KR102211062B1 - Novel naththalimide-benzothiazole based compounds and chemosensor for selective detection of cyanide ion and tryptophan amino acid comprising the same - Google Patents

Abstract

The present invention relates to a novel naphthalimide-benzocyazole compound and a method for detecting cyanide ions and tryptophan amino acids using the same, wherein the naphthalimide-benzocyazole compound comprises harmful cyanide ions and Since it has improved sensitivity and selectivity for tryptophan amino acids, a chemical sensor using the same can more quickly and simply check colorimetric or fluorescent signals to selectively detect cyanide ions and tryptophan amino acids in aqueous assay samples.

Description

A chemical sensor capable of selective detection of novel naphthalimide-benzocyazole compounds and cyanide ions and tryptophan amino acids containing the same. }

The present invention relates to a novel naphnalimide-benzocyazole compound, a composition for detecting cyanide ions and tryptophan amino acids including the same, and a method for detecting cyanide ions and tryptophan amino acids using the same. In addition, the present invention provides alginate beads for detection of cyanide ions and tryptophan amino acids containing the naphthalimide-benzocyazole compound, cyanide ions and tryptophan using alginate beads for detection of cyanide ions and tryptophan amino acids using the same It relates to a method for detecting amino acids. In addition, the present invention includes the naphthalimide-benzocyazole compound, a composition for detection of cyanide ions and tryptophan amino acids, or alginate beads for detection of cyanide ions and tryptophan amino acids, detection of cyanide ions and tryptophan amino acids It relates to a chemical sensor for use.

Anions play an important role in many fields, such as chemical, biological, environmental or industrial processes. As a more useful anion, cyanine is widely used in many fields such as gold mining and extraction, electroplating, synthetic fiber, metallurgy, resin industry and herbicide. Also, poets have been used as chemical agents (chemical weapons) and even as substances for terrorism. In addition, cyanide is highly toxic, very harmful to the human body, and is very lethal to humans when concentrated to 0.5 to 3.5 mg/kg of body weight. When cyanide is absorbed into the human body through the gastrointestinal tract, skin or lungs, it binds to the heme unit in the active site of cytochrome c and inhibits cellular respiration of living organisms. According to the World Health Organization (WHO), the maximum allowable for cyanide in drinking water is only 1.9 μM. Therefore, the cyanide ion (CN ^-) The selection and detection with high sensitivity is important also for preventing as well as environmental protection for the counter-terrorism, food analysis.

In order to detect cyanide, a number of analysis techniques such as voltammetry, titration, chromatography, potential difference and electrochemical methods have been proposed. However, these detection methods are complex and take a lot of time for real-time and field detection, and require expensive equipment and have limitations in detection. Thus, a more sensitive, selective, low-cost, and simple detection method is urgently required. On the other hand, the optical method using a low molecular weight chemical probe is widely used because it not only enables visual detection with the naked eye, but also enables simple, high sensitivity and low cost detection. Approaches to detecting cyanides such as using a probe include nucleophilic addition, hydrogen bonding interactions, cyanide complex formation/addition, supramolecular self-assembly, electron-deficient alkenes, and many others. Among them, the most widely studied reaction path for a cyanide chemodosimeter is to add a nucleophilic cyanide to electron-deficient carbon-carbon double bonds, carbon-heteroatoms and heterocyclic derivatives. However, it has low solubility in aqueous system, long reaction time, and low selectivity compared to other competing anions, so there are limitations in terms of use.

On the other hand, amino acids are low-molecular substances having side chains of various functional groups and form a structural unit of a protein. The sequence of amino acids in proteins varies during biochemical processes. Histidine is an essential amino acid that is involved in the growth and biosynthesis of animals and food development. Tryptophan deficiency can cause liver damage, muscle loss, growth retardation, loss of vision, hair bleaching, fat loss, dry mouth, swelling, and coma. Although there are many technologies for recognizing amino acids, a simple and portable real-time detection method such as a fluorescent and/or colorimetric chemical sensor capable of operating in semi-aqueous or water systems is still required.

Thus, with the above in mind, the present invention has completed a colorimetric and fluorescent sensor through a naphthalimide-benzocyazole compound and a new reaction base thereof.

Republic of Korea Patent Publication No. 2017-0090408

Y. Fu, H. Nie, R. Zhang, F. Xin, Y. Tian, J. Jing and X. Zhang, RSC Adv., 2018, 8, 1826

It is an object of the present invention to provide a novel naphthalimide-benzocyazole compound.

It is also an object of the present invention to provide a composition for detecting cyanide ions and tryptophan amino acids including the naphthalimide-benzocyazole compound.

In addition, an object of the present invention is to provide a method for detecting cyanide ions and tryptophan amino acids using the naphthalimide-benzocyazole compound or a composition for detecting cyanide ions and tryptophan amino acids.

It is also an object of the present invention to provide alginate beads for detection of the naphthalimide-benzocyazole compound or cyanide ion and tryptophan amino acid.

In addition, an object of the present invention is to provide a method for detecting cyanide ions and tryptophan amino acids using alginate beads for detection of cyanide ions and tryptophan amino acids.

Another object of the present invention is a composition for detection of the naphthalimide-benzocyazole compound, cyanide ions and tryptophan amino acids, or cyanide ions and tryptophan amino acids, including alginate beads for detection of cyanide ions and tryptophan amino acids. It is to provide a chemical sensor for detection of

For the purposes described above, a naphthalimide-benzocyazole compound of Formula 1 is provided.

