Simple synthetic route to an enzyme-inspired transesterification catalyst

Inspired by the chemical structure of chymotrypsin, we report an artificial catalytic triad with high catalytic efficiency for the transesterification reaction of vinyl trifluoroacetate and methanol. Rate accelerations of (k(cat)/k(unc)) 4.81 x 10(4)-fold over the background reaction were observed. We highlight a simple two step synthetic approach to incorporate three functional groups (-OH, -CO2H, -imidazole) on a single molecule, similar to native enzymes like chymotrypsin. The addition of a hydrophobic chain furnishes amphiphilic catalysts that form clusters for reactions in organic solvents. The cluster formation was studied using molecular dynamics (MD) simulations, dynamic light scattering (DLS) and H-1 NMR, revealing complex H-bonding interactions between the catalytic head groups of the artificial catalytic triad, drawing similarities to native enzymes.