.21umol) were added to a reaction flask, an anhydrous copper sulfate aqueous solution, an aqueous sodium ascorbate solution and 4 drops of N, N-diisopropylethylamine were added, and reacted at room temperature for 24 hours, and the solvent was evaporated under reduced pressure. Column chromatography of the crude product (distillate CH2Cl2: MeOH 8: 1) gave a purple solid (70mg, 66.84umol, 67.85%). The product structure is identified by HRMS (high resolution Mass Spectrometry) [ M + H ]]+：1047.4823。
Example 5
Under the protection of argon, compound A2(50mg, 83.94umol) and compound B4(54.36mg, 100.72umol) were added to a reaction flask, an anhydrous copper sulfate aqueous solution, an aqueous sodium ascorbate solution and 4 drops of N, N-diisopropylethylamine were added, and the solvent was evaporated under reduced pressure at room temperature for 24 hours. Column chromatography of the crude product (distillate CH2Cl2: MeOH 8: 1) gave a purple solid (50mg, 44.04umol, 52.47%). The product structure is identified by HRMS (high resolution Mass Spectrometry) [ M + H ]]+：1135.5323。
Example 6
Figure GDA0002186023720000062
Synthesis method referring to example 1, compound B5 was used in place of B1, and the product structure was identified by HRMS [ M + H ]]+：991.4164。
Example 7
Figure GDA0002186023720000063
Synthesis method referring to example 1, compound B6 was used in place of B1, and the product structure was identified by HRMS [ M + H ]]+：1047.4864。
Example 8
Figure GDA0002186023720000064
Synthesis method referring to example 1, compound B7 was used in place of B1, and the product structure was identified by HRMS [ M + H ]]+：1114.5264。
Example 9
Figure GDA0002186023720000071
Under the protection of argon, compound A1(50mg, 98.50umol) and compound B8(68.89mg, 118.21umol) were added to a reaction flask, an anhydrous copper sulfate aqueous solution, an aqueous sodium ascorbate solution and 4 drops of N, N-diisopropylethylamine were added, and reacted at room temperature for 24 hours, and the solvent was evaporated under reduced pressure. Column chromatography of the crude product (distillate CH2Cl2: MeOH 8: 1) gave a purple solid (60mg, 54.33umol, 55.15%). The product structure is identified by HRMS (high resolution Mass Spectrometry) [ M + H ]]+：1104.5356。
Example 10
Figure GDA0002186023720000072
Synthesis method referring to example 9, compound B9 was used in place of B8, and the product structure was identified by HRMS [ M + H ]]+：1038.4964。
Example 11
Figure GDA0002186023720000073
Synthesis method referring to example 9, compound B10 was used in place of B8, and the product structure was identified by HRMS [ M + H ]]+：1202.5664。
Example 12
Figure GDA0002186023720000081
Synthesis method referring to example 9, compound B11 was used in place of B8, and the product structure was identified by HRMS [ M + H ]]+：1178.5665。
Example 13
Figure GDA0002186023720000082
Synthesis method referring to example 9, compound B12 was used in place of B8, and the product structure was identified by HRMS [ M + H ]]+：1207.6031。
Example 14
Figure GDA0002186023720000083
Under the protection of argon, compound A1(50mg, 98.50umol) and compound B13(86.26mg, 118.21umol) were added to a reaction flask, an aqueous anhydrous copper sulfate solution, an aqueous sodium ascorbate solution and 4 drops of N, N-diisopropylethylamine were added, reacted at room temperature for 24 hours, and the solvent was evaporated under reduced pressure. Column chromatography of the crude product (distillate CH2Cl2: MeOH 8: 1) gave a purple solid (85mg, 68.68umol, 69.73%). The product structure is identified by HRMS (high resolution Mass Spectrometry) [ M + H ]]+：618.8258。
Example 15
Synthesis method referring to example 14, compound B14 was used in place of B13, and the product structure was identified by HRMS [ M + H ]]+：1176.6180。
Example 16
Synthesis method referring to example 14, compound B15 was used in place of B13, and the product structure was identified by HRMS [ M + H ]]+：1124.5756。
Example 17
Figure GDA0002186023720000092
Synthesis method reference is made to example 14, compound B16 was used in place of B13, and the product structure was identified by HRMS [ M + H ]]+：1096.5478。
Example 18
Figure GDA0002186023720000093
Synthesis method referring to example 14, compound A2 was used in place of A1, compound B16 was used in place of B13, and the product structure was identified by HRMS [ M + H ]]+：1121.5260。
Example 19
Under argon atmosphere, compound A3(10mg, 21.62. mu. mol) and compound B17(13.09mg, 25.94. mu. mol) were added to a reaction flask, an aqueous anhydrous copper sulfate solution, an aqueous sodium ascorbate solution, and 4 drops of N, N-diisopropylethylamine were added, reacted at room temperature for 24 hours, and the solvent was evaporated under reduced pressure. Column chromatography of the crude product (distillate CH2Cl2: MeOH 8: 1) gave a purple solid (11mg, 11.37 μmol, 52.61%). The product structure is identified by HRMS (high resolution Mass Spectrometry) [ M + H ]]+：967.4204。
