This involves an acid-base reaction with (s)-proline and restoring the enantiomer by neutralizing the salt created to find the optical purity by measuring the optical rotation using polarimetry. [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. [30][32], Extracellular succinate regulates cardiomyocyte viability through GPR91 activation; long-term succinate exposure leads to pathological cardiomyocyte hypertrophy. 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. Experts are tested by Chegg as specialists in their subject area. out to be a good recrystallization solvent for this product. Typi- cally, the less soluble diastere- omeric salt was isolated, the enantiomer of phenylsuccinic acid remains. A key candidate transporter is INDY (I'm not dead yet), a sodium-independent anion exchanger, which moves both dicarboxylate and citrate into the bloodstream. 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). This property is a direct consequence of the configuration, or orientation of bonded atoms in space, around the chiral center. Oversuccination occurs when more than one succinate adds to a substrate. 24, 861 (1995). [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. Proline likewise gains 18+, but this gives ita net + charge, making it very soluble in water. 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. In this case, the salt that contains the dextrorotatory acid ("") is the less soluble one, and precipitates. Let Cool for 15 min: very chunky, wet-sand-like consistency, almost solid - slushy, 4, 417 (2007). Its optical activity can be measured to verify that one enantiomer was isolated in excess over the other In this experiment, racemic (R+S)-phenylsuccinic acid is separated (resolved) into optically active enantiomets in a sequence of two steps. 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. produced two diastereomers Article 2. add (-) proline, then heat the mixture at reflux for 30 minutes then allow . Appearance: almost white solid. Part of their specificity lies in how they bind, or attract and hold, the molecular pieces that are to be fashioned into the product. [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. Think of a chiral center as an atom to which four different, groups are covalently attached. Home; About us; Membership & professional community . This application requires Javascript. Your email subscription to News & Announcements has been received. Pharm. Thus, via enzymatic inhibition, increased succinate load can lead to changes in transcription factor activity and genome-wide alterations in histone and DNA methylation. Exact concentration: 0 10 mL=0. [32] Furthermore, SUCNR1 synergizes with toll-like receptors to increase the production of proinflammatory cytokines such as TNF alpha and interleukin-1beta. You'll get a detailed solution from a subject matter expert that helps you learn core concepts. succinic acid and proline to pro- [22]:Section 17.4, Succinate is the re-entry point for the gamma-aminobutyric acid (GABA) shunt into the TCA cycle, a closed cycle which synthesizes and recycles GABA. 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Swirl and pour as fast as possible into a clean Buchner funnel. [34] 2-oxoglutarate-dependent dioxygenases require an iron cofactor to catalyze hydroxylations, desaturations and ring closures. If you study models of chiral molecules, it soon becomes apparent that their, mirror images are not superposable on each other. Typi- Cool 10mL of 6 M HCl in an ice bath and add all of the collected salt to this cold HCl. Vacuum filtered and flushed with 30 mL of acetone: chunky powder, roux-like (S)- [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. [5] In an aqueous solution, succinic acid readily ionizes to form its conjugate base, succinate (/sksnet/). 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] Thus, succinate is thought to play a role in liver homeostasis. In order to recrystallize the solid, boiling water was added to the solid until it fully dissolves to achieve a complete homoge-nous mixture. 9, 1436 (2009). In order to recrystallize the. Soluble in acetone, alcohols, and methanol. Give the % of each enantiomer. 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. A suitable solvent is found by trial and error. The solid was recrystallized and the final solid is filtered out. 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. Ingestion: Since PHDs have an absolute requirement for molecular oxygen, this process is suppressed in hypoxia allowing HIF1 to escape destruction. This website collects cookies to deliver a better user experience. Caution! In animal models, pharmacological inhibition of ischemic succinate accumulation ameliorated ischemia-reperfusion injury. >>
