CN114249691B - Naphthalimide enhanced mercury ion fluorescent probe, preparation method and application - Google Patents
Naphthalimide enhanced mercury ion fluorescent probe, preparation method and application Download PDFInfo
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Abstract
The invention relates to a naphthalimide enhanced mercury ion fluorescent probe, a preparation method and application thereof, in particular to a naphthalimide enhanced mercury ion fluorescent probe which can be used for measuring, detecting or screening mercury ions and living cell fluorescent imaging, in particular to the capability of multichannel detection and analysis of mercury ions, and can realize at least one of the following technical effects: the method has the advantages of simple synthesis, good selectivity, strong anti-interference capability, high sensitivity, quick response, double-channel analysis, low cytotoxicity and enhanced fluorescent probe, and can effectively measure, detect or screen mercury ions under physiological level conditions.
Description
Technical Field
The invention belongs to the field of fluorescent probes, and particularly relates to a naphthalimide enhanced mercury ion fluorescent probe and application thereof in measuring, detecting or screening mercury ions and living cell fluorescent imaging; the invention also provides a method for preparing the fluorescent probe.
Background
Mercury is a component of the earth's natural environment, accounting for about five parts per million of the crust mass, and is one of the most toxic metals. Mercury is very easy to undergo migration and transformation, can exist in nature in various forms (metallic mercury, inorganic mercury and organic mercury), but exists in a compound form in most cases, and is the only heavy metal capable of perfecting circulation in a ecological system. Mercury ion (Hg) 2+ ) Is waterThe most stable inorganic mercury form in the green environment has carcinogenicity, high solubility and cytotoxicity. Mercury ions in water can be absorbed by microorganisms and converted into methyl mercury which enters the food chain and causes various serious diseases. Long-term intake of large amounts of mercury can lead to serious health problems such as damage to the nervous system, effects on the immune system, etc. Mercury poisoning can have an extremely adverse effect on the whole society, mercury is now preferentially listed on the global environmental monitoring system list, and China has signed the "water with mercury convention" and takes effect from day 8, month 16 of 2017, gradually reduces the use of mercury-containing thermometers, and clearly specifies that mercury-containing thermometers and mercury-containing sphygmomanometers are prohibited from being produced from day 1, year 2026. Therefore, the selective recognition of mercury ions, in particular the in-situ, real-time and on-line monitoring of mercury ions, is of great importance for medicine, biology and environmental science.
At present, reported analysis methods for detecting mercury ions include atomic absorption-emission spectrometry, high performance liquid chromatography, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, electrochemical methods, and fluorescent probe analysis, among which fluorescent probe methods have been receiving attention because of their unique advantages. However, the methods reported at present have certain defects such as poor selectivity, low sensitivity, complex synthesis, poor water solubility, easy quenching and the like. Therefore, the development of highly selective, highly sensitive, synthetic simple mercury ion fluorescent probes is a current urgent need to be addressed. The mercury ions are often used as a quenching agent, and a plurality of mercury ion probes are also quenched, and the fluorescent probes of the 'closed' type are often identified by interference influence of various environmental factors in detection, so that the sensitivity is not high enough, and therefore, the fluorescent probes of the mercury ion type with good design selectivity and high sensitivity and fluorescent 'open' type are valuable.
Disclosure of Invention
In view of the above, the present invention aims to provide a naphthalimide enhanced mercury ion fluorescent probe, and a preparation method and application thereof, which have the characteristics of simple synthesis, good selectivity, high sensitivity, rapid response, enhanced fluorescent probe, and capability of performing dual-channel analysis application by using the tyndall effect, and can effectively measure, detect or screen mercury ions under physiological level conditions.
Specifically, the invention provides a compound, which has a structure shown in a formula (I):
it has the structure of formula (I) or formula (II):
in formula (I): r is R 1 ，R 2 ，R 5 ，R 6 And R is 7 Is hydrogen atom, straight-chain or branched-chain alkyl, straight-chain or branched-chain alkoxy, sulfonic acid group, ester group and carboxyl; r is R 3 ，R 4 Is straight-chain or branched alkyl, straight-chain or branched alkoxy, sulfonic acid group, ester group and carboxyl; r is R 1 ，R 2 ，R 3 ，R 4 And R is 5 ，R 6 ，R 7 May be the same or different;
in the formula (II), X is-C (R) 3 R 4 ) m -, wherein m is 1 to 12; y is-C (R) 3 ＇R 4 ＇) n -, wherein n is 1 to 12; l is independently selected in each occurrence and is-C (R 8 R 9 ) n -, -O-, -S-, -COO-or-NH-; r is R 1 ，R 2 ，R 3 ，R 4 ，R 3 ＇，R 4 ＇，R 5 ，R 6 、R 7 ，R 8 ，R 9 Is hydrogen atom, straight-chain or branched alkyl, straight-chain or branched alkoxy, sulfonic acid group, ester group, carboxyl.
