KR20100025891A - Rhodamine derivative bearing binaphthyl group, method for preparing the same, and method for detecting copper ion using the same - Google Patents

Abstract

PURPOSE: A method for detecting copper ion using rhodamine derivative having binaphthyl group is provided to react the rhodamine derivative with copper ion and quantitatively and qualitatively analyze the copper ion. CONSTITUTION: A rhodamine derivative having a binaphthyl group is denoted by chemical formula 1 or 2. A method for preparing the rhodamine derivative having binaphthyl group of chemical formula 1 comprises: a step of adding THF in which potassium hydroxide solution and phenta(ethylene glycol)-ditoxylate are dissolved in 2,2'-dihydroxy-1,1'-binaphtyl-3-carboxadehyde of chemical formula 3 and reacting under reflux condition to obtain 3-formyl-2,2'-binaphthyl-20-crown-6 of chemical formula 4(step 1); a step of adding ethanol solution in which rhodamine B hydrazide of chemical formula 5 in 3-formyl-2,2'-binaphthyl-20-crown-6 of chemical formula 4 and reacting under reflex condition to obtain a compound of chemical formula 1(step 2); and a step of adding ethanol solution and reacting under reflux condition to rhodamine derivative having binaphthyl group of chemical formula 2.

Description

Rhodamine derivative having a binaphthyl group, a preparation method thereof, and a method for detecting copper ions using the same {Rhodamine derivative bearing binaphthyl group, method for preparing the same, and method for detecting copper ion using the same}

The present invention relates to a method for detecting copper ions using a rhodamine derivative having a binaphthyl group. More specifically, the present invention provides an optical method for detecting copper ions carried out by measuring fluorescence intensity or color change generated from a compound produced by reacting a rhodamine derivative having a binaphthyl group with a copper ion. It relates to a detection method.

Various transition metal ions have a significant impact on living organisms. Among these, copper ions play an important role in metabolic processes as cofactors that catalyze various metabolisms, for example, superoxide dismutase, cytochrome oxidase, tyrosinase. However, when copper ions are present in excess in vivo, copper ions are toxic and can cause neurological diseases (eg, Alzheimer's disease, Wilson's disease) caused by free radicals. The toxicity of copper ions to humans is low compared to other heavy metals, but very small amounts can have a significant effect on microorganisms. Copper is also widely used and is considered a major metal contaminant. As such, copper ions play a variety of roles in vivo, and the contents of these copper ions need to be well controlled because they have a significant effect on the living body. The detection of copper ions must be preceded for such regulation, and thus, much research has been conducted on effective and selective methods for detecting copper ions in cells and in vivo. In recent studies on detecting copper ions, researches on fluorescent chemical sensors useful for detecting copper ions have been actively conducted. However, little is known about the "OFF-ON" type sensor for copper ions. Here, the "OFF-ON" type sensor is a sensor that detects the fact that the intensity (or intensity) of the fluorescence becomes very large (ON) when the copper ions are detected when the intensity (or intensity) of the fluorescence is low (OFF). Type of sensor.

Therefore, the present inventors use a rhodamine derivative having a binaphthyl group as a sensor of "OFF-ON" type that can detect copper ions in an aqueous solution state, and the rhodamine derivative and copper ion having the binaphthyl group at room temperature. By detecting the fluorescence intensity or color change generated by the reaction to find a detection method that can accurately detect copper ions, the present invention was completed.

An object of the present invention is to provide a rhodamine derivative having a binaphthyl group, a method for preparing the same, and a method for detecting copper ions using the same.

In order to achieve the above object, the present invention uses a rhodamine derivative having a binaphthyl group as an "OFF-ON" type sensor, and reacts it with copper ions to measure fluorescence intensity or color change generated near a wavelength of 530 nm. This provides a method for qualitatively and / or quantitatively detecting copper ions.

The present invention is useful for quantitatively and / or qualitatively analyzing copper ions by optical methods by measuring the fluorescence intensity or color change occurring near 530 nm wavelength by reacting the rhodamine derivative having the binaphthyl group with copper ions at room temperature. Can be used.