[Formula 1]

(In Formula 1,

L is C6-C20 arylene;

R ₁ and R ₂ are each independently C1-C20 alkyl, C3-C20 cycloalkyl, haloC1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C6-C20 aryl or C7-C40 arylalkyl;

R ₃ is independently C1-C20 alkyl, C1-C20 alkoxy and halogen;

X is a monovalent anion,

n is an integer from 0 to 4,

The aryl and arylalkyl of R ₁ and R ₂ may be further substituted with one or more substituted or unsubstituted C1-C10 alkyl.)

In the compound of Formula 1 according to an embodiment of the present invention, L is C6-C20 arylene; R ₁ is C7-C20 arylalkyl; R ₂ is C1-C20 alkyl; R ₃ is C1-C10 alkyl, C1-C10 alkoxy and halogen; X is a halogen monovalent anion;

n may be an integer of 0 to 1.

In the compound of Formula 1 according to an embodiment of the present invention, L is selected from phenylene, naphthalene, biphenylene, or anthracenylene; R ₁ is C7-C10 arylalkyl; R ₂ is C1-C6 alkyl; n may be an integer of 0.

The compound of Formula 1 according to an embodiment of the present invention may be represented by the following Formula 2.

[Formula 2]

The compound of Formula 1 according to an embodiment of the present invention may be for detection of cyanide ions and tryptophan amino acids.

In addition, the present invention provides a composition for detecting cyanide ions and tryptophan amino acids comprising the naphthalimide-benzocyazole compound of Formula 1 above.

In addition, the present invention comprises the steps of contacting the composition for detection of the naphthalimide-benzocyazole compound of Formula 1 or the cyanide ion and the tryptophan amino acid with an assay sample; And it provides a method for detecting a cyanide ion and tryptophan amino acid comprising; and confirming the optical change of the compound or the composition.

In the method for detecting cyanide ions and tryptophan amino acids according to an embodiment of the present invention, the optical change may be confirmed through at least one of a color change, absorbance, and fluorescence intensity combination of the compound.

In the method for detecting cyanide ions and tryptophan amino acids according to an embodiment of the present invention, the analysis sample may be an aqueous analysis sample.

In addition, the present invention provides alginate beads comprising the naphthalimide-benzocyazole compound of Formula 1 above.

Alginate beads according to an embodiment of the present invention may be alginate beads for detection of cyanide ions and tryptophan amino acids remaining in the aqueous phase.

In addition, the present invention comprises the steps of preparing alginate beads for detection of cyanide ions and tryptophan amino acids including the naphthalimide-benzocyazole compound of Formula 1; Contacting the assay sample with the alginate beads; It provides a method for detecting cyanide ions and tryptamine amino acids comprising; and confirming optical changes.

In the method for detecting cyanide ions and tryptamine amino acids according to an embodiment of the present invention, the optical change may be confirmed through at least one of a change in color, absorbance, and fluorescence intensity of the compound.

In the method for detecting cyanide ions and tryptamine amino acids according to an embodiment of the present invention, the analysis sample may be an aqueous analysis sample.

In addition, the present invention provides a chemical sensor for detection of cyanide ions and tryptamine amino acids including the naphthalimide-benzocyazole compound of Formula 1 above.

Naphthalimide according to the invention azole between benzoin compounds as a novel compound, an aqueous medium within a cyanide ion (CN ^-), and tryptophan not only has a high selectivity with respect to amino acids, and trace amounts of cyanide ion (CN ^-) and tryptophan can be despite the amino acid concentration and determine the colorimetric or fluorescent change, visual, or a cyanide ion (CN ^-) as fluorescence can be easily detected and the presence or absence of the tryptophan amino acid.

In addition, the naphthalimide-benzocyazole compound according to the present invention has excellent solubility in water, is environmentally friendly, and is advantageous for environmental and bio pre-sale applications.

In addition, the naphthalimide-benzocyazole compound according to the present invention can be applied to beads, and alginate beads for detection including the compound can be prepared. And the prepared alginate beads, as well as to facilitate the storage and movement easy to carry, cyanide ion (CN ^-) and tryptophan amino acid cyanide ion (CN ^-) always in different places because it indicates high sensitivity and high selectivity for the And tryptophan amino acids can be selectively detected and detected.

In addition, when the chemical sensor containing the naphthalimide-benzocyazole compound according to the present invention is used, the presence or absence of cyanide ions and tryptophan amino acids can be visually confirmed, so that colorimetric or fluorescent colorimetric or fluorescent light is more quickly and conveniently By confirming the signal, cyanide ions and tryptophan amino acids can be detected in an aqueous medium.

