A class of benzophenone hydrazone-TB derivatives and their synthesis method and application

Abstract

The present invention provides a class of benzophenone hydrazone-TB derivatives and their synthesis methods and applications. The structural formula thereof is shown below: #imgabs0# The first derivative 7 and the second derivative 9 exhibit excellent luminescence properties: a large Stokes shift, a significant red shift in the fluorescence emission wavelength, a large fluorescence brightness, and excellent solid-state luminescence; a wide pH range of application, and can be applied in human physiological environments; an effective and good response to viscosity, and the potential to become a viscosity-responsive fluorescent probe that can detect changes in egg white protein; and an excellent response to Al 3+ With recognition ability, it is expected to become an excellent Al 3+ Fluorescent probe; has good photodynamic therapy (PDT) effect on A549 and HepG-2 cells, providing new ideas for the synthesis of PDT photosensitizers.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis and analytical chemistry, and specifically relates to a class of benzophenone hydrazone- Synthesis of base derivatives and their applications in viscosity response, metal ion recognition and photodynamic therapy. Background Art

[0002] With the development of society and technology, aluminum plays an important role in various packaging materials, electrical equipment, clinical drugs and food industry. 3+ It is not only toxic to plants, but also has a negative impact on some human physiological activities. 3+ Or excessive intake of Al 3+ It can lead to dysfunction of different organs and cause neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. 3+ Can act as a competitive inhibitor, excessive intake of Al 3+ It also affects various essential elements such as Fe 3+ , Ca 2+ and Mg 2+ Therefore, the absorption of Al in the environment and human body 3+ The detection is of great significance and value.

[0003] Currently, more and more qualitative and quantitative detection methods for Al have been developed. 3+ There are many techniques for the detection of Al2O3, such as graphite furnace atomic absorption spectrometry, inductively coupled plasma atomic emission spectrometry, electrochemical biosensors, and X-ray diffraction. However, these methods are difficult to be widely used due to their limitations such as time-consuming, labor-intensive, and high cost. Compared with traditional methods, fluorescent probes are gaining more and more attention due to their advantages such as high selectivity, high sensitivity, strong versatility, and relatively simple operation. Therefore, fluorescent probes have been widely used in many different fields to detect Al2O3. 3+ Detection.

[0004] Benzophenone hydrazone is a photoinitiator with excellent photostability and is an important intermediate for pharmaceuticals, fragrances, and organic dyes. Introducing benzophenone into the molecular structure can further enhance the product's luminescence properties, strengthen its ion detection capabilities, and enhance its biological activity, thereby creating a fluorescent molecular probe for ion detection with excellent biological activity.

[0005] Base (TB for short) and its derivatives have a unique V-shaped skeleton and a long conjugated structure. They have multiple transition modes (π-π*, n-π*, spatial transition) under photon excitation. Theoretically, they have a large molar absorption coefficient and are an excellent basic skeleton for ultraviolet light absorption materials.

[0006] Therefore, the present invention designs and synthesizes a class of benzophenonehydrazone-TB derivatives by introducing a benzophenonehydrazone group into the TB skeleton, and applies them to the fields of viscosity response, metal ion recognition and photodynamic therapy. Summary of the Invention

[0007] Technical problem: The purpose of the present invention is to provide a class of benzophenone hydrazone-TB derivatives, their synthesis method and application. By introducing a benzophenone hydrazone group into the TB skeleton, a class of benzophenone hydrazone-TB derivatives is designed and synthesized, and applied to the fields of viscosity response, metal ion recognition and photodynamic therapy.

