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Wen Ren ; Yuling Deng ; Jacob D. Ward ; Rebecca Vairin ; Ruoli Bai b ; Hashini I. Wanniarachchi , et al.
Abstract: The synthesis and evaluation of small-molecule inhibitors of tubulin polymerization remains a promising approach for the development of new therapeutic agents for cancer treatment. The natural products colchicine and combretastatin A-4 (CA4) inspired significant drug discovery campaigns targeting the colchicine site located on the beta-subunit of the tubulin heterodimer, but so far these efforts have not yielded an approved drug for cancer treatment in human patients. Interest in the colchicine site was enhanced by the discovery that a subset of colchicine site agents demonstrated dual functionality as both potent antiproliferative agents and effective vascular disrupting agents (VDAs). Our previous studies led to the discovery and development of a 2-aryl-3-aroyl-indole analogue (OXi8006) that inhibited tubulin polymerization and demonstrated low nM IC50 values against a variety of human cancer cell lines. A water-soluble phosphate prodrug salt (OXi8007), synthesized from OXi8006, displayed promising vascular disrupting activity in mouse models of cancer. To further extend structure-activity relationship correlations, a series of 6-aryl-3-aroyl-indole analogues was synthesized and evaluated for their inhibition of tubulin polymerization and cytotoxicity against human cancer cell lines. Several structurally diverse molecules in this small library were strong inhibitors of tubulin polymerization and of MCF-7 and MDA-MB-231 human breast cancer cells. One of the most promising analogues (KGP591) caused significant G2/M arrest of MDA-MB-231 cells, disrupted microtubule structure and cell morphology in MDA-MB-231 cells, and demonstrated significant inhibition of MDA-MB-231 cell migration in a wound healing (scratch) assay. A phosphate prodrug salt, KGP618, synthesized from its parent phenolic precursor, KGP591, demonstrated significant reduction in bioluminescence signal when evaluated in vivo against an orthotopic model of kidney cancer (RENCA-luc) in BALB/c mice, indicative of VDA efficacy. The most active compounds from this series offer promise as anticancer therapeutic agents.
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Keywords: Inhibitors of tubulin polymerization ; Vascular disrupting agents ; Indole synthesis ; Molecular docking ; Antiproliferative agents ; Inhibitors of cell migration
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Purchased from AmBeed: 128796-39-4 ; 10365-98-7 ; 98-80-6 ; 98437-24-2 ; 5720-05-8 ; 64-86-8 ; 13331-27-6 ; 206551-43-1 ; 63139-21-9 ; 622864-48-6 ; 5720-07-0 ; 87199-18-6 ; 30418-59-8 ; 4521-61-3 ; 4521-61-3 ; 87199-18-6 ; 64-86-8 ; 64-86-8 ; 128796-39-4 ; 5720-05-8 ; 64-86-8
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Brian P. Radka ; Taewoo Lee ; Ivan I. Smalyukh ; Timothy J. White ;
Abstract: Polymer stabilized cholesteric liquid crystals (PSCLCs) are electrically reconfigurable reflective elements. Prior studies have hypothesized and indirectly confirmed that the electro-optic response of these composites is associated with the electrically mediated distortion of the stabilizing polymer network. The proposed mechanism is based on the retention of structural chirality in the polymer stabilizing network, which upon deformation is spatially distorted, which accordingly affects the pitch of the surrounding low molar-mass liquid crystal host. Here, we utilize fluorescent confocal polarized microscopy to directly assess the electro-optic response of PSCLCs. By utilizing dual fluorescent probes, sequential imaging experiments confirm that the periodicity of the polymer stabilizing network matches that of the low molar-mass liquid crystal host. Further, we isolate distinct ion-polymer interactions that manifest in certain photopolymerization conditions.
