A compound containing an indole and quinoline skeleton and use thereof

Abstract

The present application relates to a kind of compound containing indole and quinoline skeleton and its application, belong to chemical technical field.The structural formula of the compound is as shown in formula I.The present application also provides the application of the compound in detecting specific metal ions, and the specific metal ions include copper ion (Cu 2+ ), manganese ion (Mn 2+ ), lead ion (Pb 2+ ), iron ion (Fe 3+ ).The present application includes the following technical effects:1) the novel compound containing indole and quinoline skeleton provided by the present application, as fluorescent probe, can detect trace Cu 2+ And Mn 2+ Two metal ions in the same test system.2) the present application provides the detection method for detecting trace Cu 2+ And Mn 2+ Based on novel probe, which is simple to operate, low in cost, without the aid of large instrument.Only need to use ultraviolet visible spectrophotometer, fluorescence spectrophotometer or simple ultraviolet lamp or ordinary visual method can be qualitative or quantitative judgment.

Description

Technical Field

[0001] This invention relates to a compound containing an indole and quinoline skeleton and its applications, belonging to the field of chemical technology. Background Technology

[0002] Transition metals are widely used in chemistry, medicine, biology, and environmental fields. Cu and Mn belong to the first transition metals and are also essential trace elements for the human body. Insufficient or excessive intake can lead to specific diseases or poisoning. Manganese, in particular, can act as a cofactor for certain proteins, participating in the regulation of human immunity, energy production, growth, coagulation, and hemostasis, as well as removing abnormal oxidative stress byproducts. Manganese poisoning mainly manifests as extrapyramidal side effects, similar to Parkinson's syndrome, and is more common in specific occupational groups such as mining, welding, smelting, and battery manufacturing. Drinking contaminated water is also a significant cause of manganese poisoning. The World Health Organization's Guidelines for Drinking Water Quality (4th Edition) recommends that the manganese content in drinking water be below 400 μg / L. In addition, some stainless steel products in daily life, such as 304 stainless steel products, may have excessive manganese levels (>2%), and the use of the pesticide manganese thiocyanate also increases the risk of manganese poisoning in the environment. Copper is a cofactor in many proteins and participates in catalyzing redox processes in organisms. However, excessive copper can cause oxidative stress, induce DNA damage, and inhibit cell proliferation. Copper poisoning is usually caused by accidental ingestion of contaminated water, use of topical creams containing copper salts, or cooking acidic foods in uncoated copper cookware. Copper sulfate, as a readily available chemical, is commonly used in agriculture as a bactericide, fungicide, and algaecide, and also in industry, such as in textiles, leather, wood, batteries, inks, petroleum, and paints. Therefore, monitoring the copper and manganese content in the environment or specific industrial and agricultural products, and developing low-cost detection reagents and methods, is of great significance.

[0003] Currently, methods for detecting metal ions such as copper and manganese mainly include atomic absorption spectrometry, atomic emission spectrometry, ultraviolet-visible spectrophotometry, inductively coupled plasma atomic emission spectrometry, fluorescence methods, as well as chromatography, mass spectrometry, and electrochemical analysis. Fluorescence spectroscopy, due to its advantages of low cost, simple operation, and high sensitivity, is one of the preferred methods for detecting trace amounts of metal ions. Developing suitable fluorescent probes is the foundation and prerequisite for implementing fluorescence methods.

[0004] In recent years, various fluorescent probes with different fluorophore structures have been reported. Quinoline, as a good fluorophore framework, has been used in the development of various fluorescent probes, and the resulting probes can be used for metal ion (Zn) synthesis. 2+ Mg 2+ Fe 2+ / Fe 3+ Hg 2+ Al 3+ Co 2+ Cu 2+ (See Zhou Chen's 2015 doctoral dissertation at Jilin University, titled "Synthesis of Fluorescent Probes Based on Quinoline Derivatives and Their Application in the Detection of Metal Ions")

[0005] However, existing technologies also have the following problems:

[0006] 1. Many methods for metal ion detection, such as X-ray photoelectron spectroscopy (XPS), atomic absorption spectroscopy, and inductively coupled plasma atomic emission spectroscopy, require complex sample processing procedures and large instruments.

[0007] 2. Currently, there is a lack of methods to simultaneously detect Cu in the same testing system. 2+ and Mn 2+ Low-cost fluorescent probes for two transition metal ions.

[0008] Therefore, it is necessary to develop a method that can simultaneously detect Cu without requiring complex sample processing procedures or large instruments. 2+ and Mn 2+ The bifunctional fluorescent probes and detection methods for two transition metal ions will make detection more efficient and reduce costs. Summary of the Invention

[0009] To fill the gaps in the prior art, this invention provides a compound containing an indole and quinoline skeleton and its applications.

