metalations

Metalation refers to the introduction of a metal ion into a molecule or the replacement of a hydrogen atom by a metal atom in a chemical species. In organic chemistry, metalation typically generates organometallic reagents that can act as nucleophiles or transmetallate to other metals, enabling carbon–carbon or carbon–heteroatom bond formation. In biochemistry and bioinorganic chemistry, metalation describes the incorporation of metal ions into proteins, nucleic acids, or cofactors, a process essential for structure and catalysis.

In organic synthesis, metalation often proceeds by deprotonation with strong bases to form organolithium or organomagnesium species, or by directed metalation using coordinating groups to achieve regioselective lithiation (ortho-metalation) and subsequent trapping or transmetalation. Zincation, copperation, and other metalations expand the toolbox for functionalization. Reaction conditions vary with substrate and metal, and downstream steps frequently involve quenching with electrophiles or engaging in cross-coupling reactions such as Suzuki, Negishi, or Kumada couplings.

In biology, metalation involves the binding or incorporation of metal ions into biomolecules, influencing structure, redox properties, and catalytic activity. Metalloproteins and metalloenzymes rely on metal centers such as iron, zinc, copper, manganese, or cobalt. The process is governed by cellular metal availability, chaperone proteins, and chelation networks. Improper metalation can impair function or contribute to toxicity, so organisms Maintain metal homeostasis to ensure correct metal incorporation.

Applications of controlled metalation include the synthesis of complex organic molecules, the design of metal-centered materials, and the study of metalloproteins. Challenges include achieving regio- and chemoselectivity, avoiding side reactions, and ensuring correct metal incorporation in biological contexts.