Self-degradation fluorine ion probe based on conjugated double bonds and application of self-degradation fluorine ion probe

Abstract

The invention discloses a self-degradable fluorine ion probe based on conjugated double bonds and application thereof, and belongs to the technical field of probe detection. According to the probe, a silicon-oxygen bond group is used as a trigger group, an existing amino benzyl alcohol structure is directionally modified on the basis of conjugated double bonds, and a novel self-degradable compound is obtained by using the modified amino benzyl alcohol as a linking group and is used as a reaction type probe for fluorine ion detection. The fluorine ion donor reacts with the self-degradation probe to break a silicon-oxygen bond, so that the compound is subjected to quinone methyl rearrangement, and a signal group at the tail end is released. The invention not only develops a novel fluorine ion probe with excellent performance, but also provides a brand new thought for the design and synthesis of self-degradable compounds and the development and design of long-distance signal transduction molecules.

Description

Technical Field

[0001] The present invention belongs to the field of probe detection technology, and particularly relates to a novel self-degradable compound designed based on conjugated double bonds and its application in fluoride ion detection. Background Art

[0002] Self-degrading molecules are stimulus-responsive compounds with high thermodynamic stability. They generally consist of a trigger group, a linker group, and a reporter group. Upon response to a specific stimulus, the chemical bond in the trigger group breaks, triggering a cascade of elimination reactions in the linker group, ultimately releasing the reporter group. These molecules have enormous potential for application in numerous fields, such as addressing plastic pollution by enabling degradation products to be integrated into ecosystems or reused in synthetic processes. In biomedical applications, they can be used as temporary structures, such as tissue engineering scaffolds or drug delivery systems. It is well known that various anions play a crucial role in biological processes, participating in nearly 70% of enzymatic reactions. Fluoride, in particular, has attracted considerable attention due to its enormous potential for industrial and biological applications. Fluoride is an essential trace element for animal life, but it is also toxic and harmful. Both deficiency and excess can cause animal disease. Excessive fluoride inhibits protein and urea synthesis and significantly affects animal hematopoiesis, inhibiting protease synthesis and reducing hemoglobin, leading to anemia. High fluoride will also reduce the activity of enzymes related to calcium, manganese, magnesium, copper, iron, zinc, etc., which will directly lead to a decrease in fat utilization and sugar metabolism disorders, thereby affecting the growth and development of animals. Summary of the Invention

[0003] This study developed a novel self-degradable compound linker that not only efficiently couples the trigger group with the reporter group but also ensures effective signal transmission through the extended conjugated system. Integrating this with the probe design concept, a class of high-performance fluoride ion probe molecules was synthesized. These probe molecules produce a significant signal change in a relatively short time, enabling efficient fluoride ion detection while exhibiting strong selectivity for fluoride ions.

[0004] The technical solution adopted by the present invention is: a probe for detecting fluoride ions, which has the following general structural formula:

[0005]

[0006] Wherein, m is an integer of 1-5, n is a non-negative integer; R1, R2, and R3 are each independently selected from a C1-C10 alkyl group.

[0007] Furthermore, wherein m is 1 or 3, n is an integer of 0-5, and R1, R2, and R3 are each independently selected from a C1-C10 alkyl group.

[0008] Furthermore, wherein m is 1 or 3, n is 0, 1, or 2, and R1, R2, and R3 are each independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, and tert-butyl.

[0009] The probe preparation method is:

[0010]

[0011] Compound a is reacted with compound b in a solvent to obtain the target compound.

[0012] Furthermore, the molar ratio of compound a to compound b is 1.5-4:1.

[0013] Furthermore, in the presence of a polar organic solvent, an organic metal compound is added as a catalyst; the organic metal compound is dibutyltin dilaurate.

[0014] Furthermore, the reaction temperature is 50-70° C., and the reaction time is 30-45 min.

[0015] Application of the probe, wherein the probe is applied to the detection of fluoride ions.

[0016] Furthermore, the probe is used for fluoride ion detection in the environmental or biomedical fields.

[0017] Beneficial effects of the present invention: The present invention uses a silicon-oxygen bond group as a trigger group and, based on a conjugated double bond, conducts a directional modification on the existing aminobenzyl alcohol structure, and uses this as a connecting group to design a new self-degradable compound, which is used as a reactive probe for fluoride ion detection. The compounds designed and synthesized by the present invention are all typical "turn-on" type response probe molecules, which can complete the efficient detection of fluoride ions in a relatively short time, causing a significant change in the monitorable signal. 、 、 The fluoride ion receptor showed strong selectivity for common interfering ions such as fluoride, and even in the presence of 10 equivalents of competing anions, it maintained specific recognition of fluoride ions. The simultaneously developed linker not only achieved efficient coupling of the trigger group and the reporter group, but its extended conjugated system also ensured effective signal transmission. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is the ultraviolet absorption change diagram after the probe molecule M1-1 reacts with fluoride ions.

[0019] Figure 2 This is the ultraviolet absorption change diagram after the probe molecule M1-2 reacts with fluoride ions.

[0020] Figure 3 This is the ultraviolet absorption change diagram after the probe molecule M1-3 reacts with fluoride ions.

[0021] Figure 4 Figure 2 is the ultraviolet absorption change diagram of the reaction between the probe molecule M1-1 and the anion. a is the result of the selectivity experiment of M1-1 for fluoride ions; b is the result of the competitive experiment of M1-1 for fluoride ions.

[0022] Figure 5 Figure 2 is a graph showing the change in ultraviolet absorption of the probe molecule M1-2 when it reacts with anions. Figure a is a graph showing the selectivity experiment results of M1-2 for fluoride ions; and figure b is a graph showing the competitive experiment results of M1-2 for fluoride ions.