[0010] The concept of this invention is as follows: Based on the 8-hydroxyquinoline skeleton, this invention introduces an indole fragment for the first time, designing and synthesizing a previously unreported fluorescent probe containing both indole and quinoline skeletons. Compared with existing fluorescent probes, the probe molecule designed in this invention firstly possesses a novel chemical structure, and secondly, it can simultaneously detect Cu with extremely high sensitivity in the same testing system. 2+ and Mn 2+ Two metal ions.

[0011] The specific technical solution of the present invention is as follows:

[0012] In a first aspect of the invention, a compound containing an indole and a quinoline skeleton is provided, the compound having a structural formula as shown in general formula (I):

[0013]

[0014] Wherein, R is selected from any of the following groups: H, halogens, and other common substituents such as C1-C6 alkyl, methoxy, nitro, amino, cyano, carboxyl, ester, trifluoromethyl, trifluoromethoxy, etc. "alkyl" refers to a fully saturated hydrocarbon chain, which can be straight or branched.

[0015] Preferably, in the structural formula shown in the general formula (I), R is H or Cl.

[0016] In a preferred embodiment of the present invention, the general formula (I) of the present invention is a compound selected from any one of the following two types of compounds:

[0017] N'-{(8-hydroxy-2-quinolinyl)methylene}-1H-indole-2-formylhydrazine

[0018] 5-Chloro-N'-{(8-hydroxy-2-quinolinyl)methylene}-1H-indole-2-carboxylhydrazine

[0019] The specific structures of the two compounds are shown in the table below:

[0020] Table 1 Preferred compound structures

[0021]

[0022] In a second aspect of the invention, a composition is provided comprising the compound as described in the first aspect, as well as commonly used chemical solvents and excipients.

[0023] In a third aspect of the invention, a loading material is provided, the loading material comprising a compound as described in the first aspect or a composition as described in the second aspect, and a specific carrier material for loading or molding. In this invention, a loading material refers to a compound as described in the first aspect or a composition as described in the second aspect loaded onto a specific carrier material, the carrier material including but not limited to various membrane materials, paper materials, polymer materials, nanomaterials, and carbon-based materials.

[0024] In a fourth aspect of the invention, the use of the compound as described in the first aspect, the composition as described in the second aspect, or the loading as described in the third aspect in the detection of a metal ion, wherein the metal ion is copper ion (Cu). 2+ ), manganese ions (Mn) 2+ ), lead ions (Pb) 2+ ) or iron ions (Fe 3+ ).

[0025] Furthermore, the present invention provides for the simultaneous detection of Cu in the same test system using the compound as described in the first aspect, the composition as described in the second aspect, or the loading as described in the third aspect. 2+ and Mn2+ Applications of metal ions.

[0026] In a fifth aspect of the invention, a method for synthesizing the compound as described in the first aspect is provided.

[0027] To achieve the synthetic objective of this invention, the following synthetic technique is used to prepare compounds of general formula (I), where R in compound (I) is H or Cl:

[0028]

[0029] When R in the compound of general formula (I) is H, the compound is N'-{(8-hydroxy-2-quinolinyl)methylene}-1H-indole-2-formylhydrazine, and its preparation method includes the following steps:

[0030] 1) Compound 1a, namely ethyl indole-2-carboxylate, was subjected to a condensation reaction with 85% hydrazine hydrate to obtain compound 2a, namely 1H-indole-2-carboxylate; wherein the molar ratio of ethyl indole-2-carboxylate to hydrazine hydrate was 1:(2-10), the solvent was DMF, the reaction temperature was reflux temperature, and the reaction time was 6-18 h;

[0031] 2) Compound 3, namely 2-methyl-8-hydroxyquinoline, was oxidized with selenium dioxide to obtain compound 4, namely 8-hydroxyquinoline-2-carboxaldehyde; wherein the molar ratio of compound 3 to selenium dioxide was 1:(1.5~3), the solvent was 1,4-dioxane, the reaction temperature was 95℃, and the reaction time was 6~18h.

[0032] 3) Compound 2a and compound 4 were subjected to a condensation reaction catalyzed by acetic acid to obtain compound 5a, namely N'-{(8-hydroxy-2-quinolinyl)methylene}-1H-indole-2-carboxylhydrazine; the molar ratio of compound 2a, compound 4 and acetic acid was 1:(0.8~1.2):(0~6), the solvent was ethanol, the reaction temperature was 80℃, and the reaction time was 3~8h.

[0033] Preferably,

[0034] In step 1), the molar ratio of indole-2-carboxylic acid ethyl ester to hydrazine hydrate is 1:3 or 1:5.