In some embodiments of the invention, m is 1 to 6; n is 1-6;
in some embodiments of the invention, m is 1 to 3; n is 1-3;
in some embodiments of the invention, the compounds of the invention have the structural formula (III) or (IV):
the invention also provides a preparation method of the compounds of the formula (I) and the formula (II), which comprises the following steps:
step 1: reacting a compound of formula (V) with aqueous ammonia to produce a compound of formula (VI), which is of the formula:
step 2: reacting a compound of formula (VI) with (VII) or (VIII) to produce a compound of formula (I) or (II), respectively, of the formula:
r in the formula (I) (VI) (VII) 1 ，R 2 ，R 5 ，R 6 And R is 7 Is hydrogen atom, straight-chain or branched-chain alkyl, straight-chain or branched-chain alkoxy, sulfonic acid group, ester group and carboxyl; r is R 3 ，R 4 Is straight-chain or branched alkyl, straight-chain or branched alkoxy, sulfonic acid group, ester group and carboxyl; r is R 1 ，R 2 ，R 3 ，R 4 And R is 5 ，R 6 ，R 7 May be the same or different;
in the formula (II) (VIII), X is-C (R) 3 R 4 ) m -, wherein m is 1 to 12; y is-C (R) 3 ＇R 4 ＇) n -, wherein n is 1 to 12; l is independently selected in each occurrence and is-C (R 8 R 9 ) n -, -O-, -S-, -COO-or-NH-; r is R 1 ，R 2 ，R 3 ，R 4 ，R 3 ＇，R 4 ＇，R 5 ，R 6 、R 7 ，R 8 ，R 9 Is hydrogen atom, straight-chain or branched alkyl, straight-chain or branched alkoxy, sulfonic acid group, ester group, carboxyl.
Specifically: step (1): and (3) carrying out heating reflux reaction on the compound shown in the formula (V) and ammonia water, and carrying out vacuum filtration after the reaction is finished to obtain a solid product, and further separating the crude product through a chromatographic column to obtain the pure compound shown in the formula (VI).
Step (2): and (3) dissolving the compound shown in the formula (VI) and the compound shown in the formula (VII) or the formula (VIII) in ethylene glycol methyl ether, then carrying out heating reflux reaction, and carrying out vacuum filtration after the reaction is finished to obtain a solid product. The crude product is further separated by chromatography to obtain pure compounds of formula (I) or formula (II).
In some embodiments of the invention, the compound of formula (VI) is reacted with ammonia under reflux at 65℃for 5-10 hours.
In some embodiments of the invention, the molar ratio of the compound of formula (VI) to the compound of formula (VII) or (VIII) is from 1:1 to 1:5.
In some embodiments of the invention, the step 1 column chromatography separation uses methylene chloride as the eluent.
In some embodiments of the present invention, the step 2 of preparing the compound of formula (vii) uses a mixed system of dichloromethane and petroleum ether as eluent for column chromatography separation; the compound of formula (VIII) is prepared by column chromatography using ethanol as eluent.
The present invention also provides a fluorescent probe composition for measuring, detecting or screening mercury ions, comprising the compound of formula (I) or formula (ii) of the present invention.
In some embodiments of the invention, the compound of formula (I) has the following structure:
in some embodiments of the invention, the compound of formula (ii) has the following structure:
in some embodiments of the invention, the fluorescent probe composition further comprises a solvent, an acid, a base, a buffer solution, or a combination thereof.
The invention also provides a kit for detecting the concentration of mercury ions in a sample, comprising the compound of formula (I) according to the invention.
In some embodiments of the invention, the kit further comprises a buffer for determining the concentration of mercury ions in the sample.
The invention also provides a method for detecting the presence of mercury ions in a sample or measuring the mercury ion content in a sample, comprising:
a) Contacting the compound of formula (I) or formula (ii) with a sample to form a fluorescent compound;
b) Determining the fluorescent properties of the fluorescent compound.
In some embodiments of the invention, the sample is a chemical sample or a biological sample.
In some embodiments of the invention, the sample is a biological sample including water, blood, a microorganism, or an animal cell or tissue.
The invention also provides application of the compound shown in the formula (I) or the formula (II) in cell fluorescence imaging.
The invention also provides application of the compound shown in the formula (I) or the formula (II) in the visual analysis of mercury ions by using the tyndall effect.
Compared with the prior art, the invention has the following remarkable advantages and effects:
(1) Fast response
The mercury ion fluorescent probe can realize quick response to mercury ions, and can reach maximum fluorescence intensity within about 10 minutes, thereby being beneficial to quick detection of mercury ions.
