CN116891478A - Benzophenone hydrazone-TB derivative and synthetic method and application thereof - Google Patents

Benzophenone hydrazone-TB derivative and synthetic method and application thereof Download PDF

Info

Publication number
CN116891478A
CN116891478A CN202310851242.0A CN202310851242A CN116891478A CN 116891478 A CN116891478 A CN 116891478A CN 202310851242 A CN202310851242 A CN 202310851242A CN 116891478 A CN116891478 A CN 116891478A
Authority
CN
China
Prior art keywords
derivative
benzophenone hydrazone
follows
reacts
benzophenone
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202310851242.0A
Other languages
Chinese (zh)
Inventor
周生亮
孙雅文
庄敏艳
张宇
苑睿
吴翚
宛瑜
张鹏
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Jiangsu Normal University
Original Assignee
Jiangsu Normal University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Jiangsu Normal University filed Critical Jiangsu Normal University
Priority to CN202310851242.0A priority Critical patent/CN116891478A/en
Publication of CN116891478A publication Critical patent/CN116891478A/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C09K2211/1003—Carbocyclic compounds
    • C09K2211/1007—Non-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C09K2211/1018—Heterocyclic compounds
    • C09K2211/1025—Heterocyclic compounds characterised by ligands
    • C09K2211/1044—Heterocyclic compounds characterised by ligands containing two nitrogen atoms as heteroatoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Physics & Mathematics (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Pathology (AREA)
  • Molecular Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Materials Engineering (AREA)
  • Analytical Chemistry (AREA)
  • Optics & Photonics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention provides a benzophenone hydrazone-TB derivative, a synthetic method and application thereof, wherein the structural formula is shown as follows:the first derivative 7 and the second derivative 9 exhibit excellent light-emitting properties: the fluorescent light has large Stokes displacement, the fluorescence emission wavelength is obviously red shifted, the fluorescence brightness is large, and the solid state light is excellent; the pH value application range is wide, and the pH value can be applied to human physiological environments; effective response to viscosity, has become viscosity responseThe potential of the fluorescent probe of (2) can detect the change of egg white protein; for Al 3+ Has recognition ability and is expected to be excellent in Al 3+ A fluorescent probe; has better photodynamic therapy (PDT) effect on A549 and HepG-2 cells, and provides a new idea for synthesizing PDT photosensitizer.