[0023] Figure 6 Figure 2 is a graph showing the change in ultraviolet absorption of the probe molecule M1-3 when it reacts with anions. a is a graph showing the selectivity experiment results of M1-3 for fluoride ions; b is a graph showing the competitive experiment results of M1-3 for fluoride ions.

[0024] Figure 7 This is the ultraviolet absorption change diagram after the probe molecule M2-1 reacts with fluoride ions.

[0025] Figure 8 This is the ultraviolet absorption change diagram after the probe molecule M2-2 reacts with fluoride ions.

[0026] Figure 9 This is the ultraviolet absorption change diagram after the probe molecule M2-3 reacts with fluoride ions.

[0027] Figure 10 Figure 2 is the ultraviolet absorption change diagram of the reaction between the probe molecule M2-1 and the anion. a is the result of the selectivity experiment of M2-1 for fluoride ions; b is the result of the competitive experiment of M2-1 for fluoride ions.

[0028] Figure 11 Figure 2 is a graph showing the change in ultraviolet absorption of the probe molecule M2-2 when it reacts with anions. Figure a shows the results of the M2-2 selectivity experiment for fluoride ions; and figure b shows the results of the M2-2 competitive experiment for fluoride ions.

[0029] Figure 12 Figure 2 is a graph showing the change in ultraviolet absorption of the probe molecule M2-3 when it reacts with anions. Figure a shows the results of the selectivity experiment of M2-3 for fluoride ions; and figure b shows the results of the competitive experiment of M2-3 for fluoride ions. Specific implementation methods

[0030] The present invention will be described in detail below through examples. It is necessary to point out that the following examples are only used to further illustrate the present invention, but are not limited thereto, unless otherwise specified.

[0031] In a first aspect of the present invention, a probe molecule for detecting fluoride ions is provided, having the following structural formula:

[0032]

[0033] Where, n is an integer; R1, R 2， R3 are each independently selected from alkyl groups.

[0034] The second aspect of the present invention provides a method for preparing the aforementioned probe for detecting fluoride ions: reacting the compound represented by formula (a) with the compound represented by formula (c) to obtain the compound represented by formula (I), selecting a suitable silane group as the reaction site for the fluoride ion, selecting a suitable organometallic compound as a catalyst, adding an appropriate amount of the compound represented by formula (c), and completely reacting all the raw materials to obtain a higher yield of the compound represented by formula (I); reacting the compound represented by formula (b) with the compound represented by formula (c) to obtain the compound represented by formula (II), selecting a suitable silane group as the reaction site for the fluoride ion, selecting a suitable organometallic compound as a catalyst, and adding an appropriate amount of the compound represented by formula (c) to obtain the compound represented by formula (II). The reaction formula is as follows:

[0035]

[0036] Wherein, n in formula (a), formula (b), formula (I) and formula (II) is a natural number, R1, R 2， R3 is an alkyl group; preferably, R1 and R2 are methyl groups, and R3 is a tert-butyl group.

[0037] According to a specific embodiment of the present invention, the molar ratio of the compound represented by formula (a) to the compound represented by formula (c) is 1.5-3:1 (preferably 2:1); the molar ratio of the compound represented by formula (b) to the compound represented by formula (c) is 1.5-4:1 (preferably 3:1); the preferred reaction conditions include: 1) tetrahydrofuran is selected as the reaction solvent; 2) the reaction temperature is 50-70°C, and the reaction time is 30-45 minutes; 3) an organometallic compound dibutyltin dilaurate is added as a catalyst.

[0038] The third aspect of the present invention provides the use of the aforementioned probe compound for visually detecting fluoride ions in a solution environment, or for application in the biomedical field.

[0039] The specific embodiments of the present invention are described in detail below in conjunction with the technical solutions:

[0040] Example 1: Preparation of M1-1

[0041]

[0042] (1) Synthesis steps and characterization data of compound 2

[0043] Weigh p-hydroxybenzaldehyde (366.36 mg, 3 mmol) into a 100 mL single-necked round-bottom flask. Then, add tert-butyldimethylsilyl chloride (675 mg, 4.5 mmol) and imidazole (83.7 mg, 3.6 mmol). Finally, add 10 mL of tetrahydrofuran as the reaction solvent. The reaction mixture was stirred at room temperature for one hour and monitored by TLC. After completion, the reaction was quenched with saturated sodium bicarbonate solution. The organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and purified by column chromatography using n-hexane and ethyl acetate (v / v = 5:1) as the eluent to obtain the white intermediate 2 in approximately 90% yield.

[0044] H NMR data: 1 H NMR (400 MHz, Chloroform-d) δ 9.98 (s, 1H), 7.89(d, J = 8.6 Hz, 2H), 7.05 (d, J = 8.6 Hz, 2H), 1.10 (q, J = 2.7 Hz, 9H), 0.35(t, J = 2.0 Hz, 6H).

[0045] (2) Synthesis steps and characterization data of compound 3

[0046] Intermediate 2 (236.39 mg, 1 mmol) was weighed into a 50 mL round-bottom flask, and 10 mL of dehydrated methanol was added as the solvent. Three equivalents of sodium borohydride were dissolved in anhydrous methanol. After the reaction system was cooled to 0°C, the mixture was slowly added dropwise to the round-bottom flask using a dropping funnel, producing bubbles. After the addition was complete, the reaction was stirred at room temperature for 1 hour. After completion of the reaction, the organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and purified by column chromatography using n-hexane and ethyl acetate (v / v = 3:1) as the eluent to obtain the white product 3 in approximately 60% yield.

[0047] H NMR data: 1 H NMR (400 MHz, Chloroform-d) δ 7.20 (d, J = 8.5Hz, 2H), 6.82 (d, J = 8.5 Hz, 2H), 4.52 (m, 2H), 1.00 (s, 9H), 0.20 (s, 6H).