[0035] In step 2), the molar ratio of compound 3 to selenium dioxide is 1:2.

[0036] In step 3), the molar ratio of compound 2a, compound 4 and acetic acid is 1:1:3.

[0037] When R in the compound of general formula (I) is Cl, the compound is 5-chloro-N'-{(8-hydroxy-2-quinolinyl)methylene}-1H-indole-2-formylhydrazine, and its preparation method includes the following steps:

[0038] 1) Compound 1b, namely ethyl 5-chloroindole-2-carboxylate, was subjected to a condensation reaction with 85% hydrazine hydrate to obtain compound 2b, namely 5-chloro-1H-indole-2-carboxyhydrazide; the molar ratio of ethyl 5-chloroindole-2-carboxylate to hydrazine hydrate was 1:(2-10), the solvent was ethanol, the reaction temperature was reflux temperature, and the reaction time was 6-18 h;

[0039] 2) Compound 3, namely 2-methyl-8-hydroxyquinoline, was oxidized with selenium dioxide to obtain compound 4, namely 8-hydroxyquinoline-2-carboxaldehyde; wherein the molar ratio of compound 3 to selenium dioxide was 1:(1.5~3), the solvent was 1,4-dioxane, the reaction temperature was 95℃, and the reaction time was 6~18h.

[0040] 3) Compound 2b and compound 4 were subjected to a condensation reaction catalyzed by acetic acid to obtain compound 5b, namely 5-chloro-N'-{(8-hydroxy-2-quinolinyl)methylene}-1H-indole-2-carboxylhydrazine; the molar ratio of compound 2b, compound 4 and acetic acid was 1:(0.8~1.2):(0~6), the solvent was ethanol, the reaction temperature was 80℃, and the reaction time was 3~8h.

[0041] Preferably,

[0042] In step 1), the molar ratio of ethyl 5-chloroindole-2-carboxylate to hydrazine hydrate is 1:3 or 1:5.

[0043] In step 2), the molar ratio of compound 3 to selenium dioxide is 1:2.

[0044] In step 3), the molar ratio of compound 2b, compound 4 and acetic acid is 1:1:3.

[0045] The present invention has the following technical effects:

[0046] 1) The novel compound containing indole and quinoline skeletons provided by this invention, as a fluorescent probe, can simultaneously detect trace amounts of Cu in the same test system. 2+ and Mn 2+ The detection limits for the two metal ions are below 5 × 10⁻⁶. -7 mol / L.

[0047] 2) This invention provides a novel probe-based method for detecting trace amounts of Cu. 2+ and Mn 2+The detection method is simple to operate, low in cost, and does not require large instruments. Qualitative or quantitative judgment can be made using only a UV-Vis spectrophotometer, a fluorescence spectrophotometer, a simple UV lamp, or ordinary visual inspection.

[0048] 3) This invention also provides a method for synthesizing this fluorescent probe, which can efficiently prepare the target compound. Attached Figure Description

[0049] Figure 1 The effects of different metal ions on the fluorescence spectra of the probes are shown. In this diagram, a represents the effect of different metal ions on the fluorescence spectrum of probe 5a; and b represents the effect of different metal ions on the fluorescence spectrum of probe 5b.

[0050] Figure 2 The effect of different metal ions on the fluorescence intensity of probes 5a and 5b at specified emission wavelengths (5a: 470.2 nm, 5b: 471 nm) is shown. Figure a is a bar chart, and figure b is a tabular representation.

[0051] Figure 3 The effect of different concentrations of copper ions on the fluorescence spectrum and fluorescence intensity of the probe is shown. Here, a represents the effect of different concentrations of copper ions on the fluorescence spectrum of probe 5a; b represents the change curves of fluorescence intensity of probe 5a at an emission wavelength of 470.2 nm after treatment with different concentrations of copper ions.

[0052] Figure 4 The effect of different concentrations of manganese ions on the fluorescence spectrum and fluorescence intensity of probe 5b is shown. In figure a, the effect of different concentrations of manganese ions on the fluorescence spectrum of probe 5b is shown; in figure b, the fluorescence intensity of probe 5b at an emission wavelength of 471 nm is shown after treatment with different concentrations of manganese ions.

[0053] Figure 5 The linear relationship between the fluorescence intensity of the probe and the concentration of metal ions is given. Here, a represents the linear relationship between the fluorescence intensity of probe 5a and the concentration of metal ions; b represents the linear relationship between the fluorescence intensity of probe 5b and the concentration of metal ions.

