2-디이소프로필라미노에틸메타크릴레이트

Photodynamic therapy is an effective treatment for tumors that involves the administration of light-activated photosensitizers. However, most photosensitizers are insoluble and non-specific. To target the acid environment of tumor sites, we synthesized three poly(ethylene glycol) methacrylate-co-2-(diisopropylamino)ethyl methacrylate (PEGMA-co-DPA) copolymers capable of self-assembly to form pH sensitive nanoparticles in an aqueous environment, as a means of encapsulating the water-insoluble photosensitizer, meso-tetra(hydroxyphenyl)chlorin (m-THPC). The critical aggregation pH of the PEGMA-co-DPA polymers was 5.8-6.6 and the critical aggregation concentration was 0.0045-0.0089 wt% at pH 7.4. Using solvent evaporation, m-THPC loaded nanoparticles were prepared with a high drug encapsulation efficiency (approximately 89%). Dynamic light scattering and transmission electron microscopy revealed the spherical shape and 132 nm diameter of the nanoparticles. The in vitro release rate of m-THPC at pH 5.0 was faster than at pH 7.0 (58% versus 10% m-THPC released within 48 h, respectively). The in vitro photodynamic therapy efficiency was tested with the HT-29 cell line. m-THPC loaded PEGMA-co-DPA nanoparticles exhibited obvious phototoxicity in HT-29 colon cancer cells after light irradiation. The results indicate that these pH sensitive nanoparticles are potential carriers for tumor targeting and photodynamic therapy.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 174(SRC), determined from a structure estimation method(2), indicates that 2-(diisopropylamino)ethyl methacrylate is expected to have moderate mobility in soil(SRC). The pKa of 2-(diisopropylamino)ethyl methacrylate is estimated to be 9.53(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. Even though the vapor pressure, its estimated vapor pressure of 0.053 mm Hg(SRC), determined from a fragment constant method(2), is low environmentally at standard temperature and pressure, 2-(diisopropylamino)ethyl methacrylate exists is a liquid; therefore, 2-(diisopropylamino)ethyl methacrylate may volatilize from dry soil(SRC). Based on analogy to the similar 2-(N,N-dimethylamino)ethyl methacrylate(5), 2-(diisopropylamino)ethyl methacrylate may degrade via abiotic hydrolysis in moist alkaline and neutral soils(SRC). Utilizing the Japanese MITI test, 70% of the Theoretical BOD was reached in 4 weeks for the analogous 2-(N,N-diethylamino)ethyl methacrylate(6) indicating that biodegradation of 2-(diisopropylamino)ethyl methacrylate may be an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 174(SRC), determined from a structure estimation method(2), indicates that 2-(diisopropylamino)ethyl methacrylate is not expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 9.83(3) indicates 2-(diisopropylamino)ethyl methacrylate will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 32(SRC), from an estimated log Kow of 2.79(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). The analogous compound 2-(N,N-dimethylamino)ethyl methacrylate is hydrolyzed at pH 7 and at pH 9 with half-lives of 4.54 days and 3.31 hours, respectively (at 25 °C), whereas it is stable at pH 4(5); 2-(diisopropylamino)ethyl methacrylate is expected to have similar hydrolysis rates(SRC). Utilizing the Japanese MITI test, 70% of the Theoretical BOD was reached in 4 weeks for the analogous 2-(N,N-diethylamino)ethyl methacrylate(6) indicating that biodegradation of 2-(diisopropylamino)ethyl methacrylatemay be an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 2-(diisopropylamino)ethyl methacrylate, which has an estimated vapor pressure of 0.053 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 2-(diisopropylamino)ethyl methacrylate is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 2.9 hours(SRC), calculated from its rate constant of 1.3X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Vapor-phase 2-(diisopropylamino)ethyl methacrylate is also degraded in the atmosphere by reaction with ozone(SRC); the half-life for this reaction in air is estimated to be 24 hours(SRC), calculated from its rate constant of 1.1X10-17 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Based on analogy to a measured nitrate radical rate constant of 4.90X10-15 cu cm/molecule-sec at 25 °C for ethyl methacrylate(3), the atmospheric half-life of 2-(diisopropylamino)ethyl methacrylate is estimated to be about 6.5 days(SRC).