Hereinafter, the present invention will be described in detail.

The present invention provides a rhodamine derivative having a binaphthyl group represented by the following formula (1) or (2):

.

.

Rhodamine derivatives having the formula (I) or binaphthyl of formula (2) by selective reaction with respect to the copper ion (Cu ^{+ 2)} in the aqueous solution to cause the fluorescence emission and color change. Rhodamine derivative having a binaphthyl group of Formula 1 or Formula 2 may be useful for detecting copper ions and cells in vivo by using as a fluorescence chemical sensor in a microfluidic device due to its high selectivity to copper ions ( See FIG. 1).

In another aspect, the present invention provides a method for preparing a rhodamine derivative having a binaphthyl group represented by Chemical Formula 1 including the following steps as shown in Scheme 1 below:

.

.

Hydroxide to 2,2'-dihydroxy-1,1'-binafphyl-3-carboxaldehyde (2,2'-dihydroxy-1,1'-binaphthyl-3-carboxaldehyde) of formula (3) as starting material THF dissolved in an aqueous potassium solution and penta (ethylene glycol) -ditosylate was added and reacted under reflux conditions to react with 3-formyl-2,2′-binaphthyl- Preparing 20-crown-6 (3-formyl-2,2′-binaphthyl-20-crown-6) (step 1); And

An ethanol solution in which Rhodamine B hydrazide of Formula 5 is dissolved is added to 3-formyl-2,2′-binafphyl-20-crown-6 of Formula 4 prepared in Step 1 above. To react under reflux to prepare a compound of Formula 1 (Step 2).

In Step 1, 2,2′-dihydroxy-1,1′-binaphthyl-3-carboxaldehyde of Formula 3 may be prepared according to a known method ((a) Kim, HC; Choi, S .; Kim, H .; Ahn, K.-H. Tetrahedron Lett . 1997 , 38 , 3959. (b) Matsunaga, S .; Das, J .; Roels, J .; Vogl, EM; Yamamoto, N .; Iida, T .; Yamaguchi, K .; Shibasaki, M. J. Am . Chem . Soc . 2000 , 122 , 2252.)

The compound of Formula 4 of Step 1 or the compound of Formula 1 of Step 2 may be obtained through evaporation, extraction, washing, drying or purification processes used in conventional organic synthesis.

In another aspect, the present invention provides a method for preparing a rhodamine derivative having a binaphthyl group of formula (2) comprising the following steps, as shown in Scheme 2:

2,2'-dihydroxy- [1,1'-binaphthalene] -3,3'-dicarboxaldehyde (2,2'-dihydroxy- [1,1'-Binaphthalene-3,3) (VIII-dicarboxaldehyde) is added to an ethanol solution in which rhodamine B hydrazide of formula (5) is dissolved and reacted under reflux conditions to prepare a rhodamine derivative having a binaphthyl group of formula (2).

In the above method, 2,2'-dihydroxy- [1,1'-binaphthalene] -3,3'-dicarboxaldehyde of Chemical Formula 6 may be prepared according to a known method (Zhang, H. -C .; Huang, W.-S .; Pu, L. J. Org . Chem . 2001 , 66 , 481.).

The compound of formula 2 in the above step can be obtained through the evaporation, extraction, washing, drying, recrystallization or purification process used in conventional organic synthesis.

The present invention also provides a method for detecting copper ions using a rhodamine derivative having a binaphthal group represented by the formula (1) or (2).