Description

Benzophenone hydrazone-TB derivative and synthetic method and application thereof
Technical Field
The invention belongs to the field of organic synthesis and analytical chemistry, and in particular relates to benzophenone hydrazone with excellent optical performanceSynthesis of base derivatives and their use in viscosity response, metal ion recognition and photodynamic therapy.
Background
With the development of society and technology, aluminum plays an important role in various packaging materials, electrical equipment, clinical medicine and food industries. But Al is 3+ It is toxic to plants and has negative effects on human physiological activities. Long-term contact with Al 3+ Or take up excessive Al 3+ Can lead to dysfunction of different organs and cause neurodegenerative diseases such as Alzheimer disease, parkinson disease and the like. At the same time due to Al 3+ Can be used as competitive inhibitor for excessive intake of Al 3+ Also affects various essential elements such as Fe 3+ 、Ca 2+ And Mg (magnesium) 2+ Is not limited to the absorption of (a). Thus, to the environment and Al in the human body 3+ Has great significance and value in detection.
At present, more and more qualitative and quantitative detection of Al has been developed 3+ Such as graphite oven atomic absorption spectrometry, inductively coupled plasma atomic emission spectrometry, electrochemical biosensors, X-ray diffraction, etc. However, these methods are difficult to be widely used due to the limitations of time consuming, labor intensive, and expensive. And (3) withCompared with the traditional method, the fluorescent probe is more and more paid attention to due to the advantages of high selectivity, high sensitivity, strong universality, relatively simple operation and the like. Thus, fluorescent probes have been widely used as Al in many different fields 3+ Is detected.
Benzophenone hydrazone is a photoinitiator, has better photostability, and is an important intermediate of medicines, fragrances and organic dyes. The introduction of the benzophenone into the molecular structure is beneficial to further improving the luminous performance of the product and enhancing the ion detection capability and the biological activity of the product, so that the ion detection fluorescent molecular probe with excellent biological activity is obtained.
The Base (TB) and the derivative thereof have unique V-type frameworks and longer conjugated structures, have various transition modes (pi-pi, n-pi and space transition) under photon excitation, theoretically have larger molar absorptivity, and are excellent ultraviolet light absorbing material basic frameworks.
Therefore, the benzophenone hydrazone group is introduced into the TB skeleton, so that a benzophenone hydrazone-TB derivative is designed and synthesized, and is applied to the fields of viscosity response, metal ion identification, photodynamic therapy and the like.
Disclosure of Invention
Technical problems: the invention aims to provide a benzophenone hydrazone-TB derivative, a synthesis method and application thereof, wherein a benzophenone hydrazone group is introduced into a TB skeleton, so that the benzophenone hydrazone-TB derivative is designed and synthesized and is applied to the fields of viscosity response, metal ion identification, photodynamic therapy and the like.
The technical scheme is as follows: the structural formula of the benzophenone hydrazone-TB derivatives is shown as the following first derivatives 7 and second derivatives 9:
the synthesis method of the diphenyl ketone hydrazone-TB derivatives comprises the following steps:
step 1, 3-methoxy-4-bromoaniline 1 reacts with paraformaldehyde to obtain a first intermediate 3, and the reaction formula is as follows:
step 2, the first intermediate 3 reacts with N-butyllithium and N, N-dimethylformamide to obtain a second intermediate 4, wherein the reaction formula is as follows:
step 3, the benzophenone 5 reacts with hydrazine hydrate to obtain a third intermediate 6, and the reaction formula is as follows:
step 4, the second intermediate 4 reacts with the third intermediate 6 to obtain a first derivative 7 of the product, wherein the reaction formula is as follows:
step 5, the first derivative 7 reacts with methyl iodide to obtain a second derivative 9, and the reaction formula is as follows:
the benzophenone hydrazone-TB derivative is applied to a viscosity response probe.
The benzophenone hydrazone-TB derivative is used as Al 3+ Use of fluorescent probes in metal ion recognition.
The benzophenone hydrazone-TB derivative is applied to a photosensitizer for photodynamic therapy of tumors.
The application of the tumor photodynamic therapy photosensitizer is aimed at inhibiting human liver cancer HpeG2 cells and human lung cancer A549 cells.
The beneficial effects are that:
1. the synthesis method is simple and the post-treatment is convenient;
2. the product has excellent luminescence property: has large Stokes displacement and excellent solid state luminescence.
3. Has wide pH application range and can be applied to human physiological environment.
4. The fluorescent probe has the potential of becoming a fluorescent probe for viscosity response in response to effective viscosity.
5. For Al 3+ Has recognition ability and is expected to be excellent in Al 3+ A fluorescent probe;
