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5 mL of DI water. [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. A 71, 3 (2015). Pharm. The solubility of the complexes is poor in the top phase, where H 2 A has better solubility than in the bottom phase. Succinate thus serves as a direct electron donor to the electron transport chain, and itself is converted into fumarate. [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. Exact concentration: 0 10 mL=0. No information found. Abstract. [7] For dendritic cells, succinate functions as a chemoattractant and increases their antigen-presenting function via receptor stimulated cytokine production. 1112, 1 (2016). X. P. Dai, G. G. Hou, J. F. Sun, et al., J. Mol. [27], Succinate is produced and concentrated in the mitochondria and its primary biological function is that of a metabolic intermediate. Put the entire crude product into a small beaker or glass vial, and add approx. F. Toda and H. Miyamoto, Chem. Water tums [30], SUCNR1 is highly expressed on immature dendritic cells, where succinate binding stimulates chemotaxis. Such mirror images represent different stereoisomers , they are different molecules. Learn more about Institutional subscriptions. [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. Google Scholar. An ideal solvent would completely precipitate one diastereomer while the other coe remained in the solution. Repeat a second time with 15 ml of acetone. Oversuccination occurs when more than one succinate adds to a substrate. As the anion binds the H+, it loses its negative charge and becomes poorly soluble in water. astereomer, enantiomers are iden- [30] Depending on the cell type, GPR91 can interact with multiple G proteins, including Gs, Gi and Gq, and enabling a multitude of signaling outcomes. In order to recrystallize the solid, boiling water was added to the solid until it fully dissolves to achieve a complete homoge-nous mixture. product contains one or more chiral centers, it is optically active. S. Fernandez-Lopez, H. S. Kim, E. C. Choi, et al., Nature 412, 452 (2001). phenylsuccinic acid would bind to the proton (H+), where it loses its negative charge and be- The toxicological properties Este site coleta cookies para oferecer uma melhor experincia ao usurio. 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. phenylsuccinic salt Vis x dm) r=the observed angular rotation of planc-polarized light in degrees 1 - cell path length in decimeters (1 dm - 10 cm; use I dm in equation) c-concentration of compound in g'mL of solution The published specific rotation of (+-phenylsuccinic acid is +173.3" (Shiraiwa, T., Sado, Y, Fujii, S. Nakamura, M., Kurokawo, H., Bull. 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. CAS Number: 635-51-8. Succinate requires specific transporters to move through both the mitochondrial and plasma membrane. [26], Succinate is also a product of the glyoxylate cycle, which converts two two-carbon acetyl units into the four-carbon succinate. Let aspirator run for several minutes after the second acetone wash. Poor filtrate into the organic hazardous waste container. 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. Together, these three ions form a salt. [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. During this time, all the proline should dissolve. vacuum filter the reaction mixture & wash salt with 2 15mL of acetone. Keep adding hot water until the solid fully dissolves. The less soluble salt may precipitate. This is a preview of subscription content, access via your institution. 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. 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. ;DgEvzv {M aK. May cause eye, skin, and respiratory [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. endobj Enantiomeric excess: 60.65171=0 100 =35% of (+)-phenylsuccinic acid 15 mL) and swirl for a minute to mix, then boil gently for 30 min (add boiling chip!). Experimental Procedure: You'll get a detailed solution from a subject matter expert that helps you learn core concepts. Other information Prepared By Regulatory Affairs Thermo Fisher Scientific Email: EMSDS.RA@thermofisher.com Revision Date 24-Dec-2021 Print Date 24-Dec-2021 Lab Section 803 9:00am DL-Phenylsuccinic acid Revision Date 24-Dec-2021 Notification Requirements Butanedioic acid, phenyl- 635-51-8 Not applicableNot applicableNot applicableNot applicable 16. [31] SDH mutations have also been identified in gastrointestinal stromal tumors, renal tumors, thyroid tumors, testicular seminomas and neuroblastomas. Struct. Allow to fully dry & poor the filtrate into the aqueous hazardous waste container. M. R. Caira, Mol. CHEM: Organic Chemistry Labora- [30], In adipocytes, the succinate-activated GPR91 signaling cascade inhibits lipolysis. 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). 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Crystallographic data for the compound was collected at 150(2) K. The synthesized compound is crystallized in the monoclinic system with the space group P21/n and unit cell . In DL-Phenylsuccinic acid Revision Date 24-Dec-2021 Notification Requirements Butanedioic acid, phenyl- 635-51-8 Not applicableNot applicableNot applicableNot applicable 16. - 173.212.249.81. 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. First, we exploit its chemical nature it is an acid) by treating it with an optically active biologically produced base, L-proline. Google Scholar. 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. Through these mechanisms, succinate accumulation has been shown to regulate production of inflammatory cytokines. [12] As an excipient in pharmaceutical products, it is also used to control acidity[21] or as a counter ion. For Research Use Only. Kobra Moradifard, Derikvand, Z. [8] ROS then trigger the cellular apoptotic machinery or induce oxidative damage to proteins, membranes, organelles etc. 