Tetradentate pyridine ligand, near-infrared two-region fluorescent metal cage as well as preparation method and application of tetradentate pyridine ligand and near-infrared two-region fluorescent metal cage

Abstract

The invention relates to the technical field of supramolecular chemistry, in particular to a tetradentate pyridine ligand, a near-infrared two-region fluorescent metal cage as well as a preparation method and application of the tetradentate pyridine ligand and the near-infrared two-region fluorescent metal cage. The structural formula of the tetradentate pyridine ligand is shown in the specification, R is shown in the specification, and the element X is S or Se. The tetradentate pyridine ligand disclosed by the invention is a typical tetradentate pyridine ligand with a D-pi-A-pi-D structure and has strong near-infrared absorption capacity and efficient near-infrared two-region emission, and absorbed photon energy can be released in a fluorescent form; therefore, the metal cage prepared from the metal nano-material can be applied to in-vivo near-infrared two-region fluorescence imaging of mouse tumors. Due to the small ground state-excited state energy gap difference of the tetradentate pyridine ligand, photon energy absorbed by the metal cage prepared from the tetradentate pyridine ligand can also be released in the form of non-radiative transition, namely heat, so that the metal cage can be further applied to photo-thermal imaging and photo-thermal treatment and can play a complementary role with near-infrared two-region fluorescence imaging, and the in-vivo imaging quality is improved.

Description

Technical Field

[0001] This invention relates to the field of supramolecular chemistry, and in particular to a tetradentate pyridine ligand, a near-infrared II fluorescent metal cage, its preparation method, and its applications. Background Technology

[0002] Supramolecular cage-like compounds play a crucial role in supramolecular chemistry and materials science. Over the past few decades, structurally diverse supramolecular cages, including Platonic, Archimedes, and Goldberg polyhedra, have been successfully constructed and have demonstrated wide applications in catalysis, molecular recognition, separation, and biomedicine. Among these, fluorescent metal cages, which ingeniously integrate fluorophore frameworks into supramolecular metal cages, have attracted increasing attention in recent years. It is worth noting that although some fluorescent metal cages have been successfully prepared and shown interesting applications, these systems still face significant limitations: firstly, most reported metal cages emit wavelengths in the visible light region or the traditional near-infrared I region (400-900 nm). Due to insufficient tissue penetration depth, these materials are difficult to use for deep imaging of tumors. In recent years, near-infrared II (NIR-II, 1000-1700 nm) fluorescence imaging technology has rapidly developed due to its advantages such as high tissue penetration depth, low autofluorescence background, and low photodamage to normal tissues, showing great potential for precise cancer diagnosis. On the other hand, due to the relatively planar framework structure of traditional fluorescent building blocks, the constructed metal cages often exhibit weak fluorescence or even no fluorescence in the aggregated or solid state. This phenomenon is called aggregation-caused quenching (ACQ) effect, which seriously hinders the application of fluorescent metal cages in optoelectronic devices and biological systems.

[0003] Therefore, existing technologies still need to be improved and developed. Summary of the Invention

[0004] In view of the shortcomings of the prior art, the purpose of this invention is to provide a tetradentate pyridine ligand, a near-infrared II fluorescent metal cage, its preparation method and its application, in order to solve the problem of aggregation-induced quenching of existing near-infrared II fluorescent metal cages.

[0005] The technical solution of the present invention is as follows: The first aspect of this invention provides a tetradentate pyridine ligand with the following structural formula: , Where R is , The element X is either S or Se.

[0006] A second aspect of the present invention provides a method for preparing a tetradentate pyridine ligand, comprising the following steps: S1. Tris(4-bromophenyl)amine, 3-pyridineboronic acid, tetrakis(triphenylphosphine)palladium and potassium carbonate are placed in a solvent and reacted to generate compound 1. S2. Dissolve compound 1 in a solvent, and then react it with n-butyllithium and tributyltin chloride to generate compound 2; S3. Compound 3, tetraphenylphosphine palladium, and compound 2 were refluxed in toluene and purified by column chromatography to obtain the tetradentate pyridine ligand. Among them, compound 3 is Any one of them.

[0007] Optionally, in S1, the molar ratio of tris(4-bromophenyl)amine, 3-pyridineboronic acid, tetrakis(triphenylphosphine)palladium and potassium carbonate is 1:1.5-2.5:0.05-0.2:3-6.

[0008] Optionally, in S2, the molar ratio of compound 1, n-butyllithium, and tributyltin chloride is 1:1.05-1.3:1.05-1.3.

