KR20110020455A - Pyrene derivatives having cu(ii) ion selectivity, method for preparing therefor, detecting method using the same - Google Patents

Abstract

PURPOSE: Pyrene derivatives for detecting Cu(II) ion are provide to detect Cu(II) ions in a sample solution with selective and high sensitivity by causing excimer emission. CONSTITUTION: Pyrene derivatives are represented by chemical formula 1 and has Cu(II) ion selectivity. A method for preparing the pyrene derivatives comprises a step for preparing a pyrene derivative of chemical formula 1 by reacting 1-pyrenecarboxylic acid, dicyclohexylcarbodiimide and 8-aminoquinoline in the presence of a 4-(dimethylamino)pyridine catalyst.

Description

Pyrene derivative having divalent copper ion selectivity, preparation method thereof and method for detecting divalent copper ion using same {Pyrene derivatives having Cu (II) ion selectivity, method for preparing therefor, detecting method using the same}

The present invention relates to a pyrene derivative having divalent copper ion selectivity, a method for preparing the same, and a method for detecting divalent copper ions using the same, and more particularly, to a chemically equivalent 2: 1 complex with divalent copper ions. The present invention relates to a pyrene derivative which can detect divalent copper ions in a sample solution with high sensitivity by forming a and causing a significant excimer emission, a method for preparing the same, and a method for detecting divalent copper ions using the same.

A chemical sensor refers to a compound that causes a significant change in electrical, electronic, magnetic, or optical signals when bound to a specific detection target material. Of these sensors, fluorescent chemical sensors have several advantages over other methods because of their high sensitivity, specificity and fast real-time monitoring. Recently, the development of fluorescent chemical sensors that can selectively recognize metal ions is one of the most promising fields due to the development of organic and supramolecular chemistry. In particular, under certain circumstances, it is very necessary to selectively detect heavy metal ions such as mercury, lead, copper ions and the like.

Divalent copper ions play an important role in various fields. However, when exposed to high concentrations of copper, even if such exposure is short, gastrointestinal disease may occur, whereas if exposed for a long time, damage to the liver or kidneys may result. For these reasons, there have been studies in recent years on the design and synthesis of fluorescent sensors for the detection of divalent copper ions. For most of the reported divalent copper fluorescence sensors, although the binding of divalent copper ions causes an increase in fluorescence in some sensors, in general, the binding of divalent copper ions is paramagnetic with the divalent copper ions. Thereby causing fluorescence quenching.

Pyrene materials have often been used effectively as fluorescent probes because their luminescent properties are sensitive to their surroundings. Depending on the relative proximity between the pyrene residues, unique monomer and excimer emission is observed at significantly different wavelength bands, which allows structural information to be analyzed. Taking advantage of such unique physical properties of pyrenes, the inventors have created a series of self-assembled dimeric structures that, when combined with certain metal cations, generate a Py-Py ^* excimer fluorescent band. Pyrenylamide derivatives were studied.

The first problem to be solved by the present invention is to form a 2: 1 complex chemically equivalent to divalent copper ions, causing a significant excimer emission, thereby detecting a divalent copper ion in a sample solution with high sensitivity It is to provide a pyrene derivative for detecting divalent copper ions.

The second problem to be solved by the present invention is to provide a method for producing a pyrene derivative for detecting divalent copper ions.

The third object of the present invention is to provide a method for detecting divalent copper ions using the pyrene derivative.

The present invention provides a method for selectively detecting divalent copper ions in a sample by using a pyrene derivative represented by Chemical Formula 1 to solve the third problem.

According to a preferred embodiment of the present invention, the selective detection of the divalent copper ions can be carried out by measuring the increase in fluorescence emission according to excimer emission observed after adding the pyrene derivative represented by the formula (1) in the sample. .

The pyrene derivative according to the present invention forms a 2: 1 complex chemically equivalent to divalent copper ions, causing significant excimer emission, thereby selecting divalent copper ions from the sample solution without interference even in the presence of other metal cations. It can be detected with high sensitivity and is very useful as a high sensitivity chemical sensor for divalent copper ions.

