A bithiophene benzo-bridged ligand and a preparation method thereof, and a bithiophene benzo-bridged dinuclear metal complex and a preparation method and application thereof

Abstract

The present application relates to the development of a photosensitizer for photodynamic therapy of tumors, a sonosensitizer for sonodynamic therapy, and a photothermal reagent for photothermal therapy, and provides a bithiophene-benzene bridged ligand and a preparation method thereof, and a bithiophene-benzene bridged dinuclear metal complex and a preparation method and application thereof. The present application is based on a bithiophene-benzene bridged ligand dtdpip, and a bithiophene-benzene bridged dinuclear ruthenium complex, a bithiophene-benzene bridged dinuclear osmium complex and a bithiophene-benzene bridged dinuclear iridium complex are respectively designed and invented. The bithiophene-benzene bridged dinuclear metal complex has extremely high stability and excellent two-photon absorption characteristics, and has excellent biological toxicity and photothermal conversion capacity under the action of infrared excitation light and ultrasonic waves. The conjugated bithiophene dinuclear metal complex provided by the present application is a potential new type of infrared photodynamic photosensitizer, sonosensitizer and photothermal reagent, and has a broad application prospect in the photodynamic therapy, sonodynamic therapy and photothermal therapy of tumors.

Description

Technical Field

[0001] This invention relates to the fields of photosensitizers for tumor photodynamic therapy, photothermal reagents for photothermal therapy, and sonodynamic therapy, and particularly to a bisthiophene benzo-bridged ligand and its preparation method, as well as a bisthiophene benzo-bridged binuclear metal complex and its preparation method and application. Background Technology

[0002] Photodynamic therapy (PDT) is a novel cancer treatment method that emerged more than 40 years ago. It utilizes a photosensitizer (PS) to react with molecular oxygen in tissues, producing reactive oxygen species (ROS), such as singlet oxygen. 1 O2) and superoxide anion (O2) - Reactive oxygen species (ROS) damage tumor cells through oxidative reactions, acting on subcellular structures and biomolecules (such as proteins and nucleic acids) to achieve therapeutic goals. In practical applications, phototherapy with targeted drug delivery (PDT) typically involves intravenous administration of the drug, along with the application of light at wavelengths capable of penetrating tissues for precise, non-invasive treatment of the tumor. Compared to traditional cancer therapies, PDT offers the advantage of precise and effective treatment with minimal side effects, thus attracting widespread attention and research.

[0003] Photothermal therapy (PTT) is an emerging non-invasive method for treating localized tumors. This method uses near-infrared (NIR) light to excite photothermal conversion agents (PTAs) to generate heat, altering the tumor's physiological environment and ablating tumor cells. It has typical advantages such as minimal invasiveness to normal tissues, reduced side effects, and strong anti-tumor capabilities. To achieve better PTT treatment results and effectively inhibit tumor growth after NIR irradiation, adjustments can be made by reducing tissue scattering and absorption, and by enhancing the photothermal conversion effect of the light absorber.

[0004] Sonodynamic therapy (SDT) is a new non-invasive anti-tumor treatment method, which can activate the sonosensitizers accumulated in the tumor area by ultrasonic (US) to produce ROS and kill tumor cells. SDT has the characteristics of strong penetration depth and small side effects. In addition, according to the different use frequencies, US can accurately aim at the lesion site and activate the sonosensitizers, so as to achieve pathological apoptosis without damaging the adjacent normal tissues. SDT has the integration effect with other tumor treatment methods such as PDT, PTT and chemotherapy, and generally has a synergistic effect between mechanisms, which is expected to realize the low-dose and high-efficiency treatment of tumors in the future.

[0005] At present, the preferred drug for treating cancer in clinic is still the transition metal platinum compound, such as cisplatin, carboplatin, oxaliplatin, etc., but the application of this series of drugs in clinic has the defects of side effects and drug resistance, which limits the application prospect of transition metal platinum compound as an anti-tumor drug. Therefore, it is urgent to design some new anti-tumor drugs with low toxicity and high efficiency. In the field of transition metal compounds, ruthenium, osmium, iridium and other transition metal compounds have attracted great attention as potential anticancer agents. In addition, thiophene is used to design and synthesize transition metal compounds with specific optical physical properties, and it is found that the effect of in vitro photodynamic therapy of this series of compounds will be enhanced with the increase of thiophene in the structure of the compound.

[0006] Therefore, based on the bithiophene benzobridged ligand dtdpip, a bithiophene benzobridged binuclear metal complex is invented. The 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 reagent. SUMMARY

[0007] Therefore, the present application provides a bithiophene benzobridged ligand and a preparation method thereof, and a bithiophene benzobridged binuclear metal complex and a preparation method and application thereof. The present application provides a brand new bithiophene benzobridged ligand, and a bithiophene benzobridged binuclear metal complex is invented based on the ligand. The complex has excellent singlet oxygen yield, biological toxicity and photothermal conversion ability, and has a broad application prospect in the preparation of tumor two-photon infrared photodynamic photosensitizer and photothermal reagent.

[0008] In order to achieve the above-mentioned application purposes, the present application provides the following technical solutions:

[0009] A bithiophene benzobridged ligand, the structural formula is as shown in formula I:

[0010] Formula I;

[0011] A bithiophene benzo-bridged dinuclear metal complex, consisting of an anion and a cation, the structure of the cation is shown as Formula II, Formula III and Formula IV:

[0012] Formula II;

[0013] In Formula II, represents an auxiliary ligand L1, which is any one of the following structure of ligand:

[0014] , , .

[0015] Formula III;

[0016] In Formula II, represents an auxiliary ligand L2, which is any one of the following structure of ligand:

[0017] , , .

