Near-infrared two-region luminous multi-resonance hybrid four-free-radical molecular compound as well as preparation and application thereof

Abstract

The invention belongs to the field of organic photoelectric materials, and particularly discloses a near-infrared two-region (NIR-II) multi-resonance hybrid four-free-radical molecule and preparation and application thereof, the structure of the molecule is as follows: in addition, the research on free radical materials in the aspect of NIR-II fluorescence imaging guided photo-thermal anticancer treatment is still limited, and the molecule has a wide application prospect. And the material is mainly concentrated on a double-free-radical material. A chain D-A-A-D type organic four-free-radical compound is designed and synthesized on the basis of a classical Cichibabin skeleton, the near-infrared two-region light-emitting multiple resonance hybrid four-free-radical molecular compound is high in stability and has the near-infrared two-region photoluminescence property, the near-infrared two-region light-emitting multiple resonance hybrid four-free-radical molecular compound is applied to research in biological photo-thermal anticancer treatment, and the near-infrared two-region light-emitting multiple resonance hybrid four-free-radical molecular compound has a wide application prospect. And the photo-thermal conversion efficiency of 87% is shown.

Description

Technical Field

[0001] This invention relates to the field of functional molecular materials, and in particular to organic functional materials of a class of near-infrared II luminescent multi-resonance hybrid tetraradical molecular compounds. Background Technology

[0002] As a new generation of organic materials, organic carbon radical materials, due to their unique magnetic properties, have shown broad application prospects in fields such as flexible organic electronic devices, photonics, spintronics, and organic quantum devices. In recent years, scientists have successfully designed and synthesized a variety of stable organic single and double radical compounds, such as triphenylmethyl radical, cyclopentadiene radical, and phenanthene radical. Furthermore, compared to single and double radicals, tetraradicals continue to receive sustained attention from the scientific community due to their potential value in studying the multi-level spin interactions and magnetic response characteristics of radical electrons. Currently, their molecular framework design mainly focuses on cyclic, chain, and cage-like conjugated systems, but research on stable tetraradicals remains in the exploratory stage due to limitations in high chemical reactivity and synthetic methodologies.

[0003]

[0004] Over the past decade, organic light-emitting radicals have attracted widespread attention as novel molecular emitters. Compared to traditional closed-shell light-emitting materials, these materials exhibit unique emission characteristics and excited-state dynamics due to their distinctive open-shell electronic structure, thus possessing significant advantages in several aspects. For example, these molecules typically exhibit inherent narrow band gaps due to strong spin coupling effects and demonstrate excellent light absorption in the near-infrared (NIR) region, making them ideal candidates for photothermal therapy. However, despite their strong light absorption, their high chemical reactivity and significant self-absorption effects often lead to weak fluorescence in the NIR-II region (1000-1700 nm), or even fluorescence quenching. Therefore, current research on these materials for NIR-II fluorescence imaging-guided photothermal anticancer therapy remains relatively limited and mainly focuses on diradical materials. For tetraradical compounds, almost all reports to date have shown fluorescence quenching. Currently, the application of tetraradical materials in NIR-II fluorescence imaging-guided photothermal anticancer therapy is still an emerging field that has not been fully explored, and therefore has great research potential and application prospects, which is worthy of in-depth research and exploration.

[0005] Near-infrared II (NIR-II, 1000-1700nm) fluorescence imaging-guided photothermal therapy (PTT) has become an important research direction in cancer diagnosis and treatment in recent years, with strong application potential in the biomedical field. Because photons at NIR-II wavelengths (1000-1700nm) are less affected by absorption and scattering by biological tissues (such as hemoglobin and water molecules), micron-level resolution imaging of living blood vessels and tumor boundaries can be achieved, precisely locating lesions. NIR-II lasers can penetrate deep tissues (such as the liver and pancreas), activating targeted photothermal agents to generate localized high temperatures (42-50℃), effectively ablating tumors that are difficult to reach with traditional PTT, while reducing thermal damage to normal tissues. Despite significant progress in fluorescence imaging-guided photothermal anticancer therapy, its research is still in its very early stages and faces a series of challenges that need to be addressed, such as: 1) the emission wavelength of most fluorophores is around 1000 nm, making imaging in the NIR-II region difficult; and 2) most high photothermal efficiency materials (such as metal-based materials) are often accompanied by long-term toxicity risks, which limits the development and application of photothermal therapy. Summary of the Invention

[0006] To address the problems of existing technologies, this invention provides a class of near-infrared II luminescent multi-resonance hybrid tetraradical molecular compounds, aiming to obtain new compounds with intrinsic near-infrared II luminescence properties.

[0007] The second objective of this invention is to provide the preparation of the aforementioned near-infrared II luminescent multi-resonance hybrid tetraradical molecular compound and its application in fluorescence imaging-guided photothermal anticancer therapy.

[0008] The third objective of this invention is to provide an organic optoelectronic material comprising a multi-resonant hybrid tetraradical molecular compound that emits near-infrared luminescence in the second region.

