CN114031754A - Thermally activated delayed fluorescence polymer and application thereof - Google Patents

Thermally activated delayed fluorescence polymer and application thereof Download PDF

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CN114031754A
CN114031754A CN202110542776.6A CN202110542776A CN114031754A CN 114031754 A CN114031754 A CN 114031754A CN 202110542776 A CN202110542776 A CN 202110542776A CN 114031754 A CN114031754 A CN 114031754A
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substituted
delayed fluorescence
unsubstituted
activated delayed
polymer
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CN114031754B (en
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傅妮娜
章胜裕
赵保敏
汪联辉
刘梦梦
褚兴胜
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Nanjing University of Posts and Telecommunications
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Abstract

The invention discloses a thermal activation delayed fluorescence polymer and application thereof, wherein in the general formula of the thermal activation delayed fluorescence polymer, X represents a connection mode between a benzene ring A and a benzene ring B, the benzene ring A and the benzene ring B are not connected through X, and can be connected through a single bond and pass through-NR1Any one of-O-, -O-and-S-m + n =0.5, and 0.5>m>0; AR1 is substituted benzene, naphthalene, fluorene, carbazole, spirofluorene, anthracene, xanthene, AR1 is substituted by C1-C20 linear substituent, C1-C20The branched substituent, the linear alkoxy group of C1-C20 or the branched alkoxy group of C1-C20. The technical scheme obtains the advantages of high fluorescence quantum efficiency, longer emission wavelength, high photodynamic activity and the like through a simple synthesis method, and the nano-quantum-active material is used as an active component of a nano reagent for biomedical application.

Description

Thermally activated delayed fluorescence polymer and application thereof
Technical Field
The invention relates to a thermally activated delayed fluorescence polymer and application thereof, which can be used in the technical field of flexible photoelectric organic semiconductors.
Background
Malignant tumors (cancers) have become one of the diseases that currently pose the greatest safety hazards to human health. In clinical treatment, although the treatment means mainly including surgery, radiotherapy and chemotherapy has been developed, the problems of complex pathogenesis, easy recurrence, high metastasis and the like of malignant tumors exist, so that the common treatment methods are difficult to say to be successful. For example, chemotherapy not only presents systemic toxicity and multidrug resistance problems, but often also damages surrounding healthy tissues, ultimately affecting patient survival. In addition, in addition to malignant tumors, inflammatory-related bacterial and fungal infections, and senile degenerative diseases such as parkinson's disease are also confronted with the problem of fewer and fewer specific drugs. Compared with the lack of treatment means, the new epidemic diseases or virus infection caused by the change of human living environment poses great threat to the health and survival of the whole human. In the face of dangerous diseases, effective early detection and prevention means are lacked, and specific and special-effect medicines are also lacked, so that research ideas of researching researchers reviewing major disease detection, diagnosis and treatment schemes are urgently needed.
Among the emerging cancer therapies, Photodynamic Therapy (PDT) has received increasing attention because it is non-invasive, has few side effects, low drug resistance, low systemic toxicity, and can be used in combination with a variety of other therapies. A typical PDT procedure requires three key elements: photosensitizers (PS), light sources capable of exciting the photosensitizers, and tissue oxygen. The nontoxic PS is excited by light source to generate charge transfer (type I photodynamic) or energy transfer (type II photodynamic) to generate reactive oxygen species (ROS, typically singlet oxygen: (II))1O2)). Use of PDT for killing tumor cellsPathways include apoptosis, necrosis, stimulation of the host immune system, causing acute inflammation and leukocyte infiltration of the tumor (increased expression of T cells by tumor-derived antigens).
Photosensitizers are key to photodynamic therapy. Through the iterative development of at least two generations of PS, thousands of PSs have been developed and applied to the treatment of various diseases such as targeted antibiosis, antitumor, ophthalmology, acne, blood vessels and the like. The key to the development of PDT is the development of highly effective photosensitizers. The most effective photosensitizers have the following characteristics: 1) the rate constant of intersystem crossing from S1 to T1 is high; 2) the light stability is good; 3) the light absorption capacity in the near infrared region is strong; 4) has high selectivity and high tumor tendency in tumor cells, ensures that the tumor cells have good enough tumor cytotoxicity, and simultaneously has low photosensitizer dark toxicity and is easy to remove by tissues or human bodies. The photosensitizer is divided into the following components according to the material structure: 1) PS containing heavy metals (potential elemental toxicity); 2) precious metal nanomaterials (high density and cost); 3) all-organic small molecule PS and 4) polymer PS (including conjugated polyelectrolytes, organometallic frameworks (MOFs), Covalent Organic Frameworks (COFs), etc.). In contrast, all-organic PS is safer biologically and is more easily functionalized by chemical structure modification. At present, all-organic PS are mainly porphyrin derivatives, porphin derivatives, borofluoride dipyrrole (BODIPY) derivatives, Indocyanine (IC) derivatives, pyrrolopyrroledione (DPP) derivatives. Although these classes of conjugated organic semiconductor units can conveniently be used to obtain efficient PS via coupling reactions and other chemical modifications, more often than not, conjugation functionalization can result in compounds based on the above structures losing their PDT properties. For example, DPP coupled with triphenylamine or thienoindole units has good photothermal conversion efficiency, but does not have PDT capability. When the organic micromolecule PS is used for constructing the anti-tumor diagnosis and treatment reagent, the problems of fluorescence quenching, photodynamic efficiency loss and the like caused by leakage and aggregation of the organic micromolecule PS from a nano coating system are also easily caused.
The development of high-efficiency photosensitizers and near-infrared nanoprobes has very important theoretical significance and market value for biomedical applications no matter which aspect of integration of photodynamic therapy and diagnosis and treatment.
