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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Gentisic acid is a natural product isolated and purified from the roots of Gentiana scabra Bunge.
Synonyms: Gentisic Acid; NSC 78825; NSC 49098
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Auxetic Liquid Crystal Elastomers: Overcoming Barriers to Scale-Up
Berrow, Stuart R ; Raistrick, Thomas ; Mandle, Richard J ; Gleeson, Helen F ;
Abstract: The observation of auxetic behaviour (i.e. negative Poisson’s ratio) in liquid crystal elastomers (LCEs) presents an exciting opportunity to explore application areas previously inaccessible to LCEs. Since its initial discovery, research has focused on improving understanding of the underpinning physics that drives the auxetic response, the structure-property relationships that enable the response to be tuned, and LCE properties such as the refractive index. However, the auxetic LCE materials reported to date have made use of either mechanical strain during fabrication, or unreactive ‘templates’ to stabilize the nematic ordering in the precursors. The latter approach provides excellent monodomain films, but there is unavoidable anisotropic shrinkage of the LCE. Both processes previously employed create complications towards manufacturing and scale-up. In this article, we report the first example of an auxetic LCE synthesized through surface alignment without the use of a non-reactive ‘template’ and thus without the need for a washout. The LCE includes both terminally and laterally attached mesogens, presents an auxetic threshold of 76% strain, and displays a comparable dependence of auxetic behaviour on its glass transition temperature as that reported in the literature. This work presents an exciting milestone in the journey towards realizing applications for auxetic LCEs.
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Keywords: Liquid crystal elastomer ; Auxetic ; Mechanical metamaterials ; Elastomer ; Network
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Hassan, Sara A ; Zaater, Marwa A ; Abdel-Rahman, Islam M ; Ibrahim, Elsayed A ; El Kerdawy, Ahmed M ; Abouelmagd, Sara A
Abstract: The development of new forms of existing APIs with enhanced physicochemical properties is critical for improving their therapeutic potential. In this context, ionic liquids (ILs) and deep eutectic solvents (DESs) have gained significant attention in recent years due to their unique properties and potential for solubility enhancement. In this study, we explore the role of different counterparts in the formation of IL/DESs with piperine (PI), a poorly water-soluble drug. After screening a library of fourteen counterpart molecules, ten liquid PI-counterpart systems were developed and investigated. Thermal analysis confirmed the formation of IL/DES, while computational and spectroscopic studies revealed that hydrogen bonding played a crucial role in the interaction between PI and the counterparts, confirming DES formation. The solubility enhancement of PI in these systems ranged from ∼ 36 % to 294 %, with PI-Oxalic acid (OA) exhibiting the highest saturation solubility (49.71 μg/mL) and PI-Ibuprofen (IB) the lowest (17.23 μg/mL). The presence of hydrogen bonding groups in counterparts was key to successful DES formation. A negative correlation was observed between solubility and logP (r = − 0.75, p* = 0.0129), while a positive correlation was found between solubility and normalized polar surface area (PSA) (r = 0.68, p* = 0.029). PI-OA and PI-IB were located at the extreme ends of these regression lines, further validating the relationship between these properties and solubility enhancement. These findings highlight essential aspects of rational IL/DES design, optimizing their properties for broader applications.