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

Pyrene derivatives having divalent copper ion selectivity according to the present invention have the formula

[Formula 1]

.

.

Pyrene derivatives according to the invention can be prepared by reacting 1-pyrenecarboxylic acid, dicyclohexylcarbodiimide and 8-aminoquinoline in the presence of a 4- (dimethylamino) pyridine catalyst.

In the present invention, when the spacer length between the pyrene and the quinolinylamide groups in the compound of the formula 1 according to the present invention to determine how the detection sensitivity of the divalent copper ions are different as the reference compounds 2 and A compound of formula 3 was also prepared, and as a reference compound, a compound of formula 4 was also prepared to examine the binding mode of 8-aminoquinoline to nitrogen and carbonyl divalent copper ions.

[Formula 2]

(3)

[Formula 4]

Molecular structures for compounds having Formula 1, 2, 3 or 4 prepared by the above method were confirmed by ¹ H- and ¹³ C-NMR and FAB-MS.

1 shows a gradual change in the fluorescence spectrum of the compound of Formula 1 with the addition of divalent copper ions. The addition of divalent copper ions led to a new emission band centered at 460 nm and increasing in intensity, which is in sharp contrast to the addition of other metal cations (see FIG. 2). Compound 1 exhibited a fluorescence change in the divalent copper ion concentration range of 0-60 μM with a detection limit of 1.0 μM with U.S. EPA thresholds (˜20 μM) were met.

In order to investigate the complex formation ability of the metal cations of the compound 1, various metal cations were added and the absorption spectrum of the compound 1 was examined. As a result of the addition of the divalent copper ions, the UV spectral band of the compound 1 was widened and red. It was found that the migration phenomenon was due to the intermolecular pp lamination dimerization between two pyrene groups in the ground state.

In order to quantify the rate of complex formation between compound 1 and divalent copper ions, Job plot measurements were performed with varying concentrations of compound 1 and divalent copper ions (see FIG. 4). As a result, the maximum value was observed at mole fraction 0.65, which is close to the typical ligand mole fraction (0.66) for the 2: 1 ligand to metal complex.

In order for compound 1 to induce divalent copper ion induced pyrene excimer formation, the reaction of a quinolinylamide group with a divalent copper ion first causes an intermolecular Py-Py ^* interaction in compound 1, which is the color and fluorescence It is assumed to cause change. In the case of quinolimethylpyrene according to compound 4 in which no carbonyl group is present, the change in the fluorescence spectrum is hardly caused even if divalent copper ions are added. From this, it can be seen that both the quinoline host and the pyrenylamide moiety play an important role in the selective detection of copper ions by the 2: 1 complex formation mode and enable observation of the pyrene excimer band at 460 nm.

As mentioned above, in order to verify the importance of probe spacer length for Py-Py ^* interaction upon the addition of divalent copper ions, compound 1 and reference compounds 2 and 3 according to the present invention can be contrasted. . As shown in FIG. 3, in contrast to compound 1, compounds 2 and 3 do not show noticeable excimer release even if bivalent copper ions are added. These results indicate that intermolecular Py-Py ^* formation is optimized when no methylene spacer is present between the pyrene and carbonyl residues, and a strong excimer band can be observed. For example, if 10 equivalents of divalent copper ions are present, the excimer release strength of compound 1 is about 8 times greater than compounds 2 and 3.

To determine the molecular cause for the unique fluorescence emission properties of compounds 1 to 3, density functional theory calculations for the energy minimized structures of compounds 1 to 3 at the B3LYP / 3-21G ^* level Was performed. Due to the 2: 1 ligand to metal complex formation properties determined by both mass spectra and Job plots, the dimers of compounds 1 to 3 bound or unbound with copper ions were performed with energy minimization. From these results the lowest energy structures for the dimers of compounds 1 to 3 are shown in Figures 5a-5c below.