Disclosure of Invention
The present invention aims to solve the above problems in the prior art, and provides a thermally activated delayed fluorescence polymer and applications thereof.
The purpose of the invention is realized by the following technical scheme: a thermally activated delayed fluorescence polymer having a structural formula:
Figure BDA0003071139480000021
general formula (I)
Wherein, in the general formula (I), X represents the connection mode between the benzene ring A and the benzene ring B, can be the connection of the benzene ring A and the benzene ring B without X, can be the connection of single bond, and can be the connection of-NR1Any one of-O-, and-S-;
m + n is 0.5, and 0.5 > m > 0; AR1 is substituted benzene, naphthalene, fluorene, carbazole, spirofluorene, anthracene, xanthene, AR1 is substituted by C1-C20 straight chain substituent, C1-C20 branched chain substituent, C1-C20 straight chain alkoxy or C1-C20 branched chain alkoxy;
AR2 is selected from substituted benzene, naphthalene, fluorene, carbazole, spirofluorene, anthracene, xanthene, benzothiadiazole
Figure BDA0003071139480000031
Benzoselenadiazole
Figure BDA0003071139480000032
Pyridinothiadiazoles
Figure BDA0003071139480000033
Figure BDA0003071139480000033
5, 6-difluorobenzothiadiazole
Figure BDA0003071139480000034
5-fluorobenzothiadiazoles
Figure BDA0003071139480000035
Figure BDA0003071139480000035
4, 7-diaryl-5, 6-dialkoxybenzothiadiazole
Figure BDA0003071139480000036
Figure BDA0003071139480000036
4, 7-diarylbenzothiadiazoles
Figure BDA0003071139480000037
Figure BDA0003071139480000037
4, 7-diarylbenzoselenadiazoles
Figure BDA0003071139480000038
Figure BDA0003071139480000038
4, 7-diarylpyridothiadiazoles
Figure BDA0003071139480000039
Figure BDA0003071139480000039
4, 7-diaryl-5, 6-difluorobenzothiadiazoles
Figure BDA00030711394800000310
Or 4, 7-diaryl-5-fluorobenzothiadiazole
Figure BDA00030711394800000311
One of (1), R3Is a straight chain or branched chain alkyl with 6-16 carbon atoms, and B is thiophene, selenophene, bithiophene or benzothiophene; the substitution of AR2 is one of C1-C20 straight chain substituent, C1-C20 branched chain substituent, C1-C20 straight chain alkoxy or C1-C20 branched chain alkoxy;
AR3 is one of substituted or substituted benzene, naphthalene, pyridine and anthracene, and the substitution on AR3 is one of C1-C8 branched chain or branched chain alkyl.
Preferably, Y is taken from one of the following Y1, Y2, Y3, Y4, Y5:
Figure BDA00030711394800000312
Y1-Y5: z1 and Z2 are each independently selected from cyano, fluorine atom and trifluoromethyl; p is selected from-CH ═ or N.
Preferably, D1 and D2 are each independently selected from the group consisting of hydrogen, deuterium, cyano, fluorine, trifluoromethyl, C1-C10 alkyl, C2-C10 alkenyl, substituted or unsubstituted C1-C10 alkoxy, substituted or unsubstituted C6-C30 aryl, substituted or unsubstituted C3-C30 heteroaryl, L-NAr1Ar2One of (1); l is selected from single bond, substituted or unsubstituted C6-C30 aryl, substituted or unsubstituted C3-C30 heteroaryl.
Preferably, Ar1、Ar2Each independently selected from substituted or unsubstituted C6-C30 aryl, substituted or unsubstituted C3-C30 heteroaryl; ar (Ar)1And Ar2Are not linked to each other, or Ar1And Ar2To the carbon atom via a single bond, -O-, -S-, -C (CH)3)2-，-C(C6H5)2-linking to larger conjugated units.
Preferably, Ar is1And Ar2Any one selected from the following groups:
Figure BDA0003071139480000041
wherein the dotted line represents the attachment site of the group;
Y11、Y12、Y13、Y14、Y15、Y16、Y17、Y18、Y19、Y110、Y111、Y112each independently selected from N or C-RY；
T1Selected from O, S, N-RT1、CRT2RT3、SiRT2RT3；
RY、RT1、RT2、RT3Each independently selected from hydrogen, deuterium, cyano, halogen, substituted or unsubstituted C1-C4 linear or branched alkyl, substituted or unsubstituted C6-C18 aryl, substituted or unsubstituted C3-C18 heteroaryl, and C6-C18 arylamine; substituent RYAt least 2 substituents which are not linked or adjacent to each other are linked by a chemical bond to form a ring.
Preferably, the Ar is selected from any one of the following groups, or any one of the following groups substituted with a substituent group:
Figure BDA0003071139480000051
the substituent is selected from deuterium, fluorine, chlorine, cyano, unsubstituted or R' substituted C1-C4 straight chain or branched chain alkyl.
The invention also discloses application of the thermal activation delayed fluorescence polymer, and the thermal activation delayed fluorescence polymer can be used as a photosensitizer for photodynamic therapy and a nano probe component for biological imaging.
Preferably, the photodynamic therapy and bioimaging can be used for tumor therapy, antimicrobial therapy and other disease therapy and health care applications.
Preferably, the photosensitizer for photodynamic therapy is a thermally activated delayed fluorescence polymer as defined in any one of claims 1 to 8, which has a structure of the general structural formula (I), and all of the symbols X, AR1, AR2, AR3 and Y in the general structural formula of the photosensitizer for photodynamic therapy are in accordance with the limitations of claims 1 to 8.
