KR20110068262A - Coumarin derivatives and the method of preparing the same - Google Patents

Abstract

PURPOSE: A coumarin derivative used as a chemical sensor and a method for preparing the same are provided to generate fluorescence and to improve performance of a chemical sensor. CONSTITUTION: A coumarin derivative is denoted by chemical formula 1. The coumarin derivative is prepared by reaction formula 1. A hydrogen sulfate in a sample ion is selectively detected using the coumarin derivative. The hydrogen sulfate ion is selectively detected by measuring the fluorescence intensity. A chemical sensor for detecting the hydrogen sulfate ion contains the coumarin derivative of chemical formula 1.

Description

Coumarin derivatives and its preparation method {Coumarin derivatives and the method of preparing the same}

The present invention relates to a coumarin derivative and a chemical sensor using the same, and more particularly, to a coumarin derivative which generates fluorescence by combining with hydrogen sulfate ion and a chemical sensor capable of detecting hydrogen sulfate using the same.

In areas such as environmental measurements or clinical diagnostics, it is necessary to quickly and accurately analyze the concentration of various ions contained in specific solutions. In this analysis, various kinds of chemical sensor materials using materials that are selective for specific ions are used. The general sensing signal of the sensor uses electrical properties such as electricity, resistance, and potential difference, or optical properties such as color and fluorescence. Among these, color change and fluorescence change can be easily identified by the naked eye, so it is one of the easy methods to measure even without special equipment.

Thus, an example of the substance used as a chemical sensor by a change of color and fluorescence is an aromatic benzoxazole type molecule which has an aromatic hydroxyl group in an ortho position. The molecule may exist in two forms, an enol form and a keto form, by a nitrogen interatomic tautomerism of a hydroxyl group and a benzoxazole group at an ortho position. In general, the maximum absorption wavelength is changed due to the difference in conjugation between the keto and enol molecules of the two forms, so there is a difference in the color and fluorescence of the compound. Therefore, the addition of an ionic material capable of changing the structure by totomalism makes it impossible to convert to the keto form, the enol form is predominant, thereby showing a change in optical properties. In the above formula, the enol form having a hydroxyl group is present in a structure in which hydroxyphenyl group and benzoxazole group are twisted with each other, and the keto form having a carbonyl group has a feature that the structure of the molecule forms one plane. The keto form is characterized in that a hydrogen bond is formed between the oxygen atom of the carbonyl group and the hydrogen atom of the amine group. The development of a sensor material that detects anions among such chemical sensors is currently attracting a lot of attention, and in particular, anion detection by a change in color or fluorescence of a sensor material is widely used due to the sensitivity of the detection signal.

Since fluorescence measurement has such a high sensitivity and easy measurement, a chemical sensor based on ion-induced fluorescence change is one of the very preferred sensors. However, fluorescent turn-on sensors that can detect biologically important negative ions also have problems, which can reduce the selectivity of the predecessor because they can extinguish the generated fluorescence other than specific anions. will be. Therefore, much attention has been focused on a design for emitting an anion fluorescent sensor that can solve this problem.

Number of sulfate anion anti-inflammatory (hydrogen sulfate, HSO ₄ ^-) ions because it is widely used substance in the biological field and the industrial field is particularly important to be considered is an anion. These amphiphilic anions decompose at high pH to produce sulfate (SO ₄ ^2- ) ions, which can irritate skin and eyes and even cause respiratory distress. For this reason, research on the method of detecting hydrogen sulfate ion with high selectivity in the field of chemical sensors is actively performed.

Therefore, the first problem to be solved by the present invention is to provide a coumarin derivative having a selectivity to hydrogen sulfate salt.

The second problem to be solved by the present invention is to provide a method for producing the coumarin derivative.

A third object of the present invention is to provide a method for selectively detecting hydrogen sulfate ions using the coumarin derivative.

The fourth problem to be solved by the present invention is to provide a chemical sensor comprising the coumarin derivative.

The present invention provides a coumarin derivative represented by the following formula (1) in order to achieve the first object.

