Review Articles

  • Review Article |

    Biochemical and cellular assays are often plagued by false positive readouts elicited by nuisance compounds. A significant proportion of those compounds are aggregators. This Review discusses the basis for colloidal aggregation, experimental methods for detecting aggregates and analyses recent progress in computer-based systems for detecting colloidal aggregation with particular emphasis on machine learning [In the online version of this Review originally published, the graphical abstract image was incorrectly credited to ‘Reven T.C. Wurman / Alamy Stock Photo’ this has now been corrected].

    Oleksii Telnov / Alamy Stock Photo

    • Daniel Reker
    • , Gonçalo J. L. Bernardes
    •  & Tiago Rodrigues
  • Review Article |

    Phytochemicals exhibit great pharmaceutical importance despite their low abundance in nature. The microbial biosynthesis of complex phytochemicals offers one route to increase their availability and production. This Review discusses recent strategies to reconstruct plant biosynthetic pathways that have not been fully elucidated; enhance plant enzyme activity; and enhance overall reaction efficiency of multi-enzyme pathways.

    • Sijin Li
    • , Yanran Li
    •  & Christina D. Smolke
  • Review Article |

    Given its ubiquity, the importance of understanding the properties of water cannot be understated. Now, stemming from discussions at a National Science Foundation-supported workshop, this Review Article highlights where there is latent chemical space for potential collaborations between the physical and supramolecular communities, both of which are interested in how molecules interact with each other in water.

    • Paul S. Cremer
    • , Amar H. Flood
    • , Bruce C. Gibb
    •  & David L. Mobley
  • Review Article |

    The emergence of synthetic fluorescent nucleobases that can be incorporated into DNA and RNA in place of their natural counterparts has enabled new tools and technologies with applications in chemistry, biology and biomedicine. This Review discusses chemical insights into canonical and non-canonical nucleobase designs, relating structure to properties.

    • Wang Xu
    • , Ke Min Chan
    •  & Eric T. Kool
  • Review Article |

    DNA nanotechnology provides a versatile toolbox for engineering synthetic circuits in living cells. This Review discusses how nanostructures made from nucleic acids can enable biocomputation and also be readily interfaced with a variety of intracellular and in vivo components to facilitate synthetic biology applications.

    • Jiang Li
    • , Alexander A. Green
    • , Hao Yan
    •  & Chunhai Fan
  • Review Article |

    Recent years have witnessed a surge of interest in targeted covalent inhibition of disease-associated proteins. Among the electrophiles used to interact with nucleophilic residues in protein structures, boron is unique for its chameleonic ability to display a range of coordination modes upon interaction with protein targets.

    • Diego B. Diaz
    •  & Andrei K. Yudin
  • Review Article |

    Biological drugs can offer high potency and selectivity; however, this class of therapeutics often shows poor stability upon oral administration and during subsequent circulation. This Review highlights the materials and methods used to deliver biological drugs, and discusses how these approaches can improve their pharmacokinetics.

    • Alexander N. Zelikin
    • , Carsten Ehrhardt
    •  & Anne Marie Healy
  • Review Article |

    Numerous dynamic molecular crystals whose physical properties can be switched by external stimuli have recently been developed. This Review discusses how the precise control of the electron, proton and molecular movement within the crystals through the application of external stimuli can lead to considerable changes in their properties.

    • Osamu Sato
  • Review Article |

    Natural products are a prime source of innovative molecular fragments and privileged scaffolds for drug discovery and chemical biology. Advanced machine-learning approaches can help analyse and design synthetically accessible, natural-product-derived, compound libraries and provide insight into the high selectivity of such compounds.

    • Tiago Rodrigues
    • , Daniel Reker
    • , Petra Schneider
    •  & Gisbert Schneider
  • Review Article |

    Chemical protein synthesis can enable the preparation of proteins containing post-translational modifications or unnatural variations such as D-amino acids. Such modified proteins are not easily fabricated by other methods. This Review provides an overview of the current approaches for the chemical synthesis of proteins.

    • Somasekhar Bondalapati
    • , Muhammad Jbara
    •  & Ashraf Brik
  • Review Article |

    In enzyme-catalysed metabolic pathways, substrate channelling often directs the movement of intermediates from one active site to the next. Intramolecular tunnels, electrostatic interactions and chemical swing arms pass intermediates from one enzyme to the next, enhancing pathway catalysis. Introducing mechanisms of bounded diffusion in chemical cascades can increase selectivity, transient rates and overall yield.

