Ab initio quantum chemical and ReaxFF-based study of the intramolecular iminium–enamine conversion in a proline-catalyzed reaction

Exploring the conformational and reactive dynamics of biomolecules in solution using an extended version of the glycine reactive force field

“…To further evaluate the ReaxFF performance for proteinrelated reactions we evaluated the ReaxFF performance for H 2 /NH 3 catalyzed S-S cleavage 105 and on iminium-enamine conversions. 106 These results all indicate that ReaxFF can provide a reliable description (approaching the quality of DFT) for relevant reactive events in protein systems.…”

Theoretical chemistry in Belgium

“…The theoretical chemistry research activities from the UNamur are illustrated in the contributions by Fripiat and Harris [21], Hubin et al [22], Leherte and Vercauteren [23], as well as Liégeois and Champagne [24].…”

Parameterization of the ReaxFF reactive force field for a proline-catalyzed aldol reaction

“…Alternative methods include the Empirical Valence Bond (EVB) approach that is based on another idea: the reactive behavior is obtained by mixing two unreactive FFs describing the reactant and the product states . ReaxFF was initially designed to perform reactive Molecular Dynamics (MD) simulations on hydrocarbon compounds, and since it has been extended to numerous chemical systems, notably silicate materials, amino acids and short peptides, chemicals in lithium batteries, metal oxides interacting with water, or explosive compounds . Interested readers can find more information in two recent reviews devoted to the applications and developments of ReaxFF .…”

“…The mechanistic pathway of the proline‐catalyzed self‐aldol reaction of propanal is given in Figure . ReaxFF has been previously used to investigate the mechanism of two steps of the reaction, namely steps c and g . In the article devoted to the investigation of step g , a particular emphasis was put on the effect of explicit water molecules on this step of the reaction, a specific topic that is not our focus herein.…”

“…It appears that proline‐catalyzed reactions may occur following one or the other mechanisms depending on the reaction conditions and the electrophile used as reagent in step d . To investigate the reactions of Figure , we previously used several ReaxFF potentials, and more precisely the glycine potential (FF‐aa1), an extension of this potential accounting for the relative stabilities of several intermediates of the proline‐catalyzed aldol reaction (FF‐aa2), and a ReaxFF potential for amino acids and short peptides developed by Monti et al (FF‐aa3) . However, all of these ReaxFF potentials were obtained with the parabolic search algorithm, and, more importantly, the training set used to obtain the first and the third potentials did not include specific data for the reaction under study whereas the training set of the second potential included only data related to the relative stability of intermediates 4 , 5 , 9 , and the TS for step c .…”