View source for Thymine

{{Short description|Chemical compound of DNA}}
{{Distinguish|Thiamine|thymidine}}
{{chembox
| ImageFile1 = Thymin.svg
| ImageSize1 = 120px
| ImageClass1 = skin-invert-image
| ImageFileL2 = Thymine-3D-balls.png
| ImageClassL2 = bg-transparent  
| ImageFileR2 = Thymine-3D-vdW.png
| ImageClassR2 = bg-transparent  
| PIN = 5-Methylpyrimidine-2,4(1''H'',3''H'')-dione
| OtherNames = 5-Methyluracil
| Section1 = {{Chembox Identifiers
| IUPHAR_ligand = 4581
| CASNo = 65-71-4
| CASNo_Ref = {{cascite|correct|CAS}}
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 17821
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 993
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = QR26YLT7LT
| PubChem = 1135
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 1103
| SMILES = O=C1NC(=O)NC=C1C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C5H6N2O2/c1-3-2-6-5(9)7-4(3)8/h2H,1H3,(H2,6,7,8,9)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = RWQNBRDOKXIBIV-UHFFFAOYSA-N
| MeSHName = Thymine
  }}
| Section2 = {{Chembox Properties
|   C = 5 |H = 6 |N = 2 |O = 2
|   Appearance = 
|   Density = 1.223 g cm<sup>−3</sup> (calculated)
|   MeltingPtC = 316 to 317
|   BoilingPtC = 335
|   BoilingPt_notes = (decomposes)
|   Solubility = 3.82 g/L<ref>{{cite journal |first1= R.-M. |last1= Dannenfelser |first2= S.H. |last2= Yalkowsky |date= December 1991 |title= Data base of aqueous solubility for organic non-electrolytes |url= https://www.sciencedirect.com/science/article/abs/pii/004896979190214Y |journal= [[Science of the Total Environment]] |volume=109 |issue= C |pages= 625–628 |doi= 10.1016/0048-9697(91)90214-Y |bibcode= 1991ScTEn.109..625D |access-date = 2021-11-14|url-access= subscription }}</ref>
| pKa=9.7}}
<!---
| Section3 = {{Chembox Hazards
| MainHazards = 
| FlashPt = 
| AutoignitionPt = 
| MagSus = -57.1·10<sup>−6</sup> cm<sup>3</sup>/mol}}
--->
}}
'''Thymine''' ({{IPAc-en|ˈ|θ|aɪ|m|iː|n}}) ([[nucleoside#List of nucleosides and corresponding nucleobases|symbol]] '''T''' or '''Thy''') is one of the four [[nucleotide base]]s 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.<ref>{{cite journal
| last1      = Albrecht
| first1     = Kossel
| authorlink1= Albrecht Kossel
| last2      = Neumann
| first2     = Albert
| date       = Oct–Dec 1893
| title      = Ueber das Thymin, ein Spaltungsproduct der Nucleïnsäure
| trans-title=On thymine, a cleavage product of nucleic acid
| url        = http://gallica.bnf.fr/ark:/12148/bpt6k90730p/f455.image
| journal    = [[Berichte der Deutschen Chemischen Gesellschaft]]
| volume     = 26
| issue      = 3
| pages      = 2753–2756
| doi        = 10.1002/cber.18930260379
| access-date= 2021-11-14
| quote-page = 2754
| quote      = Wir bezeichnen diese Substanz als Thymin.
| trans-quote= We designate this substance as thymine.
}}
</ref>

==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]] ('''d'''eoxy'''t'''hymidine '''m'''ono'''p'''hosphate), [[dTDP]], or [[dTTP]] (for the '''d'''i- and '''t'''ri- phosphates, respectively).

One of the common mutations of DNA involves two adjacent thymines or cytosine, which, in presence of [[Ultraviolet|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 replication|DNA synthesis]] in actively dividing cells.

Thymine bases are frequently oxidized to [[hydantoin]]s over time after the death of an organism.<ref>{{cite journal
| last1      = Hofreiter
| first1     = Michael
| last2      = Serre
| first2     = David
| last3      = Poinar
| first3     = Henrik N.
|authorlink3 = Hendrik Poinar
| last4      = Kuch
| first4     = Melanie
| last5      = Pääbo
| first5     = Svante
|authorlink5 = Svante Pääbo
| date       = 2001-05-01
| title      = Ancient DNA
| url        = 
| journal    = [[Nature Reviews Genetics]]
| volume     = 2
| issue      = 5
| pages      = 353–359
| doi        = 10.1038/35072071
| pmid = 11331901
| s2cid = 205016024
| access-date = 
}}
</ref>