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Purchased from AmBeed: 174350-06-2 ; 124729-02-8 ; 15155-41-6 ; 123560-48-5 ; 5720-07-0 ; 1643-19-2
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BRIAN P. RADKA ;
Abstract: Dynamic reconfiguration of optical materials has and continues to be of significant interestin technological utility in displays, healthcare, automotive, aerospace, and architecture. This thesis is concerned with so-called “polymer stabilized” cholesteric liquid crystals (PSCLCs), material systems in which application of an electric field can adjust the position or bandwidth of a selective reflection. These material systems are based upon the cholesteric liquid crystal (CLC) phase, which nascently self-organizes into a periodic helical structure in which refractive index modulation results in a polarization-specific Bragg reflection. Depending on material composition, application of an electric field to a CLC can result in reflection switching or “tuning” (e.g., shift in reflection wavelength) but typically these electro-optic responses are limited in magnitude or response time (often taking days for the reflection to recover). Comparatively, the integration of small concentrations of polymer, to “stabilize” the CLC phase, creates a material system that can undergo a dynamic and reversible electro-optic response. This thesis extends upon a number of prior examinations (generally focused on phenomena or functionality) undertaken at the Air Force Research Laboratory, that have demonstrated myriad responses including reflection bandwidth broadening, reflection wavelength tuning, and switching. The systematic investigations presented in this thesis directly elucidate the underlying electromechanical mechanism that is critical to enabling further optimization and enhancement of electro-optic response necessary for implementation in functional utility in applications. More specifically, the first aim of this thesis focuses on the formation and importance of the retention of structural chirality in the polymer stabilizing network (PSN) and the intermolecular interactions between the PSN and the non-reactive CLC host. Notably, PSCLCs prepared with non-liquid-crystalline polymer networks confirm that the chiral templating does not require the monomeric precursors to be liquid crystalline. Further, the cation-mediated electromechanical response of the deformation of the polymer network was correlated to be directly associated with the host (via distinctive confocal fluorescent experiments). The second aim of this thesis is focused on identifying and understanding the interactions between the polymer network and ions, through exploring the electrochemical properties in addition to the electro-optic response. The effect of polymerization on the electrical properties was investigated through impedance spectroscopy with mixtures prepared with metallic salts, ionic liquids, and ionic polymers. The electrical properties of these formulations were then correlated to the electro-optic response of PSCLCs prepared from them. Finally, informed by these fundamental studies, this thesis explored the molecular engineering of the polymer stabilizing network. This was achieved in two ways, both focused on affecting the crosslink density of the PSN. In the first, a dithiol additive was incorporated into the polymer network through copolymerization with the acrylate functionalized liquid crystalline monomer. This reaction decreases the crosslink density through both chain extension and chain transfer. Compositional studies isolated an optimum crosslink density/concentration to retain structural chirality with maximal elasticity. Second, a monofunctional liquid crystalline monomer was incorporated into the polymer network to decrease crosslink density while retaining high liquid crystalline character in the polymer network. The electromechanical mechanism in this material system enabled the realization of a new electro-optic phenomena in PSCLCs, reflection notch splitting
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Guo, Sheng ; Wu, Yifan ; Luo, Shao-Xiong Lennon ; Swager, Timothy M. ;
Abstract: Heterogenous catalysts with confined nanoporous catalytic sites are shown to have high activity and size selectivity. A solution-processable nanoporous organic polymer (1-BPy-Pd) catalyst displays high catalytic performance (TON > 200K) in the heterogeneous Suzuki–Miyaura coupling (SMC) reaction and can be used for the preparation of the intermediates in the synthesis of pharmaceutical agents. In comparison to the homogeneous catalyst analogue (2,2′-BPy)PdCl2, the heterogenous system offers size-dependent catalytic activity when bulkier substrates are used. Furthermore, the catalyst can be used to create catalytic impellers that simplify its use and recovery. We found that this system also works for applications in heterogenous Heck and nitroarenes reduction reactions. The metal-binding nanoporous polymer reported here represents a versatile platform for size-selective heterogeneous and recyclable catalysts.