(2) Good selectivity and strong anti-interference capability
The mercury ion fluorescent probe can selectively react with mercury ions specifically to generate products with fluorescence change, and compared with other common metal ions including but not limited to sodium ions, potassium ions, magnesium ions, cobalt ions, nickel ions, manganese ions, zinc ions, copper ions, lead ions, cadmium ions, ferric ions, ferrous ions, silver ions, calcium ions, aluminum ions and chromium ions, the fluorescent probe has higher selectivity, and other metal ions have little interference on mercury ion detection by the fluorescent probe.
(3) High sensitivity
The fluorescent probe has high sensitivity and is favorable for trace detection of mercury ions.
(4) Enhanced fluorescent probe
The fluorescence of the fluorescent probe is enhanced after the fluorescent probe reacts with mercury ions, so that the fluorescent probe is an enhanced fluorescent probe, and the concentration quenching phenomenon is avoided.
(5) Has the Tyndall effect
The fluorescent probe has the Tyndall effect, can utilize the Tyndall effect to carry out visual analysis on mercury ions, and can simultaneously utilize the characteristic of fluorescence change and the Tyndall effect to carry out double-channel analysis application.
(6) Low cytotoxicity, and can be applied under physiological level
The mercury ion fluorescent probe can be applied under the physiological level condition, has low cytotoxicity, has small interference on other common metal ions in organisms, and can be applied to living cell fluorescent imaging.
(8) Good stability
The mercury ion fluorescent probe has good stability, and can be stored for a long time.
(10) Simple synthesis
The mercury ion fluorescent probe is simple to synthesize and is favorable for commercialization popularization and application.
Drawings
FIG. 1 is a graph showing the change in absorbance of a probe of formula (X) (10. Mu.M) before and after addition of mercury ions (20. Mu.M);
FIG. 2 is a graph showing the change in absorbance of the probe of formula (XI) (20. Mu.M) before and after addition of mercury ions (15. Mu.M);
FIG. 3 (a) is a graph of fluorescence intensity of a probe of formula (X) (10. Mu.M) versus mercury ions (10. Mu.M) at 550nm over time;
FIG. 3 (b) is a linear plot of fluorescence intensity of the probe of formula (X) (10. Mu.M) versus mercury ions (10. Mu.M) at 550nm over time;
FIG. 4 is a graph showing the linear relationship between the fluorescence intensity of the probe of formula (XI) (10. Mu.M) versus mercury ions (7. Mu.M) at 555nm over time;
FIG. 5 (a) is a graph of Hg at various concentrations 2+ (0-2.5. Mu.M) response to fluorescence spectrum of the probe of formula (X) (10. Mu.M);
FIG. 5 (b) is a graph of Hg at various concentrations 2+ (0-2.5. Mu.M) linearity of the fluorescent response to the probe of formula (X) (10. Mu.M);
FIG. 5 (c) is a graph showing Hg at various concentrations 2+ (2.5-7.5. Mu.M) response to fluorescence spectrum of the probe of formula (X) (10. Mu.M);
FIG. 5 (d) is a graph showing Hg at various concentrations 2+ (2.5-7.5. Mu.M) linearity of the fluorescent response to the probe of formula (X) (10. Mu.M);
FIG. 6 (a) is a graph of Hg at various concentrations 2+ (0-9. Mu.M) response to fluorescence spectrum of the probe of formula (XI) (10. Mu.M);
FIG. 6 (b) is a graph of Hg at various concentrations 2+ (2.5-9. Mu.M) linearity of the fluorescent response to the probe of formula (XI) (10. Mu.M);
FIG. 7 is a graph showing the effect of different metal ion analytes (all 25. Mu.M unless specifically indicated) on the fluorescence intensity of the probe of formula (X) (10. Mu.M), wherein the left bar graph represents the fluorescence intensity values of the probe at 550nm in the presence of the different metal ion analytes, wherein the first group is a blank group, no metal ions are added, and the right bar graph represents the fluorescence intensity values of the probe at 550nm after recognition of mercury ions (5. Mu.M) in the presence of the different metal ion analytes, wherein the first group is a blank group, only mercury ions are added;
FIG. 8 is a graph showing the effect of different metal ion analytes (25. Mu.M in each case, unless otherwise indicated) on the fluorescence intensity of the probe of the formula (XI) (10. Mu.M), wherein the left bar graph represents the fluorescence intensity values of the probe at 555nm in the presence of the different metal ion analytes, wherein the first group is a blank group, no metal ions are added, and the right bar graph represents the fluorescence intensity values of the probe at 555nm after recognition of mercury ions (5. Mu.M) in the presence of the different metal ion analytes, wherein the first group is a blank group, only mercury ions are added;
FIG. 9 (a) is an image of the Tyndall effect after the probe of formula (X) (0.1. Mu.M) has been reacted with mercury ions (0.1. Mu.M, 0.2. Mu.M, 0.3. Mu.M, 0.4. Mu.M, 0.5. Mu.M) at various concentrations in pure water.
