Bithiophene benzo-bridged ligand, preparation method thereof, bithiophene benzo-bridged binuclear metal complex, and preparation method and application of bithiophene benzo-bridged binuclear metal complex

Abstract

The invention relates to the technical field of research and development of photosensitizers for tumor photodynamic therapy, acoustic sensitizers for sonodynamic therapy and photothermal reagents for photothermal therapy, and provides a bithiophene benzo-bridged ligand and a preparation method thereof as well as a bithiophene benzo-bridged binuclear metal complex as well as a preparation method and application of the bithiophene benzo-bridged binuclear metal complex. According to the invention, on the basis of a bithiophene benzo-bridged ligand dtdpip, a bithiophene benzo-bridged binuclear ruthenium complex, a bithiophene benzo-bridged binuclear osmium complex and a bithiophene benzo-bridged binuclear iridium complex are respectively designed and invented. The bithiophene benzo-bridged binuclear metal complex has extremely high stability and excellent two-photon absorption characteristic, and has excellent biotoxicity and photothermal conversion capability under the action of infrared exciting light and ultrasonic waves. The conjugated bithiophene binuclear metal complex provided by the invention is a potential novel infrared photodynamic photosensitizer, a sound-sensitive agent and a photo-thermal reagent, and has a wide application prospect in photodynamic therapy, sonodynamic therapy and photo-thermal therapy of tumors.

Description

Technical Field

[0002] The present invention relates to the technical field of research and development of photosensitizers for tumor photodynamic therapy, photothermal agents for photothermal therapy and sonodynamic therapy, and in particular to a bithiophene benzo-bridged ligand and a preparation method thereof, and a bithiophene benzo-bridged binuclear metal complex and a preparation method and application thereof. Background Art

[0004] Photodynamic therapy (PDT) is a new tumor treatment method that appeared more than 40 years ago. It uses photosensitizers (PS) to react with molecular oxygen in tissues to produce reactive oxygen species (ROS), such as singlet oxygen ( 1 O 2 ) and superoxide anion (O 2 - ), ROS acts on subcellular structures and biomacromolecules (such as proteins and nucleic acids) through oxidation reactions to damage tumor cells to achieve the purpose of treatment. In practical applications, PDT therapy is usually administered by intravenous injection, and light with a wavelength that can penetrate tissue is applied to perform targeted, precise irradiation and non-invasive treatment of the tumor site. Compared with traditional cancer therapies, the advantage of PDT is that it can accurately and effectively treat cancer, and the side effects of this therapy are also very small, so it has received widespread attention and research.

[0005] Photothermal therapy (PTT) is an emerging non-invasive method for treating local tumors. This method uses near-infrared (NIR) light to stimulate photothermal agents (PTAs) to produce heat to change the physiological environment of the tumor and ablate tumor cells. It has typical advantages such as minimal invasiveness to normal tissues, reduced side effects, and strong anti-tumor ability. In order to obtain better PTT treatment effects and effectively inhibit the growth of tumor tissue after NIR irradiation, it can be adjusted by reducing tissue scattering and absorption and improving the photothermal conversion effect of the light absorber.

[0006] Sonodynamic therapy (SDT) is a new non-invasive anti-tumor treatment method that uses ultrasound (US) to activate sonosensitizers accumulated in the tumor area, generate ROS and kill tumor cells. SDT has the characteristics of strong penetration depth and few side effects. In addition, depending on the frequency of use, US can accurately target the lesion site and activate sonosensitizers in a targeted manner, achieving pathological cell apoptosis without damaging adjacent normal tissues. SDT has an integrated effect with other tumor treatment methods, such as PDT, PTT and chemotherapy, and there is a general synergistic enhancement effect between the various mechanisms, which is expected to achieve low-dose and high-efficacy treatment of tumors in the future.

[0007] At present, the first choice of drugs for the treatment of cancer in clinical practice is still transition metal platinum compounds, such as cisplatin, carboplatin, oxaliplatin, etc. However, this series of drugs has disadvantages such as side effects and drug resistance in clinical application, which limits the application prospects of transition metal platinum compounds as anti-tumor drugs. Therefore, it is urgent to design some new anti-tumor drugs with low toxicity and high efficiency. In the research field of transition metal compounds, transition metal compounds such as ruthenium, osmium, and iridium have attracted great attention from researchers as potential anticancer agents. In addition, thiophene is used to design and synthesize transition metal compounds with specific photophysical properties. Studies have found that the effect of in vitro photodynamic therapy of this series of compounds will be enhanced with the increase of thiophene in the compound structure.

[0008] Therefore, this patent invents a dithiophene benzo bridged binuclear metal complex based on the dithiophene benzo bridged ligand DTDPIP. This complex not only has extremely high stability and excellent two-photon absorption characteristics, but also can produce excellent singlet oxygen and biological toxicity and photothermal conversion ability under the action of infrared excitation light, effectively improving the efficiency of killing cancer cells, and is a potential new two-photon infrared photodynamic photosensitizer and photothermal agent. Summary of the invention

[0010] In view of this, the present invention provides a bithiophene benzo bridged ligand and a preparation method thereof, as well as a bithiophene benzo bridged binuclear metal complex and a preparation method and application thereof. The present invention provides a brand-new bithiophene benzo bridged ligand, and invents a bithiophene benzo bridged binuclear metal complex based on the ligand, which has excellent singlet oxygen yield, biological toxicity and photothermal conversion ability, and has broad application prospects in the preparation of tumor two-photon infrared photodynamic photosensitizers and photothermal agents.

[0011] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0012] A bithiophene benzo-bridged ligand, the structural formula of which is shown in Formula I:

[0013] Formula I;

[0014] A bithiophene benzo-bridged binuclear metal complex, consisting of anions and cations, wherein the structural formulas of the cations are shown in Formula II, Formula III and Formula IV:

[0015] Formula II;

[0016] In Formula II, represents an auxiliary ligand L1, wherein the auxiliary ligand L1 is any one of the ligands of the following structures:

[0017] , , .

[0018] Formula III;

[0019] In Formula II, represents an auxiliary ligand L2, wherein the auxiliary ligand L2 is any one of the ligands of the following structures:

[0020] , , .

[0021] Formula IV;

[0022] In Formula IV, represents an auxiliary ligand L3, wherein the auxiliary ligand L3 is any one of the ligands of the following structures:

[0023] , , , .

[0024] The present invention also provides a method for preparing the bithiophene benzo-bridged binuclear ruthenium complex described in the above scheme, comprising the following steps:

[0025] (i) mixing the auxiliary ligand L1, ruthenium trichloride, lithium chloride and an organic solvent to carry out a first coordination reaction to obtain a precursor compound having a structure shown in formula d;

[0026] Formula d;

[0027] (ii) mixing the precursor compound having the structure shown in formula (d), the bithiophene benzobridge ligand dtdpip and a solvent for a second coordination reaction to obtain an anion of Cl -A dithiophene benzo-bridged binuclear ruthenium complex, wherein the cationic structure of the dithiophene benzo-bridged binuclear ruthenium complex is shown in Formula II.