[0009] A near-infrared II luminescent, multi-resonance hybrid tetraradical molecular compound with the structure of Formula 1:

[0010]

[0011] In Formula 1, R1 and R2 are individually H, -Cl, -Br, -I, -CN, -CF3, Cl-C 24 Alkyl, C3-C 24 cycloalkyl, C1-C 24 Alkoxy, C1-C 24 Alkyl-substituted aryl, halogenated C1-C 24 Alkyl, halogenated C3-C 24 Cycloalkyl or halogenated C1-C 24 Alkoxy;

[0012] Z is O, S, NR, or P-Ph; in NR, R is a C1-C4 alkyl group;

[0013] The Ar mentioned is aryl or substituted aryl.

[0014] This invention provides a multi-resonance hybrid tetraradical molecular compound with a near-infrared II region photoluminescence structure of Formula 1, which can achieve near-infrared II region photoluminescence. Moreover, it also has excellent stability and luminescence efficiency.

[0015] The luminescent material based on multiple resonant hybrid tetraradicals described in Formula 1 of this invention has the following advantages: 1) the multiple resonant hybrid tetraradical molecules have high stability; 2) the multiple resonant hybrid tetraradical molecules have photoluminescence properties in the near-infrared II region (its emission can reach up to 1167nm); 3) when applied to near-infrared II imaging-guided photothermal anticancer research, it exhibits a high photothermal conversion efficiency of 87%.

[0016] The multi-resonance hybrid tetraradical molecule described in this invention exhibits significant absorption and emission characteristics in the near-infrared region. Furthermore, the absorption and emission wavelengths and luminescence efficiency of the material can be modulated by changing the strength of the dipole moment through the side chains, making it a promising candidate for applications in the fields of organic optoelectronic materials and interdisciplinary fields such as precision biological diagnosis and treatment.

[0017] In this invention, R1 is H, -Cl, -Br, -I, -CN, or -CF3, and is more preferably -CF3.

[0018] R2 is H, C1-C 24 Alkyl, C3-C 24 cycloalkyl, C1-C 24 Alkoxy, C1-C 24 Alkyl-substituted aryl, halogenated C1-C 24 Alkyl, halogenated C3-C 24 Cycloalkyl or halogenated C1-C 24 Alkoxy group, more preferably H.

[0019] Z is O.

[0020] In the Ar group, the aryl group includes a benzene ring, a five-membered aromatic heterocycle, a six-membered aromatic heterocycle, or a fused ring; the substituted aryl group is a group having at least one substituent selected from alkyl, alkoxy, trifluoromethyl, acyl, ester, nitro, and halogen groups on the aromatic ring.

[0021] Preferably, Ar is Further preferred

[0022] This invention includes near-infrared II luminescent multi-resonance hybrid tetraradical molecular compounds, which possess...

[0023] Structure of Equation 1-A and Equation 1-B:

[0024]

[0025]

[0026] The present invention also provides a method for preparing the near-infrared II luminescent multi-resonance hybrid tetraradical compound, wherein the raw material of Formula 2 is subjected to dehydrogenation with an alkali and an oxidant to obtain the compound.

[0027]

[0028] In this invention, the dehydrogenation can be conventional, for example: mixing Formula 2 with an alkali beforehand, and then adding an oxidant to carry out dehydrogenation.

[0029] In this invention, the alkali includes alkali metal alkali alkalis, such as potassium tert-butoxide.

[0030] The oxidant can be a quinone compound, and more specifically, tetrachlorobenzoquinone.

[0031] In the dehydrogenation process described in this invention, the alkali dosage equivalent is 50-100 Eqv, and considering cost, it can be further 60-90 Eqv; the oxidant dosage equivalent is 1-4 Eqv, and can be further 21.5-2.5 eqv; based on Formula 2.

[0032] The dehydrogenation reaction is carried out under anaerobic conditions.

[0033] The solvent for the dehydrogenation reaction includes, for example, one of THF, toluene, and DCM; more preferably, THF.

[0034] There are no special requirements for the temperature of dehydrogenation, for example, it can be 10 to 40°C, and the dehydrogenation reaction time is 1 to 4 hours.

[0035] In this invention, after dehydrogenation, an organic solvent can be used for extraction, and the collected organic phase can be concentrated and separated by chromatography to obtain the oxidation product.

[0036] In this invention, Formula 2 is obtained by self-coupling Formula 3 with a base and an oxidizing agent;

[0037]

[0038] In this invention, the self-coupling step can be conventional. For example, Formula 3 can be reacted with a base first, the reaction temperature can be below 15°C, the reaction time can be above 6 hours, and then an oxidant can be added to carry out the self-coupling reaction.

[0039] Preferably, the alkali includes an alkali metal alkali alkali;

[0040] Preferably, the oxidant is a quinone compound;

[0041] Preferably, in the self-coupling process, the dosage equivalent of the alkali is 0.5 to 5 Eqv, and more preferably 0.5 to 1 eqv, and the dosage equivalent of the oxidant is 0.2 to 4 Eqv, and more preferably 0.5 to 1 eqv; (based on Formula 3).