FIG. 9 (b) is an image of the logarithmic change in mercury ion concentration versus the average gray scale of the corresponding beam after the probe of formula (X) (0.1. Mu.M) was reacted with different concentrations of mercury ions (0.1,0.2,0.3 0.4,0.5. Mu.M) in pure water.
FIG. 10 is a graph of cytotoxicity test data for different cells at different concentrations of ((X) probe;
in FIG. 11, (a, b and c) are fluorescent microscopic imaging patterns of exogenous mercury ions in HepG2 cells with the probe of formula (X) (20. Mu.M), and (d) is the mean fluorescence intensity of the HepG2 cells without and after incubation.
In FIG. 12, (a, b and c) are fluorescence microscopic imaging patterns of the probe of formula (XI) (20. Mu.M) for exogenous mercury ions in HeLa cells, and (d) is the average fluorescence intensity of HeLa cells without and after incubation.
Detailed Description
The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it should be apparent that the described embodiments are only some of the embodiments of the present invention and should not be used to limit the protection scope of the present invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the present invention without making any inventive effort, are intended to fall within the scope of the present invention.
Example 1: synthesis of Compound of formula (IX)
The synthetic route is as follows:
embodiment 1: 4-chloro-1, 8-naphthyridine (232 mg,1 mmol) was refluxed with ammonia water (35 ml) at 65℃for 5 hours, and after the reaction was completed, the crude product containing the compound of formula (IX) was obtained by suction filtration under reduced pressure. The crude product was further separated by chromatography with dichloromethane as eluent to give 210mg of the pure compound of formula (IX) in a pale yellow yield of 90.00%.
Embodiment 2: 4-chloro-1, 8-naphthyridine (349 mg,1.5 mmol) was refluxed with ammonia water (35 ml) at 65℃for 5 hours, and after the completion of the reaction, the crude product containing the compound of formula (IX) was obtained by suction filtration under reduced pressure. The crude product was further separated by chromatography with dichloromethane as eluent to give 302mg of the pure compound of formula (IX) in a pale yellow yield of 86.53%.
Embodiment 3: 4-chloro-1, 8-naphthyridine (232 mg,1 mmol) was refluxed with ammonia water (25 ml) at 65℃for 5 hours, and after the reaction was completed, the crude product containing the compound of formula (IX) was obtained by suction filtration under reduced pressure. The crude product was further separated by chromatography using methylene chloride as eluent to give 198mg of the pale yellow pure compound of formula (IX) in 84.98% yield.
Embodiment 4: 4-chloro-1, 8-naphthyridine (349 mg,1.5 mmol) was refluxed with aqueous ammonia (40 ml) at 65℃for 5 hours, and after the completion of the reaction, the crude product containing the compound of formula (IX) was obtained by suction filtration under reduced pressure. The crude product was further separated by chromatography with dichloromethane as eluent to give 318mg of the pure compound of formula (IX) in a pale yellow yield of 91.12%.
Example 2: synthesis of Compound of formula (X)
The synthetic route is as follows:
embodiment 1: the compound of formula (IX), 4-chloro-1, 8-naphthalimide (300 mg,1.29 mmol) and diethanolamine (525 mg,5 mmol) were dissolved in 12mL of ethylene glycol methyl ether, heated under reflux for 24 hours, and after the reaction was completed, the solid product was obtained by suction filtration under reduced pressure. Separating the crude product by a chromatographic column, and performing column chromatographic separation by using a mixed system of dichloromethane and petroleum ether as an eluent to obtain a pure product. This gives 98mg of the orange pure compound of formula (X) in 27.72% yield.
Embodiment 2: the compound of formula (IX), 4-chloro-1, 8-naphthalimide (300 mg,1.29 mmol) and diethanolamine (315 mg,3 mmol) were dissolved in 12mL of ethylene glycol methyl ether, heated under reflux for 24 hours, and after the reaction was completed, the solid product was obtained by suction filtration under reduced pressure. Separating the crude product by a chromatographic column, and performing column chromatographic separation by using a mixed system of dichloromethane and petroleum ether as an eluent to obtain a pure product. This gives 90mg of the orange pure compound of formula (X) in 25.45% yield.