[0018] Formula IV;

[0019] In Formula IV, represents an auxiliary ligand L3, which is any one of the following structure of ligand:

[0020] , , , .

[0021] The application also provides a preparation method of the bithiophene benzo-bridged dinuclear ruthenium complex described in the above scheme, comprising the following steps:

[0022] (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 the structure shown in Formula d;

[0023] Formula d;

[0024] (ii) mixing the precursor compound having the structure shown in Formula d, a bithiophene benzo-bridged ligand dtdpip and a solvent to carry out a second coordination reaction, to obtain a bithiophene benzo-bridged dinuclear ruthenium complex with the anion Cl -A dithiophene benzobridged dinuclear osmium complex, a cationic structure of the dithiophene benzobridged dinuclear osmium complex is shown as formula III.

[0025] Preferably, the molar ratio of the auxiliary ligand L1 and ruthenium trichloride is 2:1; the molar ratio of the precursor compound with the structure shown in formula d and the dithiophene benzobridged ligand dtdpip is 2:1.

[0026] Preferably, the solvent in the step (ii) is an ethylene glycol solvent.

[0027] Preferably, the temperature of the second coordination reaction in the step (ii) is 120-160 °C, and the time is 6-24 h.

[0028] Preferably, after the second coordination reaction is completed in the step (ii), the method further comprises adding an aqueous solution containing an anion compound to the obtained reaction solution, and replacing Cl - in the dithiophene benzobridged dinuclear osmium complex with Cl

[0029] The application also provides a preparation method of the dithiophene benzobridged dinuclear osmium complex.

[0030] (i) mixing the auxiliary ligand L2, ammonium hexachloroosmate and an organic solvent to perform a first coordination reaction, to obtain a precursor compound with the structure shown in formula e;

[0031] formula e;

[0032] (ii) mixing the precursor compound with the structure shown in formula e, the dithiophene benzobridged ligand dtdpip and a solvent to perform a second coordination reaction, to obtain a dithiophene benzobridged dinuclear osmium complex with Cl - in the anion, a cationic structure of the dithiophene benzobridged dinuclear osmium complex is shown as formula III.

[0033] Preferably, the molar ratio of the auxiliary ligand L2 and ammonium hexachloroosmate is 2:1; the molar ratio of the precursor compound with the structure shown in formula e and the dithiophene benzobridged ligand dtdpip is 2:1.

[0034] Preferably, the solvent in the step (ii) is an ethylene glycol solvent.

[0035] Preferably, the temperature of the second coordination reaction in the step (ii) is 120-160 °C, and the time is 6-24 h.

[0036] Preferably, after the second coordination reaction is completed in the step (ii), the method further comprises adding an aqueous solution containing an anion compound to the obtained reaction solution, and replacing Cl- substituted.

[0037] The application further provides a preparation method of the bithiophene-benzene bridged dinuclear iridium complex as described in the above scheme, comprising the following steps:

[0038] (i) mixing an auxiliary ligand L3, iridium chloride and an organic solvent to perform a first coordination reaction to obtain a precursor compound having a structure shown in formula VI;

[0039] formula f;

[0040] (ii) mixing the precursor compound having a structure shown in formula f, a bithiophene-benzene bridged ligand dtdpip and a solvent to perform a second coordination reaction to obtain a bithiophene-benzene bridged dinuclear iridium complex with Cl - - as an anion, wherein a cation structure of the bithiophene-benzene bridged dinuclear iridium complex is shown in formula IV.

[0041] Preferably, a molar ratio of the auxiliary ligand L3 and iridium chloride is 2:1; and a molar ratio of the precursor compound having a structure shown in formula f and the bithiophene-benzene bridged ligand dtdpip is 1:1.

[0042] Preferably, the solvent in the step (ii) is an ethylene glycol solvent.

[0043] Preferably, a temperature of the second coordination reaction in the step (ii) is 120-160 °C, and a time is 6-24 h.

[0044] Preferably, after the second coordination reaction in the step (ii) is completed, the method further comprises adding an aqueous solution containing an anion compound to the obtained reaction solution to replace Cl - - in the bithiophene-benzene bridged dinuclear metal complex.

[0045] The application further provides an application of the bithiophene-benzene bridged dinuclear metal complex as described in the above scheme in preparation of a photosensitizer and a photothermal reagent for tumor photodynamic therapy.

[0046] The application also provides a bithiophene benzo-bridged dinuclear metal complex, which is composed of an anion and a cation, and the cation has the structures shown in formula II, formula III and formula IV.

[0047] The application further provides a preparation method of the bithiophene benzo-bridged dinuclear metal complex, and the preparation method provided by the application is simple in steps and easy for industrial production. BRIEF DESCRIPTION OF DRAWINGS

[0048] Figure 1 It is a synthesis route map of the bithiophene benzo-bridged ligand dtdpip;

[0049] Figure 2 It is a reaction formula for synthesizing the precursor compound [Ru(L)2Cl2];

[0050] Figure 3 It is a reaction formula for synthesizing the bithiophene benzo-bridged dinuclear ruthenium complex;

[0051] Figure 4 It is a reaction formula for synthesizing the precursor compound [Os(L)2Cl2];

[0052] Figure 5 It is a reaction formula for synthesizing the bithiophene benzo-bridged dinuclear osmium complex;

[0053] Figure 6 It is a reaction formula for synthesizing the precursor compound [Ir2(L)4(mu-Cl)2];

[0054] Figure 7 It is a reaction formula for synthesizing the bithiophene benzo-bridged dinuclear iridium complex;