[0054] Figure 6 The effects of different concentrations of metal ions on the UV absorption spectrum and absorption intensity of the probe are shown. In this diagram, a represents the effect of different concentrations of metal ions on the UV absorption spectrum and absorption intensity of probe 5a; b represents the effect of different concentrations of metal ions on the UV absorption spectrum and absorption intensity of probe 5b.

[0055] Figure 7 The results of the fluorescence quenching and recovery experiments for the probes are shown. Where a represents the fluorescence quenching and recovery experiment results for probe 5a; and b represents the fluorescence quenching and recovery experiment results for probe 5b. Detailed Implementation

[0056] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. Obviously, the described embodiments are only some embodiments of this invention, and not all embodiments.

[0057] The main instruments involved in this invention and their sources of purchase are as follows:

[0058] LS220A electronic balance (Shanghai Tianmei Balance Instrument Co., Ltd.); DF-101S thermostatic heating magnetic stirrer, SHZ-D(Ⅲ) circulating water vacuum pump, RE-52AA rotary evaporator (Gongyi Yuhua Instrument Co., Ltd.); ZF-2 dark box ultraviolet analyzer (Shanghai Guanghao Analytical Instrument Co., Ltd.); Agilent 1200 LC-MS mass spectrometer (Agilent Technologies, USA); Bruker AV-400 nuclear magnetic resonance spectrometer (Bruker GmbH, Switzerland); IRAffinity-1S infrared spectrometer (Shimadzu Corporation, Japan); F-7000 fluorescence spectrophotometer (Hitachi Corporation, Japan); pipette (Dalong Xingchuang Experimental Instruments (Beijing) Co., Ltd.).

[0059] The main reagents involved in this invention and their sources of purchase are as follows:

[0060] Ethyl indole-2-carboxylate (analytical grade, Shanghai Bid Pharmaceutical Technology Co., Ltd.), dimethyl sulfoxide, zinc chloride (analytical grade, Shanghai Maclean Biochemical Technology Co., Ltd.); 2-methyl-8-hydroxyquinoline, selenium dioxide, ferric chloride (analytical grade, Jiuding Chemical (Shanghai) Technology Co., Ltd.); hydrazine hydrate (85%), potassium chloride, sodium chloride, aluminum chloride, zinc chloride, titanium trichloride, cadmium chloride, silver nitrate, chromium nitrate (nonahydrate), lead nitrate, calcium nitrate, barium nitrate, strontium nitrate, magnesium sulfate, manganese sulfate monohydrate, copper sulfate (pentahydrate), mercuric sulfate (analytical grade, Sinopharm Chemical Reagent Co., Ltd.).

[0061] Example 1: Preparation of N'-{(8-hydroxy-2-quinolinyl)methylene}-1H-indole-2-carboxylhydrazine (5a, SC-1)

[0062] Step 1: Synthesis of 1H-indole-2-formylhydrazide (2a)

[0063] 1.0 g (5.29 mmol) of ethyl indole-2-carboxylate was dissolved in 10 mL of DMF, followed by the addition of 933.8 mg (15.86 mmol) of 85% hydrazine hydrate. The reaction was carried out overnight at 80 °C, and the reaction was monitored by TLC (DCM:MeOH = 10:1). After the reaction was complete, the mixture was cooled, a small amount of purified water was added, and the precipitated solid was filtered. The product was recrystallized from ethanol to give 612.4 mg of a white solid, compound 2a, in 66% yield. 1 HNMR (DMSO-d6, 400MHz), δ: 11.59 (s, 1H); 9.77 (s, 1H); 7.59 (d, J = 8.0Hz, 1H); 7.43 (d, J =8.2Hz,1H);7.22-7.12(m,1H);7.08(d,J=1.4Hz,1H);7.05-6.95(m,1H);4.50(s,2H). 13 C NMR (DMSO-d6, 101MHz), δ: 161.22, 136.32, 130.50, 127.12, 123.10, 121.40, 119.70, 112.26, 101.84.

[0064] Step 2 Synthesis of 8-hydroxyquinoline-2-carboxaldehyde (4)

[0065] 4.18 g (37.7 mmol) of selenium dioxide was added to 50 mL of 1,4-dioxane and heated to 60 °C. Then, 3.00 g (18.85 mmol) of 2-methyl-8-hydroxyquinoline was dissolved in 10 mL of 1,4-dioxane and slowly added dropwise to the above reaction solution. The temperature was raised to 95 °C and the reaction was carried out for approximately 18 h. The reaction was monitored by TLC (PE:EA = 10:1). After the reaction was complete, the solid insoluble matter was removed by filtration. Water was added to the filtrate, and the mixture was extracted twice with ethyl acetate. The combined organic layers were washed successively with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent, PE:EA = 10:1) to give 1.65 g of pale yellow solid compound 4, yield 50.56%. Melting point: 95–96 °C.

