Water-soluble photoinitiator having high light absorptivity, and preparation method therefor

Abstract

The present invention relates to a water-soluble photoinitiator having high light absorptivity, and a preparation method therefor. The water-soluble photoinitiator is a compound containing multiple radicals, provides efficient photo-cross-linking, has improved solubility in water so as to be suitable for an aqueous system, exhibits high light absorptivity even for visible light, and exhibits low toxicity, and thus can be more safely and efficiently utilized in various fields.

Description

Water-soluble photoinitiator with high light absorption rate and method for producing the same

[0001] The present invention relates to a water-soluble photoinitiator having high light absorption including multiple cleavage sites and a method for producing the same.

[0002] Photoinitiators are chemical compounds included in various formulations to convert light energy absorbed from ultraviolet and visible light into chemical energy in the form of free radicals. These compounds are typically developed for use in non-polar environments and, due to their hydrophobic nature, exhibit poor solubility in water.

[0003] However, with the recent increase in the use of hydrophilic polymerization conditions, such as in the production of hydrogels, the need for new water-soluble photoinitiators is increasing. The number of water-soluble photoinitiators currently developed is limited, and among them, 2-Hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone [Irgacure 2959 or I2959] has been universally used due to its compatibility with various cell types. However, I2959 has disadvantages such as low solubility in water and lack of reactivity in the visible light region. Recently, lithium phenyl-2,4,6-trimethylbenzoylphosphinate [Lithium phenyl-2,4,6-trimethylbenzoylphosphinate] has been developed with improved solubility and efficient initiation and crosslinking ability in a wide range including the UV region and visible light (400-420 nm). LAP] is widely used. However, LAP has limited applications in biomedical fields due to its low optical absorption in visible light and cytotoxicity at the concentrations used in polymerization reactions.

[0004] The purpose of the present invention is to provide a water-soluble photoinitiator having multiple cleavage sites, which generates more efficient and controlled active species upon photoexcitation, and has high light absorption rate and cell compatibility.

[0005] To achieve the above purpose, the present invention provides a compound represented by the following chemical formula 1:

[0006] [Chemical Formula 1]

[0007]

[0008] In the above chemical formula 1, R is Li + or Mg 2+ can be selected from.

[0009] In addition, the present invention provides a method for producing a compound, comprising the steps of: adding dimethyl phenylphosphonite dropwise to a solution containing a compound represented by the following chemical formula 2 and stirring; adding lithium bromide or magnesium bromide to the stirred mixture and heat-treating it; and filtering and washing the heat-treated mixture.

[0010] [Chemical Formula 2]

[0011]

[0012] In the above chemical formula 2, X1 and X2 can be independently selected from fluorine, chlorine, bromine or iodine.

[0013] In addition, the present invention provides a photoinitiator comprising a compound represented by the above chemical formula 1.

[0014] The water-soluble photoinitiator according to the present invention is a compound containing multiple radicals, which provides an efficient photocrosslinking process, has improved solubility in water and is therefore suitable for aqueous systems, exhibits high light absorption even in visible light, and has low toxicity, so that it has the advantage of being more safely and efficiently utilized in various fields.

[0015] FIG. 1 shows the characteristics of a water-soluble photoinitiator compound according to Example 1 of the present invention, where (a) shows solubility, (b) shows molar extinction coefficient, and (c) shows a compressive strain-stress curve for photocrosslinking of 5 w / v% methacrylated hyaluronic acid (HAMA) with 0.5 w / v% photoinitiator (light source: Omnicure equipped with a 400-500 nm bandpass filter).

[0016] Figure 2 confirms the molar absorption coefficient of a water-soluble photoinitiator compound according to Example 2 of the present invention.

[0017] Figure 3 shows the results of a cytotoxicity test of a water-soluble photoinitiator compound according to Example 1 of the present invention. (a) is the results of a cytotoxicity test according to concentration, and (b) is the results of a cytotoxicity test compared to the control group, lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP).

