acid into separable diastereomers. [41], Succinate accumulation under hypoxic conditions has been implicated in the reperfusion injury through increased ROS production. [14] Succinate can be used to derive 1,4-butanediol, maleic anhydride, succinimide, 2-pyrrolidinone and tetrahydrofuran. 24, 861 (1995). CAS Number: 635-51-8. Lexxus Pen The first source was natural products chemicals produced by living organisms. Your email subscription to News & Announcements has been received. Not Intended for Diagnostic or Therapeutic Use. comes insoluble in water. properties of this substance have not been fully investigated. It now must be recovered from the salt (the second step). [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. Zohreh Derikvand. Crystallogr. The proline, its former partner in the salt, remains soluble in the aqueous phase. Share Improve this answer Follow edited Oct 28, 2019 at 15:24 Not Intended for Diagnostic or Therapeutic Use. [5] The name derives from Latin succinum, meaning amber. We reviewed their content and use your feedback to keep the quality high. In animal models, pharmacological inhibition of ischemic succinate accumulation ameliorated ischemia-reperfusion injury. Write a review Ask a question. Expert Answer. A suitable solvent is found by trial and error. Optical Rotation: []=obscl[]=(0.03992/m)( 1 )=60 2) Pre-Lab Report: EXPERIMENTAL SECTION 1) Synthesis of diastereomeric salts: Weigh racemic phenylsuccinic acid (0,5g, 2.57 mmole) and L-prolinc (0.3 g. 2.61 mmole) into a 100 ml boiling flask, and swirl to dissolve the solid. [24][27] In rodents, mitochondrial concentrations are approximately ~0.5 mM[6] while plasma concentration are only 220 M. Single crystal structures, thermal analysis, powder X-ray analysis and equilibrium solubility in water and ethanol of the cocrystals were measured. Cloudflare has detected an error with your request. In order to recrystallize the solid, boiling water was added to the solid until it fully dissolves to achieve a complete homoge-nous mixture. Less The diastereomeric salt formed between the (+)-phenylsuccinic acid and (-)-proline is much ___ soluble in isopropyl alcohol than the diastereomeric salt formed between the . Cool 10mL of 6 M HCl in an ice bath and add all of the collected salt to this cold HCl. Appearance: almost white solid. Sorry, it seems JavaScript is not enabled in your browser. 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. DL-Phenylsuccinic acid Revision Date 24-Dec-2021 Notification Requirements Butanedioic acid, phenyl- 635-51-8 Not applicableNot applicableNot applicableNot applicable 16. Added to cooled 10 mL 6 HCl: Reaction immediately but not cloudy enough [10] Global production is estimated at 16,000 to 30,000 tons a year, with an annual growth rate of 10%. Part of their specificity lies in how they bind, or attract and hold, the molecular pieces that are to be fashioned into the product. At the end of 30 minutes, turn off and remove the heating mantle. behave identically toward physical tests like melting and boiling points and solubility in given solvents. Determine the mass of purified crystals and prepare a solution to analyze by polarimetry, first measure about 0.4g of your (S)-phenylsuccinic acid and then dissolve in exactly 10mL of HPLC-grade acetone. A. V. Trask and W. Jones, Top. These must be removed to get a good optical activity measurement. 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. 4 0 obj
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! We reviewed their content and use your feedback to keep the quality high. Thus, via enzymatic inhibition, increased succinate load can lead to changes in transcription factor activity and genome-wide alterations in histone and DNA methylation. Requested URL: www.colby.edu/chemistry/CH241F/Experiment%202.pdf, User-Agent: Mozilla/5.0 (Windows NT 10.0; Win64; x64) AppleWebKit/537.36 (KHTML, like Gecko) Chrome/103.0.5060.114 Safari/537.36 Edg/103.0.1264.62. G. M. Sheldrick, Acta Crystallogr. Molecular Formula:C10H10O4 Molecular Weight:194.19 Section 10 - Stability and Reactivity Chemical Stability:Stable under normal temperatures and pressures. This diethyl ester is a substrate in the Stobbe condensation. [16] The automotive and electronics industries heavily rely on BDO to produce connectors, insulators, wheel covers, gearshift knobs and reinforcing beams. (2018). Lowell, Massachusetts. Any rotational effect that one enantiomer has on plane-polarized light will be exactly canceled somewhere else in the mixture by its mirror image. 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. 15 mL) and swirl for a minute to mix, then boil gently for 30 min (add boiling chip!). 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. Exact concentration: 0 10 mL=0. This property is a direct consequence of the configuration, or orientation of bonded atoms in space, around the chiral center. 