Uracil

Uracil
General
Systematic name	Pyrimidine-2,4(1H,3H)-dione
Other names	Uracil, 2-oxy-4-oxy pyrimidine, 2,4(1H,3H)-pyrimidinedione, 2,4-dihydroxypryimidine, 2,4-pyrimidinediol
Molecular formula	C₄H₄N₂O₂
Molar mass	112.09 g/mol
Appearance	Solid
CAS number	^*
Properties
Density and phase
Solubility in water	Soluble.
Melting point	335 °C (? K)
Boiling point	N/A
Acidity (pK_a)	basic pK_a = -3.4, acidic pK_a = 9.38_9.
Structure
Molecular shape	pyrimidine
Hazards
MSDS	External MSDS
Main hazards	carcinogen & tetratogen with chronic exposure
NFPA 704
Flash point	non flammable
R/S statement	R
RTECS number	YQ8650000
Supplementary data page
Structure and properties	n, ε_r, etc.
Thermodynamic data	Phase behaviour Solid, liquid, gas
Spectral data	UV, IR, NMR, MS
Related compounds
Other cations
Related compounds	Thymine
Except where noted otherwise, data are given for materials in their standard state (at 25°C, 100 kPa) Chemical infobox

Uracil is a common naturally occurring pyrimidineGarrett, Reginald H.; Grisham, Charles M. Principles of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning, 1997.. Uracil was originally discovered in 1900 and it was isolated by hydrolysis of yeast nuclein that was found in bovine thymus and spleen, herring sperm, and wheat germBrown, D.J. Heterocyclic Compounds: Thy Pyrimidines. Vol 52. New York: Interscience, 1994.. Uracil is a planar, unsaturated compound that has the ability to absorb lightHorton, Robert H.; et al.Principles of Biochemistry. 3rd ed. Upper Saddle River, NJ: Prentice Hall, 2002.

Properties

Found in RNA, it base pairs with adenine and is replaced by thymine in DNA. Methylation of uracil produces thyminewww.madsci.org. It turns into thymine to protect the DNA and to improve the efficiency of DNA replication. Uracil can base pair with any of the bases depending on how the molecule arranges itself on the helix, but readily pairs with adenosine because the methyl group is repelled into a fixed positionwww.madsci.org. As stated, uracil pairs with adenosine through hydrogen bonding. Uracil is the hydrogen bond acceptor and can form up to three hydrogen bonds. Uracil can also bind with a ribose sugar to form a ribonucleoside, uridine. When a phosphate attaches to uridine, uridine 5'-monophosphate is producedHorton, Robert H.; et al.Principles of Biochemistry. 3rd ed. Upper Saddle River, NJ: Prentice Hall, 2002..

Uracil, U, undergoes keto-enol tautomeric shifts because of its resonance structures due to the NH₂ substitutents and OH substitutents. Also because any nuclear instablility the molecule may have from the lack of formal aromaticity is compensated by the cyclic-amidic stabilityBrown, D.J. Heterocyclic Compounds: Thy Pyrimidines. Vol 52. New York: Interscience, 1994.. The keto tautomer is referred to the lactam structure, while the enol 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.

Uracil also recycles itself to form nucleotides by undergoing a series of phophoribosyltransferase reactionsGarrett, Reginald H.; Grisham, Charles M. Principles of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning, 1997.. Degradation of uracil produces substrates, aspartate, carbon dioxide, and ammoniaGarrett, Reginald H.; Grisham, Charles M. Principles of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning, 1997..

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 knownZorbach, W.W. Synthetic Procedures in Nucleic Acid Chemistry: Physical and Physicochemical Aids in Determination of Structure. Vol 2. New York: Wiley-Interscience, 1973.. The negative charge is placed on the oxygen anion and produces a pK_a of less than or equal to 12. The basic pK_a = -3.4, while the acidic pK_a = 9.38_{9. In the gas phase, uracil has 4 sites that are more acidic than waterLee,J.K.; Kurinovich, Ma. J Am Soc Mass Spectrom.13(8), 2005, 985-95..}

Synthesis

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 ammoniaGarrett, Reginald H.; Grisham, Charles M. Principles of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning, 1997.. The most common way to synthesize uracil is by the condensation of maleic acid with urea in fuming sulfuric acidBrown, D.J. Heterocyclic Compounds: Thy Pyrimidines. Vol 52. New York: Interscience, 1994. as seen below also. Uracil can also be synthesized by a double decomposition of thiouracil in aqueous chloroacetic acidBrown, D.J. Heterocyclic Compounds: Thy Pyrimidines. Vol 52. New York: Interscience, 1994..

