Understanding the Physics and Chemistry of Reaction Mechanisms from Atomic Contributions: A Reaction Force Perspective

Studying chemical reactions involves the knowledge of the reaction mechanism. Despite activation barriers describing the kinetics or reaction energies reflecting thermodynamic aspects, identifying the underlying physics and chemistry along the reaction path contributes essentially to the overall understanding of reaction mechanisms, especially for catalysis. In the past years the reaction force has evolved as a valuable tool to discern between structural changes and electrons’ rearrangement in chemical reactions. It provides a framework to analyze chemical reactions and additionally a rational partition of activation and reaction energies. Here, we propose to separate these energies further in atomic contributions, which will shed new insights in the underlying reaction mechanism. As first case studies we analyze two intramolecular proton transfer reactions. Despite the atom based separation of activation barriers and reaction energies, we also assign the participation of each atom in structural changes or electrons’ rearrangement along the intrinsic reaction coordinate. These participations allow us to identify the role of each atom in the two reactions and therfore the underlying chemistry. The knowledge of the reaction chemistry immediately leads us to suggest replacements with other atom types that would facilitate certain processes in the reaction. The characterization of the contribution of each atom to the reaction energetics, additionally, identifies the reactive center of a molecular system that unites the main atoms contributing to the potential energy change along the reaction path

How Does Pin1 Catalyze the Cis–Trans Prolyl Peptide Bond Isomerization? A QM/MM and Mean Reaction Force Study

Pin1 represents an enzyme that specifically catalyzes the isomerization of peptide bonds between phosphorylated threonine or serine residues and proline. Despite its relevance as molecular timer in a number of biological processes related to cancer and Alzheimer disease, a detailed understanding of the factors contributing to the catalysis is still missing. In this study, we employ extensive QM/MM molecular dynamics simulations in combination with the mean reaction force (MRF) to discern the influence of the enzyme on the reaction mechanism and the origin of the catalysis. As a recently introduced method, the MRF separates the activation free energy barrier to reach the transition state into structural and electronic contributions providing a more detailed description of the enzyme’s function. As a reference, we first study the isomerization starting from the cis form in solution and obtain a free energy barrier and a reaction free energy, which are in agreement with previous studies and experiment. With the new mean reaction force method, intramolecular hydrogen bonds in the peptide were identified that stabilize the transition state and reduce the electronic contribution to the free energy barrier. To elucidate the mechanism of catalysis of Pin1, the reaction in solution and in the catalytic cavity of the enzyme were compared. Both yield the same free energy barrier for the isomerization of the cis form, but with different decomposition in structural and electronic contributions by the mean reaction force. The enzyme reduces the energy required for structural rearrangements to reach the transition state, pointing to a destabilization of the reactant, but increases the electronic contribution to the barrier through specific enzyme–peptide hydrogen bonds. In the reverse reaction, the isomerization of the trans form, the enzyme alters the energetics and the mechanism of the reaction considerably. Unfavorable enzyme–peptide interactions in the catalytic cavity during the isomerization change the reaction coordinate, resulting in two minima with small energy differences to the transition state. These small free energy barriers should in principle make the reaction feasible at room temperature once the conformer is bound in the right conformation

Catalytic Mechanism of H₂ Activation by a Carbenoid Aluminum Complex

The catalytic mechanism of H₂ activation by a carbenoid aluminum compound is analyzed in great detail. On the basis of the reaction force analysis, the electronic activity that takes place during the chemical reaction was identified and characterized through the reaction electronic flux and rationalized in terms of chemical events that drive the reaction. Successive transformation of the nucleophilic or electrophilic character of the reagents along the reaction coordinate monitored through the dual descriptor allows us to obtain a very complete and detailed description of the reaction mechanism that proceeds through a two-stage mechanism in a one-kinetic-step process

Basis Electronic Activity of Molecular Systems. A Theory of Bond Reactivity

In this paper, we present a new finding, the basis electronic activity (BEA) of molecular systems; it corresponds to the significant, although nonreactive, vibrationally induced electronic activity that takes place in any molecular system. Although the molecule’s BEA is composed of an equal number of local contributions as the vibrational degrees of freedom, our results indicate that only stretching modes contribute to it. To account for this electronic activity, a new descriptor, the bond electronic flux (BEF), is introduced. The BEF combined with the force constant of the potential well hosting the electronic activity gives rise to the effective bond reactivity index (EBR), which turns out to be the first density functional theory-based descriptor that simultaneously accounts for structural and electronic effects. Besides quantifying the bond reactivity, EBR provides a basis to compare the reactivities of bonds inserted in different chemical environments and paves the way for the exertion of selective control to enhance or inhibit their reactivities. The new concepts formulated in this paper and the associated computational tools are illustrated with characterization of the BEA of a set of representative molecules. In all cases, the BEFs follow the same linear pattern, whose slopes indicate the intensity of the electronic activity and quantify the reactivity of chemical bonds

