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CN-122011799-A - Amphiphilic near-infrared two-region aza-fluoroborodipyrrole dye and preparation method thereof

CN122011799ACN 122011799 ACN122011799 ACN 122011799ACN-122011799-A

Abstract

The invention relates to an amphiphilic near-infrared two-region aza-boron dipyrrole dye and a preparation method thereof, wherein the dye has a general structure that a benzene ring is respectively connected to the 3,5 positions of aza-BODIPY, substituent R 1 、R 2 、R 3 ;R 1 、R 2 、R 3 is respectively and independently connected to the para position and the two meta positions of each benzene ring and is respectively and independently selected from hydrogen, propargyloxy connected through an oxygen atom or bis (propargyl) amino connected through a nitrogen atom, at least one of R 1 、R 2 、R 3 on each benzene ring is propargyloxy or bis (propargyl) amino, and a diethylene glycol monomethyl ether chain is optionally connected to the terminal alkynyl in the propargyloxy or bis (propargyl) amino through click chemistry reaction, and the structure is- (OCH 2CH 2) 2 -OCH3. Aza-BODIPY fluorescent dye with strong absorption and emission in near infrared two regions and a high-efficiency preparation method thereof.

Inventors

  • CHEN ZHIJIAN
  • HAO MENGYU
  • KUANG XUEFENG

Assignees

  • 天津大学

Dates

Publication Date
20260512
Application Date
20260112

Claims (9)