L. Fbin, Cryst. Sorry, it seems JavaScript is not enabled in your browser. 7, 880 (2005). So, for optical activity to be evident, there must be an excess of one enantiomer over its mirror image. [36] Pathologically elevated levels of succinate lead to hypermethylation, epigenetic silencing and changes in neuroendocrine differentiation, potentially driving cancer formation. The purpose of this experiment is to be able to convert enantiomers of phenylsuccinic Correspondence to Under pathological and physiological conditions, the malate-aspartate shuttle or the purine nucleotide shuttle can increase mitochondrial fumarate, which is then readily converted to succinate. Part of Springer Nature. Not Intended for Diagnostic or Therapeutic Use. M. J. Zaworotko, Cryst. Experimental Procedure: A strong acid (6 M HCI), added in excess to the salt, is used to protonate the water-soluble anion. [42] The other two oncometabolites, fumarate and 2-hydroxyglutarate have similar structures to succinate and function through parallel HIF-inducing oncogenic mechanisms. 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. 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. Struct. Succinate and fumarate inhibit the TET (ten-eleven translocation) family of 5-methylcytosine DNA modifying enzymes and the JmjC domain-containing histone lysine demethylase (KDM). F. Toda, K. Tanaka, A. Sekikawa, J. Chem. Add 1 of finely ground (s)-proline & a magnetic stir bar then Succinate is generated in mitochondria via the tricarboxylic acid cycle (TCA). The first source was natural products chemicals produced by living organisms. No information found. It is also available as a flavoring agent, contributing a somewhat sour and astringent component to umami taste. omeric salt was isolated, the enantiomer of phenylsuccinic acid remains. T. R. Shattock, K. K. Arora, P. Vishweshwar, and M.J.Zaworotko, Cryst. The recovered diastereomer must be converted back to the original compound from which it was made -- now a single enantiomer. Succinic acid (/sksnk/) is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. Measure the specific rotation and determine the enantiomeric excess of the sample. acid into separable diastereomers. The glyoxylate cycle is utilized by many bacteria, plants and fungi and allows these organisms to subsist on acetate or acetyl CoA yielding compounds. Resolved (S)-acid: 0, Theoretical yield: 1 2 =0 This process 7, 4 (2007). Give the % of each enantiomer. To begin, dissolve 1 of racemic phenylsuccinic acid into 50mL of isopropanol in a [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. connect to this server when you are off campus. Lowell, Massachusetts. University of Massachusetts Lowell. [36] Additionally, succinate-promoted activation of HIF-1 generates a pseudo-hypoxic state that can promote tumorneogensis by transcriptional activation of genes involved in proliferation, metabolism and angiogenesis. An ideal solvent would completely precipitate one diastereomer while the other coe remained in the solution. In this experiment, a reflux reaction is conducted between the pheny-succinic acid and proline to produce salt. The phenylsuccinic acid gave up two positives, so it is a dianion. [30], Succinate signaling often occurs in response to hypoxic conditions. They are potentially separable by ordinary physical methods like different solubility in a given solvent, which allows recovery of a single diastereomer
Experts are tested by Chegg as specialists in their subject area. RECEIVE -15-CRUZ CREDITS. 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--cyclodextrin (HP--CD) in the aqueous phase. With the product collected, specific rotation was calculated where polarimetry is used to calculate the alpha observed in degrees. Both anions are colorless and can be isolated as the salts, e.g., Na(CH2)2(CO2H)(CO2) and Na2(CH2)2(CO2)2. RST is the consecutive number of the substance in the series ABC. Proceed to measure the specific rotation of the sample and calculate the enantiomeric excess 4) Recrystallization: The recovered acid contains contaminants- possibly some left-over proline and some HCl or some of the enantiomeric succinic acid. is a proton donor making proline This property is a direct consequence of the configuration, or orientation of, bonded atoms in space, around the chiral center. As a consequence, the mixture cases no net rotation, and appears optically inactive. [6][38], Metabolic signaling involving succinate can be involved in inflammation via stabilization of HIF1-alpha or GPR91 signaling in innate immune cells. stream
