The substance identifiers displayed in the InfoCard are the best available substance name, EC number, CAS number and/or the molecular and structural formulas. Give the % of each enantiomer. This property is a direct consequence of the configuration, or orientation of bonded atoms in space, around the chiral center. Call us Toll Free at 1-800-457-3801. The experiments were carried out in a traditional SS apparatus but with collaborative chiral selectors: dibenzoyl-L-tartaric acid (L-DBTA) in the organic phase and hydroxypropyl-b-cyclodextrin (HP-b-CD) in the aqueous phase. eral minutes after the second acetone wash. Poor filtrate into the organic hazardous waste con- Less The diastereomeric salt formed between the (+)-phenylsuccinic acid and (-)-proline is much ___ soluble in isopropyl alcohol than the diastereomeric salt formed between the . C. C. Seaton, CrystEngComm 13, 6583 (2011). Nonsuperposable mirror image molecules are called enantiomers. Moreover, the cold water wash and filtration performed was able to recover the crude solid. It was concluded that the aqueous solubility of the cocrystals is inversely related to their melting points and this trend can be linked to some packing features. S. Fernandez-Lopez, H. S. Kim, E. C. Choi, et al., Nature 412, 452 (2001). [ 1], Succinate can alternatively be formed by reverse activity of SDH. [12][13], Succinic acid can be dehydrogenated to fumaric acid or be converted to diesters, such as diethylsuccinate (CH2CO2CH2CH3)2. Solubility:Not available. PDF Experiment #2 Chemical Resolution of ()-phenylsuccinic Acid With Other information Prepared By Regulatory Affairs Thermo Fisher Scientific Email: EMSDS.RA@thermofisher.com Revision Date 24-Dec-2021 Print Date 24-Dec-2021 Enantioselective separation of R,S-phenylsuccinic acid by biphasic The chiral recognition abilities of the two selectors are opposite . A strong acid (6 M HCI), added in excess to the salt, is used to protonate the water-soluble anion. [citation needed], As a food additive and dietary supplement, succinic acid is generally recognized as safe by the U.S. Food and Drug Administration. << Let the clear solution rest at RT for about 20 min in order to allow for the crystallization of the desired compound. This website collects cookies to deliver a better user experience. [37] The oncogenic mechanism caused by mutated SHD is thought to relate to succinate's ability to inhibit 2-oxogluterate-dependent dioxygenases. acid into separable diastereomers. stream [27], Succinate is produced and concentrated in the mitochondria and its primary biological function is that of a metabolic intermediate. Nonsuperposable mirror image molecules are called enantiomers. Pharmacol. Phenylsuccinic acid Transamination and subsequent decarboxylation of alpha-ketoglutarate leads to the formation of GABA. solid. [6][26] Extra-mitochondrial succinate alters the epigenetic landscape by inhibiting the family of 2-oxogluterate-dependent dioxygenases. Not Intended for Diagnostic or Therapeutic Use. ACP - Reconsideration of surface tension and phase state effects on Space available to draw mechanisms. [10] 1,4-Butanediol (BDO) can be synthesized using succinic acid as a precursor. Who are the experts? [citation needed], Succinate is a key intermediate in the tricarboxylic acid cycle, a primary metabolic pathway used to produce chemical energy in the presence of O2. Target Organs: No data found. Succinate requires specific transporters to move through both the mitochondrial and plasma membrane. Some substance identifiers may have been claimed confidential, or may . [12], In 2004, succinate was placed on the US Department of Energy's list of top 12 platform chemicals from biomass. Department of Chemistry, Khorramabad Branch, Islamic Azad University, Khorramabad, Iran, Kobra Moradifard,Zohreh Derikvand&Azadeh Azadbakht, You can also search for this author in [7] Succinate may thus be produced from enhanced glutamine metabolism via alpha-ketoglutarate or the GABA shunt. [26], Succinate is also a product of the glyoxylate cycle, which converts two two-carbon acetyl units into the four-carbon succinate. Oversuccination occurs when more than one succinate adds to a substrate. Stir