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CAS No. : | 490-79-9 |
Formula : | C7H6O4 |
M.W : | 154.12 |
SMILES Code : | OC(=O)C1=C(O)C=CC(O)=C1 |
Synonyms : |
Gentisic Acid; NSC 78825; NSC 49098
|
MDL No. : | MFCD00002460 |
InChI Key : | WXTMDXOMEHJXQO-UHFFFAOYSA-N |
Pubchem ID : | 3469 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-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 |
---|---|---|
94% | With sulfuric acid; for 16h;Reflux; | Compound 1 (2,5-Dihydroxybenzoic acid) (5.00 g, 32.5 mmol) was dissolved in methanol (33 mL) and concentrated sulphuric acid (5 mL) added drop wise. The reaction mixture was heated at ref lux for 16 h. The reaction mixture was cooled to room temperature and the solvent removed in vacuo. The residue was treated with saturated aqueous NaHCO3 until pH 7 was reached. The product was extracted with ethyl acetate (50 mL x 3) and the combined organic layer was washed with brine (20 mL), dried (Mg504), filtered and the filtrate was evaporated to afford the product as a light brown powder(5.13 g, 94%). 1H NMR (CDCI3) O 10.35 (5, 1H), 7.29 (d, J= 3.2 Hz, 1H), 7.02 (dd, J= 8.7, 3.2 Hz, 1H), 6.89 (d, 8.7 Hz, 1H), 4.69 (5, 1H), 3.95 (5, 1H); 13C NMR (CDCI3) O 170.1, 155.8, 147.6, 124.0, 118.5, 114.7, 112.1, 52.4; HRMS (ESI): [M-H] calcd. for C8H704 167.0344, found 167.0359. |
88.1% | With sulfuric acid; at 65℃; for 12h; | To a 250 mL flask equipped with a magnetic stirrer, 15.4 g (0.1 mol) of 2,5-dicumylbenzoic acid, 100 mL of methanol and 10 mL of concentrated sulfuric acid were added and the temperature was raised to 65 C and refluxed for 12 hours.The reaction was cooled and poured into 1000 mL of water. The precipitate was collected by filtration, washed three times with saturated sodium hydrogencarbonate solution, and washed with water in a vacuum oven at 60 C for 24 hours to obtain a compound represented by the formula (4) = 1) 14. 8 g, yield 88.1% |
67% | With thionyl chloride; at 0℃;Reflux; Inert atmosphere; | General procedure: Thionyl chloride (1.16 g, 1.5 equiv) was added drop-wise to a solution of acid (1.0 g, 1.0 equiv) in the corresponding alcohol (15 ml) at 0&d eg;C. The solution was refluxed under a nitrogen atmosphere until all starting material was consumed (TLC monitoring). Then the solvent was removed under vacuo and the residue was purified by silica gel column chromatography eluting with ethyl acetate/n-hexane to afford the corresponding carboxylic esters. |
60% | With sulfuric acid; for 2h;Reflux; | A solution of gentisic acid (10 mmol) and sulfuric acid (0.5 mL) in methanol (20 mL) was refluxed for 2h, then diluted with 10% aq Na2CO3 (10 mL) and extracted with dichloromethane (3 × 10 mL). The combined organic layers were washed withsat aq NaHCO3 (2 × 10 mL), dried (Na2SO4), and concentrated in vacuo. Recrystallization from methanol afforded 88 (1.01 g, 60%) as yellow plates: 1H NMR (CDCl3, 500 MHz) δ 10.36 (s,1H), 7.28 (dd, J = 9.5, 3.5 Hz, 1H), 7.02(dd, J = 9.0, 3.0 Hz, 1H), 6.89 (d, J = 9.0 Hz, 1H), 4.98 (s, 1H), 3.94 (s, 3H);13C NMR (CDCl3, 125 MHz) δ 170.2, 155.7,147.7, 124.1, 118.5, 114.8, 112.2, 52.4; HRMS (ESI) m/z 169.0488 (MH+, C8H8NO4H+requires 169.0456). |
59% | With hydrogenchloride; In 1,4-dioxane; for 12h; | 5 g (32.5 mmol) of 2,5-dihydroxybenzoic acid was well dissolved in 60 mL of methanol, 41 mL (162 mmol) of hydrogen chloride 4M dioxane solution was slowly added thereto while stirring. After the reaction for 12 hours, solvent was removed and the resulting solution was extracted with water and ethyl acetate. An organic layer thus separated was neutralized with sodium bicarbonate, dried over anhydrous magnesium sulfate, and filtered off, and then solvent was removed to give 3.2g of the title compound in a yield of 59%.NMR: 1H-NMR(CDCl3) δ 7.2O(1H, d, J=3.1Hz), 6.95(1H, dd, J=3.1Hz, 9.2Hz), 6.77(1H, d, J=9.2Hz), 3.91(3H, s)Mass(EI) 168(M++1) |
2,5-Dihydroxybenzoic acid (4 g) is dissolved in 20 mL of methanol. To the solution, 3 mL of concentrated sulfuric acid is added. The reaction mixture is brought to gentle reflux over 24 hours. Methanol is removed and the residue is diluted with water. The compound of interest is extracted into ethyl acetate. The organic layer is extracted with saturated sodium bicarbonate solution and dried over anhydrous sodium sulfate. Solvent is removed and the product is in the form of off-white powders. | ||
