Thymine

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Thymine
Thymin.svg
Thymine-3D-balls.png
Thymine-3D-vdW.png
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 OOjs UI icon edit-ltr-progressive.svg
MeSH Thymine
PubChem CID
UNII
  • InChI=1S/C5H6N2O2/c1-3-2-6-5(9)7-4(3)8/h2H,1H3,(H2,6,7,8,9) X mark.svgN
    Key: RWQNBRDOKXIBIV-UHFFFAOYSA-N X mark.svgN
  • 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).
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Infobox references

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]

Contents

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

Related Research Articles

Base pair Unit consisting of two nucleobases bound to each other by hydrogen bonds

A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA and RNA. Dictated by specific hydrogen bonding patterns, "Watson–Crick" base pairs allow the DNA helix to maintain a regular helical structure that is subtly dependent on its nucleotide sequence. The complementary nature of this based-paired structure provides a redundant copy of the genetic information encoded within each strand of DNA. The regular structure and data redundancy provided by the DNA double helix make DNA well suited to the storage of genetic information, while base-pairing between DNA and incoming nucleotides provides the mechanism through which DNA polymerase replicates DNA and RNA polymerase transcribes DNA into RNA. Many DNA-binding proteins can recognize specific base-pairing patterns that identify particular regulatory regions of genes.

Cytosine Chemical compound in nucleic acids

Cytosine is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine. It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached. The nucleoside of cytosine is cytidine. In Watson-Crick base pairing, it forms three hydrogen bonds with guanine.

DNA Molecule that carries genetic information

Deoxyribonucleic acid is a molecule composed of two polynucleotide chains that coil around each other to form a double helix carrying genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids. Alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life.

Guanine Chemical compound of DNA and RNA

Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine. In DNA, guanine is paired with cytosine. The guanine nucleoside is called guanosine.

Nucleic acid Class of large biomolecules essential to all known life

Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). If the sugar is ribose, the polymer is RNA; if the sugar is the ribose derivative deoxyribose, the polymer is DNA.

Nucleotide Biological molecules that form the building blocks of nucleic acids

Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common nutrients by the liver.

Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. One of the three diazines, it has the nitrogen atoms at positions 1 and 3 in the ring. The other diazines are pyrazine and pyridazine. In nucleic acids, three types of nucleobases are pyrimidine derivatives: cytosine (C), thymine (T), and uracil (U).

RNA world Hypothetical stage in the early evolutionary history of life on Earth

The RNA world is a hypothetical stage in the evolutionary history of life on Earth, in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posits the existence of this stage.

Adenine Chemical compound in DNA and RNA

Adenine is a nucleobase. It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The three others are guanine, cytosine and thymine. Its derivatives have a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate (ATP) and the cofactors nicotinamide adenine dinucleotide (NAD), flavin adenine dinucleotide (FAD) and Coenzyme A. It also has functions in protein synthesis and as a chemical component of DNA and RNA. The shape of adenine is complementary to either thymine in DNA or uracil in RNA.

Uracil Chemical compound of RNA

Uracil is one of the four nucleobases in the nucleic acid 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 is a demethylated form of thymine.

Nucleobase Nitrogen-containing biological compounds that form nucleosides

Nucleobases, also known as nitrogenous bases or often simply bases, are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic building blocks of nucleic acids. The ability of nucleobases to form base pairs and to stack one upon another leads directly to long-chain helical structures such as ribonucleic acid (RNA) and deoxyribonucleic acid (DNA).

Thymidine Chemical compound

Thymidine, also known as deoxythymidine, deoxyribosylthymine, or thymine deoxyriboside, is a pyrimidine deoxynucleoside. Deoxythymidine is the DNA nucleoside T, which pairs with deoxyadenosine (A) in double-stranded DNA. In cell biology it is used to synchronize the cells in G1/early S phase. The prefix deoxy- is often left out since there are no precursors of thymine nucleotides involved in RNA synthesis.

Albrecht Kossel

Ludwig Karl Martin Leonhard Albrecht Kossel was a German biochemist and pioneer in the study of genetics. He was awarded the Nobel Prize for Physiology or Medicine in 1910 for his work in determining the chemical composition of nucleic acids, the genetic substance of biological cells.