    • Ian Wheeldon
    • , Shelley D. Minteer
    • , Scott Banta
    • , Scott Calabrese Barton
    • , Plamen Atanassov
    •  & Matthew Sigman
  • Review Article |

    In a remote functionalization, reaction occurs at a site distant from the site of initial activation. This Review discusses attempts to achieve this challenging goal with a particular focus on reactions that exploit alkene isomerizations to effect transit of the catalyst from a reactive alkene to a distant sp3 centre.

    • Alexandre Vasseur
    • , Jeffrey Bruffaerts
    •  & Ilan Marek
  • Review Article |

    Vinyl polymers are appealing materials owing to their ease of synthesis and broad diversity. Their carbon–carbon backbones resist degradation, however, which limits the applications for which they can be used. This Review Article considers the most promising approaches to the design of degradable vinyl polymers and discusses the potential of these materials for biomedical applications.

    • Vianney Delplace
    •  & Julien Nicolas
  • Review Article |

    Ferroelectric materials hold much promise for the development of devices such as nonvolatile memories, sensors and nonlinear optic materials. This Review describes the molecular features required to devise organic molecular ferroelectrics, and presents the supramolecular chemistry strategies available for controlling molecular organization and dynamics across different length scales.

    • Alok S. Tayi
    • , Adrien Kaeser
    • , Michio Matsumoto
    • , Takuzo Aida
    •  & Samuel I. Stupp
  • Review Article |

    Bringing porphyrins in contact with well-defined interfaces generates a rich playground of chemical behaviour and properties for exploration and exploitation. This Review examines our current understanding of surface-confined tetrapyrroles and their embedding in nanoarchitectures - discussing both the structural and functional attributes, and methods by which to manipulate their intramolecular and organizational features.

    • Willi Auwärter
    • , David Écija
    • , Florian Klappenberger
    •  & Johannes V. Barth
  • Review Article |

    Energy storage using batteries offers a solution to the intermittent nature of energy production from renewable sources; however, such technology must be sustainable. This Review discusses battery development from a sustainability perspective, considering the energy and environmental costs of state-of-the-art Li-ion batteries and the design of new systems beyond Li-ion. Images: batteries, car, globe: © iStock/Thinkstock.

    • D. Larcher
    •  & J-M. Tarascon
  • Review Article |

    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.

    • Karl D. Collins
    • , Tobias Gensch
    •  & Frank Glorius
  • Review Article |

    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.

    • Armido Studer
    •  & Dennis P. Curran
  • Review Article |

    Ion mobility-mass spectrometry (IM-MS) is enhancing many areas of (bio)chemical analysis because it can separate ions both by their mass-to-charge ratio and differences in their cross-sectional area. IM-MS can be used for structural characterization, enhanced analysis of complex mixtures or to gain insights into conformational dynamics.

    • Francesco Lanucara
    • , Stephen W. Holman
    • , Christopher J. Gray
    •  & Claire E. Eyers
  • Review Article |

    Two-dimensional polymers, which exhibit periodic bonding in two orthogonal directions, offer mechanical, electronic and structural properties distinct from their linear or irregularly crosslinked polymer counterparts. Their potential is largely unexplored because versatile and controlled synthetic strategies are only now emerging. This Review describes recent developments in two-dimensional polymerization methods.

    • John W. Colson
    •  & William R. Dichtel
  • Review Article |

    Two-dimensional materials have recently garnered much interest in the scientific and technology communities. This Review describes how ultrathin transition metal dichalcogenides combine tunable structure and electronic properties, achieved through altering their composition, with versatile chemistry. This makes them attractive in various fields, for example as lithium-ion battery electrodes and electrocatalysts for the hydrogen evolution reaction.

    • Manish Chhowalla
    • , Hyeon Suk Shin
    • , Goki Eda
    • , Lain-Jong Li
    • , Kian Ping Loh
    •  & Hua Zhang
  • Review Article |

    α-Helix-mediated protein–protein interactions (PPIs) play a key role in the development of numerous infection and disease states. Modulating such interactions offers considerable therapeutic potential, however, identifying suitable inhibitors has proved challenging. This Review highlights recent and generic approaches for designing inhibitors of helix-mediated PPIs.

    • Valeria Azzarito
    • , Kérya Long
    • , Natasha S. Murphy
    •  & Andrew J. Wilson
  • Review Article |

    The complexity of living systems makes attempts to gain a molecular-level understanding of them a unique and inspiring challenge. This Review summarizes progress in the development of bioorthogonal reaction-based fluorescent probes used to follow the spatial and temporal dynamics of biologically important analytes within living systems.

    • Jefferson Chan
    • , Sheel C. Dodani
    •  & Christopher J. Chang
  • Review Article |

    This Review describes the general trends and implications of heterogeneities within individual catalyst particles as observed by modern spatiotemporal spectroscopy. It discusses how catalytic materials have been found to display heterogeneities in structure, composition and reactivity in space and time. The implications of these findings for future catalyst design are also described.