6. has better photodynamic therapy effect on A549 and HepG-2 cells.
Drawings
Fig. 1: (a) Ultraviolet absorption of the first derivative 7 in a different solvent and (b) fluorescence emission spectrum; (c) Ultraviolet absorption of the second derivative 9 in a different solvent and (d) fluorescence emission spectrum,
fig. 2: (a) Ultraviolet absorption of the second intermediate 4, the first derivative 7, the second derivative 9 in solution and (b) fluorescence emission spectrum,
fig. 3: solid state fluorescence emission spectra of the second intermediate 4, the first derivative 7 and the second derivative 9,
fig. 4: (a) Fluorescence emission spectra of the first derivative 7 at different viscosities and (b) a line graph; (c) Fluorescence emission spectra of the second derivative 9 at different viscosities and (d) a line graph,
fig. 5: (a) Variation of fluorescence intensity of the second derivative 9 at different temperatures; (b) Fluorescence emission spectra of the second derivative 9 before and after denaturation of the protein,
fig. 6: (a) Fluorescence emission spectra of the first derivative 7 at different pH and (b) a line graph; (c) Fluorescence emission spectra of the second derivative 9 at different pH and (d) a line graph,
fig. 7: (a) Fluorescence emission spectra of the first derivative 7 in the presence of different metal ions and (b) a bar graph; (c) Fluorescence emission spectra of the second derivative 9 in the presence of different metal ions and (d) bar graphs,
fig. 8: (a) Second derivative 9 at different concentrations of Al 3+ Fluorescence emission spectrum in the presence and (b) a standard curve,
fig. 9:9-Al 3+ The Job's curve of the system,
fig. 10: second derivative 9 and Al 3+ In the form of possible coordination patterns between them,
fig. 11: (a) Viability of a549 cells or (b) HepG-2 cells in light 30 minutes or dark conditions after incubation with different concentrations of the first derivative 7.
Detailed Description
The invention is further illustrated below with reference to examples.
Embodiments of the present invention are described in detail below. The examples described below are illustrative only and are not to be construed as limiting the invention. Those skilled in the art will appreciate that various changes and modifications can be made to the invention without departing from the spirit and scope thereof.
According to the invention, a benzophenone hydrazone group is introduced into a TB skeleton, so that a benzophenone hydrazone-TB derivative is designed and synthesized, and the benzophenone hydrazone-TB derivative is applied to the fields of viscosity response, metal ion identification, photodynamic therapy and the like.
The structural formula of the benzophenone hydrazone-TB derivative is shown in table 1:
TABLE 1 Synthesis of first derivative 7 and second derivative 9
In the embodiment, the preparation method takes 4-bromo-3-methoxyaniline, paraformaldehyde, N-butyllithium, N-dimethylformamide, hydrazine hydrate, methyl iodide and the like as raw materials to prepare the catalyst through multi-step reaction. The method comprises the following steps:
the first derivative 7 reacts with methyl iodide to obtain a first derivative 9, the first intermediate 3 reacts with N-butyllithium and N, N-dimethylformamide to obtain a second intermediate 4, benzophenone 5 reacts with hydrazine hydrate to obtain a third intermediate 6, the second intermediate 4 reacts with the third intermediate 6 to obtain the first derivative 7, 3-methoxy-4-bromoaniline 1 reacts with paraformaldehyde to obtain a first intermediate 3.
By the above synthetic method, the compounds of the following examples were prepared:
(1) Into a 250mL round bottom flask, 1 (60 mmol) and 2 (150 mmol) were added, the flask was placed in a low temperature tank and adjusted to-15℃and 120mL of trifluoroacetic acid was slowly dropped thereinto through a constant pressure dropping funnel, after the dropping was completed for about 30min, the reaction system was moved to the 25℃environment for 7 days. After completion of the reaction (TLC trace), quench with ice water, adjust ph=7 with aqueous ammonia, cool to room temperature, suction filter, wash three times with purified water, recrystallise with acetone to give the first intermediate 3 (65%).
Synthesis of intermediate 3 of equation 1
(2) First intermediate 3 (5.0 mmol) was added to a 100mL two-necked round bottom flask, the flask was purged three times and then placed in a low temperature tank to adjust the temperature to-45℃and 20mL of anhydrous tetrahydrofuran was added thereto with stirring, followed by dropwise addition of 5.0mL of n-butyllithium (1.6 mol. L) -1 ) After 1h of reaction under argon, 1.2mL of anhydrous DMF was added dropwise, followed by 4h of reaction at room temperature. After completion of the reaction by TLC, water was added, extraction was performed with dichloromethane, and the crude product was obtained by spin-drying. Purification of the crude product by column chromatography (V Petroleum ether :V Acetic acid ethyl ester =5:1) to afford second intermediate 4 (75%) as yellow-white.
Equation 2 Synthesis of second intermediate 4