Nucleic acid sequence Succession of nucleotides in a nucleic acid

A nucleic acid sequence is a succession of bases signified by a series of a set of five different letters that indicate the order of nucleotides forming alleles within a DNA or RNA (GACU) molecule. By convention, sequences are usually presented from the 5' end to the 3' end. For DNA, the sense strand is used. Because nucleic acids are normally linear (unbranched) polymers, specifying the sequence is equivalent to defining the covalent structure of the entire molecule. For this reason, the nucleic acid sequence is also termed the primary structure.

Ribonucleotide nucleotide containing ribose as its pentose component

In biochemistry, a ribonucleotide is a nucleotide containing ribose as its pentose component. It is considered a molecular precursor of nucleic acids. Nucleotides are the basic building blocks of DNA and RNA. Ribonucleotides themselves are basic monomeric building blocks for RNA. Deoxyribonucleotides, formed by reducing ribonucleotides with the enzyme ribonucleotide reductase (RNR), are essential building blocks for DNA. There are several differences between DNA deoxyribonucleotides and RNA ribonucleotides. Successive nucleotides are linked together via phosphodiester bonds.

DNA glycosylases are a family of enzymes involved in base excision repair, classified under EC number EC 3.2.2. Base excision repair is the mechanism by which damaged bases in DNA are removed and replaced. DNA glycosylases catalyze the first step of this process. They remove the damaged nitrogenous base while leaving the sugar-phosphate backbone intact, creating an apurinic/apyrimidinic site, commonly referred to as an AP site. This is accomplished by flipping the damaged base out of the double helix followed by cleavage of the N-glycosidic bond.

Nucleic acid metabolism

Nucleic acid metabolism is the process by which nucleic acids are synthesized and degraded. Nucleic acids are the polymers of nucleotides. Nucleotide synthesis is an anabolic mechanism generally involving the chemical reaction of phosphate, pentose sugar, and a nitrogenous base. Destruction of nucleic acid is a catabolic reaction. Additionally, parts of the nucleotides or nucleobases can be salvaged to recreate new nucleotides. Both synthesis and degradation reactions require enzymes to facilitate the event. Defects or deficiencies in these enzymes can lead to a variety of diseases.

Pyrimidine dimer

Pyrimidine dimers are molecular lesions formed from thymine or cytosine bases in DNA via photochemical reactions. Ultraviolet light (UV) induces the formation of covalent linkages between consecutive bases along the nucleotide chain in the vicinity of their carbon–carbon double bonds. The dimerization reaction can also occur among pyrimidine bases in dsRNA —uracil or cytosine. Two common UV products are cyclobutane pyrimidine dimers (CPDs) and 6–4 photoproducts. These premutagenic lesions alter the structure and possibly the base-pairing. Up to 50–100 such reactions per second might occur in a skin cell during exposure to sunlight, but are usually corrected within seconds by photolyase reactivation or nucleotide excision repair. Uncorrected lesions can inhibit polymerases, cause misreading during transcription or replication, or lead to arrest of replication. Pyrimidine dimers are the primary cause of melanomas in humans.

Nucleic acid analogue Compound analogous to naturally occurring RNA and DNA

Nucleic acid analogues are compounds which are analogous to naturally occurring RNA and DNA, used in medicine and in molecular biology research. Nucleic acids are chains of nucleotides, which are composed of three parts: a phosphate backbone, a pentose sugar, either ribose or deoxyribose, and one of four nucleobases. An analogue may have any of these altered. Typically the analogue nucleobases confer, among other things, different base pairing and base stacking properties. Examples include universal bases, which can pair with all four canonical bases, and phosphate-sugar backbone analogues such as PNA, which affect the properties of the chain . Nucleic acid analogues are also called Xeno Nucleic Acid and represent one of the main pillars of xenobiology, the design of new-to-nature forms of life based on alternative biochemistries.

Complementarity (molecular biology)

In molecular biology, complementarity describes a relationship between two structures each following the lock-and-key principle. In nature complementarity is the base principle of DNA replication and transcription as it is a property shared between two DNA or RNA sequences, such that when they are aligned antiparallel to each other, the nucleotide bases at each position in the sequences will be complementary, much like looking in the mirror and seeing the reverse of things. This complementary base pairing allows cells to copy information from one generation to another and even find and repair damage to the information stored in the sequences.

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.