[0008] Technical solution: The present invention provides a class of benzophenone hydrazone-TB derivatives, whose structural formulas are shown below as the first derivative 7 and the second derivative 9:

[0009]

[0010] The synthesis method of a benzophenonehydrazone-TB derivative of the present invention comprises the following steps:

[0011] Step 1, 3-methoxy-4-bromoaniline 1 reacts with paraformaldehyde to obtain the first intermediate 3, the reaction formula is as follows:

[0012]

[0013] Step 2: The first intermediate 3 reacts with n-butyl lithium and N,N-dimethylformamide to obtain the second intermediate 4. The reaction formula is as follows:

[0014]

[0015] Step 3, benzophenone 5 reacts with hydrazine hydrate to obtain the third intermediate 6, and the reaction formula is as follows:

[0016]

[0017] Step 4: The second intermediate 4 reacts with the third intermediate 6 to obtain the first derivative 7. The reaction formula is as follows:

[0018]

[0019] Step 5: The first derivative 7 reacts with methyl iodide to obtain the second derivative 9. The reaction formula is as follows:

[0020]

[0021] The benzophenone hydrazone-TB derivative of the present invention is used as a viscosity-responsive probe.

[0022] The benzophenone hydrazone-TB derivative of the present invention is used as Al 3+ Application of fluorescent probes in metal ion recognition.

[0023] The benzophenone hydrazone-TB derivative of the present invention is used as a photosensitizer for tumor photodynamic therapy.

[0024] The application of the tumor photodynamic therapy photosensitizer is aimed at inhibiting human liver cancer HpeG2 cells and human lung cancer A549 cells.

[0025] Beneficial effects:

[0026] 1. The synthesis method is simple and the post-processing is convenient;

[0027] 2. The product has excellent luminescence properties: large Stokes shift and excellent solid-state luminescence.

[0028] 3. It has a wide pH range and can be used in human physiological environment.

[0029] 4. It has an effective response to viscosity and has the potential to become a viscosity-responsive fluorescent probe.

[0030] 5. Al 3+ With recognition ability, it is expected to become an excellent Al 3+ Fluorescent probes;

[0031] 6. It has good photodynamic therapy effect on A549 and HepG-2 cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 : (a) UV absorption and (b) fluorescence emission spectra of the first derivative 7 in different solvents; (c) UV absorption and (d) fluorescence emission spectra of the second derivative 9 in different solvents,

[0033] Figure 2 : (a) UV absorption and (b) fluorescence emission spectra of the second intermediate 4, the first derivative 7, and the second derivative 9 in solution,

[0034] Figure 3 : Solid-state fluorescence emission spectra of the second intermediate 4, the first derivative 7 and the second derivative 9,

[0035] Figure 4 :(a) Fluorescence emission spectra of the first derivative 7 at different viscosities and (b) a broken line graph; (c) Fluorescence emission spectra of the second derivative 9 at different viscosities and (d) a broken line graph,

[0036] Figure 5:(a) Changes in fluorescence intensity of the second derivative 9 at different temperatures; (b) Fluorescence emission spectra of the second derivative 9 before and after protein denaturation,

[0037] Figure 6 :(a) Fluorescence emission spectra of the first derivative 7 at different pH values ​​and (b) a broken line graph; (c) Fluorescence emission spectra of the second derivative 9 at different pH values ​​and (d) a broken line graph,

[0038] Figure 7 : (a) Fluorescence emission spectra of the first derivative 7 in the presence of different metal ions and (b) bar graph; (c) Fluorescence emission spectra of the second derivative 9 in the presence of different metal ions and (d) bar graph,

[0039] Figure 8 :(a) The second derivative 9 at different concentrations of Al 3+ Fluorescence emission spectra in the presence of and (b) standard curve,

[0040] Figure 9 :9-Al 3+ The Job's curve of the system,

[0041] Figure 10 : Second derivative 9 and Al 3+ The possible coordination modes between

[0042] Figure 11 : Survival rate of (a) A549 cells or (b) HepG-2 cells incubated with different concentrations of the first derivative 7 after 30 minutes of illumination or in the dark. DETAILED DESCRIPTION

[0043] The present invention will be further described below with reference to the embodiments.

[0044] The embodiments of the present invention are described in detail below. The embodiments described below are exemplary and are only used to explain the present invention, and are not to be construed as limiting the present invention. It will be appreciated by those skilled in the art that various changes and modifications may be made to the present invention without departing from the spirit and scope of the present invention.