[0048] (3) Synthesis steps and characterization data of compound M1-1

[0049] Intermediate 3 (102 mg, 0.43 mmol) was dissolved in 5 mL of anhydrous THF. 4-Nitrophenyl isocyanate (85 mg, 0.52 mmol) was added, followed by a catalytic amount of dibutyltin dilaurate (DBTL). The reaction mixture was heated to 50°C and stirred under argon for 45 minutes. The reaction was monitored by TLC. After completion of the reaction, the solvent was removed under reduced pressure, and the product was purified by column chromatography using n-hexane and ethyl acetate (v / v = 9:1) as the eluent to obtain probe M1-1 as a white powder in approximately 30% yield.

[0050] H NMR data: 1 H NMR (400 MHz, Chloroform-d) δ 8.28 (d, J = 9.2Hz, 2H), 7.65 (d, J = 9.1 Hz, 2H), 7.37 (d, J = 8.3 Hz, 2H), 6.94 (d, J = 8.5Hz, 2H), 5.25 (s, 2H), 1.09 (s, 10H), 0.30 (s, 6H).

[0051] Example 2: Preparation of M1-2

[0052]

[0053] (1) Synthesis steps and characterization data of compound 4

[0054] Intermediate 2 (236.39 mg, 1 mmol) was placed in a 100 mL single-necked round-bottom flask. Ethoxyformylmethylenetriphenylphosphine (522 mg, 1.5 mmol) was added to the flask, and 10 mL of xylene was added as the reaction solvent. The reaction mixture was heated to 110°C and stirred with a magnetic stirrer for 4 hours. After completion of the reaction, the solvent was removed under reduced pressure, and the product was purified by column chromatography using n-hexane and ethyl acetate (v / v = 20:1) as the eluent to obtain white intermediate 4 in approximately 48% yield.

[0055] H NMR data: 1H NMR (400 MHz, Chloroform-d) δ 7.58 (d, J = 16.0Hz, 1H), 7.34 (d, J = 8.6 Hz, 2H), 6.76 (d, J = 8.6 Hz, 2H), 6.24 (d, J =16.0 Hz, 1H), 4.18 (q, J = 7.1 Hz, 2H), 1.25 (t, J = 7.2 Hz, 3H), 0.92 (s,9H), 0.15 (s, 6H).

[0056] (2) Synthesis steps and characterization data of compound 5

[0057] Intermediate 4 (460 mg, 1.5 mmol) was placed in a 100 mL single-necked round-bottom flask, and 10 mL of dichloromethane was added as the reaction solvent. Under argon protection, 1.5 mL of diisobutylaluminum hydride was slowly added in an ice-water bath. After the addition was complete, the ice bath was removed and the mixture was stirred at room temperature for half an hour. After completion of the reaction, saturated ammonium chloride solution was added to quench the reaction. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and purified by column chromatography using n-hexane and ethyl acetate (v / v = 10:1) as the eluent to obtain intermediate 5 in approximately 85% yield.

[0058] H NMR data: 1 H NMR (400 MHz, Chloroform-d) δ 7.17 (d, J = 8.5Hz, 2H), 6.72 (d, J = 8.4 Hz, 2H), 6.44 (d, J = 15.9 Hz, 1H), 6.13 (dt, J =15.8, 5.9 Hz, 1H), 4.18 (d, J = 5.8 Hz, 2H), 0.94 (s, 9H), 0.14 (s, 6H).

[0059] (3) Synthesis steps and characterization data of probe M1-2

[0060] Intermediate 5 (200 mg, 0.86 mmol) was dissolved in 5 mL of anhydrous THF. 4-Nitrophenyl isocyanate (170 mg, 1 mmol) was added, followed by a catalytic amount of DBTL. The reaction mixture was heated to 50°C and stirred under argon for 45 minutes. After completion of the reaction, the solvent was removed and the product was purified by column chromatography using n-hexane and ethyl acetate (v / v = 9:1) as the eluent to obtain probe M1-2 in approximately 45% yield.

[0061] H NMR data:1 H NMR (400 MHz, Chloroform-d) δ 8.20 (d, J = 9.2Hz, 2H), 7.56 (d, J = 9.2 Hz, 2H), 7.28 (d, J = 8.6 Hz, 2H), 7.02 (s, 1H), 6.80 (d, J = 8.6 Hz, 2H), 6.66 (d, J = 15.8 Hz, 1H), 6.18 (dt, J = 15.8, 6.7Hz, 1H), 4.83 (dd, J = 6.8, 1.2 Hz, 2H), 0.97 (m, 9H), 0.20 (s, 6H).

[0062] C NMR spectrum data: 13 C NMR (101 MHz, Chloroform-d) δ 156.51, 153.14,143.51, 135.48, 129.68, 128.37, 125.67, 120.77, 118.23, 67.23, 26.11, 18.68.

[0063] High-resolution mass spectrometry data: HRMS (ESI, m / z): 452.9226 (calcd: C 22 H 28 N2O5Si,452.9225).

[0064] Example 3: Preparation of M1-3

[0065]

[0066] (1) Synthesis steps and characterization data of compound 6

[0067] Intermediate 5 (266 mg, 1 mmol) was dissolved in 5 mL of anhydrous dichloromethane, and manganese dioxide (264 mg, 3 mmol) was added. The reaction mixture was heated to 30°C and stirred for 40 minutes. After completion of the reaction, the manganese dioxide was removed by filtration, and the solvent was removed under reduced pressure. The product was then purified by column chromatography using n-hexane and ethyl acetate (v / v = 9:1) as the eluent to obtain intermediate 6 in an approximately 85% yield.