1 is an absorption spectrum showing selective detection of cyanide ions (CN-) in aqueous solution of receptor NPT (50 μM) for various anions (inside: results of observing color change with the naked eye).
2 is solution in cyanide ion (CN ^-) receptor NPT (50μM) for a variety of anionic fluorescent spectrum showing the selective detection on the (inner: As a result of observing the fluorescence variation by irradiating a UV lamp (λex = 365nm)) to be.
3 is a view showing the change in UV-vis absorption spectrum of receptor NPT (50 μM) for various concentrations (0-1.6 eqv.) of cyanide ions (CN ⁻ ) (inside: at 394 nm according to cyanide ion titration It is a graph showing the change in absorbance intensity).
Figure 4 various concentrations of cyanide ion (CN ^-) receptor view showing the fluorescence spectrum change of the NPT (50μM) (inside of the: the fluorescence intensity at 520nm changed in accordance with the cyanide ion titration (0-1.6 eqv.) Is a graph).
5 is a graph showing a Job's plot obtained from a fluorescence spectrum emitted at λ _max 520 nm with respect to the mole fraction of cyanide ions (CN ⁻ ).
6 is an absorption spectrum showing selective detection of tryptophan in an aqueous solution of receptor NPT (50 μM) for various amino acids (inside: is the result of observing color change with the naked eye, 1: NPT, 2: _L- tryptophan, _{3: L -glycine, 4: L} -alanine, 5: L -cysteine, 6: L -glutamine, 7: L -histidine, 8: L -leucine, 9: L -lysine, 10: L -methionine, 11: _L -proline, 12: _L -serine, 13: _L -threo- nine, 14: _L -tyrosine, 15: _L -asparagine).
7 is a fluorescence spectrum showing selective detection of tryptophan in an aqueous solution of receptor NPT (50 μM) for various amino acids (inside: UV lamp (λex = 365 nm) was irradiated to observe changes in fluorescence, 1: _{NPT, 2: L -tryptophan, 3} : L -glycine, 4: L -alanine, 5: L -cysteine, 6: L -glutamine, 7: L -histidine, 8: L -leucine, 9: L -lysine, 10: _L -methionine, 11: _L -proline, 12: _L -serine, 13: _L -threo- nine, 14: _L -tyrosine, 15: _L -asparagine).
8 is a view showing the change in the UV-vis absorption spectrum of receptor NPT (50 μM) for tryptophan at various concentrations (0-1.1 eqv.) (inside: absorbance intensity at 394 nm according to tryptophan titration It is a graph showing the change).
9 is a view showing the change in the fluorescence spectrum of the receptor NPT (50 μM) for tryptophan at various concentrations (0-1.1 eqv.) (inside: change in fluorescence intensity at 520 nm and 444 nm according to tryptophan titration Is a graph).
Figure 10 is a fifth embodiment of the aqueous ethanol _{(EtOH: H 2 O = 1} : 1, v / v) within the receptor NPT with cyanide ion (CN ^-), and a MALDI mass spectrometric analysis the coupling NPT at which the tryptophan amino acid present -TOF mass spectrum.
11 is a graph (fluorescence) showing the selectivity of tryptophan of receptor NPT among various natural amino acids.
12 is a photograph showing a color change of NPT beads after immersing NPT beads in cyanide (CN ^- )/tryptophan aqueous solution.

Hereinafter, the present invention will be described in more detail. If there are no other definitions in the technical and scientific terms used at this time, they have the meanings commonly understood by those of ordinary skill in the technical field to which this invention belongs, and the following description will unnecessarily obscure the subject matter of the present invention. Description of possible known functions and configurations will be omitted.

As used herein, the term "alkyl" refers to a functional group derived from a linear or branched hydrocarbon. In addition, the substituents including alkyl and alkyl according to the present invention are preferentially short-chain having 1 to 7 carbon atoms, and may be preferably selected from methyl, ethyl, propyl, and butyl, but are not limited thereto.

In the present invention, the term "aryl" or "arylene" refers to a monocyclic or heterocyclic aromatic. For example, aryl may be a phenyl group, a biphenyl group, a fluorene group, or a spirofluorene group.

In addition, the term "alkenyl" in the present specification means a functional group derived from a straight chain or branched hydrocarbon containing one or more double bonds, and "alkynyl" is a straight chain or branched form containing one or more triple bonds. It means a functional group derived from a hydrocarbon.

The present invention relates to a novel naphthalimide-benzocyazole compound and a chemical sensor for the detection of cyanide ions and tryptophan amino acids containing the same, and present in an aqueous solution using the naphthalimide-benzocyazole compound. It is intended to highly selectively detect harmful cyanide ions and tryptophan amino acids.

Hereinafter, the nattalimide-benzocyazole compound of the present invention and its application will be described in detail.

The novel naphthalimide-benzocyazole compound according to the present invention may be a compound represented by the following formula (1).

[Formula 1]

(In Formula 1,

L is C6-C20 arylene;

R ₁ and R ₂ are each independently C1-C20 alkyl, C3-C20 cycloalkyl, haloC1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C6-C20 aryl or C7-C40 arylalkyl;

R ₃ is independently C1-C20 alkyl, C1-C20 alkoxy and halogen;

X is a monovalent anion,

n is an integer from 0 to 4,

The aryl and arylalkyl of R ₁ and R ₂ may be further substituted with one or more substituted or unsubstituted C1-C10 alkyl.)

More preferably, the naphthalimide-benzocyazole compound of Formula 1 may be a naphthalimide-benzocyazole compound represented by the following Formula 2, but is not limited thereto.

[Formula 2]

The naphthalimide-benzocyazole compound of Formula 1 is a novel mixture having high sensitivity and high selectivity for cyanide ions and tryptophan amino acids.When contacted with cyanide ions and tryptophan amino acids, a nucleophilic addition reaction results in the corresponding ions. It is a novel chromosome that can be selectively detected.

In the combination of cyanide ions and tryptophan amino acids, a naph of a donor-acceptor structure in which a cyanide ion and a tryptophan amino acid, which are electron-rich species in the analysis sample of the naphthalimide-benzocyazole compound of Formula 1, are linked by a double bond. Deimide-benzocyazole and nucleophilic addition reaction may change the internal electron transfer (ICT) of the benzocyazole portion, resulting in optical color change.

