Hydroxamic acid

A hydroxamic acid is a class of chemical compounds sharing the same functional group in which an hydroxylamine is inserted into a carboxylic acid. Its general structure is R-CO-NH-OH, with an R as an organic residue, a CO as a carbonyl group, and a hydroxylamine as NH2-OH. They are used as metal chelators[1][2] in industry, e.g. benzohydroxamic acid and others in the reprocessing of irradiated fuel.[3][4] [5][6][7]

Hydroxamic acids can be synthesized from aldehydes via the Angeli-Rimini reaction. A well-known hydroxamic acid reaction is the Lossen rearrangement.

Many hydroxamic acids, such as salicylhydroxamic acid, are utilized as ligands in the synthesis of metallacrowns.

Biochemistry

Hydroxamates are essential growth factors, or vitamins, for some microbes. They function as iron-binding compounds (siderophores) that solubilise iron and transport it into the cell.[8]

Iron is a key component of cytochromes and iron-sulphur proteins (involved in electron transport) and is thus important in cellular respiration. In an environment, absent from oxygen (anoxic); iron will be present in the ferrous +2 oxidation state (Fe2+), which is water-soluble. Under oxic conditions; iron will be in the ferric +3 oxidation state (Fe3+), in insoluble mineral form. The powerful chelating properties of hydroxamic acid and its derivatives is exploited by bacteria to obtain ferric iron. Once the iron-hydroxamate complex has entered the cell, the iron is liberated and the hydroxamic acid can be excreted and reused for iron transport.

Hydroxamic acid is used extensively in floatation of rare earth minerals during the concentration and extraction of ores to be subjected to further processing.

Possible use against cancers

Some hydroxamic acids (e.g. vorinostat), belinostat, panobinostat, and trichostatin A) are HDAC inhibitors with anti-cancer properties.

References

  1. ^ Fouché, K. F.; H. J. le Roux, F. Phillips (1970-06). "Complex formation of Zr(IV) and Hf(IV) with hydroxamic acids in acidic solutions". Journal of Inorganic and Nuclear Chemistry 32 (6): 1949–1962. doi:10.1016/0022-1902(70)80604-2. ISSN 0022-1902. http://www.science-direct.com/science/article/B758S-48M3JS8-NH/2/906cec1e859eacb47bf1f0efcd27e5cc. Retrieved 2009-04-24. 
  2. ^ Agrawal, Y K (1979). "Hydroxamic Acids and Their Metal Complexes". Russian Chemical Reviews 48 (10): 948. doi:10.1070/RC1979v048n10ABEH002422. 
  3. ^ Barocas, A.; F. Baroncelli, G. B. Biondi, G. Grossi (1966-12). "The complexing power of hydroxamic acids and its effect on behaviour of organic extractants in the reprocessing of irradiated fuels--II : The complexes between benzohydroxamic acid and thorium, uranium (IV) and plutonium (IV)". Journal of Inorganic and Nuclear Chemistry 28 (12): 2961–2967. doi:10.1016/0022-1902(66)80023-4. ISSN 0022-1902. http://www.science-direct.com/science/article/B758S-48GWMMM-8P/2/0e24f83e069f7473d7b0663eea4f8302. Retrieved 2009-04-24. 
  4. ^ Baroncelli, F.; G. Grossi (1965-05). "The complexing power of hydroxamic acids and its effect on the behaviour of organic extractants in the reprocessing of irradiated fuels--I the complexes between benzohydroxamic acid and zirconium, iron (III) and uranium (VI)". Journal of Inorganic and Nuclear Chemistry 27 (5): 1085–1092. doi:10.1016/0022-1902(65)80420-1. ISSN 0022-1902. http://www.science-direct.com/science/article/B758S-48N50RN-2W/2/fc4a67c10211cd748add5daa51bb55ff. Retrieved 2009-04-24. 
  5. ^ Al-Jarrah, R. H.; A. R. Al-Karaghouli, S. A. Al-Assaf, N. H. Shamon (1981). "Solvent extraction of uranium and some other metal ions with 2-N-butyl-2-ethyl octanohydroxamic acid". Journal of Inorganic and Nuclear Chemistry 43 (11): 2971–2973. doi:10.1016/0022-1902(81)80652-5. ISSN 0022-1902. http://www.science-direct.com/science/article/B758S-48M3SCR-152/2/723dc6c17d83f6266314116734ae71e8. Retrieved 2009-04-24. 
  6. ^ Gopalan, Aravamudan S.; Vincent J. Huber, Orhan Zincircioglu, Paul H. Smith (1992). "Novel tetrahydroxamate chelators for actinide complexation: synthesis and binding studies". Journal of the Chemical Society, Chemical Communications (17): 1266–1268. doi:10.1039/C39920001266. 
  7. ^ Koshti, Nirmal; Vincent Huber, Paul Smith, Aravamudan S. Gopalan (1994-02-28). "Design and synthesis of actinide specific chelators: Synthesis of new cyclam tetrahydroxamate (CYTROX) and cyclam tetraacetonylacetone (CYTAC) chelators". Tetrahedron 50 (9): 2657–2664. doi:10.1016/S0040-4020(01)86981-7. ISSN 0040-4020. http://www.sciencedirect.com/science/article/B6THR-42GDT5D-8H/2/4625c55f99ae5f042ca3387e0fe7386c. Retrieved 2009-04-30. 
  8. ^ Miller, Marvin J. (November 1989). "Syntheses and Therapeutic Potential of Hydroxamic Acid Based Siderophores and Analogues". Chemical Reviews 89 (7): 1563–1579. doi:10.1021/cr00097a011. http://pubs.acs.org/doi/abs/10.1021/cr00097a011.