[0009] Optionally, in S3, the molar ratio of compound 3, tetratriphenylphosphine palladium and compound 2 is 1:0.1-0.3:3-4.

[0010] A third aspect of this invention provides a near-infrared II fluorescent metal cage, the structural formula of which is as follows:

[0011] Where R is , The element X is either S or Se.

[0012] A fourth aspect of this invention provides a method for preparing a near-infrared II fluorescent metal cage, comprising the following steps: The tetradentate pyridine ligand, tetradentate carboxylate ligand, and platinum ions are added to a mixed solvent of acetone and water, and then heated and stirred to obtain the near-infrared II fluorescent metal cage.

[0013] Optionally, the molar ratio of the tetradentate pyridine ligand, the tetradentate carboxylate ligand, and the platinum ion is 1:1.05-1.15:4-4.5.

[0014] Optionally, the ratio of acetone to water is 3 to 5:1, the heating and stirring temperature is 50-60°C, and the heating and stirring time is 6-12 hours.

[0015] Optionally, the chemical structural formula of the tetradentate carboxylate ligand is as follows: ; The platinum ion is cis-bis(triethylphosphine)bis(trifluoromethanesulfonic acid)platinum, and its chemical structural formula is: .

[0016] In a fifth aspect, the present invention provides an application of a near-infrared II fluorescent metal cage in in vivo near-infrared II fluorescence imaging, photothermal imaging, and photothermal therapy of animal tumors.

[0017] Beneficial effects: This invention prepares a tetradentate pyridine ligand, which is a typical D-π-A-π-D structure. It has strong near-infrared absorption and efficient near-infrared II emission (1000-1700 nm). The photon energy absorbed by it can be released in the form of fluorescence. Therefore, it can be used to prepare metal cages for in vivo near-infrared II fluorescence imaging of mouse tumors. On the other hand, due to the small ground-excited state band gap of the tetradentate pyridine ligand (D-π-A-π-D type), the photon energy absorbed by the metal cage prepared with it can also be released in the form of non-radiative transition, i.e., heat. This can be applied to photothermal imaging and photothermal therapy, and can complement near-infrared II fluorescence imaging to improve the quality of in vivo imaging. Attached Figure Description

[0018] Figure 1 Synthetic route diagram for preparing tetradentate pyridine ligand (4a) in Example 1 of the present invention.

[0019] Figure 2 The synthesis route for preparing the near-infrared II fluorescent metal cage (4b) in Example 1 of this invention is shown.

[0020] Figure 3 Synthetic route diagram for preparing tetradentate pyridine ligand (4a) in Example 2 of the present invention.

[0021] Figure 4 Synthesis route diagram for preparing near-infrared II fluorescent metal cage (4b) in Example 2 of the present invention.

[0022] Figure 5 This is the 1H NMR spectrum of the tetradentate pyridine ligand (4a) prepared in Example 1 of this invention.

[0023] Figure 6 This is the carbon NMR spectrum of the tetradentate pyridine ligand (4a) prepared in Example 1 of this invention.

[0024] Figure 7 This is the proton NMR spectrum of the near-infrared II fluorescent metal cage (5a) prepared in Example 1 of this invention.

[0025] Figure 8 This is the phosphorus NMR spectrum of the near-infrared II fluorescent metal cage (5a) prepared in Example 1 of this invention.

[0026] Figure 9 This is the 1H NMR spectrum of the tetradentate pyridine ligand (4b) prepared in Example 2 of this invention.

[0027] Figure 10 This is the carbon NMR spectrum of the tetradentate pyridine ligand (4b) prepared in Example 2 of this invention.

[0028] Figure 11 This is the proton NMR spectrum of the near-infrared II fluorescent metal cage (5b) prepared in Example 2 of this invention.

[0029] Figure 12 This is the phosphorus NMR spectrum of the near-infrared II fluorescent metal cage (5b) prepared in Example 2 of this invention.

[0030] Figure 13 These are the ultraviolet absorption and fluorescence spectra of the near-infrared II fluorescent metal cages (5a) and 5b prepared in Examples 1 and 2 of this invention.

[0031] Figure 14 This is a photothermal heating curve of the near-infrared II fluorescent metal cages (5a) and 5b prepared by this invention under 808 nm laser irradiation.

[0032] Figure 15 This is a near-infrared two-zone fluorescent metal cage (5a) prepared in Example 1 of the present invention, showing a near-infrared two-zone fluorescence image of a mouse tumor site.