[0055] Figure 8 It is a UV absorption change diagram of the singlet oxygen trapping agent ABDA in a solution after irradiation by 450 nm light in the presence of the bithiophene benzo-bridged dinuclear metal complex;

[0056] Figure 9The UV absorption change graph of singlet oxygen trapping agent ABDA in the solution after laser irradiation of 808 nm in the presence of the double thiophene benzene bridged dinuclear metal complex;

[0057] Figure 10 The UV absorption change graph of singlet oxygen trapping agent ABDA in the solution after laser irradiation of 808 nm in the presence of the double thiophene benzene bridged dinuclear metal complex;

[0058] Figure 11 The UV absorption change graph of singlet oxygen trapping agent ABDA in the solution after laser irradiation of 808 nm+US in the presence of the double thiophene benzene bridged dinuclear metal complex;

[0059] Figure 12 The photothermal conversion graph of 10 μM double thiophene benzene bridged dinuclear metal complex prepared by the application and the control group PBS under 808 nm light irradiation for different time;

[0060] Figure 13 The photothermal conversion graph of 50 μM double thiophene benzene bridged dinuclear metal complex prepared by the application and the control group PBS under 808 nm infrared light irradiation for different time;

[0061] Figure 14 The photothermal conversion graph of 100 μM double thiophene benzene bridged dinuclear metal complex prepared by the application and the control group PBS under 808 nm light irradiation for different time; DETAILED DESCRIPTION

[0062] The application provides a double thiophene benzene bridged ligand, characterized in that the structural formula is shown in formula I.

[0063] Formula I.

[0064] The application further provides a preparation method of the double thiophene benzene bridged ligand.

[0065] (1) a compound with the structure shown in formula a, potassium bromide and an organic acid solvent are mixed to react, so as to obtain a compound with the structure shown in formula b;

[0066] Formula a; Formula b;

[0067] (2) the compound with the structure shown in formula b, a compound with the structure shown in formula c and an organic solvent are mixed to carry out a condensation reaction, so as to obtain potassium bromide and an organic acid ligand with the structure shown in formula I.

[0068] Formula c.

[0069] In the present application, the synthesis route of the bithiophene benzo bridged ligand with the structure shown in formula I is as shown below Figure 1 which will be described in detail below. Figure 1

[0070] In the present application, the compound with the structure shown in formula a, potassium bromide and organic acid are mixed to react to obtain the compound with the structure shown in formula b. In the present application, the chemical name of the compound with the structure shown in formula b is 1,10-phenanthroline-5,6-dione.

[0071] In the present application, the synthesis method of the compound with the structure shown in formula b preferably comprises the following steps: 1,10-phenanthroline (structural formula is shown below Figure 1 ), potassium bromide is placed in an ice water bath and mixed with acid drop by drop, then heated to reflux in an oil bath, after the reaction is completed, the pH is adjusted with sodium hydroxide, a large amount of yellow solid is precipitated, and 1,10-phenanthroline-5,6-dione (formula b) is obtained. In the present application, 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 at 70~90 ℃, and the reaction time is preferably 6~10 h; in a specific embodiment of the present application, the reaction after heating to reflux is preferably placed open for 12 h to release bromine. After the reaction is completed, the present application preferably pours the reaction liquid into a 200 ml ice water bath, adjusts the pH to 5~6 with 10 M sodium hydroxide, the solution is yellow and a large amount of yellow solid is precipitated, then extracted with chloroform, and the collected organic phase is successively dried with anhydrous sodium sulfate, filtered, and evaporated under reduced pressure to obtain a crude product, which is recrystallized with anhydrous ethanol to obtain the compound with the structure shown in formula b.

[0072] After obtaining the compound with the structure shown in formula b, the compound with the structure shown in formula b, the compound with the structure shown in formula c (chemical name is benzo 1,2-b:4,5-b’ dithiophene-2,6-diformaldehyde), ammonium acetate and an organic solvent are mixed to react to obtain the compound with the structure shown in formula I. In the present application, the organic solvent used in the reaction is preferably glacial acetic acid; the molar ratio of the amount of the compound with the structure shown in formula b and the compound with 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 reaction temperature is preferably 100~120 °C, and the time is preferably 8~12 h; in a specific embodiment of the present application, the reaction is preferably carried out under reflux conditions. After the reaction is completed, the present application preferably cools the obtained reaction liquid to room temperature, and then successively performs suction filtration, water washing, ethanol washing, ether washing and drying to obtain the bithiophene benzo bridged ligand (denoted as dtdpip) with the structure shown in formula I ​

[0073] The present application also provides a bithiophene benzo bridged dinuclear metal complex, which is composed of an anion and a cation, and the structure of the cation is shown in formula II, formula III and formula IV:

[0074] Formula II;

[0075] In formula II, represents an auxiliary ligand L1, which is any one of the following ligands:

[0076] , , .

[0077] Formula III;

[0078] In formula II, represents an auxiliary ligand L2, which is any one of the following ligands:

[0079] , , .

[0080] Formula IV;

[0081] In formula IV, represents an auxiliary ligand L3, which is any one of the following ligands:

[0082] , , , .

[0083] In the present application, the chemical names of the above-mentioned auxiliary ligand L1 are 2,2'-bipyridine (bpy), 4,4'-di-tert-butyl-2,2'-bipyridine (tbubpy) and 4,7-diphenyl-1,10-phenanthroline (dip) in turn; the chemical names of the above-mentioned auxiliary ligand L2 are 2,2'-bipyridine (bpy), 4,4'-di-tert-butyl-2,2'-bipyridine (tbubpy) and 4,7-diphenyl-1,10-phenanthroline (dip) in turn; the chemical names of the above-mentioned auxiliary ligand L3 are 2-phenylpyridine (ppy), 2-(2,4-difluorophenyl)pyridine (Fppy), 2-phenylquinoline (pq) and 2-phenylisoquinoline (piq) in turn; the present application does not have special requirements for the source of the above-mentioned auxiliary ligand, and either commercially available ligands or ligands synthesized by methods well known to those skilled in the art can be used.

