(S)-(&)-Phenylsuccinic acid | CAS 4036-30-0 - SCBT RET at mitochondrial respiratory complex 1, the complex normally preceding SDH in the electron transport chain, leads to ROS production and creates a pro-oxidant microenvironment.[29]. 2023 Springer Nature Switzerland AG. For Research Use Only. 4, 339 (2007). Calculate the exact concentration which will be needed to calculate specific rotation. endobj Soc. Melting point-solubility-structure correlations in chiral and racemic [12] Drugs involving succinate include metoprolol succinate, sumatriptan succinate, Doxylamine succinate or solifenacin succinate. Since PHDs have an absolute requirement for molecular oxygen, this process is suppressed in hypoxia allowing HIF1 to escape destruction. This process produced two diastereomers where the more soluble compound was removed by the HCl. F. Toda, K. Tanaka, A. Sekikawa, J. Chem. The solid was recrystallized and the final solid is filtered out. As the anion binds the H+, it loses its negative charge and becomes poorly soluble in water. Specific rotation is defined as [.." - r/le where "-the specific rotation (at 200C using the "D line" of a sodium lamp: units arc (deg x ml. Such mirror images represent different stereoisomers , they are different molecules. Growth Des. [8] ROS then trigger the cellular apoptotic machinery or induce oxidative damage to proteins, membranes, organelles etc. No information found. 9, 1436 (2009). [citation needed], Succinate is one of three oncometabolites, metabolic intermediates whose accumulation causes metabolic and non-metabolic dysregulation implicated in tumorigenesis. Growth Des. Google Scholar. [6][26][31] Upon exiting the mitochondria, succinate serves as a signal of metabolic state, communicating to neighboring cells how metabolically active the originating cell population is. In living organisms, primarily succinate, not succinic acid, is found. of this substance have not been fully investigated. Let the clear solution rest at RT for about 20 min in order to allow for the crystallization of the desired compound. [30] In the second step of mitochondrial export, succinate readily crosses the outer mitochondrial membrane through porins, nonspecific protein channels that facilitate the diffusion of molecules less than 1.5 kDa. Next, place crude solid in a 125mL Erlenmeyer flask and boil 100mL of water in a 250mL Erlenmeyer flask. [42] The other two oncometabolites, fumarate and 2-hydroxyglutarate have similar structures to succinate and function through parallel HIF-inducing oncogenic mechanisms. All you are really doing is exchanging one acid for another so it is hardly an acid/base reaction. Santa Cruz Biotechnology, Inc. is a world leader in the development of products for the biomedical research market. D. K. Bucar, R. F. Henry, X. C. Lou, et al., Mol. The solid that results is now-resolved phenylsuccinic acid in its protonated form. Enantioseparation of Phenylsuccinic Acid Enantiomers Using Aqueous Two Growth Des. [29] If mitochondrial respiratory complex III is unable to accommodate excess electrons supplied by succinate oxidation, it forces electrons to flow backwards along the electron transport chain. [32] The ligand specificity of GPR91 was rigorously tested using 800 pharmacologically active compounds and 200 carboxylic acid and succinate-like compounds, all of which demonstrated significantly lower binding affinity. Curr. Filtration permits discard of the more soluble salt, which cames away one enantiomer () of the phenylsuccinic acid Once the less soluble diastereomeric salt has been isolated, only a single enantiomer of phenylsuccinic acid remains. Molecular Formula: C 10 H 10 O 4. PDF Experiment #2 Chemical Resolution of ()-phenylsuccinic Acid With November 19th, 2018 Japan (1987), 60, 824-827). acid is partially soluble in water, so HCl was used as a strong acid to protonate the anion. Rep. 64, 10381042 (2019). The toxicological The only way that these isomers differ physically is the direction in which they rotate plane-polarized light, their optical activity. astereomer, enantiomers are iden- Specific Gravity/Density:Not available. This work presents more extensive results of separation of phenylsuccinic acid enantiomers by biphasic recognition chiral extraction (BRCE), which is an important intermediate of N-methyl--phensuximide and antitumor agents (in Fig. After refluxing, cool flask for 15 minutes, As a consequence, the mixture cases no net rotation, and appears optically inactive. The phenylsuccinic acid is a proton donor making proline the proton acceptor. [27], Succinate is produced and concentrated in the mitochondria and its primary biological function is that of a metabolic intermediate. F. Toda and