==Thymine imbalance causes mutation==
During growth of [[Escherichia virus T4 |bacteriophage T4]], an imbalance of thymine availability, either a deficiency or an excess of thymine, causes increased [[mutation]].<ref>
{{cite journal
| last1      = Bernstein
| first1     = Carol
| last2      = Bernstein
| first2     = Harris
| last3      = Mufti
| first3     = Siraj
| last4      = Strom
| first4     = Barbara
| date       = October 1972
| title      = Stimulation of mutation in phage T 4 by lesions in gene 32 and by thymidine imbalance
| url        = 
| journal    = [[Mutat. Res.]]
| volume     = 16
| issue      = 2
| pages      = 113–119
| doi        = 10.1016/0027-5107(72)90171-6
| pmid       = 4561494
| access-date = 
}}
</ref> The mutations caused by thymine deficiency appear to occur only at AT [[base pair]] sites in DNA and are often AT to GC [[transition (genetics)|transition mutations]].<ref>
{{cite journal
| last1      = Smith
| first1     = M. Diane
| last2      = Green
| first2     = Ronald R.
| last3      = Ripley 
| first3     = Lynn S.
| last4      = Drake
| first4     = John W.
| authorlink4=John W. Drake
| date       = July 1973
| title      = Thymineless mutagenesis in bacteriophage T4
| journal    = [[Genetics_(journal)|Genetics]]
| volume     = 74
| issue      = 3
| pages      = 393–403
| doi        = 10.1093/genetics/74.3.393
| pmc        = 1212957
| pmid       = 4270369
}}
</ref> In the bacterium ''[[Escherichia coli]]'', thymine deficiency was also found to cause the same mutation.<ref>{{cite journal
| last1      = Deutch
| first1     = Charles E.
| last2      = Pauling
| first2     = Crellin
| date       = Sep 1974
| title      = Thymineless mutagenesis in Escherichia coli
| journal    = [[J. Bacteriol.]]
| volume     = 119
| issue      = 3
| pages      = 861–7
| doi        = 10.1128/JB.119.3.861-867.1974
| pmc        = 245692
| pmid       = 4605383
}}</ref>

==Theoretical aspects==
In March 2015, NASA scientists reported that, for the first time, complex [[DNA]] and [[RNA]] [[organic compound]]s 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 [[meteorite]]s. Pyrimidine, like [[polycyclic aromatic hydrocarbon]]s (PAHs), another carbon-rich compound, may have been formed in [[red giant]]s or in [[Cosmic dust|interstellar dust]] and gas clouds, according to the scientists.<ref name="NASA-20150303">{{cite web |last=Marlaire |first=Ruth |title=NASA Ames Reproduces the Building Blocks of Life in Laboratory |url=http://www.nasa.gov/content/nasa-ames-reproduces-the-building-blocks-of-life-in-laboratory |date=2015-03-03 |publisher=[[NASA]] |website=www.nasa.gov |access-date=2021-11-15 |archive-date=2015-03-05 |archive-url=https://web.archive.org/web/20150305083306/http://www.nasa.gov/content/nasa-ames-reproduces-the-building-blocks-of-life-in-laboratory/ |url-status=dead }}</ref> 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 [[Redox|oxidation]] reaction with [[hydrogen peroxide]].<ref>{{Cite web|url=https://blogs.scientificamerican.com/guest-blog/did-the-seeds-of-life-come-from-space/|title=Did the Seeds of Life Come from Space?|last=Tasker|first=Elizabeth|publisher=[[Scientific American]] |access-date=2016-11-24|website=blogs.scientificamerican.com|date=2016-11-10|authorlink=Elizabeth J. Tasker}}</ref>

==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:<ref>{{cite journal |last1=Wheeler |first1=H.I. |last2=Merriam |first2=H.F. |year=1903 |title=On some condensation products of the pseudothioureas: synthesis of uracil, thymine, and similar compounds. |journal=American Chemical Journal |volume=29 |issue=5 |pages=478–492 |url=https://babel.hathitrust.org/cgi/pt?id=uc2.ark:/13960/t72v2dx94&view=1up&seq=17}}</ref>
:[[File:Thymine synthesis (1903).svg|600px|class=skin-invert-image]]
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.<ref>{{cite journal |doi=10.1007/s00706-013-1128-y |title=An environmentally benign approach to the synthesis of thymine via hydroformylation of methyl acrylate |year=2014 |last1=Guo |first1=Xianghai |last2=Shen |first2=Jiaxiang |journal=Monatshefte für Chemie - Chemical Monthly |volume=145 |issue=4 |pages=657–661 |s2cid=97367180 }}</ref>

==See also==
{{Div col|colwidth=20em}}
* [[Deoxyribose]]
* [[Deoxythymidine]]
* [[Nucleobase]]  
* [[Pyrimidine]]	
* [[Thymineless death]]
* [[Uracil]]
{{div col end}}

==References==
{{reflist}}

==External links==
* [http://gmd.mpimp-golm.mpg.de/Spectrums/51a54b80-5865-40c0-8275-cf90f70d6331.aspx Thymine MS Spectrum]
*[http://www.infoplease.com/ce6/sci/A0848663.html Infoplease Encyclopedia]
*[https://web.archive.org/web/20100823233329/http://scienceaid.co.uk/biology/genetics/dna.html Science Aid: DNA Structure and Replication]

{{Nucleobases, nucleosides, and nucleotides}}

[[Category:Nucleobases]]
[[Category:Pyrimidinediones]]