Thymine

Thymine (/ˈθaɪmɪn/) (symbol T or Thy) is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nucleobase. In RNA, thymine is replaced by the nucleobase uracil. Thymine was first isolated in 1893 by Albrecht Kossel and Albert Neumann from calf thymus glands, hence its name.[2]

For the B vitamin whose name sounds and looks similar, see Thiamine.
Thymine
Names
Preferred IUPAC name
5-Methylpyrimidine-2,4(1H,3H)-dione
Other names
5-Methyluracil
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.560
IUPHAR/BPS
MeSH Thymine
UNII
CompTox Dashboard (EPA)
  • InChI=1S/C5H6N2O2/c1-3-2-6-5(9)7-4(3)8/h2H,1H3,(H2,6,7,8,9) N
    Key: RWQNBRDOKXIBIV-UHFFFAOYSA-N N
  • InChI=1/C5H6N2O2/c1-3-2-6-5(9)7-4(3)8/h2H,1H3,(H2,6,7,8,9)
    Key: RWQNBRDOKXIBIV-UHFFFAOYAL
  • O=C1NC(=O)NC=C1C
Properties
C5H6N2O2
Molar mass 126.115 g·mol−1
Density 1.223 g cm−3 (calculated)
Melting point 316 to 317 °C (601 to 603 °F; 589 to 590 K)
Boiling point 335 °C (635 °F; 608 K) (decomposes)
3.82 g/L[1]
Acidity (pKa) 9.7
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Infobox references

Derivation

As its alternate name (5-methyluracil) suggests, thymine may be derived by methylation of uracil at the 5th carbon. In RNA, thymine is replaced with uracil in most cases. In DNA, thymine (T) binds to adenine (A) via two hydrogen bonds, thereby stabilizing the nucleic acid structures.

Thymine combined with deoxyribose creates the nucleoside deoxythymidine, which is synonymous with the term thymidine. Thymidine can be phosphorylated with up to three phosphoric acid groups, producing dTMP (deoxythymidine monophosphate), dTDP, or dTTP (for the di- and tri- phosphates, respectively).

One of the common mutations of DNA involves two adjacent thymines or cytosine, which, in presence of ultraviolet light, may form thymine dimers, causing "kinks" in the DNA molecule that inhibit normal function.

Thymine could also be a target for actions of 5-fluorouracil (5-FU) in cancer treatment. 5-FU can be a metabolic analog of thymine (in DNA synthesis) or uracil (in RNA synthesis). Substitution of this analog inhibits DNA synthesis in actively dividing cells.

Thymine bases are frequently oxidized to hydantoins over time after the death of an organism.[3]

Thymine imbalance causes mutation

During growth of bacteriophage T4, an imbalance of thymine availability, either a deficiency or an excess of thymine, causes increased mutation.[4] The mutations caused by thymine deficiency appear to occur only at AT base pair sites in DNA and are often AT to GC transition mutations.[5] In the bacterium Escherichia coli, thymine deficiency was also found to be mutagenic and cause AT to GC transitions.[6]

Theoretical aspects

In March 2015, NASA scientists reported that, for the first time, 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), another carbon-rich compound, may have been formed in red giants or in interstellar dust and gas clouds, according to the scientists.[7] Thymine has not been found in meteorites, which suggests the first strands of DNA had to look elsewhere to obtain this building block. Thymine likely formed within some meteorite parent bodies, but may not have persisted within these bodies due to an oxidation reaction with hydrogen peroxide.[8]

