Uracil
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| Names |
| IUPAC name
Pyrimidine-2,4(1H,3H)-dione
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Other names
2-oxy-4-oxy pyrimidine,
2,4(1H,3H)-pyrimidinedione,
2,4-dihydroxypyrimidine,
2,4-pyrimidinediol |
| Identifiers |
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CAS Registry Number
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66-22-8 Y |
| ChEBI |
CHEBI:17568 N |
| ChEMBL |
ChEMBL566 N |
| ChemSpider |
1141 N |
InChI
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InChI=1S/C4H4N2O2/c7-3-1-2-5-4(8)6-3/h1-2H,(H2,5,6,7,8) N
Key: ISAKRJDGNUQOIC-UHFFFAOYSA-N N
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InChI=1/C4H4N2O2/c7-3-1-2-5-4(8)6-3/h1-2H,(H2,5,6,7,8)
Key: ISAKRJDGNUQOIC-UHFFFAOYAV
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| Jmol-3D images |
Image |
| RTECS number |
YQ8650000 |
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| UNII |
56HH86ZVCT N |
| Properties |
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Chemical formula
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C4H4N2O2 |
| Molar mass |
112.08676 g/mol |
| Appearance |
Solid |
| Density |
1.32 g/cm3 |
| Melting point |
335 °C (635 °F; 608 K)[1] |
| Boiling point |
N/A - decomposes |
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Solubility in water
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Soluble |
| Hazards |
| Main hazards |
carcinogen and teratogen with chronic exposure |
| NFPA 704 |
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| Flash point |
Non-flammable |
| Related compounds |
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Related compounds
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Thymine
Cytosine |
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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| N verify (what is: Y/N?) |
| Infobox references |
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Uracil // (U) is one of the four nucleobases in the nucleic acid of RNA that are represented by the letters A, G, C and U. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine. Uracil could be considered a demethylated form of thymine.
Uracil is a common and naturally occurring pyrimidine derivative.[2] The name "uracil" was coined in 1885 by the German chemist Robert Behrend, who was attempting to synthesize derivatives of uric acid.[3] Originally discovered in 1900 by Alberto Ascoli, it was isolated by hydrolysis of yeast nuclein;[4] it was also found in bovine thymus and spleen, herring sperm, and wheat germ.[5] It is a planar, unsaturated compound that has the ability to absorb light.[6]
Studies reported in 2008, based on 12C/13C isotopic ratios of organic compounds found in the Murchison meteorite, suggested that uracil, xanthine and related molecules were formed extraterrestrially.[7][8]
In 2012, an analysis of data from the Cassini mission orbiting in the Saturn system showed that Titan's surface composition may include uracil.[9]
Contents
- 1 Properties
- 2 Synthesis
- 3 Reactions
- 4 Uses
- 5 References
- 6 External links
Properties
In RNA, uracil base-pairs with adenine and replaces thymine during DNA transcription. Methylation of uracil produces thymine.[10] In DNA, the evolutionary substitution of thymine for uracil may have increased DNA stability and improved the efficiency of DNA replication. Uracil pairs with adenine through hydrogen bonding. When base pairing with adenine, uracil acts as both a hydrogen bond acceptor and a hydrogen bond donor. In RNA, uracil binds with a ribose sugar to form the ribonucleoside uridine. When a phosphate attaches to uridine, uridine 5'-monophosphate is produced.[6]
Uracil undergoes amide-imidic acid tautomeric shifts because any nuclear instability the molecule may have from the lack of formal aromaticity is compensated by the cyclic-amidic stability.[5] The amide tautomer is referred to as the lactam structure, while the imidic acid tautomer is referred to as the lactim structure. These tautomeric forms are predominant at pH 7. The lactam structure is the most common form of uracil.
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Uracil tautomers: Amide or lactam structure (left) and imide or lactim structure (right)
Uracil also recycles itself to form nucleotides by undergoing a series of phosphoribosyltransferase reactions.[2] Degradation of uracil produces the substrates aspartate, carbon dioxide, and ammonia.[2]
- C4H4N2O2 → H3NCH2CH2COO− + NH4+ + CO2
Oxidative degradation of uracil produces urea and maleic acid in the presence of H2O2 and Fe2+ or in the presence of diatomic oxygen and Fe2+.