Embodiment 3: the compound of formula (IX), 4-chloro-1, 8-naphthalimide (233 mg,1 mmol) and diethanolamine (315 mg,3 mmol) were dissolved in 10mL of ethylene glycol methyl ether, heated under reflux for 24 hours, and after the reaction was completed, the solid product was obtained by suction filtration under reduced pressure. Separating the crude product by a chromatographic column, and performing column chromatographic separation by using a mixed system of dichloromethane and petroleum ether as an eluent to obtain a pure product. This gives 85mg of the compound of formula (X) in an orange pure form in a yield of 31.02%.
Embodiment 4: the compound of formula (IX), 4-chloro-1, 8-naphthalimide (233 mg,1 mmol) and diethanolamine (525 mg,5 mmol) were dissolved in 10mL of ethylene glycol methyl ether, heated under reflux for 24 hours, and after the reaction, the solid product was obtained by suction filtration under reduced pressure. Separating the crude product by a chromatographic column, and performing column chromatographic separation by using a mixed system of dichloromethane and petroleum ether as an eluent to obtain a pure product. 88mg of the compound of formula (X) are obtained in pure orange form in a yield of 32.12%.
Example 3: synthesis of Compound of formula (XI)
The synthetic route is as follows:
embodiment 1: the compound of formula (IX), 4-chloro-1, 8-naphthalimide (300 mg,1.29 mmol) and morpholine (335 mg,3.85 mmol) were dissolved in 5mL of ethylene glycol methyl ether, heated under reflux for 12 hours, and after the reaction was completed, the solid product was obtained by suction filtration under reduced pressure. Washing with ethanol 3 times gave 204mg of the yellow solid product in 56.08% yield.
Embodiment 2: the compound of formula (IX), 4-chloro-1, 8-naphthalimide (300 mg,1.29 mmol) and morpholine (560 mg,6.45 mmol) were dissolved in 7mL of ethylene glycol methyl ether, heated under reflux for 12 hours, and after the reaction was completed, the solid product was obtained by suction filtration under reduced pressure. Washing 3 times with ethanol gave 210mg of the product as a yellow solid in 57.81% yield.
Embodiment 3: the compound of formula (IX), 4-chloro-1, 8-naphthalimide (233 mg,1 mmol) and morpholine (335 mg,3.85 mmol) were dissolved in 5mL of ethylene glycol methyl ether, heated under reflux for 18 hours, and after the reaction was completed, the solid product was obtained by suction filtration under reduced pressure. Washing with ethanol 3 times gives 228mg of the product as a yellow solid in 62.68% yield.
Embodiment 4: the compound of formula (IX), 4-chloro-1, 8-naphthalimide (233 mg,1 mmol) and morpholine (335 mg,3.85 mmol) were dissolved in 7mL of ethylene glycol methyl ether, heated under reflux for 18 hours, and after the reaction was completed, the solid product was obtained by suction filtration under reduced pressure. Washing 3 times with ethanol gave 236mg of the product as a yellow solid in 64.87% yield.
The structural characterization data for the pure compound of formula (XI) prepared in example 3 are as follows:
1 H NMR(400MHz,DMSO)δ(ppm):3.21(t,J＝4.4Hz,4H),3.92(t,J＝4.4Hz,4H),7.34(d,J＝8.0Hz,1H),7.80(t,J＝8.0Hz,1H),8.35(d,J＝8.0Hz,1H),8.42(d,J＝8.0Hz,1H),8.48(d,J＝8.0Hz,1H),11.60(s,1H). 13 C NMR(100MHz,DMSO)δ(ppm):164.73,164.21,155.89,131.81,130.96,130.86,130.40,126.47,126.13,123.55,116.87,115.46,66.67,53.50.HRMS(ESI):Calcd for C 16 H 14 N 2 O 3 [M+H] + 283.1004；Found,283.1077.
example 4: hg is added to the fluorescent probe of formula (X) 2+ Front-to-back absorption spectrum variation
Two sets of parallel samples with probe concentration of 10. Mu.M were placed in a 10mL cuvette, and Hg was added to one set 2+ (20 mu M) into the test system, shaking uniformly, standing for 15min, and adding no Hg into the other group 2+ As a control, the absorbance spectrum was then tested for changes with an absorbance photometer. The above assay was carried out in a 5mM HEPES, pH=7.4 test system using the probe of formula (X) prepared in example 2, and the fluorescence spectrum was measured at 25 ℃.
The test results are shown in FIG. 1, and by means of the absorption spectrum, we can see that the absorption peak of the probe does not change significantly after the mercury ions react with the probe.
Example 5: hg is added to the fluorescent probe of formula (XI) 2+ Front-to-back absorption spectrum variation
Two sets of parallel samples with probe concentration of 20. Mu.M were placed in a 10mL cuvette, and Hg was added to one set 2+ (15 mu M) into the test system, shaking uniformly, standing for 7min, and adding no Hg into the other group 2+ As a control, the absorbance spectrum was then tested for changes with an absorbance photometer. The above measurement was carried out in a test system of 5mM HEPES, pH=7.4, the probe used was the probe of formula (XI) prepared in example 3, and the fluorescence spectrum was measured at 25 ℃.
