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CN-122010992-A - TPA-AN and pyridine conjugated modified BODIPY fluorescent probe and preparation method and application thereof

CN122010992ACN 122010992 ACN122010992 ACN 122010992ACN-122010992-A

Abstract

The invention belongs to the technical field of organic synthesis, and particularly discloses a TPa-aN and pyridine conjugated modified BODIPY fluorescent probe, and a preparation method and application thereof. The invention adopts TPa-aN to directionally modify mose positions of BODIPY, and constructs aN extended conjugated system by Knoevenagel condensation aiming at single-side modified pyridine at alpha positions of BODIPY parent nucleus to obtain the near infrared NO-BDP fluorescent probe. Wherein TPa-aN provides a strong electron donating effect, intramolecular Charge Transfer (ICT) channels, and steric hindrance of pyridine rings distorts the molecular structure into a non-planar configuration, reduces pi-pi accumulation, and inhibits ACQ effect. Wherein, the TPa-aN group and BODIPY parent nucleus generate synergistic coordination effect, so that NO-BDP can sensitively identify phenylalanine dipeptide structural units in A beta 42 protein, thereby realizing sensitive identification of A beta protein; and the pyridine group is introduced to enable the NO-BDP to realize electron conduction, so that a D-pi-A structure is formed, more singlet oxygen is generated, a stronger antibacterial effect is shown, and photodynamic antibacterial effect is realized. Finally, the multifunctional application is realized through the NO-BDP fluorescent probe.

Inventors

  • WANG KEWEI
  • QUAN LI
  • HUANG HAO
  • GU MINGMIN
  • LIU BO

Assignees

  • 淮阴工学院

Dates

Publication Date
20260512
Application Date
20251218

Claims (10)

  1. 1. The BODIPY fluorescent probe modified by conjugate of TPA-AN and pyridine is characterized in that the molecular structure of the fluorescent probe is shown as the following formula: 。
  2. 2. The method for preparing the BODIPY fluorescent probe modified by conjugate of TPA-AN and pyridine as claimed in claim 1, which comprises the following steps: (1) Reacting 4- (bis (4-hydroxyphenyl) amino) benzaldehyde, 2, 4-dimethylpyrrole and boron fluoride diethyl ether in one pot to obtain a compound O-BDP; (2) The compound O-BDP and the-formyl-1-methylpyrrolidine iodide are subjected to condensation reaction to obtain the compound NO-BDP, namely the target BODIPY fluorescent probe; The reaction scheme is as follows: 。
  3. 3. The preparation method of the compound O-BDP, which is characterized in that in the step (1), 4- (bis (4-hydroxyphenyl) amino) benzaldehyde is dissolved in dichloromethane, 2, 4-dimethylpyrrole is added under the protection of nitrogen, trifluoroacetic acid is then dropwise added, after stirring reaction for a period of time at room temperature, 2, 3-dimethyl-5, 6-dicyanobenzoquinone is added as a catalyst, the reaction is continued for a period of time, triethylamine and boron fluoride diethyl ether are slowly added, stirring reaction is continued at room temperature, after the reaction is finished, the mixed solution is washed with water, and an organic layer is concentrated and purified by column chromatography, so that the compound O-BDP is obtained.
  4. 4. The method of claim 3, wherein the amount of 4- (bis (4-hydroxyphenyl) amino) benzaldehyde, 2, 4-dimethylpyrrole, trifluoroacetic acid, 2, 3-dimethyl-5, 6-dicyanobenzoquinone, triethylamine and boron fluoride diethyl ether is 1:2-3:0.1-0.2:0.8-1.2:10-20:10-20.
  5. 5. The preparation method of the compound NO-BDP as set forth in claim 2, wherein in the step (2), the compound O-BDP and 4-formyl-1-methylpyrrolidine iodide are added into toluene, a small amount of piperidine and acetic acid are added, the mixed solution is heated under the protection of nitrogen to react, and the compound NO-BDP is obtained after the reaction is completed and separated and purified.
  6. 6. The method of claim 5, wherein the compound O-BDP, 4-formyl-1-methylpyrrolidine iodide, piperidine and acetic acid are used in a ratio of 1:2 to 3:2 to 4:0.1 to 0.2.
  7. 7. The method of claim 5, wherein the heating reaction is carried out at a temperature of 120-130 ℃ for 1-3 hours.
  8. 8. The use of a TPA-AN and pyridine conjugated modified BODIPY fluorescent probe as claimed in claim 1 in the preparation of a medicament for diagnosis of AD.
  9. 9. The use of a TPA-AN and pyridine conjugated modified BODIPY fluorescent probe as claimed in claim 1 in the preparation of photodynamic therapy drugs.
  10. 10. The use of a TPA-AN and pyridine conjugated modified BODIPY fluorescent probe as claimed in claim 1 in the preparation of aN antibacterial agent for photodynamic therapy.