Uracil is a weak acid. The first site of ionization of uracil is not known.[11] The negative charge is placed on the oxygen anion and produces a pKa of less than or equal to 12. The basic pKa = -3.4, while the acidic pKa = 9.389. In the gas phase, uracil has 4 sites that are more acidic than water.[12]
Synthesis
In a scholarly article published in October 2009, NASA scientists reported having reproduced uracil from pyrimidine by exposing it to ultraviolet light under space-like conditions. This suggests that one possible natural original source for uracil in the RNA world could have been panspermia.[13] More recently, in March 2015, NASA scientists reported that, for the first time, additional complex DNA and RNA organic compounds of life, including uracil, cytosine and thymine, have been formed in the laboratory under outer space conditions, using starting chemicals, such as pyrimidine, found in meteorites. Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), the most carbon-rich chemical found in the Universe, may have been formed in red giants or in interstellar dust and gas clouds, according to the scientists.[14]
There are many laboratory syntheses of uracil available. The first reaction is the simplest of the syntheses, by adding water to cytosine to produce uracil and ammonia.[2] The most common way to synthesize uracil is by the condensation of maleic acid with urea in fuming sulfuric acid[5] as seen below also. Uracil can also be synthesized by a double decomposition of thiouracil in aqueous chloroacetic acid.[5]
- C4H5N3O + H2O → C4H4N2O2 + NH3
- COOH(CH)2COOH + NH2CONH2 → C4H4N2O2 + 2 H2O + CO
Photodehydrogenation of 5,6-diuracil, which is synthesized by beta-alanine reacting with urea, produces uracil.[15]
Reactions
Uracil readily undergoes regular reactions including oxidation, nitration, and alkylation. While in the presence of phenol (PhOH) and sodium hypochlorite (NaOCl), uracil can be visualized in ultraviolet light.[5] Uracil also has the capability to react with elemental halogens because of the presence of more than one strongly electron donating group.[5]
Chemical structure of uridine
Uracil readily undergoes addition to ribose sugars and phosphates to partake in synthesis and further reactions in the body. Uracil becomes uridine, uridine monophosphate (UMP), uridine diphosphate (UDP), uridine triphosphate (UTP), and uridine diphosphate glucose (UDP-glucose). Each one of these molecules is synthesized in the body and has specific functions.
When uracil reacts with anhydrous hydrazine, a first-order kinetic reaction occurs and the uracil ring opens up.[16] If the pH of the reaction increases to >10.5, the uracil anion forms, making the reaction go much more slowly. The same slowing of the reaction occurs if the pH decreases, because of the protonation of the hydrazine.[16] The reactivity of uracil remains unchanged, even if the temperature changes.[16]
Uses
Uracil's use in the body is to help carry out the synthesis of many enzymes necessary for cell function through bonding with riboses and phosphates.[2] Uracil serves as allosteric regulator and coenzyme for reactions in the human body and in plants.[17] UMP controls the activity of carbamoyl phosphate synthetase and aspartate transcarbamoylase in plants, while UDP and UTP requlate CPSase II activity in animals. UDP-glucose regulates the conversion of glucose to galactose in the liver and other tissues in the process of carbohydrate metabolism.[17] Uracil is also involved in the biosynthesis of polysaccharides and the transportation of sugars containing aldehydes.[17] It can also increase the risk for cancer in cases in which the body is extremely deficient in folate.[18] The deficiency in folate leads to increased ratio of deoxyuracilmonophosphates (dUMP)/deoxythyminemonophosphates (dTMP) and uracil misincorporation into DNA and eventually low production of DNA.[18]
Uracil can be used for drug delivery and as a pharmaceutical. When elemental fluorine is reacted with uracil, 5-fluorouracil is produced. 5-Fluorouracil is an anticancer drug (antimetabolite) used to masquerade as uracil during the nucleic acid replication process.[2] Because 5-Fluorouracil is similar in shape to, but does not undergo the same chemistry as, uracil, the drug inhibits RNA replication enzymes, thereby blocking RNA synthesis and stopping the growth of cancerous cells.[2] Uracil can also be used in the synthesis of caffeine [19]
Uracil can be used to determine microbial contamination of tomatoes. The presence of uracil indicates lactic acid bacteria contamination of the fruit.[20] Uracil derivatives containing a diazine ring are used in pesticides.[21] Uracil derivatives are more often used as antiphotosynthetic herbicides, destroying weeds in cotton, sugar beet, turnips, soya, peas, sunflower crops, vineyards, berry plantations, and orchards.[21]
In yeast, uracil concentrations are inversely proportional to uracil permease.[22]
References
- ^ Richard L. Myers, Rusty L. Myers: The 100 most important chemical compounds, 92-93 link
- ^ a b c d e f g Garrett, Reginald H.; Grisham, Charles M. Principals of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning, 1997.
- ^ Robert Behrend (1885) "Versuche zur Synthese von Körpern der Harnsäurereihe" (Experiments on the synthesis of substances in the uric acid series), Annalen der Chemie, 229 : 1-44. From page 11: "Dasselbe stellt sich sonach als Methylderivat der Verbindung: [molecular structure of uracil] welche ich willkürlich mit dem Namen Uracil belege, dar." (The same [compound] is therefore represented as the methyl derivative of the compound [illustration of uracil's structure], which I will arbitrarily endow with the name "uracil".)
- ^ Alberto Ascoli (1900) "Ueber ein neues Spaltungsprodukt des Hefenucleins" (On a new cleavage product of nucleic acid from yeast), Zeitschrift für Physiologische Chemie, 31 : 161-164.
- ^ a b c d e f Brown, D.J. Heterocyclic Compounds: Thy Pyrimidinesboner. Vol 52. New York: Interscience, 1994.
- ^ a b Horton, Robert H.; et al.Principles of Biochemistry. 3rd ed. Upper Saddle River, NJ: Prentice Hall, 2002.