[0045] The present invention designs and synthesizes a class of benzophenonehydrazone-TB derivatives by introducing a benzophenonehydrazone group into the TB skeleton, and applies them to the fields of viscosity response, metal ion recognition and photodynamic therapy.

[0046] The structural formula of benzophenone hydrazone-TB derivatives is shown in Table 1:

[0047] Table 1 Synthesis of the first derivative 7 and the second derivative 9

[0048]

[0049] In this embodiment, 4-bromo-3-methoxyaniline, paraformaldehyde, n-butyl lithium, N,N-dimethylformamide, hydrazine hydrate, iodomethane, etc. are used as raw materials to prepare the product through a multi-step reaction. The steps include:

[0050] The first derivative 7 reacts with iodomethane to obtain the first derivative 9, the first intermediate 3 reacts with n-butyl lithium and N,N-dimethylformamide to obtain the second intermediate 4, benzophenone 5 reacts with hydrazine hydrate to obtain the third intermediate 6, the second intermediate 4 reacts with the third intermediate 6 to obtain the first derivative 7, and 3-methoxy-4-bromoaniline 1 reacts with paraformaldehyde to obtain the first intermediate 3.

[0051] The compounds of the following examples were prepared by the above synthesis method:

[0052] (1) A 250 mL round-bottom flask was charged with 1 (60 mmol) and 2 (150 mmol). The flask was placed in a low-temperature tank and adjusted to -15°C. 120 mL of trifluoroacetic acid was slowly added dropwise through a constant pressure dropping funnel. After about 30 minutes of complete addition, the reaction system was moved to a 25°C environment and reacted for 7 days. After the reaction was complete (TLC tracking), it was quenched with ice water, the pH was adjusted to 7 with ammonia water, and the mixture was cooled to room temperature, filtered, washed three times with purified water, and recrystallized from acetone to obtain the first intermediate 3 (65%).

[0053]

[0054] Synthesis of intermediate 3 of formula 1

[0055] (2) The first intermediate 3 (5.0 mmol) was added to a 100 mL two-necked round-bottom flask, evacuated three times, and then placed in a low-temperature tank and adjusted to -45 °C. 20 mL of anhydrous tetrahydrofuran was added to the flask with stirring, and 5.0 mL of n-butyl lithium (1.6 mol·L -1 ), after reacting for 1 hour under argon protection, 1.2 mL of anhydrous DMF was added dropwise, and then allowed to react for 4 hours at room temperature. After TLC tracking until the reaction was complete, water was added for quenching, dichloromethane was extracted, and the crude product was dried to obtain a crude product. The crude product was purified by column chromatography (V 石油醚 :V 乙酸乙酯 =5:1) to give a yellowish-white second intermediate 4 (75%).

[0056]

[0057] Synthesis of the second intermediate 4 of Formula 2

[0058] (3) Benzophenone 5 (20.0 mmol) was added to a 50 mL two-necked round-bottom flask, followed by the addition of 5.0 mL of ethanol and 5.0 mL of 80% by volume hydrazine hydrate. The mixture was stirred and refluxed for 20 h. After the reaction was complete (TLC tracking), the reaction system was naturally cooled to room temperature. After crystals precipitated, the reaction system was placed in a 5°C low-temperature tank and stirred for about 1 h. The filter cake was then filtered and washed three times with cold ethanol. It was then vacuum-dried at 60°C for 6 h to obtain a white needle-shaped third intermediate 6 (95%).

[0059]

[0060] Synthesis of the third intermediate 6 of Formula 3

[0061] (4) The second intermediate 4 (2.0 mmol) and the third intermediate 6 (4.2 mmol) were added sequentially to a 50 mL two-necked round-bottom flask equipped with a condenser reflux tube, and 10 mL of ethanol was added. The temperature was adjusted to 80°C and refluxed for 6 h. After TLC was followed until the reaction was complete, the reaction system was moved to room temperature and cooled naturally. The organic phase was extracted with dichloromethane, and the organic phase was dried over anhydrous sodium sulfate and dried to obtain a crude product. The crude product was separated and purified by column chromatography (V 二氯甲烷 :V 甲醇 =20:1), and recrystallized from ethanol to obtain the yellow product first derivative 7 (55%).