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Keywords: nanoporous organic polymer ; heterogeneous catalyst ; Suzuki−Miyaura coupling reaction ; size-selective reaction ; catalyst processing
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Purchased from AmBeed: 128796-39-4 ; 10365-98-7 ; 98-80-6 ; 556-96-7 ; 171663-13-1 ; 71597-85-8 ; 402-43-7 ; 2042-37-7 ; 22385-77-9 ; 16419-60-6 ; 15862-18-7 ; 87199-15-3 ; 171408-84-7 ; 643-58-3 ; 591-50-4 ; 76911-73-4 ; 398-36-7 ; 14871-92-2 ; 5720-07-0 ; 945976-76-1 ; 366-18-7 ; 2920-38-9 ; 623-00-7 ; 24973-49-7 ; 588-59-0 ; 128796-39-4 ; 5723-93-3 ; 17057-88-4 ; 126485-55-0
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CAS No. : | 5720-07-0 |
Formula : | C7H9BO3 |
M.W : | 151.96 |
SMILES Code : | C1=C(C=CC(=C1)OC)B(O)O |
MDL No. : | MFCD00039139 |
InChI Key : | VOAAEKKFGLPLLU-UHFFFAOYSA-N |
Pubchem ID : | 201262 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; for 12h;Heating / reflux; | Method A: Suzuki Coupling [00523] A mixture of tetrakis(triphenylphosphine)palladium(0) (3% equiv.), aryl bromide (1 equiv.), 2 M aqueous sodium carbonate (2.5 equiv.) and boronic acid (1.2 equiv.) in equal amount of toluene and ethanol is refluxed for 12 hours. The reaction is poured into water and extracted with ethyl acetate. The organic layers are washed with base and brine, dried and concentrated. The residue is purified by column chromatography to give the product. ; 2-Hydroxy-4-methoxybenzaldehyde (20 g, 131.4 mmol) was brominated to give <strong>[57543-36-9]5-bromo-2-hydroxy-4-methoxybenzaldehyde</strong> as a light yellow solid, followed by coupling with 4-methoxyphenylboronic acid (750 mg, 4.94 mmol) using method A to give 800 mg (75%) of 4-hydroxy-6,4'-dimethoxybiphenyl-3-carbaldehyde as a light yellow solid. [00550] 1H NMR (360 MHz, DMSO-d6) delta 11.06 (s, br, 1H, OH), 10.04 (s, 1H, CHO), 7.55 (s, 1H), 7.35 (d, J=8.6 Hz, 2H), 6.94 (d, J=8.6 Hz, 2H), 6.63 (s, 1H), 3.81 (s, 3H, OCH3), 3.77 (s, 3H, OCH3). [00551] MS-EI m/z: 258 [M]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Example 58 3-(4.6-Diamino-[1,3,5]triazin-2-yl)-biphenyl-4,4'-diol One equivalent of 5-bromo-2-methoxy-benznitrile (1 mmol) was reacted with 4-methoxyphenylboronic acid (1.05 mmol), following General Procedure G, to give 4,4'-dimethoxy-3-cyanobiphenol in 90percent yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
bis(dibenzylideneacetone)-palladium(0); In 1,4-dioxane; | Reference Example 31 tert-Butyl {(3R)-1-[5-(2-chlorobenzyl)-7-(4-methoxyphenyl)-1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]piperidin-3-yl}carbamate Bis(dibenzylideneacetone)palladium (18 mg), tri-tert-butylphosphonium tetrafluoroborate (22 mg), potassium phosphate (329 mg) and 4-methoxyphenylboronic acid (236 mg) were added to a solution of tert-butyl {(3R)-1-[7-bromo-5-(2-chlorobenzyl)-1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]piperidin-3-yl}carbamate (90 mg) in dioxane (4 ml), and the resulting mixture was stirred with heating at 50°C for 15 hours. The reaction solution was filtered through Celite and washed with tetrahydrofuran and the filtrate was concentrated under reduced pressure. A 10percent aqueous potassium carbonate solution was added to the residue, followed by two runs of extraction with chloroform (50 ml). The organic layer was dried over sodium sulfate and filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (hexane / ethyl acetate = 2/1) to obtain the title compound (10 mg). 1H NMR (300 MHz, CDCl3) delta 7.41-7.37 (m, 1H), 7.26-7.10 (m, 4H), 6.92 (d, J = 8.8 Hz, 1H), 6.52-6.50 (m, 1H), 5.80 (d, J = 16.7 Hz, 1H), 5.66 (d, J = 16.7 Hz, 1H), 3.87 (s, 3H), 3.52-3.50 (m, 1H), 3.37 (s, 3H), 3.07 (s, 3H), 2.80-2.40 (m, 4H), 1.62-1.39 (m, 4H), 1.38 (s, 9H). MS (ESI+) 608 (M++1, 76percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 80℃; for 6h;Inert atmosphere; | General procedure: A 1,4-dioxane solution (3 mL) of 1, arylboronic acid (1.2 equiv), aqueous K2CO3 (2.0 M, 1.0 mL) and Pd(PPh3)4 (3 mol percent) was heated at 80 °C for 6 h under argon atmosphere. After cooling to 20 °C, H2O was added and the reaction mixture was extracted with CH2Cl2 (3×25 mL). The organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, heptane/EtOAc).