• Perspective |

    Intracellular phase separation is a major regulatory mechanism in several biochemical processes. This Perspective describes the contribution of H2O and biomolecules to this phenomenon in the framework of two well-known models.

    • Sara S. Ribeiro
    • , Nirnay Samanta
    • , Simon Ebbinghaus
    •  & João C. Marcos
  • Perspective |

    Water oxidation catalysts are key components in water-splitting devices that synthesize fuels by using energy, including that from sunlight. This Perspective presents historical developments in molecular water oxidation catalysis, emphasizing studies of ruthenium complexes that have taught us how to design optimal catalysts.

    • Roc Matheu
    • , Pablo Garrido-Barros
    • , Marcos Gil-Sepulcre
    • , Mehmed Z. Ertem
    • , Xavier Sala
    • , Carolina Gimbert-Suriñach
    •  & Antoni Llobet
  • Perspective |

    The selective conjugation of two or more molecules is readily achieved using covalent click chemistry or non-covalent click chemistry. The latter approach makes use of complementary molecular recognition partners, and its speed and reversibility are advantageous for many biological applications.

    • Cynthia L. Schreiber
    •  & Bradley D. Smith
  • Perspective |

    Automation can help in performing routine tasks quickly and consistently. Algorithms facilitate the searching of current knowledge. Combining the two could lead to a chemically intelligent approach to the discovery of not only new molecules but also novel and unpredictable reactivity.

    • Piotr S. Gromski
    • , Alon B. Henson
    • , Jarosław M. Granda
    •  & Leroy Cronin
  • Perspective |

    This Perspective introduces energy decomposition analysis as a means of providing a quantum chemically derived bonding model that we can use to rationalize molecular geometries and bonding. The model serves as a bridge between the simple Lewis electron-pair bond and the complicated quantum theoretical nature of the chemical bond.

    • Lili Zhao
    • , Markus Hermann
    • , W. H. Eugen Schwarz
    •  & Gernot Frenking
  • Perspective |

    Lewis’ shared electron-pair model was a stroke of genius, describing the structure and reactivity of molecules purely on the basis of his tremendous knowledge of empirical chemistry without any quantum chemistry. Unprecedented in simplicity, its success unfortunately concealed some misleading interpretations of the physical origin of chemical bonding.

    • Lili Zhao
    • , W. H. Eugen Schwarz
    •  & Gernot Frenking
  • Perspective |

    This Perspective describes the physical molecular driving forces that stabilize native lignocellulosic plant biomass structures and govern thermochemical biomass pretreatments. Understanding these driving forces can help us to design efficient methods for deconstructing biomass into biofuels and other bioproducts.

    • Loukas Petridis
    •  & Jeremy C. Smith
  • Perspective |

    This Perspective describes how reversible catalysis — a hallmark of enzymes — can be reproduced in synthetic catalysts by rationally designing first and second coordination spheres, as well as amino acid-based outer coordination spheres. We describe this in the context of Ni prototypes for efficient H2 oxidation and evolution.

    • Arnab Dutta
    • , Aaron M. Appel
    •  & Wendy J. Shaw
  • Perspective |

    The study of [FeFe]-hydrogenases exemplifies how one can manipulate even sophisticated metal clusters to afford insights into structure–function relationships of biological catalysts. This Perspective describes developments in designing artificial proteins and catalytically active nucleic acids towards minimalistic and robust semi-biological catalysts for chemical synthesis.

    • Anja Hemschemeier
    •  & Thomas Happe
  • Perspective |

    The discovery of bioactive small molecules is generally driven via iterative design–make–purify–test cycles. Progress has been made towards the automation and integration of adjacent stages within such discovery workflows, which can increase the efficiency and effectiveness of bioactive small-molecule discovery.

    • Shiao Chow
    • , Samuel Liver
    •  & Adam Nelson
  • Perspective |

    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.

    • Sander I. van Kasteren
    • , Jacques Neefjes
    •  & Huib Ovaa
  • Perspective |

    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.

    • Laura Riccardi
    • , Vito Genna
    •  & Marco De Vivo
  • Perspective |

    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.

    • Peter M. Kraus
    • , Michael Zürch
    • , Scott K. Cushing
    • , Daniel M. Neumark
    •  & Stephen R. Leone
  • Perspective |

    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.

    • Rommie E. Amaro
    •  & Adrian J. Mulholland
  • Perspective |

    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.

    • Alex Zunger
  • Perspective |

    Numerous fabrication methods have been developed so far for the production of graphenes and nanographenes. However, how practical is the bulk production of these fascinating materials? This Perspective discusses recent advances in graphene fabrication and possibilities for translation to large-scale production.