H. Miyamoto, Chem. Add 1.73 g of (-)-proline. Take 40mg of the resolved enantiomer and dissolve it in Iml of acetone. Experiment 4: Resolution of Phenylsuccinic Acid When the solution is cooled down at room temperature, the solubility decreases which allows the pure crystals of phenylsuccinic acid to form. Cool 10mL of 6.0 M HCl in an ice bath and add all of the collected salt to this cold HCl. To purify, recrystallize the (S)-phenylsuccinic acid precipitate from water. Your email subscription to News & Announcements has been received. You have the right to unsubscribe at any time by clicking the 'unsubscribe' link in any News & Announcement emails you receive. May cause skin irritation. Melting point-solubility-structure correlations in chiral and racemic Growth Des. 254, 41 (2005). this experiment, a reflux reaction HIF1 is known to induce transcription of more than 60 genes, including genes involved in vascularization and angiogenesis, energy metabolism, cell survival, and tumor invasion. Think of a chinal center as an atom to which four different groups are covalently attached. Alternate Names: Phenylsuccinic acid. is conducted between the pheny- 1112, 1 (2016). Experimental Procedure: In animal models, pharmacological inhibition of ischemic succinate accumulation ameliorated ischemia-reperfusion injury. [6] As such, succinate links cellular metabolism, especially ATP formation, to the regulation of cellular function. OPTICAL RESOLUTION OF 2-PHENYLSUCCINIC ACID (From R. Stephani and V. Cesare, Journal of Chemical Education 74.1226, 1997 1) Background: The purposes of this experiment are to show how enantiomers can be separated if they. Material Safety Data Sheet - Fisher Sci 1035, 203 (2013). Neutral phenylsuccinic [24] This pathway is exploited in metabolic engineering to net generate succinate for human use. 17, 550 (2017). [15], Succinic acid is a precursor to some polyesters and a component of some alkyd resins. [9], Like most simple mono- and dicarboxylic acids, it is not harmful but can be an irritant to skin and eyes. Once it was cooled, the purified crystals are collected via vacuum filtration and the final product came out to be 0.399g, thus our concentration being 0.0399g. Immediately retum the contents to the boiling flask and swirl. Heat and gently swirl the mixture on the hot plate until all the solid dissolves (add a little more water if the entire solid is not in solution just as the solution begins to gently boil). Stir the mixture with a glass rod for 5 minutes. Jump to main content Jump to site nav. The acid and base are structurally more complex than HCl and NH3, but the concept is the same. Orgo I Lab 4 - orgo - Lexxus Pen Organic Chemistry I Lab Section 803 9 Once the water is boiling, add hot water to the 125mL flask with the solid. [36][37], Succinate inhibition of prolyl hydroxylases (PHDs) stabilizes the transcription factor hypoxia inducible factor (HIF)1. [29] As of 2016 the inhibition of succinate-mediated ROS production was under investigation as a therapeutic drug target.[29]. Part of their specificity lies in how they bind, or attract and hold, the molecular pieces that, are to be fashioned into the product. [33] Therapies targeting succinate to reduce cardiovascular risk and hypertension are currently under investigation.[28]. Neutral phenylsuccinic acid is partially soluble in water, so HCl was used as a strong acid to protonate the anion. Share Improve this answer Follow edited Oct 28, 2019 at 15:24 Cloudiness and then crystals should gradually form.) It now must be recovered from the salt (the second step). Autocrine succinate signaling promotes retinal neovascularization, triggering the activation of angiogenic factors such as endothelial growth factor (VEGF). For a compound to be optimally pure, it would have to reach up to 171. Vacuum filter and wash the solid with two 15mL volumes of cold water. [24][27] In rodents, mitochondrial concentrations are approximately ~0.5 mM[6] while plasma concentration are only 220 M. S. Mittapalli, M. K. C. Mannava, U. Expert Answer. OPTICAL RESOLUTION OF 2-PHENYLSUCCINIC ACID, (From R. Stephani and V. Cesare, Journal of Chemical Education, The purposes of this experiment are to show how enantiomers can be separated if they are converted into a, mixture of diastereomers and to understand how careful choice of solvent can permit selective precipitation. This property is a direct consequence of the configuration, or orientation of, bonded atoms in space, around the chiral center. Garcia, Jessica. 