Phenanthroline compound as well as preparation method and application thereof

Abstract

The invention discloses a phenanthroline compound and a preparation method and application thereof, and belongs to the technical field of copper ion detection, the phenanthroline compound has a structure as shown in formula (I): wherein R1 and R2 are the same or different and are respectively and independently hydrophilic groups; the compound provided by the invention is high in fluorescence quantum yield and can sensitively detect copper ions in an aqueous solution. # imgabs0 #

Description

Technical Field

[0001] The invention relates to an o-phenanthroline compound and a preparation method and application thereof, and in particular to the technical field of copper ion detection. Background Art

[0002] Copper ions are the third most abundant element in biological and ecological systems after iron ions and zinc ions. Copper ions play an important role in organisms and the ecological environment. Trace amounts of copper ions can promote the growth of plants and animals, but when they accumulate in organisms to a certain extent through ecology, they will cause varying degrees of damage to the organisms, resulting in physiological stagnation, developmental stagnation, and even death; excessive copper ions will also affect and damage the function, structure, and development trend of the entire aquatic ecosystem, and even lead to collapse. Therefore, the detection of copper ions in water is crucial.

[0003] Currently, the new copper reagent is a commonly used colorimetric agent that selectively responds to copper ions, but the UV-visible absorption spectroscopy method has lower sensitivity than the fluorescence method.

[0004] The core principle of fluorescence detection of copper ions is to detect copper ions by the interaction between fluorescent probes and copper ions, resulting in changes in fluorescent signals. This method has the advantages of high sensitivity, simple operation, and fast response. At present, the specific methods include the following:

[0005] (1) Amino-functionalized zirconium dioxide nanotube array film method: This method uses amino-functionalized zirconium dioxide nanotube array film as a carrier and rhodamine B as a fluorescent probe. Copper ions and rhodamine B are immobilized on the carrier to prepare a detection sample. The detection of copper ions is achieved by testing the fluorescence intensity of the detection sample.

[0006] (2) Peptide fluorescence sensor method: Based on the fluorescence quenching effect of copper ions on rhodamine B-labeled peptides, a fluorescence sensor for copper ion detection was constructed;

[0007] (3) Functionalized carbon quantum dots method: The fluorescence properties of functionalized carbon quantum dots are used to detect copper ions. This method achieves sensitive detection of copper ions by causing changes in the fluorescence signal through the interaction between carbon quantum dots and copper ions.

[0008] Therefore, it is necessary to provide a new copper ion detection compound that can detect copper ions and has high sensitivity and high fluorescence quantum yield during the detection process. Summary of the invention

[0009] One of the purposes of the present invention is to provide a phenanthroline compound having a high fluorescence quantum yield.

[0010] The second object of the present invention is to provide a method for preparing o-phenanthroline compounds, wherein 2,9-dimethyl-1,10-phenanthroline is first oxidized with an oxidant to oxidize two methyl groups into aldehyde groups; and then the intermediate product of the previous step is reacted with a compound represented by formula (2) containing a thiol group and an amino group to obtain an o-phenanthroline compound. The synthesis method has mild reaction conditions, simple process, good selectivity, high yield, and is conducive to industrial production.

[0011] The third object of the present invention is to provide an application of o-phenanthroline compounds in detecting copper ions. The compounds can sensitively detect copper ions in aqueous solution, the compounds can specifically bind to copper ions, have no obvious fluorescence quenching for other metal binding, and have excellent selectivity.

[0012] In order to achieve the above object, the present invention provides a phenanthroline compound having a structure shown in formula (I):

[0013]

[0014] Wherein, R1 and R2 are the same or different and are each independently a hydrophilic group.

[0015] The key technology of the present invention is that the compound prepared by using 2,9-dimethyl-1,10-phenanthroline as a raw material retains its cavity structure and has a special response ability to copper ions. Furthermore, a rigid conjugated planar structure is added on the basis of the o-phenanthroline structure, which greatly improves the fluorescence yield.

[0016] In a preferred embodiment, R1 and R2 are the same or different and are independently selected from a C1-C6 alkyl group containing a carboxyl group, a C1-C6 alkyl group containing a hydroxyl group, a C1-C6 alkyl group containing a sulfonic acid group, -COOH, -OH, and -SO3H.

