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.