Rhodamine derivatives having a binaphthal group of Formula 1 or Formula 2 of the present invention selectively react with copper ions in aqueous solution. Example 3 Referring to FIGS. 1 and 2, Ag ⁺ in a HEPES buffer solution, Ca ^{2 +,} Cd ^2+, Co ^{2 +,} Cr ^{3 +,} Cs ^+, Fe ^{2 +,} Fe ^{3 +,} Hg ^{2 +, K +, Li +,} Mg 2 +, Mn 2 +, Na +, Ni 2 +, Pb 2 + , and Zn ^{2 +} and loader having a general formula (1) or by a naphthyl degassing of formula (II) of the present invention the same metal ion does not indicate the fluorescence emission case of each reaction and Min derivative, it can be seen that represents the fluorescence emission of a large width when they are reacted with rhodamine derivatives with the Cu ^{2 +} by-naphthyl degassing of formula (I) and formula (II) of the present invention (See FIGS. 1 and 2). The reaction mechanism in which the rhodamine derivative having the binaphthal group represented by the formula (1) and the formula (2) of the present invention and the copper ion are combined to cause fluorescence emission and color change is represented as in Schemes 3 and 4, respectively. As such, the rhodamine derivative having a binaphthal group represented by Formula 1 or Formula 2 of the present invention may be used as a fluorescence chemical sensor used to detect copper ions.

The fluorescence intensity generated by combining the rhodamine derivative having the binaphthyl group of Formula 1 or Formula 2 with copper ions increases as the concentration of copper ions increases. Referring to Experimental Example 1, Experimental Example 2, FIG. 3 and FIG. 4, in which the fluorescence intensity according to the concentration of copper ions of the present invention was measured, binding to a rhodamine derivative having a binaphthyl group having a certain amount of Formula 1 or Formula 2 was performed. It can be seen that the fluorescence intensity increases as the concentration of copper ions increases.

In addition, a method for detecting copper ions using a rhodamine derivative having a binaphthyl group of formula (1) or (2) according to the present invention is generated by combining a rhodamine derivative having a binaphthyl group of formula (1) or (2) with copper ions This can be done by measuring the color change. FIG. 5 is a photograph illustrating a color change generated by adding copper ions to a rhodamine derivative having a binaphthyl group represented by Chemical Formula 1 of the present invention. 6 is a photograph of fluorescence changes generated by adding copper ions to a rhodamine derivative having a binaphthyl group represented by Chemical Formula 1 of the present invention. As shown in Figure 5, it can be seen that when the addition of copper ions to the rhodamine derivative having a binaphthyl group of the present invention changes from colorless to pink. In addition, as shown in Figure 6, not only the color change depending on the concentration of copper ions but also the fluorescence change is clearly observed.

As described above, in the method for detecting copper ions using a rhodamine derivative having a binaphthyl group represented by Formula 1 or 2 of the present invention, a rhodamine derivative having a binaphthyl group represented by Formula 1 or Formula 2 is bonded to a copper ion It can be usefully used for quantitative and / or qualitative analysis by measuring the change in fluorescence intensity or color generated by the, and has the advantage that it can be detected in aqueous solution at room temperature.

Hereinafter, the present invention will be described in more detail with reference to Examples and drawings. However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited by the following examples.

< Example  1> of Formula 1 of the present invention Binaphthyl  Having Rhodamine  Preparation of Derivatives

Step 1: Aqueous solution of potassium hydroxide (0.73 g, 13 mmol) in 2,2'-dihydroxy-1,1'-binaphthyl-3-carboxaldehyde (2.0 g, 6.34 mmol) was purchased from Aldrich. THF (50 ml) dissolved in penta (ethylene glycol) -ditosylate (3.5 g, 6.34 mmol) was added. The solution was reacted for one day at 70 ° C. under reflux and then evaporated using a rotary concentrator. The residue is then extracted with methylene chloride, washed with water, dried and purified using column chromatography (3: 1 hexane / EA) to yield 1.21 g of yellow solid 3-formyl-2,2. ＇-Binaphthyl-20-crown-6 was prepared in 37% yield: mp 116 ^° C .; ¹ H NMR (CDCl ₃ , 250 MHz): δ 10.78 (s, 1H), 8.53 (s, 1H), 8.04 (d, 1H), 8.00 (d, 1H), 7.90 (d, 1H), 7.6-7.1 (m, 7H), 4.4-4.1 (m, 2H), 3.2-4.0 (m, 18H); ¹³ C NMR (DMSO- d ₆ , 62.5 MHz): δ 192.5, 156.1, 154.1, 137.2, 133.5, 133.4, 130.1, 129.8, 129.5, 129.1, 129.0, 128.7, 128.0, 127.0, 125.9, 125.6, 125.5, 124.9, 123.9, 118.2, 113.5, 73.7, 70.7, 70.6, 70.5, 70.4, 70.1, 69.9, 69.4, 69.1, 63.6. FAB MS m / z = 517.2229 [M + H] ⁺ , calc. for C ₃₁ H ₃₃ O ₇ = 517.2226.

