Recent theoretical studies suggested that hydrogen bonds between ions of like charges are of a covalent nature due to the dominating n →σ* charge-transfer (CT) interaction. In this work, energy profiles of typical hydrogen (H) and halogen (X) bonding systems formed from ions of like charges are explored using the block-localized wavefunction (BLW) method, which can derive optimal geometries and wave functions with the CT interaction "turned off." The results demonstrate that the kinetic stability, albeit reduced, is maintained for most investigated systems even after the intermolecular CT interaction is quenched. Further energy decomposition analyses based on the BLW method reveal that, despite a net repulsive Coulomb repulsion, a stabilizing component exists due to the polarization effect that plays significant role in the kinetic stability of all systems. Moreover, the fingerprints of the augmented electrostatic interaction due to polarization are apparent in the variation patterns of the electron density. All in all, much like in standard H- and X-bonds, the stability of such bonds between ions of like charges is governed by the competition between the stabilizing electrostatic and charge transfer interactions and the destabilizing deformation energy and Pauli exchange repulsion. While in most cases of "anti-electrostatic" bonds the CT interaction is of a secondary importance, we also find cases where CT is decisive. As such, this work validates the existence of anti-electrostatic H- and X-bonds. © 2017 Wiley Periodicals, Inc.

Enzymatic hydrolysis by phosphotriesterase (PTE) is one of the most effective ways to degrade organophosphorus pesticides, but the catalytic efficiency depends on structural features of substrates. Here the enzymatic degradation...

P450 TleB catalyzes the oxidative cyclization of the dipeptide Nmethylvalyl-tryptophanol into indolactam V through selective intramolecular C− H bond amination at the indole C4 position. Understanding its catalytic mechanism is instrumental for the engineering or design of P450-catalyzed C−H amination reactions. Using multiscale computational methods, we show that the reaction proceeds through a diradical pathway, involving a hydrogen atom transfer (HAT) from N1−H to Cpd I, a conformational transformation of the substrate radical species, and a second HAT from N13−H to Cpd II. Intriguingly, the conformational transformation is found to be the key to enabling efficient and selective C−N coupling between N13 and C4 in the subsequent diradical coupling reaction. The underlined conformational transformation is triggered by the first HAT, which proceeds with an energydemanding indole ring flip and is followed by the facile approach of the N13−H group to Cpd II. Detailed analysis shows that the internal electric field (IEF) from the protein environment plays key roles in the transformation process, which not only provides the driving force but also stabilizes the flipped conformation of the indole radical. Our simulations provide a clear picture of how the P450 enzyme can smartly modulate the selective C−N coupling reaction. The present findings are in line with all available experimental data, highlighting the crucial role of substrate dynamics in controlling this highly valuable reaction.

The enzymatic degradation of pesticides paraoxon (PON) and parathion (PIN) by phosphotriesterase (PTE) has been investigated by QM/MM calculations and MD simulations. In the PTE‐PON complex, Znα and Znβ in the active site are five‐ and six‐coordinated, respectively, while both zinc ions are six coordinated with the Znα‐bound water molecule (WT1) for the PTE‐PIN system. The hydrolytic reactions for PON and PIN are respectively driven by the nucleophilic attack of the bridging‐OH− and the Znα‐bound water molecule on the phosphorus center of substrate, and the two‐step hydrolytic process is predicted to be the rate‐limiting step with the energy spans of 13.8 and 14.4 kcal/mol for PON and PIN, respectively. The computational studies reveal that the presence of the Znα‐bound water molecule depends on the structural feature of substrates characterized by P=O and P=S, which determines the hydrolytic mechanism and efficiency for the degradation of organophosphorus pesticides by PTE.