[0084] The present application does not have special requirements for the anion in the double thiophene benzobridged binuclear metal complex, and the anion in the prior art can achieve the purpose of the present application. In the specific embodiments of the present application, the anion is preferably an inorganic salt anion, more preferably PF6 - , CIO4 - , or CI - , most preferably PF6 - .

[0085] The present application also provides a preparation method of the double thiophene benzobridged binuclear ruthenium complex described in the above scheme, comprising the following steps:

[0086] (i) mixing the auxiliary ligand L1, ruthenium trichloride, lithium chloride and an organic solvent to perform a first coordination reaction to obtain a precursor compound having the structure shown in formula d;

[0087] Formula d;

[0088] (ii) mixing the precursor compound having the structure shown in formula d, the conjugated double thiophene ligand having the structure shown in formula I and a solvent to perform a second coordination reaction to obtain a double thiophene benzobridged binuclear ruthenium complex with Cl - as the anion, and the cation structure of the double thiophene benzobridged binuclear ruthenium complex is shown in formula II.

[0089] In the present application, the molar ratio of the auxiliary ligand L1 to ruthenium trichloride is preferably 2:1; the molar ratio of lithium chloride to ruthenium trichloride is preferably 14:3; the organic solvent used in 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; and the first coordination reaction is preferably performed under argon protection. After the reaction is completed, the present application cools the obtained reaction solution to room temperature, then adds acetone, and then freezes overnight, followed by sequential filtration, washing and vacuum drying to obtain the precursor compound [Ru(L1)2Cl2] having the structure shown in formula d.

[0090] In the present application, the chemical reaction formula for preparing the precursor compound [Ru(L1)2Cl2] is shown in formula d. Figure 2

[0091] After obtaining the precursor compound having the structure shown in formula d, the present application mixes the precursor compound having the structure shown in formula d, the double thiophene benzobridged ligand having the structure shown in formula I and a solvent to perform a second coordination reaction to obtain a double thiophene benzobridged binuclear ruthenium complex with Cl - ​The double thiophene benzobridged dinuclear osmium complex has a cationic structure as shown in formula III. In the present application, the molar ratio of the precursor compound having the structure shown in formula e and the double thiophene benzobridged ligand having the structure shown in formula I is preferably 2:1; the solvent is preferably ethylene glycol solvent; the ethylene glycol; the temperature of the second coordination reaction is preferably 80-180 °C, more preferably 130-160 °C, and the time of the coordination reaction is preferably 2-72 h, more preferably 6-12 h; and the second coordination reaction is preferably carried out under argon protection.

[0092] In the present application, the reaction formula for preparing the double thiophene benzobridged dinuclear osmium complex is as shown in formula III. Figure 3

[0093] The present application also provides a preparation method of the double thiophene benzobridged dinuclear osmium complex as described in the above scheme, comprising the following steps:

[0094] (i) mixing an auxiliary ligand L2, ammonium hexachloroosmate and an organic solvent to carry out a first coordination reaction to obtain a precursor compound having a structure as shown in formula e;

[0095] formula e;

[0096] (ii) mixing the precursor compound having the structure shown in formula e, the double thiophene benzobridged ligand having the structure shown in formula I and a solvent to carry out a second coordination reaction to obtain a double thiophene benzobridged dinuclear osmium complex with Cl - as an anion, and the cationic structure of the double thiophene benzobridged dinuclear osmium complex is as shown in formula III.

[0097] The present application mixes an auxiliary ligand L2, ammonium hexachloroosmate and an organic solvent to carry out a first coordination reaction to obtain a precursor compound having a structure as shown in formula e. In the present application, the molar ratio of the auxiliary ligand L2 and ammonium hexachloroosmate is preferably 2:1; the organic solvent used in 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; and the first coordination reaction is preferably carried out under argon protection. After the reaction is completed, the present application cools the obtained reaction solution to room temperature, adds a saturated aqueous solution of sodium dithionite, keeps it in an ice bath for 0.5 h, and then carries out suction filtration, washing and vacuum drying in sequence to obtain the precursor compound [Os(L2)2Cl2] having the structure shown in formula e.

[0098] In the present application, the chemical reaction formula for preparing the precursor compound [Os(L2)2Cl2] is as shown in formula e. Figure 4

[0099] ​​After obtaining the precursor compound with the structure shown in formula e, the present application mixes the precursor compound with the structure shown in formula e, the bithiophene benzo-bridged ligand with the structure shown in formula I and a solvent to perform a second coordination reaction to obtain a bithiophene benzo-bridged dinuclear osmium complex with Cl - as an anion, and the cationic structure of the bithiophene benzo-bridged dinuclear osmium complex is shown in formula III. In the present application, the molar ratio of the precursor compound with the structure shown in formula e and the bithiophene benzo-bridged ligand with 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, and the time of the coordination reaction is preferably 2-72 h, more preferably 6-12 h; and the second coordination reaction is preferably performed under argon protection.

[0100] In the present application, the reaction formula for preparing the bithiophene benzo-bridged dinuclear osmium complex is shown in Figure 5 .

