A Molecular-Wide and Electron Density-Based Approach in Exploring Chemical Reactivity and Explicit Dimethyl Sulfoxide (DMSO) Solvent Molecule Effects in the Proline Catalyzed Aldol Reaction

Abstract

Modelling of the proline (1) catalyzed aldol reaction (with acetone 2) in the presence of an explicit molecule of dimethyl sulfoxide (DMSO) (3) has showed that 3 is a major player in the aldol reaction as it plays a double role. Through strong interactions with 1 and acetone 2, it leads to a significant increase of energy barriers at transition states (TS) for the lowest energy conformer 1a of proline. Just the opposite holds for the higher energy conformer 1b. Both the ‘inhibitor’ and ‘catalyst’ mode of activity of DMSO eliminates 1a as a catalyst at the very beginning of the process and promotes the chemical reactivity, hence catalytic ability of 1b. Modelling using a Molecular-Wide and Electron Density-based concept of Chemical Bonding (MOWED-CB) and the Reaction Energy Profile–Fragment Attributed Molecular System Energy Change (REP-FAMSEC) protocol has shown that, due to strong intermolecular interactions, the HN-C-COOH (of 1), CO (of 2), and SO (of 3) fragments drive a chemical change throughout the catalytic reaction. We strongly advocate exploring the pre-organization of molecules from initially formed complexes, through local minima to the best structures suited for a catalytic process. In this regard, a unique combination of MOWED-CB with REP-FAMSEC provides an invaluable insight on the potential success of a catalytic process, or reaction mechanism in general. The protocol reported herein is suitable for explaining classical reaction energy profiles computed for many synthetic processes.

Coordination Sites for Sodium and Potassium Ions in Nucleophilic Adeninate Contact ion-Pairs: A Molecular-Wide and Electron Density-Based (MOWED) Perspective

“…Hence, we embarked on computational studies to understand, on a fundamental atomic and molecular level, processes leading to regio-selectivity in general. To achieve this, we made use of the recently proposed Molecular-Wide and Electron Density-Based (MOWED) approach [29,30]. One must state that the classical approach, i.e., comparative analyses of electronic and Gibbs free energies computed for CIPs, failed as (i) at least four coordination sites were identified, in contradiction with experimental results, and (ii) the classical approach did not provide the information needed to explain regioselectivity on atomic or a molecular fragment level.…”

“…Hence, we decided to make use of the Interacting Quantum Atoms (IQA) electronic energy partitioning scheme [26] and the Reaction Energy Profile-Fragment Attributed Molecular System Energy Change (REP-FAMSEC) method [27]. This powerful combination has proved to be very useful in exploring and explaining molecules' properties, reactivity, and reaction mechanisms on the fundamental atomic, functional group and molecular levels [27][28][29]. The IQA and REP-FAMSEC methods were employed here to explore the properties of Na-and K-Ade complexes using the recently reported Molecular-Wide and Electron Density-Based (MOWED) approach [29,30].…”

“…This powerful combination has proved to be very useful in exploring and explaining molecules' properties, reactivity, and reaction mechanisms on the fundamental atomic, functional group and molecular levels [27][28][29]. The IQA and REP-FAMSEC methods were employed here to explore the properties of Na-and K-Ade complexes using the recently reported Molecular-Wide and Electron Density-Based (MOWED) approach [29,30]. In the study reported here, essentially all intuitively possible Na + and K + adeninate complexes were investigated at the coupled cluster (CCSD) and density functional theory (DFT) levels to predict the preferred site and mode of cation coordination.…”

Inhibitory Effect of Quercetin on Oxidative Endogen Enzymes: A Focus on Putative Binding Modes

“…The ED analysis involves determining the probability of locating an electron in the vicinity of a molecule [30]. This property contributes to understanding the electronic structure and behavior of Que.…”

Inhibitory Effect of Quercetin on Oxidative Endogen Enzyme: A Focus on Putative Binding Modes

“…We optimized the Que using B3LYP/6-311++G** method with Jaguar software, and calculated ESP, Average Local Ionization Energy (ALIE), Electron Density (ED), HOMO, and LUMO (Table 2). ESP is an effective tool for understanding and interpreting the chemical and reactivity properties of molecular systems [19], ALIE is the energy required to remove an electron from a specific point in a system and the lowest values reveal the locations of the least tightly held electrons [20], ED measures the probability of finding an electron in the volume surrounding a molecule [21]. HOMO and LUMO orbitals were presented in color-coded surfaces, which give the location of positive (blue) and negative (red) electrostatic potentials (Figure 2).…”