for 5 min to allow complete protonation. Succinate is generated from succinyl-CoA by the enzyme succinyl-CoA synthetase in a GTP/ATP-producing step:[22]:Section 17.1, Succinyl-CoA + NDP + Pi Succinate + CoA + NTP, Catalyzed by the enzyme succinate dehydrogenase (SDH), succinate is subsequently oxidized to fumarate:[22]:Section 17.1, SDH also participates in the mitochondrial electron transport chain, where it is known as respiratory complex II. Most often, these pieces can attach to the enzyme only in one particular, orientation. To begin, dissolve 1.94g of racemic phenylsuccinic acid into 50mL of isopropanol in a 100mL round bottom flask. Copyright 2007-2023 Santa Cruz Biotechnology Inc. All Rights Reserved. Chem. <> Vacuum filter and wash the solid with two 15mL Measure the specific rotation and determine the enantiomeric excess of the sample. Learn more about Institutional subscriptions. Molecular Formula:C10H10O4 Molecular Weight:194.19 Section 10 - Stability and Reactivity Chemical Stability:Stable under normal temperatures and pressures. 7, 880 (2005). Don't use too much water, as the product is somewhat soluble and will slowly dissolve. RECEIVE -15-CRUZ CREDITS. The enantiomeric excess (ee) can be calculated with the expression above, where []mixture and []pureenantiomer are the specific rotations of th. A. V. Trask and W. Jones, Top. You'll get a detailed solution from a subject matter expert that helps you learn core concepts. Phenylsuccinic acid Molecular Formula CHO Average mass 194.184 Da Monoisotopic mass 194.057907 Da ChemSpider ID 86155 More details: Names Properties Searches Spectra Vendors Articles More Names and Synonyms Database ID (s) Validated by Experts, Validated by Users, Non-Validated, Removed by Users ()-Phenylsuccinic acid 10424-29- [RN] These chemicals are invariably synthesized by catalysts called, enzymes, which are large chiral molecules specially designed to carry out a particular chemical, transformation. The answer lies in converting the mixture of enantiomers into different compounds - a pair of diastereomers (stereoisomers that are not mitror images of each other). Single crystal structures, thermal analysis, powder X-ray analysis and equilibrium solubility in water and ethanol of the cocrystals were measured. Typically, the less soluble diastere-. 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). Autocrine succinate signaling promotes retinal neovascularization, triggering the activation of angiogenic factors such as endothelial growth factor (VEGF). The solid that results is now-resolved phenylsuccinic acid in its protonated form. As the anion binds the H+, it loses its negative charge and becomes poorly soluble in water. Typi- cally, the less soluble diastere- omeric salt was isolated, the enantiomer of phenylsuccinic acid remains. X`I%&/m{JJt`$@iG#)*eVe]f@{{;N'?\fdlJ!?~|? [12] As an excipient in pharmaceutical products, it is also used to control acidity[21] or as a counter ion. Experts are tested by Chegg as specialists in their subject area. & Azadbakht, A. Co-Crystal of Phenylsuccinic Acid and 4,4'-Bipyridine: Synthesis, Characterization, Crystal Structure, and Supramolecular Interactions. In addition to its metabolic roles, succinate serves as an intracellular and extracellular signaling molecule. Question: In this experiment, racemic (RS)-phenylsuccinic acid is separated (resolved) into optically active cautiouets in a sequence of two steps. Pull air through the solid for a couple of minutes after the last wash to evaporate most of the acetone. Orgo exam notes - Exam noted for organic chemistry. [31] SDH mutations have also been identified in gastrointestinal stromal tumors, renal tumors, thyroid tumors, testicular seminomas and neuroblastomas. The recovered diastereomer must be converted back to the original compound from which it was made -- now a single enantiomer. Stir the mixture with a glass rod for 5 minutes. The solid was recrystallized and the final solid is filtered out. (R)-(-)-Phenylsuccinic acid | C10H10O4 | CID 736145 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological . The first source was natural products , chemicals produced by living organisms. 