4, 279 (1987). [32] Arg99, His103, Arg252, and Arg281 near the center of the receptor generate a positively charged binding site for succinate. Not Intended for Diagnostic or Therapeutic Use. Caution! You have the right to unsubscribe at any time by clicking the 'unsubscribe' link in any News & Announcement emails you receive. Provided by the Springer Nature SharedIt content-sharing initiative, Over 10 million scientific documents at your fingertips, Not logged in The chiral recognition abilities of . This process 4, 310 (2007). volumes of cold water. Oversuccination occurs when more than one succinate adds to a substrate. [27] The GABA shunt serves as an alternate route to convert alpha-ketoglutarate into succinate, bypassing the TCA cycle intermediate succinyl-CoA and instead producing the intermediate GABA. Measure the specific rotation and determine the enantiomeric excess of the sample. 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 are converted into a mixture of diastereomers and to understand how careful choice of solvent can permit selective precipitation of one compound from a mixture of compounds. 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] 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. Commun. No information found. Lett. You'll get a detailed solution from a subject matter expert that helps you learn core concepts. Swirl and pour as fast as possible into a clean Buchner funnel. A new solvent sublation (SS) system for chiral separation is introduced by using phenylsuccinic acid (H2A) as the model enantiomers. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into fumarate by the enzyme succinate dehydrogenase in complex 2 of the electron transport chain which is involved in making ATP, and as a signaling molecule reflecting the cellular metabolic state. Pharm. 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. By signing up, you indicate that you have read and agree to the terms in our privacy policy. [24] Additionally, succinic acid produced during the fermentation of sugar provides a combination of saltiness, bitterness and acidity to fermented alcohols. N. J. Babu, L. S. Reddy, and A. Nangia, Mol. In this study, we investigated CCN activity of inorganic salt (sodium chloride and ammonium sulfate) and dicarboxylic acid (including malonic acid (MA), phenylmalonic acid (PhMA), succinic acid (SA), phenylsuccinic acid (PhSA . Cloudiness and then crystals should gradually form.) Japan (1987), 60, 824-827). (If there is no precipitate, use a Pasteur pipet to remove about I mL to a small test tube. Give the % of each enantiomer. The solid was recrystallized and the final solid is filtered out. connect to this server when you are off campus. The difference, however, is subtle. eral minutes after the second acetone wash. Poor filtrate into the organic hazardous waste con- This application requires Javascript. 4, 417 (2007). 4036-30- (S)-(+)-Phenylsuccinic acid >99 223-719-3 Section 3 - Hazards Identification EMERGENCY OVERVIEW Appearance: almost white solid. & Azadbakht, A. Co-Crystal of Phenylsuccinic Acid and 4,4'-Bipyridine: Synthesis, Characterization, Crystal Structure, and Supramolecular Interactions. Department of Chemistry, Khorramabad Branch, Islamic Azad University, Khorramabad, Iran, Kobra Moradifard,Zohreh Derikvand&Azadeh Azadbakht, You can also search for this author in Let aspirator run for sev- [6][38], Metabolic signaling involving succinate can be involved in inflammation via stabilization of HIF1-alpha or GPR91 signaling in innate immune cells. [35] Simultaneous to substrate oxidation, they convert 2-oxoglutarate, also known as alpha-ketoglutarate, into succinate and CO2. S. Fernandez-Lopez, H. S. Kim, E. C. Choi, et al., Nature 412, 452 (2001). The glyoxylate cycle is utilized by many bacteria, plants and fungi and allows these organisms to subsist on acetate or acetyl CoA yielding compounds. was removed by the HCl. [35] Succinate may interfere with the enzymatic process by attaching to the Fe(II) center first, prohibiting the binding of 2-oxoglutarate. 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. It is also available as a flavoring agent, contributing a somewhat sour and astringent component to umami taste. Article 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. 2. add (-) proline, then heat the mixture at reflux for 30 minutes then allow . Experts are tested by Chegg as specialists in their subject area. This specificity of attachment means that the atoms of the product always end up being, connected to each other in only one of several possible ways. Subsequently, the primary substrate enters the binding pocket and lastly dioxygen binds to the enzyme-substrate complex. Resulting in observing another groups data: [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. In addition to its metabolic roles, succinate serves as an intracellular and extracellular signaling molecule. An ideal solvent would completely precipitate one diastereomer while the other coe remained in the solution. This experiment requires balanced chemical equations and theoretical yield calculation. C. B. Aakery and D. J. Salmon, CrystEngComm 7, 439 (2005). A strong acid (6 M HCI), added in excess to the salt, is used to protonate the water-soluble anion. Purpose: * Refer to Certificate of Analysis for lot specific data (including water content). 