Reviews & Analysis

A critical overview and analysis of contemporary screening approaches toward the discovery of new reactivity is provided. A breakdown of each approach in terms of strategy, practicality and utility from the perspective of a synthetic chemist is also given, as well as considerations on the future of high-throughput screening in reaction discovery.

Interwoven supramolecular structures are often held up as examples of beauty in chemistry, but these assemblies can be fragile depending on the environments they are exposed to. Post-assembly covalent modification can, however, trap them in robust molecular form, and a triply entwined [2]catenane is one of the most sophisticated examples so far.

Enantiomerically pure head-to-head-to-tail triple-stranded helicates synthesized using a subcomponent self-assembly approach possess high anticancer activities against cancer cell lines without significant damage to DNA and with low toxicity to bacteria.

Halogen bonding connects a wide range of subjects — from materials science to structural biology, from computation to crystal engineering, and from synthesis to spectroscopy. The 1st International Symposium on Halogen Bonding explored the state of the art in this fast-growing field of research.

Directed evolution is a powerful tool for the development of improved enzyme catalysts. Now, a method that enables an enzyme, its encoding DNA and a fluorescent reaction product to be encapsulated in a gel bead enables the application of directed evolution in an ultra-high-throughput format.

Intense laser fields can apply strong forces to molecules, distorting molecular potentials. Now, these effects have been used to precisely control the branching ratios of a polyatomic photodissociation reaction.

This Review draws an analogy between acid–base catalysis and redox catalysis. The 'electron is a catalyst' paradigm unifies mechanistically an assortment of synthetic transformations that otherwise have little or no apparent relationship. Various radical cascades catalysed by the electron are discussed.

Two reports demonstrate that with the right molecules and the right crystalline arrangement, it is not only possible to create two-dimensional crystals, but also to separate them into single-molecule-thick sheets — so-called two-dimensional polymers.

For decades chemists have focused on increasing the brightness of fluorophores. In super-resolution microscopy, however, fluorophores that preferentially exist in a non-fluorescent state, but occasionally re-arrange into a fluorescent form, can give better results.

Intramolecular aliphatic C–H amination reactions are greatly sought-after for the synthesis of N-containing heterocycles, but current methods require the use of highly activated nitrogen sources. Now, aziridination and lactamization have been achieved using fully aliphatic, unactivated, secondary amines.

Self-assembled amphiphiles are more common in the realm of aqueous systems than in organic solvents. Their scope has now been expanded with the advent of 'hydrophobic amphiphiles' of π-conjugated–alkyl systems, which show various self-assembled phases similar to classical amphiphiles.

A newly designed thiol catalyst for radical cyclization reactions is the result of a long and storied battle to control the reactivity of carbon-centred radicals.

Biological systems have evolved sophisticated machinery to assemble polymeric receptors capable of molecular recognition. Although such precise levels of structural control are currently inaccessible to chemists, impressive progress has been made towards the realization of wholly synthetic analogues of antibodies and other proteins. Protein structure from H. Li et al. Biochemistry 33, 11734–11744 (1994); © American Chemical Society.

The palladium-catalysed cross-coupling of aryl- or alkenylboronates and aryl halides has proved phenomenally successful for the formation of Csp²–Csp² bonds. Now, an alternative non-transition-metal-mediated coupling using similar reactants has been reported for the stereo-controlled formation of Csp²–Csp³ bonds.

Live-attenuated viruses used in vaccines can regain their virulence, which for deadly viruses such as HIV is an unacceptable risk. Now, attenuated HIV-1 viruses, which include mutations that genetically encode unnatural amino acids and prevent them from replicating in normal cells, have been constructed.

Protein-based protonic conductivity plays an important role in nature, but has been explored little outside of a biological setting. Now, proton conductors have been developed based on the squid protein reflectin, and integrated with devices for potential bioelectronic applications.

The ordered one-dimensional nanochannels found in covalent organic frameworks (COFs) could render them able to conduct protons. However, the frameworks' instability in acid has thus far precluded any practical implementations. Now, a strategy to overcome this instability has enabled proton conduction using a COF for the first time.

The flexibility and structural dynamics of proteins pose a big challenge for those trying to discover new bioactive compounds. Now, by using guiding crystallographic data, a method that uses the energetic balance between protein conformers to weight docking scores is shown to aid the hunt for new ligands.

RNA can carry information, self-replicate and catalyse reactions, and so is often included in scenarios for the origin of life, but was it the first self-replicator? This Perspective considers the question of whether simpler polymer structures could have encoded early life, and discusses how to seek them out.

The lomaiviticins are exceedingly potent antibiotic agents, but the mechanism responsible for this activity has so far been unclear. Now, efficient generation of double-strand breaks in DNA by lomaiviticin A has been linked to the remarkable cytotoxicity of these diazobenzofluorene-containg natural products.