May cause respiratory tract irritation. November 19th, 2018 Vacuum filter and wash the solid with two 15mL volumes of cold water. [7][32] Succinate may enhance adaptive immunity by triggering the activity of antigen-presenting cells that, in turn, activate T-cells. is conducted between the pheny- Succinate requires specific transporters to move through both the mitochondrial and plasma membrane. [30] The G-protein coupled receptor, GPR91 also known as SUCNR1, serves as the detector of extracellular succinate. Eng. Molecular Formula:C10H10O4 Molecular Weight:194.19 Section 10 - Stability and Reactivity Chemical Stability:Stable under normal temperatures and pressures. sion of an enantiomer to a di- The CAS Number: 4036-30-. 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]. This is an ordinary acid-base reaction that produces a salt. N. Shan, F. Toda, and W. Jones, Chem. [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. Molecular Weight: 194.18. Generated succinate is then available for either energy production or biosynthesis. Growth Des. ), . [30] Transport across the plasma membrane is likely tissue specific. 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. This experiment requires balanced chemical equations and theoretical yield calculation. Learn more about Institutional subscriptions. 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. Commun. (R)-(-)-Phenylsuccinic acid | C10H10O4 | CID 736145 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological . Show transcribed image text. 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. [26] As such, succinate links TCA cycle dysfunction or metabolic changes to cell-cell communication and to oxidative stress-related responses. The solubility of the complexes is poor in the top phase, where H 2 A has better solubility than in the bottom phase. [15], Succinic acid is a precursor to some polyesters and a component of some alkyd resins. bvseo-msg: The resource to the URL or file is currently unavailable.. 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. 1035, 203 (2013). These chemicals are invariably synthesized by catalysts called, enzymes, which are large chiral molecules specially designed to carry out a particular chemical, transformation. (2018). Nonsuperposable mirror image molecules are called enantiomers. this experiment, a reflux reaction 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. Put the entire crude product into a small beaker or glass vial, and add approx. 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. too much present in sample (soluble) [32] Overall, the EC50 for succinate-GPR91 is in the 2050 uM range. 2) Calculate the enantiomeric excess if the specific rotation obtained after recrystallization is 103.2. - 173.212.249.81. Succinate thus serves as a direct electron donor to the electron transport chain, and itself is converted into fumarate. Target Organs: No data found. How does one obtain optically active compounds? the proton acceptor. tical while diastereomers are not & Azadbakht, A. Co-Crystal of Phenylsuccinic Acid and 4,4'-Bipyridine: Synthesis, Characterization, Crystal Structure, and Supramolecular Interactions. [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. DL-Phenylsuccinic acid Revision Date 24-Dec-2021 Notification Requirements Butanedioic acid, phenyl- 635-51-8 Not applicableNot applicableNot applicableNot applicable 16. Inhalation: mix contents for 2 minutes and reflux for 30 minutes. S. Fernandez-Lopez, H. S. Kim, E. C. Choi, et al., Nature 412, 452 (2001). When the solution is cooled down at room temperature, the solubility decreases which allows the pure crystals of phenylsuccinic acid to form. 8, 4533 (2008). <<
A strong acid (6 M HCI), added in excess to the salt, is poorly soluble in water. [6] As such, succinate links cellular metabolism, especially ATP formation, to the regulation of cellular function. configuration enantiomer, the other diastereomer must be more soluble during the filtration Any rotational effect that one enantiomer has on plane-polarized light will be exactly canceled somewhere else in the mixture by its mirror image. Chem. This shows the degree to which a sample contains one enantiomer in greater amounts than the other. . Google Scholar. When the solution is completely ho-mogenous, remove the flask from the hot plate and allow to cool. Not Intended for Diagnostic or Therapeutic Use. [28], Succinate serves as a modulator of blood pressure by stimulating renin release in macula densa and juxtaglomerular apparatus cells via GPR91. The resulting solid acid can be recovered by filtration. 5.03E-005 mm Hg (25 deg C, Mod-Grain method) Water Solubility Estimate from Log Kow (WSKOW v1.41): Water Solubility at 25 deg C (mg/L): 4.234e+004 log Kow . ADS Let aspirator run for several minutes after the second acetone wash. Poor filtrate into the organic hazardous waste container. X`I%&/m{JJt`$@iG#)*eVe]f@{{;N'?\fdlJ!?~|? Orgo exam notes - Exam noted for organic chemistry. In humans, three HIF prolyl 4-hydroxylases regulate the stability of HIFs. Stir for 5 min to allow complete protonation. 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. M. R. Caira, Mol. The enantiomeric excess was 35.5% which is the measurement of purity. Growth Des. [12] Drugs involving succinate include metoprolol succinate, sumatriptan succinate, Doxylamine succinate or solifenacin succinate. %