[0028] Preferably, the molar ratio of the auxiliary ligand L1 to ruthenium trichloride is 2:1; the molar ratio of the precursor compound having the structure shown in formula d to the bithiophene benzobridge ligand dtdpip is 2:1.

[0029] Preferably, the solvent in step (ii) is ethylene glycol solvent.

[0030] Preferably, the temperature of the second coordination reaction in step (ii) is 120-160 °C and the time is 6-24 h.

[0031] Preferably, in the step (ii), after the second coordination reaction is completed, the step further includes adding an aqueous solution containing an anion compound to the obtained reaction solution to convert Cl - Make a replacement.

[0032] The present invention also provides a method for preparing the bithiophene benzobridged binuclear osmium complex described in the above scheme, comprising the following steps:

[0033] (i) mixing the auxiliary ligand L2, ammonium hexachloroosmate and an organic solvent to carry out a first coordination reaction to obtain a precursor compound having a structure shown in formula e;

[0034] Formula e;

[0035] (ii) mixing the precursor compound having the structure shown in formula e, the bithiophene benzobridge ligand dtdpip and a solvent for a second coordination reaction to obtain an anion of Cl - A dithiophene benzo-bridged binuclear osmium complex, wherein the cationic structure of the dithiophene benzo-bridged binuclear osmium complex is shown in formula III.

[0036] Preferably, the molar ratio of the auxiliary ligand L2 to ammonium hexachloroosmate is 2:1; the molar ratio of the precursor compound having the structure shown in formula e to the bithiophene benzobridge ligand dtdpip is 2:1.

[0037] Preferably, the solvent in step (ii) is ethylene glycol solvent.

[0038] Preferably, the temperature of the second coordination reaction in step (ii) is 120-160 °C and the time is 6-24 h.

[0039] Preferably, in the step (ii), after the second coordination reaction is completed, the step further includes adding an aqueous solution containing an anion compound to the obtained reaction solution to convert Cl- Make a replacement.

[0040] The present invention also provides a method for preparing the bithiophene benzo-bridged binuclear iridium complex described in the above scheme, comprising the following steps:

[0041] (i) mixing the auxiliary ligand L3, iridium chloride and an organic solvent to carry out a first coordination reaction to obtain a precursor compound having a structure shown in Formula VI;

[0042] Formula f;

[0043] (ii) mixing the precursor compound having the structure shown in formula f, the bithiophene benzobridge ligand dtdpip and a solvent for a second coordination reaction to obtain an anion of Cl - A dithiophene benzo-bridged binuclear iridium complex, wherein the cationic structure of the dithiophene benzo-bridged binuclear iridium complex is shown in formula IV.

[0044] Preferably, the molar ratio of the auxiliary ligand L3 to iridium chloride is 2:1; the molar ratio of the precursor compound having the structure shown in formula f to the bithiophene benzobridge ligand dtdpip is 1:1.

[0045] Preferably, the solvent in step (ii) is ethylene glycol solvent.

[0046] Preferably, the temperature of the second coordination reaction in step (ii) is 120-160 °C and the time is 6-24 h.

[0047] Preferably, in the step (ii), after the second coordination reaction is completed, the step further includes adding an aqueous solution containing an anion compound to the obtained reaction solution to convert Cl - Make a replacement.

[0048] The present invention also provides the use of the bithiophene benzo-bridged binuclear metal complex described in the above scheme in the preparation of photosensitizers and photothermal agents for tumor photodynamic therapy.

[0049] The present invention also provides a dithiophene benzo bridged binuclear metal complex, which is composed of anions and cations, and the cations have structures shown in formula II, formula III and formula IV. Based on the dithiophene benzo bridged ligand DTDPIP, the present invention designs and invents a dithiophene benzo bridged binuclear metal complex whose cations have structures shown in formula II, formula III and formula IV. The dithiophene benzo bridged binuclear metal complex has the following advantages: (1) It has extremely high stability; (2) When 808nm infrared light is used as the excitation light, it has excellent singlet oxygen yield, cytotoxicity and photothermal conversion efficiency, and can effectively kill cancer cells. The dithiophene benzo bridged binuclear metal complex provided by the present invention has certain biological toxicity and photothermal conversion ability, is a potential new type of two-photon infrared photodynamic photosensitizer and photothermal agent, and has broad application prospects in photodynamic therapy and photothermal therapy of tumors.

[0050] The present invention also provides a method for preparing the bithiophene benzo-bridged binuclear metal complex described in the above scheme. The preparation method provided by the present invention has simple steps and is easy to carry out industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] Figure 1 The synthetic route of the bithiophene benzo-bridged ligand dtdpip is shown in FIG.

[0053] Figure 2 To synthesize the precursor compound [Ru(L) 2 Cl 2 ] reaction formula;

[0054] Figure 3 The reaction formula for synthesizing bithiophene benzo-bridged binuclear ruthenium complexes;

[0055] Figure 4 To synthesize the precursor compound [Os(L) 2 Cl 2 ] reaction formula;

[0056] Figure 5 The reaction formula for synthesizing bithiophene benzo-bridged binuclear osmium complexes;

[0057] Figure 6 To synthesize the precursor compound [Ir 2 (L) 4 (μ-Cl) 2 ] reaction formula;

[0058] Figure 7 The reaction formula for synthesizing bithiophene benzo-bridged binuclear iridium complexes;

[0059] Figure 8This is the ultraviolet absorption change of the singlet oxygen scavenger ABDA in the solution after irradiation with 450 nm light in the presence of a bithiophene benzo-bridged binuclear metal complex;

[0060] Fig. 9 This is the ultraviolet absorption change of the singlet oxygen scavenger ABDA in the solution after 808 nm laser irradiation in the presence of a bithiophene benzo-bridged binuclear metal complex;

[0061] Fig.10 This is a graph showing the change in ultraviolet absorption of the singlet oxygen scavenger ABDA in the solution after US laser irradiation in the presence of a bithiophene benzo-bridged binuclear metal complex;

[0062] Fig.11 This is the ultraviolet absorption change of the singlet oxygen scavenger ABDA in the solution after 808 nm+US laser irradiation in the presence of a bithiophene benzo-bridged binuclear metal complex;

[0063] Fig.12 The photothermal conversion diagram of 10 μM bithiophene benzo-bridged binuclear metal complex prepared by the present invention and the control group PBS under 808 nm light irradiation for different time periods;

[0064] Fig.13 The photothermal conversion diagram of 50 μM bithiophene benzo-bridged binuclear metal complex prepared by the present invention and the control group PBS under 808 nm infrared light irradiation for different time periods;

[0065] Fig.14 The photothermal conversion diagram of 100 μM bithiophene benzo-bridged binuclear metal complex prepared by the present invention and the control group PBS under 808 nm light irradiation for different time periods; DETAILED DESCRIPTION

[0067] The present invention provides a bithiophene benzo-bridged ligand, characterized in that the structural formula is as shown in Formula I:

[0068] Formula I.