[0042] Preferably, the solvent for the self-coupling reaction is one of THF, toluene, and DCM; more preferably, it is DCM.

[0043] In this invention, after the self-coupling reaction, the reaction solution is concentrated and separated by chromatography to obtain the self-coupling product (Formula 2).

[0044] Formula 3 is obtained by oxidation of a mixture of Formula 4 and an oxidizing agent;

[0045]

[0046] Preferably, the oxidizing agent added during the oxidation reaction stage includes at least one of m-chloroperoxybenzoic acid, aluminum trichloride, ferric trichloride, scandium trifluoromethanesulfonate, and DDQ;

[0047] Preferably, the dosage equivalent of the oxidizing agent in the oxidation reaction stage is 1 to 5 Eqv. More preferably, it can be 2.5 to 3.5 eqv (based on Equation 4).

[0048] Preferably, the solvent for the oxidation reaction is one of THF, toluene, and DCM.

[0049] Preferably, the temperature of the oxidation reaction can be, for example, 10–40°C, or more preferably, room temperature.

[0050] Formula 4 is obtained by mixing Formula 5 with ArH and a Friedel-Crafts catalyst to carry out a Friedel-Crafts reaction.

[0051]

[0052] In this invention, the Friedel-Crafts reaction steps and conditions can be adjusted based on known principles, for example:

[0053] The Friedel-Crafts reaction catalyst can be a conventional Lewis acid or other catalyst, such as at least one of ferric chloride hexahydrate, boron trifluoride diethyl ether, gold trichloride, and zinc dichloride.

[0054] The dosage equivalent of the Friedel-Crafts reaction catalyst can be 0.1 to 0.3 Eqv (based on Equation 5).

[0055] The temperature for the Friedel-Crafts reaction is above 80°C, and can be further reduced to 90–150°C; or even further reduced to 100–130°C.

[0056] The Friedel-Crafts reaction also allows for the addition of an acid anhydride, in an amount of, for example, 5 to 10 eqv (based on Formula 5).

[0057] ArH is more than twice the molar amount of Formula 5, and can be 50 to 150 times.

[0058] In this invention, Formula 5 is obtained by performing a Suzuki coupling reaction using Formulas 6 and 7;

[0059]

[0060] In this invention, the Suzuki coupling reaction steps and conditions can be adjusted based on known principles, for example:

[0061] The catalyst for the Suzuki coupling reaction is at least one of Pd(dppf)Cl2, Pd(PPh3)2Cl2, and Pd(PPh3)4. Its dosage can be, for example, 0.01–0.05 eqv (based on Formula 7).

[0062] The Suzuki coupling reaction stage also allows the addition of an alkali, such as at least one of sodium carbonate or potassium carbonate, in an amount of, for example, 1 to 3 eqv (based on Formula 7).

[0063] Suzuki coupling is performed under anaerobic conditions.

[0064] The molar ratio of Equations 6 and 7 can be 1 to 2:1; further, it can be 1.3 to 1.8:1.

[0065] The preferred reaction temperature for Suzuki coupling is 90°C to 110°C.

[0066] The solvent for Suzuki coupling is at least one of DME, H2O, THF, Dioxane, and toluene; more preferably DME and H2O, wherein the volume ratio of DME to H2O is 3:1.

[0067] In this invention, after Suzuki coupling, extraction can be performed using an organic solvent, and the collected organic phase can be concentrated and separated by chromatography to obtain Suzuki coupling.

[0068] Preferably, Formula 6 is obtained by reacting Formula 8 with pinacol diboronic acid via a Miyaura borylation reaction;

[0069]

[0070] In this invention, the Miyaura borylation reaction steps and conditions can be adjusted based on known principles, for example:

[0071] The equivalent of the diboronic acid pinacol compound is 1 to 3 eqv; more specifically, it can be 1.5 to 2.5 eqv (based on Formula 8).

[0072] The catalyst for the Miyaura borylation reaction is Pd(dppf)Cl2. Its dosage is, for example, 0.01–0.03 eqv (based on Formula 8).

[0073] The Miyaura borylation stage also allows the addition of carboxylates, such as potassium acetate, in amounts of, for example, 1 to 3 eqv, and more specifically, 1.5 to 2.5 eqv (based on Formula 8).

[0074] The Miyaura borylation reaction is carried out under anaerobic conditions.

[0075] The preferred reaction temperature for the Miyaura borylation reaction is 80℃ to 100℃.

[0076] The solvent for the Miyaura borylation reaction is at least one of Dioxane, THF, Et3N, and DCM; Dioxane is more preferably preferred.

[0077] In this invention, after the Miyaura borylation reaction, an organic solvent can be used for extraction, and the collected organic phase can be concentrated and separated by chromatography to obtain the Miyaura borylation product.

[0078] The present invention also provides an application of the aforementioned compound with multiple resonance hybridized tetraradicals, for the preparation of organic optoelectronic materials.

[0079] Preferably, it is used to prepare near-infrared II organic optoelectronic materials.

[0080] Preferably, the organic optoelectronic material is at least one of bioimaging materials, semiconductor electronic devices, energy storage materials, and spin materials.