(3) Benzophenone 5 (20.0 mmol) was added to a 50mL two-necked round bottom flask followed by sequential addition of 5.0mL ethanol and 5.0mL of 80% volume fraction hydrazine hydrate, and reflux was condensed with stirring for 20h. After the reaction is completed (TLC tracking), the reaction system is naturally cooled to room temperature, after crystals are separated out, the reaction system is placed in a low-temperature tank at 5 ℃ and stirred for about 1h, suction filtration is carried out, a filter cake is washed three times by cold ethanol, and then vacuum drying is carried out at 60 ℃ for 6h, thus obtaining a white needle-shaped third intermediate 6 (95%).
Equation 3 Synthesis of third intermediate 6
(4) Into a 50mL two-necked round bottom flask equipped with a reflux condenser, the second intermediate 4 (2.0 mmol) and the third intermediate 6 (4.2 mmol) were successively added, followed by 10mL of ethanol, and the temperature was adjusted to 80℃for reflux condensation for 6 hours. After TLC was followed until the reaction was completed, the reaction system was cooled naturally to room temperature, extracted with dichloromethane, the organic phase was dried over anhydrous sodium sulfate, and the crude product was obtained by spin-drying, followed by separation and purification by column chromatography (V Dichloromethane (dichloromethane) :V Methanol =20:1), ethanol recrystallization gave the first derivative 7 (55%) as a yellow product.
Synthesis of first derivative 7 of equation 4
(5) Into a 50mL two-necked round bottom flask, first derivative 7 (1.0 mmol) was added, 10mL of acetonitrile was further added, methyl iodide 8 (1.0 mL) was slowly added dropwise with stirring at room temperature, the temperature was raised to 82℃after the addition, and the mixture was refluxed for 6 hours under condensation. After the reaction was completed (TLC trace), after the reaction system was naturally cooled to room temperature, diethyl ether was slowly added dropwise to give a large amount of precipitate, which was then suction-filtered, and the cake was washed three times with diethyl ether and dried to give the second derivative 9 (85%).
Equation 5 Synthesis of second derivative 9
2,8-bis((E)-((diphenylmethylene)hydrazono)methyl)-3,9-dimethoxy-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine(7)
4.57(d,J＝16.3Hz,2H),4.24(s,2H),4.10(d,J＝16.3Hz,2H),3.83(s,6H). 13 C NMR(100MHz,CDCl 3 )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.
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)
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,2H),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-d 6 )δ165.36,165.01,159.33,158.68,146.81,143.43,137.95,137.49,135.45,135.14,133.29,130.16,129.01,128.46,120.82,114.84,108.48,106.67,66.41,57.45,56.75,51.36.
Solvation effect
The solvation effect of the compounds of the invention was tested, and the specific test protocol is as follows:
the first derivative 7 and the second derivative 9 are respectively treated with n-Hexane, toluene, tetrahydrofuran (THF), chloroform (CHCl) 3 ) Ethyl Acetate (EA), acetonitrile (MeCN), methanol (MeOH) and dimethyl sulfoxide (DMSO) were formulated to a concentration of 1 x 10 -5 mol·L -1 The solution was tested for its ultraviolet absorption and fluorescence emission spectra (fig. 1).
As can be seen from FIG. 1 (a), lambda of the first derivative 7 abs At about 360nm, n-pi is assigned to the hetero atom * The transition causes the R-band to absorb. The absorbance of the first derivative 9 in n-hexane is lower because of its lower solubility in n-hexane. Drawing of the figure1 (c), lambda of the second derivative 9 in acetonitrile abs Significantly blue shifted (344 nm), while lambda in other solvents abs About 400nm. Lambda of the second derivative 9 abs Lambda greater than the first derivative 7 abs It is possible that the second derivative 9 has positive ions in its structure, increasing the degree of charge separation, decreasing Δe, and electron transition is easier and smoother.
In FIGS. 1 (b) and (d), the Relative Fluorescence Intensity (RFI) of the first derivative 7 and the second derivative 9 in toluene is large, lambda, compared with other solvents em A significant red shift occurs.
Photophysical Properties
The photophysical properties of the second intermediate 4, the first derivative 7 and the second derivative 9 in solution were investigated, the specific test protocol being as follows:
weighing 10 -5 The second intermediate 4, the first derivative 7 and the second derivative 9 are dissolved in a solution to a concentration of 1X 10 -5 mol/L, ultraviolet absorption, fluorescence emission and solid state fluorescence emission spectra (1×10) -5 mol·L -1 Fig. 2).
The spectral data of the second intermediate 4, the first derivative 7 and the second derivative 9 are shown in table 2.
Table 2 spectral data of second intermediate 4, first derivative 7 and second derivative 9
a The ultraviolet absorption wavelength in the solution; b molar extinction coefficient epsilon=a/bC in 1×10 5 L·mol -1 ·cm -1 ； c Fluorescence emission wavelength in the solution; d stokes shift in solution; e relative fluorescence quantum yield (reference: quinine sulfate); f fluorescent brightness fb=ε.Φ, unit is l·mol -1 ·cm -1 ； g A solid state excitation wavelength; h solid state fluorescence emission wavelength; i solid Stokes displacement.