Preferably, the heat-activated delayed fluorescence polymer is realized by preparing a nano reagent; the preparation method of the nanometer reagent comprises a reprecipitation method, a molecular micelle carrier, a film dispersion method, a reflux precipitation method and other common organic semiconductor nanometer reagent preparation methods.
Compared with the prior art, the invention adopting the technical scheme has the following technical effects: the technical scheme obtains the advantages of high fluorescence quantum efficiency, longer emission wavelength, high photodynamic activity and the like through a simple synthesis method, and the nano-quantum-active material is used as an active component of a nano reagent for biomedical application.
The technical scheme has near-infrared luminescence, high fluorescence quantum yield and better photodynamic therapy activity, and simultaneously gives biomedical application of the photodynamic therapy, wherein the application is photodynamic therapy and biological imaging. The thermal activation delayed fluorescence polymer is used as a photosensitizer for photodynamic therapy and a key active component of a fluorescence imaging nano reagent, can be used as the photosensitizer for photodynamic therapy and a fluorescence probe for near infrared imaging, can realize integration of nondestructive and photochemical diagnosis and treatment, and is suitable for industrial popularization and application.
According to the technical scheme, the flexible polymer is obtained without using heavy atoms and metal elements, the photodynamic and fluorescence imaging is realized, and a feasible thought is provided for the application of flexible electrons in biomedicine.
The diagnosis and treatment integrated nano reagent provided by the invention has the advantages of simple preparation method, convenience in operation, good environmental stability, easiness in drug loading and targeted treatment, and remarkable improvement on diagnosis and treatment efficiency. The invention realizes the preparation and application of diagnosis and treatment integrated nano reagent from the polymer molecule perspective through structural design and chemical synthesis, and has very definite application environment and market value.
Drawings
FIG. 1 is a scheme showing the synthesis of polymer A in example 1 of the present invention.
FIG. 2 is a synthesis scheme of Polymer B in example 2 of the present invention.
FIG. 3 is a synthesis scheme of Polymer C in example 3 of the present invention.
FIG. 4 is a synthesis scheme of Polymer D in example 4 of the present invention.
FIG. 5 is a synthesis scheme for Polymer E of example 5 of the present invention.
FIG. 6 is a synthesis scheme of Polymer F in example 6 of the present invention.
FIG. 7 is a graph showing an ultraviolet absorption spectrum of a conjugated polymer in example 3 of the present invention.
FIG. 8 is a fluorescence emission spectrum of the conjugated polymer in example 3 of the present invention.
Fig. 9 is an ultraviolet absorption spectrum of the diagnosis and treatment integrated nano-reagent based on the conjugated polymer in example 7 of the present invention.
Fig. 10 is a fluorescence spectrum of the diagnosis and treatment integrated nano-reagent based on the conjugated polymer in example 7 of the present invention.
Fig. 11 is a schematic structural diagram of the photodynamic/fluorescence diagnosis and treatment integrated nano reagent of the thermally activated delayed fluorescence conjugated polymer in example 7.
Fig. 12 is a photodynamic curve test chart of the diagnosis and treatment integrated nano reagent in embodiment 7 of the present invention.
Detailed Description
Objects, advantages and features of the present invention will be illustrated and explained by the following non-limiting description of preferred embodiments. The embodiments are merely exemplary for applying the technical solutions of the present invention, and any technical solution formed by replacing or converting the equivalent thereof falls within the scope of the present invention claimed.
The invention discloses a thermal activation delayed fluorescence polymer and application thereof, wherein the thermal activation delayed fluorescence polymer is constructed by taking a main chain ternary copolymerization framework as a self-doping main body, and the framework is also used as a thermal activation delayed fluorescence luminophor donor unit. One application of thermally activated delayed fluorescence conjugated polymers is photodynamic therapy and bioimaging.
The starting materials used in the present invention are known compounds, commercially available, or can be synthesized by methods known in the art.
A thermally activated delayed fluorescence conjugated polymer, the conjugated polymer having the formula:
Figure BDA0003071139480000071
general formula (I)
Wherein, in the general formula (I), X represents the connection mode between the benzene ring A and the benzene ring B, can be the connection of the benzene ring A and the benzene ring B without X, can be the connection of single bond, and can be the connection of-NR1Any one of- (O-O) -, - (O) -and- (S) -.
Formula (I) wherein m + n is 0.5, and 0.5 > m > 0; AR1 is substituted benzene, naphthalene, fluorene, carbazole, spirofluorene, anthracene, xanthene, AR1 is substituted C1-C20 linear substituent, C1-C20 branched chain substituent, C1-C20 linear alkoxy or C1-C20 branched chain alkoxy.
AR2 is selected from substituted benzene, naphthalene, fluorene, carbazole, spirofluorene, anthracene, xanthene, benzothiadiazole
Figure BDA0003071139480000072
Benzoselenadiazole
Figure BDA0003071139480000073
Pyridinothiadiazoles
Figure BDA0003071139480000074
Figure BDA0003071139480000074
5, 6-difluorobenzothiadiazole
Figure BDA0003071139480000075
5-fluorobenzothiadiazoles
Figure BDA0003071139480000076
Figure BDA0003071139480000076
4, 7-diaryl-5, 6-dialkoxybenzothiadiazole
Figure BDA0003071139480000077
Figure BDA0003071139480000077
4, 7-diarylbenzothiadiazoles
Figure BDA0003071139480000081
Figure BDA0003071139480000081
4, 7-diarylbenzoselenadiazoles
Figure BDA0003071139480000082
Figure BDA0003071139480000082
4, 7-diarylpyridothiadiazoles
Figure BDA0003071139480000083
Figure BDA0003071139480000083
4, 7-diaryl-5, 6-difluorobenzothiadiazoles
Figure BDA0003071139480000084
Or 4, 7-diaryl-5-fluorobenzothiadiazole
Figure BDA0003071139480000085
One of (1), R3Is a straight chain or branched chain alkyl with 6-16 carbon atoms, and B is thiophene, selenophene, bithiophene or benzothiophene; the substitution on AR2 is one of C1-C20 straight chain substituent, C1-C20 branched chain substituent, C1-C20 straight chain alkoxy or C1-C20 branched chain alkoxy.
