Intrinsic and environmental modulation of stereoselective aldol organocatalyzed reactions by proline-containing lipopeptides.

Proline, along with its derivatives, has been employed as an efficient organocatalyst for aldol reactions, with the ability to promote the creation of stereoselective C-C bonds. Even though the Houk-List transition state model is able to explain the stereoselectivity observed when proline is used as a catalyst, few studies investigate the role of microheterogeneous media in modulating the reaction outcome. In this work, molecular dynamics and electronic structure calculations were used to investigate the aldol reaction in the condensed phase. Our research focused on a lipopeptide compound incorporating the proline residue within the sequence PRWG-(C18H37), where P represents l-proline, R stands for l-arginine, W for l-tryptophan, and G for l-glycine. This sequence is covalently bonded to a hydrophobic segment formed by a long aliphatic chain, acting as an organocatalyst in an aqueous solution. This catalytic phase utilizes the complex chemical environment of the solution to achieve high selectivity. Our findings indicate a Houk-List-like mechanism, in which the amide acts as an H-bond donor, complemented by a mechanism in which the counter ion, trifluoracetic acid (TFA), acts as a proton shuttle. Both mechanisms demonstrated low energy barriers-12.23 and 1.42 kcal mol-1 for the (S,R) stereoisomer formation, computed using DLPNO-CCSD with def2-TZVPP basis set. Further, to explore the catalytic effect of the PRWG-(C18H37) lipopeptide in water, molecular dynamics simulations were conducted. It was observed that the micellar phase significantly enhances stereospecific encounters, favouring the experimentally observed ratio of (SR/SS) isomers, in contrast to reactions in a pure cyclohexanone medium. By quantifying the effects enabled by the supramolecular assembly, we were able to shed light on the factors that modify and enhance the stereoslectivity of the reaction.

Mimics of copper proteins: structural and functional aspects

The importance of copper as an essential element can be estimated by the wide range of copper proteins and enzymes playing different roles in biological systems. In the last decades many bioinorganic studies were developed on mimetic complexes of copper-dependent proteins, in order to verify the interrelations between structural and functional properties of active copper centers. Among the most studied copper ion ligand, diimine compounds have deserved special attention due their flexibility, facility of preparation, and ability to stabilize both oxidation states of this metal. In our laboratory, we have been investigating some Schiff base copper complexes as mimics of different proteins, with emphasis on functional aspects, trying to elucidate mechanisms of reaction, based on proposed intermediary species, in addition to molecular shapes. Particularly, mimics of the copper-zinc superoxide dismutase, and of monooxigenases and oxidases exhibiting dicopper sites are discussed in this work.