Example 20
Figure GDA0002186023720000102
Synthesis method referring to example 19, compound B18 was used in place of B17, and the product structure was identified by HRMS [ M + H ]]+：1051.4575。
Example 21
Figure GDA0002186023720000103
Synthesis method referring to example 19, compound B19 was used in place of B17, and the product structure was identified by HRMS [ M + H ]]+：1077.5164。
Example 22
Figure GDA0002186023720000111
Synthesis method referring to example 19, compound B20 was used in place of B17, and the product structure was identified by HRMS [ M + H ]]+：553.2718。
Example 23
Figure GDA0002186023720000112
Synthesis method referring to example 19, compound B21 was used in place of B17, and the product structure was identified by HRMS [ M + H ]]+：1071.4914。
Example 24
Figure GDA0002186023720000113
Under argon atmosphere, compound A4(10mg, 18.16. mu. mol) and compound B21(13.27mg, 21.79. mu. mol) were added to a reaction flask, an aqueous anhydrous copper sulfate solution, an aqueous sodium ascorbate solution, and 4 drops of N, N-diisopropylethylamine were added, reacted at room temperature for 24 hours, and the solvent was evaporated under reduced pressure. Column chromatography of the crude product (distillate CH2Cl2: MeOH 8: 1) gave a purple solid (10mg, 8.63 μmol, 47.49%). The product structure is identified by HRMS (high resolution Mass Spectrometry) [ M + H ]]+：1159.5560。
Example 25
Figure GDA0002186023720000121
Under argon atmosphere, compound A3(10mg, 21.62. mu. mol) and compound B22(13.71mg, 25.94. mu. mol) were added to a reaction flask, an aqueous anhydrous copper sulfate solution, an aqueous sodium ascorbate solution, and 4 drops of N, N-diisopropylethylamine were added, reacted at room temperature for 24 hours, and the solvent was evaporated under reduced pressure. Column chromatography of the crude product (distillate CH2Cl2: MeOH 8: 1) gave a purple solid (11mg, 11.10 μmol, 51.33%). The product structure is identified by HRMS (high resolution Mass Spectrometry) [ M + H ]]+：991.4204。
Example 26
Figure GDA0002186023720000122
Synthesis method referring to example 25, compound B23 was used in place of B22, and the product structure was identified by HRMS [ M + H ]]+：1047.4912。
Example 27
Figure GDA0002186023720000123
Synthesis method referring to example 25, compound B24 was used in place of B22, and the product structure was identified by HRMS [ M + H ]]+：1200.6072。
Example 28
Figure GDA0002186023720000131
Synthesis method referring to example 25, compound B25 was used in place of B22, and the product structure was identified by HRMS [ M + H ]]+：1203.5654。
Example 29
Figure GDA0002186023720000132
Synthesis method referring to example 25, compound B26 was used in place of B22, and the product structure was identified by HRMS [ M + H ]]+：1176.6099。
Example 30
Figure GDA0002186023720000133
Under argon atmosphere, compound A3(10mg, 21.62. mu. mol) and compound B27(13.71mg, 13.62. mu. mol) were added to a reaction flask, an aqueous anhydrous copper sulfate solution, an aqueous sodium ascorbate solution, and 4 drops of N, N-diisopropylethylamine were added, reacted at room temperature for 24 hours, and the solvent was evaporated under reduced pressure. Column chromatography of the crude product (distillate CH2Cl2: MeOH 8: 1) gave a purple solid (11mg, 11.10 μmol, 51.33%). The product structure is identified by HRMS, HRMS [ M ]+H]+：1006.4425。
Example 31
Figure GDA0002186023720000141
Synthesis method referring to example 30, compound B28 was used in place of B27, and the product structure was identified by HRMS [ M + H ]]+：1046.4738。
Example 32
The HoeSR compound corresponding to example 1 was subjected to DNA titration spectroscopy. The compound HoeSR is prepared into 1 μ M test solution, calf thymus DNA (ctDNA) is dissolved by using Tris-HCl buffer solution, and the solution absorbance is measured according to Law of Langberger and specific molar extinction coefficient 6600L & mol of ctDNA-1·cm-1The concentration of calf thymus DNA buffer solution was calculated to be 6.0X 10-4M。
A1. mu.M test solution of the compound HoeSR was irradiated with 530nm excitation light, and a spectrum of 560-720nm band was collected. As shown in FIG. 1, the fluorescence intensity of the compound HoeSR at 590nm all increased with the increase of the addition amount of ctDNA and finally reached saturation, and the inner panel a is a plot of fluorescence intensity at 590nm as a fit to the addition amount of ctDNA, and the binding constant of HoeSR and ctDNA is 4.2. mu.M by titration curve.