The naphthalimide-benzocyazole compound of Formula 1 may be prepared by reacting a naphthalimide derivative (2) with a benzocyazole compound (I), as shown in Scheme 1 below. The naphthalimide derivative (2) may be prepared from 1,8-naphtahlic anhydride in two steps, and the benzocyazole compound (I) may be prepared in a salt form by N-alkylation. Further details are described in Example 1 below. However, it goes without saying that the method for preparing the naphthalimide-benzocyazole compound of the present invention is not limited to the following Scheme 1, and can be synthesized in various ways using a known organic reaction.

[Scheme 1]

(In Reaction Scheme 1, L1, R1 to R3, X, and n are the same as defined in Formula 1.)

The present invention provides a composition for detecting cyanide ions and tryptophan amino acids comprising the nattalimide-benzocyazole compound of Formula 1 above.

According to an embodiment, the composition may be a composition comprising the naphthalimide-benzocyazole compound of Formula 1 and a solvent.

The solvent may be used without limitation as long as it is a solvent capable of dissolving the compound radish, and for example, methanol (MeOH), ethanol (EtOH), isopropanol, n-propanol, n-butanol, tert-butanol, benzene, Toluene, xylene, diethyl ether, diisopropyl ether, tetrahydrofuran (THF), ethylene glycol monomethyl ether, ethylene glycol methyl ether, acetone, trichloroethylene, 1,2-dichloroethane, tetrachloromethane, chloroform , Dichloromethane (DCM), acetamide, dimethylacetamide, N-methylpyrrolidone (NMP), dimethylformamide (DMf0, dimethyl sulfoxide (DMSO), water (H ₂ O), ethyl acetate (EA), etc.) I can.

Preferably, dichloromethane (DCM), chloroform, dimethylformamide (E), dimethyl sulfoxide (DMSO), ethyl acetate, water (H ₂ O), acetonitrile, methanol (MeOH), ethanol (EtOH) and It may be one or more solvents selected from tetrahydrofuran (THF). More preferably, it may be water (H ₂ O). When water is used as the solvent, toxicity due to an organic solvent can be reduced, and it can be advantageous for applications in bio and environmental fields such as cells.

The present invention provides a method for detecting cyanide ions and tryptophan amino acids using the naphthalimide-benzocyazole compound of Formula 1 or a composition for detecting cyanide ions and tryptophan amino acids.

More specifically, the detection method comprises the steps of contacting the composition for detection of the naphthalimide-benzocyazole compound or cyanide ion and tryptophan amino acid of 1 in the chemistry with an assay sample; And confirming the optical change of the compound or the composition.

The analysis sample may be an aqueous analysis sample, and when cyanide and tryptophan amino acids are present in the analysis sample by contacting the compound or the composition with the analysis sample, the compound and cyanide ions and tryptophan amino acids are condensed. It is possible to form cyanide-NPT complexes and tryptophan-NPT complexes.

The optical color change is an optical change that occurs when a cyanide-NPT complex and a tryptophan-NPT complex are formed in the compound or composition, and passes through at least one of a change in color, a change in absorbance, and a change in emission intensity of the compound or the composition. I can confirm. More specifically, by observing the color change of the compound or the composition with the naked eye to confirm the presence of cyanide or by observing the change in absorption characteristics and fluorescence characteristics using a UV-Vis spectrometer, etc., the cyanide ion and tryptophan amino acid Qualitative and quantitative analysis can be performed.

For example, when cyanide ions and tryptophan amino acids are present in the assay sample, the color of the compound or the composition changes from light yellow to pink, so the presence of cyanide ions and tryptophan amino acids can be visually detected, and In the absorbance measurement of the UV-Vis spectrometer, the intensity of the absorbance in the region of 394 nm decreases. In addition, it can be seen that both of them emit blue fluorescence by excitation light, and the luminescence intensity in the 520 nm region is reduced. In particular, in the case of tryptophan amino acid, it can be seen that a luminescence peak is generated in the 444 nm region with a decrease in the 520 nm region. In addition, changes in the absorbance and emission peaks of the compounds according to the present invention according to the concentration of cyanide ions and tryptophan amino acids can be converted into data, and used for quantitative and qualitative analysis of cyanide ions and tryptophan amino acids.

The present invention provides alginate beads for detection of cyanide ions and tryptophan amino acids comprising the naphthalimide-benzocyazole compound of Formula 1 above.

Alginate beads for detection or removal of cyanide ions and tryptophan amino acids may be prepared by using the naphthalimide-benzocyazole compound of Formula 1 and a composition thereof.

The present invention provides a method for detecting cyanide ions and tryptophan amino acids using alginate beads for detection or removal of cyanide ions and tryptophan amino acids including the naphthalimide-benzocyazole compound of Formula 1 above.

More specifically, the detection method comprises the steps of preparing alginate beads for detection or removal of cyanide ions and tryptamine amino acids including the naphthalimide-benzocyazole compound of Formula 1; Contacting the assay sample with the alginate beads; And confirming the optical change.

In one example, alginate beads for detection or removal including the naphthalimide-benzocyazole compound of Formula 1 are light yellow and non-fluorescent. Upon contact with an assay sample containing cyanide ions and tryptophan amino acids, the instantaneous detection of cyanide ions and tryptophan amino acids may exhibit a distinct color change, change in absorbance or fluorescence intensity. Therefore, the prepared detection reagent is easy to carry, and exhibits high sensitivity and high selectivity for cyanide ions and tryptophan amino acids, so that cyanide ions and tryptophan amino acids can be selectively detected and detected regardless of location and time.