[0081] The present invention also provides an organic optoelectronic material comprising or prepared therefrom the aforementioned multi-resonance hybrid tetraradical compound.

[0082] For example, the present invention also provides nanoparticles comprising a compound of the multi-resonance hybrid tetraradical described in the present invention, comprising a support and a compound of the multi-resonance hybrid tetraradical complexed in the support.

[0083] Beneficial effects

[0084] This invention discloses the design, synthesis, and application of a class of multi-resonance hybridized tetraradical molecules. The advantages of this invention are:

[0085] 1) The tetraradical molecules designed with a multi-resonance hybrid structure in this invention exhibit significantly improved thermal stability;

[0086] 2) This molecule has excellent near-infrared II (NIR-II) photoluminescence properties, with a maximum emission wavelength of up to 1167 nm;

[0087] 3) When the nanoparticles (TR-2NPs) based on the molecules of this invention are used for NIR-II imaging-guided photothermal therapy under 1064nm laser excitation, they achieve a photothermal conversion efficiency of up to 87%.

[0088] 4) Under dark conditions, TR-2NPs at a concentration of 50 μM had minimal effect on the viability of 4T1 cells (cell survival rate >90%), indicating that it has excellent biocompatibility and negligible dark toxicity.

[0089] 5) The tetraradical compound of this invention exhibits significantly enhanced absorption characteristics at 1064 nm. Combined with the high tissue penetration of this wavelength light source, it is suitable for deep tissue imaging and treatment. Attached Figure Description

[0090] Figure 1 This is the mass spectrum of the TR-1 compound obtained in Example 1.

[0091] Figure 2 This is the mass spectrum of the TR-2 compound obtained in Example 1.

[0092] Figure 3 The low-temperature NMR (-80°C) of the TR-1 compound prepared in Example 1 is shown.

[0093] Figure 4 The low-temperature NMR (-40°C) of the TR2 compound prepared in Example 1 is shown.

[0094] Figure 5 The temperature-dependent NMR of the TR-1 compound prepared in Example 1 is shown.

[0095] Figure 6 The temperature-dependent NMR of the TR-2 compound prepared in Example 1 is shown.

[0096] Figure 7 These are the temperature-dependent ESRs of the TR-1 and TR-2 compounds prepared in Example 1.

[0097] Figure 8 The images show the UV-Vis absorption spectrum, fluorescence spectrum, and cyclic voltammetry curves of the solid solutions of TR-1 and TR-2 compounds prepared in Example 1.

[0098] Figure 9 These are the single-crystal structures of the TR-1-2H and TR-2 compounds obtained in Example 1.

[0099] Figure 10 The particle size distribution (a), UV-Vis absorption spectrum (b), and fluorescence spectrum (c) of the aqueous solution of TR-1 and TR-2 compound nanoparticles prepared in Example 1 are shown.

[0100] Figure 11 The photothermal conversion properties of TR nanoparticles prepared in Example 1 were tested (a) under 1064 nm laser irradiation (0.3 W / cm²). -2 (a) Concentration-dependent photothermal heating curves of TR-2 nanoparticle aqueous solution (50 μM); (b) Relationship between temperature and power (1064 nm) of TR-2 nanoparticle aqueous solution (50 μM); (c) Photothermal heating and cooling curves of TR-2 nanoparticles, and the relationship between ln(θ) and cooling time of linear fitting.

[0101] Figure 12 This is a cell activity test of the TR-2 nanoparticles prepared in Example 1.

[0102] Figure 13 This is an application of the TR-2 compound nanoparticles prepared in Example 1 - fluorescence imaging.

[0103] Figure 14 This is a thermal imaging image of the photothermal anticancer therapy of TR-2 compound nanoparticles prepared in Example 1. Detailed Implementation

[0104] This invention provides a method for preparing optional multi-resonance hybrid tetraradicals and their derivatives, comprising the following steps:

[0105] Step (1):

[0106] Compound a undergoes a Miyaura borylation reaction with pinacol diboronic acid to prepare compound b.

[0107] Step (2):

[0108] Compound b undergoes Suzuki coupling with compound c to prepare compound d.

[0109] Step (3):

[0110] Compound d undergoes a Friedel-Crafts reaction to produce compound e.

[0111] Step (4):

[0112] Compound e undergoes an oxidation reaction to produce compound f.

[0113] Step (5):

[0114] Compound f undergoes a self-coupling reaction to produce compound g.

[0115] Step (6):

[0116] Compound g undergoes a dehydrogenation reaction to produce compound h.

[0117]

[0118]

[0119] Example 1:

[0120] The synthesis route is as follows:

[0121]

[0122] The specific steps involved in producing TR-1 nanoparticles are as follows:

[0123] (1) Under argon protection, compound 1 (1.00 g, 2.90 mmol), B2Pin2 (1.5 g, 5.80 mmol), and CH3COOK (426 mg, 4.34 mmol) were dissolved in 80 mL of dioxane solvent. The mixture was purged for half an hour, and Pd(dppf)Cl2 (42 mg, 0.06 mmol) was added. The mixture was heated to 90 °C and refluxed overnight. After the reaction was complete, the mixture was brought to room temperature and extracted with water (50 mL) and dichloromethane (100 mL). The organic phase was collected and dried over anhydrous magnesium sulfate. After filtration, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography (eluting with a gradient of PE:EA = 30:1-10:1) to obtain solid compound 2.

