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 Edit this at Wikidata
MeSH Thymine
UNII
  • InChI=1S/C5H6N2O2/c1-3-2-6-5(9)7-4(3)8/h2H,1H3,(H2,6,7,8,9) checkY
    Key: RWQNBRDOKXIBIV-UHFFFAOYSA-N checkY
  • 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).

Thymine (/ˈθmɪn/) (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]

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]

Synthesis

Laboratory synthesis

Thymine was first prepared by hydrolysis of the corresponding nucleoside obtained from natural sources. Interest in its direct chemical synthesis began in the early 1900s: Emil Fischer published a method starting from urea but a more practical synthesis used methylisothiourea in a condensation reaction with ethyl formyl propionate, followed by hydrolysis of the pyrimidine intermediate:[9]

Many other preparative methods have been developed, including optimised conditions so that urea can be used directly in the reaction shown above, preferably with methyl formyl propionate.[10]

See also

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 (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. ^ Wheeler, H.I.; Merriam, H.F. (1903). "On some condensation products of the pseudothioureas: synthesis of uracil, thymine, and similar compounds". American Chemical Journal. 29 (5): 478–492.
  10. ^ Guo, Xianghai; Shen, Jiaxiang (2014). "An environmentally benign approach to the synthesis of thymine via hydroformylation of methyl acrylate". Monatshefte für Chemie - Chemical Monthly. 145 (4): 657–661. doi:10.1007/s00706-013-1128-y. S2CID 97367180.