[0062]

[0063] Synthesis of the first derivative 7 of Equation 4

[0064] (5) The first derivative 7 (1.0 mmol) was added to a 50 mL double-necked round-bottom flask, followed by 10 mL of acetonitrile. Iodomethane 8 (1.0 mL) was slowly added dropwise with stirring at room temperature. After the addition was complete, the temperature was raised to 82°C and the mixture was refluxed under condensation for 6 h. After the reaction was complete (TLC tracking), the reaction system was naturally cooled to room temperature, and diethyl ether was slowly added dropwise. After a large amount of precipitate was produced, it was filtered with suction, and the filter cake was washed three times with diethyl ether and dried to obtain the second derivative 9 (85%).

[0065]

[0066] Synthesis of the second derivative 9 of Equation 5

[0067] 2,8-bis((E)-((diphenylmethylene)hydrazono)methyl)-3,9-dimethoxy-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine(7)

[0068]

[0069] 4.57(d,J=16.3Hz,2H),4.24(s,2H),4.10(d,J=16.3Hz,2H),3.83(s,6H). 13 CNMR (100MHz, CDCl3) δ165.49,158.60,155.29,138.61,135.64,130.58,129.15,128.89,128.27,127.63,125.84,107.25,66.73,58.27,55.80.

[0070] 2,8-bis((E)-((diphenylmethylene)hydrazono)methyl)-3,9-dimethoxy-5-methyl-5,12-dihydro-6H-5,11-methanodibenzo[b,f][1,5]diazocin-5-ium iodide(9)

[0071]

[0072] 7.14(m,6H),7.06(s,1H),5.38(d,J=11.2Hz,1H),5.07(d,J=15.3Hz,1H),5.03-4.83(m,2 H),4.71(d,J=16.9Hz,1H),4.46(d,J=17.1Hz,1H),3.96(s,3H),3.88(s,3H),3.69(s,3H). 13 C NMR(100MHz,DMSO-d6)δ165.36,165.01,159.33,158.68,146.81,143.43,137.95,137.49,135.45,13 5.14,133.29,130.16,129.01,128.46,120.82,114.84,108.48,106.67,66.41,57.45,56.75,51.36.

[0073] Solvation effect

[0074] The solvation effect of the compounds of the present invention was tested, and the specific test protocol is as follows:

[0075] The first derivative 7 and the second derivative 9 were prepared with n-hexane (n-Hexane), toluene (Toluene), tetrahydrofuran (THF), chloroform (CHCl3), ethyl acetate (EA), acetonitrile (MeCN), methanol (MeOH) and dimethyl sulfoxide (DMSO) to a concentration of 1×10-5 mol·L -1 The UV absorption and fluorescence emission spectra of the solution were tested. Figure 1 ).

[0076] Depend on Figure 1 (a) It can be seen that the λ of the first derivative 7 abs At around 360nm, it is attributed to n-π on heteroatoms * The R band absorption caused by the transition. The absorbance of the first derivative 9 in n-hexane is low due to its low solubility in n-hexane. Figure 1 In (c), the second derivative 9 in acetonitrile abs There is a clear blue shift (344 nm), while in other solvents abs The second derivative λ is about 400nm. abs Greater than the first derivative λ7 abs It may be that the presence of positive ions in the structure of the second derivative 9 increases the degree of charge separation, reduces ΔE, and makes electronic transition easier and smoother.

[0077] Figure 1 In (b) and (d), the relative fluorescence intensity (RFI) of the first derivative 7 and the second derivative 9 in toluene is larger than that in other solvents, λ em A noticeable red shift occurs.