The test results are shown in FIG. 2, and by means of the absorption spectrum, we can see that after mercury ions react with the probe, the absorption peak of the probe blue shifts and decreases, and the color of the probe changes from yellow to colorless.
Example 6: fluorescent probe pair of formula (X) 2+ Time dynamic testing of response
The probe (10. Mu.M) was placed in 10mL of the test system, and then mercury ions (10. Mu.M) were added to the test system, and immediately after shaking, the change in fluorescence intensity was measured by a fluorescence spectrometer. The above assay was carried out in a 5mM HEPES, pH=7.4 test system using the probe of formula (X) prepared in example 2, and the fluorescence spectrum was measured at 25 ℃.
The test results are shown in fig. 3 (a) and 3 (b), and it is clear that the fluorescence of the probe at 550nm increases rapidly and reaches a maximum value in about 15 minutes after the mercury ions are added, which indicates that the probe reacts rapidly with the mercury ions and can provide a rapid analysis method for the measurement of Gu Gong ions.
Example 7: fluorescent probe pair of formula (XI) 2+ Time dynamic testing of response
The probe (10. Mu.M) was placed in 10mL of the test system, and then mercury ions (7. Mu.M) were added to the test system, and immediately after shaking, the change in fluorescence intensity was measured by a fluorescence spectrometer. The above measurement was carried out in a test system of 5mM HEPES, pH=7.4, the probe used was the probe of formula (XI) prepared in example 3, and the fluorescence spectrum was measured at 25 ℃.
As shown in FIG. 4, it is clear that the fluorescence of the probe at 555nm increases rapidly and reaches a maximum value in about 7 minutes after the addition of mercury ions, indicating that the probe reacts rapidly with mercury ions and provides a rapid analytical method for the determination of Gu Gong ions.
Example 8: concentration gradient test of fluorescent probe of formula (X) on different concentrations of mercury ions
A plurality of parallel samples with probe concentration of 10 mu M are arranged in a 10mL colorimetric tube, and Hg with different concentrations is then added 2+ (0-7.5. Mu.M Hg except for blank group) 2+ The lowest concentration group was 0.5. Mu.M) was added to the test system, and after shaking uniformly, it was allowed to stand for 15 minutes, and then the change in fluorescence intensity was measured with a fluorescence spectrometer. The above assay was carried out in a 5mM HEPES, pH=7.4 test system using the probe of formula (X) prepared in example 2, and the fluorescence spectrum was measured at 25 ℃.
The test results are shown in FIGS. 5 (a) - (d), and as is clear from FIGS. 5 (a) and (c), the Hg follows 2+ The increase in concentration, the fluorescence intensity at 550nm, gradually increased, and, as can be clearly seen from FIGS. 5 (b) and (d), the fluorescence intensity value exhibited a good linear relationship with the concentration in the two concentration ranges of 0 to 2.5. Mu.M and 2.5 to 7.5. Mu.M, which demonstrates that Hg can be detected by the fluorescent probe 2+ Quantitative analysis was performed.
Example 9: detection limit test and calculation of probe
The detection limit was calculated by fluorescence titration. The detection limit calculation formula is as follows:
detection limit=3σ/k
σ is the standard deviation of fluorescence intensity of the blank probe, and k is the slope of the linear relationship diagram of fig. 3 (b).
The detection limit of the probe of formula (X) was thus calculated to be 46.7nM.
Example 10: concentration gradient test of fluorescent probe of formula (XI) for different concentration of mercury ions
A plurality of parallel samples with probe concentration of 10 mu M are arranged in a 10mL colorimetric tube, and Hg with different concentrations is then added 2+ (0-9. Mu.M, hg except for blank) 2+ The lowest concentration group was 0.5. Mu.M) was added to the test system, and after shaking uniformly, it was allowed to stand for 7 minutes, and then the change in fluorescence intensity was measured with a fluorescence spectrometer. The above measurement was carried out in a test system of 5mM HEPES, pH=7.4, the probe used was the probe of formula (XI) prepared in example 3, and the fluorescence spectrum was measured at 25 ℃.
The test results are shown in FIGS. 6 (a) - (b), and it can be seen from FIG. 6 (a) that with Hg 2+ The increase of the concentration gradually increases the fluorescence intensity at 555nm and the trend is obvious; and as is clear from FIG. 6 (b), in the concentration range of 2.5 to 9. Mu.M, the fluorescence intensity value exhibited a good linear relationship with the concentration, which proves that Hg can be bound by the fluorescent probe 2+ Quantitative analysis was performed.