[0033] Figure 16 This is a photothermal heating curve of a near-infrared II fluorescent metal cage (5a) prepared in Example 1 of this invention on a mouse tumor site. Detailed Implementation

[0034] This invention provides a tetradentate pyridine ligand, a near-infrared II fluorescent metal cage, its preparation method, and its applications. To make the objectives, technical solutions, and advantages of this invention clearer and more explicit, the invention is further described in detail below. It should be understood that the specific embodiments described herein are only for explaining the invention and are not intended to limit the invention. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or according to the product specification. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various modifications or alterations to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0035] In 2001, Professor Tang Benzhong's research group creatively proposed the concept of aggregation-induced emission (AIE) and developed a large number of fluorophores with AIE properties. These fluorophores emit almost no light in dilute solutions, but exhibit bright emission in aggregated or solid states. Therefore, the construction of metal cage-like compounds with near-infrared II aggregation-induced emission properties and the study of their applications in disease diagnosis and treatment remain to be explored.

[0036] Most reported metal cages emit wavelengths in the visible light region or the traditional near-infrared I region (400-900 nm). Due to insufficient tissue penetration depth, these materials are limited in their application for deep tumor imaging. Therefore, expanding the emission wavelength range of metal cages and developing near-infrared II emission (1000-1700 nm) metal cages will give metal cages more possibilities for in vivo imaging.

[0037] Based on this, this embodiment provides a tetradentate pyridine ligand with the following structural formula: , Where R is , The element X is either S or Se.

[0038] The tetradentate pyridine ligand in this embodiment is a typical D-π-A-π-D type tetradentate pyridine ligand. In the tetradentate pyridine ligand, triphenylamine acts as a strong electron donor, thiophene acts as a strong electron donor and π-bridge, and benzobisthiadiazole or selenized benzobisthiadiazole triazole acts as a strong electron acceptor. Therefore, the molecule has extremely strong charge transfer (DA) interaction, resulting in strong near-infrared absorption. The "intramolecular charge transfer excited state" formed after absorbing photons allows energy to be released in the form of fluorescence.

[0039] Because the tetradentate pyridine ligand of this embodiment has a strong near-infrared absorption capability, the photon energy absorbed by it can be released in the form of fluorescence. Therefore, it can be used to prepare metal cages for in vivo near-infrared II fluorescence imaging of mouse tumors. On the other hand, due to the small ground-excited state band gap difference of the tetradentate pyridine ligand (D-π-A-π-D type), the photon energy absorbed by the metal cage prepared with it can also be released in the form of non-radiative transition, i.e., heat. This can then be applied to photothermal imaging and photothermal therapy, and can complement near-infrared II fluorescence imaging to improve the quality of in vivo imaging.

[0040] This embodiment also provides a method for preparing a tetradentate pyridine ligand, comprising the following steps: S1. Tris(4-bromophenyl)amine, 3-pyridineboronic acid, tetrakis(triphenylphosphine)palladium and potassium carbonate are placed in a solvent and reacted to generate compound 1. S2. Dissolve compound 1 in a solvent, and then react it with n-butyllithium and tributyltin chloride to generate compound 2; S3. Compound 3, tetraphenylphosphine palladium, and compound 2 were refluxed in toluene and purified by column chromatography to obtain the tetradentate pyridine ligand. Among them, compound 3 is Any one of them.

[0041] It should be noted that in this embodiment, tris(4-bromophenyl)amine (containing three reaction sites) and pyridine-3-boronic acid reacted via a classic Suzuki coupling reaction under conditions of tetra(triphenylphosphine-palladium) as a catalyst and potassium carbonate as a base to generate compound 1. The use of approximately two equivalents of pyridine-3-boronic acid resulted in the bispyridine-substituted compound 1 becoming the major product. Compound 1 was then subjected to bromination with n-butyllithium at low temperature, followed by exchange with tributyltin chloride to obtain compound 2. Finally, the obtained compounds 2 and 3 were coupled via a Stille coupling reaction to obtain the tetradentate pyridine ligand of this invention.

[0042] In some embodiments, in S1, the molar ratio of tris(4-bromophenyl)amine, 3-pyridineboronic acid, tetrakis(triphenylphosphine)palladium and potassium carbonate is 1:1.5–2.5:0.05–0.2:3–6, for example, 1:1.5:0.05:3, 1:2:0.1:4, 1:2.5:0.2:6 or any value within the range.