[0078] Photophysical properties

[0079] The photophysical properties of the second intermediate 4, the first derivative 7, and the second derivative 9 in solution were investigated. The specific experimental scheme is as follows:

[0080] Weigh 10 -5 mol of the second intermediate 4, the first derivative 7, and the second derivative 9 were diluted with a solution to a concentration of 1×10 -5 mol / L, and tested its UV absorption, fluorescence emission and solid-state fluorescence emission spectrum (1×10 -5 mol·L -1 , Figure 2 ).

[0081] The spectral data of the second intermediate 4, the first derivative 7 and the second derivative 9 are shown in Table 2.

[0082] Table 2 Spectral data of the second intermediate 4, the first derivative 7 and the second derivative 9

[0083]

[0084] a UV absorption wavelength in solution; b Molar extinction coefficient ε = A / bC, unit is 1×105 L·mol -1 cm -1 ; c Fluorescence emission wavelength in solution; d Stokes shift in solution; e Relative fluorescence quantum yield (reference: quinine sulfate); f Fluorescence brightness FB = ε*Φ, unit is L·mol -1 cm -1 ; g solid-state excitation wavelength; h solid-state fluorescence emission wavelength; i Solid-state Stokes shift.

[0085] Combine Figure 2 As shown in Table 2, compared with the unmodified second intermediate 4, the λ of the first derivative 7 and the second derivative 9 is abs The red shift is obvious, ε increases, and the first derivative 7 and the second derivative 9 have longer λ em The Stokes shifts of the first derivative 7 and the second derivative 9 are also much larger than those of the second intermediate 4. However, the Stokes shift of the second derivative 9 is slightly smaller than that of the first derivative 7. This may be due to the positive charge on the TB backbone of the second derivative 9. The specific reason needs further investigation.

[0086] Therefore, the introduction of benzophenone hydrazone groups into the TB skeleton significantly improves the luminescence properties of the product, and it has the potential to be applied in the fields of ion recognition, fluorescent probes, etc.

[0087] Viscosity response

[0088] The first derivative 7 and the second derivative 9 were prepared with methanol as solvent to a concentration of 1×10 -4 mol·L -1 Take five 10 mL volumetric flasks, pipette 1.0 mL of the working solution into each volumetric flask, add 0.0 mL, 2.0 mL, 4.0 mL, 6.0 mL, and 8.0 mL of glycerol, respectively, and dilute to volume with methanol to make the concentration of the first derivative 7 or the second derivative 9 1×10 - 5 mol·L -1 , and their fluorescence emission spectra (λ ex =330nm and 340nm, slit: 5 / 10nm, Figure 4 ).

[0089] Depend on Figure 4It can be seen that when the glycerol content increases from 0% to 60%, the fluorescence intensity of the first derivative 7 and the second derivative 9 gradually increases. This may be because with the increase in viscosity, the molecular motion is restricted, preventing the π-π stacking effect, inhibiting the non-radiative transition of the molecules, and leading to fluorescence enhancement; when the glycerol content further increases to 80%, the fluorescence intensity of the first derivative 7 and the second derivative 9 decreases. The possible reason is that larger aggregates are formed, and the increase in the stacking density of the aggregates leads to a decrease in fluorescence intensity.

[0090] The above results indicate that the first derivative 7 and the second derivative 9 have the potential to become viscosity-responsive fluorescent probes. Therefore, we took the second derivative 9 as an example and conducted a protein aggregation experiment using egg white as a sample: First, the stability of the second derivative 9 was studied. The second derivative 9 was prepared with DMSO as the solvent to a concentration of 1×10 -4 mol·L -1 Take five 10 mL volumetric flasks, pipette 1.0 mL of the working solution of the second derivative 9 and 1.0 mL of PBS buffer solution into each volumetric flask, and adjust the volume with DMSO to make the concentration of 1 × 10 -5 mol·L -1 Each volumetric flask was placed in a water bath at 20℃, 40℃, 60℃, 80℃ and 100℃ for five minutes, and the changes in fluorescence intensity (λ ex =270nm, slit: 2.5 / 2.5nm, Figure 5 a).

