KR102154073B1 - Composition for detecting water comprising naphthalimide derivatives - Google Patents

Abstract

The present invention relates to a naphthalimide derivative or a pharmaceutically acceptable salt thereof, and a composition for moisture detection using the same, wherein the naphthalimide derivative emits fluorescence and double emission in the presence of moisture in a polar organic solvent without separate pretreatment. As it is confirmed that the fluorescence intensity increases due to the wavelength and moisture content contained therein, the naphthalimide derivative can be provided as a fluorescent probe for moisture detection, and the paper strip impregnated with the fluorescent probe is fast and It can be provided as a moisture detection strip that can be used to check the presence of moisture in a sample in real time and reuse in a simple way.

Description

Composition for detecting water comprising naphthalimide derivatives}

The present invention relates to a naphthalimide derivative or a pharmaceutically acceptable salt thereof, and a composition for detecting moisture using the same.

Water, which is one of the most important and essential elements chemically as well as human lifespan, is contained in a certain amount in many substances such as food, medicine, and steel materials, and it is a well-known fact that the moisture content determines the characteristics of each product. Therefore, accurate measurement and control of water content is an important factor in the factory in order to optimize product characteristics and control quality.

In a chemical reaction, the presence of water does not proceed with the reaction or produces unwanted products, so a water-free condition is required for a reliable chemical reaction. In addition, the water content of industrial oils and fuels causes corrosion and other serious mechanism problems, and the quality and shelf life of pharmaceuticals and processed foods are determined by a small amount of water.

Accordingly, in order to accurately measure moisture in various samples in human life including chemical and industrial fields, research on a simpler and more efficient moisture measurement method is required.

Various analysis methods including chromatography mass spectrometry, titration, and distillation have been developed as a method for measuring moisture in a sample, but these methods take a lot of time, cannot be monitored in real time, and require expensive equipment and operations. There is a problem that requires specialized knowledge for this.

In order to solve this problem, in recent years, a number of fluorescent probes for detecting a trace amount of moisture have been developed due to several advantages such as ease of operation, high selectivity, and sensitivity.

The ideal fluorescent probe for moisture in various samples exhibits ratiometric changes in double emission with fast reaction time and reversibility, and enables accurate analysis and real-time monitoring of moisture as well as simple analysis strip application.

Many of these probes are capable of detecting water and probes through various recognition mechanisms such as light-induced electron transfer (PET), intramolecular charge transfer (ICT), excited state intermolecular proton transfer (ESIPT), and aggregation-induced emission (AIE). It operates in “on-off” and “off-on” manners in a single emission based on a combination.

Single emission fluorescent probes suffer from interference by independent factors of various analytes, such as microenvironment around the probe molecule, photobleaching, local concentration, and tool parameters, and recently, hydrolysis of Schiff base has been opened. , A water-selective fluorescent probe using hydrolysis of aldehyde and opening of rhodamine ring was developed.

However, the reaction-based probe exhibits a relatively slow fluorescence reaction in consideration of the reaction time with water, and a problem that is affected by strong nucleophiles, oxidizing or reducing substances, and acidity of the test sample appears. There is a need for research on a simple and efficient moisture measurement method.

Republic of Korea Patent Publication No. 10-2014-0059983 (published on May 19, 2014)

In order to solve the above problems, the present invention is to provide a fluorescent probe for checking the presence of water in an organic solvent or a sample and accurately and quickly checking the moisture content contained in the organic solvent or sample, and a moisture detection method using the same. .

The present invention provides a naphthalimide derivative represented by the following formula (1) or a pharmaceutically acceptable salt thereof.

[Formula 1]

In Formula 1, at least one of R ₁ to R ₃ is halogen and the rest is hydrogen, and R ₄ is any one selected from the group consisting of phenyl, -COOH, -OH and (C1 to C6)alkyl.

The present invention provides a composition for detecting moisture comprising a naphthalimide derivative represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

The present invention provides a fluorescent probe for detecting moisture comprising a naphthalimide derivative represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

The present invention provides a strip for water detection comprising a naphthalimide derivative represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention comprises the steps of reacting by adding a sample to a composition containing the naphthalimide derivative or a pharmaceutically acceptable salt thereof; And measuring at least one index selected from the group consisting of absorbance, fluorescence intensity, and optical change of the reacted reactants.