[0124] (2) Under argon protection, compound 3 (1.00 g, 2.77 mmol), compound 2 (1.2 g, 4.15 mmol), and K2CO3 (766 mg, 5.54 mmol) were dissolved in 100 mL of a mixture of DME and water (DME / H2O = 3:1). After purging for half an hour, Pd(PPh3)4 (64 mg, 0.06 mmol) was added. The mixture was heated to 100 °C and refluxed overnight. After the reaction was complete, the mixture was allowed to return to room temperature, and water (30 mL) was added. The mixture was extracted with dichloromethane (3 × 10 mL). The organic phase was collected, dried over Na2SO4, filtered, and evaporated to dryness. The mixture was then purified by silica gel chromatography using PE:EA = 20:1 as the eluent to obtain an oily compound 4.

[0125] (3) Under argon protection, compound 4 (1 g, 1.8 mmol), acetic anhydride (1.5 g, 14.64 mmol), and FeCl3·6H2O (99 mg, 0.4 mmol) were dissolved in 30 mL of mesitylene. The mixture was heated to 110 °C and refluxed overnight. After the reaction was complete, the mixture was allowed to return to room temperature and extracted with water (100 mL) and ethyl acetate (200 mL). The organic phase was collected and dried over anhydrous magnesium sulfate. After filtration to remove the solvent, the mixture was purified by silica gel chromatography (using PE as the eluent) to obtain liquid compound 5.

[0126] (4) Compound 5 (200 mg, 0.27 mmol) was dissolved in dichloromethane (50 mL), and m-chloroperoxybenzoic acid (138 mg, 0.80 mmol) was added. The reaction was carried out at room temperature for 2-3 hours. After the reaction was completed, the reaction solution was extracted with water (10 mL) and dichloromethane (20 mL), the organic phase was collected and dried over anhydrous magnesium sulfate, the solvent was removed by filtration, and the solution was purified by silica gel chromatography (PE / DCM = 10:1) to obtain compound 6.

[0127] (5) Under argon protection, compound 6 (1.29 g, 2 mmol) was dissolved in anhydrous THF (50 mL), and anhydrous THF solution (0.1 M, 10 mL) containing potassium tert-butoxide was slowly added using a constant pressure dropping funnel. The reaction was carried out overnight (e.g., 10–16 h) at 10 °C. Then, tetrachlorobenzoquinone (1 mmol) was added, and the reaction was stopped after stirring for 2 h. The solvent was removed under vacuum, and the residue was further purified by silica gel column chromatography (PE:THF = 10:1) soaked in triethylamine to obtain compound 7 (also labeled TR-1-2H).

[0128] (6) Under a nitrogen atmosphere, compound 7 (129.0 mg, 0.1 mmol) was added to a Shrek tube and dissolved in 30 mL of anhydrous THF. Potassium tert-butoxide (897.7 mg, 8 mmol) was then added to the Shrek tube. After stirring for 1 h, tetrachlorobenzoquinone (49.17 mg, 0.2 mmol) was added and stirring was continued for 10 min to end the reaction. The solvent was removed under vacuum, and the residue was further purified by silica gel column chromatography (PE:THF = 3:1) soaked in triethylamine to obtain compound 8 (TR-1 compound).

[0129] (7) Dissolve 4 mg of the tetraradical compound (compound 8) and 10 mg of DSPE-PEG5000 in 2 mL of THF, respectively. Then, under 150 W sonication, the mixed solution is added dropwise to 10 mL of deionized water. Subsequently, the resulting dispersion is sonicated at 150 W for 5 minutes. Next, dialyze the solution in deionized water for 12 hours using a dialysis membrane with a molecular weight cutoff of 3500 D to obtain a uniform and transparent blue aqueous solution. The solution is then filtered through a 0.45 μm PVDF syringe to obtain nanoparticles (TR-1 nanoparticles, TR-1 nanoparticles, or TR-1NPs) for bioimaging.

[0130] Example 2

[0131] Compared with Example 1, the only difference is that the following compound is used. As compound 1, all other operations and parameters are the same as in Example 1; the corresponding TR-2 compound, TR-2 nanoparticles, and TR-2 nanoparticles, also known as TR-1NPs, are obtained.

[0132] The reaction equation is, for example:

[0133]

[0134] Verification of the properties of TR-1 and TR-2

[0135] In this invention, the structures of TR-1 and TR-2 were confirmed by variable-temperature nuclear magnetic resonance spectroscopy (NMR), mass spectrometry, UV-Vis-NIR absorption spectroscopy, and single-crystal diffraction (see details). Figures 1 to 7 ), and its related properties were studied.