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. Brief Profile - ECHA - Europa How does one obtain optically active compounds? Growth Des. 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 enantiomeric excess was 35.5% which is the measurement of purity. For this reason, if the biologically produced. This application requires Javascript. Optical Rotation: []=obscl[]=(0.03992/m)( 1 )=60 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. 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! This experiment requires balanced chemical equations and theoretical yield calculation. mix contents for 2 minutes and reflux for 30 minutes. The phenylsuccinic acid acts as the proton donor, while proline is the proton acceptor OH Ph OH OH Ph protoner) acid-base reaction OH SINH phreyhuccinic acid L-prolier (base) equimolarite of R+5) (5) PLUS The two salts shown above are stereoisomers that are not mirror images, so are a pair of diastereomers. D. K. Bucar, R. F. Henry, X. C. Lou, et al., Mol. An ideal solvent would completely precipitate one diastereomer while the other coe remained in the solution. ()-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. ), 2) Recovery of less soluble salt: Vacuum filter the contents of the flask using a medium Buchner funnel. After refluxing, cool flask for 15 minutes, This is an ordinary acid-basc reaction that produces a salt. Once the water is boiling, add hot water to the 125mL flask with the solid. [32] Arg99, His103, Arg252, and Arg281 near the center of the receptor generate a positively charged binding site for succinate. InChI=1S/C10H10O4/c11-9(12)6-8(10(13)14)7-4-2-1-3-5-7/h1-5,8H,6H2,(H,11,12)(H,13,14), CSID:86155, http://www.chemspider.com/Chemical-Structure.86155.html (accessed 08:22, Mar 4, 2023), Validated by Experts, Validated by Users, Non-Validated, Removed by Users, Predicted data is generated using the ACD/Labs Percepta Platform - PhysChem Module, Predicted data is generated using the US Environmental Protection Agencys EPISuite, Click to predict properties on the Chemicalize site, For medical information relating to Covid-19, please consult the. Garcia, Jessica. 1 0 obj omeric salt was isolated, the enantiomer of phenylsuccinic acid remains. SAFETY DATA SHEET - Fisher Sci [39] Other inflammatory cytokines produced by activated macrophages such as tumor necrosis factor or interleukin 6 are not directly affected by succinate and HIF1. Let aspirator run for sev- [7][32] Succinate may enhance adaptive immunity by triggering the activity of antigen-presenting cells that, in turn, activate T-cells. The solid that results is now-resolved phenylsuccinic acid in its protonated form. duce salt. You have the right to unsubscribe at any time by clicking the 'unsubscribe' link in any News & Announcement emails you receive. 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. To begin, dissolve 1 of racemic phenylsuccinic acid into 50mL of isopropanol in a [30] Stimulation of GPR91 triggers at least two signaling pathways in the heart: a MEK1/2 and ERK1/2 pathway that activates hypertrophic gene expression and a phospholipase C pathway which changes the pattern of Ca2+ uptake and distribution and triggers CaM-dependent hypertrophic gene activation. They are potentially separable by ordinary physical methods like different solubility in a given solvent, which allows recovery of a single diastereomer [32] Overall, the EC50 for succinate-GPR91 is in the 2050 uM range. of one compound from a mixture of compounds. Cool 10mL of 6 M HCl in an ice bath and add all of the collected salt to this cold HCl. Share Improve this answer Follow edited Oct 28, 2019 at 15:24 is conducted between the pheny- Pure samples of mirror image molecules. If you study models of chiral molecules, it soon becomes apparent that their, mirror images are not superposable on each other. connect to this server when you are off campus. The acid and base are structurally more complex than HCl and NH3, but the concept is the same. Zohreh Derikvand. is a proton donor making proline At the end of 30 minutes, turn off and remove the heating mantle. 