According to the present invention, the naphthalimide derivative represented by Formula 1 exhibits fluorescence emission and double emission wavelength in the presence of moisture in a polar organic solvent without separate pretreatment, and it is confirmed that the fluorescence intensity increases due to the contained moisture content. Accordingly, the naphthalimide derivative may be provided as a fluorescent probe for moisture detection, and the paper strip impregnated with the fluorescent probe checks the presence of moisture in the sample in real time and detects reusable moisture in a quick and easy way. It can be provided as a dragon strip.

Figure 1 is a result of confirming the standard absorption (Abs.) and fluorescence (Em.) spectra of each compound in water containing 10% DMS0, Figure 1 (a) is compound 1, Figure 1 (b) is compound 2, 1(c) is a result of compound 3 and FIG. 1(d) is a result of compound 4, each compound has a concentration of 5 μM, and the inserted picture is the result of confirming the visual and fluorescent color.
Figure 2 is a result of confirming the fluorescence change of Compound 1 (5 μM) in an EtOH solution containing different proportions of moisture, Figure 2 (a) is 0-50%, Figure 2b is a result of 50-90%, insert The plotted plot shows fluorescence intensity (FI) vs. It is a graph showing [Water] (%). 2C is a result of confirming the degree of visualization of the change in the fluorescence color of Compound 1 with increasing water, and all spectra were obtained using 350nm excitation.
3(a) is a result of confirming the change in the fluorescence intensity ratio of Compound 1 according to various moisture ratios (0-90%) in ACN, MeOH and EtOH solutions, and FIG. 3(b) shows the fluorescence intensity ratio in ACN solution and [ Water] is the result of confirming the linear correlation between (%), Figures 3(c) and 3(d) are the results of confirming the linear correlation between the fluorescence intensity ratio in the MeOH solution and [Water] (%), 3(e) and 3(f) are results of confirming the linear correlation between the ratio of fluorescence intensity in the EtOH solution and [Water] (%), and all data were obtained under 350 nm excitation.
Figure 4 is a result of confirming the partial 1H NMR spectra of Compound 1 in CDCl ₃ containing DMSO-d ₆ in different ratios, Figure 4 (a) 0%, Figure 4 (b) 50% and Figure 4 (c) 100 % (v/v), and an asterisk (*) indicates the residual CDCl ₃ solvent.
Figure 5 (a) is a result of confirming the change in the fluorescence color of the paper strip immersed in Compound 1 in the EtOH, MeOH and ACN solutions containing different proportions (%) of water, Figure 5 (b) is a paper strip by simple drying As a result of confirming the reversibility of the change in fluorescence color, the change in fluorescence color was confirmed using a portable UV lamp providing 365 nm excitation.
6 is a schematic diagram showing a moisture detection method using a paper strip impregnated with Compound 1.

Hereinafter, the present invention will be described in more detail.

The present invention can provide a naphthalimide derivative represented by the following Formula 1 or a pharmaceutically acceptable salt thereof.

[Formula 1]

In Formula 1, at least one of R ₁ to R ₃ is halogen and the rest is hydrogen, and R ₄ may be any one selected from the group consisting of phenyl, -COOH, -OH, and (C1 to C6)alkyl. .

In more detail, in Formula 1, at least one of R ₁ to R ₃ is fluoro and the rest is hydrogen, and R ₄ is (C1 to C6) alkyl, characterized in that a naphthalimide derivative or a pharmaceutically acceptable It can be salt.

The present invention can provide a composition for detecting moisture comprising a naphthalimide derivative represented by the following Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[Formula 1]

In Formula 1, at least one of R ₁ to R ₃ is halogen and the rest is hydrogen, and R ₄ may be any one selected from the group consisting of phenyl, -COOH, -OH, and (C1 to C6)alkyl. .

In more detail, in Formula 1, at least one of R ₁ to R ₃ is fluoro and the rest is hydrogen, and R ₄ is (C1 to C6) alkyl, characterized in that a naphthalimide derivative or a pharmaceutically acceptable It can be salt.

The naphthalimide derivative represented by Formula 1 or a pharmaceutically acceptable salt thereof exhibits a double emission wavelength in the presence of moisture in the sample, and the fluorescence intensity may be changed depending on the moisture content included.

According to an embodiment of the present invention, as a result of confirming the absorbance and fluorescence spectra for moisture of Compounds 1 to 4 represented by Formula 1, as shown in FIG. 1A, Compound 1 has an absorption band at about 350 nm, and at 452 and 558 nm. Two strong emission bands appeared. The Stoke shift (Δλ) of the double emission was 102 and 208 nm, respectively, and the pale yellow solution of Compound 1 exhibited glowing white fluorescence.

