Bare Histidine–Serine Models: Implication and Impact of Hydrogen Bonding on Nucleophilicity

Abstract

A new family of 2-hydroxyalk(en/yn)ylimidazoles has been evaluated as serine-histidine bare dyad models for the ring-opening reaction of L-lacOCA, a cyclic O-carboxyanhydride. These models were selected to unravel the implication of intramolecular hydrogen bonding and to substantiate its influence on the nucleophilicity of the alcohol moiety, as it is suspected to occur in enzyme active sites. Although designed to exclusively facilitate the preliminary step of proton transfer during the studied ring-opening reaction, these minimalistic models depicted a measureable increase in reactivity relative to the isolated fragments. A couple of reliable experimental and theoretical methods have been developed to readily monitor the strength of the intramolecular hydrogen bond in dilute solution. Results show that the folded conformers are the most nucleophilic species because of the intramolecular hydrogen bond.

A Single Amino Acid Able to Promote High‐Temperature Ring‐Opening Polymerization by Dual Activation

“…Our group, among others, has recently demonstrated that one strategy to address these thermal stability issues is the use of organocatalysts based on hydrogen bond donor–acceptor adducts. [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ] These catalysts have recently been proven to be stable and active at elevated temperatures, in some cases at temperatures close to 400 °C. Using this concept, the ring‐opening polymerization (ROP) of L‐Lactide (L‐LA) at elevated temperatures as well as some polycondensation reactions have been performed with great success.…”