Non-innocent Ligand - Redox Non-Innocent Ligands in Biology

Redox Non-Innocent Ligands in Biology

Metalloenzymes often feature non-innocent ligands. A common non-innocent ligand is found in metalloporphyrins. In the enzyme cytochrome P450, the porphyrin ligand sustains oxidation during the catalytic cycle. In other heme proteins, such as myoglobin, ligand-centered redox does not occur and the porphyrin is innocent.

Galactose Oxidase (GOase) provides a seminal example for the involvement of reactive non-innocent ligands in bio-catalytic turnover. GOase converts chemo-selectively primary alcohols with O₂ into aldehydes and H₂O₂, with impressive turnover frequencies. The active site of the enzyme GOase contains a tyrosinyl radical which is coordinated to a CuII ion. In the key steps of the catalytic cycle, a cooperative Brønsted-basic ligand-site deprotonates the alcohol, and subsequently the oxygen atom of the tyrosinyl radical abstracts a hydrogen atom from the alpha-CH functionality of the coordinated alcoholate substrate. Thus, the tyrosinyl radical is a reactive fragment in the catalytic cycle which cooperates with the Cu site. This is essential for the function of the enzyme, because the Cu-ion is only capable of one-electron transformations. It is the interplay of the 1e reactivity of the ligand radical and the 1e reactivity of the metal which makes the overall process possible. The radical abstraction nature of the process makes the process extremely fast. Anti-ferromagnetic coupling between the unpaired spins of the tyrosine radical ligand and the d9 CuII ion (open-shell singlet ground state) explains the observed diamagnetic nature of the resting state of the enzyme, as was confirmed by synthetic model studies.

The oxygen molecule in oxyhemoglobin (or oxymyoglobin) would appear to satisfy the definition of a non-innocent ligand. Deoxyhemoglobin is ferrous and pentacoordinate, the (innocent) ligands being four N of the porphyrin and Ne of the proximal histidine. An O2 molecule binds the sixth coordination position. There is evidence from a number of lines that partial electron transfer from the Fe to O2 occurs, so that the complex is better described as superoxide anion bound to ferric heme, although spin coupling makes the complex diamagnetic. The change in oxidation and spin state of the Fe results in a change of bond length to the five innocent ligands which results in the heme switching from a "domed" to a planar conformation, which in turn drives conformational changes in the protein responsible for the cooperativity of O2 binding. This cooperativity is essential for efficient oxygen transport, so in a way we all owe our lives to the suspect nature of the O2 ligand!