[0101] The present application also provides a preparation method of the bithiophene benzo-bridged dinuclear iridium complex described in the above scheme, which comprises the following steps:

[0102] (i) mixing an auxiliary ligand L3, iridium chloride and an organic solvent to perform a first coordination reaction to obtain a precursor compound with the structure shown in formula f;

[0103] formula f;

[0104] (ii) mixing the precursor compound with the structure shown in formula f, the bithiophene benzo-bridged ligand with the structure shown in formula I and a solvent to perform a second coordination reaction to obtain a bithiophene benzo-bridged dinuclear iridium complex with Cl - as an anion, and the cationic structure of the bithiophene benzo-bridged dinuclear iridium complex is shown in formula IV.

[0105] The present application mixes an auxiliary ligand L3, iridium chloride and an organic solvent to perform a first coordination reaction to obtain a precursor compound with the structure shown in formula e. In the present application, the molar ratio of the auxiliary ligand L3 and iridium chloride is preferably 2:1; the organic solvent used in the coordination reaction is preferably ethylene glycol ethyl ether; the temperature of the coordination reaction is preferably 110 °C, and the time is preferably 2 d; and the first coordination reaction is preferably performed under argon protection. After the reaction is completed, the present application cools the obtained reaction solution to room temperature, and then performs filtration, washing and vacuum drying in sequence to obtain the precursor compound with the structure shown in formula e [Ir2(L3)4(μ-Cl)2].

[0106] In the present application, the chemical reaction formula for preparing the precursor compound [Ir2(L3)4(μ-Cl)2] is shown inFigure 6 as shown in formula e.

[0107] After obtaining the precursor compound having the structure shown in formula e, the present application mixes the precursor compound having the structure shown in formula e, the bithiophene benzo-bridged ligand having the structure shown in formula I and a solvent to perform a second coordination reaction to obtain a bithiophene benzo-bridged dinuclear iridium complex with Cl - as an anion, and the cationic structure of the bithiophene benzo-bridged dinuclear iridium complex is shown in formula IV. In the present application, the molar ratio of the precursor compound having the structure shown in formula e and the bithiophene 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, and the time of the coordination reaction is preferably 2-72 h, more preferably 6-12 h; and the second coordination reaction is preferably performed under argon protection.

[0108] In the present application, the reaction formula for preparing the bithiophene benzo-bridged dinuclear iridium complex is shown in formula III. Figure 7

[0109] After the coordination reaction is completed, direct post-treatment can be performed to obtain a bithiophene benzo-bridged dinuclear ruthenium complex, a bithiophene benzo-bridged dinuclear osmium complex and a bithiophene benzo-bridged dinuclear iridium complex with Cl - as an anion; in specific embodiments of the present application, when the target product is a bithiophene benzo-bridged dinuclear metal complex with other anions, it is also preferred to add an aqueous solution containing an anion compound to the obtained reaction liquid to replace Cl - in the bithiophene benzo-bridged dinuclear metal complex, and then post-treatment is performed again; the anion in the aqueous solution containing an anion compound is preferably PF6 - or ClO4 - In specific embodiments of the present application, the aqueous solution containing an anion compound is preferably a saturated aqueous ammonium hexafluorophosphate solution; after the aqueous solution containing an anion compound is added, it is preferably left to stand for 0.5 h, and then post-treatment is performed.

[0110] In the present application, the method of post-treatment is preferably as follows: for the bithiophene benzo-bridged dinuclear ruthenium complex, the bithiophene benzo-bridged dinuclear osmium complex and the bithiophene benzo-bridged dinuclear iridium complex, the obtained reaction liquid is sequentially subjected to suction filtration, washing and vacuum drying to obtain a crude product, and the crude product is subjected to alumina column chromatography to obtain the corresponding bithiophene benzo-bridged dinuclear ruthenium complex, bithiophene benzo-bridged dinuclear osmium complex and bithiophene benzo-bridged dinuclear iridium complex; in the present application, the eluent for the alumina column chromatography is preferably a toluene-acetonitrile mixed solvent, and the volume ratio of toluene to acetonitrile in the toluene-acetonitrile mixed solvent is preferably 2:1-1:3. ​

[0111] The application also provides a use of the bithiophene-benzo bridged dinuclear metal complex in the preparation of a tumor infrared photodynamic therapy photosensitizer and a photothermal reagent. In the application, the tumor is preferably non-small cell lung cancer; the bithiophene-benzo bridged dinuclear metal complex provided by the application not only has excellent two-photon absorption properties and excellent singlet oxygen yield, but also shows high phototoxicity and low dark toxicity to non-small cell lung cancer cells, and is a potential new two-photon infrared photodynamic photosensitizer. Meanwhile, the bithiophene-benzo bridged dinuclear metal complex provided by the application also has excellent photothermal conversion efficiency under infrared excitation light, and is a potential new infrared photothermal reagent.

[0112] The technical solutions in the application will be clearly and completely described below in combination with the embodiments in the application. Obviously, the described embodiments are only some of the embodiments of the application, rather than all the embodiments. Based on the embodiments in the application, all other embodiments obtained by a person of ordinary skill in the art without creative work fall within the protection scope of the application.

[0113] Embodiment 1

[0114] The preparation of the bithiophene-benzo bridged ligand dtdpip is as follows:

[0115] (1) 1,10-Phenanthroline 4 g (22.2 mmol) and potassium bromide 4 g (33.6 mmol) were weighed into a double-necked bottle and stirred uniformly, the reaction was placed in an ice water bath, and a constant-pressure funnel was used to gradually drop a cooled mixed solution of concentrated sulfuric acid and concentrated nitric acid with a volume ratio of 2:1, 60 ml. After the solution was dropped, the ice water bath was removed, and the oil bath was refluxed at 85 °C for 6 h. The condenser was removed, and the bromine gas was placed for 12 h. Then the reaction was poured into a 200 ml ice water bath, and the pH was adjusted to 5-6 with 10 M sodium hydroxide. The solution was yellow and yellow solids were precipitated. The product was extracted with 100 ml of chloroform three times, and the product quality was 3.57 g, with a yield of 75%.

