Synthetic enzyme mimic uses oxygen to expand chemical rings with water as only waste

A team led by Penn State chemistry professor Jonathan Kuo has developed a synthetic mimic of the enzyme extradiol dioxygenase that performs a key oxygen-activation reaction using only dioxygen and producing water as the sole byproduct. The work was published in the Journal of the American Chemical Society.

Natural enzymes activate oxygen by rearranging its electrons, allowing controlled reactions with organic molecules instead of uncontrolled combustion. The researchers studied the active site of extradiol dioxygenase, which targets catechol — a compound derived from benzene — and inserts an oxygen atom to expand its stable six-carbon ring into a more reactive seven-atom ring.

Instead of the iron, cobalt, or manganese found in natural enzymes, the synthetic mimic uses iridium, a noble metal that resists unwanted reactions with oxygen. Graduate student Alexander Arnette, the paper's first author, noted that iridium's lower oxygen reactivity makes the mimic easier to build and potentially longer-lasting than iron-based versions, which can degrade through rust-like processes.

Each reaction cycle consumes one molecule of oxygen and produces one molecule of water, an atom-efficient process with essentially no waste. The expanded seven-membered ring opens new synthetic pathways for creating diverse chemical compounds from aromatic building blocks that are typically difficult to modify.

Kuo said the mimic allows researchers to test precise hypotheses about the chemical steps required for oxygen activation, since the reaction is not limited to the metal ions found in nature. The ultimate goal is to develop a sustainable chemical infrastructure that rivals nature's circularity by enabling desired transformations without harmful byproducts.

The research team included associate professor of chemistry Alexey Silakov. The study was supported by Pennsylvania State University's Eberly College of Science.