[0069] The present invention also provides a method for preparing the bithiophene benzobridged ligand described in the above scheme, comprising the following steps:

[0070] (1) mixing a compound having a structure represented by formula a, potassium bromide and an organic acid solvent for reaction to obtain a compound having a structure represented by formula b;

[0071] Formula a; Formula b;

[0072] (2) The compound having the structure shown in formula b, the compound having the structure shown in formula c and an organic solvent are mixed for condensation reaction to obtain potassium bromide having the structure shown in formula I and an organic acid ligand.

[0073] Formula c.

[0074] In the present invention, the synthesis route of the bithiophene benzobridged ligand having the structure shown in Formula I is as follows: Figure 1 As shown below, combined Figure 1 Provide detailed explanation.

[0075] The present invention mixes a compound having a structure shown in formula a, potassium bromide and an organic acid for reaction to obtain a compound having a structure shown in formula b. In the present invention, the chemical name of the compound having a structure shown in formula b is 1,10-phenanthroline-5,6-dione.

[0076] In the present invention, the method for synthesizing the compound having the structure shown in formula b preferably comprises the following steps: 1,10-phenanthroline (structural formula: Figure 1 ), potassium bromide is placed in an ice-water bath and mixed with acid dropwise, and then heated in an oil bath for reflux. After the reaction is completed, the pH is adjusted with sodium hydroxide to precipitate a large amount of yellow solid, and 1,10-phenanthroline-5,6-dione (Formula b) is obtained. In the present invention, the organic acid is concentrated sulfuric acid and concentrated nitric acid in a volume ratio of 2:1; the molar ratio of 1,10-phenanthroline and potassium bromide is preferably 2:3; the reaction is preferably carried out under reflux conditions of 70 ~ 90 ° C, and the reaction time is preferably 6 ~ 10h; in a specific embodiment of the present invention, it is preferred to first leave the reaction after heating and reflux open for 12h to release bromine gas. After the reaction is completed, the present invention preferably pours the reaction solution into a 200 ml ice water bath and adjusts the pH to 5-6 with 10 M sodium hydroxide, the solution is yellow and a large amount of yellow solid is precipitated, and then extracted with chloroform, and the collected organic phase is dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure to obtain a crude product, and the crude product is recrystallized from anhydrous ethanol to obtain a compound having a structure shown in formula b.

[0077] After obtaining the compound having the structure shown in formula b, the present invention mixes the compound having the structure shown in formula b, the compound shown in formula c (chemical name is benzo 1,2-b:4,5-b' dithiophene-2,6 dicarboxaldehyde), ammonium acetate and an organic solvent for reaction to obtain a compound having the structure shown in formula I. In the present invention, the organic solvent for the reaction is preferably glacial acetic acid; the molar ratio of the compound having the structure shown in formula b to the compound having the structure shown in formula c is preferably 2:1 (3.0 mmol:1.5 mmol), and the amount of ammonium acetate is preferably 60 mmol; the temperature of the reaction is preferably 100~120 °C, and the time is preferably 8~12 h; in a specific embodiment of the present invention, the reaction is preferably carried out under reflux conditions. After the reaction is completed, the present invention preferably cools the obtained reaction solution to room temperature, and then sequentially performs suction filtration, water washing, ethanol washing, ether washing and drying to obtain a dithiophene benzo-bridged ligand having the structure shown in formula I (denoted as dtdpip)

[0078] The present invention also provides a bithiophene benzo-bridged binuclear metal complex, which is composed of anions and cations, and the structural formulas of the cations are shown in Formula II, Formula III and Formula IV:

[0079] Formula II;

[0080] In Formula II, represents an auxiliary ligand L1, wherein the auxiliary ligand L1 is any one of the ligands of the following structures:

[0081] , , .

[0082] Formula III;

[0083] In Formula II, represents an auxiliary ligand L2, wherein the auxiliary ligand L2 is any one of the ligands of the following structures:

[0084] , , .

[0085] Formula IV;

[0086] In Formula IV, represents an auxiliary ligand L3, wherein the auxiliary ligand L3 is any one of the ligands of the following structures:

[0087] , , , .

[0088] In the present invention, the chemical names of the auxiliary ligands L1 are: 2,2'-bipyridine (bpy), 4,4'-di-tert-butyl-2,2'-bipyridine (tbubpy) and 4,7-diphenyl-1,10-phenanthroline (dip); the chemical names of the auxiliary ligands L2 are: 2,2'-bipyridine (bpy), 4,4'-di-tert-butyl-2,2'-bipyridine (tbubpy) and 4,7-diphenyl-1,10-phenanthroline (dip); the chemical names of the auxiliary ligands L3 are: 2-phenylpyridine (ppy), 2-(2,4-difluorophenyl)pyridine (Fppy), 2-phenylquinoline (pq) and 2-phenylisoquinoline (piq); the present invention has no special requirements on the source of the auxiliary ligands, and the commercially available ligands or the methods well known to those skilled in the art can be used to synthesize them.

[0089] The present invention has no special requirements for the anions in the bithiophene benzo-bridged binuclear metal complex. Conventional anions in the art can achieve the purpose of the present invention. In a specific embodiment of the present invention, the anions are preferably inorganic salt anions, more preferably PF 6 - , ClO 4 - or Cl - PF is the most preferred 6 - .

[0090] The present invention also provides a method for preparing the bithiophene benzo-bridged binuclear ruthenium complex described in the above scheme, comprising the following steps:

[0091] (i) mixing the auxiliary ligand L1, ruthenium trichloride, lithium chloride and an organic solvent to carry out a first coordination reaction to obtain a precursor compound having a structure shown in formula d;

[0092] Formula d;

[0093] (ii) mixing the precursor compound having the structure shown in formula d, the conjugated bithiophene ligand having the structure shown in formula I and a solvent for a second coordination reaction to obtain an anion of Cl - A dithiophene benzo-bridged binuclear ruthenium complex, wherein the cationic structure of the dithiophene benzo-bridged binuclear ruthenium complex is shown in Formula II.

