Reply to the comment by Amano on “Linear and bent triatomic molecules are not qualitatively different!”

In Amano’s comment on Jensen’s paper, we notice two important misconceptions: (i) Amano overlooks the fact that all features special for a linear molecule originate in the double degeneracy in the bending motion (i.e., in the fact that for a linear triatomic molecule, the description of the bending motion must necessarily also involve the rotation about the axis of least moment of inertia, the a axis, which becomes the molecular axis at equilibrium), and (ii) the expectation value generated from the wavefunction gives an “average” value of the relevant observable (coordinate); the expectation value can, in principle, be obtained experimentally as the average of very many repeated measurements of the observable. In our previous papers on this subject, in particular the paper by Jensen discussed here, we have attempted to explain our results as coherently and “pedagogically” as we can, starting with the fundamental principles of quantum mechanics, and we encourage interested readers to refer to our previous works on the subject. Thus, we maintain our assertion that the vibrationally averaged structure of a linear molecule is observed as being bent, as we have demonstrated previously from both theoretical and experimental viewpoints.

Effect of Material Properties on the Foaming Behaviors of PP-Based Wood Polymer Composites Prepared with the Application of Spherical Cavity Mixer

For the low weight and high strength, the microcellular extrusion foaming technology was applied in the preparation of polypropylene (PP)-based wood polymer composites, and the spherical cavity mixer was used to construct an experimental platform for the uniform dispersion of wood flour (WF). The effects of PP molecular configuration on the composite properties and cell morphology of samples were also investigated. The experimental results indicated that the application of a spherical cavity mixer with a cavity radius of 5 mm could effectively improve the mixing quality and avoid the agglomeration of WF. In addition, compared with the branched molecule, the linear molecule not only increased the melting temperature by about 10 °C, but also endowed composites with a higher complex viscosity at a shear rate lower than 100 s−1, which contributed to the cell morphology of more microporous samples.

Artificial-intelligence-driven discovery of catalyst “genes” with application to CO2 activation on semiconductor oxides

Using subgroup discovery, an artificial intelligence (AI) approach that identifies statistically exceptional subgroups in a dataset, we develop a strategy for a rational design of catalytic materials. We identify “materials genes” (features of catalyst materials) that correlate with mechanisms that trigger, facilitate, or hinder the activation of carbon dioxide (CO2) towards a chemical conversion. The approach is used to address the conversion of CO2 to fuels and other useful chemicals. The AI model is trained on high-throughput first-principles data for a broad family of oxides. We demonstrate that bending of the gas-phase linear molecule, previously proposed as the indicator of activation, is insufficient to account for the good catalytic performance of experimentally characterized oxide surfaces. Instead, our AI approach identifies the common feature of these surfaces in the binding of a molecular O atom to a surface cation, which results in a strong elongation and therefore weakening of one molecular C-O bond. The same conclusion is obtained by using the bending indicator only when incombination with the Sabatier principle. Based on these findings, we propose a set of new promising oxide-based catalyst materials for CO2 conversion, and a recipe to find more. Our analysis also reveals advantages of local pattern discovery methods such as subgroup discovery over standard global regression approaches in discovering combinations of materials properties that result in a catalytic activation.

MyoD is a structure organizer of 3D genome architecture in muscle cells

The genome is not a linear molecule of DNA randomly folded in the nucleus, but exists as an organized, three-dimensional (3D) dynamic architecture. Intriguingly, it is now clear that each cell type has a unique and characteristic 3D genome organization that functions in determining cell identity during development. A currently challenging basic question is how cell-type specific 3D genome structures are established during development. Herein, we analyzed 3D genome structures in primary myoblasts and myocytes from MyoD knockout (MKO) and wild type (WT) mice and discovered that MyoD, a pioneer transcription factor (TF), can function as a “genome organizer” that specifies the proper 3D genome architecture unique to muscle cell development. Importantly, we genetically demonstrate that H3K27ac is insufficient for establishing MyoD-induced chromatin loops in muscle cells. The establishment of MyoD’s “architectural role” should have profound impacts on advancing understanding of other pioneer transcription factors in orchestrating lineage specific 3D genome organization during development in a potentially very large number of cell types in diverse organisms.

The effective volumes of waters of crystallization: general organic solids

Using a list of compatible hydrate/anhydrate pairs prepared by van de Streek and Motherwell [CrystEngComm (2007), 9, 55–64], we have examined the effective volume per water of crystallization for 179 pairs of organic solids using current data from the Cambridge Crystallographic Structural Database (CSD). The effective volume is the difference per water molecule between the asymmetric unit volumes of the hydrate and parent anhydrate, and has the mean value 24 Å3. The conformational changes in the reference molecule between the hydrate and its anhydrate are shown in two figures: one for a relatively rigid standard organic molecule and (in the supplementary file) one for a more flexible linear molecule. Using data from Nyman and Day [Phys. Chem. Chem. Phys. (2016), 18, 31132–31143], we have also established a generic volumetric coefficient of thermal expansion of organic solids with a value of 147 ± 56 × 10−6 K−1. There is a significant number of outliers to the data, negative, near zero, and large and positive. Some explanation for the existence of these outliers is attempted.