[0136] Figure 8 The UV-Vis-NIR absorption spectra, fluorescence spectra, and cyclic voltammetry curves of toluene solutions of compounds TR-1 and TR-2, along with related photophysical properties, are shown in Table 1. Figure 8 In the text, the structure of TR-1-2H is that of a TR-1 oxidation precursor with Z=O, and its structure is as follows:

[0137] (That is, compound 7 of Example 1)

[0138] Electronic absorption spectroscopy results showed that the maximum absorption wavelength of compound TR-1-2H was 655 nm, while the maximum absorption wavelengths of compounds TR-1 and TR-2 were 1039 nm and 971 nm, respectively. Fluorescence spectroscopy results indicated that the emission wavelengths of compounds TR-1-2H, TR-1, and TR-2 were 792 nm, 1166 nm, and 1078 nm, with Stokes shifts of 137 nm, 124 nm, and 107 nm. Calculations yielded fluorescence quantum yields (PLQY) of compounds TR-1-2H, TR-1, and TR-2 of 6.1%, 0.02%, and 0.07%, respectively.

[0139] Table 1. Photophysical and electrical properties of TR-1-2H and TR-1, 2 in toluene.

[0140]

[0141] Figure 9 The single crystal structures of TR-1-2H and TR-2 are shown. To obtain high-quality single crystals, this invention uses a method of slowly diffusing n-hexane into its tetrahydrofuran or DCM solution for crystal growth.

[0142] Figure 11 This is a test of the photothermal conversion properties of TR nanoparticles (TR1 or TR2 nanoparticles) prepared in Example 1. The specific implementation process for testing the photothermal conversion properties of TR nanoparticles is as follows:

[0143] (1) Relationship between aqueous solution temperature and power: For a 50 μM nanoparticle solution, at different laser power densities (0.1, 0.2, 0.3, 0.4 and 0.5 W / cm²), -2 Irradiation was performed using a 1064nm laser under the following conditions;

[0144] (2) Aqueous solution concentration dependence: TR-2 nanoparticle solutions of different concentrations (0, 5, 15, 25 and 50 μM) were prepared and subjected to concentration dependence at 0.3 W / cm². -2 A 50 μM TR nanoparticle aqueous solution was irradiated with a 1064 nm laser for 5 minutes; during this process, the solution temperature change was monitored using a FLIR E8-XT camera.

[0145] (3) Photothermal heating and cooling curves, using 0.3W cm -2 A 1064nm laser was used to irradiate 50μM TR-2 nanoparticles and an ICG solution for 5 minutes. After the solution temperature reached a steady state, the laser was turned off, and the solution was cooled to room temperature. During this process, to assess its thermal stability, the change in solution temperature was recorded every 15 seconds. The photothermal conversion efficiency was derived and calculated using the following formula.

[0146]

[0147]

[0148]

[0149] In formula (a), h is the thermal conductivity coefficient, S is the container surface area, η represents the photothermal conversion efficiency, and Q... Dis For heat loss due to the solvent and container, I represents the laser power, and A represents the heat loss due to the solvent and container. 1064 The absorbance of the sample at a wavelength of 1064 nm is given by equation (b). In equation (b), m is the mass of the solution containing the photoactive substance, and C is the specific heat capacity of the solution (water is chosen as the solvent here, and its specific heat capacity C is given by equation (b)). water =4.2J g -1 In formula (C), τ s For the relevant time constant; in formula (d), T Max and T Surr These represent the maximum steady-state temperature and the ambient temperature, respectively, with temperature θ being a dimensionless driving force temperature parameter.

[0150] Unlike some photosensitizers that exhibit weak absorption at 1064 nm, these tetraradical compounds show significantly enhanced absorption at this temperature. Furthermore, the 1064 nm light source has a greater penetration depth, making it more suitable for deep tissue imaging and treatment. Simultaneously, high-power lasers can achieve more efficient photothermal conversion. Different concentrations (0, 2.5, 5, 10, 20, and 50 μM) of TR-2 nanoparticle solutions were prepared and analyzed at 0.3 W / cm². -2 The nanoparticles were irradiated with a 1064 nm laser for 5 minutes. Additionally, a 50 μM nanoparticle solution was irradiated with different laser power densities (0.1, 0.2, 0.3, 0.4, and 0.5 W / cm²). -2 The solution was irradiated with a 1064nm laser under specific conditions. During the experiment, a FLIR E8-XT infrared camera was used to monitor changes in solution temperature in real time. Figure 11 As shown in a and b, at 0.3 W cm -2 Under irradiation conditions, the maximum temperature of TR-2 nanoparticles gradually increased with increasing solution concentration; when the concentration reached 50 μM, the temperature reached a maximum of 73.1 °C after 5 minutes. On the other hand, at a fixed concentration of 50 μM, the temperature increased with increasing laser power density from 0.1 to 0.5 W / cm². -2As the concentration of the laser increases, the maximum temperature also rises accordingly, indicating that higher laser power density not only raises the temperature faster but also results in a more significant temperature rise, reaching a maximum of 68.9℃. These results demonstrate that by adjusting the nanoparticle concentration and laser power density, the maximum temperature during the PTT process can be flexibly controlled. Furthermore, the TR-2 nanoparticles achieved an ultra-high photothermal conversion efficiency of 87%, a significant improvement over compound 6 in Example 1 (from 49% to 87%).