Basis Electronic Activity of Molecular Systems. A Theory of Bond Reactivity

In this paper, we present a new finding, the basis electronic activity (BEA) of molecular systems; it corresponds to the significant, although nonreactive, vibrationally induced electronic activity that takes place in any molecular system. Although the molecule’s BEA is composed of an equal number of local contributions as the vibrational degrees of freedom, our results indicate that only stretching modes contribute to it. To account for this electronic activity, a new descriptor, the bond electronic flux (BEF), is introduced. The BEF combined with the force constant of the potential well hosting the electronic activity gives rise to the effective bond reactivity index (EBR), which turns out to be the first density functional theory-based descriptor that simultaneously accounts for structural and electronic effects. Besides quantifying the bond reactivity, EBR provides a basis to compare the reactivities of bonds inserted in different chemical environments and paves the way for the exertion of selective control to enhance or inhibit their reactivities. The new concepts formulated in this paper and the associated computational tools are illustrated with characterization of the BEA of a set of representative molecules. In all cases, the BEFs follow the same linear pattern, whose slopes indicate the intensity of the electronic activity and quantify the reactivity of chemical bonds

Mechanisms of Formation of Hemiacetals: Intrinsic Reactivity Analysis

The reaction mechanism of the hemiacetal formation from formaldehyde and methanol has been studied theoretically at the B3LYP/6-311++G­(d,p) level. In addition to the study of the reaction between the isolated reactants, three different kinds of catalysis have been explored. The first one examines the use of assistants, especially bridging water molecules, in the proton transfer process. The second one attempts to increase the local electrophilicity of the carbon atom in formaldehyde with the presence of a Brønsted acid (H⁺ or H₃O⁺). The last one considers the combined effect of both catalytic strategies. The reaction force, the electronic chemical potential, and the reaction electronic flux have been characterized for the reaction path in each case. In general, it has been found that structural rearrangements represent an important energetic penalty during the activation process. The barriers for the reactions catalyzed by Brønsted acids show a high percentage of electronic reorganization contribution. The catalytic effects for the reactions assisted by water molecules are due to a reduction of the strain in the transition state structures. The reaction that includes both acid catalysis and proton assistance transfer shows the lowest energy barrier (25.0 kJ mol^–1)

Binding of Trivalent Arsenic onto the Tetrahedral Au₂₀ and Au₁₉Pt Clusters: Implications in Adsorption and Sensing

The interaction of arsenic­(III) onto the tetrahedral Au₂₀ cluster was studied computationally to get insights into the interaction of arsenic traces (presented in polluted waters) onto embedded electrodes with gold nanostructures. Pollutant interactions onto the vertex, edge, or inner gold atoms of Au₂₀ were observed to have a covalent character by forming metal–arsenic or metal–oxygen bonding, with adsorption energies ranging from 0.5 to 0.8 eV, even with a stable physisorption; however, in aqueous media, the Au–vertex–pollutant interaction was found to be disadvantageous. The substituent effect of a platinum atom onto the Au₂₀ cluster was evaluated to get insights into the changes in the adsorption and electronic properties of the adsorbent–adsorbate systems due to chemical doping. It was found that the dopant atom increases both the metal–pollutant adsorption energy and stability onto the support in a water media for all interaction modes; adsorption energies were found to be in a range of 0.6 to 1.8 eV. All interactions were determined to be accompanied by electron transfer as well as changes in the local reactivity that determine the amount of transferred charge and a decrease in the HOMO–LUMO energy gap with respect to the isolated substrate

A Detailed Look at the Reaction Mechanisms of Substituted Carbenes with Water

Two competitive reaction mechanisms for the gas-phase chemical transformation of singlet chlorocarbene into chloromethanol in the presence of one and two water molecules are examined in detail. An analysis of bond orders and bond order derivatives as well as of properties of bond critical points in the electron densities along the intrinsic reaction coordinates (IRCs for intermediates → transition state (TS) → products) suggests that, from the perspective of bond breaking/formation, both reactions should be considered to be highly nonsynchronous, concerted processes. Both transition states are early, resembling the intermediates, yielding rate constants whose magnitudes are mostly influenced by structural changes and to a lesser degree by bond breaking/formation. For the case of one water molecule, most of the energy in the reactants region of the IRC is used for structural changes, while the transition state region encompasses the majority of electron activity, except for the formation of the C–O bond, which extends well into the products region. In the case of two water molecules, very little electron flux and comparatively less work required for structural changes is noticed in the reactants region, leading to an earlier transition state and therefore to a smaller activation energy and to a larger rate constant. This, together with evidence gathered from other sources, allows us to provide plausible explanations for the observed difference in rate constants

Reaction Electronic Flux Perspective on the Mechanism of the Zimmerman Di-π-methane Rearrangement

The reaction electronic flux (REF) offers a powerful tool in the analysis of reaction mechanisms. Noteworthy, the relationship between aromaticity and REF can eventually reveal subtle electronic events associated with reactivity in aromatic systems. In this work, this relationship was studied for the triplet Zimmerman di-π-methane rearrangement. The aromaticity loss and gain taking place during the reaction is well acquainted by the REF, thus shedding light on the electronic nature of reactions involving dibenzobarrelenes