Compound 2 showed absorption at 365 nm, emission at 550 nm (Δλ = 180 nm) and 435 nm (Δλ = 70 nm) as shown in FIG. 1B, and a pale yellow solution exhibited a glowing yellow fluorescent color.

In addition, toluene, dichloromethane (DCM), tetrahydrofuran (THF), CHCl ₃ , acetone, acetonitrile (ACN), N,N-dimethylformamide (N ,N-dimethylformamide; DMF), dimethyl sulfoxide (DMSO), methanol (Methanol; MeOH) and ethanol (ethanol; EtOH) absorption and fluorescence spectra of compounds 1, 2, 3 and 4 in various organic solvents such as As a result of confirming, as shown in Table 1, compound 1 showed two absorption bands at 350 and 460 nm with double emission of about 440 and 560 nm in DMF and DMSO, and showed yellow fluorescence.

In addition, for toluene, DCM, THF, CHCl ₃ , acetone, MeOH, and EtOH solutions, an absorption band was observed at about 350 nm, and a single emission band of the highest value was found in the range of 419-447 nm.

The toluene, DCM, THF, CHCl ₃ , acetone and ACN solutions of Compound 1 exhibited dark blue fluorescence, while bright blue fluorescence was observed in MeOH and EtOH solutions.

In the above results, the bright white fluorescence of Compound 1, which appeared in water, did not appear in the experimental organic solvent.

From the above results, it was confirmed that in ethanol and methanol, which are magnetic solvents of the same polarity as water, unique absorption and double release of water were observed. In particular, compound 1 was found to be in water contained in the organic solvent. It was confirmed that the ratio change can be provided through the double emission of light, and accurate detection and real-time monitoring are possible by easily visualizing and providing the fluorescent color change.

Accordingly, the present invention can provide a fluorescent probe for water detection comprising a naphthalimide derivative represented by the following Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[Formula 1]

In Formula 1, at least one of R ₁ to R ₃ is halogen and the rest is hydrogen, and R ₄ may be any one selected from the group consisting of phenyl, -COOH, -OH, and (C1 to C6)alkyl. .

The present invention can provide a strip for moisture detection comprising a naphthalimide derivative represented by the following Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[Formula 1]

In Formula 1, at least one of R ₁ to R ₃ is halogen and the rest is hydrogen, and R ₄ may be any one selected from the group consisting of phenyl, -COOH, -OH, and (C1 to C6)alkyl. .

According to another embodiment of the present invention, for simple moisture detection using Compound 1, a paper strip impregnated with Compound 1 was prepared by immersing a filter paper in a CHCl ₃ solution of Compound 1 (1.0 mM) and drying in an oven for one day. And, as a result of confirming the reversible fluorescence reaction of the paper strip infiltrated with Compound 1 with respect to moisture by repeatedly immersing in an EtOH aqueous solution and drying it, as shown in FIG. 5B, when the paper strip is immersed in an EtOH aqueous solution containing 10% moisture, fluorescence The color changed rapidly from blue to white, and the strip returned to blue fluorescence again by simple solvent drying.

As it is confirmed from the above results that the paper strip can be repeatedly used for moisture detection, the paper strip can be used very effectively for moisture detection by quickly and easily visualizing not only reusability but also changes in fluorescence color.

In addition, the present invention comprises the steps of reacting by adding a sample to a composition containing the naphthalimide derivative or a pharmaceutically acceptable salt thereof; And measuring one or more indicators selected from the group consisting of absorbance, fluorescence intensity, and optical change of the reacted reactants.

The sample may be an organic solvent.

Hereinafter, examples will be described in detail to aid understanding of the present invention. However, the following examples are for illustrative purposes only, and the scope of the present invention is not limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those of ordinary skill in the art.

The following experimental examples are intended to provide experimental examples commonly applied to each of the examples according to the present invention.

< Experimental example 1> Synthetic materials and methods

All reagents were purchased from Alfa (Alfa, Heysham, LA3 2XY, United Kingdom), Aldrich (Aldrich, St. Louis, MO, USA) and TCI (TCI, Tokyo, Japan), and were used without further purification.