[0091] Then, the second derivative 9 was prepared with DMSO as solvent to a concentration of 1×10 -4 mol·L -1 The working solution was prepared with PBS to a concentration of 1 × 10 -4 mol·L -1 Take two 10 mL volumetric flasks, pipette 1.0 mL of the working solution of the second derivative 9 and 1.0 mL of the egg white solution into each volumetric flask, and adjust the volume with DMSO so that the concentrations of the second derivative 9 and egg white in the system are both 1×10 -5 mol·L -1 Each volumetric flask was placed in a water bath at 25°C and 95°C for five minutes, and its fluorescence emission spectra (λ ex =270nm, slit: 2.5 / 2.5nm, Figure 5 b).

[0092] Depend on Figure 5 (a) It can be seen that the fluorescence intensity of the second derivative 9 does not change much at different temperatures, indicating that the second derivative 9 has good thermal stability. Figure 5(b) Protein denaturation (95°C) significantly increases the fluorescence intensity of the second derivative 9, demonstrating a synergistic effect of protein denaturation on its fluorescence enhancement. Increased temperature leads to protein denaturation, which increases molecular aggregation, restricts intramolecular rotation, and significantly inhibits nonradiative transitions, resulting in enhanced fluorescence intensity. Clearly, the second derivative 9 can be used as a "light-up" or "on" fluorescent probe for protein detection.

[0093] pH response

[0094] The first derivative 7 and the second derivative 9 were prepared with DMSO as solvent at a concentration of 1×10 -4 mol·L -1 1.0 mL of the working solution was measured and placed in a 10 mL volumetric flask, followed by the addition of 1.0 mL of a buffer solution with a pH value of 3-10 (citric acid / disodium hydrogen phosphate system was selected when the pH value was 3-8, and sodium bicarbonate / sodium carbonate system was selected when the pH value was 9-10), and DMSO was used to adjust the volume so that the concentration of the first derivative 7 or the second derivative 9 was 1×10 -5 mol L -1 , the fluorescence emission spectrum (λ ex =330nm and 340nm, slit: 5 / 10nm, Figure 6 ).

[0095] Depend on Figure 6 It can be seen that when the solution pH is 3-10, the fluorescence intensity of the first derivative 7 and the second derivative 9 does not change much, indicating that their pH applicability range is wide.

[0096] Recognition of metal ions

[0097] The first derivative 7, the second derivative 9 and Na + , K + Mg 2+ , Ca 2+ 、Fe 2+ 、Cu 2+ 、Zn 2+ 、Al 3+ 、Fe 3+ The fluorescence emission spectrum (λ ex =330nm and 340nm, slit: 5 / 10nm, Figure 7 ).

[0098] Depend on Figure 7 It can be seen that compared with other metal ions, the addition of Al 3+ After that, the fluorescence intensity of the first derivative 7 and the second derivative 9 increased significantly, indicating that the first derivative 7 and the second derivative 9 have a significant effect on Al 3+ It has obvious identification function.

[0099] The changes in fluorescence intensity of the first derivative 7 and the second derivative 9 after adding metal ions are shown in Tables 3 and 4.

[0100] Table 3 Effects of the first derivative 7 on different metal ions

[0101]

[0102]

[0103] a The change rate of the fluorescence intensity of the compound after adding metal ions is η = (I-I0) / I0×100%. "-" means no

[0104] Table 4 Effects of the second derivative 9 on different metal ions

[0105]

[0106] a The change rate of the fluorescence intensity of the compound after adding metal ions is η = (I-I0) / I0×100%. "-" means no

[0107] Combine Figure 7 , Table 3 and Table 4 show that adding Al 3+ After addition of the first derivative 7 and the second derivative 9, the fluorescence intensity increased by 73% and 167%, respectively. However, when other metal ions were added, the fluorescence intensity did not change significantly, indicating that the first derivative 7 and the second derivative 9 had a strong affinity for Al 3+ Compared with the first derivative 7, the second derivative 9 showed a better recognition effect on Al 3 + More efficient recognition may be due to the presence of the bridgehead nitrogen cation, which distorts the molecular structure, resulting in an increase in the exposure of the lone pair electrons on the two double-bonded N atoms and one oxygen atom at both ends that can participate in coordination, making it easier to form coordination bonds. The specific reasons need further exploration.