[0018] Figure 4 is a water-soluble photoinitiator compound according to Example 1 of the present invention. 1 As a result of the H NMR experiment, (a) is the measurement result of lithium isophthaloylbis(phenylphosphinate) (LIP), and (b) is the measurement result of lithium terephthaloylbis(phenylphosphinate) (LTP).

[0019] Hereinafter, the present invention will be described in detail.

[0020]

[0021] The present inventors propose a novel photoinitiator compound containing multiple radicals within its individual molecule, thereby providing a more efficient photocrosslinking process. The reduced amount of photoinitiator required for the process potentially reduces cytotoxicity, making it a safer alternative for a variety of applications. The molecular structure of the photoinitiator according to the present invention exhibits improved water solubility compared to existing photoinitiators, making it suitable for aqueous systems. Experiments have confirmed that the photoinitiator according to the present invention exhibits a significantly higher molar extinction coefficient (ε) at 405 nm, demonstrating improved performance compared to existing photoinitiators. Furthermore, the photoinitiator according to the present invention has been confirmed to exhibit low toxicity. Therefore, the photoinitiator according to the present invention offers a solution to the limitations of existing photoinitiators and offers a safer and more efficient alternative for a variety of applications.

[0022]

[0023] The present invention provides a compound represented by the following chemical formula 1:

[0024] [Chemical Formula 1]

[0025]

[0026] In the above chemical formula 1, R is Li + or Mg 2+ can be selected from.

[0027] Preferably, the compound represented by the above chemical formula 1 may be a compound represented by any one of the following chemical formulas 1-1 to 1-5, but is not limited thereto:

[0028] [Chemical Formula 1-1]

[0029]

[0030] [Chemical Formula 1-2]

[0031]

[0032] [Chemical Formula 1-3]

[0033]

[0034] [Chemical Formula 1-4]

[0035]

[0036] [Chemical Formula 1-5]

[0037]

[0038] The compound may be, but is not limited to, lithium isophthaloylbis(phenylphosphinate) (LIP), lithium terephthaloylbis(phenylphosphinate) (LTP), lithium phthaloylbis(phenylphosphinate) (LPP), magnesium isophthaloylbis(phenylphosphinate) (MIP), or magnesium terephthaloylbis(phenylphosphinate) (MTP).

[0039] The above compound has a molar extinction coefficient (ε) of 550 to 1400 M at a light source of 400 to 420 nm. -1 cm -1 It can be, specifically, a molar extinction coefficient (ε) of 600 to 1300 M at a light source of 400 to 420 nm. -1 cm -1 or 600 to 1200 M -1 cm -1 The compound according to the present invention having the above molar absorption coefficient can exhibit high light absorption in the visible light range.

[0040]

[0041] In addition, the present invention provides a method for producing a compound, comprising the steps of: adding dimethyl phenylphosphonite dropwise to a solution containing a compound represented by the following chemical formula 2 and stirring; adding lithium bromide or magnesium bromide to the stirred mixture and heat-treating it; and filtering and washing the heat-treated mixture.

[0042] [Chemical Formula 2]

[0043]

[0044] In the above chemical formula 2, X1 and X2 can be independently selected from fluorine, chlorine, bromine or iodine.

[0045] The compound represented by the above chemical formula 2 may be a compound represented by the following chemical formula 2-1, chemical formula 2-2, or chemical formula 2-3.

[0046] [Chemical Formula 2-1]

[0047]

[0048] [Chemical Formula 2-2]

[0049]

[0050] [Chemical Formula 2-3]

[0051]

[0052] In the above chemical formula 2-1, chemical formula 2-2 or chemical formula 2-3, X1 and X2 can be independently selected from fluorine, chlorine, bromine or iodine.

[0053] Preferably, X1 and X2 may independently be fluorine or chlorine, and more preferably, X1 and X2 may be chlorine.

[0054]

[0055] The solution containing the compound represented by the above chemical formula 2 may contain 2-butanone or tetrahydrofuran (THF) as a solvent, but is not limited thereto.

[0056] The above stirring step can be performed at 20 to 25°C for 20 to 30 hours.