Example 11: test of the selection Performance and anti-interference Performance of the Probe of formula (X)
Selection performance test: preparing a plurality of 10 mu M probe solutions, adding different analytes which are blank, sodium ion, potassium ion, magnesium ion, cobalt ion, nickel ion, manganese ion, zinc ion, copper ion, lead ion, cadmium ion, ferric ion, ferrous ion, silver ion, calcium ion, aluminum ion and chromium ion (except special indication, the concentration of other analytes is 25 mu M), shaking uniformly, standing for 15 minutes, and testing the change of fluorescence intensity by using a fluorescence spectrometer. The bar graph on the left of each set represents the fluorescence intensity values of the probe (10. Mu.M) at 550nm in the presence of different analytes. The above assay was performed in a 5mM HEPES, pH=7.4 test system using the probe of formula (X) prepared in example 2, and the fluorescence spectrum was measured at 25 ℃.
Anti-jamming capability test: preparing a plurality of 10 mu M probe solutions, and then adding different analytes, wherein the analytes are blank, sodium ion, potassium ion, magnesium ion, cobalt ion and nickel ion respectivelyIon, manganese ion, zinc ion, copper ion, lead ion, cadmium ion, ferric ion, ferrous ion, silver ion, calcium ion, aluminum ion, chromium ion (other analytes except for special designation, concentration is 25 μm), shaking uniformly, and immediately adding Hg 2+ (5. Mu.M), and after shaking uniformly, allowed to stand for 15 minutes, and then the change in fluorescence intensity was measured by a fluorescence spectrometer. The bar graph on the right side of each set represents probe (10. Mu.M) versus Hg in the presence of different analytes 2+ Fluorescence intensity value at 550nm after response. The above assay was carried out in a 5mM HEPES, pH=7.4 test system using the probe of formula (X) prepared in example 2, and the fluorescence spectrum was measured at 25 ℃.
As is clear from fig. 7, only after the addition of mercury ions can a strong change in the fluorescence intensity of the probe be caused, while the effect of other analytes is almost negligible, and the metal ions have little interference with the detection of mercury by the probe. Experiments prove that the probe has higher selectivity and anti-interference capability on mercury ions, and is favorable for detection and analysis of the mercury ions.
Example 12: probe of formula (XI) selection Performance and anti-interference Performance test
Selection performance test: preparing a plurality of 10 mu M probe solutions, adding different analytes which are blank, sodium ion, potassium ion, magnesium ion, nickel ion, manganese ion, zinc ion, copper ion, lead ion, cadmium ion, ferric ion, silver ion, aluminum ion, chromium ion, tin ion and cobalt ion respectively (except for special indication, the concentration of other analytes is 25 mu M), shaking uniformly, standing for 7 minutes, and testing the fluorescence intensity change by using a fluorescence spectrometer. The bar graph on the left of each set represents the fluorescence intensity values of the probe (10. Mu.M) at 555nm in the presence of different analytes. The above assay was performed in a 5mM HEPES, pH=7.4 test system using the probe of formula (XI) prepared in example 3, and the fluorescence spectrum was measured at 25 ℃.
Anti-jamming capability test: multiple 10. Mu.M probe solutions were prepared and then different analytes were added separatelyRespectively blank, sodium ion, potassium ion, magnesium ion, nickel ion, manganese ion, zinc ion, copper ion, lead ion, cadmium ion, ferric ion, silver ion, aluminum ion, chromium ion, tin ion and cobalt ion (other analytes with the concentration of 25 mu M except special designation), shaking uniformly, and immediately adding Hg 2+ (5. Mu.M), and after shaking uniformly, allowed to stand for 7 minutes, and then the change in fluorescence intensity was measured by a fluorescence spectrometer. The bar graph on the right side of each set represents probe (10. Mu.M) versus Hg in the presence of different analytes 2+ Fluorescence intensity value at 555nm after response. The above measurement was carried out in a test system of 5mM HEPES, pH=7.4, the probe used was the probe of formula (XI) prepared in example 3, and the fluorescence spectrum was measured at 25 ℃.
As is clear from fig. 8, only after the addition of mercury ions can a strong change in the fluorescence intensity of the probe be caused, while the effect of other analytes is almost negligible, and the metal ions have little interference with the detection of mercury by the probe. Experiments prove that the probe has higher selectivity and anti-interference capability on mercury ions, and is favorable for detection and analysis of the mercury ions.