All solutions were used for analysis or HPLC grade, HR-ESI-MS data was obtained by liquid chromatography mass spectrometry (LC/MS) of the Korea Basic Science Institute (Seoul), and Bruker (500 MHz) instrument called NMR spectra Was recorded in.

< Experimental example 2> UV/ Vis Absorption and fluorescence spectroscopy method

All solutions used for spectroscopic studies were used in HPLC grade.

Toluene, dichloromethane (DCM), tetrahydrofuran (THF), chloroform, acetone, acetonitrile (ACN), N,N-dimethylformamide (N ,N-dimethylformamide; DMF), dimethyl sulfoxide (DMSO), methanol (methanol), ethanol (ethanol) and water to prepare a compound stock solution using.

All UV/Vis absorbance and fluorescence spectra were recorded on UV-2600 (Shimadzu Corporation, Kyoto, Kyoto Prefecture, Japan) and RF-6000 (Shimadzu Corporation, Kyoto, Kyoto Prefecture, Japan) spectrometers, respectively.

< Synthesis example 1> Synthesis of compounds 1 to 4

Compound 3 and Compound 4 were previously reported (Ghorbanian, S, et al.; J Chem Technol Biotechnol 2000, 75, 1127-1134 and Lee, MH et al.; J. Am. Chem. Soc. 2012, 134, 1316-1322.), and compounds 1 and 2 were synthesized using compound 4 as a starting material.

[Scheme 1]

1. Synthesis of compound 1

[Scheme 2]

Difluoroacetate acid (0.13 mL, 2.06 mmol) dissolved in dichloromethane (DCM, 50 mL) and oxalyl chloride (0.26 mL; 3.07 mmol) were slowly added to a mixture of dimethylformamide (DMF; 0.1 mL).

The reaction mixture was stirred overnight at room temperature under N ₂ gas and confirmed by thin layer chromatography (TLC).

After evaporation of difluoroacetic acid on the TLC plate, the reaction mixture was immediately used for the subsequent reaction. A DCM solution in which Compound 4 was dissolved was added to the reaction mixture containing difluoroacetyl chloride, followed by refluxing at 60° C. for 3 hours under N ₂ gas.

The reaction mixture was quenched in aqueous sodium biscarbonate solution, diluted with DCM (50 mL), and washed with water (100 mL).

The organic layer was collected, dried with anhydrous Na ₂ SO ₄ , and the solution was removed, followed by silica gel column chromatography using ethyl acetate/hexane as an eluent to obtain a yellow solid compound 1 (0.66 g, 92%).

HR-ESI-MS m/z [M] ⁺ calc. 346.1439, [M+H] ⁺ obs. 347.1513. ¹ H NMR (DMSO-d6, 500 MHz):? 0.94 (t, J = 7.5 Hz, 3H); 1.32-1.40 (m, 2H); 1.59-1.65 (m, 2H); 4.03 (t, J = 7.5 Hz, 2H); 6.65 (t, J = 53.5 Hz, 1H); 7.90 (t, J = 7.8 Hz, 1H); 8.11 (d, J = 8.0 Hz, 1H); 8.48-8.54 (m, 3H) ppm. ¹³ C NMR (DMSO-d ₆ , 125 MHz): δ 163.2, 162.8, 162.0, 161.8, 161.6, 137.9, 131.0, 131.0, 129.1, 128.1, 126.9, 125.2, 122.3, 122.0, 119.6, 110.2, 108.3, 106.3, 39.4, 29.6, 19.8, 13.7 ppm.

2. Synthesis of compound 2

[Scheme 3]

In a mixture of compound 4 (0.14 g, 0.53 mmol) and sodium carbonate (sodium carbonate; 0.03 g, 0.26 mmol) in 1,4-dioxane (1,4-dioxane; 5 mL), trifluoroacetic anhydride ( trifluoroacetic anhydride; 0.11 mL, 0.79 mmol) was slowly added, and the reaction mixture was stirred at room temperature with N ₂ gas for 2 hours.

The mixture was diluted with ethyl acetate (50 mL), washed with water, and the organic layer was collected and dried over anhydrous Na ₂ SO ₄ .