Formula 1

The present invention provides a method for preparing a coumarin derivative of the formula (1) by the following scheme 1 in order to achieve the second object.

Scheme 1

The present invention provides a method for selectively detecting hydrogen sulfate ions in a sample by using the coumarin derivative of Formula 1 to achieve the third object.

According to one embodiment of the present invention, the hydrogen sulphate ion can be selectively detected by measuring the intensity of fluorescence generated by binding with the hydrogen sulphate ion.

According to another embodiment of the present invention, the central wavelength of fluorescence generated by binding with hydrogen sulfate ion may be 485 nm.

According to a further embodiment of the present invention, the fluorescence intensity of the generated combination with sulfuric Flame ions ^{F -, Cl -, Br -} , I -, CH 3 CO 2 -, H 2 PO 4 -, NO 3 - Or may be stronger than the intensity of fluorescence generated in combination with OH ⁻ .

According to another embodiment of the present invention, the intensity of fluorescence may be changed at pH 4 to pH 10.

The present invention provides a chemical sensor for detecting hydrogen sulfate ion using a coumarin derivative of the formula (1) in order to achieve the fourth object.

The coumarin derivative of the present invention can be used as a chemical sensor because it combines with hydrogen sulfate ions to generate fluorescence, and can improve the performance of the chemical sensor because the selectivity for anions other than hydrogen sulfate ions is very excellent. In addition, since it can be used for titration of hydrogen sulphate using the characteristic of changing the intensity of fluorescence according to the conditions of acidity, it can be usefully used in the field of hydrogen sulphate detection and physiological treatment.

The coumarin derivatives of the present invention combine with hydrogen sulfate ions to generate fluorescence and are excellent in selectivity to other anions.

Several chemical sensors have exhibited absorption or fluorescence properties for hydrogen sulphate, but no sensor has been published that has satisfactory results in terms of selectivity to anions. In the present invention, a new fluorescence sensor based on coumarin of Formula 1 showing a specific fluorescence phenomenon in the presence of hydrogen sulfate ions was developed, and the fluorescent sensor showed high selectivity for hydrogen sulfate ions. The coumarin portion of Compound 1 has a structure in which a CF ₃ group is bonded to another electron withdrawing group instead of the CF ₃ group.

Formula 1

In order to demonstrate the fluorescence change mechanism of the fluorescence sensor according to the present invention, a substance of formula 2 similar to compound 1 (hereinafter referred to as compound 2) and a substance of formula 3 (hereinafter referred to as compound 3) are synthesized, and The characteristics were compared.

Formula 2

Formula 3

1 is at 50% acetonitrile (acetonitrile) aqueous solution of ^{F -, Cl -, Br -} , I -, CH 3 CO 2 -, HSO 4 -, H 2 PO 4 -, NO 3 - (100 eq), and OH ^The result of UV spectrum measurement for Compound 1 when TBA ⁺ salt of-was added. Referring to FIG. 1, Compound 1 showed an ultraviolet-visible light absorption band centered at 355 nm, and an absorption band centered at 355 nm moved to an absorption band centered at 370 nm in the presence of hydrogen sulfate ion.

In Fig. 2 (a) F in 50% aqueous acetonitrile (acetonitrile) solution ^{-, Cl -, Br -,} I -, CH 3 CO 2 -, HSO 4 -, H 2 PO 4 -, NO 3 - (50 eq. ), And a fluorescence spectrum (using 355 nm light) for Compound 1 (3.0 μM) when TBA ⁺ salt of OH ⁻ was added, and FIG. 2B shows TBA in 50% acetonitrile aqueous solution. _{^{+ HSO 4 - (0, 0.1}} , 0.3, 0.5, 1, 3, 5, 6, 7, 8, 10, 20, 30, 50, 100 eq) fluorescence titration (titration) of compound 1 (3.0 μM) for the Spectrum (355 nm light used) result. Referring to (a) of FIG. 2, a significant increase in fluorescence intensity was observed at 485 nm in a 1: 1 solution of acetonitrile and water, and almost no change in fluorescence intensity was observed for other anions. Referring to FIG. 2 (b), an increase in fluorescence intensity of 13 times was observed in the titration spectra of the hydrogen sulfate ion at 485 nm. Job's plot analysis on the fluorescence titration spectrum showed the maximum value at 0.5 mole fraction of hydrogen sulfate, in which the hydrogen sulfate ion and compound 1 complexed 1: 1. In view of the experimental results of FIG. 2 and the stoichiometry of 1: 1, the binding constant of Compound 1 to hydrogen sulfate was calculated to be 4.86 × 10 ⁴ M ⁻¹ .