2) Calculate the enantiomeric excess if the specific rotation obtained after recrystallization is 103.2. The 'Substance identity' section is calculated from substance identification information from all ECHA databases. Add 1.15g of finely ground (s)-proline & a magnetic stir bar then mix contents for 2 minutes and reflux for 30 minutes. Cover the beaker or the vial with a watch glass, and keep the beaker covered at all times unless you need to access its contents! [6][38], Metabolic signaling involving succinate can be involved in inflammation via stabilization of HIF1-alpha or GPR91 signaling in innate immune cells. First, we exploit its chemical nature it is an acid) by treating it with an optically active biologically produced base, L-proline. In order to recrystallize the solid, boiling water was added to the solid until it fully dissolves to achieve a complete homoge-nous mixture. %PDF-1.4 Chem. 48, 5009 (2006). sion of an enantiomer to a di- High concentrations of succinate will mimic the hypoxia state by suppressing PHDs,[37] therefore stabilizing HIF1 and inducing the transcription of HIF1-dependent genes even under normal oxygen conditions. >> Space available to draw mechanisms. [6][23] Under conditions of succinate accumulation, rapid oxidation of succinate by SDH can drive reverse electron transport (RET). [39] Other inflammatory cytokines produced by activated macrophages such as tumor necrosis factor or interleukin 6 are not directly affected by succinate and HIF1. Phenylsuccinic acid Most often, these pieces can attach to the enzyme only in one particular orientation. . mix contents for 2 minutes and reflux for 30 minutes. Target Organs: No data found. Dysregulation of succinate synthesis, and therefore ATP synthesis, happens in some genetic mitochondrial diseases, such as Leigh syndrome, and Melas syndrome, and degradation can lead to pathological conditions, such as malignant transformation, inflammation and tissue injury.[6][7][8]. If you study models of chiral molecules, it soon becomes apparent that their mirror images are not superposable on each other. Copyright 2007-2023 Santa Cruz Biotechnology Inc. All Rights Reserved. [5], Historically, succinic acid was obtained from amber by distillation and has thus been known as spirit of amber. ACD/Labs Percepta Platform - PhysChem Module, US Environmental Protection Agencys EPISuite, Compounds with the same molecular formula, Search Google for structures with same skeleton, CAUTION: May irritate eyes, skin, and respiratory tract. [19] Succinic acid is used primarily as an acidity regulator[20] in the food and beverage industry. Through these mechanisms, succinate accumulation has been shown to regulate production of inflammatory cytokines. Please note, if you are trying to access wiki.colby.edu or [28], The activity of succinate dehydrogenase (SDH), which interconverts succinate into fumarate participates in mitochondrial reactive oxygen species (ROS) production by directing electron flow in the electron transport chain. [40] In spite of a general downregulation of the TCA cycle under these conditions, succinate concentration is increased. 3) Recovery of resolved acid: Add all of the solid to 8 mL of ice-cold 6 M HCl in a small beaker or glass tube, place the sample in an ice bath. Course Hero is not sponsored or endorsed by any college or university. [5], As a radical group it is called a succinyl (/sksnl/) group. 7, 4 (2007). Shop DL-Phenylsuccinic acid, 98+%, Thermo Scientific Chemicals at Fishersci.com Typi- cally, the less soluble diastere- omeric salt was isolated, the enantiomer of phenylsuccinic acid remains. The glyoxylate cycle is utilized by many bacteria, plants and fungi and allows these organisms to subsist on acetate or acetyl CoA yielding compounds. The phenylsuccinic acid gave up two positives, so it is a dianion. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. [6] The intermediate is made available for biosynthetic processes through multiple pathways, including the reductive branch of the TCA cycle or the glyoxylate cycle, which are able to drive net production of succinate. The possibility of why the specific rotation was so low was because the concentration might have been too low to consider in the first place. vacuum filter the reaction mixture & wash salt with 2 15mL of acetone. cally, the less soluble diastere- www.colby.edu/directory-profile-update-form you must use the Accumulation of either fumarate or succinate reduces the activity of 2-oxoglutarate-dependent dioxygenases, including histone and DNA demethylases, prolyl hydroxylases and collagen prolyl-4-hydroxylases, through competitive inhibition. Keep adding hot water until the solid fully dissolves. Moreover, the cold water wash and filtration performed was able to recover the crude solid. [7] Succinate may thus be produced from enhanced glutamine metabolism via alpha-ketoglutarate or the GABA shunt. Allow the flask to air-cool about 10 min. The phenylsuccinic acid is a proton donor making proline the proton acceptor. Inhalation: [30][32], Extracellular succinate regulates cardiomyocyte viability through GPR91 activation; long-term succinate exposure leads to pathological cardiomyocyte hypertrophy. [37][41] Loss-of-function mutations in the genes encoding succinate dehydrogenase, frequently found in hereditary paraganglioma and pheochromocytoma, cause pathological increase in succinate. Exact concentration: 0 10 mL=0. 