Reviews & Analysis

Humans have evolved innate and adaptive immune systems to survive infection. Chemical approaches have enabled modulation of the immune system to activate or dampen it, leading to the development of new treatments for cancer and autoimmunity.

Traditional approaches for studying glycans can lack the precision required to uncover their roles in biomolecular processes. Progress has been made in the use of single molecule techniques for examining individual events in glycobiology — such as the molecular interactions of sugars and their roles in biological processes — within challenging mixtures.

Proteins, DNA and RNA can be used to build functional nanostructures. This Review compares protein and DNA/RNA in terms of biochemical properties and ease of engineering in three major areas of application: biomolecular recognition, biocatalysis and structural support.

This Review describes excited-state intramolecular proton-transfer (ESIPT) reactions with amines as proton donors. Systematic variation of N−H bond strength, acidity and reaction rate enables ESIPT kinetics and thermodynamics to be correlated and new molecules to be designed for sensing and optoelectronics applications.

Metal–ligand interactions are attracting growing attention for the design of new drugs. Current simulation approaches help us gain deep atomistic understanding of the metal–ligand interactions for the discovery and development of potent metalloenzyme inhibitors and metallodrugs.

Ultrafast X-ray spectroscopies enable the investigation of fast chemical dynamics with time resolutions reaching the order of attoseconds. Processes such as spin crossover, structural deformations in excited states and dissociation reactions can now be studied through the use of short X-ray pulses produced by high-harmonic, free-electron-laser and synchrotron sources.

The union of theory in chemical ecology with modern methods in chemistry has enhanced our understanding of phytochemical variation among and within plants. This Review outlines these theoretical frameworks and approaches for hypothesis testing, with a focus on chemically mediated plant–insect interactions.

Single-atom catalysts are heterogeneous materials featuring active metals sites atomically dispersed on a surface. This Review describes methods by which we prepare and characterize these materials, as well as how we can tune their catalytic performance in a variety of important reactions.

A move away from fossil fuels as an energy source will also require a move to new sources for important chemical feedstocks. This Review considers the use of homogeneous catalysis to convert cellulosics into low-volume, high-value chemicals that are currently derived from crude oil.

The development of high-performance olefin polymerization catalysts is a major driving force in polyolefin studies. This Perspective discusses some alternative strategies for catalyst design — strategies in which existing systems are tuned beyond merely modifying the electronic and steric properties.

Transition-metal-catalysed hydrosilylation and hydroboration reactions are valuable in the synthesis of commodity and fine chemicals, respectively. This Review describes the catalyst design principles that enable us to perform these reactions using catalysts based on earth-abundant metals. Scenarios in which using earth-abundant metals can offer an advantage over using a precious metal are also outlined.

Simulation techniques that describe chemical processes on different spatiotemporal scales are central to drug design. Multiscale methods enable us to study processes across different scales simultaneously, thereby bridging chemical and biological complexity. This Perspective highlights how physics-based multiscale approaches are on the cusp of delivering their long-promised impact on the discovery, design and development of therapeutics.

The conventional theoretical approach to the study of materials typically involves explaining the properties of known materials. This approach is compared with the inverse design of materials, in which the desired properties are set as inputs and the material that exhibits them as the output.

Native chemical ligation (NCL) has revolutionized the field of chemical protein synthesis. This Review discusses milestones such as desulfurization, the development of thiol and selenol analogues of proteinogenic amino acids and novel acyl donors for multi-component iterative ligations. These have greatly expanded the NCL concept and enabled the synthesis of hitherto inaccessible protein targets.

Bio-interface materials inspired by natural systems that respond efficiently to various external stimuli can dynamically regulate molecular interactions between biological entities and material surfaces. In this Review, Gomes and colleagues describe advances in bio-interface materials that may provide insights into cell behaviour, biofouling and the production of on-demand devices with medical applications, among others.

Quantum electrodynamics (QED) is the most complete theoretical framework to date to complement experimental spectroscopies in chemistry. Owing to its complexity, several approximations are needed in order to be able to apply QED in practice. This Review highlights how the breakdown of some of these approximations challenges our understanding of light–matter interactions and discusses how new theoretical developments can help to overcome these approximations.

The approximation underlying most atomistic simulations to treat nuclei classically can lead to large errors and the failure to capture important physical effects. This Review reports on recent developments that enable modelling of quantum nuclei at a computational cost comparable with that of a classical simulation.

The design of synthetic systems that mimic the ability of biological systems to control chemical reactions using intricate molecular machines is a long-held dream of nanotechnology. This Review discusses how developments in controlled molecular switching and movement are being exploited in the design of catalysts that are just beginning to emulate the complexity of living systems.

Iterative approaches to synthesis have revolutionized the preparation and study of peptides, nucleic acids and sugars. This Review discusses whether and how such iterative syntheses can be applied more broadly towards an ultimate goal of developing a building block approach to the synthesis of most small organic molecules.

The metals in polyoxometalates need not be in their highest oxidation states. Indeed, polyoxometalates can exist in reduced forms, and several different metals can be incorporated into various structural archetypes. This Review describes the synthesis and characterization of these complexes, along with their topical catalytic, electronic and biological properties.