A Dicopper(II)‐Based Carbonic Anhydrase Model ‐ Quantum‐Chemical Evaluation of the Mechanistic Pathway

The cyanobacterium Prochloron didemni, an obligate symbiont of different species of colonial ascidians, occurring in the Pacific and Indian Oceans, produces a variety of cyclic peptides. These patellamide‐type macrocycles lead to relatively stable dicopper(II) complexes that are extremely efficient carbonic anhydrase mimics, the most active model systems known so far. Importantly, it recently was shown that copper(II) is coordinated to patellamide derivatives in Prochloron cells. An interesting question therefore is, whether the biological function of patellamide‐type macrocycles is related to the catalytic activity in CO2 hydration or its reverse. Here, we present a computational study to evaluate the energetics of the catalytic cycle in search of a possible answer to these questions and compare the computed energy barriers with the experimental kinetic data. It emerges that release of the bridging carbonate is a critical step and that the catalysis product inhibits catalysis at pH values above approx. 7. Therefore, carbonate transport rather than CO2 hydrolysis is proposed as the biological function of copper(II)‐patellamide complexes in the Prochloron‐Ascidian symbiosis.