[0094] The present invention mixes auxiliary ligand L1, ruthenium trichloride, lithium chloride and an organic solvent to carry out a first coordination reaction to obtain a precursor compound having a structure shown in formula d. In the present invention, the molar ratio of the auxiliary ligand L1 and ruthenium trichloride is preferably 2:1; the molar ratio of the lithium chloride and ruthenium trichloride is preferably 14:3; the organic solvent used for the coordination reaction is preferably N,N'-dimethylformamide; the temperature of the coordination reaction is preferably 140 °C, and the time is preferably 8 h; the first coordination reaction is preferably carried out under argon protection. After the reaction is completed, the present invention cools the obtained reaction solution to room temperature, adds acetone, and then freezes it overnight, and then sequentially performs suction filtration, washing and vacuum drying to obtain a precursor compound having a structure shown in formula d [Ru(L1) 2 Cl 2 ].

[0095] In the present invention, the precursor compound [Ru(L1) 2 Cl 2 The chemical reaction formula is as follows Figure 2 shown.

[0096] After obtaining the precursor compound having the structure shown in formula d, the present invention mixes the precursor compound having the structure shown in formula d, the bithiophene benzobridged ligand having the structure shown in formula I and a solvent to perform a second coordination reaction to obtain an anion of Cl - A dithiophene benzo bridged binuclear ruthenium complex, wherein the cationic structure of the dithiophene benzo bridged binuclear ruthenium complex is shown in Formula II. In the present invention, the molar ratio of the precursor compound having the structure shown in Formula D to the dithiophene benzo bridged ligand having the structure shown in Formula I is preferably 2:1; the solvent is preferably an ethylene glycol solvent; the ethylene glycol; the temperature of the second coordination reaction is preferably 80-180 °C, more preferably 130-160 °C, the time of the coordination reaction is preferably 2-72h, more preferably 6-12h; the second coordination reaction is preferably carried out under argon protection.

[0097] In the present invention, the reaction formula for preparing the bithiophene benzo-bridged binuclear osmium complex is as follows: Figure 3 shown.

[0098] The present invention also provides a method for preparing the bithiophene benzobridged binuclear osmium complex described in the above scheme, comprising the following steps:

[0099] (i) mixing the auxiliary ligand L2, ammonium hexachloroosmate and an organic solvent to carry out a first coordination reaction to obtain a precursor compound having a structure shown in formula e;

[0100] Formula e;

[0101] (ii) mixing the precursor compound having the structure shown in formula e, the bithiophene benzobridge ligand having the structure shown in formula I and a solvent for a second coordination reaction to obtain an anion of Cl - A dithiophene benzo-bridged binuclear osmium complex, wherein the cationic structure of the dithiophene benzo-bridged binuclear osmium complex is shown in formula III.

[0102] The present invention mixes the auxiliary ligand L2, ammonium hexachloroosmate and an organic solvent to carry out a first coordination reaction to obtain a precursor compound having a structure shown in formula e. In the present invention, the molar ratio of the auxiliary ligand L2 and ammonium hexachloroosmate is preferably 2:1; the organic solvent for the coordination reaction is preferably ethylene glycol; the temperature of the coordination reaction is preferably 140 ° C, and the time is preferably 1.5 h; the first coordination reaction is preferably carried out under argon protection. After the reaction is completed, the present invention cools the obtained reaction solution to room temperature and adds a saturated aqueous solution of sodium dithionite, keeps it in an ice bath for 0.5 h, and then sequentially performs suction filtration, washing and vacuum drying to obtain a precursor compound having a structure shown in formula e [Os(L2) 2 Cl 2 ].

[0103] In the present invention, the precursor compound [Os(L2) 2 Cl 2 The chemical reaction formula is as follows Figure 4 shown.

[0104] After obtaining the precursor compound having the structure shown in formula e, the present invention mixes the precursor compound having the structure shown in formula e, the bithiophene benzobridged ligand having the structure shown in formula I and a solvent to perform a second coordination reaction to obtain an anion of Cl - A dithiophene benzo bridged binuclear osmium complex, the cationic structure of the dithiophene benzo bridged binuclear osmium complex is shown in formula III. In the present invention, the molar ratio of the precursor compound having the structure shown in formula e to the dithiophene benzo bridged ligand having the structure shown in formula I is preferably 2:1; the solvent is preferably an ethylene glycol solvent; the temperature of the second coordination reaction is preferably 80-180 °C, more preferably 130-160 °C, the time of the coordination reaction is preferably 2-72 h, more preferably 6-12 h; the second coordination reaction is preferably carried out under argon protection.

[0105] In the present invention, the reaction formula for preparing the bithiophene benzo-bridged binuclear osmium complex is as follows: Figure 5 shown.

[0106] The present invention also provides a method for preparing the bithiophene benzo-bridged binuclear iridium complex described in the above scheme, comprising the following steps:

[0107] (i) mixing the auxiliary ligand L3, iridium chloride and an organic solvent to carry out a first coordination reaction to obtain a precursor compound having a structure shown in formula f;

[0108] Formula f;

[0109] (ii) mixing the precursor compound having the structure shown in formula f, the bithiophene benzobridge ligand having the structure shown in formula I and a solvent for a second coordination reaction to obtain an anion of Cl - A dithiophene benzo-bridged binuclear iridium complex, wherein the cationic structure of the dithiophene benzo-bridged binuclear iridium complex is shown in formula IV.

[0110] The present invention mixes the auxiliary ligand L3, iridium chloride and an organic solvent for a first coordination reaction to obtain a precursor compound having a structure shown in formula e. In the present invention, the molar ratio of the auxiliary ligand L3 and iridium chloride is preferably 2:1; the organic solvent for the coordination reaction is preferably ethylene glycol ethyl ether; the temperature of the coordination reaction is preferably 110 ° C, and the time is preferably 2d; the first coordination reaction is preferably carried out under argon protection. After the reaction is completed, the present invention cools the obtained reaction solution to room temperature, and then performs suction filtration, washing and vacuum drying in sequence to obtain a precursor compound having a structure shown in formula e [Ir 2 (L3) 4 (μ-Cl) 2 ].

[0111] In the present invention, the precursor compound [Ir 2 (L3) 4 (μ-Cl) 2 The chemical reaction formula is as follows Figure 6 shown.

[0112] After obtaining the precursor compound having the structure shown in formula e, the present invention mixes the precursor compound having the structure shown in formula e, the bithiophene benzobridged ligand having the structure shown in formula I and a solvent to perform a second coordination reaction to obtain an anion of Cl - The cation structure of the dithiophene benzo-bridged binuclear iridium complex is shown in Formula IV. In the present invention, the molar ratio of the precursor compound having the structure shown in Formula E to the dithiophene benzo-bridged ligand having the structure shown in Formula I is preferably 1:1; the solvent is preferably an ethylene glycol solvent; the temperature of the second coordination reaction is preferably 80-180 °C, more preferably 130-160 °C, the time of the coordination reaction is preferably 2-72 h, more preferably 6-12 h; the second coordination reaction is preferably carried out under argon protection.

