General structure-free energy relationships of hERG blocker binding under native cellular conditions

We proposed previously that aqueous non-covalent barriers arise from solute-induced perturbation of the H-bond network of solvating water ('the solvation field') relative to bulk solvent, where the association barrier equates to enthalpic losses incurred from incomplete replacement of the H-bonds of expelled H-bond enriched solvation by inter-partner H-bonds, and the dissociation barrier equates to enthalpic + entropic losses incurred during dissociation-induced resolvation of H-bond depleted positions of the free partners (where dynamic occupancy is powered largely by the expulsion of such solvation to bulk solvent during association). We analyzed blockade of the ether-a-go-go-related gene potassium channel (hERG) based on these principles, the results of which suggest that blockers: 1) project a single rod-shaped R-group (denoted as 'BP') into the pore at a rate proportional to the desolvation cost of BP, with the largely solvated remainder (denoted as 'BC') occupying the cytoplasmic 'antechamber' of hERG; and 2) undergo second-order entry to the antechamber, followed by first-order association of BP to the pore. In this work, we used WATMD to qualitatively survey the solvation fields of the pore and a representative set of 16 blockers sampled from the Redfern dataset of marketed drugs spanning a range of pro-arrhythmicity. We show that the highly non-polar pore is solvated principally by H-bond depleted and bulk-like water (incurring zero desolvation cost), whereas blocker BP moieties are solvated by variable combinations of H-bond enriched and depleted water. With a few explainable exceptions, the blocker solvation fields (and implied desolvation/resolvation costs) are qualitatively well-correlated with blocker potency and Redfern safety classification.

Study of the Rate-Determining Step of Rh Catalyzed CO2 Reduction: Insight on the Hydrogen Assisted Molecular Dissociation

In the context of climate change mitigation, CO2 methanation is an important option for the production of synthetic carbon-neutral fuels and for atmospheric CO2 recycling. While being highly exothermic, this reaction is kinetically unfavorable, requiring a catalyst to be efficiently activated. Recently Rh nanoparticles gained attention as effective photocatalyst, but the rate-determining step of this reaction on Rh surface has not been characterized yet. In this work, Density Functional Theory and Nudged Elastic Band calculations were performed to study the Rh-catalyzed rate-determining step of the CO2 methanation, which concerns the hydrogen assisted cleavage of the CO* molecule and subsequent formation of CH* and O* (* marks adsorbed species), passing through the CHO* key intermediate. The configurations of the various adsorbates on the Rh (100) surface were investigated and the reaction mechanism was studied exploiting different exchange-correlation functionals (PBE, RPBE) and the PBE+U technique. The methanation rate-determining step consists of two subprocesses which subsequently generate and dissociate the CHO* species. The energetics and the dynamics of such processes are extensively studied and described. Interestingly, PBE and PBE+U calculated activation barriers are in good agreement with the available experimental data, while RPBE largely overestimate the CHO* dissociation barrier.

Degradation of bromobenzene via external electric field

Bromobenzene is one of the organic pollutants that damage the natural environment and poses a serious threat to human health. Therefore, it is meaningful to study its degradation characteristics under the electric field. In this paper, density functional theory (DFT) at BPV86/6-311G (d, p) level are employed for the study of C–Br bond distance, total energy, charge distribution, dipole moment, lowest unoccupied molecular orbital (LUMO) level, highest occupied molecular orbital (HOMO) level, energy gap and potential energy surface (PES) of bromobenzene in external electric field ([Formula: see text]15.43[Formula: see text]V[Formula: see text][Formula: see text][Formula: see text]nm[Formula: see text]–15.43[Formula: see text]V[Formula: see text][Formula: see text][Formula: see text]nm[Formula: see text]). It shows that as the electric field increases, the C–Br bond tends to break. The changes in the HOMO level and the LUMO level result in a rapid drop in the energy gap. In addition, the dissociation barrier gradually decreases. When the applied electric field reaches 15.43[Formula: see text]V[Formula: see text][Formula: see text]nm[Formula: see text], the dissociation barrier disappears completely, which means that the C–Br bond is broken and bromobenzene is degraded.

