Although a wide range of layered covalent organic frameworks (COFs) have been made, it is difficult to prise the layers apart in a controlled fashion to generate mono- or few-layer sheets with uniform thickness. Now, a team led by Kian Ping Loh have shown that, by including crown ether hosts into layered COFs, it is possible to bind cationic guests that can disrupt stacking through charge repulsion, which facilitates exfoliation of these materials into well-defined sheets. The cover image depicts a stacked COF formed in the absence of the cationic guests and a bilayer sheet in which a cationic guest is threaded through each crown ether macrocycle.

Loh Article

There are numerous strategies for constructing protein conjugates linked through an amino acid side chain, but these approaches often suffer from poor specificity or require the incorporation of a large linker domain. A team led by Jeffrey Bode have now developed a chemoenzymatic method — known as LACE (lysine acylation using conjugating enzymes) — for the site-specific modification of proteins. This approach is based on recognizing a short genetically encoded tag to enable folded proteins to be modified at internal lysine residues; the cover image depicts the formation of a conjugate using a four-residue LACE tag.

Bode Article and Lang News & Views

Highly accurate solutions of the Schrödinger equation are required to predict subtle features in the electronic structure of molecules. Quantum Monte Carlo (QMC) methods are one of the powerful tools that form the backbone of computational chemistry and provide computational access to molecular properties. Hermann, Schätzle and Noé have now developed a method to represent the electronic wavefunction with deep neural networks and have applied the variational QMC method to learn the ground state of molecules from first principles. The cover image shows a white mesh that illustrates a neural-network trial wavefunction — the mathematical object that encodes the electronic structure of a molecule — that is iteratively optimized to minimize the ground-state energy. An artistic representation of the nuclei and electrons of lithium hydride are shown, which is one of the molecules studied using this method.

Noé Article

Light-induced ring-opening/closing reactions are important in many key processes in nature — such as the synthesis of natural products — and are attracting interest in other areas such as optical data storage and potential medical applications. Rolles, Curchod, Ashfold and colleagues have now studied the dynamics of the ring opening of a model heterocycle, thiophenone, using femtosecond photoelectron spectroscopy combined with ab initio theory, enabling the visualization of rich dynamics in both the excited and ground electronic states. The cover image shows a ‘heat map’ in the background that represents the photoproducts in a 2D space — with the C–S bond length represented on the vertical axis and the CCS angle along the horizontal axis — overlayed with drawings of the photoproducts and the initial thiophenone being hit by the 'laser'. The white lines follow the smoothed paths of reaction trajectories.

Rolles Article

The strength of electrostatic interactions in hybrid layered perovskites is known to affect their performance in optoelectronic devices, but the varied interactions at play within these materials make them difficult to tune. Now, William Tisdale, Samuel Stupp and co-workers have doped 2D perovskites — consisting of lead halide sheets alternating with naphthalene-based layers — without affecting the inorganic network. Doping the organic layers with tetrachloro-1,2-benzoquinone (TCBQ) results in naphthalene–TCBQ electron donor–acceptor interactions that influence the exciton binding energy of these materials independently of their electronic band gap (an artistic representation of this effect is shown on the cover).

Stupp Article

Water is important in molecular recognition, but its effects can be difficult to measure and its role is not always clear — similarly unclear is how these effects can be controlled. Now Henry Ashbaugh and colleagues have shown that the architecture of a molecular host’s rim can significantly affect the wettability of its non-polar pocket — and thus the binding of guest molecules. A cavitand featuring four methyl groups around its rim that point inwards, is shown to be dry (as depicted on the cover), whereas cavitands with no methyl groups (also shown on the cover), or with methyl groups pointing up, are observed to have water-filled pockets.

See Barnett et al and Garde News & Views

The methylation of drug molecules can have beneficial effects on their properties, but the ability to directly add methyl groups to complex structures late in synthetic routes remains challenging. Now, Lutz Ackermann, Magnus Johansson and Stig Friis have developed a cobalt-catalysed method for late-stage C–H methylation, which relies on a boron-based methyl source and takes advantage of functional groups already present in the molecule to guide the reaction. The methodology can be applied to complex drug molecules, such as paclitaxel (an artistic representation of this reaction is shown on the cover), without the need for pre-functionalization or post-deprotection steps.

See Friis et al and Wencel-Delord News & Views

Alzheimer's disease is linked to the self-assembly of Aß42 peptides into misfolded fibrillar aggregates. Now, a team led by Michele Vendruscolo, Sara Linse and Tuomas Knowles have obtained direct measurements of the dynamic self-assembly and disassembly of Aß42 peptide oligomers, as well as their subsequent conversion into amyloid fibrils. These findings show that although all mature amyloid fibrils must originate from oligomers, most Aß42 oligomers dissociate back to their monomeric precursors without forming new fibrils. The cover image depicts a schematic representation of the nucleation of peptide aggregates and the dynamics of peptide assembly and disassembly during the formation of an amyloid fibril.

See Michaels et al

Ionic conductors serve as solid electrolytes for fuel cells and batteries, whereas polar crystals such as ferroelectrics and pyroelectrics — which are typically insulating materials — are used in electronic devices. Now, Shin-ichi Ohkoshi and co-workers have prepared a polar crystal that shows superionic conductivity at room temperature. Based on –Fe–N≡C–Mo– units, this three-dimensional anionic network hosts Cs+ cations in every other pore and is also photo-responsive: when irradiated with light, its conductivity significantly decreases (an artistic representation of this characteristic is shown on the cover).

See Ohkoshi et al

Benzene is the archetypal aromatic molecule and it satisfies Hückel's 4n + 2 rule with its 6 π-electrons (n = 1). In a study that explores the limits of aromaticity, Harry Anderson and co-workers have now shown that Hückel's rule holds true for a large wheel-like compound in which 12 zinc porphyrins are linked together with diyne groups. In the 6+ oxidation state, the 162 π-electrons (n = 40) are delocalized around the porphyrin wheel, which is shown on the cover with two template molecules stacked inside it to form a stable 2:1 complex.

See Rickhaus et al

Electrically conductive metal–organic frameworks (MOFs) that hold promise for applications in chemical sensing and energy storage are typically layered structures exhibiting in-plane conductivity. Now, Mircea Dincă and co-workers have prepared a series of layered lanthanide MOFs where the charge transport is primarily out-of-plane, perpendicular to the ligand-based sheets (an artistic representation of the anisotropic conductivity is shown on the cover). The conductivity of the materials can be modulated by changing the lanthanide ion which, in turn, affects the interlayer distance.

See Skorupskii et al

Designing structures that can interact with antigens present in a specific arrangement on the surface of a virus particle offers a way to selectively bind different viral targets. Now, a team led by Jie Chao and Xing Wang have created a star-shaped DNA architecture that can be used as the basis for either a fluorescent sensor or a potent viral inhibitor. The cover image depicts an artistic representation of star-shaped DNA nanostructures binding to the surface of dengue virus particles.

See Kwon et al