The analysis sample may be an aqueous analysis sample, and when cyanide and tryptophan amino acids are present in the analysis sample as the analysis sample is brought into contact with the detection reagent, the formula 1 is contained in the alginate beads of the detection reagent. The naphthalimide-benzocyazole compound may react to form a cyanide-NPT complex and a tryptophan-NPT complex.

The optical change is an optical change that occurs when the cyanide-NPT complex and the tryptophan-NPT complex are formed in the detection reagent, through at least one of the change in color, absorbance, and fluorescence intensity of the alginate beads of the detection reagent. I can confirm. More specifically, the color change appearing on the alginate beads of the detection reagent is visually observed to confirm the presence of cyanide ions and tryptophan amino acids, or by observing changes in absorbance and fluorescence using a UV-Vis spectrometer, etc. And qualitative and quantitative analysis of tryptophan amino acids.

The present invention is a cyanide ion comprising a naphthalimide-benzocyazole compound of Formula 1, a composition for detection of the cyanide and tryptophan amino acids, or alginate beads for detection or removal of the cyanide ion and tryptophan amino acid And it provides a chemical sensor for detection of tryptophan amino acid.

In one example, the chemical sensor may be a chemical sensor that rapidly and accurately detects cyanide ions known as harmful components in the field of environment, food, medicine, and bio, and tryptophan amino acid, one of essential amino acids, with high selectivity and high sensitivity.

The naphthalimide-benzocyzazole compound and the composition for detecting cyanide ions and tryptophan amino acids containing the same may be applied as a powder, gel, emulsion, or liquid, or as a molded article, or as an analysis chip, an electrolysis furnace, a fiber, It can be coated or impregnated on a support such as pulp, polymer film, glass substrate, etc. and applied to the chemical sensor.

The chemical sensor detects and specifies the color change of the naphthalimide-benzocyazole compound, the composition, or the detection reagent containing the alginate with the naked eye, or electrically, or optically, and performs qualitative and/or quantitative analysis. I can.

The chemical sensor may be in the form of a kit for detecting cyanide ions and tryptophan amino acids, and the kit may further include an absorbance and fluorescence intensity meter, and the meter may be integrated with the kit or configured separately.

Hereinafter, examples of the present invention will be described. However, the following examples are only preferred examples of the present invention, and the present invention is not limited to the following examples.

All reagents and solvents were of analytical grade and were used without further purification. Structural analysis of the product was ¹ H NMR and ¹³ C NMR (Bruker Avance 300 MHz and 600 MHz instruments ( ¹ H NMR 300 and 600 MHz, ¹³ C NMR 100 and 200 MHz), ESI-mass (4000 QTRAP Mass Spectrometer), UV- It was performed using vis spectrometer (Agilent 8453 spectrophotometer), Fluorometer (RF-5301PC spectro-fluorophotometer), DFT calculations (Gaussian 09 program at the B3LYP level using 6-31G** basis set)).

[Example 1]

6-(2-styryl-N-methylbenzo[d]cyazole)-2-phenylmethylbenzo[de]isoquinoline-1,3-dione iodine salt (6-(2-styryl-N-methylbenzo[d ]thiazole)-2-phenylmethylbenzo[de]isoquinoline-1,3-dione iodine salt (hereinafter referred to as'receptor NPT '))

Step 1: intermediate One Preparation of (6-bromo-2-phenylmethylbenzo[de]isoquinoline-1,3-dione)

Ethanol (EtOH) was added to a mixture of 4-bromo-1,8-naphtahlic anhydride (1.11 g, 4.0 mmol) and benzylamine (0.22 g, 4 mmol). Then, the mixture was stirred and refluxed for 8 hours. The reaction mixture was cooled to room temperature, and the resulting precipitate was filtered and washed several times with ethanol to obtain a white solid intermediate 1 (1.07g, 73%).

¹ H NMR (CDCl ₃ , 300 MHz), S (ppm): 5.29 (2H, s), 7.14-7.26 (3H, m), 7.46 (2H, d, J = 7.2 Hz), 7.75 (1H, t, J = 7.8 Hz), 7.94 (1H, d, J = 7.8 Hz), 8.34 (1H, d, J = 7.8 Hz), 8.47 (1H, d, J = 8.4 Hz), 8.58 (1H, d, J = 7.2 Hz).

¹³ C NMR (CDCl ₃ , 150 MHz), S (ppm): 43.6, 122.1, 122.9, 127.5, 128.0, 128.4, 128.9, 129.0, 130.3, 130.5, 131.0, 131.3, 132.2, 133.3, 137.0, 163.5.

Step 2: intermediate 2 Synthesis of (6-benzaldehyde-2-phenylmethylbenzo[de]isoquinoline-1,3-dione)

In a mixture of Intermediate 1 (0.73g, 2mmol) and 4-formylphenylboronic acid (0.3g, 2mmol), tetrahydrofuran (THF) and 2M Na ₂ CO ₃ aqueous solution in 3:1 It was mixed and added. After Pd(PPh3)4 (23mg, 0.02mmol) was added to the mixed solution, the reaction mixture was stirred and refluxed overnight at 80°C under a nitrogen atmosphere. After cooling to room temperature, the reaction product was extracted with dichloromethane (DCM), dried over anhydrous Na ₂ SO _4, and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography (silica gel, hexane (Hexane):dichloromethane (DCM) = 3:2, v/v) to obtain a white solid intermediate 2 (0.65g, 83%).