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. 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 are converted into a mixture of diastereomers and to understand how careful choice of solvent can permit selective precipitation of one compound from a mixture of compounds. Conditions to Avoid:Incompatible materials, dust generation, excess heat, strong oxidants. Mutations in SDH, hypoxia or energetic misbalance are all linked to an alteration of flux through the TCA cycle and succinate accumulation. 5 mL of DI water. Skin: The solid that results is now-resolved phenylsuccinic acid in its protonated form. [18], Acylation with succinic acid is called succination. Calculate the exact concentration which will be needed to calculate specific rotation. Please enable it to get the best site experience. Allow the flask to air-cool about 10 min. [32] In inflammatory macrophages, succinate-induced stability of HIF1 results in increased transcription of HIF1-dependent genes, including the pro-inflammatory cytokine interleukin-1. The calculated specific rotation came out to be 60.65, meaning that it was not optimally pure but the fact that it was positive meaning that it was more of an S enan-tiomer than an R which was preferred. 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. Eye: The solid that results is now-resolved phenylsuccinic acid in its protonated form. Growth Des. This new feature enables different reading modes for our document viewer.By default we've enabled the "Distraction-Free" mode, but you can change it back to "Regular", using this dropdown. For Research Use Only. of this substance have not been fully investigated. Proline likewise gains 18+, but this gives ita net + charge, making it very soluble in water. 2. the phenylsuccinic acid will precipitate and can be filtered out while the proline is very soluble in water HCl can also be added to (-)-phenylsuccinic acid to release it from any salt which may have formed specific rotation = alpha (observed rotation in degrees)/ l (dm)*c (g/ml) optical purity aka = enantiomeric excess Google Scholar. This is simple since neutral phenylsuccinic acid is poorly soluble in water. 17, 550 (2017). Copyright 2023 StudeerSnel B.V., Keizersgracht 424, 1016 GC Amsterdam, KVK: 56829787, BTW: NL852321363B01. . 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)/t8-/m0/s1, CSID:643286, http://www.chemspider.com/Chemical-Structure.643286.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. not been fully investigated. This is a preview of subscription content, access via your institution. [5] In an aqueous solution, succinic acid readily ionizes to form its conjugate base, succinate (/sksnet/). This website collects cookies to deliver a better user experience. The name derives from Latin succinum, meaning amber.In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into fumarate by the enzyme succinate dehydrogenase in complex 2 of the . X. P. Dai, G. G. Hou, J. F. Sun, et al., J. Mol. Such mirror images represent different stereoisomers they are different molecules. Specific Gravity/Density:Not available. https://doi.org/10.1134/S1063774519070125, DOI: https://doi.org/10.1134/S1063774519070125. Molecular Formula: C 10 H 10 O 4. Pharm. For a compound to be optimally pure, it would have to reach up to 171. For this reason, if the biologically produced product contains one or more chiral centers, it is optically active Examples include table sugar, honey, monosodium glutamate (MSG), vitamins, paper (if we could measure it! 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. The purpose of this experiment is to be able to convert enantiomers of phenylsuccinic acid into separable diastereomers. Some substance identifiers may have been claimed confidential, or may . Generated succinate is then available for either energy production or biosynthesis. Think of a chiral center as an atom to which four different, groups are covalently attached. Nonsuperposable mirror image molecules are called enantiomers. Let Cool for 15 min: very chunky, wet-sand-like consistency, almost solid - slushy, ), . [12], In 2004, succinate was placed on the US Department of Energy's list of top 12 platform chemicals from biomass. The phenylsuccinic acid is a proton donor making proline the proton acceptor. 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. 7, 880 (2005). Experimental Procedure: Scratch inside this test tube several minutes until the contents begin to get cloudy. [30], Extracellular succinate can act as a signaling molecule with hormone-like function, targeting a variety of tissues such as blood cells, adipose tissue, immune cells, the liver, the heart, the retina and primarily the kidney. sion of an enantiomer to a di- Common industrial routes include hydrogenation of maleic acid, oxidation of 1,4-butanediol, and carbonylation of ethylene glycol. B. R. Khandavilli, et al., Cryst. ;DgEvzv