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. [36] Pathologically elevated levels of succinate lead to hypermethylation, epigenetic silencing and changes in neuroendocrine differentiation, potentially driving cancer formation. It washes away in the acidic water, leaving nearly pure phenylsuccinic acid as the solid.) tiomer behind. The Index number for each substance is in the form of a digit sequence of the type ABC-RST-VW-Y. Copyright 2007-2023 Santa Cruz Biotechnology, Inc. All Rights Reserved. 9, 1436 (2009). Organic Chemistry I This process produced two diastereomers where the more soluble compound was removed by the HCl. This is simple since neutral phenylsuccinic acid is poorly soluble in water. When the solution is cooled down at room temperature, the solubility decreases which allows the pure crystals of phenylsuccinic acid to form. bvseo-msg: The resource to the URL or file is currently unavailable.. The recovered diastereomer must be converted back to the original compound from which it was made -- now a single enantiomer. a mixture of both enantiomers tainer. PubMedGoogle Scholar. 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. [6][26] Extra-mitochondrial succinate alters the epigenetic landscape by inhibiting the family of 2-oxogluterate-dependent dioxygenases. These chemicals are invariably synthesized by catalysts called I enzymes, which are large chiral molecules specially designed to carry out a particular chemical transformation. Z. Wang, C. B. Wu, et al., CrystEngComm 14, 6221 (2012). Don't use too much water, as the product is somewhat soluble and will slowly dissolve. [35] Simultaneous to substrate oxidation, they convert 2-oxoglutarate, also known as alpha-ketoglutarate, into succinate and CO2. Part of Springer Nature. is conducted between the pheny- Multiple studies have demonstrated succinate-induced aggregation, but the effect has high inter-individual variability. [6] It is marketed as food additive E363. This enzyme complex is a 4 subunit membrane-bound lipoprotein which couples the oxidation of succinate to the reduction of ubiquinone via the intermediate electron carriers FAD and three 2Fe-2S clusters. eral minutes after the second acetone wash. Poor filtrate into the organic hazardous waste con- Soc. sion of an enantiomer to a di- This involves an acid-base reaction with (s)-proline and restor- 24, 861 (1995). RECEIVE -15-CRUZ CREDITS. To purify, recrystallize the (S)-phenylsuccinic acid precipitate from wa- Target Organs: No data found. The substance identifiers displayed in the InfoCard are the best available substance name, EC number, CAS number and/or the molecular and structural formulas. ABC corresponds to the atomic number of the most characteristic element or the most characteristic organic group in the molecule. Eng. [33] Therapies targeting succinate to reduce cardiovascular risk and hypertension are currently under investigation.[28]. Growth Des. 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. . [6][23] Under conditions of succinate accumulation, rapid oxidation of succinate by SDH can drive reverse electron transport (RET). 1 0 obj indication of why you can't access this Colby College website. [30] Transport across the plasma membrane is likely tissue specific. The phenylsuccinic acid is a proton donor making proline the proton acceptor. To get rid of 2-propanol and any unreacted phenylsuccinic acid, wash the crystals with 10 mL of acetone. Specific rotation is a property of a chiral substance that is expressed as the angle to which the material causes polarized light to rotate, passing through the tube containing solution. [35] Succinate may interfere with the enzymatic process by attaching to the Fe(II) center first, prohibiting the binding of 2-oxoglutarate. Chirality is a necessary condition for the existence of optical activity (the ability to cause rotation, of the plane of polarized light). Dehydration of succinic acid gives succinic anhydride. [28], Succinate serves as a modulator of blood pressure by stimulating renin release in macula densa and juxtaglomerular apparatus cells via GPR91. Show transcribed image text. [12][13], Succinic acid can be dehydrogenated to fumaric acid or be converted to diesters, such as diethylsuccinate (CH2CO2CH2CH3)2. Molecular Formula: C 10 H 10 O 4. [5], As a radical group it is called a succinyl (/sksnl/) group. B. R. Khandavilli, et al., Cryst. 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. Take 40mg of the resolved enantiomer and dissolve it in Iml of acetone. Scratch inside this test tube several minutes until the contents begin to get cloudy. 4 0 obj 4, 279 (1987). [6][26][38] PHDs hydroxylate proline in parallel to oxidatively decarboxylating 2-oxyglutarate to succinate and CO2. To begin, dissolve 1 of racemic phenylsuccinic acid into 50mL of isopropanol in a After refluxing, cool flask for 15 minutes, vacuum filter the reaction mixture & wash salt with 2 15mL of acetone. 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. 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. Oxidative decarboxylation then generates a ferryl intermediate coordinated to succinate, which serves to oxidize the bound primary substrate. [24] This pathway is exploited in metabolic engineering to net generate succinate for human use. 