[0116] (2) Benzene-1,2-b:4,5-b' dithiophene-2,6-dicarboxaldehyde 0.369 g (1.5 mmol), ammonium acetate 4.62 g (60 mmol), and glacial acetic acid 50 ml were weighed into a flask, and o-phenanthroline-5,6-dione 0.63 g (3 mmol) was added to the oil bath at 110 °C and refluxed for 4 h. Continue to heat and reflux for 8 h. Hot filtration was performed, a small amount of acetic acid was added for washing, a large amount of water was added for washing, a small amount of ethanol was added for washing, and drying was performed overnight. Yellow solids were obtained, which were the conjugated bithiophene ligand dtdpip, with a yield of 0.858 g and a yield of 91%.

[0117] Embodiment 2

[0118] Synthesis of precursor compound [Ru(bpy)2Cl2] :

[0119] Weigh 1.56 g (6 mmol) of ruthenium trichloride, 1.87 g (12 mmol) of auxiliary ligand bpy (2,2'-bipyridine), 1.68 g (28 mmol) of lithium chloride into a two-necked flask, add 20 mL of N,N'-dimethylformamide, heat to reflux at 140 °C under argon for 8 h, after cooling to room temperature, add 50 mL of acetone, freeze overnight, filter, wash, and dry under vacuum to obtain purple-black solid, which is the precursor compound [Ru(bpy)2Cl2], yield 1.12 g, yield: 39%.

[0120] Replace the auxiliary ligand bpy in the above scheme with tbubpy (4,4'-di-tert-butyl-2,2'-bipyridine) and dip (4,7-diphenyl-1,10-phenanthroline) respectively, and other conditions are the same as the above scheme, to obtain the precursor compounds [Ru(tbubpy)2Cl2] and [Ru(dip)2Cl2] respectively.

[0121] Example 3

[0122] Synthesis of dithienylbenzene-bridged dinuclear ruthenium complex Ru1:

[0123] Weigh 0.063 g (0.10 mmol) of ligand dtdpip and 0.104 g (0.20 mmol) of precursor [Ru(bpy)2Cl2] into a two-necked flask, add 10 mL of ethylene glycol, stir to reflux at 150 °C under argon for 12 h or more, after cooling to room temperature, add 12 mL of water and saturated aqueous ammonium hexafluorophosphate solution, stand for 0.5 h, filter, wash, and dry under vacuum to obtain black crude product, which is chromatographed on an alumina column with toluene:acetonitrile (1:2, v:v) as eluent, collect the deep red component to obtain dithienylbenzene-bridged dinuclear ruthenium complex Ru1, yield 0.092 g, yield 63%. 1H NMR (400 MHz, DMSO-d6) 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 Ru2S2[M−4PF6] 4+ :363.2981; Found: 363.2985.

[0124] Synthesis of the bis-thiophene benzo-bridged dinuclear ruthenium complex Ru2:

[0125] Preparation procedure is the same as Ru1, except that the precursor [Ru(bpy)2Cl2] is replaced by [Ru(tbubpy)2Cl2] 0.142 g (0.20 mmol), and the rest of the procedure and operating conditions remain unchanged. The yield of Ru2 is 0.126 g, 65%. 1 HNMR (400 MHz, DMSO-d6) 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 Ru2S2 [M−4PF6] 4+ : 475.6741; Found: 475.6729.

[0126] Synthesis of the bis-thiophene benzo-bridged dinuclear ruthenium complex Ru3:

[0127] Preparation procedure is the same as Ru1, the only difference is that precursor [Ru(bpy)2Cl2] in Ru1 is replaced by [Ru(dip)2Cl2] 0.175 g (0.20 mmol), other steps and operation conditions are the same, the yield of Ru3 is 0.156 g, the yield is 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), 7.71 (d, J = 7.5 Hz, 10H), 7.68 - 7.65 (m, 14H), 7.64 - 7.59 (m, 13H), 7.25 (t, J = 7.5 Hz, 7H), 7.15 (dd, J = 15.2, 7.3 Hz, 10H). HR-MS (MeOH, m / z): Calcd for C 132 H 82 N 16 Ru2S2 [M−4PF6] 4+ : 539.6115; Found: 539.6109.

[0128] Example 4

[0129] Synthesis of precursor compound [Os(bpy)2Cl2]:

[0130] Weighed ammonium hexachloroosmate 0.220 g (0.50 mmol), auxiliary ligand bpy (2,2'-bipyridine) 0.172 g (1.10 mmol) into a flask, added 10 mL ethylene glycol, refluxed at 120 °C under argon for 1 h, after cooling to room temperature, added 10 mL saturated aqueous solution of sodium dithionite, kept in ice bath for 0.5 h, suction filtered, washed, vacuum dried to obtain purple-black solid, which is the precursor compound [Os(bpy)2Cl2], the yield is 0.236 g, the yield is 77%.

[0131] The auxiliary ligand bpy in the above scheme is replaced by tbubpy (4,4'-di-tert-butyl-2,2'-bipyridine) and dip (4,7-diphenyl-1,10-phenanthroline) respectively, and other conditions are the same as the above scheme, to obtain precursor compounds [Os(tbubpy)2Cl2], [Os(dip)2Cl2] respectively.