¹ H NMR (CDCl ₃ , 600 MHz), δ (ppm): 5.35 (2H, s), 7.16-7.19 (1H, m), 7.23-7.25 (2H, m), 7.49 (2H, d, J =7.2 Hz), 7.61 (2H, d, J =7.8 Hz), 7.64-7.67 (2H, m), 8.00 (2H, d, J =8.4 Hz), 8.10 (1H, dd, J =1.2, 8.4 Hz), 8.59-8.62 (2H, m), 10.08 (1H, s).

¹³ C NMR (CDCl ₃ , 150 MHz), δ (ppm): 43.6, 122.4, 122.9, 127.3 127.5, 127.8, 128.4, 128.6, 128.9, 129.7, 129.9, 130.6, 130.9, 131.6, 132.0, 136.1, 137.1, 144.8 , 145.2, 163.9, 164.1, 191.6.

Step 3: Receptor NPT Manufacture of

In the intermediate 2 (0.39g, 1mmol) and benzocyazole iodide ( I ) (0.29g, 1mmol) prepared in step 2 , ethanol (EtOH) (20ml) was added, and a catalytic amount of pyridine (2-3 drops) was added to the mixture. After addition, the mixture was stirred and refluxed for 12 hours. After the reaction was cooled to room temperature, the solid was filtered and washed several times with alcohol to obtain a brown solid receptor NPT (0.38 g, 57%) without further purification.

¹ H NMR (DMSO-d ₆ , 600 MHz), δ (ppm): 4.43 (3H, s), 5.26 (2H, s), 7.24 (1H, t, J =7.2 Hz), 7.31 (2H, t, J =7.2 Hz), 7.38 (2H, d, J =7.2 Hz), 7.78 (2H, d, J =7.8 Hz), 7.82 (1H, t, J =7.2 Hz), 7.87-7.92 (3H, m) , 8.20 (1H, d, J =15.6 Hz), 8.27 (1H, d, J =8.4 Hz), 8.30 (3H, d, J =7.8 Hz), 8.36 (1H, d, J =16.2 Hz), 8.48 (1H, d, J =8.4 Hz), 8.57 (2H, triplet, J =8.4 Hz);

¹³ C NMR (DMSO-d ₆ , 150 MHz), δ(ppm): 36.6, 42.9, 114.8, 116.9, 121.4, 122.2, 124.2, 127.0, 127.4, 127.7, 127.8, 127.9, 128.1, 128.3, 128.5, 129.0, 129.4, 129.9, 130.5, 130.6, 131.0, 132.0, 134.1, 137.1, 141.5, 141.9, 144.9, 147.4, 163.1, 163.3, 171.6.

ESI-MS m/z: Calcd. for C35H25N2O2S (M) ⁺ : 537.2, found: 537.5.

[Example 2] Confirmation of selectivity for cyanide ions

^{Cl -, F -, Br -} , CN -, ClO 4 -, HS -, I -, N 3 -, NO 3 -, OH -, H 2 PO 4 - and SCN - carried out on a variety of anions such as for example 1 In order to examine the colorimetric or fluorescence selectivity of the receptor NPT, an experiment was performed as follows.

EtOH: H ₂ O: ethanol aqueous solution (1 1, v / v) Cl -, F -, Br -, CN -, ClO 4 -, HS -, I -, N 3 -, NO 3 -, OH - , H ₂ PO ₄ ^- and SCN ^- into a separate vial at a concentration of 50 μM, respectively, and 1.0 eq of the receptor NPT of Example 1 into the vial containing the various anions, and then the solution in each vial The change in color was confirmed by irradiation with the naked eye and UV lamp (365 nm).

1 is a UV-vis absorption wavelength different from that of the case of adding a CN- ions in the absorption spectra, as shown in (inner), cyanide ion (CN ^-) as a pink color to the naked eye at only when there are light yellow Change was observed, and the color of the solution did not change when other anions were present.

2 is different from the emission wavelength of the fluorescent spectra in the case of adding a CN-, was irradiated a, UV lamp (365nm) as shown in (inside), cyanide ion (CN ^-), only in the case where the present light green Fluorescence changed to blue, and the color of the solution did not change when other anions were present.

That is, it was found that the receptor NPT (Example 1) of the present invention reacts very selectively to cyanide ions (CN ⁻ ).

[Example 3] UV-vis absorption and fluorescence spectrum observation according to the concentration of cyanide ions

In order to observe the UV-vis absorption and fluorescence spectrum of the receptor NPT according to various concentrations of cyanide ions (CN-), experiments were performed as follows.

_{EtOH: H 2 O (1:} 1, v / v) of the receptor NPT ethanol aqueous solution fed to the 50μM concentration and receptor NPT than cyanide ion (CN ^-) a cyanide ion and added to 0 to 2.0 equivalents (CN ^- ) The UV-vis absorption spectra and fluorescence spectra of the receptor NPT in the solution according to the concentration were measured. The results are shown in Figs. 3 and 4, respectively.

3 is a UV-vis absorption spectra, it was confirmed that the intensity of the absorption band decreased at 394 nm as the concentration of cyanide ions (CN ⁻ ) increased. 4 is a fluorescent spectra, it was confirmed that the intensity of the emission peak decreased at 520 nm as the concentration of cyanide ion (CN ⁻ ) increased.

As shown in the (inside) of FIGS. 3 and 4, when the concentration of cyanide ion (CN-) is higher than 1.2 equivalents, no spectroscopic change is observed, and cyanide ion (CN ^-) had a concentration of 0 to 1 equivalent of one when the intensity change in absorbance and fluorescence in accordance with the concentration of the confirmed that comprises a straight line.