[0043] In some embodiments, in S2, the molar ratio of compound 1, n-butyllithium, and tributyltin chloride is 1:1.05 to 1.3:1.05 to 1.3, such as 1:1.05:1.05, 1:1.1:1.1, 1:1.2:1.2, 1:1.3:1.3, or any value within the range.

[0044] In some embodiments, in S3, the molar ratio of compound 3, tetraphenylphosphine palladium and compound 2 is 1:0.1 to 0.3:3 to 4, for example, 1:0.1:3, 1:0.2:3.5, 1:0.3:4 or any value within the range.

[0045] It should be noted that the solvent in S1 is dioxane and water, and the reaction conditions are nitrogen protection, 100–110°C (e.g., 105°C), 48–72 hours (e.g., 60 hours). The solvent in S2 is anhydrous tetrahydrofuran, the reaction temperature is -70 to -80°C (e.g., -75°C), and the time is 0.5–1 hour (e.g., 0.6 hours). Finally, a saturated sodium chloride solution is added to quench the reaction, and the mixed solution is extracted with ethyl acetate. The organic phase is dried over anhydrous sodium sulfate and concentrated; the resulting residue is used directly in the next reaction without further purification. The reflux temperature in S3 is 100–110°C (e.g., 105°C), and the time is 48–72 hours (e.g., 60 hours).

[0046] This embodiment also provides a near-infrared II fluorescent metal cage, the structural formula of which is as follows:

[0047] Where R is , The element X is either S or Se.

[0048] It should be noted that the metal cage is assembled from a tetradentate pyridine ligand (D-π-A-π-D type), a tetradentate carboxylate ligand, and platinum ions. The tetradentate pyridine ligand used in this embodiment has a "triphenylamine-thiophene-acceptor-thiophene-triphenylamine" backbone. Due to the typical D-π-A-π-D structure of the tetradentate pyridine ligand, it endows the metal cage with near-infrared absorption and efficient near-infrared II emission (1000-1700 nm). The tetradentate carboxylate ligand acts as an additional ligand to support the overall framework of the metal cage, and the platinum ions act as metal nodes to connect the tetradentate pyridine ligand and the tetradentate carboxylate ligand. It should be noted that platinum ions generally employ a planar quadrilateral coordination mode, giving the metal-coordinate bonds (O-Pt-N) within the metal cage good directionality, a defined angle (approximately 90 degrees), and high bond energy. Combined with the rigid ligand structure (both the tetradentate pyridine and tetradentate carboxylate ligands used are multi-aromatic ring rigid structures) and the highly symmetrical, thermodynamically controlled configuration of the metal cage, it endows the material with unique structural rigidity. The rigid framework of the metal cage also helps reduce fluorescence quenching caused by the close packing of fluorophores, further enhancing its near-infrared II luminescence efficiency in the aggregated state. The D-π-A-π-D type tetradentate pyridine ligands in the metal cage not only endow the metal cage with efficient near-infrared II luminescence but also give it good reactive oxygen species generation and photothermal properties, thus enabling its application in photoacoustic imaging and photodynamic / photothermal therapy of tumors, contributing to the development of near-infrared II optical materials with multimodal diagnostic and therapeutic properties.

[0049] This embodiment also provides a method for preparing a near-infrared II fluorescent metal cage, comprising the following steps: The tetradentate pyridine ligand, tetradentate carboxylate ligand, and platinum ions are added to a mixed solvent of acetone and water, and then heated and stirred to obtain the near-infrared II fluorescent metal cage.

[0050] It should be noted that the near-infrared II fluorescent metal cage in this embodiment is assembled from a D-π-A-π-D type tetradentate pyridine ligand, a tetradentate carboxylate ligand, and platinum ions. During the preparation process, the sodium ions in the tetradentate carboxylate sodium ligand dissociate in solution, while the cis-bis(triethylphosphine)bis(trifluoromethanesulfonic acid)platinum of the platinum ions releases two trifluoromethanesulfonate anions. Subsequently, the platinum ions combine with the nitrogen atom on the pyridine group of the D-π-A-π-D type tetradentate pyridine ligand and the oxygen atom on the tetradentate carboxylate ligand through metal-organic coordination, spontaneously assembling to form the target three-component metal cage. The released trifluoromethanesulfonate ions exist in the system as the charge balance ions of the metal cage. This synthetic route is simple to operate, the product is easy to separate and purify, and the yield of the metal cage can reach over 80%, which has the advantages of simple steps, easy purification, and high yield.