9, 1436 (2009). The proline, its former partner in the salt, remains soluble in the aqueous phase. Chem. [25], Accumulation of fumarate can drive the reverse activity of SDH, thus enhancing succinate generation. [26] As such, succinate links TCA cycle dysfunction or metabolic changes to cell-cell communication and to oxidative stress-related responses. 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. Upon reperfusion, succinate is rapidly oxidized leading to abrupt and extensive production of ROS. If you study models of chiral molecules, it soon becomes apparent that their mirror images are not superposable on each other. Such mirror images represent different stereoisomers , they are different molecules. [35] First, 2-oxoglutarate coordinates with an Fe(II) ion bound to a conserved 2-histidinyl1-aspartyl/glutamyl triad of residues present in the enzymatic center. Part of their specificity lies in how they bind, or attract and hold, the molecular pieces that, are to be fashioned into the product. Through these mechanisms, succinate accumulation has been shown to regulate production of inflammatory cytokines. Santa Cruz Biotechnology, and the Santa Cruz Biotechnology, Inc. logo, Santa Cruz Animal Health, San Juan Ranch, Supplement of Champions, the San Juan Ranch logo, UltraCruz, ChemCruz, ImmunoCruz, ExactaCruz, and EZ Touch are registered trademarks of Santa Cruz Biotechnology, Inc. All trademarks are the property of their respective owners. [29] As of 2016 the inhibition of succinate-mediated ROS production was under investigation as a therapeutic drug target.[29]. Added to cooled 10 mL 6 HCl: Reaction immediately but not cloudy enough You convert the (+)-phenylsuccinic acid to a salt with proline, separate the 2 diastereomers based on solubility differences, and recover the neutral phenylsuccinic acid through the following steps: 1. mix racemic phenylsuccinic acid with isopropyl alcohol; dissolve. This is an ordinary acid-base reaction that produces a salt. [36][37], Succinate inhibition of prolyl hydroxylases (PHDs) stabilizes the transcription factor hypoxia inducible factor (HIF)1. please email the information below to [emailprotected]. First, we exploit its chemical nature it is m acid) by treating it with an optically active biologically produced base, L-proline. GABA is then metabolized by GABA transaminase to succinic semialdehyde. Scratch inside this test tube several minutes until the contents begin to get cloudy. https://doi.org/10.1134/S1063774519070125. )-in short, most biologically produced substances are optically active But the existence of chirality is not by itself a sufficient condition for optical activity. Mass of product dissolved in acetone: 0 Safety Data Sheet It washes away in the acidic water, leaving nearly pure phenylsuccinic acid as the solid.) It is also available as a flavoring agent, contributing a somewhat sour and astringent component to umami taste. Water tums B. R. Khandavilli, et al., Cryst. product contains one or more chiral centers, it is optically active. 2) Calculate the enantiomeric excess if the specific rotation obtained after recrystallization is 103.2. [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. Optically active reagents have long been important, in studies of reaction mechanisms because they may offer glimpses at the molecular details of the process, How does one obtain optically active compounds? To place an order using RMB or to ship to mainland China, please visit www.scbio.cn, Click on image or enlarge button to enlarge. Molecular Formula: C 10 H 10 O 4. in short, most biologically. Show transcribed image text. Specific Gravity/Density:Not available. A. V. Trask, N. Shan, W. D. S. Motherwell, et al., Chem. www.colby.edu/directory-profile-update-form you must use the L. Fbin, Cryst. This is simple since neutral phenylsuccinic acid is poorly soluble in water. Let aspirator run for several minutes after the second acetone wash. Poor filtrate into the organic hazardous waste container. configuration enantiomer, the other diastereomer must be more soluble during the filtration Google Scholar. 4036-30- (S)-(+)-Phenylsuccinic acid >99 223-719-3 Section 3 - Hazards Identification EMERGENCY OVERVIEW Appearance: almost white solid. Collect the purified crystals by vacuum filtration and rinse with 10mL of ice cold water.