AR3 is one of substituted or substituted benzene, naphthalene, pyridine and anthracene, and the substitution on AR3 is one of C1-C8 branched chain or branched chain alkyl.
Y is taken from one of the following Y1, Y2, Y3, Y4 and Y5:
Figure BDA0003071139480000086
Y1-Y5: z1 and Z2 are each independently selected from cyano, fluorine atom and trifluoromethyl; p is selected from-CH ═ or N; d1 and D2 are each independently selected from the group consisting of hydrogen, deuterium, cyano, fluorine, trifluoromethyl, C1-C10 alkyl, C2-C10 alkenyl, substituted or unsubstituted C1-C10 alkoxy, substituted or unsubstituted C6-C30 aryl, substituted or unsubstituted C3-C30 heteroaryl, L-NAr1Ar2One of (1); l is selected from single bond, substituted or unsubstituted C6-C30 aryl, substituted or unsubstituted C3-C30 heteroaryl.
Ar1、Ar2Each independently selected from substituted or unsubstituted C6-C30 aryl, substituted or unsubstituted C3-C30 heteroaryl; ar (Ar)1And Ar2Are not linked to each other, or Ar1And Ar2To the carbon atom via a single bond, -O-, -S-, -C (CH)3)2-，-C(C6H5)2-linking to larger conjugated units.
Ar is1And Ar2Any one selected from the following groups:
Figure BDA0003071139480000091
wherein the dotted line represents the attachment site of the group; y is11、Y12、Y13、Y14、Y15、Y16、Y17、Y18、 Y19、Y110、Y111、Y112Each independently selected from N or C-RY。
T1Selected from O, S, N-RT1、CRT2RT3、SiRT2RT3；RY、RT1、RT2、RT3Each independently selected from hydrogen, deuterium, cyano, halogen, substituted or unsubstituted C1-C4 linear or branched alkyl, substituted or unsubstituted C6-C18 aryl, substituted or unsubstituted C3-C18 heteroaryl, and C6-C18 arylamine; substitutionRadical RYAt least 2 substituents which are not linked or adjacent to each other are linked by a chemical bond to form a ring.
The Ar is selected from any one of the following groups, or any one of the following groups substituted by substituent groups:
Figure BDA0003071139480000092
the substituent is selected from deuterium, fluorine, chlorine, cyano, unsubstituted or R' substituted C1-C4 straight chain or branched chain alkyl.
The invention also provides an application of the thermal activation delayed fluorescence polymer, and the application is to use the thermal activation delayed fluorescence polymer as a fluorescence luminous body and a photosensitizer for photodynamic therapy to construct a diagnosis and treatment integrated nano reagent.
The amphiphilic polymer is used for self-assembling and wrapping the novel heat-activated delayed fluorescence molecule prepared by the project, and the drug molecule and the target recognition unit can be introduced into a nano probe system at the same time. The method has the advantages of short preparation time, good repeatability, easy control of particle size and the like, and is very suitable for preparing the organic semiconductor nano probe.
The preparation method of the diagnosis and treatment integrated nano reagent constructed on the basis of the thermally activated delayed fluorescence polymer comprises the following steps of: reprecipitation, molecular micelle carrier, film dispersion, reflux precipitation and other common organic semiconductor nanometer reagent preparing process.
The reprecipitation method for preparing the nanometer reagent for activating the delayed fluorescence polymer comprises the following steps: firstly, respectively dissolving an organic semiconductor and a functional coating agent (such as PSMA or DSPE-PEG 2000) in Tetrahydrofuran (THF) to prepare a solution with the concentration of 1 mg/mL. After stirring overnight under inert gas, the solution of the coating agent was filtered through a 7 μm glass fiber filter to remove insoluble material from the bath. Then, the two solutions are mixed according to a certain proportion.
For example, 1mg/mL of the organic semiconductor and 0.2mg/mL of PSMA in a mixed solution. In order to control the particle size of the organic dots, the mixed solution was diluted with tetrahydrofuran (containing water at 0%, 30%, 50%, etc.) at different water contents. The concentration of each component of the diluted precursor solution is 50 mug/mL (organic semiconductor) and 10 mug/mL (PSMA), respectively. Then under the condition of ultrasonic water bath, 5mL of diluted precursor polymer mixed solution is rapidly injected into 10mL of deionized water, and the ultrasonic treatment is continued for 2 min. The obtained suspension solution was heat treated under nitrogen protection and finally concentrated to about 5 mL. Finally, the organic dot dispersion was filtered using a 0.2 μm aqueous membrane filter.
The polymer nanoparticle suspension bath prepared by the above operating scheme can maintain a stable state for a long period of time, and no significant aggregation phenomenon is observed even after several months of storage.
The method for preparing the nanometer reagent for activating the delayed fluorescence polymer by the thin film dispersion method comprises the following steps: preparing the synthesized fluorescent molecules and the functional amphiphilic polymer into an organic mixed solution by using a hydrophobic solvent chloroform (dichloromethane and the like), evaporating the organic mixed solution on a reduced-pressure evaporator under reduced pressure to remove the solvent in a rotating manner to form a uniform film on the wall of the bottle, and then placing the ultrapure water in the bottle for ultrasonic treatment to obtain the water-phase dispersible fluorescent nano probe. The method can conveniently form complex and more complex components in the nanoparticles and form stable nanoparticles. In addition, the amphiphilic molecules wrap the fluorescent molecular aggregate, so that the interface property of the nano probe can be effectively improved, and the optical property of the nano probe is favorably maintained.