[0108] The second derivative 9-Al 3+ The standard curve of the system (λ ex =340nm, slit: 10 / 10nm, Figure 8 ).

[0109] Depend on Figure 8 It can be seen that when Al 3+ The concentration is 1×10 -5 -10×10 -5 mol·L -1 Within the range, as Al 3+ As the concentration increases, the λ of the second derivative 9 emA certain blue shift occurs, and the fluorescence intensity at 443nm gradually increases, and the fluorescence intensity is similar to that of Al 3+ The concentration has a linear relationship, R 2 is 0.99780, and the linear equation y=111.62424×10 5 x+1417.06667. The second derivative 9 was calculated for Al 3+ The LOD is 1.56×10 -6 mol·L -1 , which is expected to detect Al in the human body 3+ content.

[0110] To further explore the efficient recognition of Al by the second derivative 9 3+ The Job's curve (λ ex =340nm, slit: 10 / 10nm, concentration is 1×10 -5 mol·L -1 , Figure 9 ).

[0111] Depend on Figure 9 It can be seen that the second derivative 9 and Al 3+ When the molar ratio of 9 to Al is 3:7, the fluorescence intensity shows an inflection point, which may be due to the interaction between the second derivative 9 and Al 3+ A complex was formed at a concentration ratio of 1:2. Based on this, it was speculated that the second derivative 9 and Al 3+ Possible coordination modes ( Figure 10 ):

[0112] Extracorporeal photodynamic therapy

[0113] The photodynamic therapy effect of the first derivative 7 on human non-small lung cancer cells (A549) and human liver cancer cells (HepG-2) was tested by standard MTT assay. Figure 11 ).

[0114] like Figure 11 As shown, under dark conditions, A549 and HepG-2 cells had high survival rates after co-incubation with the first derivative 7, indicating that the first derivative 7 has relatively low dark toxicity. Under light conditions, however, the mortality of A549 and HepG-2 cells increased significantly with increasing concentrations of the first derivative 7, showing a clear concentration-dependent effect. At a concentration of 100.0 μg / mL, the mortality of A549 and HepG-2 cells reached 80%.

[0115] As shown in Table 5, under dark conditions, the first derivative 7 has low toxicity to the two cell types, indicating that the first derivative 7 has good biocompatibility. After 30 minutes of illumination, the first derivative 7 has a lower IC 50values ​​(28.2 μmol·L -1 and 41.5 μmol·L -1 ), indicating that the first derivative 7 has an excellent PDT effect. Although the PDT effect of the second derivative 9 is not as good as that of the first derivative 7, the second derivative 9 has a higher fluorescence quantum yield and fluorescence brightness, showing more excellent optical properties, which may be related to the lower ΔE and better electron mobility of the second derivative 9.

[0116] Table 5 Half inhibition rate (IC) of the first derivative 7 and the second derivative 9 on two cell lines 50 )

[0117]

[0118] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A benzophenone hydrazone-TB derivative, characterized in that: Its structural formula is shown below as the first derivative (7) and the second derivative (9):

2. A method for synthesizing a benzophenonehydrazone-TB derivative according to claim 1, characterized in that: The following steps are involved: Step 1, 3-methoxy-4-bromoaniline (1) reacts with paraformaldehyde to obtain the first intermediate (3), and the reaction formula is as follows: Step 2: The first intermediate (3) reacts with n-butyl lithium and N,N-dimethylformamide to obtain the second intermediate (4). The reaction formula is as follows: Step 3, benzophenone (5) reacts with hydrazine hydrate to obtain the third intermediate (6), and the reaction formula is as follows: Step 4: The second intermediate (4) reacts with the third intermediate (6) to obtain the first derivative (7). The reaction formula is as follows: Step 5: The first derivative (7) reacts with iodomethane to obtain the second derivative (9). The reaction formula is as follows:

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