[0057] Additionally, the stirring step may be performed by mixing the compound represented by the chemical formula 2 and dimethyl phenylphosphonite in a molar ratio of (1 to 3): 1.

[0058] The above lithium bromide or magnesium bromide may be added dissolved in a solvent selected from, but not limited to, 2-butanone or tetrahydrofuran (THF).

[0059] The above heat treatment step can be performed at 40 to 100°C or 40 to 80°C for 10 to 60 minutes or 15 to 30 minutes.

[0060] Additionally, the heat treatment step may be performed by adding 0.5 to 2 mmol or 0.8 to 1.5 mmol of lithium bromide or magnesium bromide per 1 mmol of dimethyl phenylphosphonite.

[0061] The above filtering and washing steps may be performed by filtering the mixture and washing it with a solvent to recrystallize it.

[0062] The solvent may include at least one selected from the group consisting of diethyl ether, tetrahydrofuran, and acetone.

[0063] After the above filtering and washing steps, a drying step may be further included at 20 to 25°C for 1 to 5 hours under vacuum conditions.

[0064] According to one embodiment of the present invention, preferably, LIP can be synthesized by mixing dimethyl phenylphosphonite, the compound of the above formula 2, and lithium bromide in a molar ratio of 1: (2 to 2.5): (2 to 2.5), preferably in a molar ratio of 1: 2.1: 2.3, but is not limited thereto.

[0065] LTP can be synthesized by mixing dimethyl phenylphosphonite, the compound of the above chemical formula 2, and lithium bromide in a molar ratio of 1:1:(1 to 1.5), preferably in a molar ratio of 1:1:1.1, but is not limited thereto.

[0066] LPP can be synthesized by mixing dimethyl phenylphosphonite, the compound of the above chemical formula 2, and lithium bromide in a molar ratio of 1: (1.5 to 2.5): (1.5 to 2.5), preferably in a molar ratio of 1: 2: 2, but is not limited thereto.

[0067]

[0068] In addition, the present invention provides a photoinitiator comprising a compound represented by the above chemical formula 1.

[0069] The compound represented by the above chemical formula 1 may be a compound represented by the above chemical formula 1-1 to chemical formula 1-2 or chemical formula 1-3.

[0070] The above photoinitiator has a molar extinction coefficient (ε) of 550 to 1400 M at a light source of 400 to 420 nm. -1 cm -1 It can be, specifically, a molar extinction coefficient (ε) of 600 to 1300 M at a light source of 400 to 420 nm. -1 cm -1 or 600 to 1200 M -1 cm -1 The photoinitiator according to the present invention, having the above molar absorption coefficient, can exhibit high light absorption in the visible light range.

[0071] The photoinitiator may have a solubility in water of 40 to 150 mg / mL, and specifically, the solubility in water may be 45 to 120 mg / mL or 50 to 100 mg / mL. With the solubility as described above, the photoinitiator according to the present invention may exhibit hydrophilic or water-soluble properties.

[0072] Hereinafter, to aid understanding of the present invention, examples will be given in detail. However, the following examples are intended only to illustrate the scope of the present invention and are not intended to limit its scope. These examples are provided to more fully explain the present invention to those of average skill in the art.

[0073]

[0074] <Example 1> Synthesis of a photoinitiator compound containing lithium

[0075] A water-soluble photoinitiator compound was synthesized using a synthetic method according to the following reaction scheme 1.

[0076] [Reaction Formula 1]

[0077]

[0078]

[0079] 1-1. Synthesis of lithium isophthaloylbis(phenylphosphinate) (LIP)

[0080] 5 mmol of dimethyl phenylphosphonite was added dropwise to 5 mL of 2-butanone containing 2.4 mmol of isophthaloyl chloride, and the mixture was stirred at 25°C under a nitrogen atmosphere for 24 h. Then, 5.5 mmol of lithium bromide was added to 5 mL of 2-butanone under a nitrogen atmosphere, and the mixture was heated at 60°C for 20 min and then cooled to room temperature. The mixture was filtered and washed with 10 mL of diethyl ether. The crude product was recrystallized from a mixture of ethanol and diethyl ether to obtain lithium isophthaloylbis(phenylphosphinate) (LIP) as a pale yellow solid, which was dried under vacuum at 25°C for 3 h.