If there is no spacer between the pyrene and quinolinylamide groups, as in the case of compound 1, the H-bonds are considerably due to steric hindrance between adjacent pyrene groups, as shown in Figure 5a. Weaken and the distance is about 2.5Å. However, in the case of compounds 2 and 3, stable dimers are formed by the stable H-bonding between two amide groups (the distance between the dimer of compound 2 is 2.1 kV and the distance of 2.1 and 2.0 kV for dimer of compound 3). As a result, the binding energy for the dimer of Compound 3 with two H-bonds is the highest 22.4 kcal / mol, in contrast the binding energies for Compounds 2 and 1 are 19.4 and 12.0 kcal / mol, respectively. Based on the results, it can be seen that the addition of divalent copper ions to the dimers of compounds 2 and 3 breaks the stable H-bond formed between the two amide units. And addition to the dimers of 3 disrupts the stable electrostatic interaction between the two monomer units, which in turn divalent copper ions to the dimer of Compound 1 It can be seen that it is less thermodynamically friendly than the addition.

The lowest energy structure for the divalent copper ion composite of compound 1 is shown in FIG. 6A. As shown in Fig. 6A, divalent copper ions form coordination bonds with two oxygen atoms and three nitrogen atoms with an average distance of 1.99 kPa. A common structural feature for both divalent copper ion complexes of compounds 1 to 3 is that divalent copper ions are most effectively recognized by amide oxygen adjacent to the pyrene group. As a result of performing an atomic charge calculation using a natural population analysis (NPA), the electron density change was most prominently observed among the amide oxygen atoms when divalent copper ions were added to the compounds 1 to 3.

To better understand the fluorescence change with the addition of divalent copper ions, a time-dependent density funtional theory (TDDFT) calculation was performed on the divalent copper ion composites of compounds 1 to 3. Molecular orbital energy and related electron transitions were calculated from the optimized geometry of the S ₀ state at the TDDFT / B3LYP / 3-21G ^* level. Some studies have shown that hybrid functionality can yield the best results when evaluating electron transitions in organic molecules. Based on the TDDFT / B3LYP / 3-21G ^* calculation, the effective HOMO to LUMO excitation from one pyrene to another opposite pyrene (Py-Py ^* interaction) is probably due to the compound 1-Cu ²⁺ complex It is believed to contribute to the formation of strong fluorescent excimer bands.

In contrast, no pyrene excimer transition was observed for compounds 2 and 3 and complexes with divalent copper ions. In this respect, the theoretical DFT calculation results agree very well with the observed experimental results, ie the prominent fluorescence excimer emission with the addition of divalent copper ions is associated with the Py-Py ^* interactions in the compound 1-Cu ²⁺ complex. While relevant, such interactions are not observed at all in compounds 2 and 3 and divalent copper ion complexes. In conclusion, the pyrenylquinoline-based compound for the effective detection of divalent copper ions should maintain a minimum intermolecular distance between pyrene and quinoline amide groups in terms of its structure, and the significant Py- in compound 1 according to the present invention. It can be seen that the Py ^* interaction is because these conditions are met.

Accordingly, the present invention provides a method for selectively detecting divalent copper ions in a sample using the pyrene derivative represented by Chemical Formula 1 by utilizing the properties of the compound 1 described above.

As can be inferred from the job plot analysis, mass spectra and fluorescence properties, compound 1 forms a chemical equivalent equivalent 2: 1 complex with divalent copper ions. Addition of divalent copper ions to the analyte sample solution containing compound 1 causes significant excimer luminescence through 2: 1 ligand to metal complex formation. Therefore, the selective detection method of divalent copper ions in the sample according to the present invention can be performed by measuring the increase in fluorescence emission according to the excimer emission.

In addition, the present invention provides a chemical sensor for detecting divalent copper ions using the compound 1 by utilizing the properties of the compound 1 described above.

The increase in fluorescence emission of Compound 1 is caused by the addition of divalent copper ions, and using this phenomenon, Compound 1 can be used as a visual sensor for divalent copper ions or as a chemical sensor for fluorescence detection. Furthermore, compound 1 shows high selectivity with excellent sensitivity to divalent copper ions, and no interference phenomenon is caused by other metal ions. Accordingly, it can be seen that Compound 1 according to the present invention selectively and sensitively detects divalent copper ions, and thus will be applied as a chemical sensor having wide utility in biological and environmental applications.