[0066] Step 3: Synthesis of compound 5a

[0067] 150 mg (0.86 mmol) of 1H-indole-2-carboxylhydrazide and 148.27 mg (0.86 mmol) of 8-hydroxyquinoline-2-carboxaldehyde were dissolved in 20 mL of anhydrous ethanol, and 0.15 mL (approximately 3 drops) of acetic acid (157.5 mg, 2.62 mmol) was added. The reaction was carried out at 80 °C for 4 h, and monitored by TLC (DCM:MeOH = 10:1). After the reaction was completed, the mixture was directly filtered, washed with purified water, dried, and then recrystallized from ethyl acetate to give 238 mg of white solid, with a yield of 84.14%.1 H NMR (DMSO-d6, 400MHz), δ: 12.27 (s, 1H); 11.90 (s, 1H); 9.84 (s, 1H); 8.68 (s, 1H); 8.37 (d, J = 8.7Hz, 1H); 8.14 (d, J = 8. 6Hz, 1H); 7.72 (d, J = 8.0Hz, 1H); 7.55-7.33 (m, 4H); 7.29-7.21 (m, 1H); 7.15 (dd, J = 7.4, 1.5Hz, 1H); 7.12-7.03 (m, 1H). 13 C NMR(DMSO-d6,101MHz),δ:157.95,153.45,151.78,147.25,138.18,137.05,136.66,129.79 ,128.84,128.35,126.99,124.18,121.95,120.12,117.88,117.78,112.49,112.21,104.37. HR-MS(ESI),C 19 H 14 N4O2, measured (calculated), m / z: 331.1194 (331.1117) [M+H] + ;353.1013(353.1014)[M+Na] + .

[0068] Example 2 Preparation of 5-chloro-N'-{(8-hydroxy-2-quinolinyl)methylene}-1H-indole-2-carboxylhydrazide (5b, SC-2)

[0069] Step 1: Synthesis of 5-chloro-1H-indole-2-formylhydrazide (2b)

[0070] 0.7 g (3.13 mmol) of ethyl 5-chloroindole-2-carboxylate was dissolved in 30 mL of anhydrous ethanol, followed by the addition of 921.7 mg (15.65 mmol) of 85% hydrazine hydrate. The reaction was carried out overnight at 80 °C, and the reaction was monitored by TLC (DCM:MeOH = 10:1). After the reaction was complete, the mixture was cooled, and two-thirds of the solvent was removed by vacuum distillation. A small amount of purified water was added, and the precipitated solid was filtered. The product was recrystallized from ethanol to give 350.0 mg of white solid compound 2b, with a yield of 53%. 1 HNMR (DMSO-d6, 400MHz), δ: 11.81 (s, 1H); 9.86 (s, 1H); 7.67 (d, J = 1.9Hz, 1H); 7.43 (d, J=8.7Hz, 1H); 7.17 (dd, J=8.7, 2.1Hz, 1H); 7.07 (s, 1H); 4.53 (s, 2H). 13C NMR (DMSO-d6, 400MHz), δ: 160.73, 134.71, 132.05, 128.18, 124.21, 123.21, 120.46, 113.82, 101.39.

[0071] Step 2 Synthesis of 8-hydroxyquinoline-2-carboxaldehyde (4)

[0072] Refer to step 2 of Example 1.

[0073] Step 3: Synthesis of compound 5b

[0074] 100 mg (0.48 mmol) of 5-chloro-1H-indole-2-carboxylhydrazide and 82.6 mg (0.48 mmol) of 8-hydroxyquinoline-2-carboxaldehyde were synthesized according to method 5a to give 137 mg of white solid, with a yield of 78.7%. 1 H NMR (DMSO-d6, 400MHz), δ: 12.37 (s, 1H); 12.13 (s, 1H); 9.88 (s, 1H); 8.67 (s, 1H); 8.37 (d, J = 8.4Hz, 1H ); 8.13 (d, J = 7.9Hz, 1H); 7.83 (s, 1H); 7.74-7.33 (m, 4H); 7.26 (d, J = 8.5Hz, 1H); 7.15 (d, J = 7.0Hz, 1H). 13 C NMR(DMSO-d6,101MHz),δ:157.63,153.46,151.69,147.61,138.18,136.67,135.41,131.32 ,128.86,128.39,128.00,124.58,124.27,121.01,117.88,117.79,114.09,112.21,103.85. HR-MS(ESI),C 19 H 13 ClN4O2, measured value (calculated value), m / z: 365.0807 (365.0727) [M+H] + .