- ^ Martins, Zita; Botta, Oliver; Fogel, Marilyn L.; Sephton, Mark A.; Glavin, Daniel P.; Watson, Jonathan S.; Dworkin, Jason P.; Schwartz, Alan W.; Ehrenfreund, Pascale (15 June 2008). "Extraterrestrial nucleobases in the Murchison meteorite". Earth and Planetary Science Letters 270 (1–2): 130–136. arXiv:0806.2286. Bibcode:2008E&PSL.270..130M. doi:10.1016/j.epsl.2008.03.026.
- ^ AFP Staff (20 August 2009). "We may all be space aliens: study". AFP. Retrieved 2011-08-14.
- ^ Clark; Pearson, N.; Brown, R. H.; Cruikshank, D. P.; Barnes, J.; Jaumann, R.; Soderblom, L.; Griffith, C.; Rannou, P.; Rodriguez, S.; Le Mouelic, S.; Lunine, J.; Sotin, C.; Baines, K. H.; Buratti, B. J.; Nicholson, P. D.; Nelson, R. M.; Stephan, K. et al. (2012). "The Surface Composition of Titan". American Astronomical Society (Smithsonian/NASA Astrophysics Data System) 44. Bibcode:2012DPS....4420102C.
- ^ http://www.madsci.org
- ^ Zorbach, W.W. Synthetic Procedures in Nucleic Acid Chemistry: Physical and Physicochemical Aids in Determination of Structure. Vol 2. New York: Wiley-Interscience, 1973.
- ^ Lee, J.K.; Kurinovich, Ma. J Am Soc Mass Spectrom.13(8), 2005, 985-95.
- ^ Marlaire, Ruth (5 November 2009). "NASA Reproduces a Building Block of Life in Laboratory". NASA. Retrieved 5 March 2015.
- ^ Marlaire, Ruth (3 March 2015). "NASA Ames Reproduces the Building Blocks of Life in Laboratory". NASA. Retrieved 5 March 2015.
- ^ Chittenden, G.J.F.; Schwartz, Alan W. Nature.263,(5575), 350-1.
- ^ a b c Kochetkov, N.K. and Budovskii, E.I. Organic Chemistry of Nucleic Acids Part B. New York: Plenum Press, 1972.
- ^ a b c Brown, E.G. Ring Nitrogen and Key Biomolecules: The Biochemistry of N-Heterocycles. Boston: Lluwer Academic Publishers, 1998.
- ^ a b Mashiyama, S.T; et al.'Anal Biochem. 330(1),2004, 58-69.
- ^ "A Novel Method of Caffeine Synthesis from Uracil". Synthetic Communications 33 (19): 3291–3297. 2003. doi:10.1081/SCC-120023986.
- ^ Hildalgo, A; et al.'J Agric Food Chem.53(2),2005, 349-55.
- ^ a b Pozharskii, A.F.; et al.Heterocycles in Life and Society: An Introduction to Heterocyclic Chemistry and Biochemistry and the Role of Heterocycles in Science, Technology, Medicine, and Agriculture. New York: John Wiley and Sons, 1997.
- ^ http://jb.asm.org/cgi/content/full/181/6/1793
External links
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Nucleic acid constituents
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| Nucleobase |
- Purine
- Adenine
- Guanine
- Hypoxanthine
- Xanthine
- Purine analogue
- Pyrimidine
- Uracil
- Thymine
- Cytosine
- Pyrimidine analogue
- Unnatural base pair (UBP)
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| Nucleoside |
| Ribonucleoside |
- Adenosine
- Guanosine
- 5-Methyluridine
- Uridine
- Cytidine
- Inosine
- Xanthosine
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| Deoxyribonucleoside |
- Deoxyadenosine
- Deoxyguanosine
- Thymidine
- Deoxyuridine
- Deoxycytidine
- Deoxyinosine
- Deoxyxanthosine
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Nucleotide
(Nucleoside monophosphate) |
| Ribonucleotide |
- AMP
- GMP
- m5UMP
- UMP
- CMP
- IMP
- XMP
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| Deoxyribonucleotide |
- dAMP
- dGMP
- dTMP
- dUMP
- dCMP
- dIMP
- dXMP
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| Cyclic nucleotide |
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| Nucleoside diphosphate |
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| Nucleoside triphosphate |
- ATP
- GTP
- m5UTP
- UTP
- CTP
- ITP
- XTP
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- dATP
- dGTP
- dTTP
- dUTP
- dCTP
- dITP
- dXTP
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Index of biochemical families
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| Carbohydrates |
- Alcohols
- Glycoproteins
- Glycosides
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| Lipids |
- Eicosanoids
- Fatty acids
- Glycerides
- Phospholipids
- Sphingolipids
- Steroids
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| Nucleic acids |
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| Proteins |
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| Other |
- Tetrapyrroles
- intermediates
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![21038-67-5 | Pyrido[2,3-d]pyrimidine-2,4(1h,3h)-dione | Tetrahedron](https://1mg.info/0/j/v/2125.jpg)