Example 1 Synthesis of Pyrene Derivatives of Formula 1

To a 1-pyrenecarboxylic acid (2.46 g, 10 mmol) stirred suspension in THF (100 mL), dicyclohexylcarbodiimide (2.3 g, 11 mmol), 8-aminoquinoline (1.56 g, 11 mmol), and A catalytic amount of 4- (dimethylamino) pyridine (DMAP) (50 mg) was added. The mixture was stirred for 6 hours and the white N , N'- dicyclohexylurea was filtered from the lemon yellow solution. The filtrate was washed with water (3 × 50 mL), dried over anhydrous sodium sulfate, and the solvent removed in vacuo. The crude product was further purified by column chromatography on silica gel (eluent: ethyl acetate: n-hexane, 1: 2 v / v) to give a white solid (2.43 g, 63%): mp 210; ¹ H NMR (300 MHz, CDCl 3): d 10.59 (s, 1H, NH ), 9.13 (d, 1H, Arquinoline, J = 7.75 Hz), 8.82 (d, 1H, Arquinoline, J = 9.44 Hz), 8.74 (d, 1H, Arquinoline, J = 4.21 Hz), 8.42 (d, 1H, Arpyrene, J = 8.03 Hz), 8.29-8.04 (m, 6H, Arpyrene), 7.93 (d, 2H, Arpyrene, J = 8.03 Hz ), 7.68 (m, 1H, Arquinoline), 7.60 (d, 1H, Arquinoline, J = 8.32 Hz), 7.46 (m, 1H, Arquinoline) ¹³ C NMR (75 MHz; CDCl ₃ ) d 168.4, 149.8, 137.2, 136.1, 131.5, 131.1, 129.5, 128.8, 127.4, 126.8, 126.3, 126.2, 124.8, 124.6, 123.8, 122.8, 117.1. FAB-MS calc. for C ₂₆ H ₁₆ N ₂ O [M + H] ⁺ 373.13, found 373.42.

Comparative Examples 1 and 2. Synthesis of Pyrene Derivatives of Chemical Formulas 2 and 3

Compounds of formulas (2) and (3) were prepared by the same method as in Example 1 except that the starting material was 8-aminoquinoline having pyrene derivatives.

Compound of formula 2 (2- (pyren-1-yl) -N- (quinolin-8-yl) acetamide) (2.47 g, 64%): mp 208; ¹ H NMR (300 MHz, CDCl ₃ ): d 9.93 (s, 1H, NH ), 8.74 (d, 1H, Arquinoline, J = 8.15 Hz), 8.39 (d, 1H, Arquinoline, J = 9.28 Hz), 8.29 -8.10 (m, 7H, Arpyrene), 8.09 (s, 1H, Arquinoline), 8.03-7.97 (m, 2H, Arpyrene), 7.49-7.44 (m, 1H, Arquinoline), 7.39 (d, 1H, Arquinoline, J = 8.83 Hz), 7.24-7.20 (m, 1H, Arquinoline), 4.62 (s, 2H, CH2 ) 13C NMR (75 MHz; CDCl3) d 170.5, 149.0, 139.3, 137.0, 135.2, 132.3, 132.1, 131.8, 130.8 , 129.6, 129.5, 129.3, 128.7, 128.4, 128.2, 127.0, 126.3, 126.2, 126.1, 125.7, 124.3, 122.5, 122.3, 117.2, 44.5 FAB-MS calc. for C ₂₇ H ₁₈ N ₂ O [M + H] ⁺ 387.14, found 386.9.