[0075] Example 3: Establishment of Test Conditions and Ion Screening

[0076] Probe working solutions 5a and 5b were prepared using the compounds prepared in Examples 1 and 2, respectively. Additionally, various metal ion working solutions were prepared using the inorganic salts listed in the specific embodiments.

[0077] The preparation method is as follows:

[0078] (1) Preparation of stock solution and working solution. The fluorescent probe molecule is prepared into a 10 mmol / L DMSO solution and diluted with DMSO to a 100 μmol / L working solution, which is the probe working solution. Different inorganic salts are prepared into 20 mmol / L aqueous solutions and diluted with DMSO to 100 μmol / L and 500 μmol / L working solutions, which are the metal ion working solutions.

[0079] (2) Spectroscopic test parameters. Fluorescence spectroscopy was performed using a wavelength scan test type, emission scan mode, a scan rate of 1200 nm / min, fluorescence data mode, with an excitation wavelength of 345 nm, an emission wavelength range of 350–650 nm, an excitation and emission slit bandwidth of 5 nm, and a voltage of 400 V. Ultraviolet spectroscopy was performed using a scanning mode, with a scanning wavelength range of 600.0–300.0 nm.

[0080] (3) Ion recognition screening spectral test experiment. 200 μL of probe working solution (100 μmol / L), 400 μL of metal ion working solution (500 μmol / L), and 1400 μL of DMSO were added to a cuvette. After addition, the mixture was incubated in the dark for 5 min, with periodic shaking, to obtain a 2 mL detection solution system. The final concentration of the fluorescent probe was 10 μmol / L, the final concentration of the metal ions was 100 μmol / L, and the water content of the test system was less than 1%. The results were measured using a fluorescence spectrophotometer.

[0081] See results Figures 1-2 As shown. Figure 1 The effects of different metal ions on the fluorescence spectrum of the probe are shown, where a represents the effect of different metal ions on the fluorescence spectrum of probe 5a; and b represents the effect of different metal ions on the fluorescence spectrum of probe 5b. Figure 2 The effects of different metal ions on the fluorescence intensity of probes 5a and 5b at specified emission wavelengths (5a: 470.2 nm, 5b: 471 nm) are shown in bar graphs (a) and tabular data (b). The results indicate that solutions of probes 5a and 5b, upon contact with Mn... 2+ and Cu 2 + Afterwards, a significant fluorescence intensity quenching phenomenon occurs. This is particularly true for excess Cu. 2+ The addition of Mn quenched the fluorescence intensity of the 5a solution to 0.4%, and the excess Mn 2+ The addition of Cu quenched the fluorescence intensity of solution 5a to 4.4%. Probe 5b also exhibited a similar phenomenon; excess Cu quenched the fluorescence intensity of solution 5a to 4.4%. 2+ The addition of [Mn] quenched the fluorescence intensity of the 5b solution to 0.5%, and the excess Mn [was present]. 2+The addition of [a specific compound] quenched the fluorescence intensity of the 5b solution to 1.6%. Furthermore, both compounds [affected] Fe [resources / effects]. 3+ They also exhibited weak recognition ability, with the fluorescence intensities of 5a and 5b quenched to 50.5% and 65.7%, respectively. Furthermore, compound 5b showed poor recognition of Pb. 2+ It also exhibited weak recognition ability, with fluorescence intensity quenched to 39.3%.

[0082] Overall, compounds 5a and 5b are effective against Mn 2+ and Cu 2+ It exhibits very strong recognition ability, with fluorescence intensity quenching as low as 4.4%, and possesses a certain degree of selectivity.

[0083] Example 4: Probe response to metal ion concentration experiment

[0084] Following the method in Example 3, probe working solutions for probes 5a and 5b, as well as metal ion working solutions, were prepared respectively.

[0085] Using a similar ion screening method as in Example 3, 200 μL of probe working solution (100 μmol / L), 0–800 μL of metal ion working solution (100 μmol / L), and 1000–1800 μL of DMSO were added to a cuvette. After addition, the solution was incubated in the dark for 5 min, with periodic shaking, to obtain a 2 mL detection solution system. The final concentration of the fluorescent probe was 10 μmol / L, and the concentration of the metal ions was 0–40 μmol / L. Measurements were performed using a fluorescence spectrophotometer and a UV-Vis spectrophotometer; the test parameters are described in Example 3.