Step 2: Rhodamine B hydrazide (159 mg) in 20 ml of ethanol in 3-formyl-2,2′-binaphthyl-20-crown-6 (150 mg, 0.29 mmol) prepared in Step 1 , 0.35 mmol) was added to the solution. The reaction mixture was then reacted under reflux for 10 hours and then the solvent was removed under vacuum. The residue was then recrystallized with ethanol to prepare a rhodamine derivative (92 mg, 33%) having a binaphthyl group of the white gray formula (1). mp 139 141 ^o C; ¹ H NMR (CDCl ₃ , 250 MHz) δ 9.12 (s, 1H), 8.38 (s, 1H), 7.947.78 (m, 4H), 7.46 (d, 2H, J = 2 Hz), 7.39 (s, 1H), 7.24 (t, 2H, J = 7.5 Hz), 7.127.06 (m, 3H), 6.96 (t, 2H, J = 8.8 Hz), 6.566.50 (m, 2H), 6.39 (dd, 2H , J = 6.5 Hz, 2 Hz), 6.226.16 (m, 2H), 4.114.03 (m, 2H), 3.572.95 (m, 26H), 1.171.02 (m, 12H); ¹³ C NMR (CDCl ₃ , 62.5 MHz) δ 165.0, 154.3, 154.2, 153.3, 151.8, 148.8, 145.0, 134.7, 133.7, 133.3, 130.3, 129.6, 129.3, 129.1, 128.9, 127.8, 126.5, 125.4, 125.3, 124.7, 123.8, 123.6, 123.4, 119.4, 114.7, 107.8, 106.5, 106.4, 98.1, 98.0, 72.9, 70.6, 70.4, 70.3, 70.0, 69.8, 69.4, 66.2, 44.3, 12.7, 12.6. FAB MS m / z = 955.4651 [M + H] ⁺ , calc. for C ₅₉ H ₆₃ N ₄ O ₈ = 955.4646.

¹ H NMR, ¹³ C NMR, FAB mass spectrometry data of the rhodamine derivative having the binaphthyl group of Formula 1 prepared above are shown in FIGS. 7, 8, and 9, respectively.

< Example  2> of formula 2 of the present invention Binaphthyl  Having Rhodamine  Preparation of Derivatives

2,2'-Dihydroxy- [1,1'-binaphthalene] -3,3'-dicarboxaldehyde (200 mg, 0.58 mmol) to Rhodamine B hydrazide (680 mg, 1.48 mmol) It was added to the dissolved ethanol solution (50 mL). The reaction mixture was reacted for 48 hours under reflux conditions, and then the solvent was evaporated under vacuum and purified by chromatography using silica gel to prepare a rhodamine derivative having a binaphthal group of formula 2 in 22% yield. ¹ H NMR (CDCl ₃ , 250 MHz) δ (ppm): 11.1111.07 (m, 2H), 8.37-8.35 (m, 2H), 7.95 (2H, s), 7.72 (2H, s), 7.58 (2H , s), 7.44 (d, 4H, J = 5 Hz), 7.167.01 (m, 8H), 6.56 6.43 (m, 8H), 6.26 (d, 4H, J = 2.5 Hz), 3.323.31 (m 16), 1.151.14 (m, 24 H); ¹³ C NMR (CDCl ₃ , 62.5 MHz) δ (ppm): 164.13, 152.78, 152.67, 152.60, 152.55, 149.19, 149.14, 134.67, 133.62, 128.23, 128.12, 128.06, 127.94, 127.73, 127.59, 127.53, 123.53. , 123.08, 120.64, 116.89, 108.48, 108.31, 104.89, 104.28, 97.96, 97.73, 64.99, 44.38, 12.61. mp 243245 ^o C. ESI MS m / z = 1219.6 [M + H] ⁺ , calc. for C ₇₈ H ₇₅ N ₈ O ₆ = 1219.6.