[0068] H NMR data: 1H NMR (400 MHz, Chloroform-d) δ 9.64 (d, J = 7.7Hz, 1H), 7.48 – 7.43 (m, 2H), 7.40 (d, J = 15.9 Hz, 1H), 6.90 – 6.85 (m, 2H), 6.59 (dd, J = 15.8, 7.8 Hz, 1H), 0.98 (s, 9H), 0.22 (s, 6H).

[0069] (2) Synthesis steps and characterization data of compound 7

[0070] Intermediate 6 (260 mg, 1 mmol) was placed in a single-necked round-bottom flask. Ethoxyformylmethylenetriphenylphosphine (522 mg, 1.5 mmol) was added to the flask. 10 mL of xylene was added as the reaction solvent, and the reaction was heated to 110°C for 4 hours. After completion of the reaction, the solvent was removed under reduced pressure, and the product was purified by column chromatography using n-hexane and ethyl acetate (v / v = 20:1) as the eluent to obtain the white intermediate 7 in approximately 48% yield.

[0071] H NMR data: 1 H NMR (400 MHz, Chloroform-d) δ 7.43 (dd, J = 15.2,10.7 Hz, 1H), 7.38 – 7.31 (m, 2H), 6.86 – 6.79 (m, 3H), 6.73 (ddd, J = 15.6,10.7, 0.7 Hz, 1H), 5.94 (d, J = 15.2 Hz, 1H), 4.22 (q, J = 7.2 Hz, 2H), 1.31 (t, J = 7.1 Hz, 3H), 0.98 (s, 9H), 0.21 (s, 6H).

[0072] (3) Synthesis steps and characterization data of compound 8

[0073] Intermediate 7 (470 mg, 1.5 mmol) was dissolved in 10 mL of dichloromethane. Under argon, 1.5 mL of diisobutylaluminum hydride was added dropwise in an ice-water bath. After the addition was complete, the ice bath was removed and the mixture was stirred at room temperature for half an hour. Saturated ammonium chloride solution was added to quench the mixture. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and purified by column chromatography using n-hexane and ethyl acetate (v / v = 10:1) as the eluent to obtain intermediate 8 in an approximately 85% yield.

[0074] H NMR data: 1H NMR (400 MHz, Chloroform-d) δ 7.57 (d, J = 8.7Hz, 2H), 7.09 (d, J = 8.6 Hz, 2H), 6.92 (s, 1H), 6.82 (s, 1H), 6.75 – 6.64(m, 1H), 6.21 (dt, J = 15.1, 6.0 Hz, 1H), 4.54 (d, J = 5.9 Hz, 2H), 1.28 (s,10H), 0.50 (s, 6H).

[0075] (4) Synthesis steps and characterization data of compound M1-3

[0076] Intermediate product 8 (130 mg, 0.43 mmol) was dissolved in 5 mL of anhydrous THF, and 4-nitrophenyl isocyanate (85 mg, 0.52 mmol) and a catalytic amount of DBTL were added. The reaction mixture was heated to 50°C and stirred under argon for 45 minutes. After completion of the reaction, the solvent was removed under reduced pressure, and the product was purified by column chromatography using n-hexane and ethyl acetate (v / v = 9:1) as the eluent to obtain probe M1-3 in approximately 45% yield.

[0077] H NMR data: . 1 H NMR (400 MHz, Chloroform-d) δ 8.34 (d, J = 9.1Hz, 2H), 7.70 (d, J = 9.1 Hz, 2H), 7.42 (d, J = 8.6 Hz, 2H), 6.94 (d, J = 8.6Hz, 2H), 6.82 – 6.59 (m, 3H), 6.04 – 5.94 (m, 1H), 4.91 (d, J = 6.7 Hz, 2H), 1.13 (s, 9H), 0.35 (s, 6H).

[0078] C NMR spectrum data: 13 C NMR (101 MHz, Chloroform-d) δ 143.55, 136.34,134.64, 130.56, 128.22, 125.95, 125.67, 125.27, 120.79, 118.26, 66.87, 26.11,18.68, -3.95.

[0079] Mass spectral data: HRMS (ESI, m / z): 453.1856 (calcd C 24 H30 N2O5Si, 454.1924).

[0080] Example 4: Preparation of M2-1

[0081]

[0082] (1) Synthesis steps and characterization data of compound 10

[0083] Trihydroxybenzaldehyde (366.36 mg, 3 mmol) was dissolved in 10 mL of dichloromethane, and imidazole (383.7 mg, 6 mmol) was added. Tert-butyldimethylsilyl trifluoromethanesulfonate (1.18 g, 4.5 mmol) was slowly added in an ice-water bath and allowed to react for 1 hour. The reaction was stopped at the end of the reaction time and confirmed by thin-layer chromatography. Saturated sodium bicarbonate solution was added to neutralize the base in the system, and the product was washed three times with saturated brine, dried over anhydrous sodium sulfate, and rotary evaporated. Purification was performed by column chromatography using n-hexane and ethyl acetate (v / v = 90:1) as the eluent to obtain the white intermediate 10 in approximately 80% yield.

[0084] H NMR data: 1 H NMR (400 MHz, Chloroform-d) δ 10.31 (s, 1H), 5.95 (s, 2H), 0.99 (d, J = 13.2 Hz, 27H), 0.23 (d, J = 3.1 Hz, 18H).

[0085] C NMR data 13 C NMR (101 MHz, Chloroform-d) δ 188.54, 162.08, 160.35, 115.43, 106.20, 26.20, 26.03, 18.87.

[0086] (2) Synthesis steps and characterization data of compound 11

[0087] Compound 10 (993 mg, 2.0 mmol) was dissolved in 10 mL of anhydrous methanol. Three equivalents of sodium borohydride in methanol were slowly added dropwise to a round-bottom flask using a dropping funnel in an ice-water bath. Bubbling occurred in the reaction system. After the addition was complete, the ice bath was removed and the reaction was stirred at room temperature for 1 hour. After completion of the reaction, the organic phase was extracted with dichloromethane, washed with saturated brine, dried over anhydrous sodium sulfate, and purified by column chromatography using n-hexane and ethyl acetate (v / v = 20:1) as the eluent. The yield was approximately 70%.