As can be seen in combination with fig. 2 and table 2, compared withUnmodified second intermediate 4, lambda of product first derivative 7 and second derivative 9 abs Significantly red shifted, increased epsilon and the first derivative 7 and the second derivative 9 have a longer lambda em (440 nm and 444 nm), Φ and FB increase greatly. The Stokes shift of the first derivative 7 and the second derivative 9 is also much larger than the second intermediate 4, but the Stokes shift of the second derivative 9 is slightly smaller than that of the first derivative 7, possibly influenced by the positive charge on the TB skeleton of the second derivative 9, the specific reason being yet to be studied further.
Therefore, the diphenyl ketone hydrazone group is introduced into the TB skeleton, the luminous performance of the product is obviously improved, and the method has the potential of being applied to the fields of ion identification, fluorescent probes and the like.
Viscosity response
The first derivative 7 and the second derivative 9 are prepared to have a concentration of 1×10 respectively by using methanol as a solvent -4 mol·L -1 Is not used for the working solution. Taking 5 volumetric flasks of 10mL, transferring 1.0mL of working solution into each volumetric flask, adding 0.0mL, 2.0mL, 4.0mL, 6.0mL and 8.0mL of glycerol respectively, and fixing the volume with methanol to make the concentration of the first derivative 7 or the second derivative 9 1×10 - 5 mol·L -1 Respectively measuring the fluorescence emission spectrum (lambda ex =330 nm and 340nm, slit: 5/10nm, FIG. 4).
As can be seen from fig. 4, when the glycerol content is increased from 0% to 60%, the fluorescence intensity of the first derivative 7 and the second derivative 9 is gradually increased, which is probably due to the fact that the molecular movement is limited with the increase of the viscosity, the pi-pi stacking effect is prevented, the non-radiative transition of the molecules is inhibited, and the fluorescence is increased; when the glycerol content was further increased to 80%, the fluorescence intensity of the first derivative 7 and the second derivative 9 was reduced, probably because larger aggregates were formed, and the increase in bulk density of the aggregates resulted in the reduction in fluorescence intensity.
The above results demonstrate the potential of the first derivative 7 and the second derivative 9 to become viscosity responsive fluorescent probes. We therefore carried out protein aggregation experiments using the second derivative 9 as an example and egg white as a sample: first, the stability of the second derivative 9 was studied, and the second derivative was dissolved in DMSO9 is prepared to have a concentration of 1X 10 -4 mol·L -1 Taking 5 volumetric flasks of 10mL, transferring 1.0mL of working solution of the second derivative 9 and 1.0mL of PBS buffer solution into each volumetric flask, and fixing the volume of DMSO to make the concentration of the working solution be 1X 10 -5 mol·L -1 . Placing each volumetric flask in water bath kettle, maintaining temperature at 20deg.C, 40deg.C, 60deg.C, 80deg.C and 100deg.C for five minutes, and measuring fluorescence intensity change (lambda) ex =270 nm, slit: 2.5/2.5nm, FIG. 5 a).
The second derivative 9 is then formulated in DMSO as a solvent to a concentration of 1X 10 -4 mol·L -1 The working solution of (2) is prepared by preparing egg white into 1X 10 concentration by PBS -4 mol·L -1 Is a solution of (a) and (b). Taking 2 volumetric flasks of 10mL, transferring 1.0mL of working solution of the second derivative 9 and 1.0mL of egg white solution into each volumetric flask, and fixing the volume of DMSO to ensure that the concentration of the second derivative 9 and the egg white in the system is 1X 10 -5 mol·L -1 . The measuring flasks were placed in a water bath at 25℃and 95℃for five minutes, respectively, and their fluorescence emission spectra (. Lamda.) were measured ex =270 nm, slit: 2.5/2.5nm, FIG. 5 b).
As can be seen from fig. 5 (a), the second derivative 9 showed little change in fluorescence intensity at different temperatures, indicating that the second derivative 9 has good thermal stability. From FIG. 5 (b), it is evident that the fluorescence intensity of the second derivative 9 is significantly increased after the protein denaturation (95 ℃ C.), and that the protein denaturation shows a synergistic effect on the fluorescence enhancement induced thereby. The temperature rise causes protein denaturation, so that the aggregation degree of molecules is increased, the rotation in the molecules is limited, and the non-radiative transition of the molecules is obviously inhibited, so that the fluorescence intensity is enhanced. It is clear that the second derivative 9 can be used as a "light-up" or "on" fluorescent probe for protein detection.
pH response
The first derivative 7 and the second derivative 9 are prepared to have a concentration of 1×10 respectively by using DMSO as a solvent -4 mol·L -1 1.0mL of the working solution is respectively measured in a 10mL volumetric flask, and then 1.0mL of buffer solution with pH value of 3-10 is added (citric acid/disodium hydrogen phosphate system is selected when the pH value is 3-8, and sodium bicarbonate/carbon is selected when the pH value is 9-10)Sodium acid system), DMSO to a volume to give a concentration of 1 x 10 for the first derivative 7 or the second derivative 9 -5 mol L -1 Fluorescence emission spectrum (. Lambda.) was measured ex =330 nm and 340nm, slit: 5/10nm, FIG. 6).
