Iron porphyrin mediated electrophilic chlorinations (and other oxidations)

Iron porphyrins are immensely important in nature and heme-containing enzymes catalyze a wide variety of interesting chemical transformations. Of particular interest to us is chloroperoxidase: a heme containing enzyme that achieves catalytic electrophilic chlorinations by performing a two-electron oxidation of chloride with the help of hydrogen peroxide. Typically, chemists would employ atom inefficient transformations or toxic chemicals to achieve electrophilic chlorinations. To establish more sustainable alternatives, society would strongly benefit from copying nature’s ingenuity.

In her thesis, Silène Engbers uses bioinspired porphyrins to achieve similar transformations to the enzyme through a different mechanism. She inspected in more detail the species involved in the bioinspired route, with a particular focus on the influence of the porphyrin meso-substituent. Additionally, she gives an extensive characterization of the iron(III) π-dication, a transient and peculiar species that has scarcely been reported.

Further optimization of the iron porphyrin catalyzed electrophilic chlorinations did not produce high yields of chlorinated product, largely due to a persisting side reaction that is assigned to originate from the strong oxidation potential of the iron(III) π-dication. Engbers further explores the interplay between the two pathways, and discusses the opportunities and challenges for the optimization of each catalytic cycle. 

One main reason for which bioinspired iron porphyrins perform electrophilic chlorinations through a mechanism that differs from the enzyme is the reversed thermodynamic preference for a crucial step. Engbers exploits this to achieve a suppression in the accumulation of toxic chlorinated disinfection byproducts in hypochlorite-dependent water remediation processes, aiding the strive towards safe drinking water on a global scale.

Dissertation: https://hdl.handle.net/11370/faae07d1-846a-4fc9-8625-595528d65890