[0017] In a preferred embodiment, R1 and R2 are identical or different, and are independently-COOH or-OH. The inventors of the present invention have found that under this optimal condition, the hydrophilicity of o-phenanthroline compounds provided by the present invention is better. The length of the carbochain connected with hydroxyl or carboxyl can affect the hydrophilicity of o-phenanthroline compounds, and along with the minimizing of the number of carbon atoms, the hydrophilicity of o-phenanthroline compounds is better, and when R1 and R2 groups are-COOH or-OH, the hydrophilicity of o-phenanthroline compounds is best.

[0018] In a preferred embodiment, the compound represented by formula (I) is selected from any one of the following compounds:

[0019]

[0020] The inventors of the present invention have found that when the o-phenanthroline compound is selected from Compound 1 or Compound 2, its fluorescence intensity is stronger, its selectivity for copper ions is better, and its water solubility is also the strongest.

[0021] The present invention also provides a method for preparing o-phenanthroline compounds, the method comprising:

[0022] (1) in the presence of an organic solvent I, subjecting the compound represented by formula (1) to an oxidation reaction with an oxidant to obtain a dialdehyde intermediate I;

[0023] (2) in the presence of an organic solvent II, subjecting the dialdehyde intermediate I to a ring contraction reaction with a compound represented by formula (2) to obtain a phenanthroline compound;

[0024]

[0025] In formula (2), R is R1 or R2, and the definitions of R1 and R2 are the same as those of R1 and R2 described above, and are hydrophilic groups.

[0026] In a preferred embodiment, R is selected from a C1-C6 alkyl group containing a carboxyl group, a C1-C6 alkyl group containing a hydroxyl group, a C1-C6 alkyl group containing a sulfonic acid group, -COOH, -OH, and -SO3H.

[0027] In a preferred embodiment, the compound represented by formula (2) is The inventors of the present invention have found that under preferred conditions, the synthesis yield of o-phenanthroline compounds is higher, which may be due to the fact that the structure has a stronger electron-pulling ability and is more conducive to the ring-forming reaction.

[0028] In a preferred embodiment, in step (1), the oxidant is selected from at least one of selenium dioxide, manganese dioxide and chromyl chloride.

[0029] In a preferred embodiment, the conditions of the oxidation reaction include: a temperature of 105 to 110° C. and a time of 2 to 4 hours.

[0030] In a preferred embodiment, in step (2), the conditions for the ring contraction reaction include: a temperature of 80 to 90° C. and a time of 6 to 10 hours.

[0031] In a preferred embodiment, in step (1), the molar ratio of the compound represented by formula (1) to the oxidant is 1:1 to 2. The inventors of the present invention have found that in this preferred embodiment, the synthesis yield of the present invention is higher. If the content of the oxidant is too low, the methyl group in the compound represented by formula (1) cannot be completely oxidized to an aldehyde group. If the content of the oxidant is too high, the toxicity of the waste liquid will increase or excessive oxidation will generate carboxyl groups.

[0032] In a preferred embodiment, in step (2), the molar ratio of the dialdehyde intermediate I to the compound represented by formula (2) is 1:2 to 3. Studies have shown that when the amount of the compound represented by formula (2) is too low, the dialdehyde intermediate I will not react completely, resulting in a low yield, while when the amount of the compound represented by formula (2) is too high, the dialdehyde intermediate I will react completely but the compound represented by formula (2) will be wasted in excess.

[0033] It should be noted that in step (2), the method further comprises purifying the crude product obtained after the ring contraction reaction, and the present invention has no special requirements for the purification process. In order to obtain a higher purity o-phenanthroline compound, according to a preferred embodiment, the operation of the purification process comprises: purifying the crude product by a silica chromatography column, and the eluent is dichloromethane-methanol.

[0034] In a preferred embodiment, the organic solvent I is selected from 1,4-dioxane and / or propionitrile. All of these organic solvents can be used to successfully synthesize o-phenanthroline compounds, and 1,4-dioxane is the best organic solvent.

[0035] In a preferred embodiment, the method further comprises: firstly mixing an organic solvent I with water in a volume ratio of 92-98:8-2, and then subjecting the compound represented by formula (1) to an oxidation reaction with an oxidant to obtain a dialdehyde intermediate I.