[0081] Yield: 81%, 1H NMR (600 MHz, DMSO-d6): 8.06 (dd, 2H), 8.00 (t, 1H), 7.81-7.77 (m, 5H), 7.71-7.69 (m, 2H), 7.60-7.57 (m, 4H). 31 P NMR (243 MHz, DMSO-d6):12.34

[0082]

[0083] 1-2. Synthesis of lithium terephthaloylbis(phenylphosphinate) (LTP)

[0084] 5 mmol of dimethyl phenylphosphonite was added dropwise to 5 mL of 2-butanone containing 2.4 mmol of terephthaloyl chloride, and the mixture was stirred at 25°C under a nitrogen atmosphere for 24 h. Then, 5.5 mmol of lithium bromide was added to 5 mL of 2-butanone under a nitrogen atmosphere, and the mixture was heated at 60°C for 20 min and then cooled to room temperature. The mixture was filtered and washed with 10 mL of diethyl ether. The crude product was recrystallized from a mixture of ethanol and diethyl ether to obtain lithium terephthaloylbis(phenylphosphinate) (LTP) as a yellow solid, which was dried under vacuum at 25°C for 3 h.

[0085] Yield: 84%, 1 H NMR (600 MHz, DMSO-d6): 8.01 (s, 4H), 7.67-7.63 (m, 4H), 7.56-7.53 (m, 2H), 7.28 (m, 4H). 31 P NMR (243 MHz, DMSO-d6):15.03

[0086]

[0087] 1-3. Synthesis of lithium phthaloylbis(phenylphosphinate) (LPP)

[0088] 5 mmol of dimethyl phenylphosphonite was added dropwise to 5 mL of 2-butanone containing 2.4 mmol of phthaloyl chloride, and the mixture was stirred at 25°C under a nitrogen atmosphere for 24 h. Then, 5.5 mmol of lithium bromide was added to 5 mL of 2-butanone under a nitrogen atmosphere, and the mixture was heated at 60°C for 20 min and then cooled to room temperature. The mixture was filtered and washed with 10 mL of diethyl ether. The crude product was recrystallized from a mixture of ethanol and diethyl ether to obtain lithium phthaloylbis(phenylphosphinate) (LPP) as a yellow solid, which was dried under vacuum at 25°C for 3 h.

[0089] Yield: 70-80%, 1 H NMR (600 MHz, DMSO-d6)

[0090]

[0091] <Example 2> Synthesis of a photoinitiator compound containing magnesium

[0092] Using magnesium bromide instead of lithium bromide in compounds 1-1 to 1-3, MIP and MTP were synthesized as shown in the following reaction schemes 2 and 3.

[0093]

[0094] 2-1. Synthesis of magnesium isophthaloylbis(phenylphosphinate) (MIP)

[0095] [Reaction Formula 2]

[0096]

[0097] Dimethyl phenylphosphonite (2.7 mmol) was added dropwise to 5 mL of 2-butanone containing 1.2 mmol of isophthaloyl chloride, and the mixture was stirred at 25°C under a nitrogen atmosphere for 24 h. Then, 3.6 mmol of magnesium bromide was added to 5 mL of 2-butanone under a nitrogen atmosphere, and the mixture was heated at 60°C for 20 min and then cooled to room temperature. The mixture was filtered and washed with 10 mL of diethyl ether. The crude product was recrystallized from a mixture of ethanol and diethyl ether to obtain magnesium isophthaloylbis(phenylphosphinate) (MIP) as a pale yellow solid, which was dried under vacuum at 25°C for 3 h.

