NIH shift

An NIH shift is a chemical rearrangement where a hydrogen atom on an aromatic ring undergoes an intramolecular migration primarily during a hydroxylation reaction. This process is also known as a 1,2-hydride shift. These shifts are often studied and observed by isotopic labeling. An example of an NIH shift is shown below:

In this example, a hydrogen atom has been isotopically labeled using deuterium (shown in red). The process proceeds via an arene oxide, which rearrange to give the diene-ketone via the NIH shift. This is the initial step in the detoxification of benzene by cytochrome P450.[1]


Several hydroxylase enzymes are believed to incorporate an NIH shift in their mechanism, including 4-hydroxyphenylpyruvate dioxygenase and the tetrahydrobiopterin dependent hydroxylases. The name NIH shift arises from the US National Institutes of Health from where studies first reported observing this transformation.

References

  1. ^ Meunier, Bernard; De Visser, Samuël P.; Shaik, Sason (2004). "Mechanism of Oxidation Reactions Catalyzed by Cytochrome P450 Enzymes". Chemical Reviews. 104 (9): 3947–3980. doi:10.1021/cr020443g. PMID 15352783.
  • Guroff, G.; Daly, J.W.; Jerina, D.M.; Renson, J.; Witkop, B.; Udenfriend, S. (1967). "Hydroxylation-induced migration: the NIH shift. Recent experiments reveal an unexpected and general result of enzymatic hydroxylation of aromatic compounds". Science. 157 (3796): 1524–1530. Bibcode:1967Sci...157.1524G. doi:10.1126/science.157.3796.1524. PMID 6038165..
  • Bassan, A.; Blomberg, M.R.A.; Siegbahn, P.E.M. (2003). "Mechanism of Aromatic Hydroxylation by an Activated FeIV=O Core in Tetrahydrobiopterin-Dependent Hydroxylases". Chem. Eur. J. 9 (17): 4055–4067. doi:10.1002/chem.200304768. PMID 12953191..
This article is issued from Wikipedia. The text is available under Creative Commons Attribution-Share Alike 4.0 unless otherwise noted. Additional terms may apply for the media files.