AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

reaxFF Reactive Force Field for Disulfide Mechanochemistry, Fitted to Multireference ab Initio Data

Mechanochemistry, in particular in the form of single-molecule atomic force microscopy experiments, is difficult to model theoretically, for two reasons: Covalent bond breaking is not captured accurately by single-determinant, single-reference quantum chemistry methods, and experimental times of milliseconds or longer are hard to simulate with any approach. Reactive force fields have the potential to alleviate both problems, as demonstrated in this work: Using nondeterministic global parameter optimization by evolutionary algorithms, we have fitted a reaxFF force field to high-level multireference ab initio data for disulfides. The resulting force field can be used to reliably model large, multifunctional mechanochemistry units with disulfide bonds as designed breaking points. Explorative calculations show that a significant part of the time scale gap between AFM experiments and dynamical simulations can be bridged with this approach

The Steel Scrap Age

Steel production accounts for 25% of industrial carbon emissions. Long-term forecasts of steel demand and scrap supply are needed to develop strategies for how the steel industry could respond to industrialization and urbanization in the developing world while simultaneously reducing its environmental impact, and in particular, its carbon footprint. We developed a dynamic stock model to estimate future final demand for steel and the available scrap for 10 world regions. Based on evidence from developed countries, we assumed that per capita in-use stocks will saturate eventually. We determined the response of the entire steel cycle to stock saturation, in particular the future split between primary and secondary steel production.During the 21st century, steel demand may peak in the developed world, China, the Middle East, Latin America, and India. As China completes its industrialization, global primary steel production may peak between 2020 and 2030 and decline thereafter. We developed a capacity model to show how extensive trade of finished steel could prolong the lifetime of the Chinese steelmaking assets. Secondary steel production will more than double by 2050, and it may surpass primary production between 2050 and 2060: the late 21st century can become the steel scrap age

The Roles of Energy and Material Efficiency in Meeting Steel Industry CO₂ Targets

Identifying strategies for reducing greenhouse gas emissions from steel production requires a comprehensive model of the sector but previous work has either failed to consider the whole supply chain or considered only a subset of possible abatement options. In this work, a global mass flow analysis is combined with process emissions intensities to allow forecasts of future steel sector emissions under all abatement options. Scenario analysis shows that global capacity for primary steel production is already near to a peak and that if sectoral emissions are to be reduced by 50% by 2050, the last required blast furnace will be built by 2020. Emissions reduction targets cannot be met by energy and emissions efficiency alone, but deploying material efficiency provides sufficient extra abatement potential

Homoleptic Lanthanide 1,2,3-Triazolates _∞^2–3[Ln(Tz*)₃] and Their Diversified Photoluminescence Properties

The series of homoleptic lanthanide 1,2,3-triazolates _∞³[Ln­(Tz*)₃] (Ln³⁺ = lanthanide cation, Tz*^– = 1,2,3-triazolate anion, C₂H₂N₃^–) is completed by synthesis of the three-dimensional (3D) frameworks with Ln = La, Ce, Pr, Nd, and Sm, and characterization by X-ray powder diffraction, differential thermal analysis-thermogravimetry (DTA/TG) investigations and molecular vibration analysis. In addition, α-_∞²[Sm­(Tz*)₃], a two-dimensional polymorph of 3D β-_∞³[Sm­(Tz*)₃], is presented including the single crystal structure. The 3D lanthanide triazolates form an isotypic series of the formula _∞³[Ln­(Tz*)₃] ranging from La to Lu, with the exception of Eu, which forms a mixed valent metal organic framework (MOF) of different structure and the constitution _∞³[Eu­(Tz*)_6+<i>x</i>(Tz*H)_2–<i>x</i>]. The main focus of this work is put on the investigation of the photoluminescence behavior of lanthanide 1,2,3-triazolates _∞³[Ln­(Tz*)₃] and illuminates that six different luminescence phenomena can be found for one series of isotypic compounds. The luminescence behavior of the majority of these compounds is based on the photoluminescence properties of the organic linker molecules. Differing properties are observed for _∞³[Yb­(Tz*)₃], which exhibits luminescence properties based on charge transfer transitions between the linker and Yb³⁺ ions, and for _∞³[Ce­(Tz*)₃] and _∞³[Tb­(Tz*)₃], in which the luminescence properties are a combination of the ligand and the lanthanide metal. In addition, strong inner-filter effects are found in the ligand emission bands that are attributed to reabsorption of the emitted light by the trivalent lanthanide ions. Antenna effects of varying efficiency are present indicated by the energy being transferred to the lanthanide ions subsequent to excitation of the ligand. _∞³[Ce­(Tz*)₃] shows a 5d-4f induced intense blue emission upon excitation with UV light, while _∞³[Tb­(Tz*)₃] shows emission in the green region of the visible spectrum, which can be identified with 4f-4f-transitions typical for Tb³⁺ ions