IDENTIFICATION AND USE: 2-(Diisopropylamino)ethyl methacrylate is a liquid with an unpleasant, fishy or fishlike odor and in high concentrations the odor of ammonia. It used as comonomer for polymers and acrylic resins. It is also used as a component of polymersomes which offer a novel drug delivery system for the effective delivery of chemotherapeutics. HUMAN EXPOSURE AND TOXICITY: There is no data available. ANIMAL STUDIES: Diisopropylaminoethyl methacrylate was weakly irritating to skin of guinea pigs and conjunctiva of rabbits.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 2-(diisopropylamino)ethyl methacrylate can be estimated to be 174(SRC). According to a classification scheme(2), this estimated Koc value suggests that 2-(diisopropylamino)ethyl methacrylate is expected to have moderate mobility in soil. The estimated pKa of 2-(diisopropylamino)ethyl methacrylate is 9.53(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

2-(Diisopropylamino)ethyl methacrylate's production and use as a monomer in the synthesis of homopolymers and copolymers(1) and in research for the production of polymeric nanoparticles for drug delivery applications(2,3) may result in its release to the environment through various waste streams(SRC).

AEROBIC: Environmental biodegradation data specific to 2-(diisopropylamino)ethyl methacrylate were not available(SRC, 2015). However, the analogous compound 2-(N,N-diethylamino)ethyl methacrylate, present at 100 mg/L, reached 70% of its theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/L in the Japanese MITI test which classified the compound as readily biodegradable(1).

An estimated BCF of 32 was calculated in fish for 2-(diisopropylamino)ethyl methacrylate(SRC), using an estimated log Kow of 2.79(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

An estimated pKa of 9.53(1) indicates 2-(diisopropylamino)ethyl methacrylate will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). Even though the vapor pressure, its estimated vapor pressure of 0.053 mm Hg(SRC), determined from a fragment constant method(2), is low environmentally at standard temperature and pressure, 2-(diisopropylamino)ethyl methacrylate exists is a liquid; therefore, 2-(diisopropylamino)ethyl methacrylate may volatilize from dry soil(SRC).

The rate constant for the vapor-phase reaction of 2-(diisopropylamino)ethyl methacrylate with photochemically-produced hydroxyl radicals has been estimated as 1.3X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2.9 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of 2-(diisopropylamino)ethyl methacrylate with ozone has been estimated as 1.1X10-17 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 24 hours at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(1). Based on analogy to a measured nitrate radical rate constant of 4.90X10-15 cu cm/molecule-sec at 25 °C for ethyl methacrylate(2), the atmospheric half-life of 2-(diisopropylamino)ethyl methacrylate is estimated to be about 6.5 days(SRC) at an atmospheric concentration of 2.5X10+8 nitrate radicals per cu cm(3). 2-(Diisopropylamino)ethyl methacrylate is an olefin and olefins in surface waters exposed to sunlight react with photo-oxidants (such as hydroxyl radicals, peroxy radicals and singlet oxygen) with a half-life on the order of 25 days(4). The analogous compound 2-(N,N-dimethylamino)ethyl methacrylate is hydrolyzed at pH 7 and at pH 9 (25 °C) with half-lives of 4.54 days and 3.31 hours, respectively, whereas it is stable at pH 4(5); 2-(diisopropylamino)ethyl methacrylate is expected to have similar hydrolysis rates(SRC). 2-(N,N-Diethylamino)ethyl methacrylate hydrolyzed in water to form methacrylic acid and 2-diethylaminoethanol(6)

Occupational exposure to 2-(diisopropylamino)ethyl methacrylate may occur through inhalation and dermal contact with this compound at workplaces where 2-(N,N-diethylamino)ethyl methacrylate is produced or used(SRC). Based on analogy to the similar 2-(N,N-dimethylamino)ethyl methacrylate(1), the general population may be exposed to 2-(diisopropylamino)ethyl methacrylate via dermal contact with consumer products containing polymers made with the compound and resulting migration of residual monomer from the polymer matrix(SRC).