[0113] In the present invention, the reaction formula for preparing the bithiophene benzo-bridged binuclear iridium complex is as follows: Figure 7 shown.

[0114] After the coordination reaction is completed, the post-treatment is directly performed to obtain the anion Cl - In a specific embodiment of the present invention, when the target product is a dithiophene benzo-bridged binuclear metal complex of other anions, it is also preferred to add an aqueous solution containing an anion compound to the obtained reaction solution, and the Cl in the dithiophene benzo-bridged binuclear metal complex is added to the dithiophene benzo-bridged binuclear metal complex. - Replacement, and then post-treatment; the anion in the aqueous solution containing anionic compounds is preferably PF 6 - or ClO 4 - In a specific embodiment of the present invention, the aqueous solution containing anionic compounds is preferably a saturated aqueous solution of ammonium hexafluorophosphate; after adding the aqueous solution containing anionic compounds, it is preferably left to stand for 0.5 h before post-treatment.

[0115] In the present invention, the post-treatment method is preferably: for the dithiophene benzo-bridged binuclear ruthenium complex, the dithiophene benzo-bridged binuclear osmium complex and the dithiophene benzo-bridged binuclear iridium complex, the obtained reaction solution is filtered, washed and vacuum dried in sequence to obtain a crude product, and the crude product is subjected to alumina column chromatography to obtain the corresponding dithiophene benzo-bridged binuclear ruthenium complex, dithiophene benzo-bridged binuclear osmium complex and dithiophene benzo-bridged binuclear iridium complex; in the present invention, the eluent for the alumina column chromatography is preferably a toluene-acetonitrile mixed solvent, and the volume ratio of toluene and acetonitrile in the toluene-acetonitrile mixed solvent is preferably 2:1~1:3.

[0116] The present invention also provides the use of the dithiophene benzo-bridged binuclear metal complex described in the above scheme in the preparation of infrared photodynamic therapy photosensitizers and photothermal agents for tumors. In the present invention, the tumor is preferably a non-small cell lung cancer tumor; the dithiophene benzo-bridged binuclear metal complex provided by the present invention not only has excellent two-photon absorption properties and excellent singlet oxygen yield, but also exhibits high phototoxicity and low dark toxicity to non-small cell lung cancer cells, and is a potential new type of two-photon infrared photodynamic photosensitizer. At the same time, the dithiophene benzo-bridged binuclear metal complex provided by the present invention also has excellent photothermal conversion efficiency under infrared excitation light, and is a potential new type of infrared photothermal agent.

[0117] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0118] Example 1

[0119] The preparation of the bithiophene benzobridged ligand dtdpip is as follows:

[0120] (1) Weigh 4 g (22.2 mmol) of 1,10-phenanthroline and 4 g (33.6 mmol) of potassium bromide in a double-necked flask and stir evenly. Place the reaction mixture in an ice-water bath and gradually add 60 ml of a cooled mixed solution of concentrated sulfuric acid and concentrated nitric acid in a volume ratio of 2:1 using a constant pressure funnel. After the solution is added, remove the ice-water bath, reflux in an oil bath at 85 °C for 6 h, remove the condenser, and release bromine gas for 12 h. Then pour the reaction mixture into a 200 ml ice-water bath and adjust the pH to 5-6 with 10 M sodium hydroxide. The solution turns yellow and a yellow solid precipitates. Extract with 100 ml of chloroform three times to obtain a needle-shaped product with a mass of 3.57 g and a yield of 75%.

[0121] (2) Weigh 0.369 g (1.5 mmol) of benzo-1,2-b:4,5-b'-dithiophene-2,6-dicarboxaldehyde, 4.62 g (60 mmol) of ammonium acetate, and 50 ml of glacial acetic acid in a flask, add reflux in an oil bath at 110 °C for 4 h, add 0.63 g (3 mmol) of o-phenanthroline-5,6-dione, and continue heating and reflux for 8 h. Filter while hot, add a small amount of acetic acid to wash, wash with a large amount of water, wash with a small amount of ethanol, and dry overnight. A yellow solid is obtained, which is the conjugated bithiophene ligand dtdpip, with a yield of 0.858 g and a yield of 91%.

[0122] Example 2

[0123] Precursor compound [Ru(bpy) 2 Cl 2 ] Synthesis method:

[0124] Weigh 1.56 g (6 mmol) of ruthenium trichloride, 1.87 g (12 mmol) of auxiliary ligand bpy (2,2'-bipyridine), and 1.68 g (28 mmol) of lithium chloride into a two-necked flask, add 20 mL of N,N'-dimethylformamide, heat and reflux at 140 °C under argon for 8 h, let it cool to room temperature, add 50 mL of acetone, freeze overnight, filter, wash, and vacuum dry to obtain a purple-black solid, which is the precursor compound [Ru(bpy) 2 Cl 2 ], yield: 1.12 g, yield rate: 39%.

[0125] The auxiliary ligand bpy in the above scheme was replaced by tbubpy (4,4'-di-tert-butyl-2,2'-bipyridine) and dip (4,7-diphenyl-1,10-phenanthroline), respectively, and the other conditions were the same as the above scheme to obtain the precursor compounds [Ru(tbubpy) 2 Cl 2 ]、[Ru(dip) 2 Cl 2 ].

[0126] Example 3

[0127] Synthesis method of bithiophene benzo-bridged binuclear ruthenium complex Ru1:

[0128] Weigh 0.063 g (0.10 mmol) of the ligand dtdpip and the precursor [Ru(bpy) 2 Cl 2 ] 0.104 g (0.20 mmol) was placed in a two-necked flask, 10 mL of ethylene glycol was added, and the mixture was stirred and refluxed at 150 °C under argon for more than 12 h. After cooling to room temperature, 12 mL of water and a saturated aqueous solution of ammonium hexafluorophosphate were added, and the mixture was allowed to stand for 0.5 h. The mixture was filtered, washed, and dried in vacuo. The resulting black crude product was chromatographed on an alumina column with toluene:acetonitrile (1:2, v:v) as the eluent, and the dark red component was collected to obtain the bithiophene benzo-bridged binuclear ruthenium complex Ru1 with a yield of 0.092 g and a yield of 63%. 1 H NMR (400 MHz, DMSO-d 6) δ 14.73(s, 2H), 9.04 (s, 4H), 8.88 (dd, J = 15.1, 8.2 Hz, 8H), 8.63 (s, 3H), 8.36(s, 2H), 8.27 – 8.19 (m, 4H), 8.12 (t, J = 7.9 Hz, 6H), 7.87 (d, J = 5.5 Hz, 9H), 7.60 (d, J = 13.4 Hz, 8H), 7.37 (t, J = 6.6 Hz, 4H). HR-MS (MeOH, m / z):Calcd for C 76 H 50 N 16 Ru 2 S 2 [M−4PF 6 ] 4+ :363.2981; Found: 363.2985.