After removal of the solvent, the crude product was purified by silica gel column chromatography using ethyl acetate/hexane (v/v, 1:2) as an eluent to obtain a yellowish white solid compound 2 (0.16 g, 82%). . HR-ESI-MS m/z [M] ⁺ calc. 364.1342, [M+H] ⁺ obs. 365.1415. ¹ H NMR (DMSO-d ₆ , 500 MHz):? 0.93 (t, J = 7.5 Hz, 3H); 1.31-1.42 (m, 2H); 1.58-1.67 (m, 2H); 4.05 (t, J = 7.5 Hz, 2H); 7.92-7.95 (m, 1H); 7.96 (d, J = 8.0 Hz, 1H); 8.38-8.9 (m, 1H); 8.53-8.55 (m, 2H); 11.9 (s, 1H) ppm. ¹³ C NMR (DMSO-d ₆ , 125 MHz): δ 163.1, 162.7, 156.4, 156.1, 155.8, 155.5, 136.7, 131.1, 130.6, 129.3, 128.1, 127.3, 126.3, 124.4, 122.4, 121.0, 119.3, 117.0, 114.7, 112.4, 39.3, 29.5, 19.7, 13.6 ppm.

< Example 1> Check the properties of moisture sensitive compounds

The absorbance and fluorescence spectra of the compounds 1 to 4 synthesized by the above method for moisture were confirmed.

As a result, as shown in Fig. 1a, compound 1 showed an absorption band at about 350 nm and two strong emission bands at 452 and 558 nm. The Stoke shift (Δλ) of the double emission was 102 and 208 nm, respectively, and this large Stoke shift was due to the efficient intramolecular charge transfer of the naphthalimide residue. In addition, the pale yellow solution of Compound 1 exhibited glowing white fluorescence.

Compound 2 showed absorption at 365 nm, emission at 550 nm (Δλ = 180 nm) and 435 nm (Δλ = 70 nm) as shown in FIG. 1B, and a pale yellow solution exhibited a glowing yellow fluorescent color.

On the other hand, in contrast to Compounds 1 and 2 under the same conditions as shown in FIG. 1c, compound 3 exhibited absorption at 350 nm because there was no acetamide group to which fluorine was added, and single emission was confirmed at 477 nm (Δλ = 127 nm), The colorless solution of compound 3 showed light blue fluorescence.

In addition, compound 4 having an amine group instead of an acetamide group to which fluorine was added showed absorption at 435 nm as shown in FIG. 1D, and a single emission was confirmed at 545 nm (Δλ = 110 nm). The yellow solution of compound 4 exhibited a greenish yellow fluorescent color.

From the above results, it was confirmed that the fluoro-added acetamide group of Compounds 1 and 2 plays an important role in the double fluorescence emission and large Stoke shift based on ICT progression.

On the other hand, in order to understand the double emission of Compounds 1 and 2 to water, emission spectra were confirmed at two emission wavelengths.

As a result, excitation spectra of Compound 1 recorded at 452 and 558 nm appeared as one excitation band at 350 nm, respectively, and the result was confirmed to be the same as absorption of Compound 1.

From the above results, it was confirmed that two excited species are formed after excitation of Compound 1 in water.

In the case of Compound 2, the excitation spectrum recorded at 435 nm was identified as a single excitation band at 365 nm, the same as the absorption of Compound 2, but in contrast, the excitation spectrum at 550 nm appeared as an excitation band at 380 nm. The result is a red shift compared to the absorption of compound 2, which may be due to a significant increase in the ICT properties of naphthalimide.

In addition, toluene, dichloromethane (DCM), tetrahydrofuran (THF), CHCl ₃ , acetone, acetonitrile (ACN), N,N-dimethylformamide (N ,N-dimethylformamide; DMF), dimethyl sulfoxide (DMSO), methanol (Methanol; MeOH) and ethanol (ethanol; EtOH) absorption and fluorescence spectra of compounds 1, 2, 3 and 4 in various organic solvents such as Was confirmed.

As a result, the maximum values of the absorption and emission bands of Compounds 1, 2, 3 and 4 were confirmed as shown in Table 1.

Compound 1 showed two absorption bands at 350 and 460 nm with double emission of about 440 and 560 nm in DMF and DMSO, and showed yellow fluorescence.

In addition, for toluene, DCM, THF, CHCl ₃ , acetone, MeOH, and EtOH solutions, an absorption band was observed at about 350 nm, and a single emission band of the highest value was found in the range of 419-447 nm.

The toluene, DCM, THF, CHCl ₃ , acetone and ACN solutions of Compound 1 exhibited dark blue fluorescence, while bright blue fluorescence was observed in MeOH and EtOH solutions.

In the above results, the bright white fluorescence of Compound 1, which appeared in water, did not appear in the experimental organic solvent.