Figure 3 shows the binding properties of hydrogen sulfate ions and other anions of compound 1 (3.0 μM). Referring to FIG. 3, HSO ₄ ⁻ (50 equivalents) and various anions (X; F ⁻ , Cl ⁻ , Br ⁻ , I ⁻ , CH ₃ CO ₂ ⁻ , HSO ₄ ⁻ , in a 50% acetonitrile aqueous solution, ^{_{H 2 PO 4 -, NO 3}} -, each of the fluorescence spectra measured using the TBA ⁺ 355㎚ light under the presence of a salt of 50 eq.) is displayed ^{and, F -, Cl -, Br} -, I -, CH 3 ^{_{CO 2 -, H 2 PO 4}} -, NO 3 -, OH - the addition of various anionic mixture comprising TBA ⁺ salts, of the compound 1 fluorescence disappears. Here, the slow addition of the hydrogen sulfate salt to the anionic mixture fluoresces, indicating that Compound 1 has high selectivity for other anions.

FIG. 4 shows the fluorescence intensities of 485 nm for Compound 1 and Compound 1-hydrogen sulfate in 50% aqueous acetonitrile solution at different acidity conditions. The excitation light was 355 nm, Compound 1 was used at 3.0 µM, and the amount of hydrogen sulfate was 10 times that. Referring to FIG. 4, in the absence of the hydrogen sulfate salt, Compound 1 was hardly observed as the acidity condition was changed. However, as the hydrogen sulfate salt was added, the intensity of the emission band of 485 nm largely changed between pH 4 and pH 10. Such a wide range of acidity in an aqueous solution environment can be seen that it can be usefully used in the field of hydrogen sulfate detection and physiological treatment in the waste water.

5 is a result of performing a ¹ H NMR titration experiment to know the binding mode of compound 1 and hydrogen sulfate salt. (A) is TBA ⁺ HSO ₄ ^- and ¹ H NMR results in, (B) is dissolved in CD ₃ CN and TBA ⁺ HSO ₄ ^- and ¹ H NMR results in a state that there is no, (C), (D ), (E) is dissolved in CD ₃ CN and is 0.5. The ¹ H NMR results in a state that is present ^- 1, TBA ⁺ HSO ₄ 2 equivalents. Referring to FIG. 5, a peak of phenolic proton (Ha), which is intramolecular hydrogen bond with nitrogen of imine, was observed at 12.6 ppm. However, -OH disappears in the presence of hydrogen sulphate ions, indicating that the intramolecular hydrogen bond of compound 1 is interfered by the coordination of the hydrogen sulphate ion.

In order to know the role of intramolecular hydrogen bonding between phenolic -OH and imine moiety and the role of coumarin units in fluorescence of compound 1, the material of formula 2 was prepared without a hydroxyl group, and the material of formula 3 Pyrenyl moiety was made instead of rurin. FIG. 6 shows TBA ⁺ salts (F ⁻ , Cl ⁻ , Br ⁻ , I ⁻ , CH ₃ CO ₂ ⁻ , HSO ₄ ⁻ , H ₂ PO ₄ ⁻ in Compound 2 (3.0 μM) in 50% acetonitrile aqueous solution. , NO ₃ ⁻ , OH ⁻ 100 equivalents each) is shown. The wavelength of the excitation light was 355 nm. Referring to FIG. 6, when hydrogen sulfate was added to the material of Compound 2, the fluorescence change observed was insignificant and nonselective for the anions. This suggests that the hydrogen bond between phenolic -OH and imine -N played a critical role in the selectivity of compound 1.