24, 861 (1995). The recovered solid is the less-soluble diastereomeric salt of the pair that you made. with another chiral molecule. L. Fbin, Cryst. Succinate thus serves as a direct electron donor to the electron transport chain, and itself is converted into fumarate. succinic acid and proline to pro- Pharmacol. May cause eye, skin, and respiratory 4 0 obj Nonsuperposable mirror image molecules are called enantiomers. Este site coleta cookies para oferecer uma melhor experincia ao usurio. [7] For dendritic cells, succinate functions as a chemoattractant and increases their antigen-presenting function via receptor stimulated cytokine production. The solubility of the complexes is poor in the top phase, where H 2 A has better solubility than in the bottom phase. Specific Gravity/Density:Not available. In addition to its metabolic roles, succinate serves as an intracellular and extracellular signaling molecule. Enzymes required for the GABA shunt are expressed in neurons, glial cells, macrophages and pancreatic cells. [32] Arg99, His103, Arg252, and Arg281 near the center of the receptor generate a positively charged binding site for succinate. 3) Recovery of resolved acid: Add all of the solid to 8 mL of ice-cold 6 M HCl in a small beaker or glass tube, place the sample in an ice bath. Add 1 of finely ground (s)-proline & a magnetic stir bar then ACD/Labs Percepta Platform - PhysChem Module, US Environmental Protection Agencys EPISuite, Compounds with the same molecular formula, Search Google for structures with same skeleton, CAUTION: May irritate eyes, skin, and respiratory tract. Structure, properties, spectra, suppliers and links for: (+)-Phenylsuccinic acid, 4036-30-. [26] Alternative, succinate can be released into the extracellular milieu and the blood stream where it is recognized by target receptors. T. Friscic, L. Fabian, J. C. Burley, et al., Chem. May cause eye irritation. MONOCLONAL MOUSE ANTI-RABBIT/GOAT SECONDARY ANTIBODIES, POLYCLONAL GOAT/RABBIT ANTI-MOUSE SECONDARY ANTIBODIES, ISOTYPE SPECIFIC MOUSE IgG BINDING PROTEINS, PROTEIN A, G-PLUS & L AGAROSE IP REAGENTS, NUCLEOTIDES, PEPTIDES, PROTEINS & AMINO ACIDS, AUTORADIOGRAPHY FILM, TAPE AND PLASTIC WRAP. % Don't use too much water, as the product is somewhat soluble and will slowly dissolve. 2. add (-) proline, then heat the mixture at reflux for 30 minutes then allow . Lett. Stir for 5 min to allow complete protonation. Molecular Formula: C 10 H 10 O 4. M. J. Zaworotko, Cryst. The difference, however, is subtle Pure samples of mirror image molecules behave identically toward physical tests like melting and boiling points and solubility in given solvents The only way that these isomers differ physically is the direction in which they rotate plane-polarized light -their optical activity. A suitable solvent is found by trial and error. stream DL-Phenylsuccinic acid, 98+%, Thermo Scientific Chemicals The impact of chirality is assessed via comparison of structural features and properties of binary cocrystals. InChI=1S/C4H6O4/c5-3(6)1-2-4(7)8/h1-2H2,(H,5,6)(H,7,8), InChI=1/C4H6O4/c5-3(6)1-2-4(7)8/h1-2H2,(H,5,6)(H,7,8), Except where otherwise noted, data are given for materials in their, Precursor to polymers, resins, and solvents. T. R. Shattock, K. K. Arora, P. Vishweshwar, and M.J.Zaworotko, Cryst. frothy This is an ordinary acid-base reaction that produces a salt. [12][13], Succinic acid can be dehydrogenated to fumaric acid or be converted to diesters, such as diethylsuccinate (CH2CO2CH2CH3)2. 7, 1291 (2007). Subsequently, the primary substrate enters the binding pocket and lastly dioxygen binds to the enzyme-substrate complex. Generated succinate is then available for either energy production or biosynthesis. [6][26][38] PHDs hydroxylate proline in parallel to oxidatively decarboxylating 2-oxyglutarate to succinate and CO2. Let aspirator run for several minutes after the second acetone wash. Poor filtrate into the organic hazardous waste container. ()-phenylsuccinic acid N CO 2H H H (-)-Proline Week 1: Resolution of ()-phenylsuccinic acid Procedure In a clean, dry, 250 mL round-bottomed flask, dissolve 2.9 g of ()-phenylsuccinic acid in 75 mL of 2-propanol.
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