[0129] Synthesis method of bithiophene benzo-bridged binuclear ruthenium complex Ru2:

[0130] The preparation steps are the same as Ru1, except that the precursor [Ru(bpy) 2 Cl 2 ] is replaced by [Ru(tbubpy) 2 Cl 2 ] 0.142 g (0.20 mmol), the other steps and operating conditions remained unchanged, the Ru2 yield was 0.126 g, and the yield was 65%. 1 HNMR (400 MHz, DMSO-d 6 ) δ 9.07 (d, J = 7.8 Hz, 4H), 8.91 (s, 4H), 8.87 (s,4H), 8.74 (s, 2H), 8.41 (s, 2H), 7.96 (d, J = 15.6 Hz, 8H), 7.68 (d, J = 6.0Hz, 4H), 7.63 (d, J = 6.1 Hz, 4H), 7.50 (d, J = 6.1 Hz, 4H), 7.36 (d, J = 4.3Hz, 4H), 1.44 (s, 36H), 1.35 (s, 36H). HR-MS (MeOH, m / z): Calcd forC 108 H 114 N 16 Ru 2 S 2 [M−4PF6 ] 4+ : 475.6741; Found: 475.6729.

[0131] Synthesis method of bithiophene benzo-bridged binuclear ruthenium complex Ru3:

[0132] The preparation steps are the same as Ru1, except that the precursor [Ru(bpy) 2 Cl 2 ] is replaced by [Ru(dip) 2 Cl 2 ]0.175 g (0.20 mmol), the other steps and operating conditions remained unchanged, the Ru3 yield was 0.156 g, and the yield was 71%. 1 H NMR(400 MHz, Chloroform-d) δ 9.04 (s, 4H), 8.38 (d, J = 5.4 Hz, 4H), 8.30 (s,8H), 8.24 (d, J = 5.4 Hz, 4H), 7.82 (dd, J = 11.5, 5.5 Hz, 8H), HR-MS (MeOH, m / z): Calcd forC 132 H 82 N 16 Ru 2 S 2 [M−4PF 6 ] 4+ : 539.6115; Found: 539.6109.

[0133] Example 4

[0134] Precursor compound [Os(bpy) 2 Cl 2 ] Synthesis method:

[0135] Weigh 0.220 g (0.50 mmol) of ammonium hexachloroosmate and 0.172 g (1.10 mmol) of auxiliary ligand bpy (2,2'-bipyridine) into a two-necked flask, add 10 mL of ethylene glycol, reflux at 120 °C for 1 h under argon, cool to room temperature, add 10 mL of a saturated aqueous solution of sodium dithionite, keep in an ice bath for 0.5 h, filter, wash, and vacuum dry to obtain a purple-black solid, which is the precursor compound [Os(bpy) 2 Cl 2 ], yield 0.236 g, yield rate: 77%.

[0136] The auxiliary ligand bpy in the above scheme was replaced by tbubpy (4,4'-di-tert-butyl-2,2'-bipyridine) and dip (4,7-diphenyl-1,10-phenanthroline), respectively, and the other conditions were the same as the above scheme to obtain the precursor compounds [Os(tbubpy) 2 Cl 2 ]、[Os(dip) 2 Cl 2 ].

[0137] Example 5

[0138] Synthesis of dithiophene benzobridged binuclear osmium complex Os1:

[0139] Weigh 0.063 g (0.10 mmol) of the ligand dtdpip and the precursor [Os(bpy) 2 Cl 2 ] 0.115 g (0.20 mmol) was placed in a two-necked flask, 10 mL of ethylene glycol was added, and the mixture was stirred and refluxed at 150 ºC under argon for more than 24 h. After cooling to room temperature, 12 mL of water and a saturated aqueous solution of ammonium hexafluorophosphate were added, and the mixture was allowed to stand for 0.5 h. The mixture was filtered, washed, and dried in vacuo. The dark green crude product was chromatographed on an alumina column with toluene:acetonitrile (1:1, v:v) as the eluent, and the dark green component was collected to obtain the bithiophene-bridged binuclear osmium complex Os1 with a yield of 0.089 g and a yield of 55%. 1 H NMR (400 MHz, DMSO-d 6) δ 14.89 (s,2H), 10.20 (s, 1H), 8.89 (s, 4H), 8.87 (s, 3H), 8.85 (s, 3H), 8.84 (s, 3H),8.55 (s, 2H), 8.07 – 7.99 (m, 7H), 7.90 (d, J = 8.0 Hz, 7H), 7.79 – 7.76 (m,4H), 7.51 (d, J = 5.3 Hz, 9H), 7.26 (s, 5H). HR-MS (MeOH, m / z): Calcd for:C 76 H 50 N 16 Os 2 S 2 [M−4PF 6 ] 4+ : 408.5763; Found: 408.5764.

[0140] Synthesis of dithiophene benzobridged binuclear osmium complex Os2:

[0141] The preparation steps are the same as those of Os1, except that the precursor [Os(bpy) 2 Cl 2 ] is replaced by [Os(tbubpy) 2 Cl 2 ] 0.160 g (0.20 mmol), the other steps and operations remained unchanged, the yield of Os2 was 0.143 g, and the yield was 68%. 1 H NMR (400MHz, DMSO-d 6 ) δ 14.96 (s, 2H), 8.87 (s, 4H), 8.83 (s, 4H), 8.76 (s, 3H), 8.51(s, 3H), 7.76 (d, J = 33.5 Hz, 11H), 7.61 (d, J = 5.5 Hz, 4H), 7.54 (d, J =5.2 Hz, 4H), 7.37 (d, J = 6.3 Hz, 4H), 7.28 (d, J = 5.2 Hz, 3H), 1.43 (s,36H), 1.34 (s, 36H). HR-MS (MeOH, m / z): Calcd for: C 108 H 114 N 16 Os 2 S 2 [M−4PF 6 ]4+ :520.2008; Found: 520.2034.

[0142] Synthesis of dithiophene benzobridged binuclear osmium complex Os3:

[0143] The preparation steps are the same as those of complex Os1, except that the precursor [Os(bpy) 2 Cl 2 ] is replaced by [Os(dip) 2 Cl 2 ] 0.185 g (0.19 mmol), the other steps and operations remained unchanged, the yield of Os3 was 0.177 g, and the yield was 75%. 1 H NMR (400MHz, DMSO-d 6 ) δ 8.83 (s, 4H), 8.50 (s, 4H), 8.29 (s, 12H), 8.14 (d, J = 5.7Hz, 6H), 7.93 (s, 6H), 7.74 (d, J = 5.8 Hz, 8H), 7.73 – 7.70 (m, 6H), 7.69(d, J = 1.9 Hz, 8H), 7.66 (d, J = 6.8 Hz, 12H), 7.65 – 7.54 (m, 14H). HR-MS(MeOH, m / z): Calcd for: C 132 H 82 N 16 Os 2 S 2 [M−4PF 6 ] 4+ : 584.6399; Found: 584.6380.