FIG. 7 shows TBA ⁺ salts (F ⁻ , Cl ⁻ , Br ⁻ , I ⁻ , CH ₃ CO ₂ −, HSO ₄ ⁻ , H ₂ PO ₄ ⁻ in Compound 3 (3.0 μM) in 50% acetonitrile aqueous solution. , NO ₃ ⁻ , and OH ⁻ represent 100 fluorescence spectra respectively. The wavelength of the excitation light was 375 nm. Referring to FIG. 7, when hydrogen sulfate was added to the material of Compound 3, the observed fluorescence change was insignificant and nonselective for the anions. Compound 3 alone exhibits only weak fluorescence, but in the presence of hydrogen sulfate salts, the intensity of fluorescence increases as with compound 1. This phenomenon is attributed to the fact that the six intramolecular hydrogen bonds between phenolic -OH and imine -N contribute to the fluorescence disappearance of compound 1, and the fluorescence intensity of compound 1 and the compound of formula It means to increase.

To clarify the 'off-on' fluorescence mechanism, density functional theory with 6-31G * basis sets with B3LYP exchange using Gaussian 03 programs. , DFT) calculations were performed. 8 shows the optimized structure of compound 1 and the structure of the complex compound (compound 1-hydrogen sulfate) with hydrogen sulfate. Since compound 1 contains intramolecular hydrogen bonds, compound 1-hydrogen sulfate has three intramolecular hydrogen bonds, one of which is a bond between oxygen of hydrogen sulfate ion and hydrogen of hydroxy group, and the other of sulfuric acid The bond between hydrogen of the hydrogen salt ions and the oxygen of the hydroxy group, and the other is the bond between hydrogen of the hydrogen sulfate salt ions and nitrogen of compound 1. Thus, it is evident that Compound 1 has a strong interaction with the hydrogen sulfate ion.

FIG. 9 shows the results of natural bond orbital (NBO) analysis of Compound 1, Compound 2, and Compound 1-Hydrogen Sulfate Salt. Referring to FIG. 9, it was shown that when Compound 1 complexes with the hydrogen sulfate ion, a large change occurs in the charge of the -N atom. The -N atomic charges of Compound 1, Compound 2 and Compound 1-Hydrogen Sulfate salt are -0.527, -0.446 and -0.456, respectively. From these results, it can be seen that the -N atom of Compound 1 shows higher electron density, although it is due to intramolecular hydrogen bonding with phenolic-OH groups. In a similar hydrogen bonding system, electrons migrate from nitrogen to hydrogen, resulting in a decrease in the charge density of -N. In this way, the fluorescence disappears due to the negative charge of the nitrogen atom. Nevertheless, the hydrogen bonds form complexes with the hydrogen sulfate ion and consequently the intensity of fluorescence is enhanced.

Table 1 below summarizes the major electron transitions, the two strongest absorption bands in view of oscillator strength. TDDFT excitation properties including the first and second high oscillating intensities of Compound 1, Compound 2 and Compound 1-Hydrosulphate salts at low excitation energy (λ> 310 nm) were calculated. Referring to Table 1, the unbonded non-covalent electron pairs of nitrogen correspond to HOMO for Compound 1, HOMO-1 for Compound 2, and HOMO-2 for Compound 1-Hydrogen Sulfate Salt, respectively. On the other hand, the filled π-bonded orbital state of C = N corresponds to HOMO-1 for Compound 1, HOMO for Compound 2, and HOMO-4 for Compound 1-Hydrogen Sulfate. Since the non-covalent electron pairs of π-bonded orbitals and nitrogen show a small energy difference, the electron transition from the non-covalent electron pairs of nitrogen to the filled π-bonded orbitals is thought to be a trigger of the PET process, thus leading to fluorescence disappearance. In addition, referring to Table 1, the oscillator intensity for the transition from nitrogen unshared electron pairs to π * orbitals (n → π *) is 0.4084, 0.0346, 0.2812 for Compound 1, Compound 2 and Compound 1-Hydrogen Sulfate, respectively. And the transition energies are 386, 314 and 443 nm, respectively. As mentioned above, this contribution causes fluorescence disappearance of compound 1. Other important transitions for Compound 1, Compound 2 and Compound 1-Hydrosulphate salt occur at 341 nm, 357 nm and 362 nm and correspond to oscillator strengths 0.3488, 0.6360 and 0.2807, respectively. Therefore, when 355 nm light is used to reach an excited state, transition occurs in both compound 1 and compound 2. However, in the case of compound 1-hydrogen sulfate, the transition of n → π * is limited because the transition energy (443 nm) deviates from 355 nm. For compound 2, the very weak oscillator intensity of the n → π * transition will limit the n → π * transition. Thus, fluorescence is turned off for compound 1 and fluorescence is turned on for compound 2 and compound 1-hydrogen sulfate. The selective binding affinity for the hydrogen sulphate salt of compound 1 enables the preparation of ion selective electrode PVC membranes based on compound 1, thereby broadening its application.

