In this paper, two possible mechanisms (mechanisms A and B) on the stereoselective [2 + 2] cycloaddition of aryl(alkyl)ketenes and electron-deficient benzaldehydes catalyzed by N-heterocyclic carbenes (NHCs) have been investigated using density functional theory (DFT). Our calculated results indicate that the favorable mechanism (mechanism A) includes three processes: the first step is the nucleophilic attack on the arylalkylketene by the NHC catalyst to form an intermediate, the second step is the [2 + 2] cycloaddition of the intermediate and benzaldehyde for the formation of a β-lactone, and the last step is the dissociation of the NHC catalyst and the β-lactone. Notably, the [2 + 2] cycloaddition, in which two chiral centers associated with four configurations (SS, RR, SR and RS) are formed, is demonstrated to be both the rate- and stereoselectivity-determining step. Moreover, the reaction pathway associated with the SR configuration is the most favorable pathway and leads to the main product, which is in good agreement with the experimental results. Furthermore, the analysis of global and local reactivity indexes has been performed to explain the role of the NHC catalyst in the [2 + 2] cycloaddition reaction. Therefore, this study will be of great use for the rational design of more efficient catalysts for this kind of cycloaddition.

The Mad2 protein, with two distinct conformations of open- and closed-states, is a key player in the spindle checkpoint. The closed Mad2 state is more active than the open one. We carried out conventional and targeted molecular dynamics simulations for the two stable Mad2 states and their conformational transition to address the dynamical transition mechanism from the open to the closed state. The intermediate structure in the transition process shows exposure of the β6 strand and an increase of space around the binding sites of β6 strand due to the unfolding of the β7/8 sheet and movement of the β6/4/5 sheet close to the αC helix. Therefore, Mad2 binding to the Cdc20 protein in the spindle checkpoint is made possible. The interconversion between these two states might facilitate the functional activity of the Mad2 protein. Motion correlation analysis revealed the allosteric network between the β1 strand and β7/8 sheet via communication of the β5-αC loop and the β6/4/5 sheet in this transition process.

The origin of regio- and stereoselectivities of NHC-catalyzed enantioselective radical reactions of an enal and a pyridinium salt has been explored via theory for the first time.

Reaction mechanisms of the N-heterocyclic carbene (NHC)-catalyzed dimerization of methyl methacrylate were studied using density functional theory (DFT) at the M05-2X/6-31G(d,p) level of theory. Four possible reaction channels (A, B, C, and D) have been investigated in this work. Particularly, we proposed a novel reaction pathway, where the proton transfers are assisted by a different molecule. The calculated results indicate that the channels B and D are more energetically favourable channels. The obtained results suggest that the E-isomer product is the main product, which is in agreement with the experimental results. Further calculations and analyses of global and local reactivity indices reveal the role of the NHC catalysts in the title reaction. The mechanistic insights gained are valuable for not only rational design of more efficient NHC catalysts but also for understanding the similar reaction mechanism.