[0088] H NMR data: 1H NMR (400 MHz, Chloroform-d) δ 6.00 (s, 2H), 4.63 (d, J = 6.4 Hz, 2H), 0.99 (d, J = 16.9 Hz, 27H), 0.21 (d, J = 19.8 Hz, 18H).

[0089] C NMR spectrum data: 13 C NMR (101 MHz, Chloroform-d) δ 155.96, 155.48,116.59, 104.99, 77.16, 55.72, 25.82, 18.34.

[0090] (3) Synthesis steps and characterization data of compound M2-1

[0091] Compound 11 (230 mg, 0.5 mmol) was dissolved in 5 mL of anhydrous THF, and 4-nitrophenyl isocyanate (85 mg, 0.52 mmol) and a catalytic amount of DBTL were added. The reaction mixture was heated to 50°C and stirred under argon for 45 minutes. After completion of the reaction, the solvent was removed under reduced pressure, and the product was purified by column chromatography using n-hexane and ethyl acetate (v / v = 250:1) as the eluent to obtain probe M2-1 in approximately 39% yield.

[0092] H NMR spectrum data: 1 H NMR (400 MHz, Methanol-d4) δ 8.15 (s, 2H), 7.65 (s, 2H), 6.03 (s, 2H), 5.15 (s, 2H), 0.98 (d, J = 1.9 Hz, 27H), 0.23 (d, J =11.7 Hz, 18H).

[0093] C NMR spectrum data: 13 C NMR (101 MHz, Methanol-d4) δ 158.08, 155.69,125.85, 118.78, 105.56, 59.08, 26.14, 26.12, -4.11.

[0094] High-resolution mass spectrometry data: HRMS (ESI, m / z): 661.3156 (calcd C 32 H 54 N2O7Si3,662.3239).

[0095] Example 5: Preparation of M2-2

[0096]

[0097] (1) Synthesis steps and characterization data of compound 12

[0098] A dichloromethane solution of compound 10 (236.39 mg, 1 mmol) was placed in a 100 mL single-necked round-bottom flask. Ethoxyformylmethylenetriphenylphosphine (522 mg, 1.5 mmol) was added to the flask. The mixture was heated to 110°C and stirred with a magnetic stirrer for 4 hours. After completion of the reaction, the solvent was removed under reduced pressure. The product was then purified by column chromatography using n-hexane and ethyl acetate (v / v = 90:1) as the eluent to obtain colorless compound 12 in approximately 48% yield.

[0099] H NMR spectrum data: 1 H NMR (400 MHz, Chloroform-d) δ 7.96 (d, J = 16.3Hz, 1H), 6.71 (d, J = 16.3 Hz, 1H), 6.01 (s, 2H), 4.26 – 4.15 (m, 2H), 1.29(t, J = 7.1 Hz, 3H), 0.99 (d, J = 19.8 Hz, 28H), 0.23 (d, J = 15.5 Hz, 19H).

[0100] H NMR spectrum data: 13 C NMR (101 MHz, Chloroform-d) δ 168.81, 158.05,157.50, 137.17, 119.23, 112.75, 105.76, 60.18, 18.85, 14.86.

[0101] (2) Synthesis steps and characterization data of compound 13

[0102] Under argon, a dichloromethane solution of compound 12 (460 mg, 1.5 mmol) was cooled to 0°C in an ice-water bath. A magnetic stirrer was then used, and 1.5 mL of diisobutylaluminum hydride was slowly added. After the addition was complete, the ice bath was removed and the mixture was stirred at room temperature for half an hour. Saturated ammonium chloride solution was added, and the organic phase was extracted with dichloromethane. The mixture was washed with saturated brine and dried over anhydrous sodium sulfate. The mixture was then purified by column chromatography using n-hexane and ethyl acetate (v / v = 30:1) as the eluent to afford compound 13 in approximately 75% yield.

[0103] H NMR spectrum data: 1H NMR (400 MHz, Chloroform-d) δ 6.70 (s, 1H), 6.54 (dt, J = 16.1, 5.9 Hz, 1H), 6.01 (s, 2H), 4.25 (s, 2H), 0.98 (d, J = 11.0 Hz, 27H), 0.20 (d, J = 8.6 Hz, 18H).

[0104] C NMR spectrum data: 13 C NMR (101 MHz, Chloroform-d) δ 155.29, 155.21,130.64, 123.82, 113.90, 105.62, 77.16, 65.62, 25.82, 18.52.

[0105] (3) Synthesis steps and characterization data of compound M2-2

[0106] Compound 13 (104 mg, 0.43 mmol) was dissolved in 5 mL of anhydrous THF. 4-Nitrophenyl isocyanate (85 mg, 0.52 mmol) and a catalytic amount of DBTL were added. The reaction mixture was heated to 50°C and stirred under argon for 45 minutes. After completion of the reaction, the solvent was removed under reduced pressure, and the product was purified by column chromatography using n-hexane and ethyl acetate (v / v = 35:1) as the eluent to obtain probe M2-2 in approximately 40% yield.

[0107] H NMR spectrum data: 1 H NMR (400 MHz, Chloroform-d) δ 8.20 (d, J = 9.0Hz, 2H), 7.55 (d, J = 8.9 Hz, 2H), 6.89 (s, 2H), 6.58 – 6.46 (m, 1H), 6.00(s, 2H), 4.80 (s, 2H), 0.98 (d, J = 10.2 Hz, 27H), 0.20 (d, J = 11.9 Hz, 18H).