[0036] In a preferred embodiment, the organic solvent II is selected from at least one of ethanol, ethyl acetate and acetonitrile. In these organic solvents, o-phenanthroline compounds can be synthesized smoothly, and ethanol is the best organic solvent.

[0037] It should be noted that the present invention has no special requirements on the dosage of the organic solvent I and the organic solvent II, and any dosage known in the art can be used.

[0038] The present invention also provides the use of o-phenanthroline compounds in detecting copper ions. The o-phenanthroline compounds provided by the present invention have a special response ability to copper ions.

[0039] Compared with the prior art, the technical solution of the present invention brings the following beneficial technical effects:

[0040] (1) The o-phenanthroline compounds provided by the present invention retain the cavity structure of 2,9-dimethyl-1,10-phenanthroline and have a special response ability to copper ions. Furthermore, a rigid conjugated planar structure is added on the basis of the o-phenanthroline structure, which greatly improves the fluorescence yield.

[0041] (2) The hydrophilic group (carboxyl or hydroxyl) is added to the o-phenanthroline compound provided by the present invention, thereby enhancing its water solubility and being more conducive to practical application.

[0042] (3) The synthesis method has mild reaction conditions, simple process, good selectivity, high yield, and is conducive to industrial production. DETAILED DESCRIPTION

[0043] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0044] In the present invention, It means that R can be substituted at any substitutable position of the phenyl group.

[0045] In the present invention, It means that R1 can be substituted at any substitutable position of the phenyl group.

[0046] In the present invention, It means that R2 can be substituted at any substitutable position of the phenyl group.

[0047] In the present invention, "C1-C6 alkyl containing carboxyl group" refers to an alkyl group having a total of 1 to 6 carbon atoms, including straight-chain alkyl groups, branched-chain alkyl groups and cycloalkyl groups, and at least one H atom in the C1-C6 alkyl group is substituted by a carboxyl group. For example, 1, 2, 3 or 4 H atoms in the C1-C6 alkyl group are substituted by carboxyl groups, such as -CH2-COOH, -CH2-CH2-COOH, Etc. The explanations for "C1-C6 alkyl containing hydroxyl group" and "C1-C6 alkyl containing sulfonic acid group" are similar to this, except that the groups replacing the H atom are different, namely hydroxyl group and carboxyl group.

[0048] The present invention is further described below in conjunction with specific embodiments, but the protection scope of the present invention is not limited to the following specific embodiments. Obviously, the embodiments described below are only a part of the embodiments, and all other embodiments obtained by professionals in this field without creative work still belong to the protection scope of the present invention.

[0049] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present invention can be purchased from the market or prepared by existing methods.

[0050] Preparation Example 1 (Preparation of Compound 1)

[0051] (1) In a three-necked reaction flask equipped with a mechanical stirrer, a thermometer, and a condenser, in the presence of 100 mL of a 1,4-dioxane solution (the volume ratio of 1,4-dioxane to water is 95:5), 10 mmol of 2,9-dimethyl-1,10-phenanthroline and 15 mmol of selenium dioxide were reacted at 105° C. for 4 h to obtain a dialdehyde intermediate I;

[0052] (2) In the presence of 100 mL of ethanol, 2 mmol of dialdehyde intermediate I and 4 mmol The reaction was carried out at 85°C for 8 hours, and the crude product obtained by the reaction was purified by a silica chromatography column with dichloromethane-methanol (10:1, V / V) as the eluent to obtain compound 1 with a yield of 68% (calculated based on 2,9-dimethyl-1,10-phenanthroline).