The method for preparing the nanometer reagent for activating the delayed fluorescence polymer by the reflux precipitation method comprises the following steps: the fluorescent molecule containing one or more acryloyl groups is obtained by performing methacrylation treatment on the fluorescent molecule containing hydroxyl groups and amino groups synthesized in the item. The fluorescent molecule is polymerized with acrylic acid, isopropyl acrylamide and the like by a reflux precipitation method, and the functionalized nanosphere containing the fluorescent molecule with the same appearance can be prepared. The nano probe prepared by the reflux precipitation method has uniform appearance, can introduce temperature-sensitive and pH-sensitive groups into the nano probe, and is beneficial to carrying out drug adsorption loading, chemical bond bonding RGD and other targeted recognition groups in the later period. )
Based on the biomedical application of the diagnosis and treatment integrated nano reagent of the thermally activated delayed fluorescence polymer, the diagnosis and treatment integrated nano reagent can be used for injecting, spraying and the like to living bodies, cells and tissues, and realize photodynamic therapy and fluorescence imaging under the matching of proper illumination or a fluorescence instrument.
The invention applies a thermal activation delayed fluorescence conjugated polymer to a diagnosis and treatment integrated nano reagent, integrates the near infrared luminescence property, high fluorescence quantum yield, high photodynamic activity and high molar straw absorption of the conjugated polymer, obtains the diagnosis and treatment integrated nano reagent with stable fluorescence property, strong environmental tolerance, good fluorescence signal and good photodynamic treatment effect, can scientifically research living bodies, and can also be used as a nano reagent for medical application in clinical environment. The thermal activation delayed fluorescence polymer has strong main chain rigidity and reasonable distribution of conjugated units in a framework, can effectively ensure the maintenance of excellent photophysical properties in the polymer stacking process, and provides a new idea and example for the biomedical application based on the thermal activation delayed fluorescence luminophor.
The heat-activated delayed fluorescence polymer can be used as a photosensitizer for photodynamic therapy and a nanoprobe component for biological imaging. The heat-activated delayed fluorescence polymer is realized by preparing a nano reagent. The preparation method of the nanometer reagent comprises a reprecipitation method, a molecular micelle carrier, a film dispersion method, a reflux precipitation method and other common organic semiconductor nanometer reagent preparation methods. The photodynamic therapy and bioimaging of the thermally activated delayed fluorescence polymer can be applied to tumor therapy, antibacterial therapy and other disease therapy and health care.
Example 1
This example provides a thermally activated delayed fluorescence based conjugated polymer a having the following structural formula:
Figure BDA0003071139480000121
general formula A
The synthetic route of the conjugated polymer is shown as a general formula A.
0.40g (0.57mmol) of 2, 2' - (2- (4- (bis (4-bromophenyl) amino) phenyl) anthracene-9, 10-dialkylene) dimethylnitrile, 0.28g (1.42mmol) of (2, 5-dimethyl-1, 4-phenylene) diboronic acid and 0.47g (0.85 mmol) of 2, 7-dibromo-9, 9-dioctyl-9H-fluorene were charged into a 50mL reaction tube, and then 2MCs were sequentially added to the reaction tube2CO3(aq) (1mL), 9.2mg (0.008mmol) of catalyst palladium tetrakistriphenylphosphine, 5.3mg (0.013mmol) of ligand methyltrioctylammonium chloride, and 5mL of anhydrous toluene were stirred at 95 ℃ under an argon atmosphere for 96h to obtain a polymer. Cooling the polymer to room temperature, slowly pouring into 150mL of methanol to form a precipitate, filtering the precipitated polymer, washing the polymer with methanol and n-hexane in sequence in a Soxhlet extractor, dissolving the polymer with chloroform, precipitating the polymer into methanol, filtering, and vacuum-drying at 100 ℃ for 12 hours to obtain a mauve solid powder polymer, wherein the yield is 49%, and the structural formula of the general formula A is shown in figure 1.
Example 2
This example provides a polycyclic aromatic hydrocarbon-based conjugated polymer B having the following general structural formula B:
Figure BDA0003071139480000131
general formula B
The synthetic route of the conjugated polymer is shown as a general formula B.
0.50g (0.73mmol) of 2, 2' - (2- (4- (bis (4-bromophenyl) amino) phenyl) anthracene-9, 10-dialkylene) dimethylcarbonitrile, 1.17g (2.44mmol) of (9, 9-dioctyl-9H-fluorene-2, 7-diyl) diboronic acid and 0.96 g (1.71mmol) of 2, 7-dibromo 9- (heptadecan-9-yl) -9H-carbazole were taken and added to a 50mL reaction tube, and 2MCs were sequentially added to the reaction tube2CO3(aq) (1mL), 9.2mg (0.008mmol) of catalyst palladium tetrakistriphenylphosphine, 5.3mg (0.013mmol) of ligand methyltrioctylammonium chloride, and 5mL of anhydrous toluene were stirred at 95 ℃ under an argon atmosphere for 96h to obtain a polymer. After cooling the polymer to room temperature, it was slowly poured into 150mL of methanol to form a precipitate, and the precipitated polymer was filtered and then subjected to SoxhletWashing the extract with methanol and n-hexane in sequence, dissolving with chloroform, precipitating in methanol, filtering, and vacuum drying at 100 deg.C for 12 hr to obtain purple black solid powder polymer with yield of 57%, wherein the formula B is shown in FIG. 2. .
