Hemiprotonation

Hemiprotonation is the partial protonation of a molecule that contains two or more basic sites, yielding a mono-protonated species. It is commonly described as the first step in the protonation of a diprotic or multinucleophilic base, before full protonation at all available sites occurs.

Mechanism and scope. The site of protonation is governed by relative basicity, resonance, and solvent effects. In ambidentate ligands and heterocycles, protonation typically occurs at the site with higher basicity, though in some cases proton transfer can be rapidly shuttled or the proton can be delocalized through intramolecular hydrogen bonding. Hemiprotonated species can be localized, with the proton occupying a single site, or transiently delocalized across two sites via proton-hopping mechanisms in solution.

Contexts and examples. The concept is discussed in organic and inorganic chemistry and in coordination chemistry where ligands bound to metal centers undergo protonation. For example, heterocycles such as imidazole can be mono-protonated to form a hemiprotonated, or first-protonated, imidazolium species. In polyfunctional bases, the first protonation step yields a mono-protonated intermediate that may subsequently acquire a second proton to become fully protonated. In biological and chemical systems, understanding the first protonation step helps explain pH-dependent behavior of multiprotic bases and ligands.

Terminology and notes. The use of “hemiprotonation” is not universal; some authors simply refer to the first protonation as monoprotonation. The term highlights the intermediate nature of this state between the neutral base and the fully protonated form.