{M aK. Succinate exits the mitochondrial matrix and passes through the inner mitochondrial membrane via dicarboxylate transporters, primarily SLC25A10, a succinate-fumarate/malate transporter. Under anaerobic conditions certain bacteria such as A. succinogenes, A. succiniciproducens and M. succiniciproducens, run the TCA cycle in reverse and convert glucose to succinate through the intermediates of oxaloacetate, malate and fumarate. [30] This leads to stellate cell activation and fibrogenesis. In order to recrystallize the. configuration enantiomer, the other diastereomer must be more soluble during the filtration 9, 1436 (2009). 20, 2372 (2002). Note that the two diastercomeric salts (S.S) and (R.S) differ in their mions (phenylsuccinate), which are nonsuper-posable mirror images, but have identical cations (L-proline). Succinate thus serves as a direct electron donor to the electron transport chain, and itself is converted into fumarate. [7], SUCNR1 is one of the highest expressed G protein-coupled receptors on human platelets, present at levels similar to P2Y12, though the role of succinate signaling in platelet aggregation is debated. Eng. [12][13], Succinic acid can be dehydrogenated to fumaric acid or be converted to diesters, such as diethylsuccinate (CH2CO2CH2CH3)2. The The less soluble salt may precipitate. N. Shan, A. D. Bond, and W. Jones, Cryst. Commun. 2) Calculate the enantiomeric excess if the specific rotation obtained after recrystallization is 103.2. If you study models of chiral molecules, it soon becomes apparent that their, mirror images are not superposable on each other. Colby VPN to so they can be created by reacting [33] Therapies targeting succinate to reduce cardiovascular risk and hypertension are currently under investigation.[28]. [17] Succinic acid also serves as the bases of certain biodegradable polymers, which are of interest in tissue engineering applications. Shop DL-Phenylsuccinic acid, 98+%, Thermo Scientific Chemicals at Fishersci.com is conducted between the pheny- Succinate is generated in mitochondria via the tricarboxylic acid cycle (TCA). Orgo exam notes - Exam noted for organic chemistry. ()-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. Lab Section 803 9:00am Molecular Weight: 194.18. On this Wikipedia the language links are at the top of the page across from the article title. In this experiment, a reflux reaction is conducted between the pheny-succinic acid and proline to produce salt. In living organisms, primarily succinate, not succinic acid, is found. Other information Prepared By Regulatory Affairs Thermo Fisher Scientific Email: EMSDS.RA@thermofisher.com Revision Date 24-Dec-2021 Print Date 24-Dec-2021 Stir the mixture with a glass rod for 5 minutes. 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. However, if the acid is combined with an optically active base, such as (-)-proline, the diastereomers which form have different _____ in isopropyl alcohol. Commun. stream
Since our excess is very low, our substance was nowhere near being pure. Google Scholar. Experiment 4: Resolution of Phenylsuccinic Acid duce salt. L. Fbin, Cryst. Next, place crude solid in a 125mL Erlenmeyer flask and boil 100mL of water in a 250mL Erlenmeyer flask. 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. V. Trask, N. Shan, W. D. S. Motherwell, et al., Chem. Typi- cally, the less soluble diastere- omeric salt was isolated, the enantiomer of phenylsuccinic acid remains. Struct. S. Mittapalli, M. K. C. Mannava, U. 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. [30] The G-protein coupled receptor, GPR91 also known as SUCNR1, serves as the detector of extracellular succinate. Please note, if you are trying to access wiki.colby.edu or Optically active reagents have long been important in studies of reaction mechanisms because they may offer glimpses at the molecular details of the process as the reaction proceeds. Both anions are colorless and can be isolated as the salts, e.g., Na(CH2)2(CO2H)(CO2) and Na2(CH2)2(CO2)2. "R}~Q:~pgg'"l/O:OV~
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b2~P2hMD>? [30], SUCNR1 is highly expressed on immature dendritic cells, where succinate binding stimulates chemotaxis. If you have any questions Chronic: May cause eye, skin, and respiratory Show transcribed image text. succinic acid and proline to pro- Abstract. The reaction between the bis salt of proline and phenylsuccinic acid will give free phenyl succinic acid and proline hydrochloride as HCl is a much stronger acid than phenylsuccinic acid. D. K. Bucar, R. F. Henry, X. C. Lou, et al., Mol. Phenylsuccinic acid | C10H10O4 - PubChem Phenylsuccinic acid | C10H10O4 | CID 95459 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.