C₄H₅N₃O + H₂O → C₄H₄N₂O₂ + NH₃

C₄H₄O₄ + CH₄N₂O → C₄H₄N₂O₂ + 2 H₂O + CO

Reactions

Uracil readily undergoes regular reactions including oxidation, nitration, and alkylation. While in the presence of PhOH/NaOCl, uracil can be visualized in the blue region of UV lightBrown, D.J. Heterocyclic Compounds: Thy Pyrimidines. Vol 52. New York: Interscience, 1994.. Uracil also has the capability to react with elemental halogens because of the presence of more than one strongly electron donating groupBrown, D.J. Heterocyclic COmpounds: Thy Pyrimidines. Vol 52. New York: Interscience, 1994..

Uracil readily undergoes addition to ribose sugars and phosphates to partake in synthesis and further reactions in the body. Uracil becomes Uridine-monophosphate (UMP), uridine-diphosphate (UDP), uridine-triphosphate (UTP), and uracil-diphosphate glucose (UDP-glucose). Each one of these molecules in synthesized in the body and has specific functions.

When uracil reactes with anhydrous hydrazine a first order kinetic reacion occurs and the ring of uracil opens upKochetkov, N.K. and Budovskii, E.I. Organic Chemistry of Nucleic Acids Part B. New York: Plenum Press, 1972.. If the pH of the reaction increases to >10.5 the uracil anion forms making the reaction go much slower, the same slowing of the reaction occurs if the pH decreases because of the protonation of the hydrazineKochetkov, N.K. and Budovskii, E.I. Organic Chemistry of Nucleic Acids Part B. New York: Plenum Press, 1972.. The reactivity of uracil is unchanged even if the temperature changesKochetkov, N.K. and Budovskii, E.I. Organic Chemistry of Nucleic Acids Part B. New York: Plenum Press, 1972..

Uses

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 processGarrett, Reginald H.; Grisham, Charles M. Principles of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning, 1997.. The drug molecule also fools the enzymes that help in this process to incorporate this compound in the replication and not uracil, this causes the biological polymer (cancer) not to continue synthesizingGarrett, Reginald H.; Grisham, Charles M. Principles of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning, 1997..

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 phosphatesGarrett, Reginald H.; Grisham, Charles M. Principles of Biochemistry with a Human Focus. United States: Brooks/Cole Thomson Learning, 1997.. Uracil serves as allosteric regulator and coenzyme for reactions in the human body and in plantsBrown, E.G. Ring Nitrogen and Key Biomolecules: The Biochemistry of N-Heterocycles. Boston: Lluwer Academic Publishers, 1998.. 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 int he liver and other tissues in the process of carbohydrate metabolismBrown, E.G. Ring Nitrogen and Key Biomolecules: The Biochemistry of N-Heterocycles. Boston: Lluwer Academic Publishers, 1998.. Uracil is also involved in the biosynthesis of polysaccharides and the transportation of sugars containing aldehydesBrown, E.G. Ring Nitrogen and Key Biomolecules: The Biochemistry of N-Heterocycles. Boston: Lluwer Academic Publishers, 1998..

It can also increase the risk for cancer in cases where the body is extremely deficient in folateMashiyama, S.T; et al.'Anal Biochem. 330(1),2004, 58-69.. The defiency in folate leads to increased ratio of deoxyuracilmonophosphates (dUMP)/deoxythyminemonophosphates (dTMP) and uracil misincorporation into DNA and eventually low production of DNAMashiyama, S.T; et al.'Anal Biochem. 330(1),2004, 58-69..

Uracil can be used to determine microbial contamination of tomatoes. Only after lactic acid bacteria have contaminated the fruit, uracil appearsHildalgo, A; et al.'J Agric Food Chem.53'(2),2005, 349-55.. Uracil's derivatives, that contain a diazine ring, are used in pesticidesPozharskii, 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.. More often used as antiphotosynthetic herbicides and destroy weeds in cotton, sugar beet, turnips, soya, peas, sunflower crops, vineyards, berry plantations, and orchardsPozharskii, 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..

References

Pyrimidines

Gourt Home::Gourt :: Uracil

Properties

Synthesis

Reactions

Uses

References