Example 3
This example provides a polycyclic aromatic hydrocarbon-based conjugated polymer C having the following general structural formula C:
Figure BDA0003071139480000141
general formula C
The synthetic route of the conjugated polymer is shown as a general formula C.
0.2g (0.24mmol) of (4- (7- (4- (bis (4-bromophenyl) amino) phenyl) -10, 13-dicyanodibenzo [ a, c ] was taken]Phenazin-2-yl) -3, 5-dimethylphenyl), 0.46g (1.18mmol) (9- (heptadecan-9-yl) -9H-carbazole-3, 6-diyl) diboronic acid and 0.52g (0.94mmol)2, 7-dibromo-9, 9-dioctyl-9H-fluorene were added to a 50mL reaction tube, and then 2MCs were sequentially added to the reaction tube2CO3(aq) (1mL), 9.2mg (0.008mmol) of catalyst palladium tetrakistriphenylphosphine, 5.3mg (0.013mmol) of ligand methyltrioctylammonium chloride, and 5mL of anhydrous toluene were stirred at 95 ℃ under an argon atmosphere for 96h to obtain a polymer. Cooling the polymer to room temperature, slowly pouring into 150mL of methanol to form a precipitate, filtering the precipitated polymer, washing the polymer with methanol and n-hexane in sequence in a Soxhlet extractor, finally dissolving the polymer with chloroform, precipitating the polymer into methanol, filtering, and vacuum-drying at 100 ℃ for 12 hours to obtain a purple black solid powder polymer, wherein the yield is 46%, and the structural formula of the general formula C is shown in figure 3.
Example 4
This example provides a polycyclic aromatic hydrocarbon-based conjugated polymer D having the following general structural formula D:
Figure BDA0003071139480000151
general formula D
The synthetic route of the conjugated polymer is shown as a general formula D.
0.4g (0.41mmol) of 2- (4- (bis (4-bromophenyl) amino) phenyl) -7- (4- (diphenylamino) phenyl) dibenzo [ a, c ] was taken]Phenazine-10, 13-dicarbonitrile, 0.51g (1.02mmol) (9- (heptadecan-9-yl) -9H-carbazole-2, 7-diyl) diboronic acid and 0.16g (0.62mmol)1, 4-dibromo-2, 5-xylene were added to a 50mL reaction tube, and then 2MCs were sequentially added to the reaction tube2CO3(aq) (1mL), 9.2mg (0.008mmol) of catalyst palladium tetrakistriphenylphosphine, 5.3mg (0.013mmol) of ligand methyltrioctylammonium chloride, and 5mL of anhydrous toluene were stirred at 95 ℃ under an argon atmosphere for 96h to obtain a polymer. Cooling the polymer to room temperature, slowly pouring the polymer into 150mL of methanol to form a precipitate, filtering the precipitated polymer, washing the polymer by sequentially using methanol and n-hexane in a Soxhlet extractor, finally dissolving the polymer by using trichloromethane, precipitating the polymer into the methanol, filtering, and performing vacuum drying at 100 ℃ for 12 hours to obtain a purple black solid powder polymer, wherein the yield is 53 percent, and the structural formula of the general formula E is shown in figure 4.
Example 5
This example provides a polycyclic aromatic hydrocarbon-based conjugated polymer E having the following general structural formula E:
Figure BDA0003071139480000161
general formula E
The synthetic route of the conjugated polymer is shown as a general formula E.
0.30g (0.43mmol) of 2, 2' - (2- (4- (4- (3, 6-dibromo-9H-carbazol-9-yl) phenyl) anthracene-9, 10-dialkylene) dimethylnitrile, 0.70g (1.43mmol) of (9- (heptadecane-9-yl) -9H-carbazole-3, 6-diyl) diboronic acid and 0.55g (1.00mmol) of 2, 7-dibromo-9, 9-dioctyl-9H-fluorene were taken and added to a 50mL reaction tube, and then 2MCs were sequentially added to the reaction tube2CO3(aq) (1mL), 9.2mg (0.008mmol) of catalyst palladium tetrakistriphenylphosphine, 5.3mg (0.013mmol) of ligand methyltrioctylammonium chloride, 5mL of anhydrous toluene at 95 deg.C under argon atmosphere with stirringStirring and reacting for 96 hours to obtain the polymer. Cooling the polymer to room temperature, slowly pouring into 150mL of methanol to form a precipitate, filtering the precipitated polymer, washing the polymer with methanol and n-hexane in sequence in a Soxhlet extractor, finally dissolving the polymer with chloroform, precipitating into methanol, filtering, and vacuum drying at 100 ℃ for 12h to obtain a mauve solid powder polymer, wherein the yield is 56%, and the structural formula of the general formula F is shown in figure 5.
Example 6
This example provides a polycyclic aromatic hydrocarbon-based conjugated polymer F having the general structural formula F:
Figure BDA0003071139480000171
the synthetic route of the conjugated polymer of formula F is shown in FIG. 6.