[0086] Figure 3 The effects of different concentrations of copper ions on the fluorescence spectrum and fluorescence intensity of the probe are shown in Figure a. Figure a shows the effect of different concentrations of copper ions on the fluorescence spectrum of probe 5a. Figure b shows the fluorescence intensity of probe 5a at an emission wavelength of 470.2 nm after treatment with different concentrations of copper ions. Figure 4 The effects of different concentrations of manganese ions on the fluorescence spectrum and fluorescence intensity of probe 5b are shown in Figure a. Figure a represents the effect of different concentrations of manganese ions on the fluorescence spectrum of probe 5b; Figure b represents the fluorescence intensity change curves of probe 5b at an emission wavelength of 471 nm after treatment with different concentrations of manganese ions. It can be observed that the fluorescence quenching rate of the probe molecule increases with increasing metal ion concentration, exhibiting a good linear relationship within a certain concentration range.

[0087] Based on the above, we will continue to analyze the linear range and detection limit of the probe for detecting the two metal ions, providing a foundation for the subsequent establishment of quantitative detection methods. Figure 5This represents the linear relationship between the fluorescence intensity of the probe and the concentration of metal ions, where a is the linear relationship between the fluorescence intensity of probe 5a and the concentration of metal ions; and b is the linear relationship between the fluorescence intensity of probe 5b and the concentration of metal ions. For example... Figure 5 As shown in Figure a, compound 5a is used to detect Cu. 2+ The linear concentration range is 0–10 μmol / L, and the linear equation is y = -12.6394x + 167.9071, R0 2 The value is 0.9961. Based on the limit of detection (LOD) formula LOD = 3σ / m, the value of probe 5a for Cu is calculated. 2+ The detection limit is 0.095 μmol / L. For example... Figure 5 As shown in b, compound 5b is used to detect Mn. 2+ The linear concentration range is 0–25 μmol / L, and the linear equation is y = -5.0610x + 191.6499, R0. 2 The value is 0.9992. Based on the formula LOD = 3σ / m, the value of probe 5b for Mn is calculated. 2+ The detection limit was 0.33 μmol / L. These results indicate that probes 5a and 5b are effective against Cu. 2+ and Mn 2+ The detection of both ions showed high sensitivity.

[0088] In addition to using fluorescence detection, UV-Vis spectrophotometry was also used to investigate the probe's response to the concentrations of copper and manganese ions. The absorption spectra results are as follows: Figure 6 As shown. Figure 6 The effects of different concentrations of metal ions on the UV absorption spectrum and absorption intensity of the probe are shown. In this diagram, a represents the effect of different concentrations of metal ions on the UV absorption spectrum and absorption intensity of probe 5a; b represents the effect of different concentrations of metal ions on the UV absorption spectrum and absorption intensity of probe 5b.

[0089] Two compounds recognize Cu 2+ or Mn 2+ They exhibited similar UV absorption curves. Based on the spectral results, 5a-Cu was selected. 2+ At 420nm ( Figure 6 a) and 5b-Mn 2+ At 406nm ( Figure 6 b) Linear analysis was performed on the absorbance at a given wavelength corresponding to the ion concentration. The results showed that the change in probe absorbance intensity exhibited a good linear relationship with the ion concentration.

[0090] The above results indicate that this method can be used for metal ions (Mn) 2+ and Cu 2+ Content determination. Probes 5a and 5b were used for Cu content determination. 2 +and Mn 2+ The detection of both ions showed high sensitivity.

[0091] Example 5 Fluorescence Quenching and Recovery Experiment

[0092] Add 200 μL of probe working solution (100 μmol / L) and 1400 μL of DMSO to a cuvette, mix for 30 s, and record the mixture under sunlight and 365 nm UV light. Then add 400 μL of metal ion working solution (500 μmol / L), mix for 30 s, and record the mixture under sunlight and 365 nm UV light (final concentration of fluorescent probe is 10 μmol / L, final concentration of metal ions is 100 μmol / L). Finally, add 10 μL of 20 mmol / L EDTA solution (final concentration is approximately 100 μmol / L), mix for 30 s, and record the mixture under sunlight and 365 nm UV light.

[0093] See results Figure 7 As shown. Ten molar amounts of metal ions (Mn) were added to the probe solution. 2+ or Cu 2+ The solution changed from colorless to pale yellow under sunlight, and the blue fluorescence faded under a 365nm UV lamp. Subsequently, when 10 molar amounts of EDTA solution were added, the solution changed from pale yellow to colorless under sunlight, and the fluorescence was restored under UV lamp. Therefore, the probe is effective against Mn. 2+ and Cu 2+ The ion recognition process is reversible. This method can perform qualitative detection under sunlight and ultraviolet light, is simple to operate, and does not require large instruments.

[0094] The above are merely embodiments of the present invention and do not limit the scope of the patent. Any equivalent modifications made based on the content of this specification, or direct or indirect applications in other related technical fields, are similarly included within the scope of patent protection of the present invention.