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. Stir for 5 min to allow complete protonation. All you are really doing is exchanging one acid for another so it is hardly an acid/base reaction. This diethyl ester is a substrate in the Stobbe condensation. Finally, succinic semialdehyde is oxidized by succinic semialdehyde dehydrogenase (SSADH) to form succinate, re-entering the TCA cycle and closing the loop. acid into separable diastereomers. [30] In general, leakage from the mitochondria requires succinate overproduction or underconsumption and occurs due to reduced, reverse or completely absent activity of SDH or alternative changes in metabolic state. T. R. Shattock, K. K. Arora, P. Vishweshwar, and M.J.Zaworotko, Cryst. The solid that results is now-resolved phenylsuccinic acid in its protonated form. Other information Prepared By Regulatory Affairs Thermo Fisher Scientific Email: EMSDS.RA@thermofisher.com Revision Date 24-Dec-2021 Print Date 24-Dec-2021 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. 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] stream 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. They are potentially separable by ordinary physical methods like different solubility in a given solvent, which allows recovery of a single diastereomer [10] Global production is estimated at 16,000 to 30,000 tons a year, with an annual growth rate of 10%. Zohreh Derikvand. May cause eye irritation. ()-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. One proline has a position available for one extra proton, so the two protons end up on two different prolines. Two protons are transferred from the phenylsuccinic acid to the proline. The pathway avoids the decarboxylation steps of the TCA cycle via the enzyme isocitrate lyase which cleaves isocitrate into succinate and glyoxylate. For a compound to be optimally pure, it would have to reach up to 171. [41], Succinate accumulation under hypoxic conditions has been implicated in the reperfusion injury through increased ROS production. The enantiomeric excess was 35.5% which is the measurement of purity. Added to cooled 10 mL 6 HCl: Reaction immediately but not cloudy enough https://doi.org/10.1134/S1063774519070125. Soluble in acetone, alcohols, and methanol. 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. 1035, 203 (2013). Sample will be analyzed by polarimetry. 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. Pull air through the solid for a couple of minutes after the last wash to evaporate most of the acetone. Neutral phenylsuccinic Cloudiness and then crystals should gradually form.) Subsequently, the primary substrate enters the binding pocket and lastly dioxygen binds to the enzyme-substrate complex. The toxicological 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. Conditions to Avoid:Incompatible materials, dust generation, excess heat, strong oxidants. Insoluble in water. ORGO WEEK 2 PRAC QUIZ - practice for orgo quiz 1 and 2. connect to this server when you are off campus. 1).Factors affecting the extraction efficiency were investigated, namely the influence of the types of organic solvents and -CD derivatives, iso-butyl tartrate . Thus, via enzymatic inhibition, increased succinate load can lead to changes in transcription factor activity and genome-wide alterations in histone and DNA methylation. In the retina, succinate accumulates in retinal ganglion cells in response to ischemic conditions. C. B. Aakery and D. J. Salmon, CrystEngComm 7, 439 (2005). [23], Click on genes, proteins and metabolites below to link to respective articles. Eye: & Azadbakht, A. Co-Crystal of Phenylsuccinic Acid and 4,4'-Bipyridine: Synthesis, Characterization, Crystal Structure, and Supramolecular Interactions. May cause respiratory tract irritation. 2-oxoglutarate-dependent dioxygenases bind substrates in a sequential, ordered manner. The phenylsuccinic acid gave up two positives, so it is a dianion. N. J. Babu, L. S. Reddy, and A. Nangia, Mol. Vacuum filter and wash the solid with two 15mL 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. 7, 1291 (2007). Growth Des. 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. Vacuum filter and wash the solid with two 15mL volumes of cold water. 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. Let Cool for 15 min: very chunky, wet-sand-like consistency, almost solid - slushy, Article F. Toda, K. Tanaka, A. Sekikawa, J. Chem. 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. [11], Genetically engineered Escherichia coli and Saccharomyces cerevisiae are proposed for the commercial production via fermentation of glucose. [12], In 2004, succinate was placed on the US Department of Energy's list of top 12 platform chemicals from biomass. Let the clear solution rest at RT for about 20 min in order to allow for the crystallization of the desired compound. (2018). with another chiral molecule. Add 1 of finely ground (s)-proline & a magnetic stir bar then (R)-(-)-Phenylsuccinic acid | C10H10O4 | CID 736145 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological . of one compound from a mixture of compounds. this experiment, a reflux reaction Copyright 2023 StudeerSnel B.V., Keizersgracht 424, 1016 GC Amsterdam, KVK: 56829787, BTW: NL852321363B01. [30], Succinate signaling often occurs in response to hypoxic conditions. However, if the acid is combined with an optically active base, such as (-)-proline, the diastereomers which form have different _____ in isopropyl alcohol. The resulting solid acid can be recovered by filtration. Colby VPN to Because protons have +1 charge, each proline is cationic. Santa Cruz Biotechnology, Inc. is a world leader in the development of products for the biomedical research market. Who are the experts? Write a review Ask a question. [24][27] In rodents, mitochondrial concentrations are approximately ~0.5 mM[6] while plasma concentration are only 220 M. 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.