0.20g (0.28mmol) of 2, 2' - (2- (4- (bis (4-bromophenyl) amino) phenyl) anthracene-9, 10-dialkylene) dimethylcarbonitrile, 0.70g (1.41mmol) of ((9- (heptadecan-9-yl) -9H-carbazole-3, 6-diyl) diboronic acid and 0.64g (1.13mmol) of 2, 7-dibromo 9- (heptadecan-9-yl) -9H-carbazole were taken and added to a 50mL reaction tube, and then 2MCs were sequentially added to the reaction tube2C03(aq) (1mL), 9.2mg (0.008mmol) of catalyst palladium tetrakistriphenylphosphine, 5.3mg (0.013mmol) of ligand methyltrioctylammonium chloride, and 5mL of anhydrous toluene were stirred at 95 ℃ under an argon atmosphere for 96h to obtain a polymer. Cooling the polymer to room temperature, slowly pouring into 150mL of methanol to form a precipitate, filtering the precipitated polymer, washing the polymer with methanol and n-hexane in sequence in a Soxhlet extractor, finally dissolving the polymer with chloroform, precipitating the polymer into methanol, filtering, and vacuum-drying at 100 ℃ for 12 hours to obtain a mauve solid powder polymer, wherein the yield is 54%, and the structural formula of the general formula F is shown in figure 6.
Example 7
The embodiment provides a diagnosis and treatment integrated nano reagent preparation based on conjugated polymer preparation.
The preparation method of the diagnosis and treatment integrated nano reagent comprises the following steps: the polymer C and the functionalized capping agent (e.g., PSMA or DSPE-PEG2000, etc.) of example 3 were first dissolved in Tetrahydrofuran (THF) to prepare a solution having a concentration of 1mg/mL, respectively. Stirring overnight under the protection of inert gas, and filtering the coating agent solution with a 7 μm glass fiber filter to remove insoluble substances in the bath solution; then, the two solutions are mixed according to a certain proportion. For example, 1mg/mL of the organic semiconductor and 0.2mg/mL of PSMA in a mixed solution.
In order to control the particle size of the organic dots, the mixed solution was diluted with tetrahydrofuran (containing water at 0%, 30%, 50%, etc.) at different water contents. The concentration of each component of the diluted precursor solution is respectively 50 mug/mL (organic semiconductor) and 10 mug/mL (PSMA); then under the condition of ultrasonic water bath, 5mL of diluted precursor polymer mixed solution is rapidly injected into 10mL of deionized water, and the ultrasonic treatment is continued for 2 min. The obtained suspension was subjected to heat treatment under nitrogen protection, and finally the solution was concentrated to about 5mL, and finally the organic dot dispersion was filtered using a 0.2 μm aqueous membrane filter.
The polymer nanoparticle suspension bath prepared by the above operating scheme can maintain a stable state for a long period of time, and no significant aggregation phenomenon is observed even after several months of storage.
All test results show that the conjugated polymer related by the embodiment integrates the near-infrared luminescence property, the high fluorescence quantum yield, the high photodynamic activity and the high molar straw absorption, so that the diagnosis and treatment integrated nano reagent with stable fluorescence property, strong environmental tolerance, good fluorescence signal and good photodynamic treatment effect is obtained, and the nano reagent can be used for scientific research on living bodies and can also be used as a nano reagent for medical application in clinical environment.
The conjugated polymer C prepared in example 3 was dissolved using various solvents (chlorobenzene, dichloromethane, tetrahydrofuran, toluene) and tested for uv absorption and fluorescence emission using a uv-vis near absorptometer and a spectrofluorometer, and fig. 7 is a uv absorption spectrum of the conjugated polymer C prepared in example 3, with an absorption wavelength on the abscissa and an absorption intensity on the ordinate, showing that the maximum absorption wavelength of the polymer is at about 580 nm. FIG. 8 shows the fluorescence emission spectrum of conjugated polymer C, with the abscissa representing the emission wavelength and the ordinate representing the fluorescence emission intensity, wherein the maximum emission wavelength of the polymer is at 680 nm.
The nanoparticles prepared in example 7 were subjected to ultraviolet absorption and fluorescence emission tests using an ultraviolet-visible near absorptometer and a fluorescence spectrophotometer, and fig. 9 is an ultraviolet absorption spectrum, the abscissa is an absorption wavelength, and the ordinate is an absorption intensity, and it is shown that the maximum absorption wavelength of the nanoparticles is about 560 nm. FIG. 10 shows the fluorescence emission spectrum of the nanoparticle, with the abscissa representing the emission wavelength and the ordinate representing the fluorescence emission intensity, from which it can be seen that the maximum emission wavelength of the polymer is 660 nm.
The nanoparticles prepared in example 7 were characterized using Transmission Electron Microscopy (TEM). It can be seen from fig. 11 that the nanoparticles prepared in example 7 are dispersed uniformly, and the prepared nanoparticles are ellipsoidal and have similar particle sizes, and can be distributed uniformly in water. The scale in fig. 11 is 2 μm, and it can be seen that the size of the nanoparticles prepared by this method is around 100 nm.
In order to evaluate the strength of the singlet oxygen generating capacity of the nanoparticles prepared in example 7, 9, 10-anthryl-bis (methylene) dipropionic acid (ABDA) is selected as a singlet oxygen indicator in the experiment. Adding 10 μ L of prepared ABDA solvent with concentration of 2M into nanoparticle aqueous solution with appropriate concentration, using 100mW cm-2The white light source (400-800nm) is used for irradiation. The downward trend of the absorbance of the indicator at 378nm over 300s was recorded at 60s intervals. As can be seen from fig. 12, when the absorption intensity of ABDA at 378nm under the condition of illumination decreases with the increase of the illumination time, the prepared nanoparticle aqueous solution has photodynamic property.
The invention has various embodiments, and all technical solutions formed by adopting equivalent transformation or equivalent transformation are within the protection scope of the invention.