In addition, as shown in FIG. 5, when a stoichiometric analysis of the binding form between the cyanide ion and the receptor NPT decreases the luminescence intensity of the receptor NPT as the concentration of the cyanide ion (CN ⁻ ) increases, the cyanide ion (CN ^-) after one equivalent has been added it was confirmed that the fluorescence intensity is maintained constant.

That is, as can be seen from the above results and, that is, Fig. 10 (right), it was found that the receptor NPT is 1: 1 binding to the cyanide ion.

[Example 4] Confirmation of selectivity for tryptophan amino acid

tryptophan (Trp), glycine (Gly), alanine (Ala), cysteine (Cys), glutamine (Gln), histidine (Hys), leucine (Leu), lysine (Lys), methionine (Met), proline (Pro), In order to examine the colorimetric or fluorescence selectivity of the receptor NPT of Example 1 for various amino acids such as serine (Ser), threonine (Thr), tyrosine (Tyr) and asparagine (Asp), an experiment was performed as follows.

EtOH: H ₂ O (1: 1, v/v) in an aqueous ethanol solution of tryptophan (Trp), glycine (Gly), alanine (Ala), cysteine (Cys), glutamine (Gln), histidine (Hys), leucine ( Leu), lysine (Lys), methionine (Met), proline (Pro), serine (Ser), threonine (Thr), tyrosine (Tyr) and asparagine (Asp) in separate vials at a concentration of 50 μM each. After the addition, the receptor NPT of Example 1 was added at 1.0 eq to the vial containing the various amino acids, and then the color change of the solution in each vial was visually checked and a UV lamp (365 nm) was irradiated.

6 is a UV-vis absorption spectra with different absorption wavelengths when tryptophan is added, and as shown in (inside), only when tryptophan is present, the color change from light yellow to pink visually It was observed, and the color of the solution did not change when other amino acids were present.

FIG. 7 shows a different emission wavelength when tryptophan is added as a fluorescent spectra, and as shown in (inside), only when tryptophan is present when a UV lamp (365 nm) is present is light green to blue. Fluorescence changed to color, and the color of the solution did not change when other amino acids were present.

That is, it was found that the receptor NPT of the present invention (Example 1) reacts very selectively to tryptophan.

[Example 5] UV-vis absorption and fluorescence spectrum observation depending on the concentration of tryptophan

In order to observe the UV-vis absorption and fluorescence spectra of receptor NPT according to various concentrations of tryptophan, experiments were performed as follows.

EtOH: H ₂ O (1: 1, v/v) in ethanol aqueous solution of receptor NPT at a concentration of 50 μM, and tryptophan compared to receptor NPT at 0 to 1.1 equivalents, depending on the concentration of tryptophan The UV-vis absorption spectra and fluorescence spectra changes of the inner receptor NPT were measured. The results are shown in Figs. 8 and 9, respectively.

8 is a UV-vis absorption spectra, and it was confirmed that as the concentration of tryptophan increased, the intensity of the absorption band decreased at 394 nm and blue shifted to 355 nm. 9 is a fluorescence spectra, it was confirmed that the intensity of the emission peak decreased at 520 nm and a new emission peak was generated at 444 nm and increased as the concentration of tryptophan increased.

As shown in the (inside) of FIGS. 8 and 9, when the concentration of tryptophan is 0 to 1 equivalent, the change in absorbance and fluorescence intensity according to the concentration change is It was confirmed that it was made in a straight line.

That is, as can be seen from the above results and Fig. 10 (right), it was found that the receptor NPT binds tryptophan and 1:1.

In addition, it was observed that the change in fluorescence intensity at 444 nm was also increased in proportion to the concentration of tryptophan, and as a result of calculation using the 3σ method, it was confirmed that the detection limit of tryptophan was 15.2 nM.

[Example 6] Cyanide ion of receptor NPT (CN ^- ) And the detection mechanism for tryptophan

In order to investigate the detection mechanism of the receptor NPT for tryptophan amino acids under cyanide, the mass change of the products obtained from the reaction between the receptor NPT and cyanide ion light tryptophan was confirmed (FIG. 11).

As it is shown in Figure 10, the mass spectrum of the acceptor NPT is 537.5 m / z and receptor NPT with cyanide ion is the reaction product ^- showed a of 586.5 m / z [NPT-CN + Na], receptor NPT and The product reacted with tryptophan showed 763.6 m/z of [NPT-tryptophan + Na]. These results indicate that the receptor NPT binds with cyanide ions or tryptophan, respectively, to form a complex of NPT-CN or NPT-tryptophan, respectively.

That is, the binding property between the receptor NPT and cyanide ion or tryptophan was confirmed by a change in mass, and when the receptor NPT and tryptophan are combined through the fluorescence spectrum result of tryptophan (Fig. 7), the emission peak It is predicted that the conjugation of the receptor NPT is affected when tryptophan attacks the receptor NPT molecule, as is blue shifted. These results indicate that the free electron pair of the amine of tryptophan attacked the carbon of the imine group of the receptor NPT as a nucleophile, resulting in a nucleophilic addition reaction, and the imine was changed to an amine, thereby interfering with the conjugation of the receptor NPT. . In the following, the mechanism of binding of the receptor NPT and tryptophan of the present invention is shown.