CO2 capture, activation and dissociation on the Ti2C surface and Ti2C MXene: the role of surface structure

Barrier-less CO2 activation on Ti2C(100) and MXene with preferential adsorption on the (100) surface and a lower dissociation barrier on MXene.

Enhanced alkaline hydrogen evolution performance of ruthenium by synergetic doping of cobalt and phosphorus

The synergistic doping of Co and P into Ru could reduce the water dissociation barrier and optimize the hydrogen adsorption strength.

A DFT Screening of M-HKUST-1 MOFs for Nitrogen-Containing Compounds Adsorption

To develop promising adsorbent candidates for adsorptive denitrogenation, we screened the adsorption of NO, NO2, and NH3 in 19 M-HKUST-1 (M = Be, Fe, Ni, Cr, Co, Cu, V, Zn, Mo, Mn, W, Sn, Ti, Cd, Mg, Sc, Ca, Sr, and Ba) systematically using first-principle calculations. Of these, four variants of M-HKUST-1 (M = Ni, Co, V, and Sc) yield more negative adsorption Gibbs free energy ΔGads than the original Cu-HKUST-1 for three adsorbates, suggesting stronger adsorbate binding. Ti-HKUST-1, Sc-HKUST-1, and Be-HKUST-1 are predicted to have the largest NO, NO2, and NH3 adsorption energies within the screened M-HKUST-1 series, respectively. With the one exception of NO2 dissociation on V-HKUST-1, dissociative adsorption of NO, NO2, and NH3 molecules on the other considered M-HKUST-1 is energetically less favorable than molecular adsorption thermodynamically. The barrier calculations show that the dissociation is difficult to occur on Cu-HKUST-1 kinetically due to the very large dissociation barrier. Electronic analysis is provided to explain the bond nature between the adsorbates and M-HKUST-1. Note that the isostructural substitution of Cu to the other metals is a major simplification of the system, representing the ideal situation; however, the present study provides interesting targets for experimental synthesis and testing.

The studies on the physical and dissociation properties of chlorobenzene under external electric fields

Chlorobenzene is one of the Persistent Organic Pollutants (POPs) threatening human health. It is significant to study the degradation mechanism under external electric fields. Based on the density functional theory, the physical and dissociation properties including C–Cl bond length, total energy, dipole moment, frontier orbital energy, energy gap, IR spectrum, UV-vis absorption spectrum and potential energy curve are studied under external electric fields. According to these results, it is found that the C–Cl bond length becomes longer and tends to break with the increase of external electric field and the energy gap decreases with the increase of positive as well as negative external electric field. Moreover, the dissociation barrier in potential energy curve decreases and equilibrium bond length increases with increase of positive external electric field. And when external electric field reaches 0.040 atomic units ([Formula: see text], 1 atomic [Formula: see text], the dissociation barrier disappears which means that degradation of chlorobenzene occurs under strong external electric field due to the breakage of C–Cl bond. These results provide important references for studying the degradation mechanism of chlorobenzene under strong external electric fields.

Ab Initio Molecular Dynamics Simulation of Tribochemical Reactions Involving Phosphorus Additives at Sliding Iron Interfaces

We performed for the first time to our knowledge fully ab initio molecular dynamics simulations of additive tribochemistry in boundary lubrication conditions. We consider an organophosphourus additive that has been experimentally shown to reduce friction in steel-on-steel sliding contacts thanks to the tribologically-induced formation of an iron phosphide tribofilm. The simulations allow us to observe in real time the molecular dissociation at the sliding iron interface under pressure and to understand the mechanism of iron phosphide formation. We discuss the role played by the mechanical stress by comparing the activation times for molecular dissociation observed in the tribological simulations at different applied loads with that expected on the basis of the dissociation barrier.