  1. 1. The amphiphilic near infrared nitrogen-doped boron dipyrrole dye is characterized by having the following general structure: Wherein, the 3,5 positions of the aza-BODIPY are respectively connected with a benzene ring, each para position and two meta positions of each benzene ring are respectively and independently connected with substituent R 1 、R 2 、R 3 ;R 1 、R 2 、R 3 which is respectively and independently selected from hydrogen, propargyloxy connected through oxygen atoms or double (propargyl) amino connected through nitrogen atoms, at least one of R 1 、R 2 、R 3 on each benzene ring is propargyloxy or double (propargyl) amino, and the terminal alkynyl in the propargyloxy or double (propargyl) amino is optionally connected with diethylene glycol monomethyl ether chain through click chemical reaction, and the structure is- (OCH 2 CH 2 ) 2 -OCH 3 ).
  2. 2. The amphiphilic near infrared dipyrromethene azaborol dye of claim 1 characterized by comprising a material of the structure R3 on two benzene rings are bis (propargyl) amino, R1 and R2 are hydrogen, and terminal alkynyl is connected with- (OCH 2 CH 2 ) 2 -OCH 3 chain; R3 on two benzene rings are propargyloxy, R1 and R2 are hydrogen, and terminal alkynyl is connected with- (OCH 2 CH 2 ) 2 -OCH 3 chain; r1 and R2 on two benzene rings are propargyloxy, R3 is hydrogen, and the terminal alkynyl is connected with- (OCH 2 CH 2 ) 2 -OCH 3 chain; R1, R2 and R3 on the two benzene rings are propargyloxy, and the terminal alkynyl is connected with- (OCH 2 CH 2 ) 2 -OCH 3 chain, and the compound is named BF 2 -ADP-1035.
  3. 3. The method for preparing the amphiphilic near infrared dipyrromethene aza-boron dipyrromethene dye according to claim 1, wherein the equation is as follows:
  4. 4. the method for preparing the amphiphilic near infrared dipyrromethene aza-boron dipyrromethene dye according to claim 3, The method comprises the following steps: 1) Carrying out aldol condensation reaction on the aromatic ketone of the determined substituent R 1 、R 2 、R 3 and 9-aldehyde julolidine to obtain a chalcone intermediate: 2) Carrying out Michael addition reaction on the chalcone intermediate and nitromethane to obtain a nitroalkane intermediate; 3) Reflux reaction is carried out on the nitroalkane intermediate and ammonium acetate in n-butanol, and cyclized condensation is carried out, so as to obtain an aza-dipyrromethene ligand; 4) Complexing the azadipyrromethene ligand with boron trifluoride diethyl etherate to obtain an aza-BODIPY intermediate; 5) And (3) connecting an azido polyethylene glycol monomethyl ether chain to the alkynyl of the aza-BODIPY intermediate in the step (4) through cuprous iodide-catalyzed azido-alkyne cycloaddition reaction to obtain the target dye.
  5. 5. The preparation method of the amphiphilic near infrared dual-region aza-fluoroborodipyrrole dye according to claim 4, wherein in the step 1), aromatic ketone with a determined substituent R 1 、R 2 、R 3 and 9-aldehyde-group julolidine are added into a round-bottom flask, ethanol is added as a solvent, then 20% -25% (w/w) sodium hydroxide aqueous solution is prepared, the mixture is added into a system, stirring is carried out at room temperature for 20-24 hours, after the reaction is finished, orange solid is separated out, and a chalcone intermediate is obtained by filtering and washing, wherein the reaction mole ratio of the aromatic ketone, the 9-aldehyde-group julolidine and the sodium hydroxide is 1.0:1.0-1.1:5.0-5.5.
  6. 6. The method for preparing the amphiphilic near infrared amphiphilic bis (azaborol) dye according to claim 4, wherein in the step 2), chalcone intermediate and 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU) are added into a round-bottomed flask, ethanol is added as a solvent, the temperature is raised to 80-85 ℃ and stirred for 0.5-1.0 h, nitromethane is added, the reaction is continued for 20-24 h, after the reaction is finished, the solvent is removed by rotary evaporation, dichloromethane extraction is carried out, anhydrous magnesium sulfate is dried, then the solvent is removed by rotary evaporation, column chromatography separation is carried out, and a mobile phase is obtained, namely, a nitroalkane intermediate which is yellow oil is obtained, wherein the molar ratio of the chalcone intermediate to the DBU to the nitromethane is 1.0:5.0-6.0:20.0-25.0.
  7. 7. The method for preparing the amphiphilic near infrared dual-region azaboron dipyrrole dye according to claim 4, wherein in the step 3), a nitroalkane intermediate is dissolved in n-butanol, ammonium acetate is added, the mixture is heated to 115-120 ℃ for reflux reaction for 12-15 hours, after the reaction is finished, the mixture is cooled to room temperature, a solvent is removed by rotary evaporation, dichloromethane extraction is carried out, anhydrous magnesium sulfate is dried, filtration is carried out, the solvent is removed by rotary evaporation, and the azadipyrromethene ligand which is a dark blue solid is obtained, wherein the molar ratio of the nitroalkane intermediate to the ammonium acetate is 1.0:20.0-25.0.
  8. 8. The preparation method of the amphiphilic near infrared dual-region azafluoroborodipyrrole dye according to claim 4, wherein in the step 4), an azadipyrromethene ligand is added into a two-port round-bottom flask, nitrogen is filled for protection, anhydrous dichloromethane is added for dissolution, N-diisopropylethylamine is added, stirring is carried out for 30-50 min at room temperature, boron trifluoride diethyl ether is then added, the reaction is continued for 20-24 h at room temperature, after the reaction is finished, water quenching reaction is added, dichloromethane is used for extraction, an organic phase is combined, anhydrous magnesium sulfate is dried, filtration and rotary evaporation is carried out to remove a solvent, column chromatography purification is carried out, and a mobile phase is dichloromethane: methanol volume ratio=100-120:1, so as to obtain an aza-BODIPY intermediate which is green solid, wherein the molar ratio of the azadipyrromethene ligand, N-diisopropylethylamine and boron trifluoride diethyl ether is 1.0:10.0-15.0:15.0-20.0.
  9. 9. The preparation method of the amphiphilic near infrared dual-region aza-boron dipyrrole dye according to claim 4, wherein in the step 5), the aza-BODIPY intermediate, an azido polyethylene glycol monomethyl ether chain, cuprous iodide and N, N-diisopropylethylamine are added into a mixed solvent, the mixed solvent is a mixed solvent of dichloromethane and acetonitrile, the volume ratio is 1:1-1.2, the mixed solvent is heated to 55-60 ℃ for reaction for 8-8.5 hours, after the reaction is finished, the solvent is removed by rotary evaporation, dichloromethane is used for extraction, an organic phase is combined, anhydrous magnesium sulfate is dried and filtered, the solvent is removed by rotary evaporation, and the mixture is purified by column chromatography, wherein the mobile phase is DCM: meOH volume ratio=30-40:1, and the target dye is a deep blue solid, and the molar ratio of the aza-BODIPY intermediate, the azido polyethylene glycol monomethyl ether chain, the cuprous iodide and the N, N-diisopropylethylamine is 1.0:6.0:0.1-0.2:5.0-6.0.