[0144] Example 6

[0145] Precursor compounds [Ir 2 (ppy) 4 (μ-Cl) 2 ] Synthesis method:

[0146] Weigh 0.597 g (2.0 mmol) of iridium chloride and 0.775 g (5.0 mmol) of auxiliary ligand ppy (2-phenylpyridine) into a two-necked flask, add 45 mL of ethylene glycol ether and 15 mL of water, reflux at 110 °C for 48 h under argon, cool to room temperature, filter, wash, and vacuum dry to obtain a yellow solid, which is the precursor compound [Ir 2 (ppy) 4 (μ-Cl)2 ].

[0147] The auxiliary ligand ppy in the above scheme was replaced by Fppy (2-(2,4-difluorophenyl)pyridine), pq (2-phenylquinoline), and piq (2-phenylisoquinoline), and the other conditions were the same as the above scheme to obtain the precursor compound [Ir 2 (Fppy) 4 (μ-Cl) 2 ]、[Ir 2 (pq) 4 (μ-Cl) 2 ] and [Ir 2 (piq) 4 (μ-Cl) 2 ].

[0148] Example 7

[0149] Synthesis method of bithiophene benzo-bridged binuclear iridium complex Ir1:

[0150] Weigh 0.063 g (0.10 mmol) of the ligand dtdpip and the precursor [Ir 2 (ppy) 4 (μ-Cl) 2 ] 0.129 g (0.10 mmol) was placed in a two-necked flask, 10 mL of ethylene glycol was added, and the mixture was stirred and refluxed at 150 ºC under argon for more than 24 h. After cooling to room temperature, 12 mL of water and a saturated aqueous solution of ammonium hexafluorophosphate were added, and the mixture was allowed to stand for 0.5 h. The mixture was filtered, washed, and dried in vacuo. The obtained orange crude product was chromatographed on an alumina column with toluene:acetonitrile (1:1, v:v) as the eluent, and the orange-yellow component was collected to obtain bithiophene benzo-bridged binuclear iridium Ir1 with a yield of 0.109 g and a yield of 67%. 1 H NMR (400 MHz, DMSO-d 6 ) δ 9.06 (t, J =8.9 Hz, 4H), 8.64 (s, 2H), 8.33 – 8.24 (m, 6H), 8.13 (d, J = 4.7 Hz, 4H), 7.99 (d, J = 7.8 Hz, 8H), 7.90 (t, J = 7.7 Hz, 4H), 7.57 (s, 4H), 7.07 (q, J= 7.3 Hz, 8H), 6.98 (t, J = 7.5 Hz, 4H), 6.33 (d, J = 7.2 Hz, 4H). HR-MS(MeOH, m / z): Calcd for: C 80 H 50 Ir2 N 12 S 2 [M−2PF 6 ] 2+ : 814.1485; Found: 814.1489.

[0151] Synthesis method of bithiophene benzo-bridged binuclear iridium complex Ir2:

[0152] The preparation steps are the same as those of Ir1, except that the precursor [Ir 2 (ppy) 4 (μ-Cl) 2 ] is replaced by [Ir 2 (Fppy) 4 (μ-Cl) 2 ] 0.123 g (0.10 mmol), the other steps and operations remained unchanged, the yield of Ir2 was 0.136 g, and the yield was 78%. 1 H NMR (400 MHz, DMSO-d 6 ) δ 9.16 (d, J = 8.2 Hz, 4H), 8.62 (s, 2H), 8.32 (d, J = 9.1Hz, 4H), 8.24 (s, 2H), 8.15 (s, 4H), 7.99 (t, J = 8.4 Hz, 8H), 7.58 (d, J =5.4 Hz, 4H), 7.13 – 7.08 (m, 4H), 7.06 (d, J = 2.4 Hz, 1H), 7.03 (t, J = 2.8Hz, 2H), 7.01 (d, J = 2.4 Hz, 1H), 5.74 (dd, J = 8.3, 2.4 Hz, 4H). HR-MS(MeOH, m / z): Calcd for: C 80 H 42 F 8 Ir 2 N 12 S 2 [M−2PF 6 ] 2+ : 886.1109; Found: 886.1107.

[0153] Synthesis method of bithiophene benzo-bridged binuclear iridium complex Ir3:

[0154] The preparation steps are the same as those of Ir1, except that the precursor [Ir 2 (ppy) 4 (μ-Cl)2 ] is replaced by [Ir 2 (pq) 4 (μ-Cl) 2 ]0.127 g (0.20 mmol), the other steps and operations remained unchanged, the yield of Ir3 was 0.139 g, and the yield was 74%. 1 H NMR (400 MHz, DMSO-d 6 ) δ 9.02 (d, J = 8.2 Hz, 4H), 8.74 (s, 2H), 8.64 (s, 2H), 8.62 (s, 2H), 8.54 (s, 2H), 8.51 (s, 2H), 8.45 (d, J = 5.1 Hz, 4H), 8.39 (s,2H), 8.37 (s, 2H), 8.26 (s, 2H), 8.14 – 8.08 (m, 4H), 7.84 (s, 2H), 7.82 (s,2H), 7.27 (s, 1H), 7.25 (s, 3H), 7.23 (s, 3H), 7.21 (s, 1H), 7.19 (s, 2H),7.17 (s, 2H), 6.91 (s, 1H), 6.89 (s, 3H), 6.87 (d, J = 3.6 Hz, 3H), 6.84 (s,1H), 6.54 (s, 2H), 6.52 (s, 2H). HR-MS (MeOH, m / z): Calcd for: C 96 H 58 Ir 2 N 12 S 2 [M−2PF 6 ] 2+ : 914.6815; Found: 914.6808.

[0155] Synthesis method of bithiophene benzo-bridged binuclear iridium complex Ir4:

[0156] The preparation steps are the same as those of Ir1, except that the precursor [Ir 2 (ppy) 4 (μ-Cl) 2 ] is replaced by [Ir 2 (piq) 4 (μ-Cl) 2 ]0.127 g (0.20 mmol), the other steps and operations remained unchanged, the yield of Ir3 was 0.136 g, and the yield was 73%. 1H NMR (400 MHz, DMSO-d 6 ) δ 9.12 (d, J = 5.6 Hz, 4H), 9.06 (s, 2H), 9.04 (s, 2H), 8.75 (s, 1H), 8.45 (s, 2H), 8.43 (s, 2H), 8.35 (s, 2H), 8.05 (d, J = 9.3 Hz,12H), 7.94 – 7.86 (m, 10H), 7.49 (d, J = 6.6 Hz, 4H), 7.45 (d, J = 6.5 Hz,4H), 7.22 (s, 1H), 7.20 (s, 2H), 7.18 (s, 1H), 7.01 (s, 1H), 6.99 (s, 2H),6.97 (s, 1H), 6.34 (s, 1H), 6.32 (s, 2H). HR-MS (MeOH, m / z): Calcd for:C 96 H 58 Ir 2 N 12 S 2 [M−2PF 6 ] 2+ : 913.1787; Found: 913.1778.