As can be seen from fig. 6, when the pH of the solution is 3-10, the fluorescence intensity of the first derivative 7 and the second derivative 9 does not change much, indicating that the pH application range is wide.
Recognition of metal ions
First derivative 7 second derivative and 9 and Na were tested + 、K + 、Mg 2+ 、Ca 2+ 、Fe 2+ 、Cu 2+ 、Zn 2+ 、Al 3+ 、Fe 3+ Fluorescence emission spectrum (lambda) ex =330 nm and 340nm, slit: 5/10nm, FIG. 7).
As can be seen from FIG. 7, al is added as compared with other metal ions 3+ After that, the fluorescence intensity of the first derivative 7 and the second derivative 9 was significantly enhanced, indicating that the first derivative 7 and the second derivative 9 were resistant to Al 3+ Has obvious recognition effect.
The change in fluorescence intensity of the first derivative 7 and the second derivative 9 after the addition of the metal ion is shown in tables 3 and 4.
TABLE 3 effects of first derivative 7 on different Metal ions
a The change rate of the fluorescence intensity of the compound after the metal ions are added, eta= (I-I) 0 )/I 0 X 100%. "-" indicates none.
TABLE 4 effects of second derivative 9 on different Metal ions
a The change rate of the fluorescence intensity of the compound after the metal ions are added, eta= (I-I) 0 )/I 0 X 100%. "-" indicates none.
As can be seen in combination with FIGS. 7,3 and 4, al was added 3+ After that, the fluorescence intensities of the first derivative 7 and the second derivative 9 increased by 73% and 167%, respectively, whereas when other metal ions were added, the fluorescence intensity changes were not significant, indicating that the first derivative 7 and the second derivative 9 were specific to Al 3+ Has better recognition effect. The second derivative 9 exhibits a specific activity on Al as compared with the first derivative 7 3 + More efficient recognition is possible that the existence of bridgehead nitrogen positive ions causes the molecular structure to distort, so that the exposure degree of lone pair electrons on two double bond N atoms and one oxygen atom which can participate in coordination at two ends is increased, and coordination bonds are more easily formed, and the specific reasons are yet to be explored further.
Subsequently, the second derivative 9-Al was explored 3+ Standard curve of system (lambda) ex =340 nm, slit: 10/10nm, FIG. 8).
As can be seen from FIG. 8, when Al 3+ The concentration is 1X 10 -5 -10×10 -5 mol·L -1 Within the range with Al 3+ Concentration is increased, lambda of the second derivative 9 em A certain blue shift occurs, the fluorescence intensity gradually rises at 443nm, and the fluorescence intensity is equal to Al 3+ The concentration has a linear relationship, R 2 For 0.99780, the linear equation y= 111.62424 ×10 5 x+1417.06667. Calculating 9 pairs of Al of the second derivative 3+ Is 1.56X10 LOD -6 mol·L -1 Is hopeful to detect Al in human body 3+ The content is as follows.
To further explore the efficient recognition of Al by the second derivative 9 3+ For the reasons of (a), job's curve (lambda ex =340 nm, slit: 10/10nm, concentration of 1X 10 -5 mol·L -1 Fig. 9).
As can be seen from FIG. 9, the second derivative 9 is derived from Al 3+ At a molar ratio of 3:7, the fluorescence intensity becomes inflection point, possibly the second derivative 9 and Al 3+ At a concentration ratio of 1:2, a formation is formedA complex. From this, it is assumed that the second derivative 9 and Al 3+ Possible coordination modes (fig. 10):
in vitro photodynamic therapy
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 the standard MTT method (FIG. 11).
As shown in fig. 11, the survival rate of a549 and HepG-2 cells after co-incubation with the first derivative 7 was higher under dark conditions, indicating that the dark toxicity of the first derivative 7 was lower; under the illumination condition, the mortality of the A549 and HepG-2 cells is obviously increased along with the increase of the concentration of the first derivative 7, and the concentration dependence is obvious. The mortality of A549 and HepG-2 cells was as high as 80% at a concentration of the first derivative 7 of 100.0. Mu.g/mL.
As can be seen from table 5, the toxicity of the first derivative 7 to both cells was low under dark conditions, indicating that the first derivative 7 had better biocompatibility. After 30min of illumination, the first derivative 7 has lower IC on A549 cells and HepG-2 cells 50 The values (28.2. Mu. Mol.L, respectively) -1 And 41.5. Mu. Mol.L -1 ) The PDT effect of the first derivative 7 was demonstrated to be excellent. 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 higher fluorescence quantum yield and fluorescence brightness, exhibiting more excellent optical properties, which may be related to the second derivative 9 having lower Δe and better electron mobility.
TABLE 5 half-maximal Inhibition (IC) of the first derivative 7 and the second derivative 9 on both cells 50 )
The foregoing is only a preferred embodiment of the invention, it being noted that: it will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the principles of the present invention, and such modifications and adaptations are intended to be comprehended within the scope of the invention.