¹ H NMR, ¹³ C NMR, and ESI mass spectrometric data of the rhodamine derivative having a binaphthyl group of Chemical Formula 2 prepared above are shown in FIGS. 10, 11, and 12, respectively.

< Example  3> of Formula 1 and Formula 2 Binaphthyl  Having Rhodamine  Selectivity Determination for Derivatives of Copper Ions

Ag ⁺ , Ca ^{2 +} , Cd ^{2 +} , Co ^{2 +} , Cr ^{3 +} , Cs ⁺ , Cu ^{2 +} , Fe ^{2 +} , Fe ^{3 +} , Hg ^{2 +} , K ⁺ , Li ⁺ , Mg ^{2 +} , Mn ^{2 +, Na +, Ni 2+,} Pb 2 + , and using the perchlorate salt of _{^{Zn 2 + CH 3 CN-HEPES}} (0.02 M, pH 7.4) (2: 1, v / v) in buffer solution 1 and the general formula Metal binding properties of the rhodamine derivatives having a binaphthal group of the formula (2) were measured. Fluorescence spectra (near 530 nm wavelength) obtained by excitation of the rhodamine fluorescent substance generated by binding of the rhodamine derivative having the binaphthal group represented by the formula (1) and the formula (2) to the respective metal ions are shown in FIGS. 1 and 2, respectively. It was. As shown in FIGS. 1 and 2, only copper ions among the metal ions reacted with the rhodamine derivative having the binaphthal group represented by Chemical Formulas 1 and 2 react with the rhodamine derivative having the binaphthal group. It can be seen that the fluorescence change of.

< Experimental Example  1> of Formula 1 Binaphthyl  Having Rhodamine  Measurement of Fluorescence Intensity According to Concentration of Copper Ion in Derivatives

Copper ions of varying concentrations (0, 4, 8, 12, 16, 20, 40, 60, 80) in CH ₃ CN-HEPES (0.02 M, pH 7.4) (2: 1, v / v) buffer solution at room temperature μM) and a fluorescence emission spectrum generated by reacting a rhodamine derivative having a binaphthyl group represented by Chemical Formula 1 were measured using a fluorescence chemical quantitative meter and are shown in FIG. 3 (excitation wavelength: 530 nm). As shown in FIG. 3, the fluorescence intensity increases as the concentration of copper ions reacting with the rhodamine derivative having the binaphthyl group of formula 1 increases.

< Experimental Example  2> of formula 2 Binaphthyl  Having Rhodamine  Measurement of Fluorescence Intensity According to Concentration of Copper Ion in Derivatives

Various concentrations of copper ions (0, 10, 20, 50, 100, 200, 500 μΜ) and chemical formulas in CH ₃ CN-HEPES (0.02 M, pH 7.4) (2: 1, v / v) buffer solution at room temperature Fluorescence emission spectra generated by reacting with a rhodamine derivative having a binaphthyl group of 2 were measured using a fluorescence chemical quantitative meter and are shown in FIG. 4 (excitation wavelength: 530 nm). As shown in Figure 4, as in Experiment 1 using the rhodamine derivative having a binaphthyl group of formula (1), the fluorescence intensity increases as the concentration of copper ions reacted with the rhodamine derivative having a binaphthyl group of formula (2) It can be seen that increases.

1 is a rhodamine derivative (10 μM) having a binaphthal group represented by Formula 1 by adding various metal ions (100 μM) in CH ₃ CN-HEPES (2: 1, v / v, 0.02 M, pH 7.4). It is a graph showing the change in fluorescence generated by the reaction.