254, 41 (2005). ter. The toxicological Enantiomers are distinguished from cach other by designations like "R" or "S", "D" or "L", or by the direction of the rotation they cause ("+" or "-") Since the presence of optical activity is an indication of a particular configuration of atoms, any change in optical activity that occurs during a chemical reaction offers a way to study the kind of configurational change that accompanies the reaction. Growth Des. Add a magnetic stir bar and gently mix the contents of the flask until you achieve a The substance identifiers displayed in the InfoCard are the best available substance name, EC number, CAS number and/or the molecular and structural formulas. [5], As a radical group it is called a succinyl (/sksnl/) group. Scratch inside this test tube several minutes until the contents begin to get cloudy. [12], In 2004, succinate was placed on the US Department of Energy's list of top 12 platform chemicals from biomass. N. Shan, A. D. Bond, and W. Jones, Cryst. C. B. Aakery and D. J. Salmon, CrystEngComm 7, 439 (2005). tical rotation using polarimetry. The phenylsuccinic acid is a proton donor making proline the proton acceptor. [18], Acylation with succinic acid is called succination. Crystallogr. Molecular Formula: C 10 H 10 O 4. Enantiomeric excess: 60.65171=0 100 =35% of (+)-phenylsuccinic acid tract irritation. The interactive pathway map can be edited at WikiPathways: Learn how and when to remove this template message, JmjC domain-containing histone lysine demethylase, Institute for Occupational Safety and Health, "Product Information Sheet: Succinic Acid", "Succinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis", "Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS", Ullmann's Encyclopedia of Industrial Chemistry, "NNFCC Renewable Chemicals Factsheet: Succinic Acid", "Succinate production in Escherichia coli", "Industrial Systems Biology of Saccharomyces cerevisiae Enables Novel Succinic Acid Cell Factory", "Top Value Added Chemicals from Biomass, Volume 1: Results of Screening for Potential Candidates from Sugars and Synthesis Gas", "1,4-Butanediol (BDO) Market Analysis By Application (Tetrahydrofuran, Polybutylene Teraphthalate, Gamma-Butyrolactone & Polyurethanes), And Segment Forecasts To 2020", "Design and Applications of Biodegradable Polyester Tissue Scaffolds Based on Endogenous Monomers Found in Human Metabolism", "Succinic acid in the FDA SCOGS Database", "Overview of pharmaceutical excipients used in tablets and capsules", "Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning", "Improved Succinate Production by Metabolic Engineering", "Intermediates of Metabolism: From Bystanders to Signalling Molecules", "The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions", "Succinate metabolism: a new therapeutic target for myocardial reperfusion injury", "GPR91: expanding the frontiers of Krebs cycle intermediates", "Insight into SUCNR1 (GPR91) structure and function", "Inhibition of -KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors", "Oncometabolites: linking altered metabolism with cancer", "Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF", "Succinate is a danger signal that induces IL-1 via HIF-1", "Metabolic reprogramming in macrophages and dendritic cells in innate immunity", "Oncometabolites: Unconventional triggers of oncogenic signalling cascades", "Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer", Flame Retardant Finishing of Cotton Fleece Fabric: Part IV-Bifunctional Carboxylic Acids, Calculator: Water and solute activities in aqueous succinic acid, ScienceDirect: Succinic Acid - Production of organic acids and enzymes / biocatalysts from food waste, PubChem: Compound Summary for Succinic Acid, https://en.wikipedia.org/w/index.php?title=Succinic_acid&oldid=1135423431, Pages using collapsible list with both background and text-align in titlestyle, Articles containing unverified chemical infoboxes, Short description is different from Wikidata, Articles with unsourced statements from January 2021, Articles lacking reliable references from March 2017, Creative Commons Attribution-ShareAlike License 3.0, This page was last edited on 24 January 2023, at 15:55.
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