[0108] C NMR spectrum data: 13 C NMR (101 MHz, Chloroform-d) δ 154.39, 126.15,124.22, 123.00, 116.63, 104.33, 67.33, 24.87, 24.63, 17.26, -5.04, -5.35.

[0109] Mass spectral data: HRMS (ESI, m / z): 687.3319 (calcd C 34 H 56 N2O7Si3, 688.3395)

[0110] Example 6: Preparation of M2-3

[0111]

[0112] (1) Synthesis steps and characterization data of compound 14

[0113] Compound 13 (524.9 mg, 1 mmol) was dissolved in 5 mL of anhydrous dichloromethane, and manganese dioxide (264 mg, 3 mmol) was added. The reaction mixture was heated to 35°C and stirred for 40 minutes. The reaction progress was monitored by thin-layer chromatography. After completion of the reaction, the manganese dioxide was removed by filtration, the solvent was removed under reduced pressure, and the product was purified by column chromatography using n-hexane and ethyl acetate (v / v = 100:1) as the eluent to obtain compound 14 in approximately 98% yield.

[0114] H NMR spectrum data:. 1 H NMR (400 MHz, Chloroform-d) δ 9.54 (d, J = 8.1Hz, 1H), 7.75 (d, J = 16.0 Hz, 1H), 6.98 (dd, J = 16.1, 8.1 Hz, 1H), 6.02 (s,2H), 0.99 (d, J = 13.3 Hz, 27H), 0.24 (d, J = 18.4 Hz, 18H).

[0115] C NMR spectrum data: 13 C NMR (101 MHz, Chloroform-d) δ 196.14, 159.58,157.89, 146.83, 129.99, 112.50, 105.60, 77.16, 26.32, 26.04, 18.91, 18.75.

[0116] (2) Synthesis steps and characterization data of compound 15

[0117] Compound 14 (523.1 mg, 1 mmol) and ethoxyformylmethylenetriphenylphosphine (522 mg, 1.5 mmol) were dissolved in 10 mL of xylene and heated to 110°C for 4 hours. After completion of the reaction, the solvent was removed under reduced pressure, and the product was purified by column chromatography using n-hexane and ethyl acetate (v / v = 100:1) as the eluent to obtain the white intermediate 9 in approximately 48% yield.

[0118] H NMR data: 1 H NMR (400 MHz, Chloroform-d) δ 7.42 (dd, J = 15.0,11.1 Hz, 1H), 7.31 – 7.21 (m, 1H), 7.12 (d, J = 15.7 Hz, 1H), 6.04 (s, 2H), 5.86 (d, J = 15.1 Hz, 1H), 4.25 (q, J = 7.1 Hz, 2H), 1.35 (t, J = 7.1 Hz, 3H), 1.02 (d, J = 15.7 Hz, 27H), 0.25 (d, J = 13.1 Hz, 18H).

[0119] C NMR spectrum data: 13 C NMR (101 MHz, Chloroform-d) δ 168.12, 157.08,156.60, 147.96, 134.19, 128.54, 118.76, 105.90, 60.52, 26.35, 26.09, 14.82.

[0120] (3) Synthesis steps and characterization data of compound 16

[0121] Under argon, a dichloromethane solution of compound 15 (889 mg, 1.5 mmol) was cooled to 0°C and 1.5 mL of diisobutylaluminum hydride was slowly added. After the addition was complete, the temperature was raised to room temperature and the reaction was allowed to proceed for half an hour. The reaction was quenched by the addition of saturated ammonium chloride solution. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and purified by column chromatography using n-hexane and ethyl acetate (v / v = 30:1) as the eluent to obtain compound 13 in an approximately 82% yield.

[0122] H NMR spectrum data: 1H NMR (400 MHz, Chloroform-d) δ 7.06 (dd, J = 15.9,10.7 Hz, 1H), 6.68 (d, J = 16.0 Hz, 1H), 6.32 (dd, J = 14.5, 10.7 Hz, 1H), 6.00 (s, 2H), 5.84 – 5.75 (m, 1H), 4.23 (s, 2H), 0.98 (d, J = 15.7 Hz, 28H), 0.20 (d, J = 9.3 Hz, 18H).

[0123] C NMR spectrum data: 13 C NMR (101 MHz, Chloroform-d) δ 155.69, 134.88,130.69, 130.01, 126.22, 114.85, 106.03, 64.32, 26.39, 26.14, 18.89.

[0124] (4) Synthesis steps and characterization data of compound M2-3

[0125] Compound 16 (275 mg, 0.5 mmol) and 4-nitrophenyl isocyanate (85 mg, 0.52 mmol) were dissolved in 5 mL of anhydrous THF and a catalytic amount of DBTL. The reaction system was heated to 60°C and reacted under argon for 45 minutes. The reaction progress was monitored by thin-layer chromatography. After completion, the solvent was removed under reduced pressure, and the product was purified by column chromatography using n-hexane and ethyl acetate (v / v = 40:1) as the eluent to obtain probe M2-3 in approximately 35% yield.

[0126] H NMR spectrum data: 1 H NMR (400 MHz, Chloroform-d) δ 8.20 (d, J = 9.1Hz, 2H), 7.56 (d, J = 9.1 Hz, 2H), 7.11 – 6.98 (m, 2H), 6.76 (d, J = 15.9 Hz,1H), 6.42 (dd, J = 15.1, 10.8 Hz, 1H), 6.00 (s, 2H), 5.72 (dt, J = 14.6, 6.9Hz, 1H), 4.77 (d, J = 6.9 Hz, 2H), 0.98 (d, J = 14.7 Hz, 27H), 0.20 (d, J =10.1 Hz, 18H).

[0127] C NMR spectrum data: 13 C NMR (101 MHz, Chloroform-d) δ 155.86, 144.40,138.85, 129.79, 127.89, 125.70, 123.36, 118.15, 105.97, 26.37, 26.11, 18.89,-3.57.