With sulfuric acid; for 50h;Reflux; | [00281] To a solution of Example 17a (20.0 g, 130 mmol) in MeOH (200 mL) was added H2S04(8.5 mL). The mixture was heated at reflux for 50 h. The resulting mixture was concentrated under reduced pressure. The residue was washed with sat. NaHC03 (50 mL*2),and then extracted with EtOAc (50 mL*3). The combined organic phase was washed with brine, dried over Na2S04, filtrated and the filtratewas concentrated under reduced pressure to give the crude product Example 17b (20.5 g, yield 94%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | General procedure: To the solution 60% NaH (100 mg, 2.2 mmol) in DMF (5 mL) was added 2,3-dihydroxy benzoic acid at room temperature and stirred for 1 h, then benzyl bromide (0.119 mL, 1 mmol) was added to the above solution and stirred for 7 h. Then the reaction was quenched by adding H2O (20 mL) and the reaction mixture was acidified with 1 N HCl to pH 1-3. The solution was extracted with EtOAc (20 mL), washed by brine (3 × 20 mL) and dried over anhydrous Na2SO4. The solvent was removed under vacuum. The residue was purified by flash chromatography using petroleum ether/ethyl acetate (1:1) to give compound 3a as a white solid (54 mg, 22% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; In methanol; | EXAMPLE 1 4-[2'-Formyl-4'-(m-chlorophenylmethyloxy)phenoxy]butyronitrile (1) 2,5-Dihydroxybenzoic acid, 30 grams (0.195 moles), was heated to reflux with 10 ml conc'd. sulphuric acid in 500 ml methanol for 72 hours. Then it was neutralized with solid sodium bicarbonate and striped in vacuo. The product was extracted with ethyl acetate and the organic extract was dried and stripped in vacuo to give 29.8 grams of methyl 2,5-dihydroxybenzoate of >90% purity. | |
With sulfuric acid; In methanol; | A) A solution of 50 g (0.32 mole) of 2,5-dihydroxybenzoic acid in 260 ml of methanol, at 0 C., was combined with 33 ml of sulphuric acid. The resulting solution was heated to 70 C. under stirring. After 6 hours the reaction mixture was cooled to room temperature and concentrated to small volume under vacuum. The resulting oily layer was taken up with sodium hydroxyde 5N and extracted with ethyl acetate the organic layer was washed with water, dried over sodium sulphate and evaporated under vacuum, to provide 52 g of methyl 2,5-dihydroxybenzoate which were used in the next step as obtained. | |
3a Methyl 2,5-dihydroxybenzoate 2,5-Dihydroxybenzoic acid was converted to its methyl ester using catalytic sulfuric acid in methanol following the same protocol as for esterification 2c in 94% yield. mp 86.4-88.5 C. IR(KBr): cm-1 3346, 1684. |
In methanol; diethyl ether; | EXAMPLE 1 Methyl-2,5-dihydroxybenzoate 2,5-Dihydroxybenzoic acid (30 g) was added to methanol (100 ml) which had been acidified with hydrogen chloride gas. The solution was refluxed for 12 hours when the solvent was removed. The resulting solid was taken up in diethyl ether (200 ml) and washed with water (2*100 ml). The organic layer was dried over magnesium sulphate and the solvent removed under vacuum. The resulting solid (30 g) (m.p. 83-84 C.) was identified as the desired methyl ester. | |
With sulfuric acid; In methanol; | A) A solution of 50 g (0.32 mole) of 2,5-dihydroxy-benzoic acid in 260 ml of methanol, at 0C, was added with 33 ml of sulphuric acid. The resulting solution was heated to 70C under stirring. After 6 hours the reaction mixture was cooled to room temperature and concentrated to small volume under vacuum. The obtained oily layer was taken up with sodium hydroxyde 5N and extracted with ethyl acetate. the organic layer was washed with water, anhydrified over sodium sulphate and evaporated under vacuum. Thus 52 g of methyl 2,5-dihydroxy-benzoate were obtained which were used in the next step as such. |
Tags: 2,5-dihydroxybenzoic acid | Gentisic Acid | Phenols | Carboxylic Acids | Plant Standard | FGF | Organic Building Blocks | Protein Tyrosine Kinase/RTK | Exosome | By Structure | Drug Analysis | 490-79-9
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