    • Inge L. C. Buurmans
    •  & Bert M. Weckhuysen
  • Review Article |

    Novel concepts in asymmetric catalysis have the potential to open up previously inaccessible reaction space. This Review reflects on the origins of an area that has undergone dramatic recent advancement: the use of chiral anions in asymmetric catalysis. Details of a selection of the latest examples are also given.

    • Robert J. Phipps
    • , Gregory L. Hamilton
    •  & F. Dean Toste
  • Review Article |

    Thiolate-protected gold surfaces and interfaces are archetypal systems in various fields of current research in nanoscience, materials science, inorganic chemistry and surface science. Examples include self-assembled monolayers of organic molecules on gold, passivated gold nanoclusters and molecule–gold junctions. This Review discusses recent experimental and theoretical breakthroughs that highlight common features of gold-sulfur bonding in these systems.

    • Hannu Häkkinen
  • Review Article |

    Redox sites can be incorporated within dendrimers — highly branched, well-defined macromolecules — at specific locations, such as their core, branching points, periphery or inner cavities. These dendrimers can serve to functionalize surfaces, and electron-transfer processes at their redox sites show promise for various applications ranging from metallo-protein modelling to sensing to catalysis.

    • Didier Astruc
  • Review Article |

    Photosynthesis starts when light is absorbed and the associated excitation energy is directed to reaction centres by antenna complexes. The principles learned from studying these complexes are described in this Review, and provide the framework from which the authors suggest how to elucidate strategies for designing light-harvesting systems that route the flow of energy in sophisticated ways.

    • Gregory D. Scholes
    • , Graham R. Fleming
    • , Alexandra Olaya-Castro
    •  & Rienk van Grondelle
  • Review Article |

    Peptide macrocycles have a number of important applications. Among other things, the reduced conformational freedom of the cyclic structure enables strong binding to the extended contact regions of protein–protein complexes. Here, emerging methods directed towards the synthesis of these valuable molecules are reviewed.

    • Christopher J. White
    •  & Andrei K. Yudin
  • Review Article |

    Crystalline networks containing empty cavities can host a variety of molecules but also promote reactions between guests. Through robust crystallinity and a pseudo-solution state (dynamic movements) within their pores, these crystalline molecular flasks enable the direct observation of species — including unstable intermediates — during a reaction by in situ X-ray diffraction.

    • Yasuhide Inokuma
    • , Masaki Kawano
    •  & Makoto Fujita
  • Review Article |

    The programmable and reliable hybridization of DNA strands has enabled the preparation of a wide variety of structures. This Review discusses how, in addition to these static assemblies, the process of displacing — and ultimately replacing — strands also makes possible the construction of dynamic systems such as logic gates or autonomous walkers.

    • David Yu Zhang
    •  & Georg Seelig
  • Review Article |

    Chemically derived graphene oxide (GO) has recently moved on from simply being a graphene precursor to attracting interest for its own properties. This Review discusses how the presence of oxygenated groups and domains of sp2- and sp3-hybridized carbons makes GO tunable and promising for various physical and biological applications.

    • Kian Ping Loh
    • , Qiaoliang Bao
    • , Goki Eda
    •  & Manish Chhowalla
  • Review Article |

    Most synthetic polymers are made from petroleum and their production is currently not sustainable. RAFT polymerization has emerged as a powerful technique to control the synthesis of such polymers, thus expanding further their applications. This Review discusses the sustainability of RAFT in terms of process and materials.

    • Mona Semsarilar
    •  & Sébastien Perrier
  • Review Article |

    Aerosol particles are crucially important to the chemistry of the atmosphere, influencing both climate and air quality. This Review discusses progress in understanding the radical-initiated heterogeneous oxidation of atmospheric aerosols, focusing on the reaction mechanisms and kinetics, and also their effects on the physico-chemical properties of particles.

    • I. J. George
    •  & J. P. D. Abbatt
  • Review Article |

    The synthesis or separation of chiral compounds is crucial for many areas of chemistry, with chiral solids having important roles as catalysts or separating agents. This Review covers recent progress and future avenues for developing methods of preparing chiral solids from achiral starting materials.

    • Russell E. Morris
    •  & Xianhui Bu
  • Review Article |

    Rare-earth metal dialkyl complexes can be readily transformed into the corresponding cationic monoalkyl species — which have been shown to catalyse a range of (co)polymerization processes — as well as into polyhydride complexes that have unique structures and a rich reaction chemistry.

    • Masayoshi Nishiura
    •  & Zhaomin Hou
  • Review Article |

    The field of organocatalysis has grown rapidly in the past decade to become, along with metal catalysis and biocatalysis, a third pillar of asymmetric catalysis. Here, progress in the use of organocatalytic cascade reactions for total synthesis is reviewed. The elegance and efficiency of such cascades mean that they have emerged as a powerful tool in synthetic organic chemistry.

    • Christoph Grondal
    • , Matthieu Jeanty
    •  & Dieter Enders
  • Review Article |

    The formation of single-layer-thick molecular networks at metal surfaces is governed by the interplay between intermolecular and interfacial interactions. This Review highlights how, with films built by vacuum deposition, these interactions can be modulated to form substrates that may be useful as catalysts or templates for further deposition steps.

    • Ludwig Bartels
  • Review Article |

    Nature's enzymes are remarkably efficient at catalysing highly specific reactions with extraordinary selectivity. The ability to design enzymes for any desired reaction is a huge challenge. Here, the advances in the development of artificial enzymes are discussed with a particular focus on the computational advances that bring this challenge closer to reality.

    • Vikas Nanda
    •  & Ronald L. Koder
  • Review Article |

    Encapsulating guest molecules inside host structures ranging from soft, flexible enzymes to rigid, porous zeolites has led to developments in many areas, including catalysis, sensing and separation. This Review highlights how metal–organic frameworks — materials formed by linking metal centres with organic ligands — can combine softness with regularity to produce dynamic, yet crystalline, structures that may prove useful for a range of applications.

    • Satoshi Horike
    • , Satoru Shimomura
    •  & Susumu Kitagawa
  • Review Article |

    The development of general synthetic strategies for the prepartion of oligonucleotides and peptides has enabled them to be made routinely — often using automated systems. Making complex oligosaccharides is much less straightforward, but advances in areas such as one-pot multi-step protecting-group manipulations, stereoselective glycosylation protocols and chemo-enzymatic methods are offering new opportunities for carbohydrate chemistry.

    • Thomas J. Boltje
    • , Therese Buskas
    •  & Geert-Jan Boons
  • Review Article |

    Ring-opening metathesis polymerization (ROMP) is a powerful and highly functional-group-tolerant technique for synthesizing polymers. However, this tolerance presents a great challenge for the selective introduction of functional end-groups. This Review discusses currently available end-functionalization strategies and also highlights factors to be considered when choosing the most appropriate approach.

    • Stefan Hilf
    •  & Andreas F. M. Kilbinger
  • Review Article |

    Transition metals can form extremely short bonds with very high bond orders. Bimetallic chromium complexes are the best-known examples, and quintuple bonds have been reported. This Review covers recent developments in the synthesis and theoretical description of quintuply bonded transition metal coordination compounds.

    • Frank R. Wagner
    • , Awal Noor
    •  & Rhett Kempe
  • Review Article |

    The most stable fullerenes obey the isolated-pentagon rule (IPR): hexagons of carbon atoms entirely surround pentagons to minimize strain. Recently, some examples of fused-pentagon fullerenes have been reported and this Review summarizes current work to stabilize non-IPR fullerenes.

    • Yuan-Zhi Tan
    • , Su-Yuan Xie
    • , Rong-Bin Huang
    •  & Lan-Sun Zheng
  • Review Article |

    Chemical methods of achieving asymmetric protonation are classified according to reaction mechanism, with a view to developing a greater understanding of this most fundamental of asymmetric processes, and thus improving the potential for its application in synthesis.

    • Justin T. Mohr
    • , Allen Y. Hong
    •  & Brian M. Stoltz
  • Review Article |

    The simplicity and broad applicabilty of atom transfer radical polymerization make it a rapidly developing area of synthetic polymer chemistry. Here, the fundamentals of the technique are discussed, along with how it can be used to synthesize macromolecules with controlled molecular architecture, and how their self-assembly can create nanostructured functional materials.

    • Krzysztof Matyjaszewski
    •  & Nicolay V. Tsarevsky
  • Review Article |

    The use of protecting groups has been, and remains, instrumental in the development of organic synthesis. However, designing protecting-group-free strategies offers the challenge of developing useful new chemoselective processes as well as being inherently more step- and atom-economic.

    • Ian S. Young
    •  & Phil S. Baran
  • Review Article |

    Molecules with a Möbius geometry are not found in nature, and have thus been a target for synthetic chemists since the first prediction of its existence in 1964. This review summarizes recent successes in synthesizing these fascinating forms, with particular emphasis on expanded porphyrins.

    • Zin Seok Yoon
    • , Atsuhiro Osuka
    •  & Dongho Kim