[0128] Mass spectral data: HRMS (ESI, m / z): 713.3466 (calcd C 36 H 58 N2O7Si3, 714.3552).

[0129] Example 7

[0130] Time scanning experiments of the response of probe molecules M1-1, M1-2 and M1-3 to fluoride ions.

[0131] The probe molecule reacts with fluoride ions to generate p-nitroaniline, which has a specific ultraviolet absorption. After measurement, its maximum absorption wavelength is 390 nm; while the three probe molecules have ultraviolet absorption at around 330 nm. The change in absorbance of the solution containing fluoride ions over time is detected by a UV-vis spectrometer, reflecting the release behavior of p-nitroaniline. The probe molecule is prepared into a 50 μM solution with DMF, incubated at 25 ° C in the dark, and the change in absorbance is measured. Figure 1-Figure 3 It can be seen that the absorption of the three probe molecules near 33 nm gradually decreases, while the absorption at 390 nm gradually increases, which indicates that the three probe molecules are continuously releasing p-nitroaniline. At the end of the test, the absorbance of the solution no longer changes significantly, indicating the end of the release process. The absorption change curve of p-nitroaniline is obtained with the absorption wavelength as the horizontal axis and the absorbance as the vertical axis to reflect the release of p-nitroaniline by the probe molecules ( Figure 1-3 shown).

[0132] The specific testing process is as follows: 1) Using a 100,000 micrometer balance, 3.4 mg of compound M1-1 was weighed into a 2 mL EP tube and dissolved in 845 µL of dimethyl sulfoxide (DMSO) to create a 10 mM stock solution of the M1-1 probe molecule. Similarly, 10 mM stock solutions of M1-2 and M1-3 were prepared. Furthermore, a certain amount of TBAF was accurately weighed and prepared to create 10 mM DMSO solutions in each of the three solutions. 2) Using a pipette, 15 µL of the DMSO stock solution of M1-1 was pipetted into a quartz cuvette containing 2970 µL of DMSO. Then, 15 µL of the TBAF DMSO solution was added. The UV-Vis spectrometer was preheated to 25°C, and the absorption spectrum was monitored over time. The same method was used for probe molecules M1-2 and M1-3 to monitor changes in the absorption peak at 390 nm in the UV-visible absorption spectrum. 3) The heating module temperature of the Agilent Cary 3500 UV-visible spectrometer was set to 25 °C for preheating, and the changes in the absorption peak at 390 nm in the UV-visible absorption spectrum were monitored.

[0133] from Figure 1-Figure 3 It can be seen that when no fluoride ions are added, the absorbance baseline value of the system at 390 nm is The pH value was less than 0.05, with a maximum absorption peak around 335 nm, and the solution remained colorless and transparent. After the introduction of 1.0 equivalents of TBAF, the in situ release of p-nitroaniline caused a significant red-shift in the absorption peak, with the absorbance at 390 nm gradually increasing over time, and the solution color turning yellow. Comparison of the three probes revealed variability in response: M1-3 reached the color development plateau the fastest, requiring approximately 7 minutes, approximately five times faster than M1-1.

[0134] Example 8

[0135] Selectivity and competition experiments of probe molecules M1-1, M1-2 and M1-3 for fluoride ions

[0136] The specific testing procedure is as follows: 1) Pipette 15 µL of the DMSO stock solution of M1-1 into a 5 mL EP tube, dilute to 3 mL with DMSO, and mix thoroughly to achieve a probe molecule concentration of 50 µM. This solution is then mixed with 150 µL (10 equivalents) of DMSO stock solutions of tetrabutylammonium fluoride, tetrabutylbromide fluoride, sodium fluoride, sodium bromide, sodium iodide, sodium chloride, sodium bisulfite, sodium nitrite, and potassium chloride, respectively. The solution is then transferred to a quartz cuvette for testing. The UV-Vis absorption spectrum is scanned over the 300 nm-550 nm range. The same method is used for monitoring UV-Vis absorption spectra of probe molecules M1-2 and M1-3. 2) Pipette 15 µL of the DMSO stock solution of M1-1 into a 5 mL EP tube, dilute to 3 mL with DMSO, and mix thoroughly. To each EP tube, add 150 µL (10 equivalents) of a DMSO stock solution of tetrabutylammonium fluoride, tetrabutylbromide fluoride, sodium fluoride, sodium bromide, sodium iodide, sodium chloride, sodium bisulfite, sodium nitrite, and potassium chloride. Then, add 30 µL of a DMSO stock solution of TBAF to each EP tube and mix thoroughly. The mixture is then transferred to a quartz cuvette for measurement. UV-visible absorption spectroscopy is performed in the 300-550 nm range. The same method is used for monitoring UV-visible absorption changes in probe molecules M1-2 and M1-3.

[0137] like Figure 4-Figure 6 As shown, 10 equivalents of common interfering compounds (TBABr, KCl, NaCl, NaF, NaBr, NaI, NaNO 2 ⁻, NaHSO₄), only fluoride ions elicited a significant spectral response: the characteristic absorption peak red-shifted from around 335 nm to 390 nm, while the absorbance fluctuations for other ion systems were less than 0.05. Selectivity experiments demonstrated that probe molecules M1-1, M1-2, and M1-3 exhibited significant specific responses to fluoride ions. Molecules 1-9 represent only TBAF, TBAF + NaF, TBAF + NaHSO₄, TBAF + KCl, TBAF + NaI, TBAF + NaBr, TBAF + NaCl, TBAF + NaNO₃, and TBAF + NaNO₂, respectively. The results showed that the characteristic peak absorption intensities in mixed systems containing competing anions were nearly identical to those in pure fluoride systems, indicating that common anionic compounds have no significant competitive effect on the fluoride-specific cleavage reaction of silicon-oxygen bonds.