[0051] In some embodiments, the molar ratio of the tetradentate pyridine ligand, the tetradentate carboxylate ligand, and the platinum ion is 1:1.05 to 1.15:4 to 4.5, such as 1:1.05:4, 1:1.1:4.2, 1:1.15:4.5, or any value within the range.

[0052] In some embodiments, the ratio of acetone to water is 3 to 5:1, the heating and stirring temperature is 50-60°C, and the heating and stirring time is 6-12 hours.

[0053] In some embodiments, the chemical structural formula of the tetradentate carboxylate ligand is: ; The platinum ion is cis-bis(triethylphosphine)bis(trifluoromethanesulfonic acid)platinum, and its chemical structural formula is: .

[0054] This embodiment also provides an application of a near-infrared II fluorescent metal cage in animal in vivo near-infrared II fluorescence imaging, photothermal imaging, and photothermal therapy of animal tumors.

[0055] The invention will be further described below with reference to specific implementations.

[0056] Example 1 1. Preparation of tetradentate pyridine ligand (4a), the synthetic route is as follows: Figure 1 As shown, it includes the following steps: Synthesis of Compound 1: Under nitrogen protection, tris(4-bromophenyl)amine (10 g, 20.7 mmol), pyridine-3-boronic acid (5.1 g, 41.5 mmol, 2.0 equivalent), tetra(triphenylphosphine)palladium (1.2 g, 1.0 mmol, 0.05 equivalent), and potassium carbonate (14.3 g, 103.7 mmol, 5.0 equivalent) were added to a 250 mL reaction flask. After three cycles of vacuuming and nitrogen purging, 100 mL of dioxane and 25 mL of water were added. The mixture was then stirred at 100 °C for 48 hours. After cooling to room temperature, the mixture was extracted with dichloromethane. The organic phase was collected and concentrated, and purified by column chromatography (dichloromethane:methanol = 50:1) to give a pale yellow solid compound 1 (3.0 g, yield 30%).

[0057] Synthesis of compound 2: Compound 1 (500 mg, 1.05 mmol) was added to a 100 mL reaction flask. After three cycles of vacuum-nitrogen purging, 20 mL of anhydrous tetrahydrofuran was injected to dissolve compound 1, and the system was cooled to -78 °C. At this temperature, n-butyllithium (0.46 mL, 1.15 mmol, 1.1 equivalent in 2.5 mol / L hexane solution) was slowly added, and the mixture was stirred at -78 °C for 1 hour. Tributyltin chloride (0.33 mL, 1.15 mmol, 1.1 equivalent) was then added, and the reaction was maintained at -78 °C for 0.5 hours. The reaction mixture was slowly heated to room temperature and stirred overnight. The reaction was quenched by adding 20 mL of saturated sodium chloride solution, and the mixture was extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and concentrated to obtain compound 2.

[0058] Synthesis of tetradentate pyridine ligand (4a): Compound 3a (132 mg, 0.18 mmol, 1.0 equivalent) and tetrakis(triphenylphosphine)palladium (41 mg, 0.036 mmol, 0.2 equivalent) were added to a 35 mL sealed tube. Then, a solution of compound 2 (431 mg, 0.63 mmol, 3.5 equivalent) dissolved in 15 mL of anhydrous toluene was added in a glove box, and the mixture was refluxed at 110 °C for 72 hours. After cooling the reaction solution to room temperature, the solvent was removed by rotary evaporation. The product (100 mg, 40% yield) was obtained by column chromatography (dichloromethane:methanol = 20:1).

[0059] 2. Preparation of near-infrared II fluorescent metal cage (5a), its synthesis circuit is as follows: Figure 2 As shown, it includes the following steps: Tetradentate pyridine ligand 4a (2.79 mg, 2.02 μmol), tetradentate carboxylate ligand (1.00 mg, 2.00 μmol), and cis-bis(triethylphosphine)bis(trifluoromethanesulfonic acid)platinum (5.90 mg, 8.09 μmol) were accurately weighed into a glass sample vial. A mixed solvent of 1.0 mL acetone and 0.25 mL water (volume ratio 4:1) was added to the vial, and the solution was stirred at 60°C for 12 hours to form a homogeneous system. After cooling to room temperature, the solvent was removed by a nitrogen stream, and 1.0 mL acetonitrile was added to dissolve the residue. The mixture was stirred at room temperature for 6 hours. After filtering the solution, 10 mL of diethyl ether was added to the filtrate to precipitate the precipitate, which was then centrifuged. The precipitate was washed with diethyl ether and dried under vacuum to finally obtain solid cage-like compound 5a (6.81 mg, yield 82%).