    • Xiao-Ye Wang
    • , Akimitsu Narita
    •  & Klaus Müllen
  • Perspective |

    Metal–ligand cooperative catalysis involves both the metal and the ligand moieties present in a complex interacting with substrates. Cooperative catalysis is central to the mechanisms of hydrogenases, lactate racemase and alcohol dehydrogenase. This Perspective describes these enzymes, as well as the small-molecule mimics inspired by these elaborate natural catalysts.

    • Matthew D. Wodrich
    •  & Xile Hu
  • Perspective |

    Light-driven artificial molecular switches and motors afford dynamic control of various molecular systems, ranging from catalytic to biological. This Perspective provides insight into the challenges that must be addressed to transition the field from the proof-of-concept stage to realization of its myriad applications.

    • Thomas van Leeuwen
    • , Anouk S. Lubbe
    • , Peter Štacko
    • , Sander J. Wezenberg
    •  & Ben L. Feringa
  • Perspective |

    Reviewing the applications of a solvent would ordinarily be an unusual thing to do, but the unique properties of hexafluoroisopropanol and its applications across a huge swathe of chemistry make that both a viable and interesting undertaking.

    • Ignacio Colomer
    • , Anna E. R. Chamberlain
    • , Maxwell B. Haughey
    •  & Timothy J. Donohoe
  • Perspective |

    Blue energy can be cleanly and renewably harvested from a salinity gradient. The large-scale viability of this non-intermittent source is restricted by certain challenges, including the inefficiency of present harvesting technologies. This Perspective describes how nanofluidics can afford membranes better able to convert chemical potentials to electrical potentials.

    • Alessandro Siria
    • , Marie-Laure Bocquet
    •  & Lydéric Bocquet
  • Perspective |

    Redox reactions related to renewable energy challenges can be mediated by molecular electrocatalysts. Intelligent design of these catalysts calls for systematic catalyst benchmarking. This Perspective presents examples of analysing catalytic Tafel plots, noting through-structure and through-space effects on the performance and mechanism. This approach is preferred to oversimplifications inherent in using volcano plots.

    • Cyrille Costentin
    •  & Jean-Michel Savéant
  • Perspective |

    The unusual electronic characteristics of boron atoms lead boron clusters to adopt a wide variety of structural arrangements, most of which are 2D. This Perspective discusses the possibility of expanding the range of boron-based 2D structures by metal doping, as well as the use of the resulting clusters for conceptualizing metalloborophenes.

    • Wan-Lu Li
    • , Xin Chen
    • , Tian Jian
    • , Teng-Teng Chen
    • , Jun Li
    •  & Lai-Sheng Wang
  • Perspective |

    The unique properties of ferrocene-containing compounds make them useful for treating many diseases. The most notable drug candidates — the antimalarial ferroquine and the anticancer agent ferrocifen — have been studied for more than two decades but have not yet met clinical approval. This Review describes the design of ferrocene-containing drugs as well as the challenges faced in bringing them into clinical use.

    • Malay Patra
    •  & Gilles Gasser
  • Perspective |

    The cross-electrophile coupling approach to stereocontrolled C–C bond formation provides a complementary alternative to traditional cross-coupling methods. This Perspective provides an overview of the recent development of nickel-catalysed asymmetric cross-electrophile coupling reactions. Both stereoconvergent and stereospecific examples are considered and mechanistic details are highlighted.

    • Erika L. Lucas
    •  & Elizabeth R. Jarvo
  • Perspective |

    Bis(β-diketiminato)dimagnesium(I) complexes are low-valent reagents that can each deliver two electrons in a selective and stoichiometric manner. Easily handled and dissolved, these species effect reduction of many inorganic and unsaturated organic substrates. This Perspective covers the development of magnesium(I) dimers and the scope of their reactivity.

    • Cameron Jones
  • Perspective |

    Covalent organic frameworks (COFs) have potential applications in, for example, gas storage and separation. The pore sizes in these materials are tunable by selection of the building blocks, and materials with multiple pore sizes are desirable. This Perspective considers synthetic approaches to 2D COFs that rely on tessellation to prepare such multiporous materials.

    • Yinghua Jin
    • , Yiming Hu
    •  & Wei Zhang
  • Perspective |

    Quadruplex DNA structures were first observed more than 50 years ago, but have only relatively recently attracted interest for their role in the development of cancer. This Perspective considers attempts to selectively bind and stabilize these structures using small molecules, with the aim of developing anticancer therapeutics.

    • Stephen Neidle
  • Perspective |

    The technological progress made since the industrial revolution has brought with it one of our greatest challenges: how to power our world while also minimizing environmental harm. This Perspective highlights the important role that quantum chemistry has in sustainable energy research.

    • Johannes M. Dieterich
    •  & Emily A. Carter
  • Perspective |

    Recent developments in systems chemistry have shown how the molecular building blocks of life could have arisen from plausible prebiotic feedstocks. This Perspective argues that we remain a long way from a full picture and speculates on what pieces of the puzzle are still missing.

    • John D. Sutherland