[0132] Example 5

[0133] Synthesis of bis-thiophene benzene bridged dinuclear osmium complex Os1:

[0134] Ligand dtdpip 0.063 g (0.10 mmol) and precursor [Os(bpy)2Cl2] 0.115 g (0.20 mmol) were weighed into a two-necked flask, 10 mL ethylene glycol was added, stirred under argon at 150 ºC for 24 h above reflux, after cooling to room temperature, 12 mL water and saturated aqueous ammonium hexafluorophosphate solution were added, left for 0.5 h, suction filtered, washed, vacuum dried, the obtained black green crude product was chromatographed on an alumina column with toluene: acetonitrile (1:1, v:v) as eluent, the dark green fraction was collected, bis-thiophene bridged dinuclear osmium complex Os1 was obtained, yield 0.089 g, yield 55%. 1 H NMR (400 MHz, DMSO-d6) 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 Os2S2 [M−4PF6] 4+ : 408.5763; Found: 408.5764.

[0135] Synthesis of bis-thiophene benzene bridged dinuclear osmium complex Os2:

[0136] Preparation procedure was the same as Os1, except that the precursor [Os(bpy)2Cl2] was replaced by [Os(tbubpy)2Cl2] 0.160 g (0.20 mmol), the rest of the steps and operations were unchanged, Os2 yield 0.143 g, yield 68%. 1H NMR (400MHz, DMSO-d6) 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 Os2S2 [M−4PF6] 4+ :520.2008; Found: 520.2034.

[0137] Synthesis of bis-thiophene benzo bridged dinuclear osmium complex Os3:

[0138] Preparation procedure is same as complex Os1, except that precursor [Os(bpy)2Cl2] is replaced by [Os(dip)2Cl2] 0.185 g (0.19 mmol), and the rest of the procedure and operation is same, Os3 yield 0.177 g, yield 75%. 1 H NMR (400MHz, DMSO-d6) 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 Os2S2 [M−4PF6] 4+ : 584.6399; Found: 584.6380.

[0139] Example 6

[0140] Synthesis of precursor compound [Ir2(ppy)4(μ-Cl)2]

[0141] Iridium chloride 0.597 g (2.0 mmol) and auxiliary ligand ppy (2-phenylpyridine) 0.775 g (5.0 mmol) were weighed into a two-necked flask, 45 mL of ethylene glycol ethyl ether and 15 mL of water were added, and the mixture was refluxed at 110 °C under argon for 48 h. After cooling to room temperature, the mixture was filtered, washed, and dried under vacuum to obtain a yellow solid, which was the precursor compound [Ir2(ppy)4(μ-Cl)2].

[0142] 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 those in the above scheme to obtain the precursor compounds [Ir2(Fppy)4(μ-Cl)2], [Ir2(pq)4(μ-Cl)2], and [Ir2(piq)4(μ-Cl)2].

[0143] Example 7

[0144] Synthesis of dithienylbenzene-bridged dinuclear iridium complex Ir1

[0145] The ligand dtdpip 0.063 g (0.10 mmol) and the precursor [Ir2(ppy)4(μ-Cl)2] 0.129 g (0.10 mmol) were weighed into a two-necked flask, 10 mL of ethylene glycol was added, and the mixture was stirred and refluxed at 150 °C under argon for 24 h or more. 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 under vacuum to obtain an orange crude product. The crude product was chromatographed on an alumina column using toluene:acetonitrile (1:1, v:v) as the eluent, and the orange-yellow component was collected to obtain the dithienylbenzene-bridged dinuclear iridium Ir1, with a yield of 0.109 g and a yield of 67%. 1H NMR (400 MHz, DMSO-d6) 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 Ir2N 12 S2 [M−2PF6] 2+ : 814.1485; Found: 814.1489.

[0146] Synthesis of Ir2:

[0147] Preparation procedure is the same as Ir1, except that the precursor [Ir2(ppy)4(μ-Cl)2] is replaced by [Ir2(Fppy)4(μ-Cl)2] 0.123 g (0.10 mmol), and the rest of the procedure and operation are the same. The yield of Ir2 is 0.136 g, 78%. 1 H NMR (400 MHz, DMSO-d6) 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 42 F8Ir2N 12 S2 [M−2PF6] 2+: 886.1109; Found: 886.1107.

[0148] Synthesis of bis-thiophene benzo-bridged dinuclear iridium complex Ir3:

[0149] Preparation procedure is the same as Ir1, except that the precursor [Ir2(ppy)4(μ-Cl)2] is replaced by [Ir2(pq)4(μ-Cl)2] 0.127 g (0.20 mmol), the rest of the steps and operations are unchanged, the yield of Ir3 is 0.139 g, the yield is 74%. 1 H NMR (400 MHz, DMSO-d6) 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 Ir2N 12 S2 [M−2PF6] 2+ : 914.6815; Found: 914.6808.

[0150] Synthesis of bis-thiophene benzo-bridged dinuclear iridium complex Ir4:

[0151] Preparation procedure is the same as Ir1, except that the precursor [Ir2(ppy)4(μ-Cl)2] is replaced by [Ir2(piq)4(μ-Cl)2] 0.127 g (0.20 mmol), the rest of the steps and operations are unchanged, the yield of Ir3 is 0.136 g, the yield is 73%. 1H NMR(400 MHz, DMSO-d6) 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 Ir2N 12 S2 [M−2PF6] 2+ Found: 913.1787; Found: 913.1778.