Claims (6)

1. A benzophenone hydrazone-TB derivative is characterized in that: the structural formula of the compound is shown as the following first derivative (7) and second derivative (9):
2. a method for synthesizing a benzophenone hydrazone-TB derivative according to claim 1, wherein: the method comprises the following steps:
step 1, 3-methoxy-4-bromoaniline (1) reacts with paraformaldehyde to obtain a first intermediate (3), and the reaction formula is as follows:
step 2, the first intermediate (3) reacts with N-butyllithium and N, N-dimethylformamide to obtain a second intermediate (4), wherein the reaction formula is as follows:
step 3, the benzophenone (5) reacts with hydrazine hydrate to obtain a third intermediate (6), and the reaction formula is as follows:
step 4, the second intermediate (4) reacts with the third intermediate (6) to obtain a first derivative (7) of a product, wherein the reaction formula is as follows:
step 5, the first derivative (7) reacts with methyl iodide to obtain a second derivative (9), and the reaction formula is as follows:
3. use of a benzophenone hydrazone-TB derivative according to claim 1 as a viscosity response probe.
4. A benzophenone hydrazone-TB derivative as claimed in claim 1 as Al 3+ Use of fluorescent probes in metal ion recognition.
5. Use of a benzophenone hydrazone-TB derivative according to claim 1 as a photosensitizer for photodynamic therapy of tumors.
6. The use according to claim 5, wherein the use of the photosensitizer for photodynamic therapy of tumors is directed against the inhibition of human liver cancer HpeG2 cells and human lung cancer a549 cells.
CN202310851242.0A 2023-07-12 2023-07-12 Benzophenone hydrazone-TB derivative and synthetic method and application thereof Pending CN116891478A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202310851242.0A CN116891478A (en) 2023-07-12 2023-07-12 Benzophenone hydrazone-TB derivative and synthetic method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202310851242.0A CN116891478A (en) 2023-07-12 2023-07-12 Benzophenone hydrazone-TB derivative and synthetic method and application thereof