From the above results, it was confirmed that even in ethanol and methanol, which are magnetic solvents of polarity such as water, compound 1 exhibits unique absorption and double release of water, which is distinct from various organic solvents.

Accordingly, Compound 1 can provide a rate change through double release of moisture contained in an organic solvent, and can easily visualize and provide a change in fluorescence color, thereby enabling accurate detection and real-time monitoring.

Solvent One 2 3 4 λ _abs (nm) λ _em (nm) λ _abs (nm) λ _em (nm) λ _abs (nm) λ _em (nm) λ _abs (nm) λ _em (nm) Toluene 350 419 345 414 345 434 405 480 DCM ^a 350 419 345 414 345 439 405 490 THF 350 428 344 414 344 444 420 502 CHCl ₃ 350 423 350 414 352 442 405 495 Acetone 350 427 350 418 358 448 420 508 445 534 ACN ^b 350 427 350 418,537 352 450 415 514 445 461 432 553 DMF ^c 350 435,560 350 424,537 363 457 430 520 460 444 443 537 DMSO ^d 350 444,560 350 424,537 365 463 435 530 460 446 445 537 MeOH 350 447 350 434,550 352 467 430 535 430 542 EtOH 350 444 350 434,550 363 463 430 530 430 550 H ₂ O 350 452,558 365 435,550 350 477 435 545

^a Dichloromethane, ^b Acetonitrile, ^c N,N -Dimethylformamide, ^d Dimethyl sufoxide

In addition, it was confirmed that Compound 2 exhibited two absorption wavelengths at 350 and 440 nm with two emission wavelengths at about 430 and 550 nm in several polar solvents such as ACN, MeOH, EtOH, DMF, and DMSO. Solutions showed various fluorescent colors from light blue to yellow green.

From the above results, it was confirmed that Compound 2 significantly increased the ICT process of the naphthalimide moiety in a polar solvent, and this result was due to the strong electron withdrawal of Compound 2, compared to Compound 1 having a fluoroacetyl group. This is by ICT of the 4-amino naphthalimide residue, which is very sensitive to solvents.

However, in toluene, DCM, THF and CHCl3 solvents, compound 2 showed absorption of about 350 nm and single emission at about 420 nm with deep blue fluorescence.

In contrast to Compounds 1 and 2, Compounds 3 and 4 without a fluorinated acetamide group showed only a simple solvation color change and a single absorption and emission band according to the polarity of the experimental solvent, as shown in Table 1.

Based on the above results, using Compound 1 as a representative moisture-sensitive fluorescent probe that can easily visualize the change in fluorescence color in various non-polar/polar organic solvents and detect water through ratiometric fluorescence, each different ratio of moisture ([Water ] %, v/v) in EtOH, MeOH, and ACN solutions containing the moisture detection effect.

As a result, as shown in FIG. 2, the change in fluorescence of Compound 1 in the EtOH solution containing different proportions of moisture was confirmed. Referring to FIG. 2A, in anhydrous EtOH solution, Compound 1 exhibited a central emission band of 442 nm and gradually decreased, and a new emission band centered on 558 nm appeared, increasing within 50% of [Water], and 526 nm Shows a clear isoelectric point at.

However, when [Water] increased from 50% to 90%, it was confirmed that the emission of 442 nm slightly increased to 452 nm by the maximum wavelength shift, while the emission of 558 nm decreased to the isoabsorption point of 515 nm.

In addition, it is suggested that Compound 1 can easily visualize the change in fluorescence color according to the moisture ratio contained in the EtOH solution, and in fact, a parallel experiment was performed using MeOH and ACN solutions containing various ratios of moisture. It could be confirmed that appears.

The fluorescence intensity ratio versus [Water] (%) value was obtained from the quantitative fluorescence change of the ratio of Compound 1 to moisture in various organic solvents such as ACN, MeOH, and EtOH, as shown in FIG. 3, and the values are ACN, MeOH, and It shows a linear correlation between the ratio of the fluorescence intensity and the water ratio of compound 1 in the EtOH solvent, enabling accurate moisture detection.

In the linear correlation of FIG. 3b, the moisture in ACN was 0-70%, and as shown in FIGS. 3c and 3d, the moisture of MeOH was 0-30% and 50-90%, and in FIGS. 3e and 3f 0-15% and 60-90% moisture were found in EtOH.

From the above results, it was confirmed that Compound 1 can confirm a wide range of moisture content contained in the sample under various analysis conditions.