[0053] The NMR characterization results of compound 1 are as follows:

[0054] 1 HNMR (CDCl3, 400MHz), δ: 8.77-8.79 (d, 2H), 8.42-8.45 (d, 2H), 8.18-8.20 (d, 2H), 8.15-8.16 (d, 2H), 7.91-7.93 (d, 2H), 7.56-7.59 (d, 2H)

[0055] Preparation Example 2 (Preparation of Compound 2)

[0056] (1) In a three-necked reaction flask equipped with a mechanical stirrer, a thermometer, and a condenser, in the presence of 100 mL of a 1,4-dioxane solution (the volume ratio of 1,4-dioxane to water is 95:5), 10 mmol of 2,9-dimethyl-1,10-phenanthroline and 10.5 mmol of selenium dioxide were reacted at 110° C. for 2 h to obtain a dialdehyde intermediate I;

[0057] (2) In the presence of 100 mL of ethanol, 2 mmol of dialdehyde intermediate I and 5 mmol The reaction was carried out at 80°C for 10 hours, and the crude product was purified by silica chromatography with dichloromethane-methanol (10:1, V / V) as the eluent to obtain compound 2 with a yield of 65% (calculated based on 2,9-dimethyl-1,10-phenanthroline).

[0058] The NMR characterization results of compound 2 are as follows:

[0059] 1HNMR (CDCl3, 400MHz), δ: 8.61-8.63 (d, 2H), 8.17-8.19 (d, 2H), 8.03-8.05 (d, 2H), 7.97-7.99 (d, 2H), 7.75-7.77 (d, 2H), 7.41-7.43 (d, 2H)

[0060] Test Case

[0061] The compounds prepared in the above preparation examples were investigated for their selectivity to metal ions.

[0062] 0.5 μmol of the compound prepared in the above preparation example and were added to 100 mL of different types of metal ions, and the fluorescence intensity of the solution was tested. The specific information is shown in Table 1.

[0063] The fluorescence intensity was detected by using a fluorescence spectrophotometer, with λex: 365 nm, λem: 416.6 nm, and a slit width of 2.5 nm.

[0064]

[0065] From the above data, it can be seen that the o-phenanthroline compounds provided by the present invention only selectively respond to copper ions and have no selectivity for other metals. In a solution without copper ions, the compound has a high fluorescence intensity and no fluorescence quenching, indicating that other metals have no response. When in a solution containing copper ions, the fluorescence is quenched and the fluorescence intensity is greatly reduced.

[0066] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A phenanthroline compound, characterized in that: The compound has a structure shown in formula (I): Wherein, R1 and R2 are the same or different and are each independently a hydrophilic group.

2. A phenanthroline compound according to claim 1, characterized in that: R1 and R2 are the same or different, and are independently selected from a C1-C6 alkyl group containing a carboxyl group, a C1-C6 alkyl group containing a hydroxyl group, a C1-C6 alkyl group containing a sulfonic acid group, -COOH, -OH, and -SO3H.

3. A phenanthroline compound according to claim 1 or 2, characterized in that: R1 and R2 are the same or different and are each independently -COOH or -OH.

4. A phenanthroline compound according to claim 1 or 2, characterized in that: The compound represented by formula (I) is selected from any one of the following compounds:

5. A method for preparing the o-phenanthroline compound according to any one of claims 1 to 4, characterized in that: The method includes: (1) in the presence of an organic solvent I, subjecting the compound represented by formula (1) to an oxidation reaction with an oxidant to obtain a dialdehyde intermediate I; (2) in the presence of an organic solvent II, subjecting the dialdehyde intermediate I to a ring contraction reaction with a compound represented by formula (2) to obtain a phenanthroline compound; In formula (2), R is R1 or R2, and R1 and R2 have the same definition as described in any one of claims 1 to 4, and are hydrophilic groups.

6. The method for preparing o-phenanthroline compounds according to claim 5, wherein: In step (1), the molar ratio of the compound represented by formula (1) to the oxidant is 1:1-2; And / or, in step (2), the molar ratio of the dialdehyde intermediate I to the compound represented by formula (2) is 1:2-3.

7. The method for preparing o-phenanthroline compounds according to claim 5 or 6, characterized in that: In step (1), the oxidant is selected from at least one of selenium dioxide, manganese dioxide and chromyl chloride.

8. The method for preparing o-phenanthroline compounds according to any one of claims 5 to 7, characterized in that: The conditions of the oxidation reaction include: temperature of 105-110° C. and time of 2-4 hours.

9. The method for preparing o-phenanthroline compounds according to any one of claims 5 to 8, characterized in that: In step (2), the conditions for the ring contraction reaction include: temperature of 80 to 90° C. and time of 6 to 10 hours.

10. Use of the o-phenanthroline compound according to any one of claims 1 to 4 in detecting copper ions.

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