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.

These shifts are often studied and observed by isotopic labeling.

As the hydroxylase adds a hydroxyl (the −OH group), the labeled site shifts one position around the aromatic ring relative to the stationary methyl group (−CH3).

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.

Example of NIH shift
Example of NIH shift