In addition, the limits of moisture detection using Compound 1 in ACN, MeOH and EtOH solvents were 0.78, 0.26 and 0.024% (v/v), respectively.

From the above results, it was confirmed that Compound 1 can be used as a ratiometric fluorescent moisture sensitive probe that enables not only simple visual analysis but also quantitative analysis of moisture.

In order to confirm the detection mechanism of Compound 1 against moisture, other parts of DMSO-d ₆ and CDCl ₃ were confirmed in the ¹ H NMR spectrum of Compound 1 as shown in FIG. 4B.

As a result, in order to avoid the proton-deuterium exchange in the difluoroacetamide group of compound 1, DMSO-d ₆ was used instead of D2O.

In addition, referring to FIG. 4A, protons Ha and Hb for the difluoroacetamide moiety in the ¹ H NMR spectrum of CDCl ₃ were identified at 8.6 and 6.2 ppm, respectively. However, as the DMSO-d ₆ ratio increased as shown in FIGS. 4b and 4c, Ha and Hb were moved to 11.3 and 6.7 ppm, respectively.

The downfield shift is due to intermolecular hydrogen bonds between the difluoroacetamide proton of compound 1 and the sulfonyl oxygen atom of the DMSO-d ₆ solvent.

Hydrogen bonds played an important role in significantly increasing the electron pull-push effect for the ICT of naphthalenimide, which accompanies a fluorescent color change from blue to yellow.

This effect can be demonstrated by a clear upfield shift of the ¹ H NMR signal from the directional proton of compound 1 in DMSO-d ₆ , and in compound 2, a similar ¹ H NMR spectrum with an increase in the ratio of DMSO-d ₆ in CDCl ₃ Change was confirmed.

< Example 2> Manufacture and check the strip for moisture detection in organic solvents

For simple moisture detection using Compound 1, a filter paper was immersed in a CHCl ₃ solution of Compound 1 (1.0 mM) and dried in an oven for one day to prepare a paper strip impregnated with Compound 1.

Dipping the strip in EtOH, MeOH and ACN solutions containing moisture (0, 5, 10, 20 and 30%, v/v) in various ratios in the same process as in FIG. 6 and using a portable UV lamp at 365 nm The change in fluorescence color was visualized with excitation light.

As a result, it was confirmed that the paper strip impregnated with Compound 1 exhibited dark blue fluorescence as shown in FIG. 5A.

Blue fluorescent color appeared in the paper strip dipped in pure EtOH, MeOH and ACN solvents, and a characteristic fluorescent color change rapidly appeared as the moisture ratio increased, and the color change was observed similarly to FIG. 2.

In addition, it was repeatedly immersed in an EtOH aqueous solution and dried to confirm the reversible fluorescence reaction of the paper strip infiltrated with Compound 1 with respect to moisture.

As a result, as shown in FIG. 5B, when the paper strip was immersed in an EtOH aqueous solution containing 10% moisture, the fluorescence color changed rapidly from blue to white, and the strip returned to blue fluorescence again by simple solvent drying.

As it is confirmed from the above results that the paper strip can be repeatedly used for moisture detection, the paper strip can be used very effectively for moisture detection by quickly and easily visualizing not only reusability but also changes in fluorescence color.

As described above, specific parts of the present invention have been described in detail, and for those of ordinary skill in the art, it is obvious that these specific techniques are only preferred embodiments, and the scope of the present invention is not limited thereby. something to do. Therefore, it will be said that the practical scope of the present invention is defined by the appended claims and their equivalents.

Claims (9)

delete delete A composition for detecting moisture comprising a naphthalimide derivative represented by the following Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]

delete The method according to claim 3, wherein the naphthalimide derivative represented by Formula 1 or a pharmaceutically acceptable salt thereof exhibits double emission wavelength and fluorescence in the presence of moisture in the sample, and the fluorescence intensity varies depending on the moisture content contained. A composition for detecting moisture. A fluorescent probe for water detection comprising a naphthalimide derivative represented by the following Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]

Moisture detection strip comprising a naphthalimide derivative represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]

Reacting by adding a sample to a composition containing the naphthalimide derivative or a pharmaceutically acceptable salt thereof according to claim 3; And
Moisture detection method comprising the step of measuring at least one index selected from the group consisting of absorbance, fluorescence intensity, and optical change of the reactant reacted. The method of claim 8, wherein the sample is an organic solvent.

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