[0098] Yield: 49%, 1 H NMR (600 MHz, DMSO-d6): 8.06 (dd, 2H), 8.00 (t, 1H), 7.81-7.77 (m, 5H), 7.71-7.69 (m, 2H), 7.60-7.57 (m, 4H). 31 P NMR (243 MHz, DMSO-d6):12.34

[0099]

[0100] 2-2. Synthesis of magnesium terephthaloylbis(phenylphosphinate) (MTP)

[0101] [Reaction Formula 3]

[0102]

[0103] Dimethyl phenylphosphonite (2.7 mmol) was added dropwise to 5 mL of 2-butanone containing 1.2 mmol of terephthaloyl chloride, and the mixture was stirred at 25°C under a nitrogen atmosphere for 24 h. Then, 3.6 mmol of magnesium bromide was added to 5 mL of 2-butanone under a nitrogen atmosphere, and the mixture was heated at 60°C for 20 min and then cooled to room temperature. The mixture was filtered and washed with 10 mL of diethyl ether. The crude product was recrystallized from a mixture of ethanol and diethyl ether to obtain magnesium terephthaloylbis(phenylphosphinate) (MTP) as a yellow solid, which was dried under vacuum at 25°C for 3 h.

[0104] Yield: 52%, 1 H NMR (600 MHz, DMSO-d6): 8.01 (s, 4H), 7.67-7.63 (m, 4H), 7.56-7.53 (m, 2H), 7.28 (m, 4H). 31 P NMR (243 MHz, DMSO-d6):15.03

[0105]

[0106] <Experimental Example 1> Confirmation of the characteristics of photoinitiator compounds

[0107] In order to confirm the characteristics of the water-soluble photoinitiator compound according to the present invention, solubility, molar absorption coefficient, compressive strain-stress curve and mechanical property tests were performed on the photoinitiators prepared according to 1-1 and 1-2 of Example 1 and 2-1 and 2-2 of Example 2, and the results are shown in FIGS. 1 and 2.

[0108]

[0109] 1) Solubility experiment

[0110] A saturated solution of a water-soluble photoinitiator dissolved in deionized water at room temperature (25°C) was prepared, and then filtered through a 0.2 μm hydrophilic syringe filter. The filtered solution was then freeze-dried, and the weight of the resulting solid was measured.

[0111]

[0112] 2) Molar absorption coefficient experiment

[0113] The molar extinction coefficient was measured by dispensing the photoinitiator dissolved in deionized water into a 10 mm diameter quartz cuvette using a UV-vis spectrometer.

[0114]

[0115] 3) Mechanical property test (stress-strain diagram)

[0116] The mechanical properties of the specimens according to the photoinitiator were measured by compressive modulus through compression experiments. The compression tests were performed using an Instron universal testing machine, cylindrically molded specimens according to the ASTM test method, at a speed of 1 mm / min. The compressive modulus was measured by measuring the slope of the stress and strain in the stress-strain curve.

[0117]

[0118] Looking at Fig. 1(a), the solubility of the control group, lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), and the photoinitiators of Examples 1-1 and 1-2 in water was measured, and it was confirmed that the photoinitiator according to the present invention has a better solubility in water than LAP. In particular, it was confirmed that the photoinitiator (LTP) of Example 1-2 has the best solubility. Looking at Fig. 1(b), the molar absorption coefficients of the photoinitiators of Examples 1-1 and 1-2 are shown, and when the molar absorption coefficients of the same concentration were confirmed, LAP (350 M) was higher in the visible light region of 405 nm. -1 cm -1 ) showed a higher ε (molar extinction coefficient) value. Looking at Fig. 1(c), the compressive strength of the polymer (HAMA) crosslinked using the photoinitiator of LAP, Example 1-1, and Example 1-2 as a control group is shown, and it can be confirmed that the polymer crosslinked using the photoinitiator (LIP) of Example 1-1 shows a higher compressive strength than the polymer using LAP. In addition, the polymer synthesized with LTP was confirmed to have mechanical properties at a level similar to that of the polymer crosslinked with LAP.

[0119] In addition, looking at Figure 2, the molar absorption coefficients of the photoinitiators of Examples 2-1 and 2-2 are shown, and when the molar absorption coefficients of the same concentration were confirmed, LAP (350 M) was observed in the visible light region of 405 nm. -1 cm -1 ) showed a higher ε (molar extinction coefficient) value.

