The hydration of carbodiimide, isoelectronic with carbon dioxide, mediated by human carbonic anhydrase (EC 4.2.1.1) was studied at theoretical level in comparison with the native substrate. Quantum-mechanical (QM) and combined quantum-mechanics/molecular-mechanics (QM/MM) approaches indicate that human carbonic anhydrase is able to catalyze also the hydration of carbodiimide to urea with an energy barrier higher than that required by the native CO2. The rate-determining step for both substrates is represented by the nucleophilic addition to the double bond, showing the final product ureate more strongly anchored to the enzyme active site than the hydrogen carbonate. The reduced catalytic activity for the carbodiimide substrate can be ascribed not only to the highest barrier but also to the difficulty in releasing the product in favor of the water molecule, delaying the catalytic turnover as indicated by QM and QM/MM analyses.

Recently, a new artificial carbonic anhydrase enzyme in which the native zinc cation has been replaced with a Rh(I) has been proposed as a new reductase able to efficiently catalyze the hydrogenation of olefins. In this paper we propose the possible use of this modified enzyme in the direct hydrogenation of carbon dioxide.In our theoretical investigation we have considered different reaction mechanisms such as reductive elimination and σ-bond metathesis. In addition, the release of the formic acid and the restoring of the catalytic cycle have also been studied. Results show that the σ-bond metathesis potential energy surface lies below the reactant species. The rate-determining step is the release of the product with an energy barrier of 12.8 kcal mol -1 . On the basis of our results we conclude that this artificial enzyme can efficiently catalyze the conversion of CO 2 to HCOOH by a direct hydrogenation reaction.

The promiscuous activity of human carbonic anhydrase (hCAII) against a non-physiological cyanic acid substrate has been investigated by using a combined QM and QM/MM level of theory. Results show that the hCAII is able to hydrate the cyanic acid by a reaction mechanism similar to that of the CO2 native substrate. The energy barrier for the nucleophilic attack is found to be 15.6 and 4.3 kcal mol(-1) at QM and QM/MM levels, respectively. This result underlines the importance of taking into account the surrounding residues around the active site in the presence of the substrate having small molecular sizes. The carbamate is strongly stabilized with respect to the bicarbonate of the native substrate indicating a more difficult release of the reaction product.

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Abstract:The efficient conversion of carbon dioxide (CO2) into useful products represents a prime challenge to modern chemistry. We describe an alternative route to address this challenge based on a rhodium-substituted human carbonic anhydrase (Rh-hCA) that can be considered the first cofactor-independent reductase. With respect to the native enzyme, this artificial one is able to convert it into formic acid with potential applications in the context of renewable energy. Our QM/QM' investigation, which considers the entire catalytic pocket (390 atoms), provides evidence that the catalytic process is governed by an energetically favored -bond metathesis mechanism and the rate-limiting step is the formic acid release (11.7 kcal mol −1). In particular, we find that water molecules play an active role during the chemical process, contributing to reduce dramatically the energy of the rate-limiting step and favoring an efficient regeneration of the catalyst.