N-heterocyclic carbene-capped cyclodextrin (ICyD) ligands, α-ICyD and β-ICyD derived from α- and β-cyclodextrin, respectively give opposite regioselectivities in a copper-catalyzed hydroboration. The site-selectivity results from two different mechanisms: the conventional parallel one and a new orthogonal mechanism. The shape of the cavity was shown not only to induce a regioselectivity switch but also a mechanistic switch. The scope of interest of the encapsulation of a reactive center is therefore broadened by this study.

Acetylcholinesterase (AChE) is an enzyme of the serine hydrolase superfamily and a mediator of the signal transmission at cholinergic synapses catalysing acetylcholine cleavage into an acetate and a choline. This enzyme is vulnerable to covalent inhibition by organophosphate compounds. The covalent inhibition of AChE does not revert spontaneously and in order to restore catalytic activity known reactivator compounds have limited action. Simulations of VX-inhibited AChE reactivation by pralidoxime, a classical reactivator, were performed by QM/MM. These simulations allowed for a broader view of the effect of protonation states of active site residues. These calculations provide evidence for the role of Glu202, which needs to be protonated for reactivation to occur. In situ deprotonation of 2-PAM was also explored in both protonation states of Glu202, showing that His447 is able to deprotonate 2-PAM with the assistance of Glu202. Since the active site of serine hydrolases is highly conserved, this work shades new insights on the interplay between the triad residues of the catalytic center and this glutamate newly identified as protonatable.