TABLE 1

Potentiometric cells used in the present invention are Ag / AgCl (3.0M KCl) /1.0×10 ⁻² M TBA ⁺ HSO ₄ ⁻ / PVC membrane / test solution / (3.0M KCl) AgCl / Ag Has a structure. The composition of the membrane is shown in Table 2.

Table 2

10 shows the potentiometric response curves of Compound 1 for various anions. Referring to FIG. 10, it can be seen that in the preliminary experiment, the ion permeation carrier compound 1 functions as an effective ion transporter for the hydrogen sulfate anion compared with other anions.

FIG. 11 shows (A): 1.0 × 10 ⁻⁵ M, [B]: 1.0 × 10 ⁻⁴ M, [C]: 1.0 × 10 ⁻³ M, [D]: 1.0 × under various hydrogen sulfate ion conditions 10 ⁻² M, [E]: 1.0 × 10 ⁻¹ M) The time response curves for the selective electrodes of compound 1 are shown. FIG. 12 also shows the acidity effect of the potential reaction on the hydrogen sulfate ion of the selective electrode based on compound 1. FIG. Referring to Figures 11 and 12, the reaction rate for the hydrogen sulfate salt was less than 10 seconds at operating conditions of pH 1.4 to pH 4.9.

)는 고정된 농도의 간섭 이온(1.0×10^-2M)과 황산 수소염의 이온의 농도를 변화시킨 용액에서 포텐샬을 측정하여 결정된다. 표 3은 간섭 음이온에 대한 이온투과담체 화합물 1-PVC 막 전극의 황산 수소염 이온에 대한 상대적인 포텐셔메트릭 선택 계수 데이터를 나타낸 것이다. 표 3을 참조하면, 본 발명에 따른 전극이 여러 가지 다른 음이온들에 비하여 선택성이 뛰어나다는 것을 알 수 있다. 황산 수소염 이온 선택성 전극에서 다른 2차 음이온들에 대한 선택 계수를 얻을 수 있었으며, 이로부터 정상적인 작동조건에서 이러한 음이온들의 간섭이 일어나지 않고, 음이온의 농도가 1.0×10^-2 M의 고농도일 경우에도 마찬가지라는 것을 알 수 있다. Next, the potentiometric selectivity coefficient for the interfering ions was determined using a fixed interferometry. Potentiometric selection factor (

) Is determined by measuring the potential in a solution with varying concentrations of interference ions (1.0 × 10 ^-2 M) and ions of hydrogen sulfate. Table 3 shows the relative potentiometric selectivity data for hydrogen sulfate ions of the ion permeate compound 1-PVC membrane electrode for interfering anions. Referring to Table 3, it can be seen that the electrode according to the present invention has excellent selectivity compared to various other anions. The selectivity coefficients for the other secondary anions could be obtained at the hydrogen sulfate ion selective electrode, from which no interference of these anions would occur under normal operating conditions, even at high concentrations of 1.0 × 10 ^-2 M It can be seen that the same.