[0060] Figure 5 This is the 1H NMR spectrum of the tetradentate pyridine ligand 4a prepared in Example 1 of this invention; Figure 6 This is the carbon NMR spectrum of the tetradentate pyridine ligand 4a prepared in Example 1 of this invention; the results show that the D-π-A-π-D type tetradentate pyridine ligand 4a was successfully synthesized. The NMR structure is as follows: 1 H NMR (500 MHz, CDCl3) δ 8.88 (s, 2H), 8.81 (s, 1H), 8.58 (s, 2H), 7.88 (d, J = 8.0 Hz, 2H), 7.60 – 7.50 (m, 6H), 7.38-7.36(m, 2H), 7.29 (d, J = 8.6 Hz, 4H), 7.24 (d, J = 8.0 Hz, 2H), 2.80 (d, J = 7.1 Hz, 2H), 1.79-1.74 (m, 1H), 1.41 – 1.26 (m, 8H), 0.88 – 0.84 (m, 6H). 13 C NMR (126MHz, CDCl3) δ 151.09, 148.04, 147.86, 147.33, 146.61, 144.32, 138.95, 136.19,136.08, 135.55, 133.97, 132.42, 130.40, 129.78, 128.10, 124.72, 124.23,123.68, 112.88, 40.59, 32.87, 32.64, 28.74, 25.85, 23.15, 14.26, 10.90. Figure 7This is the proton NMR spectrum of the near-infrared II fluorescent metal cage 5a prepared in Example 1 of this invention. Figure 8 This is the phosphorus NMR spectrum of the near-infrared II fluorescent metal cage 5a prepared in Example 1 of this invention. The results show that the near-infrared II fluorescent metal cage 5a was successfully synthesized. The NMR structure is as follows: 1 H NMR (400 MHz, CD3CN) δ 8.85(s, 2H), 8.72 (s, 2H), 8.52 (s, 1H), 8.17 (s, 2H), 7.84-7.76 (m, 3H), 7.59(s, 2H), 7.51 (s, 2H), 7.42 (d, J = 8.1 Hz, 2H), 7.28 (s, 4H), 7.06 (s, 4H), 6.95 (d, J = 7.8 Hz, 2H), 2.69 (s, 2H), 2.06-1.97 (m, 12H), 1.90 – 1.78 (m,12H), 1.71 (s, 1H), 1.37 – 1.18 (m, 44H), 0.90 – 0.81 (m, 6H). 31 P NMR (162MHz, CD3CN) δ 6.02 (d, 2 J P-P = 21.06 Hz, 195 Pt satellites, 1 J Pt-P = 3249.72 Hz), 0.72(d, 2 J P-P = 21.06 Hz, 195 Pt satellites, 1 J Pt-P = 3470.04 Hz).

[0061] Example 2 1. Preparation of tetradentate pyridine ligand (4b), the synthetic route is as follows: Figure 3 As shown, the synthesis process of tetradentate pyridine ligand (4b) is the same as that of tetradentate pyridine ligand (4a).

[0062] 2. Fabrication of a near-infrared II fluorescent metal cage (5b), the synthesis circuit is as follows: Figure 4As shown, the near-infrared II fluorescent metal cage (5b) is the same as the near-infrared II fluorescent metal cage (5a), except that the R groups in the two are different. The R group in 5a is... The R group in 5b is .

[0063] from Figure 2 , Figure 4 It is understood that the metal cage of the present invention is obtained by assembling a D-π-A-π-D type tetradentate pyridine ligand, a tetradentate carboxylate ligand, and platinum ions through coordination bonds.

[0064] Figure 9 This is the 1H NMR spectrum of the tetradentate pyridine ligand 4b prepared in Example 2 of this invention.