Compound of formula 3 (4- (pyren-1-yl) -N- (quinolin-8-yl) butanamide). (2.69 g, 65%): mp 220; ¹ H NMR (300 MHz, CDCl ₃ ): d 9.77 (s, 1H, NH ), 8.80 (d, 1H, Arquinoline, J = 7.51 Hz), 8.71 (d, 1H, Arquinoline, J = 4.26 Hz), 8.34 (d, 1H, Arpyrene, J = 9.01 Hz), 8.17-7.91 (m, 8H, Arpyrene), 8.02 (s, 1H, Arquinoline), 7.56-7.47 (m, 2H, Arquinoline), 7.43-7.39 (m, 1H, Arquinoline), 3.53-3.47 (m, 2H, CH 2 ), 2.71-2.65 (m, 2H, CH 2 ), 2.44-2.35 (m, 2H, CH 2 ), ¹³ C NMR (75 MHz; CDCl ₃ ) d 171.7 , 148.4, 138.5, 136.6, 136.1, 134.7, 131.6, 131.2, 130.2, 129.1, 128.2, 127.7, 126.9, 126.1, 125.1, 123.6, 121.7, 116.7, 37.7, 33.0, 27.5. FAB-MS calc. for C ₂₉ H ₂₂ N ₂ O [M + H] ⁺ 415.17, found 415.49.

Comparative Example 3. Synthesis of Pyrene Derivative of Chemical Formula 4

8-aminoquinoline (1.44 g; 10 mmol), 1- (bromomethyl) pyrene (2.95 g; 10 mmol), TEA (1.01 g, 10 mmol), and THF (100 mL) were refluxed for 24 h. After the solvent was removed in vacuo, the resulting solid was dissolved in CH ₂ Cl ₂ (100 mL). The filtrate was washed with water (3 × 50 mL) and dried over anhydrous sodium sulfate and the solvent was removed in vacuo. The crude product was further purified by column chromatography on silica gel (eluent: ethyl acetate: n-hexane, 1: 2 v / v) to give compound 4 as a white solid (1.58 g; 44%) Mp: 235-237 ; ¹ H NMR (300 MHz, CDCl 3): d 8.64 (d, 1H, Arquinoline, J = 4.31 Hz), 8.33 (d, 1H, Arpyrene, J = 9.07 Hz), 8.17 (d, 1H, Arpyrene, J = 8.02 Hz), 8.12-7.96 (m, 7H, Arpyrene), 8.02 (s, 1H, Arquinoline), 7.38-7.31 (m, 2H, Arquinoline), 7.09 (d, 1H, Arquinoline, J = 8.88), 6.79 (d , 1H, Arquinoline, J = 7.61), 6.67 (s, 1H, NH ), 5,18 (d, 2H, CH 2 , J = 5.18), 13 C NMR (75 MHz; CDCl 3) d 136.3, 135.5, 135.3, 131.4 , 131.1, 131.0, 130.8, 130.7, 130.6, 130.5, 130.3, 128.8, 127.3, 127.1, 127.0, 126.8, 126.5, 124.5, 122.9, 121.9, 30.3. FAB-MS calc. for C ₂₆ H ₁₈ N ₂ [M + Na] ⁺ 381.14, found 381.2.

Experimental Example 1 Fluorescence Analysis

Cu (ClO ₄ ) with varying copper ion concentrations (0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 equivalents, respectively) in a CH ₃ CN solution containing Compound 1 (6.0 μM) After adding ₂ , the change in fluorescence emission was observed. The excitation wavelength was 360 nm, and FIG. 1 shows a fluorescence titration curve indicating fluorescence intensity at 460 nm for each concentration. As can be seen from FIG. 1, when divalent copper ions were added, a new emission band was observed, centered at 460 nm and increasing in intensity. The detection limit of Compound 1 was 1.0 μM, which met the US EPA limit (˜20 μM) for the detection of divalent copper ions in drinking water.

Experimental Example 2: Divalent Copper Ion Selectivity

Li ⁺ , Na ⁺ , K ⁺ , Rb ⁺ , Cs ⁺ , Ag ⁺ , Cd ²⁺ , Mg ²⁺ , Sr ²⁺ , Ba ²⁺ , Zn ^{2 in} a CH ₃ CN solution containing Compound 1 (6.0 μM) Changes in fluorescence emission were observed after addition of ClO ₄ ^- salts (10 equivalents each) of ⁺ , Ca ²⁺ , Pb ²⁺ , Co ²⁺ , Hg ²⁺ , Cu ²⁺ , and Cu ²⁺ + other metal cations. . As can be seen from FIG. 2A, the addition of Cu ²⁺ ions to Compound 1 or the addition of Cu ²⁺ + other metal cations resulted in a new emission band centered at 460 nm and increasing in intensity. In FIG. 2B, the selectivity for divalent copper ions of Compound 1 is expressed by the magnitude of relative fluorescence intensity. As can be seen from FIGS. 2a and 2b, Compound 1 according to the present invention has a high selectivity among various kinds of metal cations, especially for divalent copper ions, and changes in fluorescence emission for Cu ²⁺ + other metal cations. As can be seen from the results, the selectivity to divalent copper ions is maintained without any interference even when other metal cations are present.