Publications (1)

Publication Number Publication Date
CN116891478A true CN116891478A (en) 2023-10-17

Family

ID=88314480

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202310851242.0A Pending CN116891478A (en) 2023-07-12 2023-07-12 Benzophenone hydrazone-TB derivative and synthetic method and application thereof

Country Status (1)

Country Link
CN (1) CN116891478A (en)

Similar Documents

Publication Publication Date Title
Jiang et al. Double-detecting fluorescent sensor for ATP based on Cu2+ and Zn2+ response of hydrazono-bis-tetraphenylethylene
CN109867611B (en) Water-soluble two-photon hydrogen sulfide fluorescent probe for detecting red wine and hydrogen sulfide in vivo and preparation method and application thereof
Tarakanov et al. Porphyrazines with annulated diazepine rings. 3.⊗ MgII complex of 4-tert-Butylphenyl substituted tetra (1, 4-diazepino) porphyrazine: synthesis and peculiar effect of solvent on its spectral properties
Jiang et al. Dimethoxy triarylamine-derived terpyridine–zinc complex: a fluorescence light-up sensor for citrate detection based on aggregation-induced emission
Begum et al. Synthesis, characterization, photoluminescence and electrochemical studies of NiII, CuII, ZnII, CdII and PdII complexes of the bidentate S-hexyl-β-N-(2-thienyl) methylenedithiocarbazate ligand
Eçik et al. Synthesis of BODIPY-cyclotetraphosphazene triad systems and their sensing behaviors toward Co (II) and Cu (II)
CN111793371B (en) 3, 5-asymmetrically modified BODIPY near-infrared fluorescent dye and preparation method thereof
CN113004313A (en) Double-thiophene-double-coumarin-based BODIPY near-infrared fluorescent dye and preparation method thereof
CN116891478A (en) Benzophenone hydrazone-TB derivative and synthetic method and application thereof
EP3757111A1 (en) Ruthenium (ii) complexes and conjugates thereof for use as photosensitizer agent in photodynamic therapy
KR100963136B1 (en) Derivative of Coumarin capable of using Cu II selectivity and manufacturing method thereof
EP2758391B1 (en) Luminescent probes for biological marking and imagery, and preparation method thereof
Safonova et al. 5, 8-Disubstituted crown-naphthalonitriles as a platform for highly soluble naphthalocyanines
Bayar et al. The synthesis of some phthalocyanines derived from bulky substituted phthalonitriles
CN111579542B (en) Application of derivative
CN114736153A (en) AIE type azozyme fluorescent small-molecule probe and preparation method thereof
JP3817637B2 (en) Dipyridylbenzothiadiazole derivatives
CN117024433A (en) naphthalimide-TB compound and synthetic method and application thereof
CN115521293B (en) Hydrazide luminescent dye, and preparation method and application thereof
CN105911038B (en) It is a kind of to detect aluminum ions method using reactive dye fluorescence probe
Ortiz et al. Nitric oxide binding and photodelivery based on ruthenium (II) complexes of 4-arylazo-3, 5-dimethylpyrazole
Tikhomirova et al. Synthesis and spectral luminescent properties of 4, 4´, 4´´, 4´´´-tetra (tert-butyl)-5, 5´, 5´´, 5´´´-tetrakis (phenylsulfanyl) phthalocyanines and their sulfo acids
WO2023037843A1 (en) Novel double-squaraine dye and method for producing same
CN113735864B (en) D-benzothiadiazole-TB (-D) derivative and synthetic method and application thereof
CN117402165A (en) pyridine-TB derivatives, and synthetic method and application thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination