Oleksandr

While machine learning has been making enormous strides in many technical areas, it is still massively underused in transmission electron microscopy. To address this, a convolutional neural network model was developed for reliable classification of crystal structures from small numbers of electron images and diffraction patterns with no preferred orientation. Diffraction data containing 571,340 individual crystals divided among seven families, 32 genera, and 230 space groups were used to train the network. Despite the highly imbalanced dataset, the network narrows down the space groups to the top two with over 70% confidence in the worst case and up to 95% in the common cases. As examples, we benchmarked against alloys to two-dimensional materials to cross-validate our deep-learning model against high-resolution transmission electron images and diffraction patterns. We present this result both as a research tool and deep-learning application for diffraction analysis.

The successful construction of sophisticated tetrahedral anion–π receptors has been achieved by a macrocycle‐directed approach. With the enclosed three‐dimensional cavity surrounded by four‐electron‐deficient triazine faces, the tetrahedral receptors are able to selectively accommodate a series of tetrahedral and relevant anions through unprecedented complementary and cooperative anion–π interactions.

Abstract

Manipulation of the emerging anion–π interactions in a highly cooperative manner through sophisticated host design represents a very challenging task. In this work, unprecedented tetrahedral anion–π receptors have been successfully constructed for complementary accommodation of tetrahedral and relevant anions. The synthesis was achieved by a macrocycle‐directed approach by using large macrocycle precursors bearing four reactive sites, which enabled a kinetic‐favored pathway and afforded the otherwise inaccessible tetrahedral cages in considerable yields. Crystal structure suggested that the tetrahedral cages have an enclosed three‐dimensional cavity surrounded by four electron‐deficient triazine faces in a tetrahedral array. The complementary accommodation of a series of tetrahedral and relevant anions including BF₄ ⁻, ClO₄ ⁻, H₂PO₄ ⁻, HSO₄ ⁻, SO₄ ²⁻ and PF₆ ⁻ was revealed by ESI‐MS and DFT calculations. Crystal structures of ClO₄ ⁻ and PF₆ ⁻ complexes showed that the anion was nicely encapsulated within the tetrahedral cavity with up to quadruple cooperative anion–π interactions by an excellent shape and size match. The strong anion–π binding was further confirmed by negative ion photoelectron spectroscopy measurements.

Reversible covalent bonds play a significant role in achieving the high‐yielding synthesis of mechanically interlocked molecules. Still, only a handful of such bonds have been successfully employed in synthetic procedures. Herein, we introduce a novel approach for the fast and simple preparation of mechanically interlocked molecules, combining the dynamic bond character of bis(acyloxy)iodate(I) anions with macrocyclic bambusuril anion receptors. The proof of principle was demonstrated on rotaxane synthesis, with near‐quantitative yields observed in both the classical and “in situ” approach. The rotaxane formation was confirmed in the solid state and solution by the X‐ray and NMR studies, respectively. Our novel approach could be utilized in the fields of dynamic combinatorial chemistry, supramolecular polymers, or molecular machines, as well inspire further research on molecules that exhibit dynamic behavior, but due to their high reactivity, have not been considered as constituents of more elaborate supramolecular structures.

A radical shielding approach based on supramolecular complexation exploits the protection offered by a [10]cycloparaphenylene ([10]CPP) nanobelt encircling C₅₉N^. to stabilize this radical. The EPR signal of C₅₉N^.⊂[10]CPP showing characteristic ¹⁴N hyperfine splitting was observed even several weeks after its generation.

Abstract

A major handicap towards the exploitation of radicals is their inherent instability. In the paramagnetic azafullerenyl radical C₅₉N^., the unpaired electron is strongly localized next to the nitrogen atom, which induces dimerization to diamagnetic bis(azafullerene), (C₅₉N)₂. Conventional stabilization by introducing steric hindrance around the radical is inapplicable here because of the concave fullerene geometry. Instead, we developed an innovative radical shielding approach based on supramolecular complexation, exploiting the protection offered by a [10]cycloparaphenylene ([10]CPP) nanobelt encircling the C₅₉N^. radical. Photoinduced radical generation is increased by a factor of 300. The EPR signal showing characteristic ¹⁴N hyperfine splitting of C₅₉N^.⊂ [10]CPP was traced even after several weeks, which corresponds to a lifetime increase of >10⁸. The proposed approach can be generalized by tuning the diameter of the employed nanobelts, opening new avenues for the design and exploitation of radical fullerenes.

Nature, Published online: 26 September 2019; doi:10.1038/d41586-019-02918-5

What a ligand! With bifunctional ligands specifically designed for gold catalysis, acetylenic amides are efficiently transformed into 2‐aminofurans in a single step. The highly electron‐rich nature of these furans makes them difficult to access by other means, but also endows them with exceptional synthetic value. D‐A=Diels–Alder, EWG=electron‐withdrawing group.

Abstract

By using biphenyl‐2‐ylphosphines functionalized with a remote tertiary amino group as a ligand, readily available acetylenic amides are directly converted into 2‐aminofurans devoid of any electron‐withdrawing and hence deactivating/stabilizing substituents. These highly electron‐rich furans have rarely been prepared, let alone applied in synthesis, because of their high reactivities and low stabilities associated with the electron‐rich nature of the furan ring. In this work, these reactive furans smoothly undergo either in situ intermolecular Diels–Alder reactions to deliver highly functionalized/substituted aniline products or intramolecular ones to furnish carbazole‐4‐carboxylates in mostly good to excellent yields. This work offers general and expedient access to this class of little studies electron‐rich furans and should lead to exciting opportunities for their applications.

Nature, Published online: 09 September 2019; doi:10.1038/s41586-019-1539-y

Nature, Published online: 09 September 2019; doi:10.1038/s41586-019-1544-1

Molecular machines: Four [3]rotaxane‐based molecular shuttles with two interacting macrocycles have been synthesized. The interactions among the three components (two macrocycles and one axle) were shown to not only affect the relative positions of the macrocycles along the axles with different spacer lengths, but also cause a synchronized motion of the two macrocycles when adding stimuli.

Abstract

Noncovalent interactions between all the neighboring components in biomolecular machines are responsible for their synchronized motion and thus complex functions. This strategy has rarely been used in multicomponent molecular machines. Here, we report four [3]rotaxane‐based molecular shuttles. Noncovalent interactions among the three components (two interacting macrocycles and one axle) not only cause a “systems‐level” effect on the relative positions of the two macrocycles along the axle, but also result in a synchronized motion of the two macrocycles when adding partial amount of stimuli. Moreover, the intermediate state with one shuttled macrocycle even exist predominantly in the solution during the titration of stimuli, which is theoretically unexpected for the [3]rotaxane with two non‐interacting rings. This biomimetic strategy may provide a method for constructing highly complex molecular machines.

The synthesis of complex organic molecules requires several stages, from ideation to execution, that require time and effort investment from expert chemists. Here, we report a step toward a paradigm of chemical synthesis that relieves chemists from routine tasks, combining artificial intelligence–driven synthesis planning and a robotically controlled experimental platform. Synthetic routes are proposed through generalization of millions of published chemical reactions and validated in silico to maximize their likelihood of success. Additional implementation details are determined by expert chemists and recorded in reusable recipe files, which are executed by a modular continuous-flow platform that is automatically reconfigured by a robotic arm to set up the required unit operations and carry out the reaction. This strategy for computer-augmented chemical synthesis is demonstrated for 15 drug or drug-like substances.

Nature Communications, Published online: 08 August 2019; doi:10.1038/s41467-019-11467-4

The host with the most: An acid‐functionalized self‐assembled host catalyzes the thioetherification of alcohols by high affinity molecular recognition and activation of the reactants.

Abstract

A self‐assembled Fe₄L₆ cage complex internally decorated with acid functions is capable of accelerating the thioetherification of activated alcohols, ethers and amines by up to 1000‐fold. No product inhibition is seen, and effective supramolecular catalysis can occur with as little as 5 % cage. The substrates are bound in the host with up to micromolar affinities, whereas the products show binding that is an order of magnitude weaker. Most importantly, the cage host alters the molecularity of the reaction: whereas the reaction catalyzed by simple acids is a unimolecular, S_N1‐type substitution process, the rate of the host‐mediated process is dependent on the concentration of nucleophile. The molecularity of the cage‐catalyzed reaction is substrate‐dependent, and can be up to bimolecular. In addition, the catalysis can be prevented by a large excess of nucleophile, where substrate inhibition dominates, and the use of tritylated anilines as substrates causes a negative feedback loop, whereby the liberated product destroys the catalyst and stops the reaction.

Nature Chemistry, Published online: 29 July 2019; doi:10.1038/s41557-019-0299-5

Nature Chemistry, Published online: 22 July 2019; doi:10.1038/s41557-019-0301-2

Inspired by the dynamics of the dissipative self-assembly of microtubules, chemically fueled synthetic systems with transient lifetimes are emerging for nonequilibrium materials design. However, realizing programmable or even adaptive structural dynamics has proven challenging because it requires synchronization of energy uptake and dissipation events within true steady states, which remains difficult to orthogonally control in supramolecular systems. Here, we demonstrate full synchronization of both events by ATP-fueled activation and dynamization of covalent DNA bonds via an enzymatic reaction network of concurrent ligation and cleavage. Critically, the average bond ratio and the frequency of bond exchange are imprinted into the energy dissipation kinetics of the network and tunable through its constituents. We introduce temporally and structurally programmable dynamics by polymerization of transient, dynamic covalent DNA polymers with adaptive steady-state properties in dependence of ATP fuel and enzyme concentrations. This approach enables generic access to nonequilibrium soft matter systems with adaptive and programmable dynamics.

Nature, Published online: 17 July 2019; doi:10.1038/s41586-019-1384-z

The generation of topologically complex nanocarbons can spur developments in science and technology. However, conventional synthetic routes to interlocked molecules require heteroatoms. We report the synthesis of catenanes and a molecular trefoil knot consisting solely of para-connected benzene rings. Characteristic fluorescence of a heterocatenane associated with fast energy transfer between two rings was observed, and the topological chirality of the all-benzene knot was confirmed by enantiomer separation and circular dichroism spectroscopy. The seemingly rigid all-benzene knot has rapid vortex-like motion in solution even at –95°C, resulting in averaged nuclear magnetic resonance signals for all hydrogen atoms. This interesting dynamic behavior of the knot was theoretically predicted and could stimulate deeper understanding and applications of these previously untapped classes of topological molecular nanocarbons.