Production

Patented 2013, the current method used for the manufacturing of thymine is done by dissolving the molecule Methyl methacrylate in a solvent of methanol. The solvent is to be maintained at a pH of 8.9-9.1 by addition of a base like sodium hydroxide and a temperature of 0-10 degrees Celsius.  30% Hydrogen peroxide is then added to the solution to act as an oxygen giver, and the entire solution is heated for 2-20 hours to form 2,3-epoxy-2-methyl methacrylate, which is extracted by drying the solution with magnesium sulphate. The 2,3-epoxy-2-methyl methacrylate is then put into a separate flask containing 100% alcohol (ethanol or methanol), urea, and tosic acid after the mixture is heated to the point that the alcohol-urea-tosic acid solution starts refluxing (boiling and feeding back into solution ). After adding 2,3-epoxy-2-methyl methacrylate to the refluxing solution, it is left in its refluxing state for 1-3 hours. After this period, the solution is cooled to 65 degrees Celsius and sodium methylate (sodium methoxide) is added at 30% concentration within a solution of ethanol or methanol and left to react for 1-3 hours. After this period thymine should have formed in the solution. The solution is then concentrated by removing excess methanol through keeping the heat at 65 degrees celsius (slightly above boiling point of methanol) and allowing the methanol to vaporize out of the solution instead of reflux. The concentrated solution is then neutralized and precipitated by adding hydrochloric acid, forming waste sodium chloride and the desired thymine crystals among the solution. The solution is temporarily warmed up to re-dissolve the crystals, then passed through a reverse osmosis filter to remove the sodium chloride formed and isolate the solution containing the thymine. This solution is cooled to precipitate the crystals and  then air-dried to yield pure thymine crystals in the form of a white powder. [9]

See also
  • Deoxyribose
  • Deoxythymidine
  • Nucleobase
  • Pyrimidine
  • Thymineless death
  • Uracil

References
  1. Dannenfelser, R.-M.; Yalkowsky, S.H. (December 1991). "Data base of aqueous solubility for organic non-electrolytes". Science of the Total Environment. 109–110 (C): 625–628. Bibcode:1991ScTEn.109..625D. doi:10.1016/0048-9697(91)90214-Y. Retrieved 2021-11-14.
  2. Albrecht, Kossel; Neumann, Albert (Oct–Dec 1893). "Ueber das Thymin, ein Spaltungsproduct der Nucleïnsäure" [On thymine, a cleavage product of nucleic acid]. Berichte der Deutschen Chemischen Gesellschaft. 26 (3): 2753–2756. doi:10.1002/cber.18930260379. Retrieved 2021-11-14. p. 2754: Wir bezeichnen diese Substanz als Thymin. [We designate this substance as thymine.]
  3. Hofreiter, Michael; Serre, David; Poinar, Henrik N.; Kuch, Melanie; Pääbo, Svante (2001-05-01). "Ancient DNA". Nature Reviews Genetics. 2 (5): 353–359. doi:10.1038/35072071. PMID 11331901. S2CID 205016024.
  4. Bernstein, Carol; Bernstein, Harris; Mufti, Siraj; Strom, Barbara (October 1972). "Stimulation of mutation in phage T 4 by lesions in gene 32 and by thymidine imbalance". Mutat. Res. 16 (2): 113–119. doi:10.1016/0027-5107(72)90171-6. PMID 4561494.
  5. Smith, M. Diane; Green, Ronald R.; Ripley, Lynn S.; Drake, John W. (July 1973). "Thymineless mutagenesis in bacteriophage T4". Genetics. 74 (3): 393–403. doi:10.1093/genetics/74.3.393. PMC 1212957. PMID 4270369.
  6. Deutch, Charles E.; Pauling, Crellin (Sep 1974). "Thymineless mutagenesis in Escherichia coli". J. Bacteriol. 119 (3): 861–7. doi:10.1128/JB.119.3.861-867.1974. PMC 245692. PMID 4605383.
  7. Marlaire, Ruth (2015-03-03). "NASA Ames Reproduces the Building Blocks of Life in Laboratory". www.nasa.gov. NASA. Retrieved 2021-11-15.
  8. Tasker, Elizabeth (2016-11-10). "Did the Seeds of Life Come from Space?". blogs.scientificamerican.com. Scientific American. Retrieved 2016-11-24.
  9. CN 103232399, Duo, Wenbin, "Synthetic method of thymine", published 2013-08-07, assigned to Tianjin Jude Technology Co. Ltd.
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