TABLE 3

The applicability to the hydrogen sulphate ion selective electrode of the present invention was tested through the potentiometric titration of hydrogen sulfate ions to sodium hydroxide solution (1.0 × 10 ⁻² M). Figure 13 shows the ^{1.0 × 10 -2 1.0 × 10 -2} M in number (derivative curve) suitable derivative curve the anti-inflammatory solution of sulfuric acid with sodium hydroxide solution in the M. Referring to FIG. 13, it can be seen that the electrode of the present invention can be effectively used for potentiometric titration through a drastic change in potential near the titration end point.

14 shows a method for synthesizing Compound 1, Compound 2 and Compound 3. FIG. Referring to (a) of FIG. 14, Compound 1 is synthesized by a reaction in which an amine group of a reactant reacts with an aldehyde group of another reactant to generate imine. (B) and (C) of FIG. 14 also synthesized Compound 2 and Compound 3 by similar reaction, respectively.

FIG. 1 is a UV spectrum measurement result of Compound 1 when various kinds of TBA ⁺ salts were added in an aqueous 50% acetonitrile solution.

(A) of FIG. 2 shows fluorescence spectra of Compound 1 when various kinds of TBA ⁺ salts are added in 50% acetonitrile solution, and FIG. 2 (b) shows TBA ⁺ HSO ₄ in 50% acetonitrile solution. ^- an appropriate fluorescent spectrum of the compound 1 on.

Figure 3 shows the binding properties of hydrogen sulfate ions and other anions of compound 1.

FIG. 4 shows the fluorescence intensities of 485 nm for Compound 1 and Compound 1-hydrogen sulfate in 50% aqueous acetonitrile solution at different acidity conditions.

5 is a result of performing a ¹ H NMR titration experiment to know the binding mode of compound 1 and hydrogen sulfate salt.

FIG. 6 shows fluorescence spectra of various kinds of TBA ⁺ salts added to Compound 2 in a 50% acetonitrile aqueous solution.

FIG. 7 shows fluorescence spectra of various kinds of TBA ⁺ salts added to compound 3 in a 50% acetonitrile aqueous solution.

 8 shows the optimized structure of compound 1 and the structure of compound 1-hydrogen sulfate.

9 shows the results of natural bond orbital analysis of Compound 1, Compound 2, and Compound 1-Hydrogen Sulfate Salt.

10 shows the potentiometric response curves of Compound 1 for various anions.

FIG. 11 shows time response curves for the selective electrode of Compound 1 under various hydrogen sulfate ion conditions.

12 shows the acidity effect of the potential reaction on hydrogen sulfate ions of a selective electrode based on compound 1. FIG.

Figure 13 shows the 1.0 × 10 ^-2 M sulfuric acid solution, an appropriate number of anti-inflammatory derivative curve of the sodium hydroxide solution of 1.0 × 10 ^-2 M.

14 shows a method for synthesizing Compound 1, Compound 2 and Compound 3. FIG.

Claims (8)

Coumarin derivatives represented by the following formula (1). Formula 1

To prepare a coumarin derivative of claim 1 by the following scheme 1. Scheme 1

A method for selectively detecting hydrogen sulfate ions in a sample using the coumarin derivative of claim 1. The method of claim 3, wherein A method for selectively detecting hydrogen sulfate ions by measuring the intensity of fluorescence generated by binding with hydrogen sulfate ions. The method of claim 3, wherein A method for selectively detecting hydrogen sulphate ions, characterized in that the central wavelength of fluorescence generated by binding with hydrogen sulphate ions is 485 nm. The method of claim 3, wherein The fluorescence intensity of the generated combination with sulfuric Flame ions ^{F -, Cl -, Br -} , I -, CH 3 CO 2 -, H 2 PO 4 -, NO3 - , or OH ^- fluorescence intensity of the generated combination with A method for selectively detecting hydrogen sulfate ions, characterized in that it is stronger. The method of claim 3, wherein A method for selectively detecting hydrogen sulphate ions, characterized in that the intensity of fluorescence varies from pH 4 to pH 10. A chemical sensor for detecting hydrogen sulfate ion using the coumarin derivative of the formula (1) according to claim 1.

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