Robust Supramolecular Nano-Tunnels Built from Molecular Bricks

Chemists are always seeking new methods to construct porous lattice frameworks using simple motifs as the impetus. Different from the extensively reported frameworks which were stabilized by extended bonding, porous crystals of discrete organic molecules is an emerging area of porous materials with dynamic and flexible conformation, consisting exclusively of non-covalent interactions. Herein we report geometrically simple linear molecule that assemble into a supramolecular nano-tunnel through synergy of anionic trident and multiple intermolecular pi-pi stacking interactions. The nano-tunnel crystal exhibit exceptional chemical stability in concentrated HCl and NaOH aqueous solutions, which is rarely been seen in supramolecular organic frameworks and often related to designed extensive hydrogen bonding interactions. Upon thermal treatment, the formed nano-tunnel crystals go through multistage single-crystal-to-single-crystal phase transformations accompanied by thermosalient effect. Aggregation-induced emission joins with the adaptive pores render the crystals with responsive fluorescent change from blue to yellow and visible self-healing porosity transformation upon being stimulated. Furthermore, the desolvated pores exhibit highly selective CO2 adsorption at ambient temperature. <br>

Robust Supramolecular Nano-Tunnels Built from Molecular Bricks

Chemists are always seeking new methods to construct porous lattice frameworks using simple motifs as the impetus. Different from the extensively reported frameworks which were stabilized by extended bonding, porous crystals of discrete organic molecules is an emerging area of porous materials with dynamic and flexible conformation, consisting exclusively of non-covalent interactions. Herein we report geometrically simple linear molecule that assemble into a supramolecular nano-tunnel through synergy of anionic trident and multiple intermolecular pi-pi stacking interactions. The nano-tunnel crystal exhibit exceptional chemical stability in concentrated HCl and NaOH aqueous solutions, which is rarely been seen in supramolecular organic frameworks and often related to designed extensive hydrogen bonding interactions. Upon thermal treatment, the formed nano-tunnel crystals go through multistage single-crystal-to-single-crystal phase transformations accompanied by thermosalient effect. Aggregation-induced emission joins with the adaptive pores render the crystals with responsive fluorescent change from blue to yellow and visible self-healing porosity transformation upon being stimulated. Furthermore, the desolvated pores exhibit highly selective CO2 adsorption at ambient temperature. <br>

Automated Design of Macrocycles for Therapeutic Applications: from Small Molecules to Peptides and Proteins

<div>Macrocycles and cyclic peptides are increasingly attractive therapeutic modalities as they often have </div><div>improved affinity, are able to bind to extended protein interfaces and otherwise have favorable </div><div>properties. Macrocyclization of a known binder molecule has the potential to stabilize its bioactive </div><div>conformation, improve its metabolic stability, cell permeability and in certain cases oral </div><div>bioavailability. Herein, we present an in silico approach that automatically generates, evaluates and </div><div>proposes cyclizations utilizing a library of well-established chemical reactions and reagents. Using the </div><div>three-dimensional (3D) conformation of the linear molecule in complex with a target protein as </div><div>starting point, this approach identifies attachment points, generates linkers, evaluates the </div><div>conformational landscape of suitable linkers and their geometric compatibility and ranks the resulting </div><div>molecules with respect to their predicted conformational stability and interactions with the target </div><div>protein. As we show here with several prospective and retrospective case studies, this procedure can </div><div>be applied for the macrocyclization of small molecules and peptides and even PROTACs and proteins.</div><div>The presented approach is an important step towards the enhanced utilization of macrocycles and</div><div>cyclic peptides as attractive therapeutic modalities.</div>

Automated Design of Macrocycles for Therapeutic Applications: from Small Molecules to Peptides and Proteins

<div>Macrocycles and cyclic peptides are increasingly attractive therapeutic modalities as they often have </div><div>improved affinity, are able to bind to extended protein interfaces and otherwise have favorable </div><div>properties. Macrocyclization of a known binder molecule has the potential to stabilize its bioactive </div><div>conformation, improve its metabolic stability, cell permeability and in certain cases oral </div><div>bioavailability. Herein, we present an in silico approach that automatically generates, evaluates and </div><div>proposes cyclizations utilizing a library of well-established chemical reactions and reagents. Using the </div><div>three-dimensional (3D) conformation of the linear molecule in complex with a target protein as </div><div>starting point, this approach identifies attachment points, generates linkers, evaluates the </div><div>conformational landscape of suitable linkers and their geometric compatibility and ranks the resulting </div><div>molecules with respect to their predicted conformational stability and interactions with the target </div><div>protein. As we show here with several prospective and retrospective case studies, this procedure can </div><div>be applied for the macrocyclization of small molecules and peptides and even PROTACs and proteins.</div><div>The presented approach is an important step towards the enhanced utilization of macrocycles and</div><div>cyclic peptides as attractive therapeutic modalities.</div>

Linear and bent triatomic molecules are not qualitatively different!

I, and other authors, have discussed in several recent publications that “linear” triatomic molecules (defined as having linear equilibrium structures) are necessarily observed as being bent on ro-vibrational average. We have demonstrated this theoretically by calculations of the rotation–vibration expectation values, [Formula: see text], where [Formula: see text] is the bond angle supplement, [Formula: see text] being the instantaneous value of the bond angle of the triatomic molecule A–B–C. Direct experimental evidence of bent average structures has been obtained by other authors in Coulomb explosion imaging experiments, and indirect evidence from re-interpretation of experimentally derived rotational constant values. In spite of a rather significant amount of evidence in support of the bent average structures, the idea has been heavily criticized. In the present work I discuss in more detail some of the arguments for the bent average structures put forward in previous papers, and I hope to correct and clarify some of the misunderstandings leading to the criticisms. Part of the criticism originates in a widespread, but fallacious, belief among spectroscopists that linear and bent chain molecules have qualitatively different energy-level and spectral intensity patterns. This is not true. One can view the linear-molecule energy level and spectral patterns as limiting cases of the bent-molecule ones.