[0138] Example 9

[0139] Time scanning experiments of the response of probe molecules M2-1, M2-2 and M2-3 to fluoride ions.

[0140] The specific testing procedure is as follows: 1) Using a 1 / 100,000 balance, 4 mg of compound M2-1 was weighed into a 2 mL EP tube and dissolved in 604 µL of dimethyl sulfoxide (DMSO) to create a 10 mM stock solution of the M2-1 probe molecule. Similarly, 10 mM stock solutions of M2-2 and M2-3 were prepared. A certain amount of TBAF was then accurately weighed and prepared to create 10 mM DMSO solutions in each of these solutions. 2) Using a pipette, 15 µL of the M2-1 DMSO stock solution was pipetted into a quartz cuvette containing 2970 µL of DMSO. 15 µL of the TBAF DMSO solution was then added. The UV-Vis spectrometer's heating module was set to 25°C for preheating, and the absorption spectrum was monitored over time. The same method was used for probe molecules M1-2 and M1-3 to monitor changes in the absorption peak at 390 nm in the UV-visible absorption spectrum. 3) The heating module temperature of the Agilent Cary 3500 UV-visible spectrometer was set to 25 °C for preheating, and the changes in the absorption peak at 390 nm in the UV-visible absorption spectrum were monitored.

[0141] The results are as follows Figure 7-Figure 9 As shown in the figure, after the introduction of 1.0 equivalent of TBAF, the absorbance at 390 nm gradually increased with the production of p-nitroaniline, while the solution color changed from its initial transparent state to light yellow. Comparison of the three probes revealed some variability in their responses: M2-1 reached the reaction plateau the fastest, at approximately 2 minutes, while M2-2 and M2-3 required approximately 10 minutes.

[0142] Example 10

[0143] Selectivity and competition experiments of probe molecules M1-1, M1-2 and M1-3 for fluoride ions

[0144] The specific testing procedure is as follows: 1) Pipette 15 µL of the DMSO stock solution of M1-1 into a 5 mL EP tube, dilute to 3 mL with DMSO, and mix thoroughly to achieve a probe molecule concentration of 50 µM. This solution is then mixed with 150 µL (10 equivalents) of DMSO stock solutions of tetrabutylammonium fluoride, tetrabutylbromide fluoride, sodium fluoride, sodium bromide, sodium iodide, sodium chloride, sodium bisulfite, sodium nitrite, and potassium chloride, respectively. The solution is then transferred to a quartz cuvette for testing. The UV-Vis absorption spectrum is scanned over the 300 nm-550 nm range. The same method is used for monitoring UV-Vis absorption spectra of probe molecules M1-2 and M1-3. 2) Pipette 15 µL of the DMSO stock solution of M1-1 into a 5 mL EP tube, dilute to 3 mL with DMSO, and mix thoroughly. To each EP tube, add 150 µL (10 equivalents) of a DMSO stock solution of tetrabutylammonium fluoride, tetrabutylbromide fluoride, sodium fluoride, sodium bromide, sodium iodide, sodium chloride, sodium bisulfite, sodium nitrite, and potassium chloride. Then, add 30 µL of a DMSO stock solution of TBAF to each EP tube and mix thoroughly. The mixture is then transferred to a quartz cuvette for measurement. UV-visible absorption spectroscopy is performed in the 300-550 nm range. The same method is used for monitoring UV-visible absorption changes in probe molecules M1-2 and M1-3.

[0145] The experimental results are as follows Figure 10-12 As shown, after adding 10 equivalents of a common interfering compound to a 50 μM DMSO solution of the probe, only fluoride ion caused a significant shift in the UV-visible absorption spectrum, red-shifting the characteristic absorption peak to 390 nm, while other anionic compounds barely altered the position of the characteristic absorption peak. Therefore, selectivity experiments demonstrate that probe molecules M2-1, M2-2, and M2-3 exhibit highly selective responses to fluoride ions. The shift in the absorption peak at 390 nm for the mixed system is not significantly different from that for the pure fluoride system, indicating that the presence of other anions does not affect the recognition of fluoride ions by the three probe molecules, demonstrating their high sensitivity and selectivity stability for fluoride ions.

[0146] The above embodiments are only used to illustrate the present invention. Any equivalent transformations and improvements based on the technical solution of the present invention should not be excluded from the protection scope of the present invention.

Claims

1. A probe for detecting fluoride ions, characterized in that: The probe has the following general structural formula: ； Wherein, m is an integer of 1-5, n is a non-negative integer; R1, R2, and R3 are each independently selected from a C1-C10 alkyl group.

2. The probe according to claim 1, wherein: in, m is 1 or 3, n is an integer of 0-5, and R1, R2, and R3 are each independently selected from a C1-C10 alkyl group.

3. The probe according to claim 1, wherein: in, m is 1 or 3, n is 0, 1, or 2, and R1, R2, and R3 are each independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, and tert-butyl.

4. The method for preparing a probe according to any one of claims 1 to 3, characterized in that: ； Compound a is reacted with compound b in a solvent to obtain the target compound.

5. The preparation method according to claim 4, characterized in that: The molar ratio of compound a to compound b is 1.5-4:

1.

6. The preparation method according to claim 4, characterized in that: In the presence of a polar organic solvent, an organic metal compound is added as a catalyst; the organic metal compound is dibutyltin dilaurate.

7. The preparation method according to claim 4, characterized in that: The reaction temperature is 50-70°C and the reaction time is 30-45 min.

8. Use of the probe according to any one of claims 1 to 3, characterized in that: The probe is used for detecting fluoride ions.

9. The use according to claim 8, characterized in that: The probe is used for fluoride ion detection in the environmental or biomedical fields.

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