[0151] Figure 12 4T1 cells were tested under dark conditions and with a 1064nm laser (0.3W cm⁻¹). -2 Five minutes after irradiation, cell viability was tested using different concentrations of TR-2 compound nanoparticles. The specific procedure was as follows: HeLa cells were cultured in DMEM medium containing FBS (10%) and penicillin / streptomycin (1%) at 37°C and 5% CO2 in a humidified incubator. When the cells reached the logarithmic growth phase, they were collected into wells and cultured for another day. Then, the medium was replaced with DMEM medium containing different concentrations of TR nanoparticles, and incubation continued for 20 hours to observe the effect of the nanoparticles on the cells. Subsequently, some cells were exposed to a 1064nm laser (0.3W cm⁻¹). -2 One group of cells was irradiated for 12 min to assess its cytotoxicity under light conditions; another group of cells was incubated in the dark to detect the toxic effects of the nanoparticles in a light-free environment. Subsequently, all cells were incubated for another 4 h, the culture medium was removed, and the cells were washed three times with PBS before being added with freshly prepared MTT solution (5 mg / mL). -1 Cells were incubated for 4 hours (using PBS) to assess cell viability. Afterward, 100 μL of dimethyl sulfoxide (DMSO) was added to each well to dissolve the formazan crystals, a metabolite of MTT, and the absorbance was measured at 490 nm using a microplate reader. In this experiment, the relative viability of cells in each treatment group was expressed as a percentage relative to the untreated control group and calculated using the following formula:

[0152]

[0153] Depend on Figure 12 It can be seen that even at a high concentration of 50 μM without light treatment, the viability of 4T1 cells remained above 90%, indicating that the dark toxicity of TR-2 nanoparticles to 4T1 cells is negligible, thus demonstrating good biocompatibility. However, under 1064 nm laser (power density of 0.3 W / cm²), the cell viability remained above 90%, indicating that the dark toxicity of TR-2 nanoparticles to 4T1 cells is negligible, thus demonstrating good biocompatibility. -2After 5 minutes of irradiation, cells treated with TR-2 nanoparticles showed significant concentration-dependent photoinduced cell death; when the concentration reached 50 μM, the viability of 4T1 cells dropped sharply to about 6%, which fully demonstrates that TR-2 nanoparticles have excellent therapeutic effects in photothermal therapy at the cellular level.

[0154] Figure 13 For the application of compound TR-2—fluorescence imaging; because the compound's emission wavelength reaches the near-infrared II region, and it is well known that near-infrared II emission has low scattering in biological tissues, enabling deeper tissue penetration, which is particularly important for imaging deep tissues or organs. Therefore, compound TR-2 was tested for in vivo fluorescence imaging in mice (in vivo fluorescence imaging was acquired using a commercial NIR-II small animal imaging system Series III 9001700S). First, TR-2 nanoparticles (700 μM, 200 μL, PBS solution) were subcutaneously injected into 4T1 tumor-bearing nude mice. Before and after injection, NIR-II fluorescence images of the entire nude mouse body were recorded using a 1000 nm filter. (See attached image.) Figure 13 As shown, compared with the blank group, the TR-2 nanoparticle-treated group exhibited bright near-infrared II fluorescence, with a fluorescence intensity 5 times that of the blank group.

[0155] Figure 14 This is a thermal imaging image of TR-2 compound nanoparticles used in photothermal anticancer therapy. Further investigation using an infrared thermal imager revealed the thermal imaging characteristics of TR-2 nanoparticles in mice. Experimental results showed that after subcutaneous injection of TR-2 nanoparticles into BALB / c mice, after 2 minutes of exposure to 1064 nm (0.3 W cm⁻¹)... -2 Laser irradiation caused the temperature at the injection site to rise rapidly to 47.36℃; in contrast, under the same laser irradiation conditions, the temperature at the PBS injection site in mice only rose to 39.20℃. These results demonstrate that TR-2 nanoparticles possess excellent photothermal conversion properties and show great application potential in fluorescence-photothermal imaging-guided photothermal anticancer research.

[0156] In summary, the near-infrared II luminescent multi-conjugated tetraradical molecule of the present invention possesses near-infrared II photoluminescence properties (its emission can reach up to 1167 nm) and a high photothermal conversion efficiency of 87%, making it a promising candidate for applications in organic optoelectronic materials and precision biological diagnostics.

Claims

1. A multi-resonance hybrid tetraradical molecular compound exhibiting near-infrared II emission, characterized in that, It has the structure of Formula 1: In Formula 1, R1 and R2 are individually H, -Cl, -Br, -I, -CN, -CF3, Cl-C 24 Alkyl, C3-C 24 cycloalkyl, C1-C 24 Alkoxy, C1-C 24 Alkyl-substituted aryl, halogenated C1-C 24 Alkyl, halogenated C3-C 24 Cycloalkyl or halogenated C1-C 24 Alkoxy; Z is O, S, NR, or P-Ph; in NR, R is a C1-C4 alkyl group; The Ar mentioned is aryl or substituted aryl.