Claims (10)

1. A thermally activated delayed fluorescence polymer characterized by: the structural formula of the heat-activated delayed fluorescence polymer is as follows:
Figure FDA0003071139470000011
wherein, in the general formula (I), X represents the connection mode between the benzene ring A and the benzene ring B, can be the connection of the benzene ring A and the benzene ring B without X, can be the connection of single bond, and can be the connection of-NR1Any one of-O-, and-S-;
m + n is 0.5, and 0.5 > m > 0; AR1 is substituted benzene, naphthalene, fluorene, carbazole, spirofluorene, anthracene, xanthene, AR1 is substituted by C1-C20 straight chain substituent, C1-C20 branched chain substituent, C1-C20 straight chain alkoxy or C1-C20 branched chain alkoxy;
AR2 is selected from substituted benzene, naphthalene, fluorene, carbazole, spirofluorene, anthracene, xanthene, benzothiadiazole
Figure FDA0003071139470000012
Benzoselenadiazole
Figure FDA0003071139470000013
Pyridinothiadiazoles
Figure FDA0003071139470000014
5, 6-difluorobenzothiadiazole
Figure FDA0003071139470000015
5-fluorobenzothiadiazoles
Figure FDA0003071139470000016
4, 7-diaryl-5, 6-dialkoxybenzothiadiazole
Figure FDA0003071139470000017
4, 7-diarylbenzothiadiazoles
Figure FDA0003071139470000018
4, 7-diarylbenzoselenadiazoles
Figure FDA0003071139470000019
4, 7-diarylpyridothiadiazoles
Figure FDA00030711394700000110
4, 7-diaryl-5, 6-difluorobenzothiadiazoles
Figure FDA00030711394700000111
Or 4, 7-diaryl-5-fluorobenzothiadiazole
Figure FDA0003071139470000021
Wherein R3 is a straight chain or branched chain alkyl with 6-16 carbon atoms, B is thiophene, selenophene, bithiophene or benzothiophene; the substitution of AR2 is one of C1-C20 straight chain substituent, C1-C20 branched chain substituent, C1-C20 straight chain alkoxy or C1-C20 branched chain alkoxy;
AR3 is one of substituted or substituted benzene, naphthalene, pyridine and anthracene, and the substitution on AR3 is one of C1-C8 branched chain or branched chain alkyl.
2. The thermally activated delayed fluorescence polymer of claim 1, wherein: y is taken from one of the following Y1, Y2, Y3, Y4 and Y5:
Figure FDA0003071139470000022
Y1-Y5: z1 and Z2 are each independently selected from cyano, fluorine atom and trifluoromethyl; p is selected from-CH ═ or N.
3. A thermally activated delayed fluorescence polymer according to claim 2, wherein: d1 and D2 are each independently selected from hydrogen, deuterium, cyano, fluoro, trifluoromethyl, C1-C10 alkyl, C2-C10 alkenyl, substituted or unsubstituted CAlkoxy of 1-C10, substituted or unsubstituted aryl of C6-C30, substituted or unsubstituted heteroaryl of C3-C30, L-NAr1Ar2One of (1); l is selected from single bond, substituted or unsubstituted C6-C30 aryl, substituted or unsubstituted C3-C30 heteroaryl.
4. A thermally activated delayed fluorescence polymer according to claim 2, wherein: ar (Ar)1、Ar2Each independently selected from substituted or unsubstituted C6-C30 aryl, substituted or unsubstituted C3-C30 heteroaryl; ar (Ar)1And Ar2Are not linked to each other, or Ar1And Ar2To the carbon atom via a single bond, -O-, -S-, -C (CH)3)2-，-C(C6H5)2-linking to larger conjugated units.
5. The thermally activated delayed fluorescence polymer of claim 1, wherein: ar is1And Ar2Any one selected from the following groups:
Figure FDA0003071139470000031
wherein the dotted line represents the attachment site of the group;
Y11、Y12、Y13、Y14、Y15、Y16、Y17、Y18、Y19、Y110、Y111、Y112each independently selected from N or C-RY；
T1Selected from O, S, N-RT1、CRT2RT3、SiRT2RT3；
RY、RT1、RT2、RT3Each independently selected from hydrogen, deuterium, cyano, halogen, substituted or unsubstituted C1-C4 linear or branched alkyl, substituted or unsubstituted C6-C18 aryl, substituted or unsubstituted C3-C18 heteroaryl, and C6-C18 arylamine; substituent RYAre not connected to each otherAt least 2 adjacent substituents are linked by chemical bonds to form a ring.
6. The thermally activated delayed fluorescence polymer of claim 1, wherein: the Ar is selected from any one of the following groups, or any one of the following groups substituted by substituent groups:
Figure FDA0003071139470000032
the substituent is selected from deuterium, fluorine, chlorine, cyano, unsubstituted or R' substituted C1-C4 straight chain or branched chain alkyl.
7. The use of a thermally activated delayed fluorescence polymer according to claim 1, wherein: the heat-activated delayed fluorescence polymer can be used as a photosensitizer for photodynamic therapy and a nanoprobe component for biological imaging.
8. The use of a thermally activated delayed fluorescence polymer according to claim 7, wherein: the photodynamic therapy and bioimaging can be used for tumor therapy, antimicrobial therapy and other disease therapy and health care applications.
9. The use of a thermally activated delayed fluorescence polymer according to claim 7, wherein: the photosensitizer for photodynamic therapy is the thermally activated delayed fluorescence polymer as claimed in any one of claims 1 to 8, which has a structure with a general structural formula (I), wherein all the symbols X, AR1, AR2, AR3 and Y in the general structural formula of the photosensitizer for photodynamic therapy are consistent with the limitations of claims 1 to 8.
10. The use of a thermally activated delayed fluorescence polymer according to claim 7, wherein:
the thermal activation delayed fluorescence polymer is realized by preparing a nano reagent; the preparation method of the nanometer reagent comprises a reprecipitation method, a molecular micelle carrier, a film dispersion method, a reflux precipitation method and other common organic semiconductor nanometer reagent preparation methods.
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