Example 13: probe Tyndall effect test
A test system with a probe concentration of 0.1. Mu.M was prepared, then mercury ions (0.1. Mu.M, 0.2. Mu.M, 0.3. Mu.M, 0.4. Mu.M, 0.5. Mu.M) were added to the test system, and after shaking uniformly, photographs were taken in a darkroom by irradiation with a red laser, as shown in FIG. 9 (a). FIG. 9 (b) is an image of the logarithmic change in mercury ion concentration versus the average gray scale of the corresponding light beam after the probe (0.1. Mu.M) was reacted with different concentrations of mercury ions 0.1. Mu.M, 0.2. Mu.M, 0.3. Mu.M, 0.4. Mu.M, 0.5. Mu.M in pure water.
The probe used was the probe of the formula (X) prepared in example 2
As can be seen from fig. 9 (a), in the system with only the probe, the tyndall effect is not obvious, only one weaker beam is provided, and after the identifier mercury ions are added, the probe and the mercury ions act together, so that the tyndall effect is enhanced, and a more obvious beam can be seen. As can be seen from fig. 9 (b), as the concentration of mercury ions increases, the average gray level change of the corresponding light beam has a good linear relationship with the logarithm of the concentration of mercury ions, so that the probe can ultra-sensitively observe the change after mercury ions are added through the tyndall effect, thereby realizing detection of mercury ions by multiple channels; and the operation is completed in pure water, which shows that the probe can realize naked eye detection of an actual water sample.
Example 14: cytotoxicity test of probes
Different concentrations (0, 5, 10, 20 and 30. Mu.M) of probe were tested for cytotoxicity against HepG2 cells using the cell counting kit (CCK-8).
All cells were seeded in 96-well plates at a seeding density of 1×106 cells/mL -1 Incubating for 12h at 37℃in 5% carbon dioxide-95% air. The corresponding groups of cells were then incubated with different concentrations of probes for 10h. Subsequently, CCK-8 solution was added to each well plate, and after 2 hours, absorbance was measured at 550 nm.
The probe used was the probe of the formula (X) prepared in example 2
The test results are shown in fig. 10, and the results show that the NIDEA-Hg with different concentrations has no significant effect on the cell viability, indicating that the probe has low cytotoxicity.
Example 15: fluorescent probe cell fluorescence imaging performance test of formula (X)
The first group of HepG2 cells was not probed and Hg 2+ Incubating; incubating the second group of HepG2 cells for 20 minutes by using a probe solution, and performing cell fluorescence imaging; after incubation of the third group of HepG2 cells with the probe for 20 min, hg was again used 2+ Cell fluorescence imaging is carried out after the probe is incubated for 20 minutes; the cell fluorescence imaging map and the data calculation map are shown in fig. 11.
The probe used was the probe of the formula (X) prepared in example 2
As can be seen from fig. 11, the control group cells showed no fluorescence without probe (fig. 11 a), the cells incubated with the probe only showed weak green fluorescence (fig. 11 b), and the fluorescence intensity of the experimental group cells was significantly enhanced (fig. 11 c). The results indicate that fluorescent probes of formula (X) can be used for Hg in living cells 2+ Is detected.
Example 16: fluorescent probe cell fluorescence imaging performance test for XI
The first group of HeLa cells were not probed and Hg 2+ Incubating; incubating the second group of HeLa cells for 20 minutes by using a probe solution, and performing cell fluorescence imaging; after incubating the third group of HeLa cells with the probe for 20 minutes, hg was used again 2+ Cell fluorescence imaging is carried out after the probe is incubated for 20 minutes; the cell fluorescence imaging map and the data calculation map are shown in fig. 12.
The probe used was the probe of formula (XI) prepared in example 3
As can be seen from fig. 12, the control group cells showed no fluorescence without probe (fig. 12 a), the cells incubated with the probe only showed weak green fluorescence (fig. 12 b), and the fluorescence intensity of the experimental group cells was significantly enhanced (fig. 12 c). The results indicate that fluorescent probes of formula (XI) can be used for Hg in living cells 2+ Is detected.
While the invention has been described with reference to the above embodiments, it will be understood that the invention is capable of further modifications and variations without departing from the spirit of the invention, and these modifications and variations are within the scope of the invention.
Claims (6)
1. A compound having the structure of formula (iii):
。
2. a fluorescent probe composition for measuring, detecting or screening mercury ions comprising a compound of formula (iii)
。
3. The fluorescent probe composition of claim 2, further comprising a solvent, an acid, a base, a buffer solution, or a combination thereof.
4. A method for detecting the presence of mercury ions in a sample or determining the mercury ion content in a sample, comprising:
a) Contacting the compound of claim 1 with a sample to form a fluorescent compound;
b) Determining the fluorescent properties of the fluorescent compound.
5. Use of a compound according to claim 1 for the visual analysis of mercury ions using the tyndall effect.
6. Use of a compound according to claim 1 for fluorescence imaging of cells for non-therapeutic or diagnostic purposes.
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