[0065] Figure 10 This is the carbon NMR spectrum of the tetradentate pyridine ligand 4b prepared in Example 2 of this invention. The results show that the tetradentate pyridine ligand 4b was successfully synthesized. The NMR structure is as follows: 1 H NMR (600 MHz, CDCl3) δ 8.88 (s,2H), 8.58 (d, J = 3.7 Hz, 2H), 7.95 – 7.89 (m, 2H), 7.70 – 7.60 (m, 2H), 7.56 –7.51 (m, 4H), 7.40 (dd, J = 7.8, 4.8 Hz, 2H), 7.36 (s, 1H), 7.31 – 7.27 (m,4H), 7.23 – 7.20 (m, 2H), 2.63-2.52 (m, 2H), 1.37-1.33 (m, 1H), 1.12 – 0.88(m, 8H), 0.64 (td, J = 7.1, 2.1 Hz, 3H), 0.48 (t, J = 7.4 Hz, 3H). 13 C NMR (126MHz, CDCl3) δ 152.15, 146.93, 146.78, 146.25, 145.70, 145.21, 143.75, 135.04,132.99, 131.33, 128.40, 128.10, 127.05, 126.00, 124.81, 123.63, 123.58,122.62, 115.37, 39.57, 33.41, 31.45, 27.56, 24.57, 21.76, 13.00, 9.60.

[0066] Figure 11 This is the proton NMR spectrum of the near-infrared II fluorescent metal cage 5b prepared in Example 2 of this invention. Figure 12 This is the phosphorus NMR spectrum of the near-infrared II fluorescent metal cage 5b prepared in Example 2 of this invention. The results show that the near-infrared II fluorescent metal cage 5b was successfully synthesized. The NMR structure is as follows: 1 H NMR (400 MHz, CD3CN) δ 8.88(s, 2H), 8.70 (s, 2H), 8.14 (s, 2H), 7.84 (s, 3H), 7.57-7.46 (m, 6H), 7.35(s, 1H), 7.24 (s, 4H), 7.10-6.80 (m, 6H), 2.45 (s, 2H), 2.09-1.96 (m, 12H), 1.92-1.77 (m, 12H), 1.38 – 1.16 (m, 37H), 0.96 – 0.67 (m, 8H), 0.50 (t, J = 6.6Hz, 3H), 0.34 (s, 3H). 31 P NMR (162 MHz, CD3CN) δ 5.96 (d, 2 J P-P = 19.44 Hz, 195 Ptsatellites, 1 J Pt-P = 3256.20 Hz), 0.67 (d, 2 J P-P = 19.44 Hz, 195 Pt satellites, 1 J Pt-P =3457.08 Hz).

[0067] Figure 13 These are the ultraviolet absorption and fluorescence spectra of the near-infrared II fluorescent metal cages 5a and 5b prepared in Examples 1 and 2 of this invention. Figure 13 (a) is the UV absorption spectrum of metal cage 5a in DMF. Figure 13 (b) shows the fluorescence emission spectrum of metal cage 5a in DMF. Figure 13 (c) is the UV absorption spectrum of metal cage 5b in DMF. Figure 13The middle (d) is the fluorescence emission spectrum of metal cage 5b in DMF, indicating that metal cages 5a and 5b have significant absorption in the near-infrared region (700-800 nm) and bright fluorescence emission in the near-infrared II region (1000-1300 nm).

[0068] Figure 14 This is a photothermal heating curve of the near-infrared II fluorescent metal cages 5a and 5b prepared by this invention under 808nm laser irradiation. Figure 14 (a) shows the photothermal heating curve of the near-infrared II fluorescent metal cage 5a under 808nm laser irradiation. Figure 14 Figure (b) shows the photothermal heating curve of near-infrared II fluorescent metal cage 5b under 808nm laser irradiation. As can be seen from the figure, the temperature of the DMSO solution of metal cages 5a and 5b gradually increases with the extension of laser irradiation time. Moreover, the higher the concentration of metal cages 5a and 5b, the higher the maximum temperature value that the solution can reach, indicating that 5a and 5b have good photothermal conversion performance.

[0069] Figure 15 This is a near-infrared II fluorescence imaging image of a mouse tumor site obtained from the near-infrared II fluorescent metal cage 5a prepared in Example 1 of this invention. Figure 15 It can be seen that 5a has strong penetrating power and can be used for in vivo imaging of tumor sites in mice.

[0070] Figure 16 This is a photothermal heating curve of a near-infrared II fluorescent metal cage 5a prepared in Example 1 of this invention on a mouse tumor site. Figure 16 It can be seen that 5a has good photothermal properties, and the temperature of the tumor site in mice gradually increases with the extension of light exposure time.

[0071] In summary, the tetradentate pyridine ligand of the present invention is a typical tetradentate pyridine ligand with a D-π-A-π-D structure, possessing strong near-infrared absorption and efficient near-infrared II emission. The absorbed photon energy can be released in the form of fluorescence. Therefore, it can be used to prepare metal cages for in vivo near-infrared II fluorescence imaging of mouse tumors. Due to the small ground-excited state bandgap of the tetradentate pyridine ligand, the photon energy absorbed by the metal cage prepared using it can also be released in the form of non-radiative transitions, i.e., heat. This allows it to be applied to photothermal imaging and photothermal therapy, and can complement near-infrared II fluorescence imaging, thereby improving the quality of in vivo imaging.