2. The near-infrared II luminescent multi-resonance hybrid tetraradical molecular compound as described in claim 1, characterized in that, The R1 is H, -Cl, -Br, -I, -CN or -CF3, and is more preferably -CF3; Preferably, R2 is H, Cl-C 24 Alkyl, C3-C 24 cycloalkyl, C1-C 24 Alkoxy, C1-C 24 Alkyl-substituted aryl, halogenated C1-C 24 Alkyl, halogenated C3-C 24 Cycloalkyl or halogenated C1-C 24 Alkoxy group, more preferably H.

3. The near-infrared II luminescent multi-resonance hybrid tetraradical molecular compound as described in claim 1, characterized in that, Z is O; Preferably, in the Ar, the aryl group includes a benzene ring, a five-membered aromatic heterocycle, a six-membered aromatic heterocycle, or a fused ring; the substituted aryl group is a group having at least one substituent selected from alkyl, alkoxy, trifluoromethyl, acyl, ester, nitro, halogen, and cyano groups on the aromatic ring. Preferably, Ar is Further preferred 4. A method for preparing a near-infrared II luminescent multi-resonance hybrid tetraradical molecular compound according to any one of claims 1 to 3, characterized in that, The raw materials of Formula 2 are subjected to dehydrogenation with alkali and oxidant to obtain the product; Preferably, the alkali includes an alkali metal alkali alkali; Preferably, the oxidant is a quinone compound; Preferably, in the dehydrogenation process, the dosage equivalent of the alkali is 50-100 Eqv, and the dosage equivalent of the oxidant is 1-4 Eqv. Preferably, the dehydrogenation reaction is carried out under anaerobic conditions; Preferably, the solvent for the dehydrogenation reaction includes one of THF, toluene, and DCM; The reaction time for dehydrogenation is 1 to 4 hours.

5. The preparation method according to claim 4, characterized in that, Formula 2 is obtained by self-coupling Formula 3 with a base and an oxidizing agent; Preferably, the alkali includes an alkali metal alkali alkali; Preferably, the oxidant is a quinone compound; Preferably, in the self-coupling process, the dosage equivalent of the alkali is 0.5 to 5 Eqv, and the dosage equivalent of the oxidant is 0.2 to 4 Eqv; Preferably, the solvent for the self-coupling reaction is one of THF, toluene, and DCM.

6. The preparation method according to claim 5, characterized in that, Formula 3 is obtained by oxidation of a mixture of Formula 4 and an oxidizing agent; Preferably, the oxidizing agent added during the oxidation reaction stage includes at least one of m-chloroperoxybenzoic acid, aluminum trichloride, ferric trichloride, scandium trifluoromethanesulfonate, and DDQ; Preferably, the dosage equivalent of the oxidizing agent in the oxidation reaction stage is 1–5 Eqv; Preferably, the solvent for the oxidation reaction is one of THF, toluene, and DCM.

7. The preparation method according to claim 6, characterized in that, Formula 4 is obtained by mixing Formula 5 with ArH and a Friedel-Crafts catalyst to carry out a Friedel-Crafts reaction. Preferably, the Friedel-Crafts catalyst comprises at least one of ferric chloride hexahydrate, boron trifluoride diethyl ether, gold trichloride, and zinc dichloride; Preferably, the dosage equivalent of the Friedel-Crafts catalyst can be 0.1–0.3 Eqv; Preferably, the temperature of the Friedel-Crafts reaction is above 80°C, and more preferably 90–150°C.

8. The preparation method according to claim 7, characterized in that, Equation 5 is obtained by performing a Suzuki coupling reaction using Equations 6 and 7. Preferably, the catalyst for the Suzuki coupling reaction is at least one of Pd(dppf)Cl2, Pd(PPh3)2Cl2, and Pd(PPh3)4; Preferably, the reaction temperature for Suzuki coupling is 90°C to 100°C; Preferably, Formula 6 is obtained by reacting Formula 8 with pinacol diboronic acid via a Miyaura borylation reaction; Preferably, the catalyst for the Miyaura borylation reaction is Pd(dppf)Cl2; Preferably, the Miyaura borylation reaction is carried out under anaerobic conditions; Preferably, the reaction temperature of the Miyaura borylation reaction is 90℃~100℃; Preferably, the solvent for the Miyaura borylation reaction is at least one of Dioxane, THF, Et3N, and DCM; more preferably, it is Dioxane.

9. The application of a multi-resonance hybrid tetraradical molecular compound exhibiting near-infrared II emission according to any one of claims 1 to 3, characterized in that, It can be used to prepare organic optoelectronic materials; Preferably, it is used to prepare near-infrared II organic optoelectronic materials; Preferably, the organic optoelectronic material is at least one of bioimaging materials, semiconductor electronic devices, energy storage materials, and spin materials.

10. An organic optoelectronic material, characterized in that, The compound comprising or prepared therefrom the near-infrared luminescent quadratic molecular compound of any one of claims 1 to 3.

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