#10; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 120℃; for 8h;Inert atmosphere; | General procedure: A 1,4-dioxane solution (3 mL) of 1, arylboronic acid (2.2 equiv), aqueous K2CO3 (2.0 M, 1.0 mL) and Pd(PPh3)4 (6 mol percent) was heated at 120 °C for 8 h under argon atmosphere. After cooling to 20 °C, H2O was added and the reaction mixture was extracted with CH2Cl2 (3×25 mL). The organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, heptane/EtAOc).#10; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With potassium phosphate; (NC5H3(N2C7H4(CH2)3CH3)2)NiBr(1+)*Br(1-)=Ni(NC5H3(N2C7H4(CH2)3CH3)2)Br2; triphenylphosphine; In 1,4-dioxane; at 80℃; for 24h;Schlenk technique; | General procedure: To a 50mL Schlenk tube containing benzylic ammonium iodide (0.5mmol), arylboronic acid (2.0mmol), K3PO4 (2.25mmol), castalyst (5molpercent) and PPh3 (20molpercent) were added and the tube was purged with N2 for 3 times. Then 1,4-dioxane (2.0mL), subsequently, was introduced to the tube. The resulted mixture was allowed to stir for 24h at 80°C under atmosphere of N2. After the completion of the reaction, the resulting mixture was filtered through a Celite pad and concentrated under the vacuum and directly purified by flash chromatography to give the desired product. |
82% | With potassium phosphate; palladium diacetate; XPhos; In tetrahydrofuran; at 50℃; for 14h;Sealed tube; Inert atmosphere; | General procedure: The desired amount of substrate, boronic acid (3 equiv), base (3equiv), Pd(OAc)2 (2.5 molpercent) and ligand (5 molpercent) were weighed out as solids, the vial was sealed and purged with argon, then solvent was added and the vial was purged again. The reactions were run for 14 h at the specified temperature. The crude material was filtered through a pad of Celite and washed three times with CHCl3. The solvent was removed under reduced pressure, an internal standard was added and the reaction was analysed by 1H NMR spectroscopy. For purification, the analysed mixture was concentrated, the product extracted with Et2O and filtered through anhydrous MgSO4 and further purified by flash column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | General procedure: To an oven dried round bottomed flask with a stir bar and rubber septum was added 1,4-dibromo-2-nitrobenzene (1) (70 mg, 0.25 mmol), 4-methoxyphenylboronic acid (2) (38 mg, 0.25 mmol), Pd(OAc)2 (4 mg, 7 mol%) and K2CO3 (69 mg, 0.5 mmol). A mixture of THF/H2O (1/1) (2 mL) at 0 C was added by syringe and the resulting mixture was stirred for 4 h at 0 C. The second boronic acid (0.25 mmol) was then added and the resulting mixture was stirred at 25 C for 16 h before quenching the reaction with water (50 mL) and extraction with CH2Cl2. The CH2Cl2 extract was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel. The conversion and product ratios were calculated from the 1H NMR spectra of the crude products, using the integration of the proton para to the nitro group at ca 7.9 ppm (alternatively, integration ofthe proton adjacent to the nitro group at ca 7.7 ppm could be used). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With trisodium tris(3-sulfophenyl)phosphine; palladium diacetate; sodium carbonate; In water; acetonitrile; at 100℃;Inert atmosphere; | General procedure: 31 (1 eq.), boronic acid (1.5 eq.) or pinacol ester [for compound14 (1.5 eq.)], Na2CO3 (9 eq.), Pd(OAc)2 (0.05 eq.) and TPPTS (0.15 eq.)were added to a 10mL round-bottom flask, equipped with a stir bar.Next, the flask was evacuated and refilled with argon. This procedure was repeated three times in total. Next, degassed MeCN(2 mL/mmol SM) and H2O (4 mL/mmol SM) were added to the solids under argon. After 5 min of stirring, the mixture was heatedto 100 C in a pre-heated oil bath. When the starting material was fully consumed (usually 1e3 h), the mixture was cooled to ambient temperature, and neutralized (pH ~ 7) with 0.5M