[0157] Example 8

[0158] Singlet oxygen generation properties of dithiophene benzo-bridged binuclear metal complexes:

[0159] ABDA (9,10-anthracenediyl-bis(methylene)dimalonic acid) was used as singlet oxygen ( 1 O 2 ) scavenger, and the absorption spectrum changes of ABDA solution containing bithiophene benzo-bridged binuclear metal complexes (Ru1-3, Os1-3 and Ir1-4) were measured by UV / visible spectrophotometer to study the singlet oxygen generation efficiency of the complex. In the presence of bithiophene benzo-bridged binuclear metal complexes, the UV absorption change spectrum of the singlet oxygen scavenger ABDA in the solution after excitation at 450 nm, 808 nm, US and 808 nm+US is shown in the figure below. Figure 8-11 shown.

[0160] When measuring the singlet oxygen yield, the complex solution was prepared with pure water. The complex concentration was 10 μM and the ABDA concentration R was 100 μM. The [Ru(bpy) 3 ] 2+ and [Os(bpy)3 ] 2+ As a comparison, the singlet oxygen yields were obtained by linear fitting. Under 450 nm, 808 nm, US and 808 nm+US excitation, the singlet oxygen generation rates of the bithiophene benzo-bridged binuclear metal complexes (Ru1-3, Os1-3 and Ir1-4) were all higher than those of the control complex [Ru(bpy) 3 ] 2+ The singlet oxygen yields of the complexes Ru2 and Ru3 under 808 nm+US excitation reached [Ru(bpy) 3 ] 2+ The results show that the ruthenium complex provided by the present invention has an excellent ability to induce the production of singlet oxygen under infrared light excitation.

[0161] Example 9

[0162] Infrared photothermal conversion capability of dithiophene benzo-bridged binuclear metal complexes:

[0163] Using PBS buffer containing 10% DMSO as a control, 808 nm infrared light was used to illuminate 10 μM, 50 μM and 100 μM dithiophene benzobridged binuclear metal complexes (Ru1-3, Os1-3 and Ir1-4, all solvents were PBS buffer containing 10% DMSO), and thermal imaging of the solution was performed from 0 to 10 minutes (once every one minute) ( Figure 12-14 ), and calculated the heat Q generated and the photothermal conversion efficiency η of the bithiophene benzo-bridged binuclear metal complex.

[0164] according to Figure 12-14 The recorded temperature data shows that compared with the control group PBS, the bithiophene benzo-bridged binuclear metal complex of the present invention generates a certain amount of heat under 808 nm illumination. The photothermal conversion efficiency PCE of Os2 under 808 nm illumination is the largest, reaching 16.2%. The above results show that the bithiophene benzo-bridged binuclear metal complex provided by the present invention has excellent infrared photothermal conversion capability at 808 nm.

Claims

1. A bithiophene benzo-bridged ligand, characterized in that: The structural formula is shown in Formula I: Formula I.

2. The method for preparing the bithiophene benzo-bridged ligand according to claim 1, characterized in that: The following steps are involved: (i) mixing a compound having a structure represented by formula a, potassium bromide and an organic acid to react to obtain a compound having a structure represented by formula b; Formula a; Formula b; (ii) mixing the compound having the structure shown in formula b, the compound having the structure shown in formula c and an organic solvent for condensation reaction to obtain a bithiophene benzobridged ligand having the structure shown in formula I. Formula c.

3. The preparation method according to claim 2, characterized in that: The reaction temperature in step (i) is 60-80 °C and the reaction time is 6-8 h; The condensation reaction temperature in step (ii) is 100-120 °C and the reaction time is 1-10 h.

4. A bithiophene benzo-bridged binuclear metal complex consisting of anions and cations, characterized in that: The structural formulas of the cations are shown in Formula II, Formula III and Formula IV: Formula II; In Formula II, represents an auxiliary ligand L1, wherein the auxiliary ligand L1 is any one of the ligands of the following structures: , , . Formula III; In formula III, represents an auxiliary ligand L2, wherein the auxiliary ligand L2 is any one of the ligands of the following structures: , , . Formula IV; In Formula IV, represents an auxiliary ligand L3, wherein the auxiliary ligand L3 is any one of the ligands of the following structures: 、 、 、 。 5. The method for preparing the bithiophene benzo-bridged binuclear ruthenium complex according to claim 4, characterized in that: The following steps are involved: (i) mixing the auxiliary ligand L1, ruthenium trichloride, lithium chloride and an organic solvent to carry out a first coordination reaction to obtain a precursor compound having a structure shown in formula d; Formula d; (ii) mixing the precursor compound having the structure shown in formula d, the bithiophene benzobridge ligand dtdpip and a solvent for a second coordination reaction to obtain an anion (PF6) - A dithiophene benzo-bridged binuclear ruthenium complex, wherein the cationic structure of the dithiophene benzo-bridged binuclear ruthenium complex is shown in Formula II.

6. The method for preparing the bithiophene benzo-bridged binuclear osmium complex according to claim 4, characterized in that: The following steps are involved: (i) mixing the auxiliary ligand L2, ammonium hexachloroosmate and an organic solvent to carry out a first coordination reaction to obtain a precursor compound having a structure shown in formula e; Formula e; (ii) mixing the precursor compound having the structure shown in formula e, the bithiophene benzobridge ligand dtdpip and a solvent for a second coordination reaction to obtain an anion (PF6) - A dithiophene benzo-bridged binuclear osmium complex, wherein the cationic structure of the dithiophene benzo-bridged binuclear osmium complex is shown in formula III.

7. The method for preparing the co-bithiophene benzo-bridged binuclear iridium complex according to claim 4, characterized in that: The following steps are involved: (i) mixing the auxiliary ligand L3, iridium chloride and an organic solvent to carry out a first coordination reaction to obtain a precursor compound having a structure shown in formula f; Formula f; (ii) mixing the precursor compound having the structure shown in formula f, the bithiophene benzobridge ligand dtdpip and a solvent for a second coordination reaction to obtain an anion (PF6) - A dithiophene benzo-bridged binuclear iridium complex, wherein the cationic structure of the dithiophene benzo-bridged binuclear iridium complex is shown in formula IV.

8. Use of the bithiophene benzo-bridged binuclear metal complex according to claim 4 in the preparation of photosensitizers, sonosensitizers, and photothermal agents in tumor photodynamic therapy.

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