Claims

1. A compound containing an indole and a quinoline skeleton, characterized in that, The compound has the structural formula shown in general formula (I): （I） In the general formula (I) described above, R is H or Cl; When R is H, the compound is N'-{(8-hydroxy-2-quinolinyl)methylene}-1H-indole-2-formylhydrazine; When R is Cl, the compound is 5-chloro-N'-{(8-hydroxy-2-quinolinyl)methylene}-1H-indole-2-carboxylhydrazine.

2. A composition, characterized in that, The composition comprises the compound as described in claim 1, as well as commonly used excipients.

3. A load, characterized in that, The loading material comprises the compound as described in claim 1 or the composition as described in claim 2, and a specific carrier material for loading or molding.

4. The application of the compound of claim 1, the composition of claim 2, or the loading material of claim 3 in the detection of metal ions for non-disease diagnostic purposes, characterized in that, The metal ion mentioned is a +2 valent copper ion (Cu). 2+ ) or +2 valent manganese ions (Mn 2+ ).

5. The compound of claim 1, the composition of claim 2, or the loading of claim 3, for simultaneous detection of Cu in the same test system for non-disease diagnostic purposes. 2+ and Mn 2+ Applications of metal ions.

6. The method for synthesizing the compound according to claim 1, characterized in that, When R in the compound of general formula (I) is H, the compound is N'-{(8-hydroxy-2-quinolinyl)methylene}-1H-indole-2-formylhydrazine, and its preparation method includes the following steps: 1) Compound 1a, namely ethyl indole-2-carboxylate, was subjected to a condensation reaction with 85% hydrazine hydrate to obtain compound 2a, namely 1H-indole-2-carboxylate; wherein the molar ratio of ethyl indole-2-carboxylate to hydrazine hydrate was 1:(2-10), the solvent was DMF, the reaction temperature was reflux temperature, and the reaction time was 6~18h; 2) Compound 3, namely 2-methyl-8-hydroxyquinoline, was oxidized with selenium dioxide to obtain compound 4, namely 8-hydroxyquinoline-2-carboxaldehyde; The molar ratio of compound 3 to selenium dioxide was 1:(1.5~3), the solvent was 1,4-dioxane, the reaction temperature was 95 °C, and the reaction time was 6~18 h; 3) Compound 2a and compound 4 were subjected to a condensation reaction catalyzed by acetic acid to obtain compound 5a, namely N'-{(8-hydroxy-2-quinolinyl)methylene}-1H-indole-2-carboxylhydrazine; the molar ratio of compound 2a, compound 4 and acetic acid was 1:(0.8~1.2):(0~6), the solvent was ethanol, the reaction temperature was 80 °C, and the reaction time was 3~8 h.

7. The method for synthesizing the compound according to any one of claims 1, characterized in that, When R in the compound of general formula (I) is Cl, the compound is 5-chloro-N'-{(8-hydroxy-2-quinolinyl)methylene}-1H-indole-2-formylhydrazine, and its preparation method includes the following steps: 1) Compound 1b, namely ethyl 5-chloroindole-2-carboxylate, was subjected to a condensation reaction with 85% hydrazine hydrate to obtain compound 2b, namely 5-chloro-1H-indole-2-carboxylate; the molar ratio of ethyl 5-chloroindole-2-carboxylate to hydrazine hydrate was 1:(2-10), the solvent was ethanol, the reaction temperature was reflux temperature, and the reaction time was 6~18h; 2) Compound 3, namely 2-methyl-8-hydroxyquinoline, was oxidized with selenium dioxide to obtain compound 4, namely 8-hydroxyquinoline-2-carboxaldehyde; The molar ratio of compound 3 to selenium dioxide was 1:(1.5~3), the solvent was 1,4-dioxane, the reaction temperature was 95 °C, and the reaction time was 6~18 h; 3) Compound 2b and compound 4 were subjected to a condensation reaction catalyzed by acetic acid to obtain compound 5b, namely 5-chloro-N'-{(8-hydroxy-2-quinolinyl)methylene}-1H-indole-2-carboxylhydrazine; the molar ratio of compound 2b, compound 4 and acetic acid was 1:(0.8~1.2):(0~6), the solvent was ethanol, the reaction temperature was 80 °C, and the reaction time was 3~8 h.

8. The synthesis method as described in claim 6 or 7, characterized in that, In step 1), the molar ratio of 1a or 1b to hydrazine hydrate is 1:3 or 1:

5. In step 2), the molar ratio of compound 3 to selenium dioxide is 1:

2. In step 3), the molar ratio of compound 2a or 2b, compound 4, and acetic acid is 1:1:3.

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