Black TiO₂ Nanotubes: Cocatalyst-Free Open-Circuit Hydrogen Generation

Here we report that TiO₂ nanotube (NT) arrays, converted by a high pressure H₂ treatment to anatase-like “black titania”, show a high open-circuit photocatalytic hydrogen production rate without the presence of a cocatalyst. Tubes converted to black titania using classic reduction treatments (e.g., atmospheric pressure H₂/Ar annealing) do not show this effect. The main difference caused by the high H₂ pressure annealing is the resulting room-temperature stable, isolated Ti³⁺ defect-structure created in the anatase nanotubes, as evident from electron spin resonance (ESR) investigations. This feature, absent for conventional reduction, seems thus to be responsible for activating intrinsic, cocatalytic centers that enable the observed high open-circuit hydrogen generation

Synthesis, Structure, and Reactivity of Pentamethylcyclopentadienyl 2,4,6-Triphenylphosphinine Iron Complexes

The potassium salt [K([18]­crown-6)­(THF)₂]­[Cp*Fe­(η⁴-2,4,6-triphenyl­phosphinine)}] (<b>K1</b>, Cp* = C₅Me₅) can be isolated in 68% yield by reacting the anionic naphthalene complex [K([18]­crown-6)­{Cp*Fe­(η⁴-C₁₀H₈)}] (C₁₀H₈ = naphthalene) with 2,4,6-triphenylphosphinine. Compound <b>K1</b> reacts with water to afford [K([18]-crown-6)]­{Cp*Fe­(η⁴-2,4,6-triphenyl-2,3-dihydrophosphinine 1-oxide)}] (<b>K2</b>) with a novel 2,3-dihydrophosphinine 1-oxide ligand. Oxidation of <b>K1</b> with one equivalent of ferrocenium hexafluorophosphate yields the P–P-bonded diphosphinine complex [Cp*Fe­(η⁵-2,4,6-triphenyl­phosphinine)]₂ (<b>3</b>), while the iodide salt [Cp*Fe­(η⁶-2,4,6-triphenyl­phosphinine)]­I (<b>4</b>) can be obtained by reacting <b>K1</b> with one equivalent of iodine. Reactions of <b>4</b> with LiNMe₂, Cp*Li, LiBHEt₃, and Ga­(nacnac^Dipp) (nacnac^Dipp = HC­{C­(Me)­N­(C₆H₃-2,6-<i>i</i>Pr₂)}₂) afford [Cp*Fe­(η⁵-1-dimethylamino-2,4,6-triphenyl­phosphacyclohexadienyl)] (<b>5</b>), [Cp*Fe­(η⁵-1-(η¹-Cp*)-2,4,6-triphenyl­phosphacyclohexadienyl)] (<b>6</b>), [Cp*Fe­(η⁵-1-hydro-2,4,6-triphenyl­phosphacyclohexadienyl)] (<b>7</b>), and [Cp*Fe­((η⁵-1-{Ga­(nacnac^Dipp)­I}-2,4,6-triphenyl­phosphacyclohexadienyl] (<b>8</b>). The molecular structures of <b>5</b>–<b>8</b> display η⁵-coordinated λ³σ³-phosphinine anions. All new complexes were fully characterized by spectroscopic techniques (¹H, ¹³C, and ³¹P NMR, UV–vis, and IR spectroscopy), elemental analysis, and X-ray crystallography. The electronic structures of these new phosphinine complexes were investigated theoretically at the DFT level, using molecular orbital and population analyses. The nature of the electronic transitions observed in the UV–vis spectra was analyzed using TD-DFT calculations