How a Quantum Chemical Topology Analysis Enables Prediction of Electron Density Transfers in Chemical Reactions. The Degenerated Cope Rearrangement of Semibullvalene

Recent works on the reaction mechanism for the degenerated Cope rearrangement (DCR) of semibullvalene (SBV) in the ground state prompted us to investigate this complex rearrangement in order to assign experimentally observed contrast features in the simulated electron distribution. We present a joint use of the electron localization function (ELF) and Thom's catastrophe theory (CT) as a powerful tool to analyze the electron density transfers along the DCR. The progress of the reaction is monitored by the structural stability domains of the topology of ELF, while the change between them is controlled by turning points derived from CT. The ELF topological analysis shows that the DCR of SBV corresponds to asynchronous electron density rearrangement taking place in three consecutive stages. We show how the pictures anticipated by drawing Lewis structures of the rearrangement correlate with the experimental data and time-dependent quantum description of the process

Joint Use of Bonding Evolution Theory and QM/MM Hybrid Method for Understanding the Hydrogen Abstraction Mechanism via Cytochrome P450 Aromatase

Bonding evolution theory (BET), as a combination of the electron localization function (ELF) and Thom’s catastrophe theory (CT), has been coupled with quantum mechanics/molecular mechanics (QM/MM) method in order to study biochemical reaction paths. The evolution of the bond breaking/forming processes and electron pair rearrangements in an inhomogeneous dynamic environment provided by the enzyme has been elucidated. The proposed methodology is applied in an enzymatic system in order to clarify the reaction mechanism for the hydrogen abstraction of the androstenedione (ASD) substrate catalyzed by the cytochrome P450 aromatase enzyme. The use of a QM/MM Hamiltonian allows inclusion of the polarization of the charges derived from the amino acid residues in the wave function, providing a more accurate and realistic description of the chemical process. The hydrogen abstraction step is found to have five different ELF structural stability domains, whereas the C–H breaking and O–H forming bond process rearrangements are taking place in an asynchronous way

Penetrating the Elusive Mechanism of Copper-Mediated Fluoromethylation in the Presence of Oxygen through the Gas-Phase Reactivity of Well-Defined [LCuO]⁺ Complexes with Fluoromethanes (CH_{(4–<i>n</i>)}F_<i>n</i>, <i>n</i> = 1–3)

Traveling wave ion mobility spectrometry (TWIMS) isomer separation was exploited to react the particularly well-defined ionic species [LCuO]⁺ (L = 1,10-phenanthroline) with the neutral fluoromethane substrates CH_{(4–<i>n</i>)}F_<i>n</i> (<i>n</i> = 1–3) in the gas phase. Experimentally, the monofluoromethane substrate (<i>n</i> = 1) undergoes both hydrogen-atom transfer, forming the copper hydroxide complex [LCuOH]^•+ and concomitantly a CH₂F^• radical, and oxygen-atom transfer, yielding the observable ionic product [LCu]⁺ plus the neutral oxidized substrate [C,H_3,O,F]. DFT calculations reveal that the mechanism for both product channels relies on the initial C–H bond activation of the substrate. Compared to nonfluorinated methane, the addition of fluorine to the substrate assists the reactivity through a lowering of the C–H bond energy and reaction preorganization (through noncovalent interaction in the encounter complex). A two-state reactivity scenario is mandatory for the oxidation, which competitively results in the unusual fluoromethanol product, CH₂FOH, or the decomposed products, CH₂O and HF, with the latter channel being kinetically disfavored. Difluoromethane (<i>n</i> = 2) is predicted to undergo the analogous reactions at room temperature, although the reactions are less favored than those of monofluoromethane. The reaction of trifluoromethane (<i>n</i> = 3, fluoroform) through C–H activation is kinetically hindered under ambient conditions but might be expected to occur in the condensed phase upon heating or with further lowering of reaction barriers through templation with counterions, such as potassium. Overall, formation of CH_{(3–<i>n</i>)}F_<i>n</i>^• and CH_{(3–<i>n</i>)}F_<i>n</i>OH occurs under relatively gentle energetic conditions, which sheds light on their potential as reactive intermediates in fluoromethylation reactions mediated by copper in the presence of oxygen

Following the Molecular Mechanism for the NH₃ + LiH → LiNH₂ + H₂ Chemical Reaction: A Study Based on the Joint Use of the Quantum Theory of Atoms in Molecules (QTAIM) and Noncovalent Interaction (NCI) Index

The molecular mechanism for the NH₃ + LiH → LiNH₂ + H₂ reaction has been elucidated by the combined use of quantum theory of atoms in molecules (QTAIM) and noncovalent interactions (NCI) index. The topology of the electron density, obtained by QTAIM/NCI, is able to identify the evolution of strong and weak interactions, recovering the bonding patterns along the reaction pathway. Thus, the combination of these two techniques is a useful and powerful tool in the study of chemical events, providing new strategies to understand and visualize the molecular mechanisms of chemical rearrangements. Also, for the first time, the topology of the reduced density gradient has been analyzed, taking into account saddle points for the construction of bifurcation trees. This approach has demonstrated the ability of NCI to account for delocalized interactions, very often characteristic of transitions states