Example 33
A DNA titration spectroscopic experiment was carried out on the HoeSR-1 compound corresponding to example 19. The HoeSR-1 was prepared as a 1. mu.M test solution, bovine thymus DNA (ctDNA) was dissolved in Tris-HCl buffer, and the absorbance of the solution was measured according to the Law of Lanberger and the specific molar extinction coefficient of ctDNA 6600L. mol-1·cm-1The concentration of calf thymus DNA buffer solution was calculated to be 6.0X 10-4M。
A1. mu.M test solution of the compound HoeSR-1 was irradiated with 530nm excitation light, and a spectrum of 560-720nm band was collected. As shown in FIG. 2, the fluorescence intensity of the compound HoeSR-1 at 590nm all increased with the increase of the addition amount of ctDNA and finally reached saturation, and the inner panel b is a fitting graph of the fluorescence intensity at 590nm to the addition amount of ctDNA. By titration curve, the binding constant of HoeSR-1 and ctDNA was found to be 8.12. mu.M.
Example 34
Cell imaging experiments were carried out on the HoeSR compound corresponding to example 1, HeLa cells and MCF-7 cells at 37 ℃ with 5% CO2After 24 hours incubation in the cell incubator, confocal imaging was performed to verify nuclear localization using 1 μ M HoeSR staining for 30 minutes. As shown in FIG. 3, panel c is a HeLa cell staining effect diagram, the left side is a fluorescence field diagram, and the right side is a fluorescence field and bright field mixed diagram; FIG. d is a graph showing the effect of staining MCF-7 cells, with a fluorescence field on the left and a mixture of fluorescence and bright fields on the right. The localization of the compound HoeSR to the nuclei of HeLa cells and MCF-7 was clearly observed by confocal imaging pictures.
Example 35
Cell imaging experiments were carried out on the compound HoeSR-1 corresponding to example 19, and MCF-7 cells were incubated at 37 ℃ and 5% CO2After 24 hours incubation in the cell incubator, confocal imaging was performed using 1 μ M HoeSR-1 solution staining for 30 minutes and 405nm light excitation dual channel acquisition. As shown in FIG. 4, the channel I is a 450-540nm fluorescence collection image, the channel II is a 560-660nm fluorescence collection image, the bright field is a nuclear imaging bright field image, the superimposed field is a superimposed image of the channel I, the channel II and the bright field, and the compound HoeSR-1 can be clearly observed to be positioned in the nuclear of the MCF-7 through a confocal imaging image.

Claims (2)

1. A DNA dye compound with a cell nucleus targeting function is characterized by having the following structural general formula:
Figure FDA0002186023710000011
in the general formula, R1，
Figure FDA0002186023710000012
Figure FDA0002186023710000013
Wherein: n is an integer of 0 to 18, m is an integer of 0 to 18, X-Is an anion, the anion being BF4 -、Cl-、Br-、I-、NO3 -、SO4 2-、ClO4 -、CH3COO-、CH3SO3 -Or CF3SO3 -(ii) a The above-mentioned
Figure FDA0002186023710000014
The total number of positive charges being equal to the anion X-Total number of negative charges, R1And R2Can be different groups;
R3,
Figure FDA0002186023710000015
R3and R4Can be different groups;
R5,or a six-membered ring structure consisting of N atoms on the same side and carbon atoms on a benzene ring, wherein: n is60-18, R5And R6Can be different groups;
Figure FDA0002186023710000017
R7,
Figure FDA0002186023710000018
wherein: n is1N is an integer of 0 to 1120 to 5, m1N is an integer of 0 to 1130 to 11, m2N is an integer of 0 to 114Is an integer of 0 to 5, n50 to 5, m3An integer of 0 to 11, R7And R8May be different groups.
2. The method for preparing a DNA dye compound with a cell nucleus targeting function according to claim 1, wherein the method comprises the following steps: the compound is obtained by reacting alkynyl rhodamine sulfonate and azido Hoechst or reacting the azido rhodamine sulfonate and alkynyl Hoechst through Click reaction, and the preparation method comprises the following steps:
Figure FDA0002186023710000021
wherein: r1，R2，R3，R4，R5，R6，R7，R8And Y is as defined in the general formula of claim 1,X2＝N3or X1＝N3，
Figure FDA0002186023710000023
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