Description

Amphiphilic near-infrared two-region aza-fluoroborodipyrrole dye and preparation method thereof Technical Field The invention relates to the technical field of organic functional dye synthesis, in particular to an aza-BODIPY (aza-BODIPY) fluorescent dye with strong absorption and emission in a near infrared two-region (NIR-II, 900-1700 nm) and a high-efficiency preparation method thereof. The dye is prepared by introducing a modifiable alkynyl into a benzene ring side chain of the dye and further connecting a hydrophilic polyethylene glycol chain, has excellent amphipathy and biocompatibility, and is suitable for the fields of biomedical imaging, photo-thermal treatment (PTT) and the like. Background Near infrared two-region (NIR-II, 1000-1700 nm) fluorescence imaging has been of interest in the biomedical field due to its deeper tissue penetration and lower autofluorescence background. The development of this technology has demanded high-performance small-molecule fluorescent dyes with emission wavelengths in this window. Aza-BODIPY is a classical fluorophore with high molar extinction coefficient and good photostability, but its intrinsic absorption and emission are usually in the visible or near infrared (NIR-I) region. In order to red shift its spectrum effectively to the NIR-II region, common molecular engineering strategies include extension of pi conjugated systems (j. Wang, c. Yu, e.hao, l. Jiao, coord. Chem. Rev. 2022, 470, 214709.) and construction of strong "push-pull" structures (J. Su, X. Zhang, Z. Dong, H. Pan, F. Zhang, X. Li, S. Wang,Z. Chen, ACS Appl. Mater. Interfaces 2024, 16, 51241-51252.). however, these strategies, while pursuing red shifting, often face challenges such as complex synthesis, increased molecular hydrophobicity or aggravated non-radiative decay, resulting in limited practical application properties of the dye (x.li, y. Yang, r. Zhang, w. Huang, chem. Soc. Rev. 2025, 54, 11184-11225.). In recent years, a julolidine group (9-aldehyde julolidine (CAS: 33985-71-6) with a rigid planar structure is a heterocyclic aldehyde compound with a molecular formula of C 13H15 NO, is mainly applied to dye-sensitized solar cells (DSSCs) and organic synthesis intermediates, has a chemical name of 2,3,6, 7-tetrahydro-1H, 5H-benzo [ ij ] quinolizine-9-formaldehyde, takes a tricyclic condensed system as a mother nucleus, connects aldehyde groups at the 9-position to form an alpha, beta-unsaturated conjugated system, has a molecular weight of 201.26, has an accurate mass of 201.115 and a LogP value of 2.74, and shows medium lipid solubility, and is introduced into an azaBODIPY system as a strong electron donor, so that a new way is provided for promoting charge transfer in molecules and realizing high-efficiency spectrum red shift. For example, the successful push of the emission wavelength to 1060 nm by the julolidine modified dye reported by Bai et al, verifies how the effectiveness (L. Bai, P. Sun, Y. Liu, H. Zhang, W. Hu, W. Zhang, Z. Liu, Q. Fan, L. Li,W. Huang, Chem. Commun. 2019, 55, 10920-10923.). of this group, despite the initial exploration, further pushes the emission of aza-BODIPY deep and stable into the NIR-II long wave region (> 1100 nm) through the molecular design of the system, remains the focus and difficulty of current research. Disclosure of Invention The invention aims to provide an aza-BODIPY fluorescent dye which has novel structure, NIR-II optical performance and functionalization, and a simple and efficient preparation method thereof. According to the invention, a strong electron donating julolidine group is introduced into the 1,7 sites of the aza-BODIPY core, a series of novel derivatives are designed and synthesized, and the enhancement effect of the structural unit on the spectral red shift is explored. The result shows that the strategy can effectively promote intramolecular charge transfer, so that the emission of all target dyes covers an NIR-II window, wherein the maximum emission wavelength of the optimal dye in a polar solvent can reach 1109 nm, and the NIR-II emission capability of the dye is obviously expanded. At least one propargyloxy or di (propargyl) amino is introduced on benzene rings at 3 and 5 positions as an intermediate, and diethylene glycol monomethyl ether chain can be further connected through click chemistry, so that excellent optical performance of a dye core is maintained, good water solubility and amphipathy are provided, and a new material foundation is provided for constructing a high-performance NIR-II biological probe. The technical scheme of the invention is as follows: the amphiphilic near infrared dipyrromethene aza-boron dipyrromethene dye has the following general structure: Wherein, the 3,5 positions of the aza-BODIPY are respectively connected with a benzene ring, each para position and two meta positions of each benzene ring are respectively and independently connected with substituent R 1、R2、R3;R1、R2、R3 which is respectivel