FIG. 2 shows the addition of various metal ions (100 μM) in CH ₃ CN-HEPES (2: 1, v / v, 0.02 M, pH 7.4) to a rhodamine derivative having a binaphthal group of Formula 2 (10 μM). It is a graph showing the change in fluorescence generated by the reaction.

Figure 3 is generated by reacting various concentrations of copper ions with rhodamine derivatives having a binaphthal group of Formula 1 (10 μM) in CH ₃ CN-HEPES (2: 1, v / v, 0.02 M, pH 7.4) It is a graph showing the fluorescence change.

4 is generated by reacting various concentrations of copper ions with rhodamine derivatives having a binaphthal group of formula 2 (10 μM) in CH ₃ CN-HEPES (2: 1, v / v, 0.02 M, pH 7.4) It is a graph showing the fluorescence change.

FIG. 5 is a photograph showing the color change generated before adding copper ions and after adding copper ions (10 eq.) To a rhodamine derivative (50 μM) having a binaphthyl group represented by Chemical Formula 1 of the present invention.

FIG. 6 is a photograph of fluorescence changes generated before and after adding copper ions to a rhodamine derivative (50 μM) having a binaphthyl group represented by Formula 1 of the present invention.

FIG. 7 is a ¹ H NMR (250 MHz) analysis data obtained by preparing and analyzing a rhodamine derivative having a binaphthyl group represented by Chemical Formula 1 in Example 1.

FIG. 8 is ¹³ C NMR (62.5 MHz) analytical data obtained by preparing and analyzing a rhodamine derivative having a binaphthyl group represented by Chemical Formula 1 in Example 1.

9 is FAB mass spectrometry data obtained by analyzing and preparing a rhodamine derivative having a binaphthyl group represented by Chemical Formula 1 in Example 1. FIG.

FIG. 10 is a ¹ H NMR (250 MHz) analysis data obtained by analyzing and preparing a rhodamine derivative having a binaphthyl group represented by Chemical Formula 2 in Example 2.

FIG. 11 is a ¹³ C NMR (62.5 MHz) analysis data obtained by analyzing and preparing a rhodamine derivative having a binaphthyl group represented by Chemical Formula 2 in Example 2.

FIG. 12 is ESI mass spectrometry data obtained by analyzing and preparing a rhodamine derivative having a binaphthyl group represented by Chemical Formula 2 in Example 2.

Claims (5)

Rhodamine derivative having a binaphthyl group represented by Formula 1 or Formula 2 below: [Formula 1]

[Formula 2]

. As shown in Scheme 1 below, As a starting material, an aqueous potassium hydroxide solution and penta (ethylene glycol) -ditosylate (penta (ethylene glycol)-) in 2,2'-dihydroxy-1,1'-binaphthyl-3-carboxaldehyde of the formula (3) reacting under reflux conditions with the addition of THF in which ditosylate was dissolved to prepare 3-formyl-2,2′-binafphyl-20-crown-6 of Chemical Formula 4 (step 1); And Reaction under reflux condition by adding an ethanol solution in which rhodamine B hydrazide of Formula 5 was dissolved in 3-formyl-2,2′-binafphyl-20-crown-6 of Formula 4 prepared in Step 1 To prepare a compound of Formula 1 (Step 2) Method for preparing a rhodamine derivative having a binaphthyl group of formula 1 comprising: Scheme 1

. As shown in Scheme 2 below, 2,2'-Dihydroxy- [1,1'-binaphthalene] -3,3'-dicarboxaldehyde of Formula 6 was added to an ethanol solution in which Rhodamine B hydrazide of Formula 5 was dissolved to reflux. Method for preparing a rhodamine derivative having a binaphthyl group of the formula (2) reacted under conditions: Scheme 2

. A method for detecting copper ions using the rhodamine derivative having a binaphthyl group according to claim 1, wherein the rhodamine derivative having a binaphthyl group is performed by measuring a change in fluorescence intensity or color generated by reaction with the copper ions. 5. The method of claim 4, wherein the fluorescence intensity increases as the concentration of copper ions increases.

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