aq. HCl. Themixture was evaporated till dryness, resuspended in MeOH and evaporated (three times). Next, the mixture was adsorbed onto Celite (fromMeOH) and eluted over a short silica pad (~5 cm) with 20% MeOH/DCM. The liquid was evaporated in vacuo and purified by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In toluene; at 110.0℃; for 3.0h; | General procedure: To an argon degassed solution of 6-halogeno-2,4-dichloropyrido[2,3-d]pyrimidine 6 or 7 (0.5 mmol) in toluene (6mL) the desired (Het)aryl boronic acid was added then (1.5 equiv)potassium carbonate and (0.05 equiv) Pd(PPh3)4 were also added.The reaction was stirred at 110C for the desired time. After completion of the reaction, 10 mL of water was added, and then extracted with dichloromethane (3 10 mL), the organic layers were combined and dried using magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained material was purified on silica gel by column chromatography (CH2Cl2/PE: 90/10)to afford compounds 8-12. 2,4-Dichloro-6-(4-methoxyphenyl)pyrido[2,3-d]pyrimidine (8) (C14H9Cl2N3O): Compound 8 was obtained from 2,4,6-trichloropyrido[2,3-d]pyrimidine 6 using 4-methoxyphenyl boronic acid (1.05 equiv), as a white solid in 83%yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36%; 7% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In toluene; at 110.0℃; for 3.0h; | General procedure: To an argon degassed solution of 6-halogeno-2,4-dichloropyrido[2,3-d]pyrimidine 6 or 7 (0.5 mmol) in toluene (6mL) the desired (Het)aryl boronic acid was added then (1.5 equiv)potassium carbonate and (0.05 equiv) Pd(PPh3)4 were also added.The reaction was stirred at 110C for the desired time. After completion of the reaction, 10 mL of water was added, and then extracted with dichloromethane (3 10 mL), the organic layers were combined and dried using magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained material was purified on silica gel by column chromatography (CH2Cl2/PE: 90/10)to afford compounds 8-12. 2,4-Dichloro-6-(4-methoxyphenyl)pyrido[2,3-d]pyrimidine (8) (C14H9Cl2N3O): Compound 8 was obtained from 2,4,6-trichloropyrido[2,3-d]pyrimidine 6 using 4-methoxyphenyl boronic acid (1.05 equiv), as a white solid in 83%yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78.6% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 24h;Inert atmosphere; | Under argon protection,<strong>[121554-10-7]5-bromo-2-iodo-benzonitrile</strong> (1.5 g, 5 mmol),4-methoxyphenylboronic acid (1.1 g, 7.5 mmol), K2CO3 (2.8 g, 20 mmol),Tetrakistriphenylphosphorus palladium (0.3g, 0.3mmol) and DMF (6mL) were added to a 30mL two-necked flask, reacted at 120 C for 24h, after TLC monitoring reaction was completed, cooled to room temperature, diluted with ethyl acetate 30mL, added The organic layer was combined with ethyl acetate (25 mL×3), and the organic phase was washed with saturated brine (100 mL×2), dried over anhydrous magnesium sulfate and evaporated.Purified on silica gel column (V ethyl acetate: V petroleum ether = 1:20)There was obtained 1.1 g of 2-(4'-methoxy-phenyl)-5-bromo-benzonitrile (a2) as a white solid, yield 78.6%. |
70% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 2h;Inert atmosphere; | General procedure: A mixture of (4-(tert-butyl)phenyl)boronic acid (7.5 mmol),K2CO3 (20 mmol), Pd[P(C6H5)3]4 (0.25 mmol), and compound 14(5 mmol) in DMF was stirred at 120 C for 24 h under an argonatmosphere. The reaction was diluted with H2O (30 mL) andextracted with ethyl acetate (20 mL 2). The organic phases werecombined, washed with brine (30 mL 3), dried over anhydrousNa2SO4, and concentrated under vacuum to yield the crude product,which was purified by flash column chromatography (0e10%ethyl acetate in petroleum ether). |
Tags: 4-Methoxyphenylboronic acid | Benzene Compounds | Organoboron | Boronic Acids | Aryls | Ethers | Organometallic Reagents | Boronic Acids/Esters | Organic Building Blocks | 5720-07-0
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P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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