[0072] The metal cage of this invention is assembled from a D-π-A-π-D type tetradentate pyridine ligand, a tetradentate carboxylate ligand, and platinum ions. The D-π-A-π-D type tetradentate pyridine ligand adopts a "triphenylamine-thiophene-receptor-thiophene-triphenylamine" framework. UV absorption and fluorescence spectroscopy experiments show that the metal cage exhibits near-infrared absorption and near-infrared II fluorescence emission (1000-1700 nm). The rigid framework of the metal cage helps reduce fluorescence quenching caused by the close packing of fluorophores, further enhancing its near-infrared II luminescence efficiency in the aggregated state. The D-π-A-π-D type tetradentate pyridine ligand in the metal cage not only endows it with efficient near-infrared II luminescence but also gives it good photothermal properties, enabling its application in near-infrared II fluorescence and photothermal imaging of tumors, and contributing to the development of near-infrared II optical materials with multimodal diagnostic and therapeutic properties.

[0073] It should be understood that the application of the present invention is not limited to the examples above. Those skilled in the art can make improvements or modifications based on the above description, and all such improvements and modifications should fall within the protection scope of the appended claims.

Claims

1. A tetradentate pyridine ligand characterized in that, The structural formula is: ， wherein R is , wherein X is S or Se.

2. A process for the preparation of a tetradentate pyridine ligand, characterized in that, The method comprises the following steps: S1, tri(4-bromophenyl)amine, 3-pyridine boronic acid, tetrakis triphenylphosphine palladium and potassium carbonate are put into a solvent to react to generate compound 1; S2, the compound 1 is dissolved in a solvent, and then reacts with n-butyllithium and tributyltin chloride to generate compound 2; S3, compound 3, tetrakis triphenylphosphine palladium and the compound 2 are refluxed in toluene to react, and column chromatography purification is performed to obtain the tetradentate pyridine ligand, wherein the compound 3 is any one of any one of the compounds 3.

3. The method of claim 2, wherein the four-dentate pyridine ligand is prepared by the reaction of a compound of formula (II) with a compound of formula (III) in the presence of a base. In S1, the molar ratio of tri(4-bromophenyl)amine, 3-pyridine boronic acid, tetrakis triphenylphosphine palladium and potassium carbonate is 1:1.5-2.5:0.05-0.2:3-6.

4. The method of claim 2, wherein the four-dentate pyridine ligand is prepared by the reaction of a compound of formula (II) with a compound of formula (III) in the presence of a base. In S2, the molar ratio of compound 1, n-butyllithium and tributyltin chloride is 1:1.05-1.3:1.05-1.

3.

5. The method of claim 2, wherein the four-dentate pyridine ligand is prepared by the reaction of a compound of formula (II) with a compound of formula (III) in the presence of a base. In S3, the molar ratio of compound 3, tetrakis triphenylphosphine palladium and the compound 2 is 1:0.1-0.3:3-4.

6. A near-infrared two-region fluorescent metal cage, characterized by, The structural formula is: wherein R is , wherein element X is S or Se.

7. A method of preparing a near-infrared two-zone fluorescent metal cage, characterized by, The method comprises the following steps: The tetradentate pyridine ligand, tetradentate carboxylate ligand and platinum ion are added into a mixed solvent of acetone and water, and then heated and stirred to obtain the near-infrared two-region fluorescent metal cage.

8. The method for preparing a near-infrared II fluorescent metal cage according to claim 7, characterized in that, The molar ratio of the tetradentate pyridine ligand, tetradentate carboxylate ligand and platinum ion is 1:1.05-1.15:4-4.

5.

9. The method for preparing a near-infrared II fluorescent metal cage according to claim 7, characterized in that, The ratio of the acetone and water is 3-5:1, the temperature of the heating and stirring is 50-60 DEG C, and the time of the heating and stirring is 6-12h; The chemical structural formula of the tetradentate carboxylate ligand is: ； The platinum ion is cis-bis(triethylphosphine)bis(triflate) platinum, with the chemical structure: .

10. The application of a near-infrared two-region fluorescent metal cage in near-infrared two-region fluorescent imaging, photothermal imaging of an animal living body and photothermal treatment of an animal tumor.

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