[Example 6] Selective sensing properties of tryptophan of receptor NPT

A binding competition experiment was performed to check whether tryptophan was selectively detected among various amino acids, and an aqueous ethanol solution (EtOH: H ₂ O = 1) of an equivalent amount of receptor NPT (50 μm) prepared in Example 1 above: 1, v/v) was observed for luminescence characteristics according to the addition of 1 equivalent of amino acids and 1 equivalent of tryptophan.

As shown in FIG. 11, when tryptophan was added to the mixture of receptor NPT and amino acids, a new luminescence peak of 444 nm was clearly expressed, and even if other amino acids were present, it was expressed according to tryptophan. It was confirmed that there was no significant change in luminescence intensity. It can be seen that the receptor NPT's ability to detect tryptophan is not disturbed by other amino acids, and it has been shown that receptor NPT has higher selective detection properties for tryptophan than other competing amino acids.

[Example 7] Preparation of alginate beads and cyanide ions (CN ^- ) And tryptophan amino acid detection

A mixture of receptor NPT (2%) and sodium alginate (1 g) was dispersed in distilled water (10 ml) and then a solution heated and stirred for 2 hours was slowly added dropwise to a saturated aqueous CaCl ₂ solution to obtain beads formed to prepare an NPT probe. I did.

As shown in the image shown in FIG. 12, when the beads are immersed in an alcoholic aqueous solution (EtOH: H ₂ O = 1: 1, v/v) containing cyanide ions and tryptophan, the color of the beads is yellow. The color change to red was observed with the naked eye.

As described above, the receptor NPT of the present invention is a naphthalimide-benzocyazole-based receptor, and can act as a colorimetric and fluorescent probe that enables detection and recognition of cyanide ions (CN-) and tryptophan amino acids with the naked eye. have. In addition, since it exhibits very high selectivity even in the presence of other competing anions or amino acids, cyanide ions can be easily detected in the field of environmental protection and food analysis, and tryptophan amino acids are conveniently used in pharmaceutical and biological samples such as human secretions or serum. As a chemical sensor that can be detected, it can be applied to various fields. In addition, the receptor NPT of the present invention can be used as an alginate bead as a detection probe, and the beaded receptor NPT has a color change according to the detection of cyanide ions and tryptophan amino acids in an aqueous medium, that is, an aqueous solution containing water. Because it is clear and fast, alginide beads made with receptor NPT can easily detect cyanide ions and tryptophan amino acids in aqueous solutions without the need for a separate tool.

Therefore, it can be seen that the receptor NPT of the present invention is very easy to detect cyanide ions and tryptophan amino acids in water.

As described above, the present invention has been described by specific matters and limited embodiments, but these are provided only to help a more general understanding of the present invention, and the present invention is not limited to the above embodiments, and the field to which the present invention pertains. Those of ordinary skill in the art can make various modifications and variations from these descriptions.

Therefore, the spirit of the present invention is limited to the described embodiments and should not be defined, and all things that are equivalent or equivalent to the claims as well as the claims to be described later fall within the scope of the spirit of the present invention. .

Claims (15)

A composition comprising a naphthalimide-benzocyazole compound represented by the following Formula 1:
[Formula 1]

(In Formula 1,
L is C6-C15 arylene;
R ₁ and R ₂ are each independently C1-C7 alkyl, C6-C10 aryl or C7-C20 arylalkyl;
R ₃ is independently C1-C7 alkyl;
X is a monovalent anion,
n is an integer of 0 or 1,
The aryl and arylalkyl of R ₁ and R ₂ may be further substituted with one or more substituted or unsubstituted C1-C7 alkyl.) The method of claim 1,
In Formula 1
L is selected from phenylene, naphthalene, biphenylene or anthracenylene;
R ₁ is C7-C20 arylalkyl;
R ₂ is C1-C7 alkyl;
X is a halogen monovalent anion;
The composition comprising a naphthalimide-benzocyazole compound wherein n is an integer of 0. The method of claim 1,
In Formula 1
L is phenylene;
R ₁ is C7-C10 arylalkyl;
R ₂ is C1-C6 alkyl;
The composition comprising a naphthalimide-benzocyazole compound wherein n is an integer of 0. The method of claim 1,
A composition comprising a naphthalimide-benzocyazole compound represented by the following Formula 2.
[Formula 2]

The method of claim 1,
The naphthalimide-benzocyazole compound is for detection of tryptophan amino acid, a composition comprising a naphthalimide-benzocyazole compound. delete Contacting the composition for detection of tryptophan amino acid of claim 1 and an assay sample; And
Confirming the optical change of the composition;
Comprising, the detection method of tryptophan amino acid. The method of claim 7,
The optical change is confirmed through at least one of a change in color, absorbance, and fluorescence intensity of the compound. The method of claim 7,
The analysis sample is an aqueous analysis sample, a method of detecting tryptophan amino acid. Alginate beads comprising the composition of claim 1. The method of claim 10,
Alginate beads are alginate beads for detection of tryptophan amino acids remaining in the aqueous phase. Preparing alginate beads for detection of tryptophan amino acids remaining in the aqueous phase, including the composition of claim 1;
Contacting the assay sample with the alginate beads; And
Identifying optical changes;
A method for detecting tryptophan amino acids comprising a. The method of claim 12,
The optical change is confirmed through at least one of a change in color, absorbance, and fluorescence intensity of the compound. The method of claim 13,
The assay sample is a water-soluble assay sample, a method of detecting tryptophan amino acid. A chemical sensor for detecting tryptophan amino acids comprising the composition of claim 1.

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