Experimental Example 3: Comparison of Fluorescence Properties of Compounds 1 to 3

In order to verify the importance of probe spacer length for Py-Py ^* interaction upon addition of divalent copper ions, the fluorescence properties of Compound 1 and Reference Compounds 2 and 3 according to the present invention were compared. Compounds 1 to 3 each had a concentration of 6.0 μM to which 10 equivalents of Cu (ClO ₄ ) ₂ in CH ₃ CN solution were added (excitation wavelength: 360 nm).

3A shows the fluorescence emission spectrum observed when the divalent copper ions of Compounds 1 to 3 are added, and FIG. 3B shows the relative fluorescence intensity at 460 nm for each compound as a bar graph. As shown in FIGS. 3A and 3B, in contrast to Compound 1, Compounds 2 and 3 did not show significant excimer release even when bivalent copper ions were added.

Experimental Example 4: Job Plot Measurement

In order to quantify the rate of complex formation between compound 1 and divalent copper ions, Job plot measurements were performed with varying concentrations of compound 1 and divalent copper ions. The plotting results are shown in FIG. 4, where the difference in absorbance at 360 nm is plotted against the mole fraction of compound 1 at a total constant concentration of 10 μM in CH ₃ CN solution. As can be seen from FIG. 4, the maximum value of the absorbance difference was observed at mole fraction 0.65, which is close to the typical ligand mole fraction (0.66) for the 2: 1 ligand to metal complex.

1 is a graph showing a gradual change in the fluorescence spectrum of the compound of Formula 1 according to the addition of divalent copper ions, a fluorescence titration curve showing the fluorescence intensity at 460nm for each concentration.

FIG. 2A is a graph illustrating fluorescence intensities according to wavelengths of fluorescence emission after adding various kinds of metal cations to the compound of Formula 1, and FIG. 2B illustrates various kinds of metal cations including divalent copper ions of Compound 1. The relative fluorescence intensity magnitude at 460 nm for is shown as a bar graph.

FIG. 3A shows the fluorescence emission spectrum observed upon addition of the divalent copper ions of Compounds 1 to 3, and FIG. 3B shows the relative fluorescence intensity at 460 nm for each compound in a bar graph.

FIG. 4 illustrates the results of performing job plots with varying concentrations of compounds 1 and 2 in order to quantify the complex formation rate between compounds 1 and 2.

5a to 5c schematically show the lowest energy structures for the dimers of compounds 1 to 3, in which hydrogen bonds are indicated by pink dotted lines.

Figure 6a, 6b and 6c are diagrams illustrating the minimum energy structures of the LUMO of each of the compounds 1-Cu ²⁺ complex, compound 1-Cu ²⁺ HOMO, and the compound 1-Cu ²⁺ complex of the conjugate.

Claims (4)

Pyrene derivative represented by the following general formula (1) having divalent copper ion selectivity: [Formula 1]

. A method of preparing a pyrene derivative represented by the following Chemical Formula 1 by reacting 1-pyrenecarboxylic acid, dicyclohexylcarbodiimide and 8-aminoquinoline in the presence of a 4- (dimethylamino) pyridine catalyst: [Formula 1]

A method for selectively detecting divalent copper ions in a sample using a pyrene derivative represented by the following formula (1): [Formula 1]

. The divalent copper ions according to claim 3, wherein the selective detection of the divalent copper ions is performed by measuring an increase in fluorescence emission according to excimer emission observed after adding a pyrene derivative represented by Chemical Formula 1 to the sample. A method for selectively detecting copper ions.

Images