Although organic photocatalysts are an attractive option for water splitting because they can be tuned relatively easily through synthesis, they tend not to be very efficient. Now, a team led by Andrew Cooper has shown that a covalent organic framework (COF) comprising β-ketoenamine nodes and benzothiophene sulfone-based linkers is a good hydrogen-evolution catalyst (an artistic representation of the process is shown on the cover). Its activity — attributed to the COF’s crystallinity, strong visible-light absorption and the wettable, hydrophilic nature of its sulfone-lined mesopores — can be further improved by dye sensitization.

See Wang et al.

Knotted molecular chains can be found in DNA, proteins and polymers, and can have a significant influence on their properties. Most small-molecule knots reported so far are 'prime' knots; much rarer are 'composite' knots, which consist of two or more prime knots that have been ring-opened and the loose ends connected to one another. Now, a team led by David Leigh has used a circular metal helicate to make a nine-crossing composite knot that contains three trefoil tangles (as shown schematically on the cover). The backbone of the knot is a single molecular chain — a 324-membered ring — wound around six Fe(II) ions that all have the same chirality in any given knot (either all Δ or all Λ).

See Leigh et al.

Layered coordination polymers (LCPs) are usually too fragile to withstand the ‘Scotch-tape method’ widely used to mechanically exfoliate a variety of materials. Now a team led by Guillermo Mínguez Espallargas and Eugenio Coronado has successfully stripped a family of five isoreticular crystalline, magnetic LCPs – based on Fe(II) centres and five benzimidazole derivatives – down to monolayers (an artistic representation of a single sheet is shown on the cover). The use of functionalized ligands in the bulk LCPs means that the magnetic 2D materials obtained on exfoliation are already functionalized; this approach avoids the need for a surface-engineering step which is known to introduce defects.

See Coronado et al.

Protein kinases perform essential regulatory roles in the biochemical pathways of eukaryotic cells and therefore represent important drug targets. However, modelling the dynamic fluctuations to identify potentially drugable non-native states remains very difficult – particularly if the aim is to reveal differences between similar kinases. Now, a team led by Vijay Pande has studied the dynamics of seven members of the Src family of kinases. A quantitative comparison of the structural ensembles formed by these kinases provides detailed insight into their activation mechanisms. The cover image depicts a stylized image of an Src kinase undergoing dynamic fluctuations.

See Pande et al.

There are a number of factors that control product selectivity and catalyst lifetime in acid-catalysed reactions using zeolites. Now, by analysing the catalytic behavior of zeolites with different textural and acidic properties, a team led by Jorge Gascon has developed structure–performance descriptors for the methanol-to-propylene process. They have shown that Brønsted acidity is key for propylene selectivity and that Lewis acidity is responsible for prolonging the lifetime of the catalyst. The image on the cover is an artistic representation of the zeolitic microenvironment, inhabited by methanol and olefins interacting with each other.

See Gascon et al.

Selecting one supramolecular structure from many different possible assemblies that are formed through competing pathways is a challenging problem. Now, a team led by Rein Ulijn has shown how amino acids and an enzyme can be used in situ to covalently modify peptide-based building blocks – that have an organic semiconductor core – to control their self-assembly pathways. This approach was used for the transient formation of conducting nanostructures whereby electronic wires could be formed and then subsequently degraded. This process is depicted schematically on the cover where an amphiphilic bilayer core gives rise to the formation of a helical structure.

See Ulijn et al.

The direct installation of nitrogen into selected positions of complex molecules can have a significant effect on their chemical and biological properties. Now, a team led by M. Christina White has shown that a highly reactive and site-selective manganese perchlorophthalocyanine catalyst can promote late-stage intermolecular benzylic C–H amination reactions on a broad range of pharmaceuticals and natural-product derivatives under conditions that are tolerant of basic amines and heterocycles. The image on the cover is an artistic representation of the catalyst abstracting a benzylic hydrogen atom from a salt of the antidepressant drug citalopram, with other amination substrates shown in the background.

See Clark et al.

Gene-expression studies are typically carried out in the bulk by pooling cells, but analysis of cell-to-cell variation — which is of particular interest for rare circulating tumour cells — requires techniques that can characterize levels of expression in individual cells. Now, a new technique that enables rare cells to be isolated from whole blood based on target mRNA sequences has been developed by a team led by Shana Kelley. The cover image depicts the mRNA-induced intracellular self-assembly of magnetic nanoparticles to form large magnetic clusters that enables the graded separation of individual cells based on their expression levels of the target mRNA

See Labib et al.

The fabrication of foldamer–peptide hybrids offers the opportunity to create molecules with properties that are not exhibited by natural peptides. Now, a team led by Hiroaki Suga and Ivan Huc have shown that it is possible to attach a foldamer to the N-terminus of a peptide that can subsequently be extended by ribosomal synthesis. The foldamer must be unfolded to pass through the ribosome exit tunnel, but once it has emerged it can re-fold and also influence the folding of the peptide chain. The image on the cover shows one foldamer–peptide hybrid passing through the ribosome along with others that have regained their folded conformation after emerging from it.

See Rogers et al.

The targeted delivery of cells and therapeutics with systems that respond to disease-related biomarkers could improve the efficiency and efficacy of drug delivery and regenerative medicine. A team led by Cole A. DeForest has now made a range of stimuli-responsive hydrogels that collectively provide all possible YES/OR/AND logical outputs from input combinations involving an enzyme, a reducing agent and light. The sequential and environmentally stimulated release of multiple cell lines was demonstrated with these hydrogels. The image shown on the cover of this issue depicts the concept of a cross-linked polymer hydrogel network in which there are cyclic moieties containing scissile bonds that respond to the appropriate stimuli.

Article p251

IMAGE: BARRY BADEAU, COLE DEFOREST AND ALEXANDER TOKAREV (ELLA MARU STUDIO, INC.)

COVER DESIGN: TULSI VORALIA

Although enzymes that catalyse transformations in the biosynthesis of natural products often demonstrate remarkable activity and selectivity, there are typically challenges — usually relating to substrate scope and stability — that must be overcome before they can be used effectively in the laboratory by synthetic chemists. Now, a team led by Alison Narayan has shown how three related enzymes that are known to catalyse the oxidative dearomatization of phenols and resorcinols can be used to make ortho-quinol products (an example of which is depicted on the cover) with impressive site- and stereoselectivity. The method is robust enough to be scaled-up to gram-scale reactions and its use in multi-enzyme and chemoenzymatic cascades has also been demonstrated.Article p119IMAGE: STEPHANIE KING, THE UNIVERSITY OF MICHIGAN LIFE SCIENCES INSTITUTECOVER DESIGN: TULSI VORALIA

Accumulating multiple redox equivalents at catalytic sites is crucial to driving light-initiated multiple-electron-transfer reactions such as water splitting. However, generating and observing catalytic centres that have been reduced or oxidized twice under diffuse illumination is not a trivial task because of detrimental charge-recombination reactions. Now Hsiang-Yun Chen and Shane Ardo show that, on excitation with low-intensity visible light, a molecular proxy for a multiple-electron-transfer electrocatalyst can be oxidized twice by Ru—polypyridyl dye molecules when anchored to a titania film. This is depicted on the cover with the brown and red spheres representing the dye and proxy catalyst molecules, respectively.Article p17News & Views p3IMAGE: DARIUS SIWEKCOVER DESIGN: TULSI VORALIA