Large protein macromolecules in enzymatic catalysis have been shown to exert a specific electric field that reduces the reorganization energy upon barrier crossing and thus reduces the reaction free energy barrier. In this work we suggest that the charge density in the active site of an enzyme investigated using formalisms embodied by the quantum theory of atoms in molecules (QTAIM) provides a sensitive and quantum field-reactant state charge density-reaction barrier correlation. Hence, QTAIM can be used for the analysis of electric field in enzyme active sites, and further investigations and exploitations of the found correlations may prove useful in enzyme design where preorganization is optimized.

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Our curiosity‐driven desire to “see” chemical bonds dates back at least one‐hundred years, perhaps to antiquity. Sweeping improvements in the accuracy of measured and predicted electron charge densities, alongside our largely bondcentric understanding of molecules and materials, heighten this desire with means and significance. Here we present a method for analyzing chemical bonds and their energy distributions in a two‐dimensional projected space called the condensed charge density. Bond “silhouettes” in the condensed charge density can be reverse‐projected to reveal precise three‐dimensional bonding regions we call bond bundles. We show that delocalized metallic bonds and organic covalent bonds alike can be objectively analyzed, the formation of bonds observed, and that the crystallographic structure of simple metals can be rationalized in terms of bond bundle structure. Our method also reproduces the expected results of organic chemistry, enabling the recontextualization of existing bond models from a charge density perspective.

Visualizing and predicting the response of the electron density, ρ(r), to an external perturbation provides a portion of the insight necessary to understand chemical reactivity. One strategy used to portray electron response is the electron pushing formalism commonly utilized in organic chemistry, where electrons are pictured as flowing between atoms and bonds. Electron pushing is a powerful tool, but does not give a complete picture of electron response. We propose using the motion of zero-flux surfaces (ZFSs) in the gradient of the charge density, ∇ρ(r), as an adjunct to electron pushing. Here we derive an equation rooted in conceptual density functional theory showing that the movement of ZFSs contributes to energetic changes in a molecule undergoing a chemical reaction. Using a substituted acetylene, 1-iodo-2-fluoroethyne, as an example, we show the importance of both the boundary motion and the change in electron counts within the atomic basins of the quantum theory of atoms in molecules for chemical reactivity. This method can be extended to study the ZFS motion between smaller gradient bundles in ρ(r) in addition to larger atomic basins. Finally, we show that the behavior of ∇ρ(r) within atomic basins contains information about electron response and can be used to predict chemical reactivity.