[0120] Through this, it can be seen that the photoinitiator according to the present invention is suitable for application under hydrophilic and water-soluble conditions, has an improved molar absorption coefficient, and exhibits improved performance compared to existing photoinitiators.

[0121]

[0122] <Experimental Example 2> Confirmation of cytotoxicity of photoinitiator compounds

[0123] In order to confirm the cytotoxicity of the water-soluble photoinitiator compound according to the present invention, a cytotoxicity test was performed on the photoinitiators prepared in Examples 1-1 and 1-2, and the results are shown in Fig. 3.

[0124] Cytotoxicity experiments were conducted using fibroblasts, and cell viability was measured according to the concentration of the photoinitiator treated using the water-soluble tetrazolium-1 (WST-1) assay.

[0125] Looking at Fig. 3(a), it was confirmed that the photoinitiator (LIP) of Example 1-1 exhibited superior cytocompatibility compared to LAP at the same concentration. Looking at Fig. 3(b), it was confirmed that the photoinitiator (LTP) of Example 1-2 exhibited lower cytotoxicity compared to LAP at the same concentration, indicating improved cytocompatibility.

[0126] Through this, it can be seen that the photoinitiator according to the present invention has reduced cytotoxicity and can be applied as a safe material in various fields.

[0127]

[0128] While specific aspects of the present invention have been described in detail above, it will be apparent to those skilled in the art that these specific descriptions merely represent preferred embodiments and are not intended to limit the scope of the present invention. Therefore, the substantial scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A compound represented by the following chemical formula 1: [Chemical Formula 1] In the above chemical formula 1, R is Li + or Mg 2+ lim.

2. In paragraph 1, The compound represented by the above chemical formula 1 is A compound characterized by being a compound represented by any one of the following chemical formulas 1-1 to 1-5: [Chemical Formula 1-1] [Chemical Formula 1-2] [Chemical Formula 1-3] [Chemical Formula 1-4] [Chemical Formula 1-5] 3. In paragraph 1, The above compound is, Molar extinction coefficient (ε) of 550 to 1400 M at a light source of 400 to 420 nm -1 cm -1 A compound characterized by:

4. A step of adding dimethyl phenylphosphonite dropwise to a solution containing a compound represented by the following chemical formula 2 and stirring; A step of adding lithium bromide or magnesium bromide to the stirred mixture and heat treating it; and A method for preparing a compound, comprising the steps of filtering and washing a heat-treated mixture: [Chemical Formula 2] In the above chemical formula 2, X1 and X2 are independently fluorine, chlorine, bromine or iodine.

5. In paragraph 4, The compound represented by the above chemical formula 2 is A method for producing a compound, characterized in that the compound is represented by the following chemical formula 2-1, chemical formula 2-2 or chemical formula 2-3: [Chemical Formula 2-1] [Chemical Formula 2-2] [Chemical Formula 2-3] In the above chemical formula 2-1, chemical formula 2-2 or chemical formula 2-3, X1 and X2 are independently fluorine, chlorine, bromine or iodine.

6. In paragraph 4, The above heat treatment step is, A method for producing a compound, characterized by heating at 40 to 100°C for 10 to 60 minutes.

7. A photoinitiator comprising a compound represented by the following chemical formula 1: [Chemical Formula 1] In the above chemical formula 1, R is Li + or Mg 2+ lim.

8. In paragraph 7, The compound represented by the above chemical formula 1 is A photoinitiator characterized by being a compound represented by any one of the following chemical formulas 1-1 to 1-5: [Chemical Formula 1-1] [Chemical Formula 1-2] [Chemical Formula 1-3] [Chemical Formula 1-4] [Chemical Formula 1-5] 9. In paragraph 7, The above photoinitiator is, Molar extinction coefficient (ε) of 550 to 1400 M at a light source of 400 to 420 nm -1 cm -1 A photoinitiator characterized by:

10. In paragraph 7, The above photoinitiator is, A photoinitiator characterized by having a solubility in water of 40 to 150 mg / mL.

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