Description

TPA-AN and pyridine conjugated modified BODIPY fluorescent probe and preparation method and application thereof Technical Field The invention belongs to the technical field of organic synthesis, relates to synthesis of BODIPY fluorescent probes, and in particular relates to a TPA-AN and pyridine conjugate modified BODIPY probe capable of sensitively identifying Abeta protein and photodynamic antibacterial, a preparation method thereof and application thereof in preparing related medicines. Background The BODIPY is considered as one of the most common fluorophores due to the excellent characteristics of photophysical property, high photostability, high fluorescence quantum yield, easiness in modification, narrower absorption and emission spectrum peaks and the like, and is widely applied to detection and identification of Abeta protein and photodynamic therapy. The triphenylamine group has a unique equilateral triangle non-planar molecular configuration, and the three-blade propeller-shaped structure is favorable for avoiding aggregation-induced fluorescence quenching (ACQ) phenomenon caused by pi-pi accumulation, and generally, the crop electron donating group can enable the absorption and emission spectrum of an organic fluorescent compound to generate red shift, so that the organic fluorescent compound is combined with a phenylalanine dipeptide structural unit in the Abeta 42 protein, the signal response of a BODIPY compound probe is enhanced, the sensitivity of probe detection is improved, and the quick identification of the Abeta 42 protein is realized. And a pyridine group is introduced into a single side of the NO-BDP probe, energy absorption is transited from a stable ground state to an unstable singlet excited state, then intersystem crossing is carried out by the singlet excited state to generate a triplet excited state, and the photosensitizer in the excited state can generate more singlet oxygen through energy transfer or electron transfer and the reaction of surrounding macromolecules, so that a stronger antibacterial effect is shown, photodynamic antibacterial is realized, a D-pi-A structure is further formed, and finally the multifunctional application of the NO-BDP probe is realized. Disclosure of Invention Aiming at the defects of the prior art, the invention aims to provide a TPA-AN and pyridine conjugated modified BODIPY fluorescent probe, which not only can sensitively identify Abeta 42 protein, but also can realize self electron conduction so as to form a D-pi-A structure, generate more singlet oxygen, display stronger antibacterial effect and realize photodynamic antibacterial. Another object of the present invention is to provide a method for preparing the fluorescent probe. The invention is realized by the following technical scheme: A molecular structure of the TPA-AN and pyridine conjugated modified BODIPY fluorescent probe is shown as the following formula: 。 The invention further improves the scheme as follows: The preparation method of the TPA-AN and pyridine conjugated modified BODIPY fluorescent probe comprises the following steps: (1) Reacting 4- (bis (4-hydroxyphenyl) amino) benzaldehyde, 2, 4-dimethylpyrrole and boron fluoride diethyl ether in one pot to obtain a compound O-BDP; (2) The compound O-BDP and the-formyl-1-methylpyrrolidine iodide are subjected to condensation reaction to obtain the compound NO-BDP, namely the target BODIPY fluorescent probe; The reaction scheme is as follows: 。 Further, in the step (1), 4- (bis (4-hydroxyphenyl) amino) benzaldehyde is dissolved in dichloromethane, 2, 4-dimethylpyrrole is added under the protection of nitrogen, trifluoroacetic acid is then dropwise added, after stirring reaction for a period of time at room temperature, 2, 3-dimethyl-5, 6-dicyanobenzoquinone is added as a catalyst, the reaction is continued for a certain period of time, triethylamine and boron fluoride diethyl ether are slowly added, stirring reaction is continued at room temperature, after the reaction is finished, the mixed solution is washed with water, and an organic layer is subjected to concentration and column chromatography purification to obtain the compound O-BDP. Further, the molar ratio of the 4- (bis (4-hydroxyphenyl) amino) benzaldehyde to the 2, 4-dimethylpyrrole to the trifluoroacetic acid to the 2, 3-dimethyl-5, 6-dicyanobenzoquinone to the triethylamine to the boron fluoride diethyl ether is 1:2-3:0.1-0.2:0.8-1.2:10-20:10-20. In the step (2), the compound O-BDP and 4-formyl-1-methylpyrrolidine iodide are added into toluene, a small amount of piperidine and acetic acid are added, the mixed solution is heated to react under the protection of nitrogen, and the compound NO-BDP is obtained after the reaction is finished and separated and purified. Further, the mol ratio of the compound O-BDP to the 4-formyl-1-methylpyrrolidine iodide to the piperidine to the acetic acid is 1:2-3:2-4:0.1-0.2. Further, the temperature of the heating reaction is 120-130