[0152] Example 8

[0153] Singlet oxygen generation properties of bisthiophene-bridged binuclear metal complexes:

[0154] Using ABDA (9,10-anthratridimyl-bis(methylene)dimalonic acid) as the singlet oxygen ( 1 The singlet oxygen generation efficiency of ABDA solutions containing bisthiophene-bridged dinuclear metal complexes (Ru1-3, Os1-3, and Ir1-4) was studied by measuring the absorption spectra changes of the complexes using a UV / Vis spectrophotometer. The UV absorption spectra of ABDA solutions containing bisthiophene-bridged dinuclear metal complexes after excitation at 450 nm, 808 nm, US, and 808 nm+US in the presence of the bisthiophene-bridged dinuclear metal complexes are shown below. Figures 8-11 As shown.

[0155] 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. [Ru(bpy)3] is a well-known complex to those skilled in the art. 2+ and [Os(bpy)3] 2+For comparison, the singlet oxygen yield was obtained through linear fitting. Under excitation at 450 nm, 808 nm, US, and 808 nm+US, the singlet oxygen generation rates of the bisthiophene benzo[3]-bridged dinuclear metal complexes (Ru1-3, Os1-3, and Ir1-4) were all higher than those of the control complex [Ru(bpy)3]. 2+ Furthermore, the singlet oxygen yields of the complexes Ru2 and Ru3 under 808 nm + US excitation reached [Ru(bpy)3]. 2+ The 6.62 and 6.59 times higher values ​​indicate that the ruthenium complex provided by this invention has excellent ability to induce singlet oxygen generation under infrared light excitation.

[0156] Example 9

[0157] Infrared photothermal conversion capability of bisthiophene-bridged binuclear metal complexes:

[0158] Using PBS buffer containing 10% DMSO as a control, bisthiophene benzo-bridged dinuclear metal complexes (Ru1-3, Os1-3, and Ir1-4, all in PBS buffer containing 10% DMSO) at concentrations of 10 μM, 50 μM, and 100 μM were irradiated with 808 nm infrared light. Thermal imaging of the solutions was performed every minute from 0 to 10 minutes. Figures 12-14 The heat Q and photothermal conversion efficiency η generated by the bisthiophene benzo-bridged binuclear metal complex were calculated.

[0159] according to Figures 12-14 The recorded temperature data showed that, compared with the control group PBS, the bisthiophene benzo-bridged binuclear metal complex of the present invention generated a certain amount of heat under 808 nm illumination. Os2 exhibited the highest photothermal conversion efficiency (PCE) at 808 nm illumination, reaching 16.2%. These results demonstrate that the bisthiophene benzo-bridged binuclear metal complex provided by the present invention possesses excellent infrared photothermal conversion capability at 808 nm.

Claims

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

2. The method for preparing the bisthiophene benzo-bridged ligand according to claim 1, characterized in that, Includes the following steps: (i) A compound having the structure shown in formula a, potassium bromide and an organic acid are mixed and reacted to obtain a compound having the structure shown in formula b. (ii) The compound having the structure shown in Formula b, ammonium acetate, the compound having the structure shown in Formula c, and an organic solvent are mixed and subjected to a condensation reaction to obtain a bisthiophene benzo-bridged ligand having the structure shown in Formula I; 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 hours. The condensation reaction in step (ii) is carried out at a temperature of 100–120°C for 1–10 hours.

4. A bisthiophene benzo-bridged binuclear metal complex, composed of anion and cation, characterized in that, The structural formulas of the cations are shown in Formulas II, III and IV: In formula II, Let L1 be the auxiliary ligand, which is any one of the following structures: In Equation III, This refers to the auxiliary ligand L2, which is any one of the following structures: In Equation IV, This refers to the auxiliary ligand L3, which is any one of the following structures:

5. The method for preparing the bisthiophene benzo-bridged binuclear metal complex according to claim 4, characterized in that, Includes the following steps: (i) The auxiliary ligand L1, ruthenium trichloride, lithium chloride and organic solvent are mixed to carry out the first coordination reaction to obtain a precursor compound having the structure shown in formula d; (ii) The precursor compound having the structure shown in formula d, the bisthiophene benzo-bridged ligand of formula I according to claim 1, and the solvent are mixed to carry out a second coordination reaction to obtain an anion of (PF6). - The bisthiophene benzo-bridged binuclear ruthenium complex has a cationic structure as shown in Formula II.

6. The method for preparing the bisthiophene benzo-bridged binuclear metal complex according to claim 4, characterized in that, Includes the following steps: (i) The auxiliary ligand L2, ammonium hexachloroosmium tetroxide and an organic solvent are mixed to carry out the first coordination reaction to obtain a precursor compound having the structure shown in formula e; (ii) The precursor compound having the structure shown in Formula e, the bisthiophene benzo-bridged ligand of Formula I according to claim 1, and a solvent are mixed to carry out a second coordination reaction to obtain an anion of (PF6). - The bisthiophene benzo-bridged binuclear osmium complex has a cationic structure as shown in Formula III.

7. The method for preparing the bisthiophene benzo-bridged binuclear metal complex according to claim 4, characterized in that, Includes the following steps: (i) The auxiliary ligand L3, iridium chloride and organic solvent are mixed to carry out the first coordination reaction to obtain a precursor compound having the structure shown in formula f; (ii) The precursor compound having the structure shown in formula f, the bisthiophene benzo-bridged ligand of formula I according to claim 1, and a solvent are mixed to carry out a second coordination reaction to obtain an anion of (PF6). - The bisthiophene benzo-bridged binuclear iridium complex has a cationic structure as shown in Formula IV.

8. The use of the bisthiophene benzo-bridged binuclear metal complex according to claim 4 in the preparation of photosensitizers, sonosensitizers, and photothermal reagents for tumor photodynamic therapy.

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