Electrochemical production of H2O2 is more benign and affordable than the conventional route, yet its adoption requires the discovery of robust, cost‐effective catalysts. DFT‐based models lead to conspicuous breakthroughs but had some known limitations, for instance the poor description of molecules with certain chemical bonds. Here, the errors in H2O2 and O2 displayed by various GGAs, meta‐GGAs and hybrids were assessed and semi empirically corrected. The errors in O2 with respect to experiments were in the range of −0.95 to −0.22 eV, whereas those in H2O2 spanned from −0.53 to −0.04 eV. Thus, single and double O−O bonds were poorly described in general, and the errors were nearly twice as negative for double bonds. Furthermore, these errors introduced large deviations in the predictions of free energies for O2 reduction to H2O2, and the equilibrium potentials and optimal adsorption energies of *OOH could either be sizably overestimated or underestimated.

Invited for this month's cover picture is the group of Federico Calle‐Vallejo and Francesc Illas from the University of Barcelona (Spain). The cover picture shows that there are three ways of simulating the energy landscape of oxygen reduction to hydrogen peroxide with density functional theory: without any corrections (yellow), with O2 corrections (yellow/red), and with O2 and H2O2 corrections (red); only the latter agrees with experiments. Read the full text of the Research Article at 10.1002/celc.202200210

Activin-like kinase 5 (ALK-5) is involved in the physiopathology of several conditions, such as pancreatic carcinoma, cervical cancer and liver hepatoma. Cellular events that are landmarks of tumorigenesis, such as loss of cell polarity and acquisition of motile properties and mesenchymal phenotype, are associated to deregulated ALK-5 signaling. ALK-5 inhibitors, such as SB505154, GW6604, SD208, and LY2157299, have recently been reported to inhibit ALK-5 autophosphorylation and induce the transcription of matrix genes. Due to their ability to impair cell migration, invasion and metastasis, ALK-5 inhibitors have been explored as worthwhile hits as anticancer agents. This work reports the development of a structure-based virtual screening (SBVS) protocol aimed to prospect promising hits for further studies as novel ALK-5 inhibitors. From a lead-like subset of purchasable compounds, five molecules were identified as putative ALK-5 inhibitors. In addition, molecular dynamics and binding free energy calculations combined with pharmacokinetics and toxicity profiling demonstrated the suitability of these compounds to be further investigated as novel ALK-5 inhibitors.